Antimicrobial Therapy in Veterinary Medicine

Table 29.2. Specific therapeutic antimicrobial application suggestions.

Label applications are U.S. labels except for those in bold print, which are E.U. labels.

Category Disease/Pathogen(s) Drugs for which this disease Extra-label antimicrobials Unreasonable extra-label Comments
is a label application that are a reasonable choice antimicrobal selections for

(therapy and/or prevention) this disease

Respiratory disease Pneumonia—Mannheimia Ampicillin trihydrate, ceftiofur Oxytetracycline, Gentamicin due to potential Antimicrobials with bovine
haemolytica., Pasteurella (sodium, hydrochloride, spectinomycin, toxicity in dehydrated respiratory disease on the
Respiratory disease multocida, Histophilus and crystalline free acid fluoroquinolones* animals and prolonged label may be indicated for
Respiratory disease somni salts), chlortetracycline, renal residues in cattle. one or all of these pathogens.
danofloxacin, enrofloxacin, The italicized antimicrobials
Pneumonia—Mycoplasma florfenicol, gamithromycin, Any beta-lactam (penicillins, are the author’s primary U.S.
bovis oxytetracycline, procaine cephalosporins) due to choices for cattle in advanced
penicillin G, spectinomycin lack of a cell wall. stages of the disease or
Diphtheria (necrotic sulfate, sulfadimethoxine, which have experienced
laryngitis)— sulfamethazine, tildipirosin, extensive stress. Not all of the
Fusobacterium tilmicosin, tulathromycin, antimicrobials are labeled for
necrophorum tylosin, cefquinome, all respiratory pathogens. The
trimethoprim/ labels should be consulted for
sulfadiazine. complete indications.
trimethoprim/
sulfadoxine, procaine See text for comments. *In the
penicillin/ USA, fluoroquinolones would
dihydrostreptomycin, only be legal when used for
amoxicillin trihydrate, the purpose of respiratory
amoxicillin/clavulanic disease due to the primary
acid label pathogens.

Enrofloxacin, gamithromycin, Extra-label recommendations are
florfenicol, tulathromycin, made based on published MIC
tylosin (Mycoplasma on values that are in the range of
label) other pathogens succesfully
treated by these
Oxytetracycline Ampicillin, ceftiofur, antimicrobials and/or label
florfenicol, penicillin G, inclusion of foot rot due to
sulfadimethoxine, tylosin Fusobacterium necrophorum.
and other macrolides such (Baba, 1989; Berg, 1982;
as tulathromycin

Infectious enteric disease Scours, neonatal diarrhea Chlortetracycline, neomycin, Ceftiofur, potentiated (These extra-label Druan, 1991; Jousimies-Somer,
Infectious enteric disease due to E. coli oxytetracycline, sulfonamides (all only indications demonstrated 1996; Jang, 1994; Lechtenberg,
sulfachlorpyridazine, after susceptibility testing) very high MICs to most 1998; Mateos, 1997; Piriz,
Scours, neonatal diarrhea sulfamethazine, isolates.) Erythromycin, 1990; Samitz, 1996) . All of
due to Salmonella spp. tetracycline (all of these Ceftiofur, potentiated tylosin, tilmicosin, these isolates were from other
antimicrobials display sulfonamides (all only lincomycin, penicillin, sites than necrotic laryngitis.
consistently high MICs after susceptibility testing) ampicillin, florfenicol. The nature of the site of
that suggest the drugs necrotic laryngitis may make
would be ineffective), Gentamicin will cause therapy with less lipid soluble
Amoxicillin/clavulanic extended withdrawal antimicrobials more of a
acid bolus, cefquinome times that will compromise challenge.
(septicemia), the ability to slaughter an Recommended extra-label
danofloxacin, animal that recovers from antimicrobials are based on
enrofloxacin the acute disease but does susceptibility data and serum
(septicemia and not return to satisfactory pharmacokinetics and should
colibacillosis), production. therefore be interpreted as
marbofloxacin bolus, relating to septicemia
trimethiprim/ associated with enteric
sulfadiazine, disease. See text for
trimethiprim/ additional discussion.
sulfadoxine
Recommended extra-label
Chlortetracycline, antimicrobials are based on
oxytetracycline (these susceptibility data and serum
antimicrobials display pharmacokinetics and should
consistently high MICs therefore be interpreted as
that suggest the drugs relating to septicemia
would be ineffective), associated with enteric disease.
Enrofloxacin, See text for additional
trimethoprim/ discussion.
sulfadiazine,
trimethoprim/ (continued)
sulfadoxine, procaine
penicillin/
dihydrostreptomycin

Table 29.2. Specific therapeutic antimicrobial application suggestions. (continued)

Label applications are U.S. labels except for those in bold print, which are E.U. labels.

Category Disease/Pathogen(s) Drugs for which this disease Extra-label antimicrobials Unreasonable extra-label Comments
is a label application that are a reasonable choice antimicrobal selections for
Antiserum therapy is more likely
(therapy and/or prevention) this disease related to therapeutic success.
Septicemia resulting from
Infectious enteric disease Enterotoxemia, overeating Amoxicillin, ampicillin, enterotoxemia may involve
disease—Clostridium penicillin G multiple gut-related bacteria.
perfringens type C,D Antimicrobial selection should
reflect this possibility (see
Infectious enteric disease Hemorrhagic bowel Penicillin G, florfenicol septicemia related to neonatal
disease—Clostridium diarrhea above).

perfringens type A Prognosis of hemorrhagic bowel
disease is very guarded, with
Infectious enteric disease Cryptosporidiosis— Halofuginone lactate For prevention: lasalocid in Amprolium, sulfas surgery necessary for
Infectious enteric disease Cryptosporidium parvum (prevention, and calves ≥ 1 week old (toxic resolution in many cases
reduction in excretion in neonates at effective (Dennison, 2002). There is no
in affected calves) doses!) published evidence that
antimicrobial intervention
Giardia Albendazole, fenbendazole, changes the clinical outcome.
metronidazole (see While there is no published
comments) data to support florfenicol
efficacy in this disease, the
general activity against
anaerobes make it a
reasonable consideration.

See text for comments on clinical
trial data for cryptosporidiosis.
Affected calves have severe
acid/base and hydration
insults.

The extra-label use of
nitroimidazoles (e.g.,
metronidazole) in food
animals is banned in the
United States. Fenbendazole
regimens of 5 mg/kg q 12H
for 3 days or 5 mg/kg q 24H
for 5 days, PO, have been
suggested (Rings, 1996).
Fenbendazole liquid is labeled
for giardia in puppies and
kittens in the E.U.

Infectious enteric disease Coccidiosis—Eimeria bovis, Prevention/control: Sulfadimethoxine, Amprolium and sulfadimidine
Genitourinary Eimeria zeurnii monensin, lasalocid, sulfadimidine were found superior to
Genitourinary amprolium, decoquinate, halofuginone in an induced
Leptospirosis sulfaquinoxaline; therapy Penicillin/dihydro- Eimeria bareillyi calf model
Genitourinary of acute disease: streptomycin, ceftiofur (Sanyal, 1985). Toltrazuril was
Metritis/endometritis sulfaquinoxaline, found effective in a dose-
sulfamethazine, Antimicrobial therapy has dependent manner against an
Seminal vesiculitis— amprolium not been shown to make a induced Eimeria bovis model in
Arcanobacterium difference in clinical calves (Mundt, 2003).
pyogenes, Brucella Oxytetracycline, outcome. Oxytetracycline
abortus., E. coli, dihydrostreptomycin, in the feed at various Ceftiofur was effective in clearing
Pseudomonas spp., tylosin (spirochetes on doses has been used for induced leptospirosis (hardjo)
Actinobacillus seminis, label) prevention. Tilmicosin in cows at 2.2 and 5.0mg/kg
Actinomyces bovis, phosphate, long-acting q24h for 5 days. These
Histophilus somni oxytetracycline, and Intrauterine administration of regimens were not effective
(Haemophilus somnus), florfenicol have been used penicillins, when administered for 3 days.
Salmonella spp., in therapeutic attempts. aminoglycosides, and Long-acting 200mg/ml
Chlamydia spp. sulfonamides is oxytetracycline (20mg/kg) and
questionable, as these may penicillin/dihydrostreptomycin
undergo enzymatic (25mg/kg) were effective after
cleavage, operate poorly in single doses (Alt, 2001).
an anaerobic environment,
or lose activity in the Chenault (2004) reported 14-day
presence of pus. cure rates of 77%, 65%, and
62% for cows suffering from
acute postpartum metritis
treated with 2.2 mg/kg IM/SQ
ceftiofur HCl (CE) q 24h for
5 days, 1.1 mg/kg CE q 24h for
5 days, and controls, respectively.
Königsson (2000) demonstrated
that cows treated with 10mg/kg
IM oxytetracycline SID for 5 days
demonstrated a shorter
time to eradication of
intrauterine A. pyogenes and
F. necrophorum than untreated
controls (p < 0.05).

Arcanobacterium pyogenes is the
most common agent in the
United States. Brucella abortus
is the most common in
countries with this disease.
There is debate as to the role of
bacterial or viral pathogens in
the pathogenesis of seminal
vesiculitis (Larson, 1997).

(continued)

Table 29.2. Specific therapeutic antimicrobial application suggestions. (continued)

Label applications are U.S. labels except for those in bold print, which are E.U. labels.

Category Disease/Pathogen(s) Drugs for which this disease Extra-label antimicrobials Unreasonable extra-label Comments
is a label application that are a reasonable choice antimicrobal selections for
Antimicrobials for cystitis have
(therapy and/or prevention) this disease traditionally been chosen for
their urine concentrations.
Genitourinary Nephritis/ pyelonephritis— Trimethoprim/ For C. renale, Arcanobacterium However, the infection of
Genitourinary Corynebacterium renale, sulfadiazine, pyogenes—penicillin G, concern is in the wall of the
Arcanobacterium trimethoprim/ ampicillin; E. coli—ceftiofur, bladder, not the urine. Therefore,
pyogenes, E. coli sulfadoxine fluoroquinolones (where while urine concentrations may
legal) be of benefit, lack of significant
Cystitis Amoxicillin, trimethoprim/ urine concentrations does not
sulfadiazine, amoxicillin Amoxicillin, ampicilllin, necessarily preclude selection
trihydrate ceftiofur, oxytetracycline, for cystitis.
florfenicol,
fluroquinolones (where Other pathogens may be present
legal), penicillin G, as listed for neonatal arthritis.
trimethiprim/sulfa However, therapy of adult
bovine arthritis should include
Musculo/skeletal Adult arthritis—Histophilus Oxytetracycline, florfenicol, If M. bovis is suspected, any consideration of these
Musculo/skeletal somni, Mycoplasma bovis fluoroquinolones (where beta-lactam would be an organisms unless ruled out by
allowed by law), unreasonable choice. If culture. Arthritis due to
tulathromycin, another organism is M. bovis is often characterized
spectinomycin, confirmed, then ceftiofur as a tenosynovitis. An
gamithromycin, and ampicillin may be extended duration of therapy
lincomycin (given due considered. (1–2 weeks) and a prolonged
consideration to potential recovery period are necessary.
rumen flora alterations)
The potential presence of E. coli
Neonatal arthritis—E. coli, Amoxicillin trihydrate, Potentiated sulfonamides, and the varied susceptibility
Arcanobacterium amoxicilin/clavulanic flouroquinolones (where results of ampicillin,
pyogenes, Staphylococcus acid, procaine allowed by law) florfenicol, and oxytetracycline
spp., Streptococcus spp. penicillin/ suggest they are not primary
dihydrostreptomycin, considerations for this
procaine penicillin G disease. The primary
metabolite of ceftiofur has
a greatly elevated MIC90 value
for Staphylococcus spp. as
compared to the parent

Central nervous system Listeriosis—Listeria Procaine penicillin/ Penicillin G, oxytetracycline, compound (Salmon, 1996),
disease monocytogenes dihydrostreptomycin, enrofloxacin (depending indicating it is not a primary
procaine penicillin G on legal status). Therapy choice where Staph. spp. may
Central nervous system durations of 1–2 weeks be part of the infection.
disease Thromboembolic meningo- may be necessary.
encephalitis (TEME), Varying results are reported for
Central nervous system Histophilus somni Oxytetracycline, florfenicol the recomended drugs. Five of
disease (Haemophilus somnus) 6 bulls in a case report
Ceftiofur, fluoroquinolones survived after therapy with
Meningitis—E. coli in Procaine penicillin/ (where legal), Due to inconsistent coverage oxytetracycline and
neonates, multiple other dihydrostreptomycin trimethoprim/sulfa of the potential dexamethasone (Ayars, 1999).
pathogens possible Enterobacteriacae A sheep and goat case report
component: penicillin G, indicated poor response to
first-generation chloramphenicol and
cephalosporins, oxytetracycline, but 6 of 9
macrolides, tetracyclines, animals recovered when
florfenicol treated with penicillin and
gentamicin (Braun, 2002).
Enrofloxacin has been
reported as effective (Tripathi,
2001) but is illegal in
countries with a ban on
extra-label use of
fluoroquinolones in food
animals (e.g., United States).

Oxytetracycline is a standard
drug of choice for this
application. Florfenicol is also
suggested due to low MICs
for H. somni combined with
high lipid solubility.

While consideration of
penetration of the blood-brain
barrier is valid, it is likely that
this barrier is disrupted in
meningitis, allowing greater
penetration of water-soluble
compounds. Doxycycline is a
lipid-soluble tetracycline, but
the high protein binding in
serum limits the amount
available to the diffusionary
pool, and therefore CNS
penetration.
(continued)

Table 29.2. Specific therapeutic antimicrobial application suggestions. (continued)

Label applications are U.S. labels except for those in bold print, which are E.U. labels.

Category Disease/Pathogen(s) Drugs for which this disease Extra-label antimicrobials Unreasonable extra-label Comments
is a label application that are a reasonable choice antimicrobal selections for
Without adequate trial data,
(therapy and/or prevention) this disease extra-label recommendations
are made on the basis of
Central nervous system Otitis media and interna— Trimethoprim/sulfadiazine In cattle where respiratory Aminoglycosides may be reported pathogen population
disease potential pathogens (infections of the ear pathogens are suspected: expected to have MICs and lipid solubility of the
include respiratory (all on the label), tylosin macrolides, florfenicol, extensive binding to compound. Many of the
ages) and enteric fluoroquinolones (where protein debris at the site extra-label recommendations
pathogens (neonates) . legal). Beta-lactams might of infection and are less would have a hole in the
Mycoplasma bovis should be expected to have lower active in areas with spectrum for at least one
be suspected in dairy calves concentrations in remote lowered pH. possible pathogen (e.g.,
where M. bovis mastitis is otic tissues. enrofloxacin—Strep. spp.,
present in the herd. ceftiofur—Staph. spp. and
M. bovis, macrolides and
Tissue/integumentary Infectious bovine kerato- oxytetracycline, topical penicillin G, florfenicol, florfenicol—inconsistent against
disease conjunctivitis (Pinkeye)- gentamicin, tulathromycin tilmicosin, topical Enterobacteriacae, penicillin G
Moraxella bovis benzathine cloxacillin and ampicillin—
Enterobacteriacae and M. bovis).

Florfenicol was found to be
effective against IBK at either
of the label dose regimens
(Angelos, 2000, Dueger,
1999). Topical benzathine
cloxacillin, 250 or 375 mg/eye,
has been shown to be
effective in naturally occurring
and induced pinkeye models
(Daigneault, 1990). Tilmicosin
was shown to be effective at
both 5 and 10 mg/kg
(Zielinski, 1999). Although
local penicillin G is a standard
treatment, one report
indicated no difference in
healing of naturally occurring
IBK after subconjunctival
administration (Allen, 1995).

Tissue/integumentary Infectious pododermatitis Amoxicillin, ceftiofur Procaine penicillin G, Different labels will have
disease (foot rot)—Fusobacterium (sodium, hydrochloride, ampicillin trihydrate, different pathogens. Severe
necrophorum, Bacteroides crystalline free acid), florfenicol tissue reactions result from
Tissue/integumentary melaninogenicus, erythromycin, florfenicol, intramuscular use of tylosin
disease Porphyromonas levii oxytetracycline, Streptomycin, sodium iodide and erythromycin.
sulfadimethoxine, combined with
Tissue/integumentary Actinobacillosus, “wooden sulfamethazine, antimicrobial therapy for A case report indicated that
disease tongue”—Actinobacillus tulathromycin, tylosin, effect on granulomatous cattle receiving IV sodium
lignieresii cefquinome, tilmicosin, tissue iodide and intralesional
Tissue/integumentary sulfadiazine/ streptomycin regressed
disease Actinomycosis, “lumpy trimethoprim Penicillin G, ampicillin lesions faster than negative
jaw”—Actinomyces bovis trihydrate, oxytetracycline. controls or penicillin-treated
Long-acting oxytetracyclines Sodium iodide may be cattle (Campbell, 1975). No
Blackleg—C. chauvoei; (200 and 300 mg/ml), combined with clinical trials are available.
malignant edema— amoxicillin trihydrate, antimicrobial therapy for
C. sordellii, C. septicum; amoxicillin/clavulanic effect on granulomatous No clinical trials are available to
tetanus—Clostridium acid, cefalexin tissue confirm efficacy of these
tetani; bacillary dihydrostreptomycin, antimicrobials. Prolonged
hemoglobinuria— trimethoprim/ Penicillin G therapy is recommended with
Clostridium hemolyticum; sulfadiazine surgical debridement of the
Black disease—C. novyi (Actinobacilli on label) lesion if possible.

Amoxicillin trihydrate, All of the approved drugs have
amoxicilin/ “clostridia” on the label
clavulanic acid, without indications for
dihydrostreptomycin, specific clostridial diseases
cefalexin, trimethoprim/ unless indicated. Japanese
sulfadiazine isolates of C. perfringens,
(Actinomycae on label) C. septicum, and C. sordellii
displayed phenotypic
Amoxicillin trihydrate, resistance to oxytetracycline
amoxicillin/clavulanic and were confirmed to carry
acid, cefalexin, procaine oxytetracycline-resistance
penicillin G (C. chauvoei), genes (Sasaki, 2001).
procaine/benzathine (continued)
penicillin G (C. chauvoei),
tylosin

Table 29.2. Specific therapeutic antimicrobial application suggestions. (continued)

Label applications are U.S. labels except for those in bold print, which are E.U. labels.

Category Disease/Pathogen(s) Drugs for which this disease Extra-label antimicrobials Unreasonable extra-label Comments
is a label application that are a reasonable choice antimicrobal selections for

(therapy and/or prevention) this disease

Tissue/integumentary Peritonitis—Escherichia coli, Trimethoprim/sulfa (probably Penicillin/gentamicin is No clinical trials are available in
disease Arcanobacterium pyogenes, the most consistent for reasonable as to spectrum cattle. Recommendations are
Clostridium perfringens, E. coli), florfenicol, but gentamicin engenders based on wide-spectrum, lipid
Tissue/integumentary multiple Gram-positive and oxytetracycline (both an extreme withdrawal solubility, and duration of
disease Gram-negative aerobes inconsistent on E. coli), that precludes salvage activity. An extended duration
and anaerobes. Isolate ceftiofur for short slaughter attempts in of therapy (≥ 1 week) is
Tissue/integumentary reports in other species withdrawal but may not recovered animals. necessary. Prognosis is
disease include organisms in all 4 cover Staph. spp. extremely poor in advanced
quadrants. Amoxicillin trihydrate, cases. Note that the MIC90 of
Tissue/integumentary amoxicilin/clavulanic Topical iodine solution/scrub, the ceftiofur metabolite
disease Omphalophlebitis (navel ill) acid, procaine systemic griseofulvin* against Staph. spp is
penicillin/ approximately 8 times that of
Trichophytosis (ringworm) dihydrostreptomycin, Penicillin G, oxytetracycline the parent compound.
procaine penicillin G
Rainrot (Dermatophilosis)— *Regulations and availability of
Dermatophilus Benzalkonium chloride extra-label slaughter
congolensis (0.15% topical solution), withdrawal time information
enilconazole, natamycin should be confirmed prior to
using griseofulvin in countries
without a label for this
application. Griseofulvin is
teratogenic.

Penicillin G and oxytetracycline
are often cited for therapy of
dermatophilosus. A paper
evaluating MIC and MBC
concentrations, in vitro data,
and unbound serum
concentrations also
recommended erythromycin,
ampicillin, streptomycin,
amoxicillin, and
chloramphenicol (Hermoso-de
Mendoza, 1994).

Cardiovascular/systemic Anaplasmosis Chlortetracycline in the feed Oxytetracycline, imidocarb The chloramphenicol results
for control of active diproprionate suggest potential for
infection florfenicol efficacy.

Cardiovascular/systemic Endocarditis— Penicillin G, presence of a Prevention or amelioration of
Arcanobacterium Gram-negative on blood clinical signs with
pyogenes and culture indicates oxytetraycline are well
Streptococcus spp. are ampicillin, amoxicillin, or established. However, there
most common. Escherichia cefiofur. are reports in the literature
coli, other organisms also citing both successful and
possible. unsuccesful clearance of
carriers with oxytetracycline.
Recent work has documented
unsuccessful clearance of
induced anaplasmosis carrier
status with the OIE regimen of
22 mg/kg oxytetracycline, IV, q
24h, for 5 days (Coetzee,
2005). Clearance of the carrier
state with imidocarb has been
documented (Roby, 1972).

Prolonged therapy is necessary.
Addition of rifampin (5 mg/kg,
PO, q 12h) has been
suggested to improve
response. Prolonged therapy
(4–6 weeks) has been
suggested as an appropriate
duration of therapy. (Dowling,
1994; McGuirk, 1991). Lack of
clinical efficacy may be due to
lack of antimicrobial
penetration into vegetative
lesions. Florfenicol would be
appropriate for pathogens
with appropriate MICs
(variable on E. coli).

In cases where the law and
economics permit,
fluoroquinolones would be
appropriate if an organism
other than a Strep. spp. was
confirmed.
(continued)

Table 29.2. Specific therapeutic antimicrobial application suggestions. (continued)

Label applications are U.S. labels except for those in bold print, which are E.U. labels.

Category Disease/Pathogen(s) Drugs for which this disease Extra-label antimicrobials Unreasonable extra-label Comments
is a label application that are a reasonable choice antimicrobal selections for
A study evaluating the MICs
(therapy and/or prevention) this disease of 25 geneticially diverse
B. anthracis isolates from
Cardiovascular/systemic Anthrax—Bacillus anthracis Amoxicillin, amoxicillin/ Penicillin G, oxytetracycline, multiple countries reported
clavulanic acid, tylosin fluoroquinolones (where MIC90 values as follow:
(Bacillus on label) legal) doxycycline, ciprofloxacin 0.09 μg/ml,
first-generation penicillin 0.2 μg/ml,
cephalosporins. doxycycline 0.34 μg/ml,
Chloramphenicol results cefuroxime 32 μg/ml,
suggest florfenicol may be cephalexin 0.25 μg/ml,
an option. cefachlor 1.65 μg/ml, and
tobramycin 0.97 μg/ml (Coker,
2002). Except for cefuroxime,
and possibly cefachlor, these
MIC90 values are in a range
where efficacy might be
expected with typically used
doses. Universally
“susceptible” disk diffusion
results with unvalidated
interpretive criteria have been
reported for tetracycline,
ampicillin, streptomycin,
chloramphenicol, and
erythromycin in South African
isolates (Odendaal, 1990).

Chapter 29. Antimicrobial Drug Use in Cattle 515

Table 29.3. Mycoplasma bovis susceptibility data.

Rosenbusch (2005) 223 U.S. Isolates Ayling (2000) 62 British Isolates Label Data as Indicated by Footnote

Antimicrobial MIC50 MIC90 Range MIC50 MIC90 Range MIC50 MIC90 Range
(μg/ml) (μg/ml) (μg/ml) (μg/ml) (μg/ml) (μg/ml) (μg/ml) (μg/ml) (μg/ml)
Enrofloxacin
Danofloxacin 0.25 0.5 0.03–4 NA NA NA NA NA NA
Florfenicol NA NA NA 0.5 0.5 0.25–8 NA NA NA
Chlortetracycline 1 4 0.06–8 4 16 4–128 1.0a 1.0a 0.5–1.0a
Oxytetracycline 4 16 0.25 to > 32 NA NA NA NA NA NA
Spectinomycin 2 16 0.125 to > 32 32 64 2 to > 128 NA NA NA
Tilmicosin 2 4 1 to > 16 4 > 128 2 to > 128 NA NA NA
Tulathromycin 64 > 128 0.5 to > 128 > 128 > 128 16 to > 128 NA NA NA
NA NA NA NA NA NA 0.125b 1b ≤0.063 to > 64b

aNuflor Gold label (2009), 59 U.S. isolates.
bDraxxin label (2009), 43 U.S. isolates.
NA = data not available.

Enteric Disease and Septicemia Associated that were adapted from human medicine. There are now
with Escherichia coli and Salmonella spp. also “generic” breakpoints developed, and in develop-
ment, by the CLSI. However, these generic breakpoints
A previous review of the literature showed that there is a have not been directed toward enteric disease as of the
paucity of data to support the efficacy of antimicrobial writing of this chapter.
therapy for bacterial enteric disease in calves (Constable,
2004). Little has changed between the time of this review CLSI breakpoints are developed based on a combina-
and the writing of this chapter (2012). tion of in vitro efficacy data coupled with susceptibility
testing, “wild-type” isolate MIC profiles, and pharmacoki-
The practitioner is hampered by two obstacles. The netic/ pharmacodynamic (PK/PD) data. When applying
previously mentioned lack of clinical data from prospec- these breakpoints to other indications, such as enteric
tive controlled and randomized clinical trials, and the disease, it is hoped that the PK/PD indices and the changes
lack of validated susceptibility testing breakpoints for in MIC due to a resistance gene are at least similar.
classification of enteric pathogens as susceptible or Therefore, we might more accurately refer to the process
resistant. for enteric disease as “resistance testing,” where resistant
isolates would be considered more likely to possess
However, the author’s discussions with practitioners resistance genes rendering the antimicrobial incapable of
indicate that few would be willing to forego antimicro- having an effect on growth or viability of the pathogen.
bial therapy considering that a proportion of calves with
enteric disease are likely septicemic. Also, the potential Therefore, a reasonable approach is to first rule out any
for septicemia in adult cattle with coliform masitits and of the potential enteric therapeutics based on legal issues
salmonellosis call for guidance in reasonable antimicro- relevant to the practice area. Next, empirical therapy may be
bial selection. guided by accessing enteric culture susceptibility summa-
ries available from your diagnostic laboratory, or by
From an empirical approach, reasonable initial monitoring susceptibility trends within specific produc-
considerations include third-generation cephalosporins, tion units. A preponderance of resistant classifications for
potentiated aminopenicillins, fluoroquinolones (not legal a potential antimicrobial would indicate that the popula-
in the United States), potentiated sulfas, and florfenicol. tion of pathogens being submitted to that laboratory likely
The confirmation of these initial selections would depend carry some type of resistance gene. This antimicrobial
on susceptibility testing as presently available. could therefore be moved down on the list of potential
selections.
Susceptibility testing for enteric disease is not based
on CLSI-approved breakpoints but rather on break-
points developed for another veterinary indication or

516 Section IV. Antimicrobial Drug Use in Selected Animal Species

A finding of “susceptible” does not have any validated lenge study found no difference in days to diarrhea, days
correlation with the likelihood of therapeutic success in to shedding, or duration of diarrhea or oocyst shedding
the patient for enteric disease. However, we would in calves  given 2 mg/kg decoquinate in milk replacer
assume that in the lack of the presence of resistance (Moore, 2003).
genes, the antimicrobial would at least be capable of aid-
ing in clinical recovery to the extent possible with the In naturally occurring Cryptosporidium parvum
regimen and site of infection. infections, halofuginone lactate administered in the
milk replacer at 60 μg/kg per day cleared all shedding of
There are obviously a lot of assumptions in this oocysts within 6 days after the start of treatment in 98%
discussion, highlighting the need for controlled clinical of the treated animals. It should be noted that 93% of the
trials addressing the antimicrobial treatment compo- untreated controls in this study also cleared the organ-
nent of neonatal enteric disease in calves. ism within 10 days of arrival at the facility (Villacorta,
1991). In a natural disease model, calves receiving 5 mg
Cryptosporidium parvum of halofuginone lactate daily in milk replacer were 70%
less likely to shed C. parvum oocysts as compared to
Multiple antimicrobials have been evaluated in untreated controls. Weight gain and milk and starter
Cryptosporidium parvum calf disease models. Antimi- intakes were not significantly different between groups
crobials reported as ineffective in calves up to 14 days of (Jarvie, 2005). In a challenge study, halofuginone
age when administered in the milk replacer during a reduced disease at 60 and 120 μg/kg per day but was
10-day challenge model include amprolium, sulphad- ineffective at 30 μg/kg per day (Naciri, 1993).
imidine, dimetridazole, metronidazole, ipronidazole,
quinacrine, and monensin. Trimethoprim/ sulfadiazine Other antimicrobials such as paromomycin, azithro-
was also ineffective when administered daily as a bolus. mycin, and clarithromycin, have been demonstrated to
Lasalocid was ineffective at 0.8 mg/kg per day. At 8 mg be efficacious in murine models or human therapy
lasalocid/kg per day, 6 of the 10 treated calves died, with (Fichtenbaum, 1993; Rehg, 1991, Holmberg, 1998).
1 of the 4 surviving calves becoming infected (Moon, The  prophylactic potential of paromomycin was also
1982). Sulfadimethoxine has also been shown to be demonstrated in a calf model (Fayer, 1993). However, the
ineffective against C. parvum in a 1- to 7-day-old calf costs of these 3 agents are prohibitive for food animal
challenge model (Fayer, 1992). applications and have prevented their use.

Lasalocid has been used as a preventive or therapeutic Bibliography
agent for cryptosporidium in calves based on anecdotal
reports. This use in neonatal calves has resulted in reported 21 CFR Part 530. 2012. Docket No. FDA-2008-N-0326. New
toxicities after 100mg twice daily in milk replacer or Animal Drugs; Cephalosporin Drugs; Extralabel Animal
200mg oral once-daily doses starting at birth, with death Drug Use; Order of Prohibition. Federal Register, vol. 77,
occurring after 1–3 administrations (Benson, 1998). The no. 4. Friday, January 6, 2012. Available at http://www.gpo.
authors confirmed this toxicity experimentally by dosing gov/fdsys/pkg/FR-2012-01-06/pdf/2012-35.pdf.
neonatal calves once at 5mg/kg.
Allen LJ, et al. 1995. Effect of penicillin or penicillin and dex-
In other studies, Lasalocid doses of 15 mg/kg have amethasone on cattle with infectious keratoconjunctivitis,
been tolerated in calves ≥ 7 days old with cessation of J Am Vet Med Assoc 206:1200.
oocyst shedding 3 days after the last of 3 daily doses of
15 mg/kg (Gobel, 1987). These data would suggest that Alt DP, et al. 2001. Evaluation of antibiotics for treatment of
effective doses of lasalocid are toxic in neonatal calves cattle infected with Leptospira borgpetersenii serovar hardjo,
but may be used in calves of at least 1 week of age. J Am Vet Med Assoc 219: 636.

A trial evaluating decoquinate in a calf Crypto- AMDUCA. 1996. Federal Register, November 7, 1996, vol. 61,
sporidium parvum challenge model found a significant no. 217, p.  57731, 21 CFR Part 530, Extralabel Drug Use in
decrease in number of days with abnormal stool scores Animals; Final Rule, Department Of Health And Human
in the treated groups given 875 or 1750 mg (10X label Services, Food and  Drug Administration, Docket No.
dose) decoquinate per day, but no difference in oocyst 96N-0081, RIN 0910-AA47, ACTION: Final rule. From the
shedding or weight gain (Redman, 1994). Another chal- Federal Register Online via GPO Access (wais.access.gpo.gov).

Angelos JA, et al. 2000. Efficacy of florfenicol for treatment of
naturally occurring infectious bovine keratoconjunctivitis.
J Am Vet Med Assoc 216: 62.

Chapter 29. Antimicrobial Drug Use in Cattle 517

Apley MD. 2003. Susceptibility testing for bovine respiratory and Draxxin (tulathromycin) product label. 2005. Pfizer Animal
enteric disease. Vet Clin North Am Food Anim Pract 19:3. Health.

AVMA. 2003. Judicious Therapeutic Use of Antimicrobials, Fayer R. 1992. Activity of sulfadimethoxine against
accessed October 2005 at http://www.avma.org/scienact/ Cryptosporidiosis. J Parasit 78:534.
jtua/default.asp.
Fayer R, William E. 1993 Paromomycin is effective as prophy-
Ayars WHJ, et al. 1999. An outbreak of encephalitic listeriosis laxis for cryptosporidiosis in dairy calves. J Parisitol 79:771.
in Holstein bulls. Bovine Practitioner 33:138.
FDA/CVM. 2005. www.fda.gov/cvm. Search “prohibited
Ayling RD, et al. 2000. Comparison of in vitro activity of extralabel use.”
danofloxacin, florfenicol, oxytetracycline, spectinomycin
and tilmicosin against recent field isolates of Mycoplasma Fichtenbaum CJ, et al. 1993. Use of paromomycin for
bovis. Vet Rec 146:745. treament of Cryptosporidiosis in patients with AIDS. Clin
Infect Dis 16:298.
Baba E, et al. 1989. Antibiotic susceptibility of Fusobacterium
necrophorum from bovine hepatic abscesses. British Vet J Gobel E. 1987. Diagnose und therapie der akuten krypto-
145:195. sporidiose beim kalb [Diagnosis and treatment of acute
cryptosporidiosis in the calf]. Tierarztliche-Umschar 42:863.
Benson JE, et al. 1998. Lasalocid toxicosis in neonatal calves.
J Vet Diagn Invest 10:210. Hermoso-de Mendoza J, et al. 1994. In vitro studies of
Dermatophilus congolensis antimicrobial susceptibility
Berg JN, Scanlan CM. 1982 Studies of Fusobacterium necropho- by  determining minimal inhibitory and bacteriocidal
rum from bovine hepatic abscesses: biotypes, quantitation, concentrations. British Vet J 150:189.
virulence, and antibiotic susceptibility. Am J Vet Res 43:1580.
Hoffman L, Klinefelter T. 2000–2005 Iowa State
Braun U, et al. 2002. Clinical findings and treatment of University Diagnostic Microbiology Laboratory. Personal
listeriosis in 67 sheep and goats. Vet Rec 150:38. communications.

Campbell SG, et al. 1975. An unusual epizootic of actinobacil- Holmberg SD, et al. 1998. Possible effectiveness of clarithromy-
losis in dairy heifers. J Am Vet Med Assoc 166:604. cin and rifabutin for cryptosporidiosis chemoprophylaxis
in HIV disease. J Am Med Assoc 279:384.
Chenault JR, et al. 2001 Efficacy of ceftiofur hydrochloride
administered parenterally for five consecutive days for Jang S, Hirsh DC. 1994. Characterization, distribution, and
treatment of acute post-partum metritis in dairy cows. microbiological associations of Fusobacterium spp. in clin-
34th Annual Convention of the AABP, pp. 137–138. ical specimens of animal origin. J Clin Microbiol 32:384.

CLSI. 2008. Publication M31-A3: Performance Standards for Jarvie BD, et al. 2005. Effect of halofuginone lactate on the
Antimicrobial Disk and Dilution Susceptibility Tests for occurrence of Cryptosporidium parvum and growth of
Bacteria Isolated form Animals; Approved Standard— neonatal dairy calves. J Dairy Sci 88:1801.
Third Edition (ISBN 1-56238-659-X). Copies of the current
edition and supplemental tables may be obtained from Jousimies-Somer H, et al. 1996. Susceptibilities of bovine
CLSI, 940 West Valley Road, Suite 1400, Wayne, PA 19087- summer mastitis bacteria to antimicrobial agents.
1898, phone 610-688-0100, fax 610-699-0700, e-mail at Antimicrob Agents Chemotherapy 40:157.
[email protected], or on the web at www.clsi.org.
Konigsson K, et al. 2000. Effects of NSAIDs in the treatment
Coetzee JF, et al. 2005. Comparison of three oxytetracycline of postpartum endometritis in the cow. Reprod Domest
regimens for the treatment of persistent Anaplasma mar- Anim 35:186.
ginale infections in beef cattle. J Vet Parasit 127:61.
Larson RL. 1997 Diagnosing and controlling seminal vesicu-
Coker PR, et al. 2002. Antimicrobial susceptibilities of litis in bulls. Vet Med 12:1073.
diverse Bacillus anthracis isolates. Antimicrob Agents
Chemother 46:3843. Lechtenberg KF, et al. 1998. Antimicrobial susceptibility of
Fusobacterium necrophorum insolated from bovine hepatic
Daigneault J, George LW. 1990. Topically applied benzathine abcesses. Am J Vet Res 59:44.
cloxacillin for treatment of experimentally induced
infectious bovine keratoconjunctivitis. Am J Vet Res 51:376. Mateos E, et al. 1997. Minimum inhibitory concentrations
for selected antimicrobial agents against Fusobacterium
Dennison AC, et al. 2002. Hemorrhagic bowel syndrome in necrophorum isolated from hepatic abscesses in cattle.
dairy cattle: 22 cases (1997–2000). J Am Vet Med Assoc J Vet Pharmacol Therap 20:21.
221:686.
McGuirk, SM. 1991. Treatment of cardiovascular disease in
Dowling PM, Tyler, JW. 1994. Diagnosis and treatment of cattle. Appl Pharmacol Therap 7:729.
bacterial endocarditis in cattle. J Am Vet Med Assoc
204:1013. Moon HW, et al. 1982 Attempted chemopophylaxis of
cryptosporidiosis in calves. Vet Rec 110:181.
Dueger EL, et al. 1999. Efficacy of florfenicol in the treatment
of experimentally induced infectious bovine keratocon- Moore DA, et al. 2003. Prophylactic use of decoquinate for
junctivitis. Am J Vet Res 60:960. infections with Cryptosporidium parvum in experimen-
tally challenged neonatal calves. J Am Vet Med Assoc
Duran SP, et al. 1991. Comparative in-vitro susceptibility of 223:839.
Bacteriodes and Fusobacterium isolated from footrot in sheep
to 28 antimicrobial agents. J Vet Pharmacol Therap 14:185. Mundt HC, et al. 2003. Efficacy of toltrazuril against artificial
infections with Eimeria bovis in calves. Parasitol Res 90
Suppl 3: S166.

518 Section IV. Antimicrobial Drug Use in Selected Animal Species

Naciri MR, et al. 1993. The effect of halofuginone lactate on 2003. J Vet Diag Invest 17:436.
experimental Cryptosporidium parvum infections in Salmon SA, et al. 1996. In vitro activity of ceftiofur and its
calves. Vet Parasitol 45:199.
primary metabolite, desfuroylceftiofur, against organisms
Odendall MW, et al. 1990. The antibiotic sensitivity patterns of veterinary importance. J Vet Diag Invest 8:332.
of Bacillus anthracis isolated from the Kruger National Samitz EM, et al. 1996. In vitro susceptibilities of selected
Park. J Vet Res 58:17. obligate anaerobic bacteria obtained from bovine and
equine sources to ceftiofur. J Vet Diag Invest 8:121.
Piriz Duran S, et al. 1990 Susceptibilities of Bacteroides and Sanyal PK, et al. 1985. Chemotherapeutic effects of sulphad-
Fusobacterium spp. from foot rot in goats to 10 beta-lactam imidine, amprolium, halofuginone and chloroquine
antibiotics. Antimicrob Agents Chemother 34:657. phosphate in experimental Eimeria bareillyi coccidiosis of
buffaloes. Vet Parasitol 17:117.
Redman DR, Fox JE. 1994. The effect of varying levels of Sasaki Y, et al. 2001. Tetracycline-resistance genes of Clostridium
DECCOX on experimental cryptosporidia infections in perfringens, Clostridium septicum and Clostridium sordellii
Holstein bull calves. Proceedings, 26th Annual American isolated from cattle affected with malignant edema.
Association of Bovine Practitioners Conference, p. 157. Vet Micro 83:61.
Tripathi D, et al. 2001. Serodiagnosis and treatment of listeri-
Rehg JE. 1991. Activity of azithromycin against Cryptosporidia osis in repeat breeder cattle. Indian J Anim Sci 71:3.
in immunosuppressed rats. J Infect Dis 163:1293. Villacorta I, et al. 1991. Efficacy of halofuginone lactate against
cryptosporidium parvum in calves. Antimicrob Agents
Rings DM, Rings MB. 1996. Managing Cryptosporidium and Chemother 35:283.
Giardia infections in domestic ruminants. Vet Med 12:1125. Zielinski GC, et al. 1999. Efficacy of different dosage levels and
routes of inoculation of tilmicosin in a natural outbreak of
Roby TO. 1972. Elimination of the carrier state of bovine infectious bovine keratoconjunctivitis. Proceedings of the
anaplasmosis with imidocarb. Am J Vet Res 33:1931. 32nd Annual Convention of the American Association of
Bovine Practitioners 32:261.
Rosenbusch RF. 1998. Antibiotic Susceptibility of Mycoplasma
bovis Strains Recovered from Mycoplasmal Pneumonia
and Arthritis in Feedlot Cattle. AS leaflet R1548. 1998 Beef
Research Report—Iowa State University.

Rosenbusch RF, et al. 2005. In vitro antimicrobial inhibition
profiles of Mycoplasma bovis isolates recently recovered
from various regions of the United States from 2002 to

Antimicrobial Drug Use in Mastitis 30

Sarah Wagner and Ron Erskine

Introduction Mastitis During Lactation

The most common use of antimicrobial drugs on Cow Factors
dairy farms is to treat mastitis (Mitchell et al., 1998).
The expenses associated with mastitis (decreased milk A number of questions should be asked about the
production, decreased milk quality, drug costs, and affected cow before deciding how or even whether to
discarded milk) may be considerable, and have led initiate treatment of a case of mastitis. Depending on
many dairy producers to implement management cow factors, one may decide to treat the mastitis using
programs focused on mastitis prevention. Money a label-prescribed or extra-label protocol, or it may be
spent on an effective protocol for prevention of masti- more rational not to treat the mastitis, either because
tis is likely to lead to an overall financial benefit to the treatment is unnecessary or because treatment is
dairy. On a farm that is experiencing high somatic cell unlikely to result in resolution of clinical signs. Risk
counts, high rates of clinical mastitis, high levels of factors that have been found to decrease therapeutic
subclinical mastitis, or all of these, investigation into efficacy include increasing cow age, high SCC before
the reason for the problem, followed by development treatment, long duration of infection, multiple infected
and implementation of a program to alleviate the quarters, and infections caused by Staphylococcus aureus
cause and to prevent new occurrence, is recom- (Deluyker et al., 2005; Barkema et al., 2006; Bradley and
mended. Treatment alone is unlikely to solve herd- Green, 2009; Pinzon-Sanchez and Ruegg, 2011). In par-
level mastitis problems. ticular, chronic infections are likely to have poor thera-
peutic outcomes and may require extended duration of
Even on well-managed farms with mastitis antimicrobial therapy (Owens and Nickerson, 1990;
prevention protocols in place, treatment of clinical Oliver et al., 2004).
mastitis may sometimes be desirable. Subclinical
mastitis may be detected through a combination of Questions to ask before treatment is instituted
individual cow Somatic Cell Counts (SCCs) as meas- include:
ured by DHI testing or the California Mastitis Test
(CMT), and microbial culture of milk samples. 1. Is this a new case of mastitis or a relapse? Repeated
Although the discussion presented here is addressed treatment of a recurrent case of mastitis is fre-
to clinical cases of mastitis, the principles described quently unrewarding. If a recurrent case of mastitis
are also generally applicable to the treatment of is to be treated, the therapeutic regimen should be
subclinical mastitis. more extensive than what would be used for a mild,
acute case.

Antimicrobial Therapy in Veterinary Medicine, Fifth Edition. Edited by Steeve Giguère, John F. Prescott and Patricia M. Dowling.
© 2013 John Wiley & Sons, Inc. Published 2013 by John Wiley & Sons, Inc.

519

520 Section IV. Antimicrobial Drug Use in Selected Animal Species

2. How severe is it? A case of mastitis in a cow that has Table 30.1. Common mastitis pathogens unlikely to
become systemically ill (septic/toxic), will require a respond to antimicrobial drug treatment.
therapeutic protocol that includes systemic antibi-
otic therapy, intramammary therapy, supportive Arcanobacterium pyogenes
therapy and closer monitoring than a case in which Bacillus spp.
clinical signs are limited to the udder and milk Mycobacterium spp.
(Erskine et al., 2002). Mycoplasma bovis
Nocardia spp.
3. How many quarters are affected? The expense and Pasteurella spp.
the likelihood of treatment failure increase as the Proteus spp.
number of affected quarters increases. Prototheca spp. (algae)
Pseudomonas spp.
4. What is the cow’s stage of lactation? For a cow in late Serratia spp.
lactation, economic and therapeutic advantages may Yeasts (e.g., Candida spp.; antibiotic treatment will delay spontaneous
be gained by treating the cow simultaneously with cure)
drying-off.
The Gram-negative coliform organisms (Escherichia
5. Does the cow have other health problems? It has been coli, Enterobacter spp., Klebsiella spp.) are variable in
established that the likelihood of a cow developing their clinical expression and response to antimicrobial
mastitis is increased by the presence of other health therapy. Infections with coliform organisms may cause
problems such as ketosis and hypocalcemia (Kremer mild or no clinical signs and occasionally resolve
et al., 1993). It is reasonable to expect, therefore, that on  their own, but they may also cause severe, life-
the likelihood of successful therapy of mastitis may threatening illness or chronic infections. As with other
be decreased in cows with concurrent illnesses. pathogens, treatment decisions should be based on the
severity of disease and chronicity of infection; mild
Pathogen Factors acute infections may resolve with no therapy or limited
therapy. Recent work has demonstrated that treatment
Microbial culture of mastitis infections is an invaluable of mild or moderate clinical mastitis due to E. coli
aid in determining whether to initiate drug therapy, and or Klebsiella spp. with intramammary ceftiofur signifi-
if so, what approach to use. Infections with certain path- cantly improves the cure rate when compared to
ogens are likely to respond to antimicrobial drug ther- untreated controls (Schukken et al., 2011). Chronic
apy, while some pathogens may or may not respond to infections may require longer term, possibly extra-label
antimicrobial therapy. Some infections are likely to therapy, and severely ill cows will require supportive
resolve without any treatment. Common mastitis patho- care in addition to treatment with antimicrobial drugs.
gens that are likely to be unresponsive to antimicrobial
therapy are listed in Table 30.1. A brief overview of some Mycoplasma bovis is a unique mastitis pathogen.
other commonly encountered pathogens follows. Mastitis caused by Mycoplasma may occasionally resolve
without treatment, but antimicrobial therapy will not
Streptococcus agalactiae is a contagious mastitis path- affect the outcome (Gonzalez and Wilson, 2003).
ogen. It is considered highly responsive to therapy with
nearly any antimicrobial drug. Selecting an Antimicrobial Drug

Chronicity decreases the responsiveness of Staphylo- Intramammary Antimicrobial Drug Use
coccus aureus infection to antimicrobial therapy. A new
case in one quarter of a young cow is more likely to After cow and pathogen factors have been weighed and
respond to appropriate therapy than one or more quarters the decision has been made to treat a case of mastitis,
chronically infecting an older cow (Owens and Nickerson, a  suitable therapeutic regimen must be designed.
1990). Other Staphylococcus species have shown better Components of a therapeutic regimen include the drug
response to therapy (Owens et al., 1997). Extra-label
extension of the duration of therapy may increase the
likelihood of therapeutic success for chronic or recurrent
infections with Streptococcus or Staphylococcus species
(Morin et al., 1998; Oliver et al., 2004).

Chapter 30. Antimicrobial Drug Use in Mastitis 521

to be used and the drug dose, route of administration, The drug is inactive against the Enterobacteriaceae and
frequency of administration, duration of use, and meat resistance by staphylococci is likely to be common.
and milk withholding times. For mild to moderate
mastitis (abnormal milk with or without mammary Amoxicillin and hetacillin are aminopenicillins with
swelling), antibiotic therapy is usually administered similar spectrum of activity. The aminopenicillins are
by  the intramammary route, if it is administered at active against bacteria susceptible to penicillin G, as well
all.  Table  30.2 lists antimicrobial drug preparations as some Enterobacteriaceae such as E. coli. Many E. coli
approved by the U.S. Food and Drug Administration isolates are now resistant to the aminopenicillins through
(FDA) for intramammary administration to lactating beta-lactamases (chapters 8 and 10). Combination with a
dairy cows. There are eight antimicrobial drugs availa- beta-lactamase inhibitor such as clavulanic acid (chapter
ble for intramammary use in the United States: amoxi- 10) is not available for intramammary administration.
cillin, ceftiofur, cephapirin, cloxacillin, erythromycin,
hetacillin, penicillin, and pirlimycin. Cloxacillin is a penicillinase-resistant penicillin active
against penicillinase-producing S. aureus strains resist-
Intramammary use of drugs or preparations not spe- ant to the natural penicillins and aminopenicillins but is
cifically manufactured for intramammary administra- less active against other penicillin-sensitive organisms
tion is not recommended; such substances may be (chapter 8).
irritating to udder tissues and promote inflammation.
In addition, compounded preparations are at risk for Cephapirin is a first-generation cephalosporin drug
contamination with infectious pathogens, and milk and generally active against staphylococci and streptococci,
meat withholding times recommended for other routes sometimes against Enterobacteriaceae such as E. coli
of administration are likely to be inaccurate for and Klebsiella spp. but not against Enterococcus spp.
intramammary administration. It is also advised not to “Third-generation” cephalosporins such as ceftiofur are
use 2 different antimicrobial preparations simultane- less active than first-generation cephalosporins against
ously in one quarter, since interactions between the two Gram-positive cocci but more active against the
drugs may decrease efficacy. For example, macrolides Enterobacteriaceae (chapter 9).
and lincosamides bind at such close sites on the bacte-
rial ribosome that when they are administered simulta- The prognosis for resolution of the intramammary
neously, they compete for binding and the net effect infection may be poor even when a pathogen is consid-
of  the combination of the two drugs is not additive. ered to be within the spectrum of activity of an antimi-
Consequently, simultaneous use of the macrolide drug crobial drug. For example, Pasteurella spp. are within
erythromycin and the lincosamide drug pirlimycin, the spectrum of activity of several drugs available for
both of which are available in formulations for intramammary administration, yet the prognosis for
intramammary use, would not provide additional ther- resolution of mastitis caused by Pasteurella is always
apeutic benefit and might actually reduce efficacy as poor (National Mastitis Council, 1999).
compared to either drug alone.
All of the drugs currently available as intramammary
Spectrum of activity is a key consideration when preparations are time-dependent inhibitors of bacterial
selecting an antimicrobial drug for intramammary ther- growth (chapter 5). From a pharmacodynamic stand-
apy of mastitis. Erythromycin, a macrolide, and pirlimy- point, efficacy is maximized by keeping the concentra-
cin, a lincosamide, are the only drugs available as tion of drug at the site of infection above the level
intramammary preparations that are not members of necessary to inhibit microbial growth (minimum inhib-
the beta-lactams. Both macrolide and lincosamide drugs itory concentration; MIC) as long as possible between
have primarily Gram-positive antimicrobial spectra, doses of the drug. The drug concentration should be
without activity against coliform mastitis pathogens. above the MIC for at least half the dosing interval for
Gram-positive pathogens and for the entirety of the dos-
One of the earliest beta-lactam drugs to be developed, ing interval for Gram-negative pathogens (chapter 5).
benzathine penicillin G, is available for intramammary
administration. This drug is active against many strep- Once the MIC of the drug is achieved at the site of
tococci and non-penicillinase-producing staphylococci. infection, increased drug concentrations above the MIC
are unlikely to improve efficacy for those drugs available
as intramammary preparations. Maintaining the con-
centration at 25% greater than MIC for a certain length

Table 30.2. Intramammary preparations available for lactating cows in the United States.

Drug Name and Class Product Name Label Regimen and Indications Other Label Claims

Amoxicillin Amoxi-Mast 3 treatments at 12-hour intervals Susceptibility shown by E. coli in vitro
Aminopenicillin (Merck Animal Health) Most Enterobacter, Klebsiella, and
Subclinical S. aureus mastitis
Ceftiofur Spectramast Pseudomonas resistant
Subclinical S. agalactiae mastitis
third-generation cephalosporin (Zoetis) 2–8 treatments at 24-hour intervals Shown to be efficacious against susceptible strains of
Clinical coagulase-negative Staphylococcus S. agalactiae and S. aureus
Cephapirin Today, Cefa-lak
mastitis There is laboratory evidence that indicates cloxacillin is
first-generation cephalosporin (Fort Dodge Animal Health) Clinical S. dysgalactiae mastitis resistant to destruction by penicillinase-producing
Clinical E. coli mastitis organisms
Cloxacillin Dariclox 2 treatments at a 12-hour interval
1Works against both acute and chronic cases
penicillin (penicillinase-resistant) (Merck Animal Health) Mastitis in lactating cows
3 treatments at 12-hour intervals Shown to be efficacious in treatment of mastitis in lactating
Erythromycin 1Gallimycin-36 (Agri-Labs) cows caused by susceptible strains of S. agalactiae,
macrolide 2Gallimycin®-36 (Durvet) Clinical S. aureus mastitis S. dysgalactiae, S. aureus, and E. coli
(non-penicillinase producing strains)
Hetacillin Hetacin-K Intramammary Has been proven effective only against Staphylococcus
Aminopenicillin Infusion Clinical S. agalactiae mastitis species such as S. aureus and Streptococcus species
(Fort Dodge Animal Health) 3 treatments at 12-hour intervals such as S. dysgalactiae and S. uberis
Penicillin
penicillin Masti-Clear Clinical S. aureus mastitis
(G.C. Hanford) Clinical S. agalactiae mastitis
Pirlimycin Clinical S. dysgalactiae mastitis
Lincosamide Pirsue Aqueous Gel Clinical S. uberis mastitis
(Zoetis)
3 treatments at 24-hour intervals
Acute, chronic, or subclinical mastitis

Not more than 3 treatments at 12-hour intervals

Clinical S. agalactiae mastitis
Clinical S. dysgalactiae mastitis
Clinical S. uberis mastitis
2 treatments at a-24 hour interval
Clinical and subclinical mastitis

Note: Although every effort has been made to ensure that the information presented here is accurate and complete, the authors cannot bear responsibility for any errors or omissions.
Readers are advised to contact drug manufacturers and/or read package inserts for complete information about the products listed herein.

Chapter 30. Antimicrobial Drug Use in Mastitis 523

of time should be as effective as maintaining the drug negative bacterial etiology. For mastitis due to coliform
level at 100% above the MIC for the same time period. bacterial infection, research suggests that by the time
Consequently, if one wishes to prescribe extra-label clinical signs appear, bacterial numbers in the mam-
therapy for a case of mastitis that may be difficult to mary gland have already peaked (Erskine et al., 1989).
resolve using label dosing regimens, extending the dura- Consequently, a rational approach to therapy of severe
tion of therapy (provided drug concentrations are main- acute mastitis would be to address the possibility of coli-
tained above the MIC between doses) is expected to be form bacteremia by using a systemic drug with a
more effective than giving a higher dose at each treat- spectrum of activity including Gram-negative patho-
ment time without extending the duration of therapy. gens, combined with an intramammary preparation that
The only exception to this rule would be if the drug is is active against Gram-positive pathogens.
cleared so slowly that drug accumulation following a
higher dose results in the drug concentration remaining In the United States, any systemic use of an antimi-
above MIC for additional dosing intervals. Available crobial drug as a therapy for mastitis is an extra-label
mastitis preparations are unlikely to accumulate in the use, as there is currently no antimicrobial drug approved
mammary gland to the point that administering two by the FDA for systemic administration for mastitis.
tubes will result in extension of therapeutic concentra- Extra-label drug use in food animals requires extending
tions for one or more additional dosing intervals. meat and milk withholding periods. Drugs available for
use in lactating dairy cattle, with appropriate spectra of
Regardless of the approach, it is critical that extra-label activity against coliform bacteria, include oxytetracy-
use of any drug in a food animal such as a dairy cow be cline, sulfadimethoxine, ampicillin, and amoxicillin.
accompanied by extended milk and meat withholding
times. For help in setting extended withholding times Although tetracyclines have both Gram-positive and
following extra-label use, the Food Animal Residue Gram-negative activity in their spectrum of activity,
Avoidance Databank provides free assistance. They can be some coliforms and Staphylococcus species may not be
reached in the United States by dialing 1-888-US-FARAD. susceptible (chapter 15). The use of sulfadimethoxine to
treat mastitis in a lactating cow is illegal in the United
Systemic Antimicrobial Drug Use States, as mastitis is not a labeled indication for the drug
and extra-label use of sulfonamides in lactating dairy
For acute mild to moderate mastitis, systemic antimi- cows is prohibited by the regulations codified in the
crobial therapy is not generally indicated or undertaken. Animal Medicinal Drug Use Clarification Act. Similarly
For severe cases of mastitis (those that involve systemic to the tetracyclines, resistance to sulfonamide drugs is
clinical signs such as fever or depression in addition to now widespread. The aminopenicillins have a spectrum
abnormal milk and udder swelling), systemic adminis- of activity that includes the Enterobacteriaceae but
tration of antimicrobial drugs is an appropriate part of resistance is also widespread (chapters 8 and 10).
therapy. Supportive care by administration of fluids and
other methods is also critical in such cases, and has been Ceftiofur, a third-generation cephalosporin, also has
discussed elsewhere (Morin, 2004). Mastitis with sys- a spectrum of activity that includes coliform mastitis
temic illness is commonly caused by coliform organisms pathogens, and it is relatively resistant to beta-lactamases
such as E. coli and Klebsiella spp. An investigation of produced by those bacteria. When used in combina-
naturally occurring cases of coliform mastitis with sys- tion  with intramammary antimicrobial drugs, anti-
temic illness has demonstrated that 42% of cows with inflammatory drugs, and other supportive therapy, the
severe illness due to coliform mastitis had concurrent addition of intramuscular ceftiofur to the treatment
bacteremia (Wenz et al., 2001) Although systemic illness regimen for severe acute mastitis decreased the likeli-
due to mastitis is frequently caused by Gram-negative hood of a cow subsequently dying or being culled
pathogens, it may also be caused by Gram-positive path- (Erskine et al., 2002). In the United States, the extra-
ogens such as S. aureus (Erskine et al., 2002). Because label use of cephalosporins has recently been banned in
microbial culture generally takes 24 hours to yield a pre- food animals, with the exception of use of cephapirin
liminary result, therapy of severe mastitis must initially mastitis preparations (chapter 9; FDA, 2012).
be based on the possibility of a Gram-positive or Gram-
Questions frequently arise about florfenicol and the
lincosamide drug tilmicosin for systemic use against

524 Section IV. Antimicrobial Drug Use in Selected Animal Species

coliform mastitis, since they are active against the Gram- bility testing for combinations of drug, pathogen,
negative pathogens that cause respiratory disease in cat- species, and/or disease that may or may not have vali-
tle. These drugs are not, however, good choices for dated breakpoints; when there are no validated break-
Gram-negative septicemia associated with severe masti- points, breakpoints are used that are derived from data
tis. Although the Gram-negative respiratory pathogens about different pathogens, species, and/or diseases. This
Mannheimia and Pasteurella may be susceptible to these extrapolation should be borne in mind when interpret-
drugs, the Gram-negative coliform organisms that com- ing the results of susceptibility testing. Currently, vali-
monly cause mastitis are either entirely resistant to these dated breakpoints are available for two preparations for
drugs, or the drug concentration required to inhibit intramammary treatment of lactating cows (ceftiofur,
their growth is so high that administration of an impos- pirlimycin) and one intramammary preparation for
sibly high dose of these drugs would be necessary to treatment of dry cows (penicillin and novibiocin).
obtain any benefit.
In the Kirby-Bauer method of susceptibility testing, an
Antimicrobial Susceptibility antibiotic disk containing a known amount of each drug
Testing and Mastitis under test is placed onto an agar gel plate inoculated with
the pathogen under test. The area around the disk where
Antimicrobial susceptibility testing is a way of quantify- microbial growth is inhibited is called the zone of inhibi-
ing the interaction between microbes and antimicrobial tion, and the diameter of this zone is used as the break-
drugs in the laboratory (chapter 2). Susceptibility testing point to classify microbes as susceptible, intermediate, or
may be performed using serial dilution or agar gel diffu- resistant to the drugs under test (chapter 2). Proper exe-
sion (Kirby-Bauer) methods. For the serial dilution cution of either method of susceptibility testing requires
method, the lowest concentration of each drug that skill, training, attention to detail, and quality control
inhibits microbial growth is the MIC. This may not be measures. For accurate results, it is recommended that
the same as the concentration of drug necessary to steri- samples for susceptibility testing be submitted to a vet-
lize the culture, called the minimum bactericidal con- erinary diagnostic laboratory that is accredited, for
centration (MBC). Using the MIC instead of the MBC to example in the United States by the American Association
draw conclusions about antimicrobial efficacy is con- of Veterinary Laboratory Diagnosticians.
sistent with the therapeutic goal: to assist the cow’s own
immune system in clearing the infection. Even when properly executed, susceptibility testing
has limited value as an aid to therapeutic decision-
Breakpoints are used to classify MICs as indicators of making in bovine mastitis. The relationship between
microbial susceptibility or resistance. For many combi- susceptibility as determined by laboratory susceptibility
nations of drug and microbe, susceptibility testing testing and the outcome of clinical cases of mastitis
results are typically reported as “intermediate,” “suscep- appears to be inconsistent at best. Many publications
tible,” or “resistant” (chapter 2). Susceptibility testing is have described patterns of susceptibility seen in the labo-
based on the theory that a finding of susceptibility in the ratory, but several reports have determined little predic-
laboratory indicates that a favorable outcome of antimi- tive value of susceptibility testing for clinical outcomes of
crobial drug therapy is likely, while a finding of resist- mastitis (Owens et al., 1997; Constable and Morin, 2003;
ance in the laboratory is associated with a poor prognosis Hoe and Ruegg, 2005; Apparao et al., 2009.) The issue is
for therapeutic success. further complicated by the use of variable outcomes in
trials assessing resolution of clinical mastitis: the achieve-
Validated veterinary breakpoints are specific for a ment of a cure may defined as resolution of clinical signs,
drug, treatment regimen, pathogen, affected species, or one or more negative microbial cultures, or some
and disease condition. Validated veterinary breakpoints combination of these outcomes. A more practical
are developed by a committee of experts in veterinary approach to assessing whether a mastitis therapy works
microbiology and pharmacology in cooperation with is to design farm protocols for treatment of clinical mas-
the Clinical and Laboratory Standards Institute (chapter titis with selected antimicrobial drugs, then periodically
2). Veterinary diagnostic laboratories provide suscepti- evaluate the protocols for the efficacy of the selected
drugs in achieving the farm’s therapeutic objectives.

Chapter 30. Antimicrobial Drug Use in Mastitis 525

Herd-Based Therapeutic Protocols provides. On-farm microbial milk culture requires time,
training, and organization, but the financial rewards to a
Modern management strategies frequently involve a farm may be significant. No growth results are typical
standardized approach to mastitis prevention and ther- obtained for 25–50% of all cases of clinical mastitis, and
apy. Key benefits to standardizing the farm approach to antimicrobial therapy is probably not indicated in such
mastitis therapy are that treatment decisions are made cases (Hess et al., 2003). Decreasing the number of
in advance instead of “cow-side” and that a consistent treated cows on farms that have previously treated every
approach is developed. This results in simpler, less time case of mastitis may result in financial benefit to the
consuming tasks on the farm, from deciding whether or farm, even after the cost of conducting microbial culture
not to treat a case of mastitis to selecting a drug and of each new case is factored in. Some farms have also
regimen and assigning an appropriate withholding time elected not to treat cows with Gram-negative pathogens
for milk and meat from treated cows. Moreover, when isolated on milk culture; this practice may reduce the
treatments are standardized and good records are kept, percentage of clinical mastitis cases treated to less than
evaluating whether or not a given treatment is successful half of all new cases, depending on the predominant
on the farm is simplified. pathogens on the farm. If this approach is taken, it is
imperative that it be undertaken in the knowledge that
Microbial culture of clinical mastitis cases can be Gram-negative mastitis, although it will frequently
boon to designing a farm protocol for treatment of clini- resolve on its own, may also develop into a chronic
cal mastitis. By culturing all new cases of mastitis, the infection or severe illness. In addition, as mentioned
organisms that are causing clinical mastitis on the farm above, recently published research has demonstrated
can be identified and an appropriate therapeutic regi- that intramammary antimicrobial drug treatment of
men can be developed. In addition, microbial culture clinical mastitis caused by E. coli and Klebsiella spp. sig-
results can be used to direct efforts at prevention to nificantly improves the cure rate for such cases
appropriate areas. Even if microbiological culture is not (Schukken et al., 2011).
performed on every case of mastitis on a particular
farm, periodic cultures are still useful as a guide to the Microbial culture of milk is a practical tool to identify
development of treatment strategies and protocols. pathogens and design specific therapeutic regimens for
Culture of chronic mastitis cases is also an irreplaceable mastitis treatment. A recent multistate study found a
aid to determining whether a chronic case of mastitis reduction in antimicrobial usage when culture-based
might be resolved by antimicrobial therapy, or if the treatments replaced empirical therapy (Lago et al.,
pathogen causing the mastitis is not amenable to ther- 2011). Whichever culture-based treatment protocol is
apy and the greatest financial benefit to the farm would adopted, it is prudent to save pretreatment milk samples
be not to treat. in the freezer for submission to a diagnostic laboratory
for definitive organism identification in the event that
Some farms have incorporated routine culture of the case of mastitis does not resolve.
every case of mastitis into their treatment protocol.
Farms can use a simple classification system for all cases An example of a herd mastitis treatment protocol is
of mastitis following a 24-hour milk culture of each case given in Figure 30.1.
using “biplates” which are petri dishes with MacConkey’s
agar gel, which selects for Gram-negative bacterial Antimicrobial Therapy of Dry Cows
growth, on one half, and blood agar gel, which is non-
selective, or Factor medium, which is selective for The dry (non-lactating) period of the lactation cycle is a
Gram-positive bacterial growth, on the other half. Using critical time for dairy cattle. The major proportion of
these culture media, each case of mastitis may be classi- calf-growth occurs during this time. Balanced nutrition,
fied as no growth, Gram-positive growth, Gram- especially in the last 2–3 weeks before calving, is essential
negative growth, or contaminated sample, and treatment for prevention of post-parturient metabolic disease. The
regimens may be designed for each possibility. udder undergoes marked biochemical, cellular and
Mycoplasma spp. require special media and more strin- immunological changes during the dry period. Involution
gent incubation conditions than this simple approach

526 Section IV. Antimicrobial Drug Use in Selected Animal Species

Does the cow have abnormal milk?
Yes No Stop here.
Take a milk sample from the affected quarter using aseptic technique and write the cow
number, date, AM or PM, and quarter on the sample container.

Is the cow acting sick / depressed? Are her eyes sunken? Does she have diarrhea?
Is she down? Does she have a temperature over 104° F?

Yes to any No to all

Treat with intramammary and Begin microbial culture of milk
systemic antibiotics (farm sample. Incubate for 24 hours.
choice), oral and intravenous
fluids, and anti-inflammatory Check culture after 24 hours and
drugs. Monitor closely. record result.

Begin microbial culture of milk No growth or Gram-positive:
sample. Incubate for 24 hours. contaminated: IMM treatment.
Do not treat.
Check culture in 24 hours,
modify treatment if necessary. Gram-negative:
Continue close monitoring and IMM treatment or not,
treatment. depending on farm protocol.

Recheck milk culture for microbial pathogen growth after 48 hours.
Record milk culture results, treatment administered, if any, and treatment outcome, so
that patterns of microbial etiology and treatment efficacy can be determined.

Figure 30.1. Herd mastitis treatment protocol.

of the mammary parenchyma begins 1–2 days after the greatest risk for new IMI in the lactation cycle of the cow.
end of lactation and continues for 10–14 days. During Once involution is complete, however, a more hostile
this time, the gland is particularly vulnerable to new immune environment for bacterial pathogens exists. The
intramammary infections (IMI). The periparturient most important defense against IMI, as with lactating
period and the early dry period constitute the times of cows, remains the teat canal. This barrier is enhanced

Chapter 30. Antimicrobial Drug Use in Mastitis 527

during the dry period by the formation of a keratin plug. dry period, IMI during the dry period, and clinical mas-
Additionally, during the dry period the mammary gland titis in early lactation, as compared to herds that treat all
contains increased numbers of macrophages and lym- cows at dry-off (Berry and Hillerton, 2002) Additionally,
phocytes and higher concentrations of complement and a recent review of the literature determined that, to date,
immunoglobulins that can help orchestrate more effi- no evidence exists that supports the concept of emerg-
cient phagocytosis. Lactoferrin, a potent iron chelating ing antimicrobial resistance in mastitis pathogens
protein, also markedly increases in dry cow secretions, (Erskine et al., 2004). Thus, the evidence suggests that,
helping to inhibit growth of Gram-negative bacteria, par- for most herds, intramammary antimicrobial drug treat-
ticularly E. coli. Consequently, the dry period is an ideal ment of all dry cows is preferred over selective dry cow
time to attain synergy between antibacterial therapy and therapy. In addition, use of an internal teat sealant at dry
immune function to eliminate pathogens from the gland, off in conjunction with antimicrobial therapy reduced
without incurring the extensive milk withholding costs new intramammary infections during the dry period by
typical of lactating cow therapy. 30%, and clinical mastitis in the first 60 days in milk by
33%, as compared to antimicrobial use alone (Godden
Intramammary administration of antibacterial drugs et al., 2003).
at the end of lactation has been a standard practice in
dairy mastitis management for over 35 years. Cure rates As with therapy during lactation, systemic antimicro-
for IMI caused by all Gram-positive cocci (those IMI bial drug administration as an adjunct to intramam-
that existed prior to the dry period, but were not detected mary administration of dry cow therapy has been
following calving) have been reported in numerous investigated. Subcutaneous norfloxacin nicotinate
studies to average 75% (Nickerson et al., 1999). However, administered at the start of the dry period achieved a
the efficacy of conventional dry cow treatments in elim- better cure rate and lower new infection rate over the
inating chronic IMI is realistically closer to 15–30% (Sol dry period for S. aureus infections, as compared to
et al., 1990; Erskine et al., 1994). Most commercial dry untreated cows and cows administered intramammary
cow products have little or no activity against Gram- cephapirin benzathine preparations (Soback et al.,
negative pathogens, so that cure rates for coliform 1990). However, the systemic administration of tilmi-
organisms are low. In one study, cows treated with a cosin resulted in lower drug concentrations in milk
product with significant activity against Gram-negative and  lower cure rates for S. aureus mastitis than
bacteria had decreased clinical coliform mastitis during intramammary administration (Nickerson et al., 1999).
the dry period and early lactation as compared to as Additionally, cows administered intramuscular oxytet-
compared to cows treated with cloxacillin (Bradley and racycline and intramammary cephapirin did not have
Green, 2001). better cure rates for quarters infected with S. aureus than
cows treated with cephapirin alone (Erskine et al., 1994).
Because of concern regarding overuse of antibacterial Clinical failure in these trials reflects the importance
drugs and potential effects on antimicrobial resistance of  designing a therapeutic regimen that will main-
of bacteria, selective dry cow therapy (treatment of tain  an  effective concentration of an appropriate drug
infected cows only) versus total or blanket dry cow ther- at  the  site of infection for an adequate duration, and
apy (treatment of all cows) had been discussed. Decisions the  poor  prognosis of chronic infections. Systemic
should be made on an individual herd basis, and results therapy should be approached judiciously, using sound
monitored to determine the success of a dry cow masti- pharmacological principles.
tis program based on numbers of new IMI during the
dry period, cures of existing infections, and effect on the In summary, the important considerations for dry
rate of clinical mastitis, particularly in early lactation. cow treatment include: (1) commercial dry cow treat-
An important role of dry cow therapy in addition to ments are generally effective against Gram-positive
eliminating existing IMI is the prevention of new IMI. cocci in preventing and eliminating IMI; (2) because of
Intramammary infusion of tilmicosin reduced new enhanced immune function and decreased discarded
infection rates by greater than 33% in a Canadian study milk costs, dry cows should be preferentially treated as
(Dingwell et al., 2002). Selective dry cow therapy can compared to lactating cows for subclinical and chronic
result in herd-wide increases in clinical mastitis in the IMI; (3) most commercial intramammary products

528 Section IV. Antimicrobial Drug Use in Selected Animal Species

have little efficacy against Gram-negative pathogens; the dry and early-lactation periods in dairy cows when
and (4) treatment of more chronic IMI may include used with a dry cow intramammary antibiotic. J Dairy Sci
systemic drug regimens, preferably with antimicrobials 86:3899.
that distribute well in mammary tissue, such as tetracy- Gonzalez RN, Wilson DJ. 2003. Mycoplasmal mastitis in dairy
clines and macrolides. herds. Vet Clin North Am Food Anim Pract 19:199.
Hess JL, et al. 2003. Rethinking clinical mastitis therapy. Proc
Bibliography 42nd Ann Meet Nat Mastitis Coun, Fort Worth, TX.
Hoe FG, Ruegg PL. 2005. Relationship between antimicrobial
Apparao MD, et al. 2009. Relationship between in vitro sus- susceptibility of clinical mastitis pathogens and treatment
ceptibility test results and treatment outcomes for gram- outcome in cows. J Am Vet Med Assoc 227:1461.
positive mastitis pathogens following treatment with Kremer WDJ, et al. 1993. Severity of experimental Escherichia
cephapirin sodium. J Dairy Sci 92:2589. coli mastitis in ketonemic and nonketonemic dairy cows.
J Dairy Sci 76:3428.
Barkema HW, et al. 2006. Invited review: the role of cow, Lago A, et al. 2011. The selective treatment of clinical mastitis
pathogen, and treatment regimen in the therapeutic based on on-farm culture results: I. Effects on antibiotic
success of bovine Staphylococcus aureus mastitis. J Dairy use, milk withholding time, and short-term clinical and
Sci 89:1877. bacteriological outcomes. J Dairy Sci 94:4441.
Mitchell JM, et al. 1998. Antimicrobial drug residues in milk
Berry EA, Hillerton JE. 2002. The effect of selective dry cow and meat: causes, concerns, prevalence, regulations, tests,
treatment on new intramammary infections. J Dairy Sci and test performance. J Food Protect 61:742.
85:2512. Morin DE. 2004. Beyond antibiotics—what else can we do?
Proc 43rd Ann Meet Nat Mastitis Coun, Charlotte, NC.
Bradley AJ, Green MJ. 2001. An investigation of the impact of Morin DE, et al. 1998. Comparison of antibiotic administra-
intramammary antibiotic dry cow therapy on clinical coli- tion in conjunction with supportive measures versus
form mastitis. J Dairy Sci 84:1632. supportive measures alone for treatment of dairy cows
with clinical mastitis. J Am Vet Med Assoc 213:676.
Bradley AJ, Green MJ. 2009. Factors affecting cure when National Mastitis Council. 1999. Laboratory Handbook
treating bovine clinical mastitis with cephalosporin-based on  Bovine Mastitis. Madison, WI: National Mastitis
intramammary preparations. J Dairy Sci 92:1941. Council Inc.
Nickerson SC, et al. 1999. Comparison of tilmicosin and cep-
Constable PD, Morin DE. 2003. Treatment of clinical masti- hapirin as therapeutics for Staphyloccoccus aureus mastitis
tis: using antimicrobial susceptibility profiles for treatment at dry-off. J Dairy Sci 82:696.
decisions. Vet Clin North Am Food Anim Pract 19:139. Oliver SP, et al. 2004. Extended ceftiofur therapy for treat-
ment of experimentally-induced Streptococcus uberis mas-
Deluyker HA, et al. 2005. Factors affecting cure and somatic titis in lactating dairy cattle. J Dairy Sci 87:3322.
cell count after pirlimycin treatment of subclinical mastitis Owens WE, Nickerson SC. 1990. Treatment of Staphylococcus
in lactating cows. J Dairy Sci 88:604. aureus mastitis with penicillin and novobiocin: antibiotic
concentrations and bacteriologic status in milk and mam-
Dingwell RT, et al. 2002. The efficacy of intramammary tilm- mary tissue. J Dairy Sci 73:115.
icosin at drying-off, and other risk factors for the preven- Owens WE, et al. 1997. Comparison of success of antibiotic
tion of new intramammary infections during the dry therapy during lactation and results of antimicrobial
period. J Dairy Sci 85:3250. susceptibility tests for bovine mastitis. J Dairy Sci
80:313.
Erskine RJ, et al. 1989. Induction of Escherichia coli mastitis Pinzon-Sanchez C, Ruegg PL. 2011. Risk factors associated
in cows fed selenium-deficient or selenium-supplemented with short-term post-treatment outcomes of clinical mas-
diets. Am J Vet Res 50:2093. titis. J Dairy Sci 94:3397.
Schukken YH, et al. 2011. Randomized clinical trial to evalu-
Erskine RJ, et al. 1994. Efficacy of intramuscular oxytetracy- ate the efficacy of a 5-day ceftiofur hydrochloride
cline as a dry cow treatment for Staphylococcus aureus intramammary treatment on non-severe Gram-negative
mastitis. J Dairy Sci 77:3347. clinical mastitis. J Dairy Sci 94:6203.
Sol J, et al. 1990. Factors affecting the result of dry cow treat-
Erskine RJ, et al. 2002. Efficacy of systemic ceftiofur as a ment. Proc Int Symp Bovine Mastitis, p. 118.
therapy for severe clinical mastitis in dairy cattle. J Dairy Wenz JR, et al. 2001. Bacteremia associated with naturally
Sci 85:2571. occurring acute coliform mastitis in dairy cows. J Am Vet
Med Assoc 219:976.
Erskine RJ, et al. 2004. Bovine mastitis pathogens and trends
in resistance to antibacterial drugs. Proc 43rd Ann Meet
Nat Mastitis Coun, Charlotte, NC.

FDA. 2012. New animal drugs; Cephalosporin drugs; extral-
abel animal drug use; order of prohibition. Federal Register
77:735.

Godden S, et al. 2003. Effectiveness of an internal teat seal in
the prevention of new intramammary infections during

Antimicrobial Drug Use in 31
Sheep and Goats

Chris R. Clark

Although sheep and goats are important agricultural and Baird, 2011). Prudent antimicrobial use first
animals worldwide, they remain relatively minor species requires a tentative diagnosis followed by confirmation
within the North American market and many veterinar- of the etiological agent by microbiological culture and
ians will have had limited exposure to them. In the antimicrobial susceptibility testing before commencing
United States and Canada, there are few licensed veteri- therapy. However, collection of samples from sheep and
nary pharmaceutical products available for sheep and goats is not always feasible and even if samples are
goats. For sheep, there are a few approved antimicrobials obtained, results usually take at least 2–3 days to pro-
but there is only 1 antimicrobial approved for use in cess. So empirical therapy is common and should be
goats. Furthermore, sheep and goats are classed as sepa- determined by a thorough physical examination and a
rate species by the regulatory authorities. This means presumptive diagnosis, knowledge of the most common
that approved drugs are specifically licensed and with- pathogens, the expected antimicrobial susceptibility of
drawal times and maximum residue limits (MRLs) have those organisms, and the pharmacokinetics/pharmaco-
been set for each species. This situation creates a great dynamics of the antimicrobial in the species being
deal of confusion for veterinarians as well as sheep and treated. Tables 31.1 and 31.2 contain information to help
goat producers. Journal articles, textbooks, and the inter- make these decisions.
net provide accessible information from clinical trials
and dose regimens for a wide variety of antimicrobials Once an antimicrobial drug is selected, proper admin-
that are not licensed in North America. In many cases, istration is important. The label claim (when available)
the safety and efficacy of the drug is well documented should be followed closely for dose, frequency, route of
and the antimicrobial product is actually available in administration and dose volume. Any deviation from the
North America; it is just not licensed for sheep or goats. label constitutes extra-label drug use. For quality assur-
ance, it is also important to administer parenteral anti-
General Recommendations microbial drugs in a way that minimizes damage to
muscle tissues. Clean syringes and fresh needles should
Sheep and goats are not simply “small cows”; they react be used. The volume of drug per injection site should
differently to certain medications and suffer from differ- generally be limited to five milliliters or less. The subcu-
ent diseases. A good resource specific for the North taneous, oral or intravenous routes should be selected
American situation is Sheep and Goat Medicine (Pugh over the intramuscular route if possible. Intramuscular
injections should be given only in the neck. Subcutaneous
injections should be given in the neck also. Small volumes

Antimicrobial Therapy in Veterinary Medicine, Fifth Edition. Edited by Steeve Giguère, John F. Prescott and Patricia M. Dowling.
© 2013 John Wiley & Sons, Inc. Published 2013 by John Wiley & Sons, Inc.

529

Table 31.1. Antimicrobial drug selection for common conditions of sheep and goats.

Condition Species Affected Etiological Agent(s) Recommended Treatment Comments

Infectious abortion Chlamydophila abortus Tetracycline Prophylaxis in high-risk flocks: tetracycline in feed for 6–8 weeks prior to
Enzootic abortion of ewes Sheep and goats Oxytetracycline breeding at a dose of 200–400mg/head/day until lambed.
C. jejuni Tylosin
(EAE) C. fetus spp. fetus Outbreak: 400–500mg/head/day tetracycline in feed until lambing
Penicillin G-streptomycin; finished. Poor efficacy if placental damage already present.
Campylobacter abortion Sheep L. monocytogenes tetracycline
(Vibrionic) T. gondii Not recommended for dairy goats because of milk withdrawal.
S. typhimurium, S. abortus Oxytetracycline (resistance Vaccination or biosecurity should be considered.
Listeria abortion Sheep and goats commonly reported)
Toxoplasma abortion Sheep and goats ovis, S. montevideo, Outbreak or previous diagnosis: long-acting oxytetracycline at label
S. dublin Tylosin dosage starting 6–8 weeks before start of lambing every 10–14 days
Salmonella abortion Sheep and goats L. hardjo, L. pomona Sulfamethazine until finished.
C. burnetii Oxytetracycline
Leptospira abortion Sheep and goats Prophylaxis: injections of penicillin-streptomycin for 2–5 days.
Coxiellosis (Q fever) Sheep and goats Monensin Antimicrobial susceptibility patterns should be established from
Decoquinate any isolates. Vaccination in the face of an outbreak also very
successful.
IM or SC broad-spectrum
antimicrobials Injectable long-acting tetracycline to all animals at risk in the face of
an outbreak.
Penicillin G-streptomycin;
tetracyclines Mixed in feed at a dose of 15 mg/head/day from breeding to lambing.
Mixed in feed or premix to feed at a dose of 2 mg/ kg/day for last 14
Tetracycline; (fluoroquinolone
where permitted) weeks of gestation.
Often widespread by the time diagnosis is made. Requires culture and

susceptibility testing. Antimicrobials may not eliminate organism;
consider culling and environmental management.
Treat all pregnant animals at risk with injections.

Abortions are more common in goats than in sheep. Long-acting
injectable oxytetracycline (IM or SC) to all pregnant does every
10–14 days until kidded.

Watch withdrawal for milk in dairy goats.

Other infectious reproductive disorders

Metritis Sheep and goats Trueperella pyogenes, E. coli, Penicillin G; ceftiofur; Treat for 3–4 days after clinically normal. Uterine evacuation with
prostaglandins and tetanus vaccination should also be considered.
mixed anaerobes including broad-spectrum
Prophylaxis: low levels in feed in situations where rams intensively
Clostridium spp. antimicrobials managed, or injectable long-acting oxytetracycline (IM or SC).
Responds poorly to treatment.
Lamb epididymitis Sheep H. somni, A. seminis, Oxytetracycline
Remove from high-protein diet and treat locally with antibiotic
Corynebacterium ointments. May treat systemically for severe cases.

pseudotuberculosis

Enzootic posthitis Sheep and goats C. renale group Penicillin G; oxytetracycline

Brucella ovis ram Sheep Brucella ovis Oxytetracycline with 20 mg/ kg oxytetracycline at 3-day intervals for 5 treatments and
epididymitis dihydrostrepto-mycin 12.5 mg/ kg streptomycin 2 x/day for 7 days decreases shedding of
bacteria and improves semen quality but may not cure. Should
consider culling.

Infectious diseases of lambs and kids, systemic

Enterotoxemia/pulpy Sheep and goats C. perfringens type C Oral virginiamycin, penicillin G, Vaccinate all animals at risk. Withdraw carbohydrate source in diet,
and D
kidney or bacitracin give C&D antitoxin and a balanced electrolyte solution (BES)

parenterally.

Omphalophlebitis Sheep and goats T. pyogenes, E. coli, mixed Penicillin G; broad-spectrum Antibiotic therapy alone not often effective. Local drainage and
Watery mouth (lambs) Sheep anaerobes
antimicrobialsa treatment and possibly surgical removal should be considered.
Probable E. coli endotoxin
Oral amoxicillin; apramycin Prevention by ensuring clean environment and good colostrum

ingestion. Early prophylactic treatment with oral antibiotics.

Metabolic acidosis without Goats Unknown Broad-spectrum antimicrobials Isotonic bicarbonate solutions to correct acid-base deficit followed by

dehydration (kids) Anaplasma balanced electrolyte solution (BES).
phagocytophilum and/or
Tickborne fever (tick Sheep S. aureus Long-acting oxytetracycline At 1–3 weeks of age and repeated at 5–7 weeks, in addition to

pyemia) E. rhusiopathiae dipping with an acaricide at those times.

Erysipelothrix Sheep Enterotoxigenic E. coli Penicillin G Treat minimum of 3 days.
polyarthritis

Infectious diseases of lambs and kids, digestive

Colibacillosis Sheep and goats Broad-spectrum anti Appropriate diagnosis is necessary (culture and susceptibility testing),

microbials parenterally also treat with BES. Clean environment and adequate colostrum is

important. Consider vaccination. Resistance to antimicrobials is

common.

Salmonella dysentery Sheep and goats S. typhimurium and others Broad-spectrum antimicrobials Often poor efficacy due to unpredictable susceptibility patterns. May
Sheep and goats Clostridium spp.
Abomasitis/abomasal not eliminate carriers if host-adapted species.
hemorrhage Sheep and goats Eimeria spp.
Oral penicillins Rarely effective. Should treat symptomatically with antitoxins,
Coccidiosis
non-steroidal anti- inflammatory drugs, and BES. Use polyvalent

clostridial vaccine.

Monensin; lasalocid; Mixing should be done at a feed mill and all feeds pelleted. Some

decoquinate; salinomycin; products can be mixed with salt. Dose varies with feed

amprolium; or sulfonamides management. Artificially raised lambs/kids can be medicated via

milk replacer. Feed from 2 weeks of age until market age.

Ionophores toxic to horses and dogs.

Infectious conditions of lambs and kids, respiratory Tilmicosin; oxytetracycline; Long-acting oxytetracycline, tilmicosin, or florfenicol can be used as a
Pneumonic pasteurellosis Sheep and goats M. haemolytica, ceftiofur; florfenicol prophylaxis and during an outbreak therapeutically. Tilmicosin
should not be used in goats (therapeutic dose very close to toxic
P. multocida As with M. haemolytica dose). Ceftiofur for daily treatment of affected animals when meat
or milk withdrawal is an issue (e.g., market lambs close to
Pasteurella septicemia Sheep Bibersteinia trehalosi slaughter, lactating dairy sheep).

B. trehalosi shows more resistance and because the disease is
peracute, vaccination is recommended for susceptible animals.
(continued )

Table 31.1. Antimicrobial drug selection for common conditions of sheep and goats. (continued )

Condition Species Affected Etiological Agent(s) Recommended Treatment Comments

Necrotic laryngitis Sheep and goats Fusobacterium Penicillin G; oxytetracycline
necrophorum
Mycoplasma pneumonia Sheep and goats Oxytetracycline; tylosin Often seen in conjunction with pasteurellosis (atypical pneumonia) or
M. ovipneumoniae, alone.
Mycoplasma mycoides Goats M. arginini Oxytetracycline; lincomycin; or
tylosin Treatment of peracute septicemia often ineffective. If goat survives, it
M. mycoides ss. mycoides will probably be a carrier.
large colony type
Infectious conditions of the integument
C. psittaci,
Pinkeye (infectious Sheep and goats M. conjunctivae, Spiramycin; oxytetracycline; Spiramycin or oxytetracycline repeated days 1, 5, and 10; tiamulin
R. conjunctivae, tiamulin IM repeated days 1, 3, 6, and 9. Oxytetracycline eye ointment.
keratoconjunctivitis) Neisseria Conjunctival injection of penicillin (least effective).
Tilmicosin; oxytetracycline;
Secondary infection of Sheep and goats S. aureus ampicillin May also try local antimicrobials but wear gloves, as is a zoonosis.
contagious ecthyma
(Orf) Sheep Dermatophilus Long-acting oxytetracycline Decrease humidity (ventilation) if possible, and protect from rain.
Sheep and goats congolensis Powder sheep with powdered alum to help prevent reinfection.
Dermatomycosis (lumpy No effective treatment
wool) Corynebacterium Although susceptible to penicillin, not effective because of the thick
pseudotuberculosis abscess wall. Recommend cull infected animals and avoid opening
Caseous lymphadenitis abscesses as it spreads the pathogen.

Infectious conditions of the foot and musculoskeletal system

Contagious foot rot Sheep and goats D. nodosus F. Long-acting oxytetracycline 10–20% zinc sulphate with 2% w/v sodium lauryl sulphate, as a foot
bath with or without foot trimming. Must remain in bath 20
necrophorum As with lumpy wool minutes. Repeat in 5–7 days. Can use in conjunction with systemic
Oxytetracycline antimicrobials and/or vaccination. Cull chronic non- responders.
Foot scald Sheep and goats F. necrophorum Oxytetracycline; tylosin
Strawberry foot rot Sheep and goats D. congolensis Zinc sulfate foot bath as above.
Polyarthritis Sheep and goats Chlamydophila pecorum Verify that condition is not chorioptic mange.
Polyarthritis Goats Mycoplasma mycoides Poor response, may relapse.
subsp.mycoides,LC other Poor response, may relapse.

Infectious conditions of the mammary gland Mycoplasma spp.

Gangrenous mastitis Sheep and goats S. aureus, Tilmicosin; broad-spectrum Gland will be lost if animal survives, so should probably be culled.
M. haemolytica antimicrobials Probably ineffective, so animal should be culled. Carrier state likely.
Contagious agalactia Sheep and goats
M. agalactiae, Tetracyclines; tylosin
M. mycoides

ss mycoides (goats)

Subclinical and clinical Sheep and goats S. aureus, M. haemolytica, Tilmicosin; cloxacillin; Dry treatment to be used at the end of lactation in dairy goats or at
mastitis environmental cephapirin benzathine; weaning for prevention of new infections in high-risk sheep flocks.
streptococci, coagulase- oxytetracycline Do not split tubes. Tilmicosin should not be used in goats
negative Staphylococcus (therapeutic dose very close to toxic dose).
spp.

Infectious conditions of the oral cavity

Periodontal disease Sheep Many species No effective treatment
Many species Oxytetracycline; florfenicol;
Tooth root abscess Sheep and goats broad-spectrum antimicrobials 4–6 weeks of therapy. Consider surgical intervention if antimicrobials
Actinobacillus lignieresii Sodium iodide fail.
Actinobacillosis Sheep Actinomyces bovis Sodium iodide;
Actinomycosis Sheep 70 mg/ kg as 10–20% solution every 2 weeks for 2–3 doses.
sulfadimethoxine; isoniazid As for actinobacillus. Treat for weeks to months. Prognosis poor.

Infectious conditions of the urinary tract

Leptospirosis Sheep and goats Leptospira interrogans Dihydrostreptomycin; Drugs are potentially nephrotoxic, questionable efficacy.

Corynebacterium renale, oxytetracycline
other species
Cystitis Sheep and goats Broad-spectrum antimicrobials Therapy should be based on culture and sensitivity and should be

given for 10–14 days.

Infectious conditions of the nervous system

Bacterial meningitis Sheep and goats Many species Broad-spectrum antimicrobials Anti-inflammatory drugs important.
L. monocytogenes
Listeriosis Sheep and goats Oxytetracycline; penicillin G Injectable long-acting formulation. 22,000–44,000 IU/ kg IM twice per
day. Broad-spectrum antimicrobials include: ampicillin-sulbactam,
ceftiofur, fluoroquinolones, trimethoprim-sulfamethazine, or other
potentiated sulfonamide combinations.

Table 31.2 Common antimicrobial dosage regimens for sheep and goats. Many of the drugs listed are not approved for use in sheep and goats in the
United States and elsewhere, so that their use constitutes extra-label drug use (ELDU). ELDU of feed additives is prohibited in the United States and
fluoroquinolones are banned from ELDU in food-producing animals in the United States.

Drug Route Species Dose Rate Units Frequency (h)

Amoxicillin–clavulanic acid IV, IM Sheep and goats 20 mg/ kg 8
Amoxicillin trihydrate IM Sheep and coats 10 mg/ kg 8
Ampicillin sodium IV, IM Sheep and goats 10–20 mg/ kg 12
Amprolium PO in feed or water Sheep and goats 10–60 ppm 24, for 5–21 days for control; high dose 5 days for treatment
10 mg/ kg
Ceftiofur sodium IM Sheep* 1.1–2.2 mg/ kg 24, for 3 days
Goats* 1.1–2.2 mg/ kg 24, for 3 days
Chlortetracycline PO Sheep* 22 ppm Daily during late gestation to prevent infectious abortion
Goats 22 ppm Daily during late gestation to prevent infectious abortion
Decoquinate PO in feed Sheep and goats 25–100 ppm Daily in feed for period of coccidiosis risk
0.5 mg/ kg Daily during gestation to prevent T. gondii abortion
Danofloxacin IM, SC Sheep and goats 1.25 mg/ kg 24 3–5 days
Enrofloxacin IV, IM Sheep and goats 5 mg/ kg 24
Erythromycin IM Sheep and goats 3–5 mg/ kg 8–12 up to 5 days
Florfenicol IM, SC Sheep and goats 20 (IM), 40 (SC) mg/ kg 48(IM) 96(SQ)
Gamithromycin SQ Sheep and goats 6 mg/ kg
Lasalocid PO in feed Sheep and goats 30 ppm Daily in feed for period at risk
1 mg/ kg
Lincomycin hydrochloride IM Sheep and goats 10–20 mg/ kg 12–24
Marbofloxacin SC, IM Sheep and goats 2 mg/ kg 24
Monensin PO in feed Sheep and goats 11–22 ppm Daily in feed for period of coccidiosis risk
1 mg/ kg Daily during gestation for prevention of T.gondii
Neomycin sulfate PO in feed or water Sheep and goats 22 mg/ kg 24 for up to 14 days

Oxytetracycline PO in feed Sheep* and goats 22 ppm 12–24
Oxtetracycline IV, IM Sheep* and goats 10 mg/ kg
48–72
hydrochloride IM Sheep and goats 20 mg/ kg
Oxytetracycline 6
IV Sheep and goats 20,000–40,000 IU/ kg
long-acting 12
Penicillin G potassium or IM Sheep* and 20,000–40,000 IU/ kg
goats In feed for period of risk
sodium PO in feed 11–16 ppm 24
Penicillin G procaine PO in water Sheep and goats 50 mg/ kg
Sheep* and (loading 100) Single treatment
Salinomycin SC 10 mg/ kg Do not use due to toxicity
Sulfonamides goats 24
IM Sheep* 24–30 mg/ kg Single treatment
Tilmicosin SC Goats 2.5 mg/ kg 12
IM Sheep and goats 20 mg/ kg
Trimethoprim-sulfonamide Sheep and goats
Tulathromycin Sheep and goats
Tylosin

*Indicates that this product is licensed for use in some areas of North America. For withdrawal times consult the product label or the U.S. FARAD or Canadian gFARAD.

536 Section IV. Antimicrobial Drug Use in Selected Animal Species

(< 5 ml) can be given subcutaneously in the axilla or the antimicrobials is supportive, and a broad-spectrum
medial aspect of the thigh. antimicrobial will help reduce bacterial overgrowth in
the hindgut and treat bacteremia resulting from translo-
Since owners will often do follow-up treatment, they cation from the gut through the damaged intestinal wall.
should be counseled on proper drug handling and If very young animals are affected, the feces should be
administration, and warned of the potential for disease cultured and the presence of ETEC confirmed.
transmission and injection site abscesses if needles are Antimicrobial susceptibility testing is vital as many
reused. Good record-keeping practices for both the strains carry multidrug resistance. In the event of a sal-
owner and veterinarian, and individual animal identifi- monellosis outbreak, culture and susceptibility testing
cation are key to preventing violative residues in meat are also vital. When faced with a coccidiosis outbreak,
and milk. Good records are also necessary so that injec- sulfonamides are the treatment of choice for clinical
tion site reactions are not confused with lesions of case- cases. Coccidiostats in a creep feed or milk replacer may
ous lymphadenitis, which is an important contagious be indicated to prevent further outbreaks. The use of
disease of sheep and goats. Tilmicosin, which is approved antimicrobials in other circumstances is controversial
for use in sheep, can cause fatal reactions in humans and and prudent antimicrobial use guidelines should be
goats. This drug should not be dispensed without care- followed.
ful consideration of the safety issues. The manufacturer
of tilmicosin provides education materials for owners to Pneumonia
read and sign, indicating that they understand the
potential for toxicity. Pneumonia can be a problem in all ages of sheep and
goats, but the etiology changes with age (Scott, 2011).
Administration of antimicrobials orally via food and Acute pneumonia characterized by fever, nasal dis-
water for treatment of infections should be avoided. charge, coughing, dyspnea and in some cases sudden
Intake is hard to control, especially in ill animals in death is most commonly seen in growing lambs and is
which intake may be decreased. In large flocks with dif- in many ways analogous to shipping fever seen in
fuse disease this may be the only practical option despite growing calves. The most common pathogens include
its limitations; examples include flock and herd out- Mannheimia haemolytica, Bibersteinia trehalosi,
breaks of coccidiosis and infectious abortion. Mycoplasma ovipneumoniae, and parainfuenza virus
3 (PI-3). Clinical disease is most commonly the result
Neonatal Enteritis of infection with a combination of pathogens.
Fortunately, there are a number of antimicrobials
Like most species, neonatal lambs and kids are prone to licensed for sheep pneumonia in North America
enteric infections. These infections can be largely con- including: tilmicosin, florfenicol, ceftiofur and
trolled by strict attention to the hygiene of the lambing/ short-acting oxytetracycline. Unfortunately, the long-
kidding area and by ensuring that all newborns receive acting oxytetracycline formulations are not licensed
adequate good quality colostrum. The causes of enteritis for sheep in North America. Only ceftiofur sodium
in small ruminants are very similar to those seen in cat- licensed for goats in the USA and although there is
tle. The use of antimicrobials for diarrhea in neonatal evidence to support many of the products approved
calves has been extensively reviewed and is largely appli- for sheep in goats, tilmicosin is toxic in goats and
cable in small ruminants (Constable, 2004). Under a should never be used.
week of age, the most likely causes of enteritis are
Enterotoxigenic E. coli (ETEC), and potentially Chronic pneumonia most commonly seen in adult
Salmonella spp. Clostridial disease may also be seen but sheep and goats due to pathogens such as Maedi-visna
this more commonly results in sudden death and is eas- (Ovine Progressive Pneumonia), Caprine Arthritis
ily prevented by vaccinating with a multivalent clostrid- and Encephalitis virus, caseous lymphadenitis and
ial vaccine in late pregnancy. After kids or lambs are a other forms of chronic abscessation. These diseases
week of age, enteric viruses, Cryptosporidium, and coc- are typified by weight loss and exercise intolerance.
cidiosis more commonly cause enteritis. These conditions do not respond to antimicrobial
therapy and affected animals should be culled.
Consequently, antimicrobials have a very limited role
in managing neonatal enteritis. The main role of

Chapter 31. Antimicrobial Drug Use in Sheep and Goats 537

Infectious Abortion species but can also circulate within the flock/herd. The
disease can be managed by using in feed antiprotozoal
Infectious abortion is a very significant problem in sheep medications such as monensin or decoquinate.
and goats. The agents are shed in the vaginal secretions
and the maternal behavior of ewes and does in confine- Other less common causes of abortion include:
ment driving them to lick newborn animals means that Q-fever, listeriosis, and salmonellosis. All animals that
the diseases can spread very rapidly within a flock/herd abort should be isolated. Only once a diagnosis is made
resulting in catastrophic abortion storms. With any case and antimicrobial susceptibility has been confirmed,
of abortion in small ruminants it is vital to define the should mass medication with antimicrobials may be
etiology so that appropriate control measures can be considered to control the outbreak.
instigated. The fetus and placenta must be submitted to a
diagnostic laboratory to confirm the diagnosis (Menzies, Infectious Keratoconjunctivitis (“Pinkeye”)
2011). It is also important to warn the client that most
causes of abortion in small ruminants are zoonotic. In sheep and goats, infectious keratoconjunctivitis is
most commonly caused by Mycoplasma spp. and
Enzootic Abortion/Chlamydophila abortus Chlamydia spp., not Moraxella bovis. Topical antimicro-
This pathogen is normally brought into the flock/herd bial therapy with oxtetracycline ophthalmic ointment is
by a carrier animal that aborts at end of its first preg- indicated; although when large numbers are affected
nancy. The agent is shed from the vagina and infects parenteral oxytetracycline therapy is often used.
many other animals with a potential abortion storm
occurring at the next lambing/kidding. The disease is Bacterial Pododermatitis
best prevented by good biosecurity practices and the use
of a bacterin vaccine. Sheep and goats are prone to a number of bacterial foot
problems. It is import to determine the exact cause
In event of abortions, the affected animals should be before commencing treatment (Winter, 2011).
immediately quarantined. The size of the outbreak can Interdigital dermatitis or scald is an inflammation of the
be controlled using oxytetracycline to suppress the interdigital skin caused by Fusobacterium necrophorum
pathogen growth on the placenta until the lamb/kid can and is associated with wet and dirty conditions. It is sim-
be delivered at term. In small flocks, this may be ply managed by moving the herd or flock to drier areas
achieved using extra-label long-acting oxytetracycline at and potentially using a zinc sulfate footbath.
20 mg/ kg IM administered every 3–5 days. In larger
flocks, the only option may be to medicate the feed with Contagious footrot is caused by strains of Dichelobacter
a tetracycline product at 200 ppm. nodosus. This is a serious condition resulting in
significant pain and inflammation. Ideally, this condi-
Vibrio-abortion/Campylobacter fetus Subsp tion should be managed by eradication. Eradication is
fetus and Campylobacter jejuni difficult and typically involves culling of chronically
This pathogen is normally introduced to the flock/herd infected animals; foot trimming, zinc sulfate footbaths
by carrier animals or contaminated feed. The pathogen and moving the animals to pasture that have not been
infects and kills the fetus; the fetus is then typically grazed for 2 weeks. Single injections of long-acting oxy-
aborted approximately 2 weeks later. The antimicrobial tetracycline have also been shown to be effective in
susceptibility of Campylobacter can be variable so cul- treating affected animals.
ture and susceptibility testing is indicated. Since the
fetus has typically been dead for some time when abor- Contagious ovine digital dermatitis has only been
tion occurs, antimicrobial therapy is not useful for con- diagnosed in sheep in the United Kingdom. If diagnosed
trolling the number of future abortions. promptly, it has been successfully treated with
systemic tilmicosin or topical oxytetracycline or tylosin
Toxoplasmosis (Winter, 2011).
Toxoplasma gondii can cause abortion at any stage of
pregnancy. The disease typically comes from feline Mastitis

There is very little specific evidence on the approp-
riate antimicrobial treatment of mastitis in sheep
and  goats, but the topic has been well reviewed

538 Section IV. Antimicrobial Drug Use in Selected Animal Species

(Mavrogianni et al., 2011). In meat producing herds Extra-Label Drug Use and Residue
and flocks, acute disease is commonly managed by Avoidance
the administration of systemic antimicrobials and
animals are then culled after weaning. The situation It is difficult to raise sheep and goats without extra-
is obviously more complex when animals are used for label use of antimicrobials, as sheep and goats are
milk production as mastitis is more common, has a prone to a number of infectious diseases that require
great impact on productivity, and there is the issue of treatment to maintain herd/flock productivity and to
antimicrobial residues in milk. ensure animal welfare. Producers and practitioners
may be unaware that even “pet” sheep and goats are
Mastitis in small ruminants is most commonly considered food animals by the regulatory authorities
caused by either Staphylococcus aureus or Mannheimia and that extra-label drug use (ELDU) regulations
haemolytica, with Staphylococcus being more com- apply to their animals as well (Fajt, 2011). It is vital
mon in milking flocks/herds. It is important to know that veterinarians, agricultural producers and owners
what pathogens are actually involved on a particular of small ruminant pets are aware of ELDU and ensure
farm so routine culture is vital to determining which that the appropriate regulations are followed. The
antimicrobials should be used. Intramammary treat- U.S. Animal Medicinal Drug Use Clarification Act
ment can be effective and is commonly employed in and Health Canada’s Policy on Extra-Label Drug Use
milk producing animals. Great care should be taken provide guidance (see chapter 26). Such ELDU should
to ensure that the teat is completely clean before always be based on a valid veterinarian-client-patient
administration and particular care should be taken to relationship and involve a written prescription in
avoid damaging the teat sphincter when treating. An which the prescribing veterinarian sets appropriate
entire intramammary infusion tube should be used withdrawal intervals for meat and/or milk. In the
for treatment of the gland. There are no products United States and Canada, prescribing veterinarians
licensed for intramammary use in either sheep or can contact their Food Animal Residue Avoidance
goats. Systemic therapy is often used in meat produc- Databank (United States: www.farad.org; Canada:
ing animals and in cases where there are systemic www.cgfarad.usask.ca) for evidence-based withdrawal
signs or the disease has become chronic resulting in information.
occlusion of the ducts within the mammary gland
due to inflammatory debris. Macrolides, tetracyclines Bibliography
and trimethoprim all penetrate well into the mam-
mary gland when administered systemically. However, Clothier KA, et al. 2011. Pharmacokinetics of tulathromycin
the success rate of treating clinical mastitis in small after single and multiple subcutaneous injections in
ruminants is poor, similar in many ways to the situa- domestic goats (Capra aegagrus hircus). J Vet Pharmacol
tion in cattle. Treatment is often started too late, is Therap 34:448.
not continued for long enough, the wrong antimicro-
bial was used, or the pathology of the disease prevents Constable PD. 2004. Antimicrobial use in the treatment of
adequate antimicrobial concentration at the site of calf diarrhea. J Vet Intern Med 18:8.
infection. Sheep and goats are prone to severe masti-
tis infections that result in gangrenous mastitis. Such Elsheikh HA, et al. 1997. Comparative pharmacokinetics of
cases are typified by a hard, swollen, cold mammary ampicillin trihydrate, gentamicin sulphate and oxytetra-
gland, which develops a characteristic blue color cycline hydrochloride in Nubian goats and desert sheep.
(“blue bag”). Treatment is routinely unsuccessful and J Vet Pharm Therap 20:262.
if affected animals survive they should be culled. If
the doe or ewe has considerable economic value she Fajt VR. 2011. Drug laws and regulations for sheep and goats.
will require systemic antimicrobial therapy and inten- Vet Clin North Am Food Anim Pract 27:1.
sive supportive care and the affected mammary gland
should be amputated. Fariborz S, et al. 2001. Pharmacokinetics and pharmacody-
namics of danofloxacin in serum and tissue fluids of goats
following intravenous and intramuscular administration.
Am J Vet Res 62:1979.

Jianzhong S, et al. 2004. Bioavailability of florfenicol in
healthy sheep. J Vet Pharm Therap 27:163.

Chapter 31. Antimicrobial Drug Use in Sheep and Goats 539

Mavrogianni VS, et al. 2011. Principles of mastitis treatment Sargison ND, et al. 2011. Metaphylactic gamithromycin
in sheep and goats. Vet Clin North Am Food Anim Pract treatment for the management of lameness in ewes
27:115. putatively caused by Bacteroides melaninogenicus. Vet Rec
169:556
Menzies PI. 2011. Control of important causes of infectious
abortion in sheep and goats. Vet Clin North Am Food Scott PR. 2011. Treatment and control of respiratory disease
Anim Pract 27:81. in sheep. Vet Clin North Am Food Anim Pract 27:175.

Mordric S, et al. 1998. Pharmacokinetics and pharmacody- Washburn KE, et al. 2011. The safety of tulathromycin
namics of tilmicosin in sheep and cattle. J Vet Pharm administration in goats. J Vet Pharmacol Ther 30:267.
Therap 21:444.
Winter 0 2011. Treatment and control of hoof disorders in
Pugh DG, Baird AN. 2011. Sheep and Goat Medicine, 2nd ed. sheep and goats. Vet Clin North Am Food Anim Pract
St. Louis: Elsevier Health Sciences. 27:187.

Antimicrobial Drug Use in 32
New World Camelids

Christopher K. Cebra and Margaret L. Cebra

Over the last 30-plus years, the populations of llamas The choice of antimicrobial medication is also usually
and alpacas, the two domestic and most common spe- empirical, with broad-spectrum coverage desired. This
cies of New World camelid, have increased rapidly in leads to the next frustration: there is a persistent paucity
North America, Australia, and most recently Europe. of disease prevalence data and pharmacokinetic data
The combined numbers of these species are roughly from New World camelids. Camelids are anatomically
seven million in South America (Peru, Chile, Bolivia, and physiologically unique, making any sort of extrapo-
and Argentina), 300,000 in North America, 80,000 in lation dangerous. No medications are approved for use
Australia, and 30,000 in Europe. Population growth out- in New World camelids, and dosages found in clinical
side of South America has slowed considerably in recent reports can differ from each other as much as 25-fold.
years, but llamas and alpacas continue to be cherished Although camelids are generally considered pets in
pets whose owners expect quality health care. North America, their rising population coupled with
economic issues has led to increasing events of reverting
Veterinarians in North America have historically to one of their traditional South American roles, as a
found New World camelids to be medically frustrating, meat source. This increases the need for veterinarians to
because camelids hide disease signs, physical examina- be aware of individual circumstances, consider residues
tion and laboratory evaluation often yield no immediate and the legality of using certain medications, and poten-
answers, disease pathogenesis and progression is often tially discussing these issues with owners.
unique, and reference material lags behind medical
advances. One distinct feature of the sick camelid is that A variety of antimicrobial agents have been adminis-
it often has impressive leukogram changes, particularly tered to camelids. Some reasonable dosages for these
neutrophilia with or without a left shift. These changes agents can be devised by examining the available infor-
may or may not reflect infectious disease—stress neu- mation (Table 32.1). However, most have not been stud-
trophilia is common and can lead to nucleated cell ied scientifically, and the attending veterinarian must
counts as high as 50,000 cells/ul, as well as moderate assume the responsibility for extra-label drug use and
increases in band cell counts—but in the absence of potential adverse effects on the animal. As a general
other definitive diagnostic information, neutrophilia is rule, antibiotics appear to have longer elimination
often used to justify empirical use of antibiotics. In addi- half-lives in camelids than in domestic ruminants,
tion to this empirical approach, there is rising recogni- potentially prolonging their therapeutic effect but also
tion of a number of specific infectious conditions increasing their risk of toxicity. This may be due to a
affecting camelids. lower rate of urine production in camelids (Lackey,

Antimicrobial Therapy in Veterinary Medicine, Fifth Edition. Edited by Steeve Giguère, John F. Prescott and Patricia M. Dowling.
© 2013 John Wiley & Sons, Inc. Published 2013 by John Wiley & Sons, Inc.

541

542 Section IV. Antimicrobial Drug Use in Selected Animal Species

Table 32.1. Common antimicrobial drug dosage in adult New World camelids.a

Drug Preparation Dose Dose Interval (h) Route of Administration

Beta-lactamsb,c,d 22,000–44,000 IU/kg 6 IV
Benzyl penicillins: 22,000–44,000 IU/kg 12–24 IM or SC
Penicillin G (Na, K)
Penicillin G (procaine) 10–20 mg/kg 8–12 IV or IM
Aminobenzyl penicillins: 10–20 mg/kg 12–24 IM or SC
Ampicillin sodium
Ampicillin trihydrate 2.2–4.4 mg/kg (up to 8 mg/ kg 12–24 IV,IM,or SC
q12 h in neonates)
Third-generation cephalosporin: 12–24 IM or SC
Ceftiofur sodium 2.2–4.4 mg/kg 48–120 SC axilla
6.6 mg/kg
Ceftiofur HCl 24 IV,IM,or SC
Ceftiofur CFA 18–21 mg/kg 24 IV,IM,or SC
Aminoglycosidese 4.4–6.6 mg/kg
Amikacin 12–24 IV,IM,or SC
Gentamicin 5 mg/kg 24 PO
Fluoroquinolones 10 mg/kg
Enrofloxacinf 12–24 IV
10 mg/kg 24–72 IM or SC
Tetracyclinesb,c 20 mg/kg
Oxytetracycline (100 mg/ml) 24–48 IM or SC
Oxytetracycline (200 mg/ml) 20 mg/kg 8–12 PO or per rectum
15–25 mg/kg 12 IV,IM,or SC
Other 18 mg/kg (comb.)
Florfenicolg
Metronidazoleh
Trimethoprim-sulfomethoxazole

aAlthough these medications at these dosages have been used repeatedly for camelid patients in referral hospitals in North
America, pharmakokinetic data are lacking for most of these agents in camelids, as are safety studies. All medications must be
used with caution in camelids and the patient must be monitored carefully for adverse reactions or toxic effects.
bThe higher dosages and/or shorter dosing intervals are indicated in camelids with more severe infections.
cThe higher dosages and/or shorter dosing intervals may be indicated in alpacas or llamas with lower gastric fill or body fat.
dThe higher dosages and/or shorter dosing intervals may be indicated in young camelids.
eThe large differences in volume of distribution between individual camelids and risk of nephrotoxicosis with overdose support caution
in the use of this medication at any dose, especially the higher dosages, and especially in camelids with decreased urine production.
fShould not be used in young growing camelids because of the risk of arthropathy.
gForty-eight-hour dosing may be adequate for highly sensitive organisms, such as those typically present in tooth root abscesses.
For more general antimicrobial coverage, daily dosing may be required.
hOral dosing in juvenile and adult camelids will affect the gastric microbial population. Per rectum administration is preferred in these
age groups.

1995), which may increase half-life of antibiotics dosages are generally recommended to avoid subthera-
excreted primarily through the kidneys (e.g., penicillins, peutic drug concentrations in some camelids. Thus, the
aminoglycosides). This slower renal excretion in turn most useful antibiotics are those with a high margin of
may be affected by concurrent fluid treatments, such safety. Pharmacokinetic data for selected antimicrobials
that camelids in referral hospital situations may be in llamas and alpacas are presented in Table 32.2.
treated similarly to domestic ruminants, whereas came-
lids treated in the field must be dosed more conserva- A survey of the recent scientific literature suggests
tively. As another general rule, volume of distribution that the most commonly used antibiotics in New World
varies tremendously among individual camelids. Higher camelids are the beta-lactams. The different formula-
tions of ceftiofur predominate, followed by crystalline

Table 32.2. Pharmacokinetic data for selected antimicrobials in llamas and alpacas.

Agent Dose Vol Dist Clearance Elim Half-Life AUC Peak Conc Time to Peak
(mg/ kg) (L/ kg) (ml/min/ kg) (Hours) (μg h/ml) (μg/ml) (Hours)
Species Route

Ampicillina Llama 12 IV 0.28 ± 0.09 0.88 ± 0.28 3.33 ± 0.50 228 ± 73 5.52 ± 1.11 0.77 ± 0.56
Ceftiofura Llama 2.2 IV 0.19 ± 0.02 0.98 ± 0.15 2.19 ± 0.14 38.4 ± 5.8 6.33 ± 2.20 0.91 ± 0.55
Ceftiofurb Llama 2.2 IM 0.61 ± 0.19 1.03 ± 0.41 8.00 ± 1.85 40.1 ± 12.9
Ceftiofurb Llama 2.62–2.99 IM 0.61 ± 0.20 0.97 ± 0.36 8.81 ± 3.04 54.8 ± 20.8 2.09 ± 0.42 0.49 ± 0.16
Ceftiofurb Alpaca 1 IV 0.54 ± 0.15 1.36 ± 0.39 5.60 ± 1.57 13.4 ± 4.4 3.52 ± 0.47 0.5 ± 0.0
Ceftiofurb Alpaca 1.27–1.44 IV 0.55 ± 0.18 1.44 ± 0.37 4.62 ± 1.18 14.6 ± 3.1 2.65 ± 0.85 36
Ceftiofurb Alpaca 1 IM 0.57 ± 0.12 1.12 ± 0.36 4.31 ± 1.35 15.4 ± 5.1 1.97 ± 0.44 17 ± 16
Ceftiofurb Alpaca 1.30–1.51 IM 0.64 ± 0.14 1.15 ± 0.27 7.42 ± 1.41 20.9 ± 3.9
Ceftiofur CFAc Alpaca 6.6 SC 4.06 ± 2.18 64.6 ± 31.4 199 ± 42 4.2 (1.5−1.7) 6.0 (4.0−8.0)
Ceftiofur CFAc Alpaca 6.6 SC q5d 4.18 ± 1.14 11.67 ± 3.5 52.4 217 ± 85 1.4 (0.8−4.0) 4.0 (0.5−8.0)
Enrofloxacina Llama 5 IV 3.46 ± 0.98 84.5 (41.5−115.7) 3.38 ± 2.13 7.0 ± 2.3 1.95 ± 0.94 2.50 ± 1.07
Enrofloxacind Alpaca 5 IV 0.44 (0.32-1.07) 13.0 (6.3−46.6) 58.4 (43.2−120.6) 7.54 ± 3.62 2.81 ± 1.21
Enrofloxacind Alpaca 5 SC 6.73 ± 1.55 7.83 (3.4−15.6) 41.9 (33.5−89.0) 4.31 ± 3.03 1.00 ± 0.65
Enrofloxacind Alpaca 10 PO 11.1 ± 8.1 7.04 ± 1.75 15.3 (8.3−25.0) 32.5 (29.3−42.7) 1.95 ± 0.94 2.50 ± 1.07
Florfenicole Alpaca 40 SC 55.7 ± 25.9 99.7 ± 59.9 99.8 ± 23.6 4.48 ± 1.28 2.50 ± 0.93
Florfenicol Golde Alpaca 40 SC 0.51 41.6 ± 21.9 125.2 ± 38.2
Florfenicolf Alpaca 20 IM 0.12 1.10 ± 0.14 17.6 ± 11.7 51.8 ± 11.7 38.2 ± 12.3
Florfenicolf Alpaca 40 SC 0.25 ± 0.03 1.33 ± 0.47 99.7 ± 59.9 99.8 ± 23.6
Florfenicolf Alpaca 40 SC q2d 0.46 ± 0.08 1.90 ± 0.77 90.2 ± 55.5 158.3 ± 189.3 2 (2–4)
Gentamicing Llama 4 IV 0.35 ± 0.09 3.03 125.7 3.9 ± 1.5
Gentamicinh Llama 5 IV 0.73 ± 0.22 2.77 ± 0.34 77.3 ± 10.3 237 ± 27 17.6 ± 9.2
Sulfamethoxazole +TMPa Llama 15 IV 0.44 ± 0.05 4.28 ± 0.53 187 ± 47 21.7 ± 14.1 (continued )
Sulfamethoxazole +TMPi Alpaca 12.5 IV 2.20 ± 0.60 124.4 ± 64
Sulfamethoxazole +TMPj Llama 45 PO 4.0 (3.2-7.2) 34.1 ± 12.8
Sulfadimethoxinek Llama 55.6–62.4 IV 9.4 ± 2.0 1403 ± 311
Sulfadimethoxinek Llama 50.2–72.4 PO 11.7 ± 6.7 765 ± 210

Table 32.2. Pharmacokinetic data for selected antimicrobials in llamas and alpacas. (continued )

Agent Species Dose Route Vol Dist Clearance Elim Half-Life AUC Peak Conc Time to Peak
(mg/ kg) (ml/min/ kg) (μg/ml) (Hours)
Tobramycina Llama IV (L/ kg) (Hours) (μg h/ml)
Trimethoprim + SMXi Alpaca 1 IV 0.43 ± 0.07 10.75 ± 2.12 5.37 ± 3.36
Trimethoprim + SMXa Llama 2.5 IV 0.14 ± 0.05 21.63 ± 9.85 3.68 ± 1.26 39.5 ± 6.6
Trimethoprim + SMXj Llama 3 PO 2.33 ± 1.15 1.4 ± 1.1 0.74 ± 0.1 364 ± 4.45 undetectable
Voriconazolel Alpaca 9 IV 0.40 ± 0.15 3.31 ± 0.56 39.9 ± 16.6 5.93 ± 1.13
Voriconazolel Alpaca 4 PO 1.82 ± 0.42 undetectable 1.70 ± 2.71
4 1.19 ± 0.14 9.43 ± 4.57 8.01± 2.88 33.9 ± 5.2
aChristensen et al., 1996. 7.11 ± 5.41 8.75 ± 4.31 8.76 ± 6.80
bDrew et al., 2004
cDechant et al., 2012.
dGandolf et al., 2005.
eBedenice et al., 2012.
fHolmes et al., 2011.
gDowling et al., 1996.
hLackey et al., 1996.
iChakwenya et al., 2002.
jSnook et al., 2002.
kJunkins et al., 2003.
lChan et al., 2008.

Chapter 32. Antimicrobial Drug Use in New World Camelids 545

(sodium or potassium) and procaine penicillin. These routes without reported problems (Lewis et al., 2009).
reports are probably skewed toward referral hospital Ceftiofur crystalline free acid is also seeing increasing
use, particularly in regards to crystalline penicillin and clinical use where long-acting coverage is desired (Jones
repeated intravenous dosing, but use of this class of anti- et al., 2009). A recent study demonstrated that a single
biotic is also common in practice. Ampicillin, amoxicil- 6.6 mg/ kg subcutaneous injection in the axillary region
lin, and other cephalosporins have seen limited use. The resulted in plasma concentrations of ceftiofur and
beta-lactam antibiotics, particularly ceftiofur products, active metabolites that remained above 0.25 μg/ml for
are used as single agents, or less frequently in combina- 6 days in adult alpacas, but also suggested that higher
tion, usually with an aminoglycoside. Of the aminogly- concentrations were necessary to be effective against
cosides, gentamicin is most commonly reported, with the majority of recent bacterial isolates (Decant et al.,
amikacin used mainly in crias and via regional perfu- 2012). Fifty-four percent of Gram-positive and 27% of
sion. Oxytetracycline, florfenicol, and enrofloxacin Gram-negative isolates from camelids showed sensitiv-
account for most of the rest of the reports. Enrofloxacin ity to ceftiofur concentrations ≤ 0.25 μg/ml, 71% of
is used in a variety of situations, usually to replace Gram-positive and 45% of Gram-negative isolates
an aminoglycoside in Gram-negative coverage. showed sensitivity to concentrations ≤ 0.5 μg/ml, and
Oxytetracycline, florfenicol, and ceftiofur crystalline 88% of Gram-positive and 64% of Gram-negative
free acid are most commonly used against selected isolates showed sensitivity at ≤ 1.0 μg/ml. Thus, every
organisms, such as oxytetracycline versus Mycoplasma 2- to 5-day dosing may be necessary to achieve true
haemolamae, when a lengthy course makes infrequent broad-spectrum coverage.
injections preferable, or when repeated dosing is
impractical. Single doses of ceftiofur crystalline free acid were well
tolerated, but repeated dosing led to local, non-painful
Ceftiofur sodium has been studied in both llamas reactions in half the test alpacas. Ceftiofur is usually
and alpacas, and also has the broadest range of dosages highly protein-bound, which affects its distribution.
in clinical reports (Christensen et al., 1996; Drew et al., Hypoproteinemia is common in sick camelids, but how
2004). The two main studies provide conflicting infor- this affects distribution and other pharmacokinetic
mation concerning the volume of distribution at steady parameters has not been tested.
state and half-lives, but similar information concerning
clearance and area under the curve. Additionally, indi- Even though penicillin is commonly used in New
vidual camelids in the larger study had volumes of dis- World camelids, no pharmacokinetic studies are availa-
tribution at steady state that differed by up to 100%. ble, and most dosages are extrapolated from other large
Thus while the larger study reports pharmacokinetic animal species. Crystalline penicillin (22,000 U/ kg, IV,
parameters similar to those seen in small ruminants, q 6 h) or procaine penicillin (22,000 U/ kg, SC or IM, q
twice-daily dosing to adults at 2.2 mg/ kg intravenously 12 h) are the most commonly used products. Doses are
or intramuscularly is recommended to avoid subthera- often doubled when Clostridium or similar pathogens
peutic concentrations in the camelids with greater vol- are suspected. Adverse reactions are reported rarely,
umes of distribution. Subcutaneous administration at most commonly either acute procaine-type reactions or
the same dose and interval has become popular, and is rarely hypersensitivity-type reactions after prolonged
empirically successful, but has not been studied scien- use. Clinical efficacy appears to be satisfactory.
tifically. Higher doses (4–8 mg/ kg, IV, IM, or SC q 12 h) Ampicillin is excreted by similar renal mechanisms and
have been used in crias up to around 12 weeks of age has a similar half-life as penicillin G in other species.
and in adults for which more aggressive antibiotic pro- However, the half-life of ampicillin in llamas is 2–4
tocols were deemed necessary (Buchheit et al., 2010; times longer than in horses or sheep, respectively, its
Simpson et al., 2011); no complications have been volume of distribution at steady state is about 50%
reported with these higher doses, but they also have not greater than sheep and about the same as horses
been studied scientifically. Ceftiofur hydrochloride is (Christensen et al., 1996). The longer half-life may be
also being used somewhat interchangeably with ceftio- the result of low urine production, which could prolong
fur sodium by the intramuscular and subcutaneous the action of renally excreted medications, and suggests
that lower dosages or less frequent dosing intervals of

546 Section IV. Antimicrobial Drug Use in Selected Animal Species

the penicillins in camelids may achieve sufficient thera- Ceftiofur sodium and gentamicin appear to have
peutic effect. Treating the camelid with fluids during the similar enough pharmacokinetic properties when given
course of antibiotic treatment may negate this effect by intravenously or intramuscularly, that the same dosage
enhancing excretion. and dosing frequency may be used for either route.
Additionally, recent evidence from other species sug-
Gentamicin sulfate, or the similar compound, gests that many antibiotics have comparable absorption
tobramycin, has been studied in llamas and camels from the subcutaneous route. The subcutaneous route
(Christensen et al., 1996; Dowling et al., 1996; Hadi et has become very popular in camelids for all antibiotics
al., 1994; Lackey et al., 1996). Again, conflicting infor- formerly administered intramuscularly due to lack of
mation concerning volume of distribution was gener- large muscle masses and ease of administration. Unless
ated from the different studies, with the largest study a very fast effect is desired or the particular antibiotic is
reporting volumes of distribution at steady state that dif- known to cause adverse reactions when given subcuta-
fer up to 150% between animals. Because aminoglyco- neously, this route is considered acceptable.
side antibiotics generally have poor lipid solubility and
move into the extracellular space slowly, these differ- Intravenous sulfa antibiotics and trimethoprim-sulfa
ences in volume of distribution could relate to differ- combinations have been studied and used on clinical
ences in gastric fill and body fat in the individual cases. The trimethoprim studies show poor agreement.
camelids. The studies agree on prolonged elimination In alpacas, trimethoprim has a large volume of distribu-
half-lives of around 3 hours. tion and rapid clearance, similar to the rat, and rapidly
drops to subtherapeutic concentrations (Chakwenya et
As with other species, once-daily dosing of camelids al., 2002). Trimethoprim (3 mg/ kg) in llamas acts more
with aminoglycosides has become more popular than similarly to the horse, resulting in plasma concentra-
more frequent dosing. The rationale for this is to allow tions > 1 μg/ml for up to 12 hours; its reported volume of
trough concentrations to drop below 2.0 μg/ml to prevent distribution is smaller than many other species
nephrotoxicity, while at the same time maintaining effi- (Christensen et al., 1996). Thus, trimethoprim appears
cacy due to the agent’s post-antibiotic effect. Because of to offer little advantage in the alpaca, but may be useful
camelids’ slow elimination of aminoglycosides, this strat- in llamas against sensitive microorganisms.
egy appears to be especially valid. Dosing camelids at
2.5 mg/ kg intravenously maintains concentrations above Sulfamethoxazole acts more similarly in llamas and
the toxic threshold for at least 6 hours after each dose in alpacas (Christensen et al., 1996; Chakwenya et al.,
many camelids (Lackey et al., 1996), which would repre- 2002), but with a smaller volume of distribution and
sent a high risk for toxicosis with 3-times-a-day dosing. faster clearance in alpacas. Camelids are fairly similar to
Dosing at 4.0–5.0 mg/ kg maintains concentrations above sheep and cattle in these regards, with considerably
the toxic threshold for about 12 hours (Dowling et al., faster clearance than horses or people. Active secretion
1996; Lackey et al., 1996), and also provides peak concen- into the renal tubules and trapping of the excreted agent
trations necessary for antimicrobial activity. in alkaline urine may contribute to this rapid clearance.
It may also reflect a significant difference between New
Nephrotoxicoses in camelids administered aminogly- World camelids and camels, which are reported to have
cosides both once a day and more frequently have been acidic urine and slow sulfa clearance (Kumar et al.,
reported in the literature (Hutchison et al., 1993) and 1998). Injectable sulfamethoxazole may have some value
anecdotally. The slow elimination, spare urine produc- in treating sensitive infections, especially in llamas.
tion, and extreme variability in volumes of distribution
potentially make camelids very susceptible to relative At metabolically scaled doses of 55–62 mg/ kg, sul-
overdose, especially when they are dehydrated or drink fadimethoxine in llamas has a higher volume of distri-
insufficient water. Such problems have not been reported bution at steady state and a shorter half-life than in
(scientifically or anecdotally to the authors) in camelids cattle, and also may reach only subtherapeutic blood
administered aminoglycosides and concurrent intrave- concentrations (Junkins et al., 2003; Boxenbaum et al.,
nous fluids. Thus, it is especially important to ascertain 1977). Similar volumes of distribution and peak concen-
hydration status before administering aminoglycosides trations and even faster clearance have been described
to camelids and during the course of treatment. in dromedary camels (Chatfield et al., 2000). No

Chapter 32. Antimicrobial Drug Use in New World Camelids 547

evaluation of higher doses has been described, but a injections of more than a few ml are usually given to
metabolically scaled dose of 69 mg/ kg was suggested for llamas and alpacas over the dorsal thorax. In contrast,
camels, and a higher, and possibly unsafe, dose might be subcutaneous florfenicol in cattle is specifically sup-
necessary to reach desirable concentrations in New posed to be administered in the neck. Camelids’ dorsal
World camelids. The role of protein-binding of sul- thoracic skin is seasonally covered with fiber, and plays
fadimethoxine on clearance has been investigated in little role in thermoregulation. It is poorly vascularized
other species, and shown to be essential to the long half- compared to axillary skin, potentially slowing the uptake
life (Bevill et al., 1982). This has not been investigated in of agents injected there, and yielding a long elimination
camelids, but the likelihood that hypoproteinemia, a half-life that is actually a reflection of slow absorption.
common finding in sick camelids, will alter drug excre- Serial injections may increase blood flow and eventually
tion must be considered. For these reasons, intravenous lessen the differences between the intramuscular and
sulfadimethoxine appears unsuitable for most antimi- subcutaneous routes (Holmes et al., 2011). Administering
crobial applications in camelids. florfenicol, or any other medication, in the axillary
region may result in faster peaks and a shorter elimina-
Florfenicol use has become more popular, especially tion half-life, but this has not been tested.
in the treatment of tooth root abscesses, and other con-
ditions where a longer dosing interval is desirable. The recent studies suggest that daily intramuscular
Recent clinical and experimental results suggest its value florfenicol (20 mg/ kg) may be effective against very to
may be greatest against highly susceptible pathogens in moderately sensitive microorganisms, which do not
focal infections rather than as a broad-spectrum treat- include Staphylococcus aureus, Pseudomonas aerugi-
ment. This relates to its pharmacokinetic properties and nosa, and many Gram-negative enteric bacteria. An
the potential adverse effects. ideal subcutaneous regimen has not been described.
Lower doses (20 mg/ kg, SC, q 24 h) may become ade-
Intravenous florfenicol had a lower volume of distri- quate against sensitive pathogens, if greater absorption
bution in New World camelids than in sheep, goats, or with serial dosing may be inferred. Higher doses
camels, and a slightly longer half-life than in sheep or (40 mg/ kg, SC, q 24 h) maintain therapeutic steady-state
goats; a 20 mg/ kg dose yields plasma concentrations > 1 concentrations, but are associated with evidence of tox-
μg/ml in both llamas and alpacas for about 12 hours (Ali icity, including reductions in blood proteins and cell
et al., 2003; Christensen et al., 2001). When given intra- counts, abnormal feces, and clinical disease.
muscularly at 20 mg/ kg, peak plasma concentrations are
achieved quickly, and are comparable between llamas Intravenous and subcutaneous enrofloxacin, and
and beef cattle, and higher in alpacas (Holmes et al., intravenous and intramuscular oxytetracycline have
2011). Elimination also appears to be similar to cattle or also been studied in llamas and alpacas. Intravenous
prolonged, but plasma concentrations generally drop oxytetracycline in llamas had a similar volume of distri-
below 1 μg/ml within 14–24 hours. As with other medi- bution to camels, but a much longer half-life (Oukessou,
cations, the variation between individual adult camelids 1992). Alpacas had a larger volume of distribution, but a
is considerable: volume of distribution after intravenous similar half-life to camels. Subcutaneous administration
administration ranged from 0.25 to 2.54 L/ kg in one is common in clinical practice, particularly for the treat-
study, and peak plasma concentrations after 20 mg/ kg ment of Mycoplasma haemolama or Anaplasma phago-
intramuscular injection were 4.3 ± 3 μg/ml in another. cytophilum infection, but has not been evaluated
Single dose subcutaneous administration over the dor- scientifically, and is likely to have the same pitfalls as
sal thorax takes slightly longer (2–3 hours) to reach a subcutaneous florfenicol. Preparations using a propyl-
lower peak, followed by an extensive elimination phase ene glycol carrier are anecdotally associated with more
(Holmes et al., 2011). Regardless of whether 20 or local muscle irritation, shaking, and collapse than those
40 mg/ kg is given subcutaneously, plasma concentra- using polyvinylpyrrolidone (povidone); reactions with
tions are generally below 1 μg/ ml within 18–24 hours. either carrier are rare in New World camelids.

The long elimination half-lives (31–100 hours) fol- Enrofloxacin reaches therapeutic concentrations after
lowing subcutaneous injection may reflect important intravenous or subcutaneous dosing, but conflicting
considerations related to camelid skin. Subcutaneous information regarding its half-life is available (Christensen

548 Section IV. Antimicrobial Drug Use in Selected Animal Species

et al., 2001; Gandolf et al., 2004). There is a single report Data from studies involving glucose indicate that
of retinopathy after enrofloxacin administration to a gua- adult alpacas have an extracellular (interstitial) fluid
naco (Harrison et al., 2006). compartment that is approximately 37% larger than
adult llamas (Cebra et al., 2006a). This is similar to the
A variety of other parenteral antibiotics have been difference in volume of distribution for oxytetracycline
used in individual camelids without full knowledge of found in one study (Christensen et al., 2001), whereas
safety or efficacy. For the most part, reasonable extrapo- the volume of distribution for ceftiofur is reported to be
lation can be made from similar species, with caution 2.5–3 times larger in alpacas than llamas (Drew et al.,
remaining the overarching principle. As an example of 2004; Christensen et al., 1996).
this, tilmicosin, which is labeled for use in cattle and
sheep, but reported to have cardiotoxic effects in horses A physical basis for the difference in volumes of dis-
and goats, is also reported to have toxic effects in New tribution is found in the contributions of various organs
World camelids (Lakritz et al., 2012). to whole body weight. The full gastric viscera of llamas
make up approximately 4% more of whole body weight
Oral antibiotics have been studied less extensively in llamas than alpacas, meaning alpacas generally have
than injectable preparations. Adult camelids should be proportionally more soft tissue and interstitial fluid
expected to have similar problems with absorption as (Cebra et al., 2006b). Very lipophilic compounds such as
adult ruminants, and several studies demonstrate the florfenicol distribute into the gastric compartments and
flip-flop phenomenon, where apparent prolonged elimi- hence have similar volumes of distribution between lla-
nation actually reflects prolonged absorption. mas and alpacas, whereas hydrophilic compounds do
Trimethoprim, sulfamethoxazole, and sulfadiamethox- not, and are hence distribute over a proportionally larger
ine antibiotics appear to have poor absorption at rumi- volume in alpacas than in llamas. Dosage adjustment
nant dosages and cannot be recommended for systemic may be necessary, and has been demonstrated with oxy-
disorders (Chakwenya et al., 2002; Junkins et al., 2003; tetracycline. Aminoglycoside antibiotics, which,
Snook et al., 2002). Trimethoprim is virtually undetect- although hydrophilic, appear to diffuse more slowly out
able in the blood after oral dosing, and ion-trapping of of the vascular compartment would be less affected by
sulfas, which is a relatively greater problem in a forage- this, and hence should not be dosed higher in alpacas.
fed camelid versus a steer on an acidifying feedlot ration,
and likely to be worse in any ruminant or camelid with The same argument can be used to adjust dosages
inappetance and relative forestomach alkalinization, for younger camelids. Glucose studies suggest that
may contribute to their poor absorption. unweaned llama crias between 2 and 4 weeks of age have
an extracellular fluid compartment that is approximately
Oral tetracycline, amoxicillin-clavulanic acid, isonia- 30% larger than adult llamas (Cebra et al., 2005).
zid, and chloramphenicol use have also been reported, Unfortunately, the importance of this difference in anti-
but no pharmacokinetic studies have been performed. microbial dosages has not been investigated.
Oral enroflaxacin has a 29.3% bioavailability and reaches
therapeutic concentrations after dosing at 10 mg/ kg Compared with many other common domestic spe-
(Gandolf et al., 2004). Oral antibiotics might be more cies, much less information is available concerning the
useful in pre-ruminant camelids, but this usage has not frequency and importance of bacterial isolates. A table
been investigated. of what has been seen at Oregon State University and
what is available in the scientific literature is included
One topic that has received attention in recent years is (Table  32.3). Others have compiled similar findings
the dosing difference between llamas and alpacas. from other institutions in unpublished formats (Dechant
Pharmacokinetic studies have approximately followed et al., 2012; Anderson, 2009). Sufficient data were not
species popularity, with the earlier studies concerning lla- available to derive meaningful in vitro susceptibility
mas and more recent studies concerning alpacas, though conclusions. Since many of these bacteria are opportun-
the greater availability of llamas as test subjects has influ- ists, they would likely have similar sensitivity profiles to
enced the continued appearance of studies on llamas. Few isolates from other species. Of particular note here are
studies have compared the two species, which recently the α-hemolytic streptococci, which often are resistant
have been declared members of separate genera.

Chapter 32. Antimicrobial Drug Use in New World Camelids 549

Table 32.3. Bacterial isolates from camelid lesions at the Oregon State University Veterinary Diagnostic Laboratory and in
selected scientific publications. Non-OSU cases are listed in parentheses.

Wound or Superficial Tooth Root Female Repro Soft Tissue Myositisf
Lesiona Abscessb Tract Sepsis Adultc Sepsis Criad Abscesse

Gram-positive 1 (1) 31
Staphylococcus spp. 5
1 1
(coagulase −) (2)
Staphylococcus spp. 3 (2) (5) (1)
7 (57)
(coagulase +) 1 (1) 2 (5) 3 (5) 1 2 (1) 2
Non-hemolytic 1 1 5 (7) 3

Streptococcus 5 2 1 (4) (1)
α-hemolytic Streptococcus
β-hemolytic (1)

Streptococcus 6 (5) (1) 1 (2)
Enterococcus spp.
Rhodococcus equi 1 (1) 7 (1)
Clostridium spp.
Actinomyces spp. (1)
Peptostreptococcus
Arcanobacterium 21

pyogenes 2 (6) (4)
Listeria monocytogenes 2 (1)
Bacillus spp.
Corynebacterium (89)

pseudotuberculosis

aStone, 1993; Watt, 2000.
bCebra, 1996; Coyne, 1995; Niehaus, 2007.
cAnderson, 1995; Bedford, 1996; Butt, 1991; Cebra, 1998; Firshman, 2008; Fowler, 1992; Hamir, 2000; Hewson, 2001; Hutchison, 1992; Jones, 2009;
McLane, 2008; Middleton, 2006; Pearson, 2000; Quist, 1998; Ramos-Vara, 1998; Saulez, 2004; Seehusen, 2008; Sivasankar, 1999; Stone, 1993;
Tillotson, 1997; Tyler, 1996; Underwood, 1992; van Metre, 1991.
dAdams, 1992; Anderson, 1995; Cebra, 2000; D’Alterio, 2003; Dolente, 2007, Frank, 1998; Parreno, 2001; Sura, 2008.
eAnderson, 2004; Aubry, 2000; Braga, 2006; D’Alterio, 2003; Dwan, 2008; Hong, 1995; Koenig, 2001; St. Jean, 1993; Talbot, 2007.
fBurkhardt, 1993; Tyler, 1996; Uzal, 2000.

to penicillin and may be the cause of some treatment camelids. As the popularity of camelids increases, the
failures. Also of note are the increasing published and danger of transmissible diseases and cross-species trans-
anecdotal reports of Salmonella and Streptococcus equi mission also increases. This includes increasing risk of
subspecies zooepidemicus infection (Tillotson et al., transmission to people, particularly with microorgan-
1997; Saulez et al., 2004; Middleton et al., 2006; Hewson isms such as Salmonella, Listeria, and E. coli O157
et al., 2001; Jones et al., 2009). These last microorgan- (Featherstone et al., 2011).
isms are primary pathogens in camelids, and may affect
multiple, healthy camelids on one property. With As stated above, specific localized syndromes (such as
Salmonella, camelids may also be involved in multispe- bacterial pneumonia or enteritis) are rare, so aside from
cies outbreaks. Corynebacterium pseudotuberculosis is the chronic, focal infections, most bacterial diseases have
another primary pathogen involved in multispecies out- been grouped together as septic conditions. These ani-
breaks that is being increasingly recognized as a cause mals usually present with general systemic signs includ-
of  peripheral or internal lymph node abscessation in ing fever, inappetance, obtundation, and weakness, but
may also have specific signs referable to the affected

550 Section IV. Antimicrobial Drug Use in Selected Animal Species

organs. As a general conclusion, the relative equality dermatitis. As with antibacterial use, all antifungal use
between Gram-negative and Gram-positive isolates from in camelids is extra-label.
wounds and camelids with sepsis supports the initial use
of broad-spectrum antibiotics. Combinations of an ami- Bibliography
noglycoside with a beta-lactam antibiotic, or of ceftiofur
alone or in combination are most common. Other single Ali BH, et al. 2003. Comparative plasma pharmacokinetics
medications, such as oxytetracycline, enrofloxacin, or and tolerance of florfenicol following intramuscular and
florfenicol may be useful in some situations. Collection intravenous administration to camels, sheep and goats. Vet
and culture of pertinent body fluids (blood, peritoneal Res Commun 27:475.
fluid, pleural fluid, cerebrospinal fluid, urine, feces, aspi-
rates, etc.) may yield information about specific patho- Anderson DE. 2009. Analysis of antimicrobial cultures from
gens and allow refinement of antibiotic selection. llamas and alpacas: a review of 1821 cultures (2001–2005).
Proceedings of the International Camelid Health Conference.
Female reproductive tract infections frequently
involve Gram-negative enteric bacteria and are fre- Bedenice D, et al. 2012. Florfenicol pharmacokinetics in
quently treated with gentamicin infusions, whereas healthy adult alpacas evaluating two commercially availa-
tooth root abscesses and other tissue abscesses more fre- ble drug formulations. J Vet Intern Med. In press.
quently involve Gram-positive or anaerobic bacteria
and are most commonly treated with long courses (20– Boxenbaum HG, et al. 1977. Pharmacokinetics of sulphad-
60 days) of penicillin, ceftiofur, or florfenicol. The imethoxine in cattle. Res Vet Sci 23:24.
camelid blood parasite, Mycoplasma haemolamae, is
most commonly treated with long-acting oxytetracy- Buchheit TM, et al. 2010. Use of a constant rate infusion of
cline preparations. Chapters on the individual antibiot- insulin for the treatment of hyperglycemic, hypernatremic,
ics should be consulted for additional information hyperosmolar syndrome in an alpaca cria. J Am Vet Med
concerning use and specific contraindications. Assoc 236:562.

A variety of fungal diseases are reported in camel- Cebra CK, et al. 2005. Glucose tolerance and insulin sensitiv-
ids, but only a single antifungal study has been con- ity in crias. Am J Vet Res 66:1013.
ducted (Chan et al., 1998). Systemic mycoses include
aspergillosis, cocciodiomycosis, cryptococcosis, his- Cebra CK, et al. 2006a. Meta-analysis of glucose tolerance in
toplasmosis, and mucormycosis. Dermal or superfi- llamas and alpacas. In: Gerken M, Renieri C (eds). South
cial mycoses include candidiasis, ringworm, and American Camelids Research, vol. 1. Proceedings of the
entomophthoramycosis. 4th European Symposium on South American Camelids
and DECAMA European Seminar. The Netherlands:
Voriconazole given intravenously (4 mg/ kg) main- Wageningen Academic Publishers, p. 161.
tains plasma concentrations > 0.1 μg/ml for at least 24
hours (Chan et al., 1998). Clearance and volume of dis- Cebra CK, et al. 2006b. Determination of organ weights in
tribution are comparable to horses but lower than in llamas and alpacas. In: Gerken M, Renieri C (eds). South
humans. Absorption after oral dosing is noted within 5 American Camelids Research, vol. 1. Proceedings of the
minutes, but bioavailability is less than 23%. Absorption 4th European Symposium on South American Camelids
is generally slow and unpredictable, and the need for and DECAMA European Seminar. The Netherlands:
higher doses has been postulated. Other systemic anti- Wageningen Academic Publishers, p. 233.
fungal use has been largely extrapolated from rumi-
nants. Agents used empirically include fluconazole Chakwenya J, et al. 2002. Pharmacokinetics and bioavailabil-
(14 mg/ kg, IV or PO as a loading doses, followed by ity of trimethoprim-sulfamethoxazole in alpacas. J Vet
5 mg/ kg, q 24 h), itraconazole (5 mg/ kg, IV or PO, q Pharmacol Ther 25:321.
24 h), and amphotericin B (0.5 mg/ kg diluted in 0.5–1 L
of 5% dextrose IV over 1 h, q 24; after pretreatment with Chan HM, et al. 2008. Pharmacokinetics of voriconazole
flunixin meglumine [0.25 mg/ kg, IV]). Miconazole and after single dose intravenous and oral administration to
clotrimazole have been used topically for fungal alpacas. J Vet Pharmacol Ther 32: 235.

Chatfield J, et al. 2001. Disposition of sulfadimethoxine in
camels (Camelus dromedarius) following single intrave-
nous and oral doses. J Zoo Wildl Med 32:430.

Christensen JM, et al. 1996. The disposition of five therapeu-
tically important antimicrobial agents in llamas. J Vet
Pharmacol Ther 19:431.

Christensen JM, et al. 2001. Comparative metabolism of oxy-
tetracycline and florfenicol in the llama and alpaca.
Unpublished data.

Dechant J, et al. 2012. Pharmacokinetics of ceftiofur crystal-
line free acid after single and multiple subcutaneous
administrations in healthy alpacas (Vicugna pacos). J Vet
Pharmacol Therap 36:122.

Chapter 32. Antimicrobial Drug Use in New World Camelids 551

Dowling PM, et al. 1996. Pharmacokinetics of gentamicin in Kumar R, et al. 1998. Pharmacokinetics, bioavailability and
llamas. J Vet Pharmacol Ther 19:161. dosage regimen of sulphadiazine (SDZ) in camels (Camelus
dromedarius). J Vet Pharmacol Ther 21:393.
Drew ML, et al. 2004. Pharmacokinetics of ceftiofur in llamas
and alpacas. J Vet Pharmacol Ther 27:13. Lackey MN, et al. 1995. Urinary indices in llamas fed differ-
ent diets. Am J Vet Res 56:859.
Featherstone CA, et al. 2011. Verocytotoxigenic Escherichia
coli O157 in camelids. Vet Rec 16:194. Lackey MN, et al. 1996. Single intravenous and multiple dose
pharmacokinetics of gentamicin in healthy llamas. Am
Gandolf AR, et al. 2005. Pharmacokinetics after intravenous, J Vet Res 57:1193.
subcutaneous, and oral administration of enrofloxacin to
alpacas. Am J Vet Res 66:767. Lewis CA, et al. 2009. Colonic impaction due to dysautono-
mia in an alpaca. J Vet Intern Med. 23:1117.
Hadi AA, et al. 1994. Pharmacokinetics of tobramycin in the
camel. J Vet Pharmacol Ther 17:48. Middleton JR, et al. 2006. Dysautonomia and salmonellosis
in an 11-year-old female llama (Lama glama). J Vet Intern
Harrison TM, et al. 2006. Enrofloxacin-induced retino- Med 20:213.
pathy in a guanaco (Lama guanicoe). J Zoo Wildl Med
37:545. Oukessou M, et al. 1992. Pharmacokinetics and local toler-
ance of a long-acting oxytetracycline formulation in cam-
Hewson J, et al. 2001. Peritonitis in a llama caused by els. Am J Vet Res 53:1658.
Streptococcus equi subsp. zooepidemicus. Can Vet J 42:465.
Saulez MN, et al. 2004. Necrotizing hepatitis associated with
Holmes K, et al. 2011. Florfenicol pharmacokinetics in enteric salmonellosis in an alpaca. Can Vet J 45:321.
healthy adult alpacas after subcutaneous and intramuscu-
lar injection. J Vet Pharmacol Ther 35:382. Simpson KM, et al. 2011. Acute respiratory distress syn-
drome in an alpaca cria. Can Vet J 52:784.
Hutchison JM, et al. 1993. Acute renal failure in the llama
(Lama glama). Cornell Vet 83:39. Snook CS, et al. 2002. Plasma concentrations of trimetho-
prim and sulfamethoxazole in llamas after orogastric
Jones M, et al. 2009. Outbreak of Streptococcus equi ssp. zooepi- administration. J Vet Pharmacol Ther 25:383.
demicus polyserositis in an alpaca herd. J Vet Intern Med
23:220. Tillotson K, et al. 1997. Outbreak of Salmonella infantis infec-
tion in a large animal veterinary teaching hospital. J Am
Junkins K, et al. 2003. Disposition of sulfadimethoxine in Vet Med Assoc 211:1554.
male llamas (Llama glama) after single intravenous and
oral administrations. J Zoo Wildl Med 34:9.

Antimicrobial Drug Use in Swine 33

David G.S. Burch

Introduction The concerns regarding antimicrobial use in animals
and their relation to man regarding resistance transmis-
Antimicrobial drug use in swine has always been substan- sion via zoonotic bacteria such as Salmonella spp.,
tial and in some cases, the swine industry has been Campylobacter coli, and more recently methicillin-
considered overreliant on their use. As farms have evolved resistant Staphylococcus aureus (MRSA) or more indi-
from small back-yard operations, only 50 years ago, to rectly via Escherichia coli or Enterococcus spp. is under
today’s substantially larger units, it is not surprising that huge review at the moment and a number of changes
antibiotics have been used to help farmers maintain their can be anticipated over the next 5 years. In the United
production under these major management, housing and States there are calls to ban the use of antibiotic growth
disease pattern changes. It must be remembered that promoters and only use antimicrobials for prevention
antibiotics have a cost and that farmers are unlikely to pay and treatment (chapter 22). The European Union (EU)
for them unless they can see a benefit from their use. banned the use of antimicrobial growth promoters in
2006, and now there are calls from the European
Swine farming has made great steps forward in man- Parliament to go a step further and stop all prophylactic
agement and husbandry systems to reduce antimicro- use. The United States has banned the use of fluoroqui-
bial use. Examples are the improvement of biosecurity nolones in poultry (drinking water use) but permitted
(keeping diseases out), sourcing of high-health genetic the use of injectables in swine, but in Europe there are
stock and the utilization of 3-site production. The latter calls to ban the use of all fluoroquinolones and third-
enables “all-in and all-out” procedures to be followed and fourth-generation cephalosporins in veterinary
with the accompanying improvements in hygiene and medicine. The United States has already put restrictions
infection control and the prevention of back infection on the use of all cephalosporins to “on-label” use only
from older pigs on the farm. Unlike the broiler industry, and in the EU the cessation of use is being implemented
which pioneered this system and where stock is reared for third-generation cephalosporins, such as ceftiofur, in
for only 5–6 weeks before slaughter, pigs are raised for the poultry industry. There was a high level of extended-
nearly 6 months, making it not so easy to follow. In spectrum beta-lactamases (ESBLs) found in E. coli, on
farrow-to-finish operations, often family farms, which average 8.5% (range 0–26.4%), from chickens (Anon.,
are still the most common operation, there is still a need 2011). It was thought to be associated with the extensive
for antimicrobial medication to assist with health and use of injections in ovo and in day-old-chicks, even
production, in spite of the use of vaccination, as not all
diseases can be controlled sufficiently that way.

Antimicrobial Therapy in Veterinary Medicine, Fifth Edition. Edited by Steeve Giguère, John F. Prescott and Patricia M. Dowling.
© 2013 John Wiley & Sons, Inc. Published 2013 by John Wiley & Sons, Inc.

553

554 Section IV. Antimicrobial Drug Use in Selected Animal Species

though it was not an approved use. By comparison, highly effective route of administration to an individual
ESBL production in porcine E. coli in the EU was low at animal, but many antibiotics require repeated injections
about 2.3% (range 0–3.8%; Anon., 2011). Contamination on a daily basis. The development of long-acting formu-
of both broiler and pig meat with ESBL-producing E. coli lations has improved the issue regarding compliance, to
was also reported, hence the public health concern. complete the course of treatment. There has been an
increase in the prophylactic use of third-generation
In the face of all this, the swine industry in conjunc- cephalosporins in baby piglets to prevent a variety of
tion with other industries is advocating the responsible wound infections post-processing (tail docking and cas-
use of antimicrobials via various bodies such as the UK’s tration) and also early infections with Streptococcus suis
Responsible Use of Medicines Alliance (RUMA), the EU and Haemophilus parasuis. This may have triggered the
via EPRUMA and the United States via their National selection of MRSA clones (specifically CC398), which
Pork Board. This is seen as the only way forward to has become widespread on the continent of Europe
maintain the availability of antimicrobials, which are (Anon., 2009) and also in North America (Khanna et al.,
needed in veterinary medicine to treat and prevent dis- 2008). It has also probably led to the very high level of
ease and to maintain the health and welfare of the ani- resistance (41.8%) to ceftiofur that has been reported in
mals under their care. At the same time, efforts are being isolates of porcine E. coli from clinical cases in the
made to reduce unnecessary use and the use of critical United States (Frana et al., 2012).
human antibiotics where suitable alternatives are avail-
able. In the EU antimicrobial drugs are prescription- Oral administration of antibiotics is the most com-
only medicines (POMs) and used under veterinary mon route of application in swine medicine. Piglets may
supervision or prescription. In the United States, their be treated individually by oral dosers containing anti-
use is much freer, in that many drugs can be used in feed biotics. These have proved most useful for the control of
without a prescription but their inclusion level is nor- neonatal usually associated with E. coli and gut active
mally regulated by the feed mill. This may also change in and systemically active formulations of enrofloxacin,
the future. In some EU countries, the use of antimicro- trimethoprim/sulfonamide and amoxycillin have proved
bials in feed is being stopped; for example, in the very effective. Later on, when the infection is primarily
Netherlands, in an attempt to reduce overall antimicro- in the gut, gut-active antibiotics, such as the amino-
bial usage, and it is strongly restricted in Germany and glycosides neomycin, aminocyclitol spectinomycin and
Denmark. However, neither the third- and fourth- the polymixin colistin, are widely used. Toltrazuril is
generation cephalosporins nor fluoroquinolones are also highly effective for the prevention and treatment of
used in feed in the EU. coccidiosis caused by Isospora suis in piglets.

Responsible use calls for vets and farmers to use anti- Water medication is widely used and in some coun-
microbials “as little as possible but as much as needed.” tries becoming more popular due to the introduction of
There are a number of guidelines on how to use antimi- effective automatic dosing machines. In the past it was
crobials properly and it is the aim of this chapter to help limited to pen troughs or individual pen tanks. Larger
with the decision making regarding the right antibiotic header tanks allowed whole sheds/barns to be treated
for the right infection, to be administered at the right but in some cases it was difficult depending on the size of
dose via the appropriate route. tank and frequently required 2–3 applications of a drug
each day to ensure an adequate intake and duration of
Antimicrobial Administration in Swine activity. Automatic water proportioner machines, where
the antibiotic is dissolved in a concentrate, which flows
In general, the injection of pigs, other than baby piglets, into the main water system at a set target rate (approxi-
is laborious and is used primarily to treat clinically ill mately 1–2%, depending on the solubility of the drug)
pigs either with acute respiratory infections such as have proved most popular on larger sites. However, the
Actinobacillus pleuropneumoniae or enteric infections antibiotic needs to be sufficiently soluble. In many cases
such as swine dysentery caused by Brachyspira hyod- the advantages of prompt treatment, controlled dose
ysenteriae, which may be too sick to eat or drink. It is a rates and duration of treatment has helped the replace-
ment of medication via the feed for treatment purposes.

Chapter 33. Antimicrobial Drug Use in Swine 555

Feed medication in most countries is still the main the multiplication of the organism, so to be effective
route of antimicrobial administration in the swine drug concentrations in the gut contents must exceed the
industry. For treatment of disease it can be argued that it minimum inhibitory concentration (MIC) of the bacte-
is not the most efficient route of administration, as it rium. In some countries, like the United States, anti-
may take some days for the feed to be manufactured, biotics can be still used for growth promotion. This is
delivered and work through the storage bin system to sometimes a gray area between prevention concentra-
get to the pigs. For ease of administration, it is the sim- tions and subinhibitory concentrations, which can pro-
plest route. For the prevention of disease, for the early duce improvements in growth rate and feed conversion
treatment (metaphylaxis), it is ideal, as it can be planned efficiency. Many successful growth promoters actually
that the pigs receive the medicated feed on arrival or have a prevention of disease effect/claim, such as virgin-
transfer from one shed/barn to another, especially when iamycin, prevents Clostridium perfringens infections;
they are known to come from an infected source. The carbadox prevents swine dysentery (B. hyodysenteriae)
aim of metaphylaxis is to eliminate or reduce as much as and tylosin prevents porcine proliferative enteropathy
possible the infectious agent, so that it does not cause “ileitis” (Lawsonia intracellularis). This possibly explains
disease in the next growing phase. The drug is adminis- the reason why it could be relatively easy for a switch
tered at a therapeutic dose in an attempt to eliminate the from growth promotion claims to prevention claims for
infection, whether it is B. hyodysenteriae or S. suis. Low some of these antimicrobials.
concentrations of bacteria (say 102) respond better to
lower levels of antibiotic and are less likely to mutate There are some pharmacokinetic disadvantages to
than high concentrations of microorganisms (> 106; administering medication via the feed, as sometimes the
Drlica, 2003), which are found in clinical infections. feed interferes with the absorption of a drug and reduces
This actually supports early treatment or preventative its bioavailability (Nielsen, 1997) and thereby plasma con-
use rather than waiting for high levels of disease before centrations. This can have an impact particularly when
treatment. Antibiotics are often used at lower levels to treating systemic or respiratory infections (Figure 33.1).
prevent infection or re-infection from a contaminated
environment, especially in the case of swine dysentery. On the other hand, oral medication whether by
The concentrations in feed are generally lower than the water  or in feed is very effective for treating enteric
treatment level but are effectively inhibitory, preventing infections, especially E. coli, Salmonella spp., C. perfrin-
gens, L. intracellularis, and Brachyspira spp., as effective
drug concentrations in the gut contents, whether it is in

Bioavailability (%) 100
90
80
70
60
50
40 Fasted
30 Fed
20
10
0

ChOlSxoTuyrrlEttiLpnSiPeerttmhpnerrioeacrfntaalidoacchicoiyyloxammlccipzllyayiiirniccciininnennVmene

Figure 33.1. Bioavailability (%) of antimicrobials when given fasted or after feeding to pigs (Nielsen, 1997).