Guide to Antimicrobial Use in Animals

11 Dogs & Cats

Table 11.2 Recommendations on antibacterial therapy of integumentary infections. Antimicrobial options are listed in order of preference within each category 188 Guide to antimicrobial use in animals

Infection/ Commonly Second choice Last resort Comments
disease isolated pathogen First choice (empirical) (based on culture)

Surface S. intermedius Generally does not require systemic antimicrobial therapy. Treatment with shampoos containing
Topical antimicrobials should be used if focal superficial lesions are observed. antiseptics such as chlorhexidine or
pyoderma astringent antimicrobial spray.

Localized S. intermedius Chlorhexidine gel Amoxicillin, Doxycycline Fluoroquinolone d To be combined with shampoos
pyoderma a Benzol peroxide gel Lincosamide b containing antiseptics. Identify and cure
Fusidic acid the primary cause
Mupirocin TMS
As above
Lincosamide b and/or Amox/clav
antiseptic shampoos First-generation cephalosporin c As above

First-time S. intermedius Amox/clav Amoxicillin Fluoroquinolone d Flush with antiseptics (e.g. povidone-
First-generation iodine, chlorhexidine or 2% acetic acid).
superficial Doxycycline
Cephalosporin c As above.
pyoderma TMS To be combined with application of
(diffuse)a Fusidic acid
Amox/clav EDTA.
First-generation Cephalosporin c

Recurrent S. intermedius Amoxicillin Fluoroquinolone d
superficial Gram+ cocci Doxycycline Cefovecin e
or deep Lincosamide Cefpodoxime e
pyoderma a
TMS
Otitis f
Topical aminoglycoside g Fluoroquinolone d (topical)

Otitis f Gram– rods Polymixin/Oxytetracycline Topical aminoglycoside g Fluoroquinoloned (topical)
Otitis f P. aeruginosa Topical aminoglycoside g Ticarcillin (topical)
Polymixin
Bite wounds Pasteurella Silver sulfadiazine Doxycycline BAST
Staphylococci Enrofloxacin (topical)h TMS
Other Lincosamide b
Amoxicillin Amox/clav

Amox/clav, amoxicillin/clavulanate; TMS, trimethoprim/sulfonamide.

BAST, based on antimicrobial susceptibility testing.
aCytology should always be done. Culture and antimicrobial susceptibility testing are recommended in all cases of deep and/or recurrent pyoderma, when infection fails to respond to

empirical treatment, if mixed infection is shown by cytology and in immunosuppressed animals.
bAvailable lincosamides: clindamycin or lincomycin.
cAvailable first-generation cephalosporins: cefalexin and cefadroxil.
dAvailable fluoroquinolones: enrofloxacin, marbofloxacin, difloxacin and orbifloxacin.
eThird-generation cephalosporins should only be used for treated deep lesions contaminated with Enterobacteriaceae or in cases at high risk of non-compliance.
fCytology is recommended to guide drug choice. Culture and antimicrobial susceptibility testing should be performed if rods are present.
gTopical aminoglycosides: gentamycin, neomycin, framycetin/gramicidin or amikacin.
hChoice based on clinical experience and drug availability.

Table 11.3 Recommended dosages of systemic antimicrobial agents used in small animals

Administration

Drug route Dose(s)a Dose interval Comments

Amikacin IV, IM, SC Dog: 15–30 mg/kg q24 h Dog (avoid use in renal disease). Guidelines for antimicrobial use in dogs and cats
IV, IM, SC Cat: 10–14 mg/kg q24 h Cat (avoid use in renal disease).
Amoxicillin/ PO Dog: 12.5–25 mg/kg q12 h Dose listed is based on combined ingredients (amoxicillin +
clavulanate Cat: 62.5 mg per cat clavulanate).
Amoxicillin PO 22 mg/kg q8–12 h For β-lactamase-producing strains, consider amoxicillin-clavulanate
as an alternative.
Ampicillin IM, SC, IV 10–20 mg/kg q8 h
Ampicillin/ PO 20–40 mg/kg q8 h Dose is higher for oral dose because of low systemic absorption.
sulbactam IV, IM 10–20 mg/kg q8 h Dose is listed for the ampicillin component. Note: sulbactam is not as
Azithromycin
PO Dog: 3–5 mg/kg q24 h to q48 h effective for β-lactamase inhibition as clavulanate.
Cefadroxil Cat: 5–10 mg/kg Often, once daily administration is used for the first 3–5 days, then
PO Dog: 22–20 mg/kg Dog: q12 h
Cefazolin Cat: 22 mg/kg Cat: q24 h every 48 h thereafter.
IV, IM 20–35 mg/kg q8 h First-generation cephalosporin.
Cefepime IV 22 mg/kg q2 h (during surgery)
Cefovecin IV, IM 40 mg/kg q6 h First-generation cephalosporin. Therapy.
Cefpodoxime SC Dog, cat: 8 mg/kg q14d Prophylaxis.
PO Dog: 5–10 mg/kg q24 h Fourth-generation cephalosporin.
Cefotaxime Cat: dose not Third-generation cephalosporin.
Cefoxitin IV, IM established q12 h Third-generation cephalosporin.
Ceftiofur IV, IM 50 mg/kg q6–8 h
SC 30 mg/kg q24 h Third-generation cephalosporin.
Cefalexin 4.4 mg/kg Second-generation cephalosporin.
PO q12 h Urinary tract infections only.
Chloramphenicol 10–30 mg/kg Third-generation cephalosporin.
PO Dog: q8 h Most common dose is 25 mg/kg q12 h PO. First-generation
Dog: 40–50 mg/kg Cat: q12 h cephalosporin.
Cat: 12.5–20 mg/kg Prolonged use can lead to bone marrow depression, especially in

cats.

Continued 189

11 Dogs & Cats

11 Dogs & Cats

Table 11.3 (Continued) 190 Guide to antimicrobial use in animals

Administration

Drug route Dose(s)a Dose interval Comments

Ciprofloxacin PO 20 mg/kg q24 h Fluoroquinolone. Use of veterinary-labelled quinolones should be
Clarithromycin considered first.
Clindamycin PO 7.5 mg/kg q12 h Derivative of erythromycin. May cause GI problems in some animals.
May cause GI problems in some animals.
Difloxacin PO Dog: 11–22 mg/kg Dog: 11 mg/kg q12 h
Dihydrostreptomycin Fluoroquinolone. Refer to precautions in text about using this class of
Doxycycline Cat: 11 mg/kg up to or 22 mg/kg q24 h drug. Do not use in cats (safety not established).
Enrofloxacin
33 mg/kg Cat: q24 h Treatment of Rickettsia or Ehrlichia may use 5 mg/kg q12 h.
Erythromycin Fluoroquinolone. Refer to precautions in text about using this class of
Gentamicin PO Dog: 5–10 mg/kg q24 h
Imipenem-cilastatin drug.
No dose established In cats, do not exceed 5 mg/kg. Although not licensed for IV use in
Lincomycin dogs, it has been given this route (cautiously) if necessary.
PO Dog, Cat: 3–5 mg/kg q12 h Gastrointestinal problems, especially vomiting, are common.
Linezolid q24 h Can be nephrotoxic; ensure adequate hydration and renal function
PO, IM Dog: 5–20 mg/kg before use.
Cat: 5 mg/kg Penems are critically important drugs in human medicine.
Do not use unless it is a life-threatening infection and susceptibility
PO 10–20 mg/kg q8–12 h tests have shown resistance to any antimicrobials except penems.
IV, IM, SC q24 h Use of lincomycin has been replaced in many hospitals
Dog: 9–14 mg/kg by clindamycin, which is similar in activity, but has better
IM, IV Cat: 5–8 mg/kg q6–8 h pharmacokinetic characteristics.
Critically important drugs in human medicine.
5 mg/kg Do not use unless it is a life-threatening infection and susceptibility
tests have shown resistance to any antimicrobials except linezolid.
PO 15–25 mg/kg; for q12 h

pyoderma 10 mg/kg

has been used

Oral Dog, cat: 10 mg/kg q12 h

Marbofloxacin Oral 2.2–5.75 mg/kg q24 h Fluoroquinolone. Guidelines for antimicrobial use in dogs and cats
Meropenem SC, IV 8.5 mg/kg Refer to precautions in text about using this class of drug.
q12 h SC or q8 h IV Penems are critically important drugs in human medicine.
Metronidazole Oral Dog: 12–15 mg/kg Do not use unless it is a life-threatening infection and susceptibility
Cat: 10–25 mg/kg Dog: 15 mg/kg q12 h tests have shown resistance to any antimicrobials except penems.
Neomicin Oral 10–20 mg/kg or 12 mg/kg q8 h Do not exceed recommended doses per day or neurotoxicity is likely.
Nitrofuraontoin Oral 10 mg/kg Cat: q24 h Metronidazole is unpalatable in cats and metronidazole benzoate
q12 h (ester) can be considered as an alternative.
Orbifloxacin Oral 2.5–7.5 mg/kg Daily dose which Not recommended as oral treatment for diarrhoea.
13.5 mg/kg can be divided into This drug is a urinary antiseptic and should not be used for systemic
Ormethoprim- Oral 20 000–40 000 4 times daily infections.
sulfadimethoxine U/kg treatments
Penicillin G IM, IV 5 mg/kg q24 h Fluoroquinolone.
50 mg/kg Refer to precautions in text about using this class of drug.
Penicillin V Oral q24 h Similar in activity as trimethoprim-sulfonamides.
Rifampin Oral 15 mg/kg
Ticarcillin IV, IM q6–8 h If IM route is used, less frequent intervals (q24 h) can be used.
15 mg/kg
Trimethoprim- Oral q12 h Not recommended (not active orally due to poor absorption).
sulfadiazine IV q6h IV Caution: may turn urine, saliva and tears orange colour.

Vancomycin Once or Last resort drug against multi-resistant Pseudomonas.
twice daily, or Do not use unless susceptibility tests have shown resistance to any
30 mg/kg once daily antimicrobials except ticarcillin.
q8 h, IV infusion for Caution with use of sulfonamides in dogs (see Section Canine
30 min pyoderma).

Glycopeptide antibiotic of critical importance in human medicine.
Do not use unless it is a life-threatening infection and susceptibility
tests have shown resistance to any antimicrobials except
glycopeptide. Give IV only, by slow infusion.

aDoses listed in this table are taken from Papich 2007(89)

191

11 Dogs & Cats

192 Guide to antimicrobial use in animals

11 Dogs & Cats resulting in less antibiotic use in treated animals. Furthermore, moderately resistant organisms can be
These drugs have good activity against staphylococci, treated by achieving high antimicrobial concentra-
and are also registered for skin infections. Despite tions locally.
their convenient administration and pharmacoki-
netic properties, third-generation cephalosporins are 11.3.2 Ear infections
active against a wide range of Gram-negative bacte-
ria that are normally not associated with pyoderma, Otitis externa is very common in the dog but rare in
and their activity against S. intermedius is not superior the cat. Inflammation of the external ear canal may
to first-generation compounds. Furthermore, these be due to many causes and is frequently complicated
drugs have potential for selection of both methicil- by infection with bacteria, yeasts or both. Therefore,
lin resistance in staphylococci and ESBL-producing when managing otitis externa, it is important to
organisms. Cefovecin and cefpodoxime proxetil are identify the infectious agent as well as the underlying
only recommended as first-line agents if there is a cause (e.g. allergy, foreign body, or chronic moisture
substantial problem with compliance. According to from swimming or conformation). The keys to suc-
the label instructions of cefovecin in Europe, it is cessful management of otitis externa are: (i) identifi-
prudent to reserve third-generation cephalosporins cation of the infectious agent via cytology; (ii) topical
for the treatment of clinical conditions, which have treatment with otic cleansers, to remove the excess
responded poorly, or are expected to respond poorly, wax, and medication; (iii) use of topical steroids when
to other classes of antimicrobials or first-generation indicated to open the ear canal and decrease inflam-
cephalosporins. Use of the product should be based mation; (iv) frequent monitoring of the treatment
on susceptibility testing and take into account official progress; and (v) a maintenance plan consisting of
and local antimicrobial policies. regular ear cleaning once the infection has resolved to
keep it from recurring.
Deep pyoderma
The most common organisms associated with
Deep skin infections occur when the follicular infec- acute otitis externa are the yeast Malassezia pachyder-
tion ruptures into the dermis, producing furunculo- matis and various bacterial species, most commonly
sis and cellulitis. In addition to staphylococci, deep S. intermedius and Pseudomonas aeruginosa, Proteus,
lesions can also be contaminated with Pseudomonas E. coli, β-haemolytic streptococci, Corynebacterium
and E. coli organisms. Therefore, culture and sus- and S. schleiferi. Acute otitis responds readily to most
ceptibility testing should be performed on all cases. combination treatments that include a topical anti-
Cephalosporins and amoxicillin/clavulanate are the fungal, antibacterial and corticosteroid agent. Topical
drugs of choice for empirical treatment, which may be products that are used for treatment of otitis are
necessary whilst waiting for susceptibility test results. listed in Table 11.4. Both solutions, suspensions and
As a rule, treatment of deep pyoderma requires a lon- ointments, may be effective. Because topical antimi-
ger course of treatment than superficial pyodermas. crobials are administered in concentrated formula-
A minimum of four weeks should be considered with tions (mg/ml), susceptibility tests that are based on
the endpoint being two weeks past clinical resolution achieved plasma concentrations (µg/ml) are mis-
of the lesions. This additional length of treatment is leading because they will greatly underestimate the
indicated because of the fibrosis or the granuloma- drug’s activity. As a general rule, solutions or sus-
tous nature of the lesions. Dogs with deep pyoderma pensions are recommended for more stenotic canals,
usually benefit from concurrent topical therapy and a sufficient volume needs to be applied to ensure
such as whirlpool baths using dilute chlorhexidine treatment of the infection in the horizontal ear canal
and antibacterial shampoos. When lesions are local- (and bulla if the tympanic membrane is ruptured).
ized, topical antimicrobials should be used instead of Many cases of otitis externa are complicated by otitis
systemic drugs. For example, topical therapy with media, which is confirmed by presence of a ruptured
fusidic acid, mupirocin or benzoyl peroxide gel may tympanic membrane. However, examination of the
be sufficient to treat focal deep infections over pres- tympanic membrane is not always possible and the
sure points. In these situations, topical antimicrobials tympanic membrane may heal, leaving residual oti-
should be preferred as they exert a lower antimi- tis media. Regardless of whether or not the tympanic
crobial selective pressure on commensal bacteria. membrane is ruptured, all infections of the ear canal

Guidelines for antimicrobial use in dogs and cats 193

Table 11.4 Topical antibacterial options for treatment Although P. aeruginosa isolates are often sensitive to
of otitisa gentamicin in vitro, treatment with topical products
containing gentamicin or neomycin is rarely success-
Antimicrobial drug Potential ful because aminoglycosides are inactivated by puru-
Topical concentration ototoxicity lent material present in the ear canal. Furthermore,
Amikacin many gentamicin topical preparations are in an oint-
Gentamicin 50 mg/ml b Yes ment base, which may be too viscous to penetrate
Neomycin 3 mg/ml c (Yes)h through the stenotic ear canal, and the recommended
Enrofloxacin 3.2 mg/ml c Yes dosage may be too small to achieve an adequate con-
Fusidic acid 10–20 mg/ml d No centration in the horizontal ear canal.
Polymixin B 0.2 mg/ml c No
Tetracycline 10 000 U/ml e Yes Although resistance to fluoroquinolones can develop
Ticarcillin 2.2 mg/ml c No during therapy (63), topical treatment with enro-
Tobramycin 25 mg/ml f No floxacin can be even successful with strains defined as
Silver sulfadiazine 0.3%c No resistant in vitro according to standard-setting com-
0.5–1%g No mittees such as the Clinical and Laboratory Standards
Institute (CLSI, formerly NCCLS). In fact, such
a In case of P. aeruginosa infection, all products should be preceded breakpoints are based on plasma concentrations
by application of Tris EDTA and should be used twice daily. obtained by oral dosing (µg/ml) and much higher
b 3 ml amikacin (250 mg/ml) are mixed with 12 ml glycerine. Apply concentrations can be achieved when enrofloxacin
is administered topically (mg/ml). Fluoroquinolone
0.5 ml twice daily into affected ear. resistance in P. aeruginosa is conferred by chromo-
c Commercial products available. somal mutations and overexpression of efflux pumps
d Dilute 1:6 in Tris EDTA or sterile water. Apply 0.5 ml twice daily (64). Topical use of a calcium-chelating agent such
into affected ear. as Tris-ethylene diamine tetra acetic acid (EDTA)
e Mix 50 ml saline into a vial containing 500 000 U polymixin B. This may help to override the resistance attributed to the
efflux pump by opening up pores in the bacteria and
gives a final concentration of 10 000 U/ml and is stable for 60 days facilitating drug penetration (65–67). Because the ear
canals are often stenotic, it is essential to open the
when refrigerated. Apply ½ ml twice daily into affected ear. canals to allow penetration of the topical treatments.
f Reconstitute the 3 g vial with 6 ml saline and freeze in 2 ml This can be accomplished through systemic and/or
topical corticosteroids. Often the systemic steroids
aliquots. These are stable for 3 months. Thaw one 2 ml aliquot are used initially followed by topical steroids once the
canal is less stenotic and ulcerated.
and dilute with 40 ml saline (25 mg/ml), divide into 10 ml-aliquots
11.3.3 Urinary tract infections (UTI)
and freeze. Remove one 10 ml aliquot at a time and apply ½ ml
twice daily into affected ear. Cystitis
g This product is supplied as a 1% cream or a micronized powder.
This can be mixed as a suspension in sterile water at 0.5–1.0%. Cystitis and lower UTIs are generally more common
h Gentamicin sulfate in the ear of dogs with intact or ruptured in the dog than in the cat, with a higher frequency
tympanic membranes was shown not to induce detectable in castrated bitches and males. The most common
alteration of cochlear or vestibular function (87). bacterium causing cystitis in the dog is E. coli, which
has been estimated to account for 70–75% of cases,
are managed topically. Systemic antimicrobial therapy followed by staphylococci, Proteus and enterococci. 11 Dogs & Cats
is more expensive and usually offers no benefit for Urine analysis including physico-chemical analysis
otitis externa or media since it is difficult to achieve and cytology is important to guide in the diagnosis as
adequate concentrations in the ear tissue and middle well as in the choice of the antimicrobial agent. The
ear, even if maximum doses are administered (58). number of bacteria and the presence of granulocytes
provide diagnostic evidence of infection. Urine should
P. aeruginosa is the most common organism be collected by cystocentesis as this method avoids
associated with chronic otitis externa and media in
the dog and the most frustrating to deal with (59).
P. aeruginosa is typically multi-resistant due to intrinsic
resistance properties. The only oral drugs with activity
against P. aeruginosa are fluoroquinolones. All other
active drugs must be given by injection or topically.
Based on various studies on in vitro susceptibility of
canine P. aeruginosa isolates (60–62), the most effective
antimicrobials include aminoglycosides (gentamicin,
neomycin, tobramycin and amikacin), polymixin B, flu-
oroquinolones, ticarcillin, ceftazidime and imipenem.

194 Guide to antimicrobial use in animals

contamination with commensal bacteria from the Antimicrobial drugs should be selected based on the
urethra; concentrations above 1,000 CFU/ml should resistance profiles of urinary pathogens (Table 11.5)
be regarded as infection. Measurement of urine pH as well as on the drug concentrations that can be
combined with Gram staining and morphology of the achieved in urine (Table 11.6). Avoid the use of
bacteria present in the urine can enable prediction of drugs that are highly metabolized prior to excre-
the bacterial species involved. As a consequence of tion because the urine concentrations may not be
their metabolism, staphylococci and Proteus generally active. Aminopenicillins (ampicillin and amoxicillin),
cause urine alkalinization, whereas E. coli and entero- trimethoprim and fluoroquinolones are eliminated
cocci cause urine acidification. This information, by renal excretion and accumulate in urine at con-
combined with knowledge of the antimicrobial sus- centrations higher than in serum. The drugs can be
ceptibility patterns in the species, can lead to rational efficacious in vivo even if the bacterial strain involved
selection of the antimicrobial agents to be used. is regarded as intermediate based on antimicrobial

Table 11.5 Prevalences (%) of antimicrobial resistance in clinical E. coli isolates from dogs in different countries

Antimicrobial agent Denmark (71) Sweden (70) Canada (31) USA (45)
2000–2005 2002–2003 2002–2003 1990–1998
n=201 n=121 n=205 n=444

Ampicillin 22 15 33 42
Amoxicillin/clavulanate 4 ND 16 20
Cefalothin a 6 ND 39 42
Fluoroquinolones 7 8 3 18
Gentamicin 4 1 1 6
Tetracycline 26 10 14 31
Trimethoprim/sulfonamide 11/20 b 14 8 23

ND, not determined.
a Cefalothin is the antibiotic used for testing susceptibility to first-generation cephalosporins.
b Sulfamethoxazole and trimethoprim were tested separately.

Table 11.6 Mean urine concentrations and E. coli minimum inhibitory concentrations (MICs) of antimicrobial agents
used for treatment of urinary tract infections. Modified from Barsanti 2006 (88)

11 Dogs & Cats Antimicrobial agent Dosage (mg/kg) Route Interval (h) Concentration (mg/l)a MIC (mg/l) E. colib

Ampicillin 22 PO 8 309 NA
Cefalexin 8 PO 8 225 NA
Chloramphenicol PO 8 124 2–16
Amikacin 33 SC 8 342 0.5–8
Gentamicin 5 SC 8 107 0.125–2
Enrofloxacin 2 PO 12 0.032–0.125
Nitrofurantoin 2.5 PO 8 40 4–32
Tetracycline 4.4 PO 8 100 NA
Trimethoprim 18 PO 12 138 0.125–2
Sulfonamides PO 12 8–128
13 26
13 79

NA Not available.
a Concentrations were measured in healthy dogs. Patients with lower urinary tract infections may have bacteria in tissue layers of the

urinary system, for which high urine concentrations may not be sufficient. Moreover, many patients with lower urinary tract infections

have concurrent glucocorticoid therapy, diuretics, chronic renal failure, fluid therapy, or diabetes mellitus, all of which may dilute the urine.
b Antimicrobial wild-type MIC distributions of E. coli according to the European Committee on Antimicrobial Susceptibility Testing

(EUCAST) (www.srga.org/eucastwt/WT_EUCAST.htm).

Guidelines for antimicrobial use in dogs and cats 195

susceptibility testing. However, these interpretations Within sulfonamides, sulfamethoxazole is metabolized
should be made cautiously. With the exception of more extensively than sulfadiazine and the latter drug
ampicillin (68), specific resistance breakpoints for attains higher active concentrations in urine.
urinary tract pathogens have never been standardized
by CLSI. Thus, MICs should be interpreted using the Treatment of acute bacterial cystitis requires a one
same criteria as for systemic infections. One should to three week course of antimicrobials. Different
not assume that concentrations in urine are sufficient approaches should be used for treating first case,
to eradicate UTI with intermediate or resistant strains. uncomplicated and recurrent infections. Accurate
In fact, uropathogenic bacteria may involve the deeper clinical examination aimed at identification of under-
layers of the mucosa, the renal tissue or the prostate lying factors (e.g. cystic calculi, anatomical anomalies,
tissue. In these instances, it is the tissue concentration metabolic diseases, nervous system abnormalities,
– which is correlated to the plasma concentration – bladder neoplasia, etc.) should be undertaken in cases
that will be predictive of a bacteriologic cure (69). of relapsing or persistent UTIs. Urine culture and sus-
ceptibility testing are recommended because previous
Species-specific guidelines for treatment of exposure to antimicrobial drugs may predispose the
UTIs in dogs and cats are presented in Table 11.7. patient to infection or re-infection with resistant bac-
Aminopenicillins and amoxicillin-clavulanate are the teria. Antimicrobial therapy should be continued for
antimicrobial drugs of choice for empirical treatment six weeks and urine cultures should be performed five
of cystitis associated with enterococci and staphylo- to seven days after therapy to confirm resolution of
cocci respectively. Limited to the dog, TMS can be used infection.
empirically if bacilli are detected by microscopic exam-
ination. In E. coli, resistance to ampicillin and TMS Pyelonephritis
ranges between 15–42% and 8–23% respectively (31,
45, 70, 71) (Table 11.5). When available, local patterns Diagnosis of pyelonephritis is important because the
of antimicrobial resistance in E. coli should be consid- prognosis of antimicrobial therapy is worse than for
ered in order to select the most appropriate drug for lower UTIs. Drug selection should be based on the
empirical treatment of UTI associated with this species. antimicrobial susceptibility pattern of the pathogen

Table 11.7 Recommendations on antibacterial therapy of genito-urinary tract infections. Antimicrobial options are
listed in order of preference within each category

Infection/ Commonly First choice Second choice
disease (based on culture) Last resort
isolated pathogen (empirical) Comments

Cystitis S. intermedius Amoxicillin Amox/clav Fluoroquinolone Cytology should 11 Dogs & Cats
Enterococci Cephalosporin guide drug selection.
Pyelonephritis Streptococci TMS (dog) Fluoroquinolone 2–3 weeks treatment.
Acute prostatitis E. coli Amoxicillin (cat) Chloramphenicol Fluoroquinolone
Proteus TMS or Cephalosporin Fluoroquinolone 6 weeks treatment.
As above, mainly Cephalosporin Fluoroquinolone
amox/clav 4 weeks treatment.
E. coli TMS Erythromycin
As above Fluoroquinolonea 6–8 weeks treatment.
TMS Erythromycin
Chronic As above Fluoroquinolonea 5 days treatment.
prostatitis As above TMS (dog) BAST Surgical treatment
Pyometra Amoxicillin (cat) required.

Amox/clav, amoxicillin/clavulanate; TMS, trimethoprim/sulfonamide.

BAST, based on antimicrobial susceptibility testing.
a Because many dogs are sensitive to the adverse effects of sulfonamides, especially when long treatment periods are required (e.g.

prostatitis), fluoroquinolones should be considered as an alternative in these dogs.

196 Guide to antimicrobial use in animals

Table 11.8 Estimation of dose and dosage interval for prostate because they will be unionized at plasma pH.
antimicrobial therapy of pyelonephritis in patients with Antimicrobial drugs with good prostatic penetration
renal failure are those with high lipid solubility such as TMS, mac-
rolides and fluoroquinolones. However, macrolides
New dose Recommended dose × normal are usually not appropriate because of poor activity
New interval l (hr) creatinine conc./patient’s against Gram-negative bacteria, which are commonly
creatinine conc. involved. Chloramphenicol and tetracyclines are
Dosage interval × patient’s creatinine ordinarily considered drugs with good tissue penetra-
conc./normal creatinine conc. tion but, according to research performed in dogs (72),
penetrate the canine prostate poorly. Acute prostatitis
11 Dogs & Cats involved, generally E. coli. When possible, TMS or requires four weeks of antimicrobial therapy whereas
amoxicillin/clavulanic acid should be preferred to chronic prostatitis necessitates six to eight weeks.
cephalosporins and fluoroquinolones. However, the
use of either a third-generation cephalosporin or a 11.3.4 Gastrointestinal and
fluoroquinolone may be considered in Gram-negative intra-abdominal infections
infections, as long-term therapy with sulfonamides
has been associated with a risk of adverse effects (see Bacterial infections in the oral cavity
Section 11.3.1). A six-week antimicrobial course is
necessary for successful treatment. Aminoglycosides Periodontal disease is typically a mixed infection asso-
and nitrofurantoin should not be used because of ciated with proliferation of spirochetes and Gram-
nephrotoxicity and low serum levels (bacteraemia is negative anaerobic rods such as Porphyromonas and
common), respectively. If the animal presents signs of Prevotella species. Treatment requires tooth cleaning
systemic illness, empirical treatment is justified and and extraction, tartar removal by ultrasonic scaling
intravenous antimicrobial administration should be and root planning under general anaesthesia, and
started in combination with supportive therapy. For antiseptic treatment with chlorhexidine-based gels or
cephalosporins and penicillin derivatives, dose and solutions. Tetracycline-based preparations are avail-
interval should be tuned proportionately to the loss able for topical antimicrobial application into single
of renal function (Table 11.8). There is no evidence periodontal pockets (perioceutics). Systemic antimi-
that doses should be adjusted for fluoroquinolones. crobial treatment should be limited to severe cases
and immunosuppressed patients, and mainly directed
Prostatitis against anaerobes (Table 11.9). Home dental care
(tooth brushing) and client education play a major
Urethral haemorrhagic discharge is frequent, but this role in control and prevention of periodontal disease.
clinical finding is also associated with non-infectious Ulcerative stomatitis is a disease condition character-
pathologies of the urogenital tract (e.g. cystic degen- ized by the presence of ulcers and secondary bacterial
eration or prostatic hypertrophy). Thus, antimicro- infection of the oral mucosa. Local irrigation with 1%
bials should only be prescribed if the diagnosis is hydrogen peroxide or 0.2% chlorhexidine is recom-
confirmed on the basis of complete blood counts, mended. Serious anaerobic infections can be treated
urinalysis and urine culture. The organisms involved systemically as suggested for severe periodontitis.
are the same as for cystitis but therapy is more dif-
ficult because the blood–prostatic barrier limits drug Helicobacteriosis
penetration. This is only true in chronic prostatitis
since the blood–prostatic barrier is not intact during Helicobacter pylori and Helicobacter-like organisms
acute inflammation of the organ. To cross an intact have been identified in biopsy specimens from dogs
blood–prostate barrier, a drug must be: (a) unionized and cats, but their role in gastritis and ulcers has yet
or lipophilic, (b) have low protein binding, and (c) to be established. Some studies have found no asso-
administered in high enough doses to provide a con- ciation between Helicobacter infection and gastritis
centration gradient that drives the drug from the plasma (73, 74) and antimicrobial combinations used in
to the prostate compartment. Drugs that are weak human medicine seem not to result in long-term
bases, although ionizable, are able to diffuse into the eradication in dogs (75).

Table 11.9 Recommendations on antibacterial therapy of gastrointestinal and intra-abdominal infections. Antimicrobial options are listed in order of
preference within each category

Infection/disease Commonly isolated First choice (empirical) Second choice Comments Guidelines for antimicrobial use in dogs and cats
pathogen (based on culture) Last resort

Gingivitis Spirochetes Chlorhexidine Tetracycline Metronidazole Dental therapy and prophylaxis are essential.
Periodontitis Porphyromonas (topical) (topical) Metronidazole Systemic antimicrobial treatment
Prevotella Ampicillin should be limited to severe cases and
Clindamycin immunosuppressed patients.
Ulcerative stomatitis As above, mainly Hydrogen peroxide with Amoxicillin
E. coli chlorhexidine Clindamycin Systemic antimicrobial treatment
(topical) should be limited to severe cases and
BAST immunosuppressed patients.
None Erythromycin
Gastroenteritis Salmonella None
Campylobacter
Fluoroquinolones Bacterial gastroenteritis is usually self-limited
C. difficile None Metronidazole and antimicrobials should only be used in
Fluoroquinolone case of clinical signs of systemic infection.
Acute peritonitis Various Cefoxitin or cefotetan Aminoglycoside with penicillin, Bacterial gastroenteritis is usually self-limited
with penicillin, clindamycin or and antimicrobials should only be used in
Amoxicillin or doxycycline clindamycin or metronidazole case of clinical signs of systemic infection.
TMS or amoxicillin metronidazole
Cholangio-hepatitis Various Aggressive therapy, IV administration.
BAST Control source of infection and drainage are
Anal sacculitis None essential.
BAST
May need surgery to restore bile flow.

Require topical treatment with chlorhexidine.

Amox/clav, amoxicillin/clavulanate; TMS, trimethoprim/sulfonamide.
BAST, based on antimicrobial susceptibility testing.

197

11 Dogs & Cats

198 Guide to antimicrobial use in animals

11 Dogs & Cats Gastroenteritis combination of Gram-negative bacilli, obligate anaer-
obes, and ocassionally Enterococcus. Samples of abdomi-
According to an Australian survey (76), 59% of small nal effusions should be obtained for culture and
animal practitioners prescribe antimicrobial drugs sensitivity testing. Cephamycins (cefoxitin and cefo-
for acute unspecified gastroenteritis. However, most tetan) are an excellent empirical choice because of their
cases of diarrhoea and vomiting in pets are not caused activity against both anaerobic (including Bacteroides)
by bacteria but rather by viruses or non-infectious and Gram-negative bacteria. Alternatively, aminoglyco-
causes. Furthermore, even in bacterial gastroenteri- sides (gentamicin or amikacin) can be combined with
tis, infection is usually self-limiting and antimicrobial drugs active against anaerobes (penicillin, metronida-
treatment has not been proven to have positive effects zole or clindamycin). In addition to medical therapy,
on patient recovery. Following a protocol generally the successful treatment of septic peritonitis requires
employed in human medicine,empirical antimicrobial surgical control of the source of infection and drainage.
use should be limited to cases associated with signs of Although often recommended in veterinary literature
severe systemic infection (fever, depression and leuco- and commonly practiced, there is a lack of evidence that
penia or leucocytosis with a marked left shift). Where peritoneal lavage with saline or mixtures of saline with
available, injectable formulations of TMS may be used antimicrobials are of any benefit to the patient.
in combination with supportive care (rehydration
and fasting). When signs of acute sepsis are evident, 11.3.5 Respiratory infections
administration of injectable, broad-spectrum antimi-
crobial combinations is recommended (see Section Upper respiratory infections
11.3.10). Rectal swabs should be routinely submitted
to laboratory analysis for identification of Salmonella, Bacterial infections of the upper respiratory tract
Campylobacter and toxigenic clostridia. When one of such as rhinitis, sinusitis, tonsillitis and pharyngi-
these organisms is detected, antimicrobial therapy can tis are either self-limiting or secondary to underly-
be used to eradicate pathogen carriage and avoid risks ing causes. Bacterial rhinitis requires flushing with
of zoonotic transmission. The choice of the antimi- physiological saline solution or antiseptic solutions to
crobial agent should be based on antibiograms (Table remove exudates and to keep the nasal cavity clean.
11.9) and therapeutic efficacy should be monitored Antimicrobial therapy is not required unless clinical
after discontinuation of treatment. signs are severe or persistent (Table 11.10). Similarly,
studies on human cases have led to the conclusion
Some forms of chronic diarrhoea in animals appear that antimicrobials do not show any benefit on the
to be responsive to the macrolide tylosin and have been resolution of acute bacterial sinusitis. Chronic bacte-
regarded as ‘Tylosin-Responsive Chronic Diarrhoea in rial sinusitis occurs in cats, mainly as a consequence
Dogs’ (77). This syndrome is most likely caused by bac- of feline viral respiratory infections and leukaemia. In
teria but the specific aetiology has not been identified. this disease also, the efficacy of antimicrobial therapy
Campylobacter jejuni and Clostridium perfringens have is limited because of the secondary nature of the bac-
been identified in some animals. Tylosin has been effec- terial infection, presence of biofilms in sinus cavities
tive at improving clinical signs, whereas other antimi- and poor drug penetration into the sinus. Primary
crobials (metronidazole, TMS, doxycycline) appear not bilateral tonsillitis in young, small-breed dogs has
to be effective (78). Metronidazole has been found to unclear aetiology. For all upper respiratory infections,
alter the indigenous bacterial population (78) and may systemic antimicrobials should only be used follow-
have an immunosuppressive effect on the GI mucosa ing bacterial culture and antibiogram (Table 11.10).
(decreased cell-mediated response) as well as adverse
effects on the CNS (tremors, seizures and other). CNS Bronchitis
problems may be prevented by avoiding high doses.
Canine acute tracheobronchitis or kennel cough
Peritonitis generally does not endanger the dog’s life, is self-
limiting, and there is no evidence that antimicrobial
Septic peritonitis is a life-threatening infection gener- therapy speeds recovery. The causative pathogen,
ally due to contamination from the gastrointestinal Bordetella bronchiseptica, resides on the surface of
tract. Consequently, the bacteria involved are often a

Guidelines for antimicrobial use in dogs and cats 199

Table 11.10 Recommendations on antibacterial therapy of respiratory infections. Antimicrobial options are listed in
order of preference within each category

Commonly isolated First choice Second choice
(based on culture) Last resort
Infection pathogen (empirical)

Rhinitis Various None Doxycycline BAST
Sinusitis Amoxicillin
Tonsillitis B. bronchiseptica Self-limiting infection Amox/clav Cephalosporin or
Acute bronchitis Antimicrobial therapy fluoroquinolone with
Various is not needed BAST metronidazole
(kennel cough) Various None BAST As above
Amox/clav Cephalosporin a
Chronic bronchitis Various Fluoroquinolone a BAST
Pneumonia
Penicillin with
Pyotorax aminoglycoside
Pleuritis

Amox/clav, amoxicillin/clavulanate; TMS, trimethoprim/sulfonamide.

BAST, based on antimicrobial susceptibility testing.
aThird-generation cephalosporins or a fluoroquinolones are indicated in case of severe pneumonia. See Table 11.1 for available

compounds.

the respiratory epithelium and many antimicrobials organisms.Due to the large variety of organisms that can 11 Dogs & Cats
do not penetrate the blood–bronchus barrier suf- be implicated in bacterial pneumonia, it is important
ficiently to be effective against this pathogen. to select antimicrobial agents on the basis of bacterial
Antimicrobials are only required if secondary identification and antimicrobial susceptibility testing.
bronchopneumonia or interstitial pneumonia is Furthermore, it is important to select drugs that are able
demonstrated by radiographic signs. B. bronchiseptica to reach active concentrations in bronchial secretions
is often resistant to penicillins and cephalosporins such as erythromycin, clindamycin, chlorampheni-
(79). The recommended antimicrobial drugs are col, TMS and fluoroquinolones. Although penicillins,
doxycycline, TMS and amoxicillin/clavulanate. cephalosporins and aminoglycosides will not achieve
high drug concentrations in bronchial secretions, they
Bacteria usually play a secondary role in chronic will achieve adequate concentrations in the interstitial
bronchitis in dogs and cats. Collection of bronchoal- fluid of the lungs and airway mucosa. Therefore, these
veolar lavage (BAL) fluid is recommended to guide drugs may be effective for treating bronchopneumo-
drug selection for therapy of chronic bronchitis, that nia, but no well controlled studies of efficacy have been
is, a chronic cough for two months or longer without reported in veterinary medicine to determine which
signs of respiratory distress or pneumonia. Bacterial drug has the highest efficacy. If the infection is life-
counts higher than 103 CFU/ml BAL indicate bacterial threatening, empirical antimicrobial treatment starting
infection. Antimicrobial agents should be prescribed with IV administration may be needed.
on the basis of antimicrobial susceptibility testing.

Pneumonia Pyothorax and pleuritis

Bacterial pneumonia is more common in the dog than Periodical drainage of pleural exudates and saline
in the cat. B. bronchiseptica and Streptococcus zooepi- lavage of the pleural cavity are essential to successful
demicus are the most common bacteria implicated treatment of pyothorax. Without drainage and lavage,
in primary bacterial pneumonia in dogs. However, systemic antimicrobial therapy is ineffective. The effi-
pneumonia is more frequently associated with oppor- cacy of local antimicrobial therapy is controversial
tunistic pathogens, which may include staphylococci, since most antimicrobial agents are rapidly adsorbed
β-haemolytic streptococci (mainly groups C and G), by the pleural mucosa. No single antimicrobial prepa-
E. coli, Pasteurella multocida, P. aeruginosa, Klebsiella ration can ensure success of therapy since pleural infec-
pneumoniae, Mycoplasma and a variety of anaerobic tions are usually associated with multiple organisms,

200 Guide to antimicrobial use in animals

11 Dogs & Cats often including distinct aerobic and anaerobic of osteomyelitic lesions or material from sequestra,
species. Cytology of pleural aspirates facilitates ratio- necrotic tissue or implants should be submitted to both
nal antimicrobial selection by providing information aerobic and anaerobic culture, and sensitivity testing. If
on bacterial Gram staining, morphology and intra- the ischaemic necrotic environment is not improved by
cellular location. Parental administration of peni- drainage and surgical treatment, eradication of infec-
cillin G or ampicillin ensures activity against most tion will not occur despite the administration of effec-
anaerobic (except Bacteroides) and Gram-positive tive antimicrobials. Drug selection should be guided
bacteria (except staphylococci). Other antimicrobials by bacteriological culture and susceptibility testing.
such as gentamicin or amikacin are necessary when Clindamycin, amoxicillin-clavulanate or cephalospo-
infection is associated with Gram-negative bacilli. rins may be appropriate first choices depending on the
Antimicrobial therapy should be continued for four bacteria being involved. Long-term oral therapy (three
to six weeks and radiological monitoring can be use- to eight weeks or more) is usually necessary to control
fully employed to monitor efficacy. chronic cases of traumatic osteomyelitis. Local delivery
of antimicrobials, such as placement of gentamicin-
11.3.6 Eye infections impregnated poly-methyl methacrylate (PMMA) at
the site of infection, has also been used (80).
Conjunctivitis is a common disease in cats and a frus-
trating clinical problem to the veterinarian due to the 11.3.8 Arthritis
frequent occurrence of recurrent episodes associated
with carrier state of the pathogens most frequently Infectious arthritis is relatively uncommon in small
involved, herpesvirus-1 (FHV-1) and Chlamydophila animals. Definitive diagnosis requires arthrocentesis
felis. The veterinarian should educate clients about and subsequent synovial fluid analysis. Macroscopic
the chronic nature of feline conjunctivitis and prepare and cytological examination reveals signs consistent
them for the possibility of treatment failures, particu- with suppurative inflammation with or without the
larly in herpes-infected animals. The identification of presence of bacteria. Staphylococcus and Streptococcus
cytoplasmic elementary bodies in conjunctival epi- are the most common isolates in septic arthritis due
thelial cells, a positive fluorescent antibody test on a to surgery or penetrating wounds. Differential diag-
conjunctival scraping, or a positive chlamydial culture, nosis is essential in case of polyarthritis, which may be
can all be used to confirm the diagnosis of C. felis. consequent to bacteraemia, immune complex-medi-
Infection control measures should be taken to avoid ated damage of articular tissues, or infections with
dissemination to other cats. Tetracyclines are first Anaplasma phagocytophilum, various Ehrlichia spp.
choice agents, as this obligate intracellular bacterium (e.g. Rocky Mountain spotted fever), Borrelia burg-
can be resistant to many common topical ophthalmic dorferi, Leishmania, and Mycoplasma. Synovial fluid
antimicrobials including bacitracin, neomycin and or, when possible, joint capsule biopsies should always
gentamicin. In case of recurrent episodes, systemic be submitted to laboratory analysis and susceptibility
antimicrobial therapy should be considered to elimi- testing prior to the administration of antimicrobials
nate carriage. In the dog, infectious conjunctivitis is (Table 11.11). Immediate inoculation onto culture or
usually a secondary complication of entropion, kera- transport media may enhance bacterial detection.
toconjunctivitis sicca, penetration with foreign bodies
and canine distemper. Macrolides and derivatives can 11.3.9 Central nervous system (CNS)
be used for empirical treatment, taking the precaution infections
to submit ocular swabs for bacteriological analysis.
Cytology should be used to guide antimicrobial choice Definitive diagnosis of bacterial CNS infection
(Table 11.11). In case of deep corneal ulcerations, sys- requires analysis and culturing of cerebrospinal fluid
temic antimicrobial treatment should be used. (CSF), but in practice antimicrobial therapy is often
empirical. Antimicrobials capable of penetrating the
11.3.7 Osteomyelitis blood–brain barrier in bactericidal concentrations
are TMS, metronidazole and some fluoroquinolones.
Osteomyelitis may be associated with a large Other antimicrobials such as ampicillin and third-
variety of bacterial species, including Gram-positive, generation cephalosporins are capable of crossing
Gram-negative and anaerobic bacteria. Aspirates the blood–brain barrier when inflammation of the

Table 11.11 Recommendations on antibacterial therapy of selected miscellaneous infections. Antimicrobial options are listed in order of preference within
each category

Commonly isolated

Infection pathogen First choice Second choice Comments

Conjunctivitis Chlamydophila Doxycycline Chloramphenicol Differential diagnosis with herpes virus infections. Guidelines for antimicrobial use in dogs and cats
felis (cat) Tetracycline Cytology should be used to guide drug selection.
Osteomyelitis Gram-rods Polymixin/oxytetracycline Chloramphenicol Erythromycin or derivatives can be used empirically if
Staphylococci Fusidic acid Aminoglycoside cocci are seen in the microscope.
CNS infections Streptococci Erythromycin Tetracycline
Arthritis
Bacteraemia Various Clindamycin Amox/clav BAST No antibiotic can cover all the possible types of bacteria.
Anaplasmosis Cephalosporin The choice depends on the likelihood of Gram-negative
Rocky Mountain fever Gentamicin (local) and anerobic bacteria being involved.
Lyme disease
Leptospirosis Various TMS Metronidazole and/or Metronidazole with fluoroquinolone is recommended
Brucellosis Amoxicillin or amox/clav
fluoroquinolone only in case of life-threatening infections.
Plague
Tularemia Various BAST Therapy should be continued for 3–8 weeks and
monitored by cytology and culture.

Various Ampicillin with aminoglycoside BAST

Anaplasma Doxycycline Chloramphenicol Resistance has never been described in this species.
phagocytophila

Ehrlichia rusticii Doxycycline Chloramphenicol Resistance has never been described in this species.

Borrelia burgdorferi Doxycycline Amoxicillin

Leptospira interrogansPenicillin G, amoxicillin Doxycycline Doxycycline is recommended to remove carriage after
the acute phase.

None Dihydrostreptomycin Euthanasia is recommended since treatment is
with a tetracycline expensive and infection is difficult to be cured.
Isolation and monitoring is required for at least 3 months.

Yersinia pestis Streptomycin Doxycycline Suspected samples must be handled by a class 3
Gentamicin Chloramphenicol laboratory.

Francisella Gentamicin Doxycycline Suspected samples must be handled by a class 3
tularensis Chloramphenicol laboratory.

Amox/clav, amoxicillin/clavulanate; TMS, trimethoprim/sulfonamide.
BAST, based on antimicrobial susceptibility testing.

201

11 Dogs & Cats

202 Guide to antimicrobial use in animals

11 Dogs & Cats meninges is present. TMS are a logical first choice if prophylaxis, the USA National Research Council
available in parenteral formulations. Alternatively, (NRC) wound classification system and the American
ampicillin administered intravenously may also Society of Anaesthesiologists preoperative assess-
be effective if meningeal inflammation is present. ment scores (82) should be taken into consideration
Although chloramphenicol can achieve bactericidal together with other risk factors. These might include:
concentrations, this may not be the case with recom- the surgeons experience; whether or not veterinary
mended dosages in dogs and cats (81). The use of students are involved; the need for IV and urinary
fluoroquinolones or third generation cephalosporins catheters; contamination of the surgical site; drains;
combined with metronidazole should be reserved to expected hospitalization time and and underlying
life-threatening CNS infections or limited to failure of disease. Perioperative prophylaxis is generally more
empirical treatment with TMS or ampicillin. effective than postoperative prophylaxis, although the
latter is still frequently used in veterinary medicine.
11.3.10 Bacteraemia and sepsis
We have identified at least five types of surgery
Common causes of bacteraemia and sepsis include where antimicrobial prophylaxis may be recom-
gastrointestinal, genitourinary tract, skin, wound, mended as a routine practice: any surgery requir-
respiratory tract, abdomen, biliary tract and IV ing more than 90 min, elective orthopaedic surgery,
catheter-related infections. Bacteraemia may occur with bowel surgery at risk of anastomotic leakage, severe
routine dental prophylaxis, but current recommenda- skin or muscle lacerations, and dentistry associated
tions from dentists do not suggest that treatment with with severe periodontal disease or immunocompro-
antibiotics is necessary, because this is only transient mised patients. In long or elective orthopaedic sur-
and resolves without systemic infection. Definitive gery, IV administration of penicillin G, ampicillin
diagnosis requires positive blood cultures (prefer- or cefazolin prior to surgery and repeated after 90
ably two or three over a 24 h period) along with clini- min may be indicated. Wounds that fall into either
cal signs and laboratory findings that are compatible the contaminated or dirty category according to the
with bacteraemia/sepsis. Samples should be obtained NRC classification can be treated by post-operative
prior to antimicrobial administration. Clinical signs oral administration of amoxicillin/clavulanate or by
of bacteraemia warrant immediate parenteral (preferably perioperative injections of ampicillin-sulbactam or
IV) antimicrobial therapy against both Gram-positive cefazolin. If anaerobic bacteria are suspected (e.g.
and Gram-negative organisms. An aminoglycoside such deep puncture wounds), metronidazole can be added.
as gentamicin or amikacin combined with ampicillin or Antimicrobial prophylaxis for bowel surgery should
cephalosporin can be selected for patients in which renal only be used when leakage is observed or expected.
compromise and/or hypovolemia is not an issue. If the In this case, preoperative administration of intrave-
conditions are severe (e.g. temperature above 41°C), it is nous ampicillin or metronidazole combined with
also acceptable to administer a fluoroquinolone alone or an aminoglycoside or fluoroquinolone is indicated.
in combination with penicillin, ampicillin, potentiated In patients at risk, dental scaling or tooth extraction
ampicillin (e.g. ampicillin-sulbactam) or clindamycin, can be accompanied by prophylaxis mainly targeting
especially if anaerobic bacteria are suspected. Parenteral anaerobes (penicillin G, ampicillin or clindamycin).
administration of antimicrobials should continue for
five to seven days, followed by four to six weeks of oral 11.4 Final remarks
administration. If the condition is refractory, there
should be time for culture and susceptibility testing to The recommendations presented in this chapter aim
indicate and justify appropriate drugs. at minimizing and rationalizing the use of antimicro-
bials without affecting clinical efficacy. Although this
11.3.11 Antimicrobial prophylaxis is not an easy task, it is possible to use antimicrobi-
als in a prudent and rational manner without con-
Antimicrobial prophylaxis can in no way function as sequences on clinical outcome. Achievement of this
a substitute for the maintenance of a proper surgical ambitious goal necessitates that (i) antimicrobials
environment, the use of proper aseptic technique or are only used when required; (ii) empirical treatment
the practice of effective non-traumatic surgical proce- with broad-spectrum antimicrobials is limited to
dures. When evaluating the need for surgical wound infections threatening the patient’s life and otherwise

Guidelines for antimicrobial use in dogs and cats 203

untreatable by drugs with narrower spectrum; pyoderma: a prospective study of first-time and recurrent 11 Dogs & Cats
(iii) anamnesis, clinical signs, cytology and local cases in Sweden. Vet. Rec. 151: 600–5.
data on antimicrobial susceptibility are used to pre- 5. Ogeer-Gyles, J., Mathews, K.A., Sears, W., et al. (2006).
dict the resistance profile of the pathogen involved Development of antimicrobial drug resistance in rectal
and to select the most appropriate drug for empiri- Escherichia coli isolates from dogs hospitalized in an inten-
cal treatment; (iv) selected samples are submitted for sive care unit. J. Am. Vet. Med. Assoc. 229: 694–9.
laboratory analysis to confirm diagnosis, to monitor 6. Trott, D.J., Filippich, L.J., Bensink, J.C. et al. (2004).
the efficacy of antimicrobial therapy, to evaluate the Canine model for investigating the impact of oral enro-
effects of antimicrobial policies and to generate local floxacin on commensal coliforms and colonization with
data on antimicrobial resistance; (v) disease-specific multidrug-resistant Escherichia coli. J. Med. Microbiol.
dosage regimens are prescribed taking into consid- 53: 439–3.
eration drug pharmacokinetics and infection site; 7. Guardabassi, L., Schwarz, S. and Lloyd, D.H. (2004).
and (vi) pet owners are informed about the risk of Pet animals as reservoirs of antimicrobial-resistant bacte-
treatment failure and the importance of prudent ria. J. Antimicrob. Chemother. 54: 321–32.
antimicrobial use and treatment compliance. The 8. Pak, S.I., Han, H.R. and Shimizu, A. (1999).
authors are aware that prudent antimicrobial use is Characterization of methicillin-resistant Staphylococcus
more difficult to practice in countries where liability aureus isolated from dogs in Korea. J. Vet. Med. Sci.
can be associated with treatment failure and adverse 61: 1013–8.
reactions. Furthermore, financial constraints may 9. Owen, M.R., Moores, A.P. and Coe, R.J. (2004).
limit the availability of bacterial culture and suscep- Management of MRSA septic arthritis in a dog using a
tibility testing as aids to drug selection. However, gentamicin-impregnated collagen sponge. J. Small Anim.
the use of a‘best-guess’ approach based on microscopy Pract. 45: 609–12.
would facilitate choice of appropriate drugs targeting 10. van Duijkeren, E., Box, A.T., Heck, M.E., et al. (2004).
the relevant pathogen, thereby reducing the ecological Methicillin-resistant staphylococci isolated from animals.
impact on the commensal flora and the risk of select- Vet. Microbiol. 103: 91–97.
ing for resistance to last resort antibacterial drugs. 11. Morris, D.O., Mauldin, E.A., O’Shea, K., et al. (2006).
Clinical, microbiological, and molecular characterization
Acknowledgements of methicillin-resistant Staphylococcus aureus infections of
cats. Am. J. Vet. Res. 67: 1421–5.
The authors thank Lina Petterson (Uppsala University, 12. Loeffler, A., Boag, A.K., Sung, J., et al. (2005). Prevalence
Sweden) and Christina Greko (National Veterinary of methicillin-resistant Staphylococcus aureus among staff
Institute, Uppsala, Sweden) for kindly providing and pets in a small animal referral hospital in the UK.
Figure 11.1. J. Antimicrob. Chemother. 56: 692–7.
13. O’Mahony, R., Abbott, Y., Leonard, F.C., et al. (2005).
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Patterns and mechanisms of resistance to β-lactams and
β-lactamase inhibitors in uropathogenic Escherichia coli

Guidelines for antimicrobial use in dogs and cats 205

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J. Clin. Microbiol. 40: 3586–95. 64. Tejedor, M.T., Martin, J.L., Navia, M., et al. (2003).
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11 Dogs & Cats

Chapter 12

GUIDELINES FOR ANTIMICROBIAL
USE IN AQUACULTURE

Peter R. Smith, Alain Le Breton, Tor Einar Horsberg and
Flavio Corsin

Aquaculture is a very significant and rapidly terms, however, shrimp and salmonids become more 12 Aquaculture
expanding industry, with a production in 2004 of 60 significant. In addition to the production of fish for
million tonnes with an estimated value of US$ 70.3 consumption there is also a large market in non-
billion (FAO, 2006). Farmed fish now contribute food, ornamental fish where there is little regulation,
approximately 50% of the world’s fish food produc- although this is beginning to change.
tion. Food production in the aquatic environment is
largely an Asian activity with over 90% of world pro- 12.1 Aquaculture diversity
duction coming from this region. In quantity terms,
China is responsible for approximately 70% of world It is impossible to overstate the diversity of activities
production, Japan and the rest of the Asia-Pacific that must be included under the term aquaculture.
region for a further 22%. Western Europe (3.5%) and Although, in 2004, 25 species belonging to a num-
North America (1.3%) account for only a small frac- ber of different phyla accounted for over 80% of the
tion of world production (1). Approximately 40% world aquaculture production, the farming of a total
of the global fish production, most of which derives of 442 species is reported in the FAO FISHSTAT Plus
from aquaculture, is traded internationally, with database as having occurred at any time between 1950
exports exceeding that of commodities such as meat, and 2004 or still ongoing.
dairy, cereals, sugar and coffee (1).
The vast range of species farmed is reflected in the
Aquaculture production is divided roughly equally diversity of culture systems and environments encoun-
between marine or brackish water (57%) and fresh- tered. Temperatures can vary over at least a 30°C
water (43%) and in terms of value, fish are the range and salinity can vary from zero to 40 g/l. The
dominant aquaculture product (54%) followed by nutrient levels in aquaculture systems also vary over
crustaceans (20%) and molluscs (14%). When con- a wide range. Some systems operate best with pure
sidered by species, the world production is dominated spring water whilst, at the other end of the spectrum,
by carp (18 million tonnes) followed by oysters and some involve the deliberate eutrophication of the
kelp (both over 4 million tonnes). Considered in value

Guide to Antimicrobial Use in Animals. Edited by Luca Guardabassi, Lars B. Jensen and Hilde Kruse
© 2008 Blackwell Publishing Ltd. ISBN: 978-1-4051-5079-8

208 Guide to antimicrobial use in animals

12 Aquaculture water. Aquaculture can be conducted in freshwater, representative for other European countries where
brackishwater and full strength seawater. Equally, sys- Atlantic salmon is the dominant species, whereas in
tems vary with respect to their exposure to bacteria other European countries (4, 5) the use has been esti-
present in human or animal wastes. mated to lie in the range 10–100 g/t. In Chilean salmo-
nid culture, where there is as yet no effective vaccine
The socio-economic environments within which of the dominant bacterial disease, piscirickettiosis, use
aquaculture operates also vary over the full range has been estimated at 200 g/t (6). There are very few
found in the world, from small-scale systems most data allowing any estimate for use in Asian aquacul-
popular in the Asian region, to industrial-level opera- ture, but there are indications for a significantly higher
tions, and both the scientific and technical infra- consumption than recorded for Europe (7).
structure available to aquaculture producers and the
regulatory environments within which they operate With respect to the range of agents that are
show wide variations (1). employed in aquaculture there are wide variations
in the quality of the available data (8). At one end of
A significant proportion of aquacultural produc- the spectrum there are countries, mainly in northern
tion occurs in low-income, food-deficient countries Europe and northern America, where availability is
(LIFDC). In such countries, small scale ‘peasant’ very highly regulated and where, in general, very few
aquaculture plays a major role in meeting subsis- (two or three) agents have been granted Marketing
tence nutritional requirements and as a vital source Authorisations (MA) (9). At the other end there are
of employment, profit and foreign exchange earn- countries where use is limited only by market avail-
ings. At the other end of the spectrum, aquaculture is ability and price. Despite huge country-to-country
often run by sophisticated, multinational companies. variations, the agents most frequently reported as
It would, however, be a mistake to associate the size being used belong to the tetracyclines, the potentiated
of aquaculture operations and the extent to which sulfonamides and to the first- and second-generation
they are involved in international trade with any geo- quinolones.
graphical location or with any species. Small-scale
and large industrial aquaculture operations coexist in There are few data relating to the rationale for
most countries. antimicrobial use in aquaculture and we are forced
to offer only a series of generalisations. The evidence
12.2 Antimicrobial use in suggests that the vast majority of antimicrobial use in
aquaculture aquaculture involves the presentation of medicated
feed, is mostly metaphylactic and is only initiated
Given the huge diversity characterising the aquacul- in response to an overt infection in farmed animals.
ture sector, it is obvious that by treating antimicrobial There are, however, consistent reports of prophylac-
agent use in aquaculture as a single category only very tic use in shrimp and mollusc hatchery production.
broad generalisations can be made. Possibly the most Voluntary use of antimicrobials as growth promoters
valid is that, with few exceptions (2), we have limited in any aspect of aquaculture is generally rare.
data relating to aspects of antimicrobial use in world
aquaculture, such as the amounts used, the range of A very significant proportion of world aquacul-
agents employed and the rationale for their use. For ture production occurs in LIFDC where the techni-
most species farmed we also lack adequate knowledge cal or professional support available to producers is
of the pharmacokinetics and pharmacodynamics of very limited. As a consequence it is probable that the
administrations. majority of antimicrobial use in world aquaculture is
not associated with any classification of the target bac-
Some estimates of the amounts of antimicrobial terium or of its susceptibility to the range of available
agent use can be made for some countries. In Europe, antimicrobials. This situation can be contrasted with
the amounts of antimicrobial use would appear to be the conditions obtaining in the more industrialised
related to the extent to which appropriate husbandry part of the sector. Here technical support is increas-
techniques have been developed and to the availability ingly available, but it can be argued that we still face a
of vaccines effective against the dominant diseases. In serious shortfall in the science that is needed to advise
Norway (3), use has been estimated at 2 g per met- the advisors and in servicing the millions of produc-
ric tonnes production. This figure is most likely also ers involved in the aquaculture sector, especially in
Asian countries.

Guidelines for antimicrobial use in aquaculture 209

12.3 Therapy of diseases At the present state of our knowledge it is not 12 Aquaculture
encountered in aquaculture possible to provide a list of the antimicrobial agents
that would be most effective in treating any specific
In commercial aquaculture the diseases to which disease condition. The diversities among aquacul-
antimicrobial therapies are most commonly applied ture species and aquatic farming environments and
are those occurring in the production of finfish and technologies are much bigger than for terrestrial ani-
crustaceans (shrimp and prawns). In mollusc culture mals, making any such attempts bogus. Table 12.1 is
systems the use of antimicrobials is almost completely a compilation of the licensing status for antimicrobial
confined to the very early larval stages of production, agents in several countries. It demonstrates a great
and the amounts used are therefore relatively small. variation in licensed products, a variation that is a
Antimicrobial use in ornamental fish is largely unreg- result of tradition and economy rather than scien-
ulated and has rarely been quantified, but is thought tific data. The table summarises the various disease
to be considerable and the significance of this use is conditions that have been treated by various agents
increased by the proximity of these fish to humans. and lists the countries in which those agents have
been licensed. In several countries, off-label use of
In human and land-based animal medicine, where antibacterials is the rule rather than the exception. It
a wide range of agents are available to health-care spe- should be noted that the association in the table of a
cialists, it is possible for them to select an appropriate particular agent with a particular disease should not
therapeutic agent on the basis of records of its past be taken to imply that there are good-quality data
performance in reducing losses to the specific infectious demonstrating efficacy. Equally, the demonstration of
disease they are faced with. These conditions do not, efficacy in one fish species in one environment cannot
however, apply in aquaculture. A distinguishing char- be taken as evidence that efficacy will be achieved in
acteristic of this industry is the very limited number of treating the same species or another species in a dif-
antimicrobials that are available. In those countries that ferent environment. Many environmental conditions
have a significant scientific infrastructure and a devel- such as water quality parameters will interfere with
oped regulatory environment, the range of agents from the efficacy of the treatment, especially when immer-
which a choice can be made is frequently extremely lim- sion treatments are done. Table 12.1 does not include
ited. For example, with respect to 25 European coun- any data or recommendation as to the most appropri-
tries, the mean number of antimicrobials licensed ate treatment regimen for any agent. This omission
for use in aquaculture is currently 2±1.2 and in none is partly a consequence of the general lack of good
of these countries have more than five agents been empirical data. However, factors such as fish species
licensed (9). In countries with a less developed sci- and the salinity and temperature of the environment
entific infrastructure, regulations tend to be limited of the treated animals will have significant pharma-
or only weakly enforced. Thus, in these countries the cokinetic impacts.
range of agents used in aquaculture tends to be greater.
In these countries therapeutic agents are frequently 12.4 Pharmacokinetics and
chosen by the farmers themselves with very limited pharmacodynamics
input from trained health-care professionals, although
things have changed significantly over the years. Pharmacokinetic (PK) studies address the time course
of antimicrobial concentrations in the body, while
The choice of therapeutic agents in aquaculture is pharmacodynamic (PD) studies address the relation-
further complicated by the general absence of stan- ship between those concentrations and the antimicro-
dardised therapeutic regimen and by the serious bial effect (10). The relationship between PK and PD
lack of field data on clinical efficacy of any therapies. parameters are discussed in great detail in Chapter 6,
Scanning the published scientific literature reveals thus, only aspects regarding bacteria pathogenic to
that even data on the efficacy generated in small- aquaculture species are discussed here. PK and PD
scale laboratory trials have been rarely reported. In studies have an important role in determining break-
practice, the choice of therapeutic agent is frequently points suitable for interpreting susceptibility tests
influenced as much by considerations of agent avail- (see below). They also have a major, but with respect
ability, regulations and bacterial susceptibility as it is
by considerations of the nature of the disease being
treated.

12 Aquaculture

Table 12.1 Antimicrobial agents and their applications in aquaculture 210 Guide to antimicrobial use in animals

Antimicrobial Indication Licensed for aquatic species

Family Drug Species Diseases Country

β-Lactamas Amoxicillin Salmonids, sea bass, sea bream, Furunculosis, bacterial gill diseases, pasteurellosis, UK, Romania, Italy, Greece
yellowtail, catfish, eels, tilapia edwardsiellosis, streptococcosis

Tetracyclines Oxytetracycline and Salmonids, channel catfish, Vibriosis, pasteurellosis, flexibacteriosis, infections EU countries, most Asian
chlortetracycline carps, marine species, with segmented filamentous bacteria, columnaris, countries, USA, Canada,
ornamental fish yersiniosis, furunculosis, cold water vibriosis, Japan
botulism, Pseudomonas infections, Aeromonas
infections flavobacteriosis, streptococcosis

Quinolones and Nalidixic acid Salmonids, eels, carps, goldfish Furunculosis, vibriosis, Pseudomonas infections Japan
fluoroquinolones ornamental fish
Eels, carps, goldfish, salmonids, Pseudomonas infections, Serratia infections, Denmark, Greece, France,
Oxolinic acid turbot edwardsiellosis, vibriosis, cold water vibriosis, Norway, Iceland, Bulgaria
furunculosis
Flumequine Salmonids, marine species, Pasteurellosis, vibriosis, flexibacteriosis, Croatia, Czech Rep, France,
ornamental fish furunculosis, yersiniosis Hungary, Italy, Latvia,
Enrofloxacin Slovakia
Sarafloxacin
Salmonids, ornamental fish Bacterial kidney disease, vibriosis, furunculosis,
Salmonids, channel catfish streptococcosis
Furunculosis, yersiniosis, edwardsiellosis

Macrolides Erythromycin Yellowtail, salmonids Streptococcosis, lactococcosis, bacterial kidney
disease, piscirickettiosis, Chlamydia infections
Spiramycin, josamycin Yellowtail Streptococcosis Japan

Amphenicols Florfenicol Salmonids, marine species, Flavobacterium psychrophilum infections, UK, Ireland, Latvia,
eels, ornamental fish furunculosis, vibriosis, flexibacteriosis, Slovenia, Norway,
pasteurellosis, edwardsiellosis Bulgaria, Denmark,
Lithuania

Sulfonamides Sulfamerazine Fresh water salmonids Furunculosis USA
Sulfadimethoxine Rainbow trout, Channel catfish
Sulfadimidine Fresh water salmonids, carps

Potentiated Trimetoprim + Salmonids, ornamental fish, Aeromonas infections, yersiniosis, edwardsiellosis, USA, Canada, UK,
sulfonamides catfish, marine species
sulfadiadine or vibriosis, pasteurellosis Denmark, Croatia, Norway,
sulfamethoxazole Salmonids, channel catfish
France, Slovenia, Italy,
Ormethoprim +
Greece, Germany
sulfadimethoxine
Furunculosis, edwardsiellosis USA

Guidelines for antimicrobial use in aquaculture 211

to aquaculture, largely unfulfilled, potential in the Unfortunately, the available studies of MIC have
design of therapeutic regimen. In considering PK/PD used a variety of test protocols and this limits the
approaches it is important to note that what data we extent to which the numerical values they have
have relates almost exclusively to species farmed in reported can be compared. It is only very recently that
Europe. Studies relating to those species that contrib- standard protocols for determining MIC values for
ute to the vast majority of world aquaculture produc- aquatic bacteria have been published (21). Miller and
tion are rare to non-existent (11). Reimschuessel (18) (Table 12.2) have used these pro-
tocols to establish epidemiological cut-off values that
12.4.1 Pharmacodynamics allow the characterisation of isolates of Aeromonas sal-
properties monicida as wild type (WT) or non-wild type (NWT)
according to the procedures recommended by the
The minimum concentration required to inhibit European Committee on Antimicrobial Susceptibility
in vitro growth (MIC) of different antimicrobial Testing (EUCAST) (22, 23). The cut-off values esti-
agents against fish pathogenic bacteria is a key phar- mated for WT isolates represent the type of data that
macodynamic parameter. A large number of reports will be of most value in PK/PD modelling.
of MIC values for bacteria associated with disease
in aquatic organisms have been published over the 12.4.2 Pharmacokinetic properties
years (12–18). Other parameters that measure bacte-
rial susceptibility, such as the concentration required A number of pharmacokinetic studies in different fish
to kill (MBC), the concentration required to prevent species have been published over the years, and results
mutations emerging (MPC) (19) and the minimum from more than 400 papers have recently been com-
concentration that exerts selective pressure for resis- piled in a searchable database (11). Samuelsen (24)
tant variants (MSC) (20) have been reported much has recently published a valuable review of the phar-
less frequently. macokinetic data available for the quinolone group of
agents.
When applying MIC values to PK/PD modelling,
three factors must be considered: Unfortunately, the quantitative data that has been
generated in different studies shows very significant
1. The concentrations required to inhibit a bacte- variation. In part, this variation is a function of the
rium in laboratory media may not be the same as very many factors that complicate the measurement
the concentration required in the host. of the pharmacokinetic properties of agents in fish.
Variation can be expected when different administra-
2. Any numerical value of any in vitro MIC is depen- tion regimen are used and when different fish spe-
dent on the test protocol used to determine it. cies are studied. Equally, environmental factors such

3. In PK/PD modelling it is the MIC characterising
susceptible strains that is needed.

Table 12.2 Epidemiological cut-off values estimated by Miller and Reimschuessel (18) from data on 217 strains
of Aeromonas salmonicida

Epidemiological cut-off values

MIC (mg/l) M49-A (CLSI, 2006b) Disc diffusion (mm) M42-A (CLSI, 2006a)

Agent WTa NWTa WTa NWTa 12 Aquaculture

Oxytetracycline ≤1 ≤8 ≤28 ≤23
Florfenicol ≤4 ≤8 ≤31 ≤30
Oxolinic acid ≤0.125 ≤1 ≤30 ≤25
Ormetoprim- sulfadimethoxine ≤10 ≤30 ≤20 ≤16

a The terms WT and NWT have been defined by EUCAST (22).

212 Guide to antimicrobial use in animals

as temperature (25–28) and salinity (29) will also sub-optimal tissue concentrations in a large pro-
influence PK values. portion of the treated population, they also raise
serious questions as to the appropriate statistic that
Difficulties in estimating relevant measures for PK should be used to characterise the concentrations
parameters also arise from the fact that most admin- achieved in a population (32, 33). The inappetance
istrations to fish are metaphylactic treatments of large of infected fish also raises problems for estimation
populations performed by the presentation of medi- of PK values for oral administrations. In a number
cated feed. In such treatments, large inter-individual of studies of treatments on commercial farms, agent
variations in plasma- and tissue concentrations of the concentrations were below the limit of detection in
agent are inevitable. The limited data available sug- all moribund fish examined at the end of a period of
gests that, with respect to florfenicol, the degree of therapy.
fish-to-fish variation is greater in the field (30) than
in laboratory trials where healthy fish were given Thus, there are major theoretical and practical
a standard treatment (31). Not only do these varia- problems associated with the collection of PK val-
tions in the concentration achieved in different mem- ues relevant to commercial treatments. The data in
bers of the population result in a substantial risk of Table 12.3 allows a comparison of the PK parameters

Table 12.3 Some pharmacokinetic properties of antimicrobial agents in Atlantic salmon held at 10–12°C in
seawater (34)

Route and VDss CLT AUC Cmax
(l hkg) (μg h ml) (μg ml)
Agent dose (mg/kg) (l kg) 0.14 t1/2β (h) Tmax (h) F (%)
0.10 34.2 72.4 1.54
12 Aquaculture Enrofloxacin IV (10) 6.1 0.07 24.0 40.2 0.08 6 55
Sarafloxacin oral (10) 2.3 0.18 46.4 0.53 12 2
Difloxacin 4.2 0.28 22.8 100.7 1.42
Flumequine IV (10) 3.5 0.02 18.2 2.2 0.61 6 57
Oxolinic acid oral (10) 5.4 0.05 63.9 1.80 6 45
Oxytetracycline 1.3 0.09 67.2 59.0 12 30
Doxycycline IV (4) 4.0 0.23 12.2 33.6 <0.1 63
Florfenicol oral (4) 1.1 0.07 13.4
Amoxicillin 2.1 0.02 22.4 140.2 4.41 — <2
Trimethoprim IV (25) 2.0 21.5 62.7
Sulfadiazine oral (25) 0.7 <0.1 12 96
89.1
IV (25) 26.8 1.52 — <2
oral (25) 7.92
2692.2 12 96
IV (50) 77.7 24 50
oral (50)
238.4
IV (12.5)
oral (12.5) <4.6

IV (10) 116.3
oral (10) 112.0

IV (50) 220.6
oral (50)
<4.6
IV (5)
oral (5) 69,5
66.7
IV (25)
oral (25) 1121.9
556.8

VDss, volume of distribution at steady state;
CLT, total body clearance;
t1/2 β, elimination half-life;
AUC, area under the plasma concentration versus time curve;

Cmax, maximum plasma concentration;
Tmax, time to maximum plasma concentration;
F, bioavailability.

Guidelines for antimicrobial use in aquaculture 213

for a number of agents following their single-dose be applied to disc diffusion data generated by M42-A 12 Aquaculture
administration to Atlantic salmon (34). (36) for this species. A comparison of these values
(Table 12.2) with the breakpoints currently in use in
12.5 Antimicrobial susceptibility laboratories surveyed by Smith (37) is disturbing. The
testing of fish pathogens extent to which these cut-off values are considerably
larger than the majority of breakpoints in use, raises
In recent years, some progress has been made in devel- the possibility that many laboratories are reporting
oping standard methods for determining the in vitro isolates with NWT susceptibilities as clinically suscep-
susceptibility of bacteria associated with aquatic ani- tible. In the period before appropriate cut-off values
mal disease. Alderman and Smith (35) reported a set or breakpoints can be established from empirical data
of susceptibility test protocols that had been developed there is an urgent requirement to reduce the errors
by a group of 24 scientists from 17 countries. These associated with the interpretation of disc diffusion
protocols have been modified and importantly associ- data.
ated with appropriate control criteria in the Clinical
and Laboratory Science Institute’s (CLSI) guidelines Kronvall et al. (40) have suggested that epidemio-
M42-A (36) and M49-A (21). Given the extent of their logical cut-off values can usefully be set by calculat-
development, the degree of consultation that has been ing the mean less 2.5 standard deviations of the zones
involved in the production and the absence of any generated for fully susceptible strains. The standard
serious alternative, it is argued that these protocols deviations of the distributions of zone sizes for nine
should be adopted as the industry standard methods agents against fully susceptible A. salmonicida and
for determining in vitro susceptibility. The recent sur- four agents against Vibrio anguillarum have all been
vey of current practice (37) revealed that the major- shown to be within the range 3–4 mm (unpublished
ity (90%) of responding laboratories employed disc data). If this holds true for other species, calculating
diffusion protocols in susceptibility testing of clinical the mean zone size for susceptible species and sub-
isolates from aquatic animals. tracting 10 mm would represent a simple, if crude,
method for generating a first approximation of a cut-
The practical determination of resistance or sus- off value. This work suggests that, in the period before
ceptibility in a bacterium in a clinical context is, how- consensus breakpoints become available, a recom-
ever, a two-step process. After laboratory tests have mendation not to proceed with a treatment should be
been employed to obtain a measure of in vitro sus- given by a laboratory every time the isolated bacte-
ceptibility, the essential second step is to interpret the rium generated a zone that was 10 mm smaller that
meaning of that measure, in any specific clinical con- the mean normally recorded, in that laboratory, for
text, by applying appropriate breakpoints. At the pres- fully susceptible isolates of the same species.
ent moment no clinically relevant breakpoints have
been established for susceptibility test data generated 12.6 Negative impacts of
from bacteria associated with aquatic animal disease antimicrobial use in
by the application of standard minimum inhibitory aquaculture
concentration or disc diffusion methods. Current
studies have been focused on establishing epidemio- 12.6.1 Negative aspects associated
logical cut-off values (22) that can be used as a first with resistance
approximation for such breakpoints (23). The issue
as to whether useful laboratory-independent cut-off Antimicrobial use in aquaculture will and does pro-
values can be established or whether the degree of vide the conditions for the emergence of bacteria that
inter-laboratory variation (38, 39) will require that are resistant to antimicrobials. The bacteria in which
we establish standard protocols for generating labo- such resistant variants are most likely to occur are
ratory- and species-specific values (40) has yet to be those associated with fish diseases (41). Thus, there is a
resolved. However, following a study of the distribu- negative feedback loop in aquacultural use. The more
tion of data from 217 strains of A. salmonicida, Miller antimicrobials are used, the more likely they are to be
and Reimschuessel (18) have suggested laboratory-in- rendered useless. This negative feedback provides the
dependent epidemiological cut-off values that could most compelling reasons for prudence in the use of

214 Guide to antimicrobial use in animals

12 Aquaculture antimicrobials in aquaculture. Irrational or excessive 12.6.2 Negative impacts associated
use of any agent will have a direct impact on the with residues
future therapeutic value of any agent. In many coun-
tries there is an extremely limited number of agents Although arguably the most significant adverse effects
licensed for use and this exacerbates the problem. resulting from aquacultural use of antimicrobials
may be those associated with the emergence of resis-
The possibility that antimicrobial use in aquacul- tant bacteria (41), it is probable that on a global scale
ture might also have an impact on the treatment of considerations of drug residues have had a greater
infections in human and other land-based animals impact on antimicrobial agent use, in addition to sig-
was first raised close to 40 years ago (42), but in nificant economic consequences for several export-
the intervening years we have failed to characterise, ing countries. There are few, if any, reports of adverse
either qualitatively or quantitatively, the extent of this reactions in humans to drug residues in aquaculture
risk. Smith (43) has presented mathematical mod- products. There are significant regulations governing
els suggesting that the significance of selection of the presence of such residues (1). These regulations,
bacteria with transferable resistances as a result of particularly those that govern international trade,
the non-human use of antimicrobials, is only likely have stimulated rapid improvements in the ability
to impact on human therapy in situations where the of many countries to detect and monitor such resi-
frequency of those resistances in human pathogens dues, although in view of the paucity of aquaculture
is low. commodities covered by the Codex Alimentarius, the
requirements imposed by countries to a great extent
The potential risks presented by aquacultural still lack harmonisation. The introduction of residue
use are significantly different from those presented testing by large retailers has also had a major impact
by use in land-based animals. With respect to agri- on antimicrobial agent use.
cultural use of antimicrobials, the major risks are
associated with the selection, in treated animals, of 12.7 Towards improvements
resistant variants of bacteria capable of infecting of antimicrobial use in
humans (44). With aquacultural use this exposure aquaculture
pathway is generally considered to be less significant,
and the major risks are those associated with selec- Improvements in the use of antimicrobials in aqua-
tion of bacteria containing resistance genes that could culture would require the design of administration
be transferred to human pathogens. There are ample regimen that optimise clinical efficacy whilst minimis-
data (45) that the genes encoding resistance in human ing the development of resistance, the environmental
pathogens and in bacteria associated with aquacul- impact and the presence of residues in food products.
ture are highly related indicating that, in nature, these The lack of fundamental data presents major diffi-
genes are capable of transfer between the two groups culties for the task of generating specific guidelines
of bacteria. There are, however, much less data dem- for the rational, evidence-based use of antimicrobial
onstrating the dominant direction of this gene flow agents in aquaculture. Although for some fish species
or the consequence of increased frequencies of these such as salmonids, progress has been made in collect-
genes in aquaculture on their frequencies in human ing the PK/PD data that this task would require, for
pathogens. others, and notably those that make the largest con-
tribution to world production, data collection has
The recent WHO/FAO/OIE Expert Group (46) hardly begun (11).
identified the major risks to human health associated
with aquacultural use of antimicrobials as being those The example of northern European salmonid cul-
arising from the emergence of transferable resistances ture in general and that of Norwegian in particular
in the bacteria associated with fish disease and in those (3, 47), demonstrates that economically successful
present in the aquacultural environment. They rec- aquaculture can be achieved without extensive use of
ommended that the emergence of such transferable antimicrobials. Equally, some National Federations
resistances should be regularly monitored. However, of Producers, such as the French, strongly promote
any calls for such monitoring and surveillance will be this approach and have published a handbook of
of little value until validated and standardised labo-
ratory methods that would be capable of generating
relevant data have been developed.

Guidelines for antimicrobial use in aquaculture 215

Good Health Management Practices in Aquaculture be expected only when the bacterial infection is a 12 Aquaculture
(48). Several examples from the shrimp farming sec- major factor in the morbidity or mortality of a popu-
tor have also indicated that the application of Better lation. The aim of any diagnosis must not only be the
Management Practice protocols can lead to successful detection of a particular bacterium but also, and criti-
production without reliance on antimicrobials. Corsin cally, an assessment of its role in the disease process.
et al. (49) and Padiyar et al. (50) have demonstrated
that the application of these production management The isolation of a particular bacterium from a
approaches is gradually expanding in scope. moribund host cannot be taken as evidence that the
infection is the cause of the morbidity. Many bacte-
The wide variety of situations where antimicrobi- rial infections detected in aquatic animals are second-
als are used in aquaculture also presents difficulties in ary or opportunistic and the underlying cause may
making specific recommendation as to how the use of be environmental, infection by viruses or infestation
these agents can be improved. However, a number of by parasites. In such situations antimicrobial therapy
general considerations can be identified. would frequently be inappropriate.

12.7.1 Disease prevention ‘Diagnosis from a distance’ must always be treated
with some caution. The examination in a labora-
Well-fed animals that are living in an environment tory of a diseased animal will always tend to lead to
that is compatible with their physiological needs are an exaggeration of the role of the isolated pathogen.
less likely to be infected by pathogenic bacteria. As a Whenever possible laboratory studies must be associ-
consequence, optimising husbandry practices must ated with field observation and interpreted within the
always be first line of defence against infectious dis- context of the total clinical picture.
ease. In this context it is worth noting that adverse
living conditions frequently arise as a function of 12.7.3 Appropriate therapy
overstocking. The specific stocking densities appro-
priate for any environment are determined by the In any situation, the success of any antimicrobial
innate quality of that environment, but overstocking therapy will be a function of the choice of the most
will always lead to an increased disease risk. Here the appropriate agent. Ideally, a recommendation could
appropriate long-term response is not to continue to be made that the selection of agent should be made by
rely on antimicrobials to control the losses to disease, a trained fish health professional from those licensed
but to reduce the stocking densities to a more appro- for the application. The selection of an agent that
priate level. had been granted an MA for a particular applica-
tion would go a long way to reducing inappropriate
Many aquaculture enterprises require that animals choices. However, in many countries, there is not only
be imported into the farm. Monitoring the health sta- a lack of trained fish health professionals, but there is
tus of these animals and particularly their examina- also a complete absence of agents licensed for use in
tion for sub-clinical or covert infection, is an essential aquaculture. Even in countries that have issued MAs
step in reducing subsequent disease and, therefore, in for aquaculture, the number of agents that have been
avoiding the need for antimicrobials. licensed is normally so small that the degree of choice
is very limited.
Vaccines have been developed for some diseases of
fin-fish. The use of some of these vaccines has been The administration of antimicrobials to treat
demonstrated to have a major role in reducing infec- infections associated with bacteria that are clinically
tion and therefore the need for therapy. However, resistant cannot benefit the infected animal and can
crustaceans lack an adaptive immune system and, have only negative impacts. Antimicrobial use should,
therefore, vaccines cannot provide a method of reduc- therefore, always be informed by data from suscepti-
ing antimicrobial use in shrimp aquaculture. bility testing of the target bacterium. The current lack
of validated breakpoints for the correct interpretation
12.7.2 Appropriate diagnosis of these data does not mean that such data has no
value. The reduction in susceptibility that arises from
Antimicrobial therapy can only function by reducing the acquisition by a bacterium of a gene encoding a
the impact of a bacterium on the health of the host. specific, positive-function resistance is normally so
Beneficial consequences for the hosts can, therefore, significant that it is relatively easy for anybody with a

216 Guide to antimicrobial use in animals

12 Aquaculture little experience to detect. It should be noted that this It is highly unlikely that progress towards
type of mechanism is involved in the majority of cases prudent use could be made simply by formulating
of clinical resistance (45). Problems with the interpre- further regulations if developmental and educational
tation of disc diffusion data arise only when resistance programmes are not initiated at the same time. If
is mediated by chromosomal mutations in the target prudent antimicrobial use is to be achieved in global
bacterium or by other mechanisms that result in low, aquaculture the primary focus must be on the devel-
but clinically significant, reductions in susceptibility. opment of scientific infrastructures and the educa-
tion of fish health workers and fish farmers. Several
The success of antimicrobial therapy is a func- efforts are now ongoing towards the introduction of
tion of its efficacious administration to the infected better management of farms to prevent health prob-
population. In the majority of cases antimicrobials lems. The implementation of Better Management
are administered in medicated feed. When this is the Practices (BMP) especially in shrimp farming have
case, care should be taken to ensure that the target proven particularly successful in countries like India
population is feeding at an adequate level to ensure and Vietnam and successfully led to the prudent
that therapeutic concentrations of the agent can be use of antimicrobials by farming communities (52).
achieved. These approaches are generally strengthened through
the establishment of farmer groups which, among
12.8 The way forward other benefits, improves access to extension services
and reduces the risks of experiencing animal health
Prudent use of antimicrobials has the overall aim of problems (49).
reducing antimicrobial use and the example of the
Norwegian salmon farming industry illustrates that Regulation and education, if they are to be effec-
this is an achievable goal. It has been argued that, in tive, will have to be based on the product of research.
this industry, a combination of improved husbandry This chapter has clearly identified the need for more
(51) and the availability of vaccines that provided effi- research, but we must be careful to identify the ques-
cacious protection against the dominant diseases (47), tions that we require to be investigated. There is an
made a major contribution to the dramatic decline in urgent need for veterinarians and other health care
antimicrobial use. However, it also important to note workers to identify the types of information they
that this industry was farming a high value product require and to communicate these requirements both
in a country with a highly developed scientific infra- to research scientists and those that fund their work.
structure; and that there were a significant number
of trained professionals involved in providing a fish References
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42. Watanabe, T., Aoki, T., Ogata, Y. and Egusa, S.R. (1971). 51. Smith, P. and Hiney, M. (2000). Oil-adjuvanted furun-
Factors related to fish culture. Ann. N. Y. Acad. Sci. 182: culosis vaccines in commercial fish farms: a preliminary
383–410. epizootiological investigation. Aquaculture 190: 1–9.

43. Smith, D.L., Harris, A.D., Johnson, J.A., Silbergeld, E.K. and 52. Annon (1999). Food safety issues associated with products
Morris, G.J. (2002). Animal antibiotic use has an early but from Aquaculture. Report of a joint FAO/NACA/WHO
important impact on the emergence of antibiotic resis- Study Group. WHO Technical Report Series 883. World
tance in human commensal bacteria. Proc. Natl. Acad. Sci. Health Organization, Geneva, p. 68.
USA 99: 6434–9.

12 Aquaculture

INDEX

abscesses, 143, 155, 165, 169, 170–71, Anaplasma phagocytophilum, 87, 180, mechanisms of spread, 13, 78–82
174, 176 201 non-inherited, 84
problems in human medicine, 44–50
Acinetobacter, 44, 48, 163, 172 ansamycins, see rifamycins risk assessment (ARRA), 64–8
Actinobacillus, 169, 172, 175–6 antibiotics, 1 routes of zoonotic transmission, 7,
Actinobacillus equuili, 163–4, 180 antibacterial, see antimicrobial
Actinobacillus pleuropneumoniae, 8, 87, anticoccidials, 61, 68, 107, 127, 130, 136 13, 16–20
antimicrobial agents antimicrobial susceptibility testing, 8
104, 106–107, 121–2, 117, 119,
112 adverse effects, 1, 10, 46, 48, 50, 62, in aquaculture, 211, 213, 215
Actinobacillus suis, 104 77–8, 85, 130, 145, 147, 162, 187, in cattle, 135–40, 149–50, 153
Aeromonas, 17, 210 190–91, 193, 195–6, 198 in horses, 163–5, 167, 170
Aeromonas salmonicida, 211, 213 in poultry, 129–30
amikacin, 9, 52, 82, 107, 114, 163, 166, availability, 69–71 in small animals, 187–8, 192, 194,
169, 172–4, 177–8, 180, 186, associations between use and
188–9, 193–4, 198, 200, 202 195, 197–200, 202–203
aminocyclitols resistance, 14–16 in swine, 122
lipid solubility and pharmacokinetics classification based on clinical antimicrobial use in animals, 3–5, 68–71
properties, 86 metaphylaxis, 3, 9, 77, 104, 117, 149
mechanism of action, 79 importance, 50–56, 65, 67 prophylaxis, 3, 9, 77, 104, 117, 119,
aminoglycosides combinations, 9, 85, 162–3, 165, 167,
adverse effects, 50, 85, 145, 168, 165, 189, 197, 202
193, 196 196, 198, 202 therapy, 3–4, 8–10
importance in human medicine, concentration-dependent, 82, 93 antiseptics, 1, 180, 187–8
48–9, 51, 55–6 control of use and off-label use, 71–3 apramycin, 21, 107–109, 112, 120, 129,
killing action, 82 data requirements for approval, 62–4
lipid solubility and pharmacokinetics definition, 1 134, 138
properties, 86 history, 45–6 Arcanobacterium pyogenes, 144, 147–8,
mechanism of action, 79 lipid solubility, 86
aminopenicillins, see penicillins mechanisms of action, 79 150
amoxicillin, 1, 47, 52, 82, 106, 108–109, pharmacodynamics, 82–5, 211 arthritis, 104, 108, 121, 139, 144, 146–7,
112, 115, 120, 121, 183, 129–31, pharmacokinetics, 85–9, 212–13
137–9, 144–5, 147, 149, 155, pharmacovigilance, 73–5 155, 170, 172–3, 176, 200–201
186–90, 192, 194–7, 199–202, regulatory authority and registration avilamycin, 4, 15, 61, 107, 133
210 avoparcin, 2, 4, 14–15, 18, 61, 107, 126,
amphenicols principles, 59–62
adverse effects, 187 time-dependent, 82, 94 133
importance in human medicine, 54–5 use in aquaculture, 208, 210 azithromycin, 51, 82, 92, 168–70, 189
killing action, 82 use in horses, 161–2
lipid solubility and pharmacokinetics use in poultry, 130–31 bacitracin, 4–5, 64, 51, 79, 107, 110, 126,
properties, 86 use in small animals, 183–4 133, 171, 174
mechanism of action, 79 use in swine, 103–107
ampicillin, 40, 48, 50, 52, 55, 82, 106, antimicrobial residues, 7, 20, 60, 62–5, bacteraemia, 20, 22, 44, 46–9, 104–105,
108–109, 111, 114, 120–22, 120, 143–6, 152–3, 155–6, 165,
131–4, 136–9, 144–5, 147–51, 77–8, 86, 128, 131, 148, 151–2, 180, 196, 198, 201–202
155, 163, 166, 171, 175–7, 180, 161, 214
189, 194–5, 197, 200–202 antimicrobial resistance bactericidal drugs, 79, 82
acquired, 2 bacteriostatic drugs, 79, 82
breakpoints, 89–94 Bacteroides, 147, 148, 150, 167, 171,
co-selection, 2, 13, 21, 63
cross-selection, 2, 5, 18, 52, 63 198, 200
intrinsic, 2 benzoyl peroxide, 187, 192
mechanisms, 2 benzylpenicillin, see penicillin G
beta-lactams, see cephalosporins;

penicillins
biofilms, 92, 173, 175, 198

Guide to Antimicrobial Use in Animals. Edited by Luca Guardabassi, Lars B. Jensen and Hilde Kruse
© 2008 Blackwell Publishing Ltd. ISBN: 978-1-4051-5079-8

220 Index

bloodstream infections, see bacteraemia Clostridium, 104, 119, 121, 127, 130, 133, 149, 155, 162, 166, 169, 171–2,
Bordetella avium, 137–40 136, 137, 150, 162, 167–72, 176, 175–9, 184, 186, 188, 190, 193–4,
Bordetella bronchiseptica, 8, 104, 106, 169, 198 196, 210, 212
enteritis, see gastro-intestinal infections
198–9 cloxacillin, 9, 45, 49, 50, 54, 82, 150–51, Enterobacter, 8, 48, 163, 172, 175
Borrelia burgdorferi, 180, 200–201 153, 155 Enterococcus faecium/faecalis
Brachyspira hyodysenteriae, 104, 117, 121 antimicrobial resistance, 2, 9, 14–16,
Brucella, 173, 201 CNS (central nervous system) 44, 46, 48, 54
infections, see neurological in cattle, 14, 153
Campylobacter jejuni/coli infections in horses, 163–4, 170
antimicrobial resistance, 5–6, 15 in poultry, 14–15, 133–4
consequences of antimicrobial coagulase-negative staphylococci risk assessment, 29, 38
resistance, 21–3 (CoNS), 56, 133, 151, 153, in small animals, 193–5
in poultry, 15, 115, 132–3 163, 174 in swine, 14, 20
risk assessment, 29–30, 35, 37–40 zoonotic transmission, 16–18, 20, 45,
in small animals, 19, 197–8 coccidiostats, see anticoccidials 51–2, 55, 56
in swine, 115 colibacillosis, 84, 133, 136–8 enzootic pneumonia, 104, 117–18, 120,
therapy in humans, 15, 49, 51–2, colistin, 53, 82, 90, 94, 107, 120, 129–31, 148
55–6 Erysipelothrix rhusiopathiae, 104, 119,
zoonotic transmission, 16–17, 19 137–8 121, 140
colitis, 104, 120, 162, 166–70, 172 erythromycin, 1–2, 4, 22, 49, 51, 66, 82,
carbadox, 4, 107, 110, 121 competitive exclusion (CE), 141 87, 92, 110, 115, 129, 133, 137,
cefalexin, 9, 53, 82, 106, 166, 185–9, 194 conjunctivitis, 143, 155, 174, 187, 139, 144, 147–9, 155, 162–3, 166,
cefalothin, 185 168, 170–71, 176, 185, 187, 190,
cefapirin, 82, 151 200–201 195, 197, 199, 201, 210
cefazolin, 9, 166, 173–4, 189, 202 copper sulphate, 2, 15 Escherichia coli
cefepime, 166, 189 co-resistance, see antimicrobial resistance antimicrobial resistance, 8, 16, 47–8,
cefotaxime, 51, 80, 166, 176, 180, 189 81, 83, 90–91, 94
cefotetan, 53, 197–8 co-selection in cattle, 144–7, 149–50, 153
cefovecin, 187–9, 192 Corynebacterium, 151, 171–2, 174, 192 in horses, 169, 172, 175–8, 180
cefoxitin, 53, 164, 166, 172, 180, 189, coryza, 137, 139 in poultry, 130, 132–4, 136, 138–41
cross-resistance, see antimicrobial in small animals, 184–6, 192–7, 199
197–8 in swine, 103, 106–107, 119–22
cefpodoxime, 51, 187–9, 192 resistance cross-selection zoonotic transmission, 16–19, 45,
cefquinome, 9, 106, 144–9, 153, 155, 166 cystitis, see urinary tract infections 51–3
ceftiofur, 9, 82, 84, 106, 108–12, 114–15, extended-spectrum beta-lactamase
dermatitis, see skin infections (ESBL), 48, 81, 186, 192
122, 129, 143–5, 147–53, 155, 163, Dermatophilus congolensis, 179
166, 169, 171–80, 189 diaminopyrimidines fistulous withers, 172
ceftriaxone, 17, 51, 144, 166, 176, 180 Flavobacterium psychrophilum, 210
cephalosporins importance in human medicine, 53 flavophospholipol, 61, 107, 133
importance in human medicine, killing action, 82 flexibacteriosis, 210
49–51, 53, 55 lipid solubility and pharmacokinetics florfenicol, 11, 106, 108–109, 111–12,
killing action, 82
lipid solubility and pharmacokinetics properties, 86 114, 121, 122, 144, 147–9, 155,
properties, 86 mechanism of action, 79 187, 210–12
mechanism of action, 79 diarrhoea, see gastro-intestinal infections flumequin, 108–109, 129
cephamycins, 53, 198 dicloxacillin, 45 fluroquinolones
Chlamydia, 53, 144, 147, 200, 210 difloxacin, 9, 82, 129, 131, 133, 155, 186, adverse effects, 147, 162
chloramphenicol, 16, 20, 54–5, 82, 85, importance in human medicine, 49,
108–109, 114, 132, 163, 166, 168, 190, 212 52, 55–6
170–74, 176–7, 185, 187, 189, dihydrostreptomycin, see streptomycin killing action, 82
194–6, 199, 201–202 disinfectants, 1 lipid solubility and pharmacokinetics
chlorhexidine, 178–80, 187–8, 192, doxycycline, 1, 53, 82, 86, 96, 106, 108, properties, 86
196–7 mechanism of action, 79
chlortetracycline, 1, 53, 82, 106, 110–11, 109, 111, 129, 137, 162, 166, folliculitis, see skin infections
121, 129, 131, 146, 155, 210 171–2, 174, 180, 187–8, 190, fowl cholera, 137, 139–40
ciprofloxacin, 2, 15, 49, 52, 56, 85, 93, 197–9, 212 Francisella tularensis, 201
108, 109, 114–15, 131–3, 174, 190 drug interactions, 162–3
clindamycin, 54, 82, 164, 187–8, 190, dry cow therapy, 154
197–202 dysbacteriosis, 136–7
dysentery, 104, 117, 120

ear infections, 47, 176, 186, 188, 192, 193
Ehrlichia, 190, 200–201
endocarditis, 48, 51, 104, 144, 175, 176
enrofloxacin, 2, 5, 9, 14–16, 52, 82, 85, 87,

90, 106, 108, 109, 111–12, 114,
120–22, 130–34, 137, 139, 147,

Index 221

furunculosis, see skin infections mechanism of action, 79 necrobacillosis, 148, 155
fusidic acid, 20, 54, 79, 174, 180, 187–8, linezolid, 45–9, 52, 55, 185, 190 necrotic enteritis, 104, 120, 136
Listeria monocytogenes, 177 neomycin, 11, 18, 51, 55, 107–109,
192–3, 201 Lyme disease, 180, 201
Fusobacterium necrophorum, 148, 150 112, 120, 129, 134, 137–8,
145–6, 155, 174, 180, 188,
gastro-intestinal infections macrolides 193, 200
in cattle, 144–6 adverse effects, 162, 187, 190 neonatal scours, 104, 108, 120
in horses, 170–71 importance in human medicine, 47–9, netilmicin, 94
in poultry, 136–40 51, 55, 56 neurological infections
in small animals, 196–8 killing action, 82 in horses, 176
in swine, 103–104, 120–21 lipid solubility and pharmacokinetics in humans, 47, 49–51, 54
properties, 86 in small animals, 200–202
gatifloxacin, 52, 93, 133 mechanism of action, 79 in swine, 104, 118
gentamicin, 9, 18, 50–51, 55, 82, 87–8, nitrofurantoin, 54, 133, 194, 196
Mannheima haemolytica, 69, 91–2, 143, nitroimidazoles
107, 109, 112–15, 129, 133, 144, 148–50 importance in human medicine, 54
147, 155, 162–3, 165–7, 169, 172, killing action, 82
173–5, 177–8, 185, 190, 193, 194, marbofloxacin, 9, 82, 87, 92, 96, 106, 147, lipid solubility and pharmacokinetics
198, 200–202 149, 155, 167, 186, 191 properties, 86
gingivitis, 197 mechanism of action, 79
glycopeptides mastitis, 4, 9, 151–4, 156, 178
importance in human medicine, 46, maximum plasma concentration omphalophlebitis
50, 51, 66 in cattle, 143, 145–6
killing action, 82 (Cmax), 89–90 in horses, 180
mechanism of action, 79 meningitis, see neurological infections
growth promoters, 3–6, 14–16 meropenem, 50–51, 90, 191 ormethoprim, 9, 191, 210
use in poultry, 126–7, 136, 141 methicillin-resistant Staphylococcus Ornithobacterium rhinotracheale, 134,
use in swine, 102–103, 107
guttural pouch empyema, 179 aureus (MRSA), 9, 19, 46–7, 137–40
49–50, 55, 114, 116, 164, 180, osteomyelitis, 136, 143, 172–3,
Haemophilus paragallinarum, 137, 139 185–7
Haemophilus parasuis, 104, 117 methicillin-resistant Staphylococcus 200–201
Histophilus somni, 147–8 intermedius (MRSI), 185–6 otitis, see ear infections
Helicobacter, 196 metritis, 150–51, 155–6, 177–8, 195 oxacillin, 45, 54, 133, 164
hepatobiliary infections, 136, 176, metronidazole, 50, 54, 82, 87–8, 167, oxolinic acid, 210–12
169–72, 176, 191, 197–202 oxytetracycline, 53, 82, 86, 88, 106,
177, 197 minimum inhibitory concentration
(MIC), 83 111, 129, 137, 144, 146–52, 155,
imipenem, 511, 90, 167, 186, 190, 193 monensin, 4, 61, 107, 133 162–3, 167, 170, 172, 180, 201,
ionophores, 4, 54, 127, 136–7, 139 Monte Carlo simulation, 95–6 210, 212
Moraxella equi, 174
kanamycin, 18, 51, 55, 108–109, 133–4 mupirocin, 54, 66, 179–80, 187–8, 192 Pasteurella, 140, 162, 175
kennel cough, 198–9 mutant prevention concentration Pasteurella gallinarum, 139
keratoconjunctivitis, 155, 187, 200 (MPC), 83 Pasteurella multocida, 104, 117, 137, 148,
Klebsiella, 18, 44, 48, 81, 143, 163, 169, mutant selection window (MSW), 83
Mycoplasma, 87, 177, 122, 129, 137–40, 149, 199
172, 175, 178, 180, 199 144, 147–9, 167, 199, 200 penicillin G, 8, 45–7, 52, 55, 82, 87–8,
Mycoplasma bovis, 144, 147–9
Lawsonia intracellularis, 103, 104, 106, Mycoplasma felis, 169 94, 106, 110, 129–31, 136–7, 139,
110, 117, 119–21, 171 Mycoplasma gallisepticum, 138, 140 151, 156, 167, 169, 177, 191,
Mycoplasma hyopneumoniae, 117, 119, 200–202
Leptospira interrogans, 201 122 penicillin V, 52, 106, 130, 192
levofloxacin, 52, 93–4, 96, 133 Mycoplasma hyosynoviae, 104, 107, 111, penicillins
lincomycin, 54, 107, 110–11, 120–22, 129, 121, 122 adverse effects, 162
Mycoplasma hyorhinis, 122 importance in human medicine, 46–8,
137–8, 139, 144, 147–8, 162, Mycoplasma meleagridis, 138 52–6
187–8, 190 Mycoplasma mycoides, 148 killing action, 82
lincosamides Mycoplasma synoviae, 138 lipid solubility and pharmacokinetics
adverse effects, 162 properties, 86
importance in human medicine, 54 nalidixic acid, 16, 22, 62, 90, 108, 112, mechanism of action, 79
killing action, 82 132–3, 210 pericarditis, 104, 175–6
lipid solubility and pharmacokinetics perioceutics, 196
properties, 86 narasin, 133 periodontitis, 196–7

222 Index

peritonitis, 93, 104, 136, 144, 165, 167, Rickettsia, 53, 190 therapy in humans, 46–7, 49–50, 51,
170–71, 197, 198 Riemerella anatipestifer, 137, 139 54–5
rifampicin, 51, 86, 162–3, 166–71, 175,
phenicols, see amphenicols zoonotic transmission, 19, 55, 114,
phenotypic tolerance, see antimicrobial 177, 191 116, 164, 185
rifamycins
resistance non-inherited Staphylococcus intermedius, 19, 184–6,
PK-PD indexes, 89–90 importance in human medicine, 51 188, 192, 195
lipid solubility and pharmacokinetics
integration and modelling, 90–91 Staphylococcus pseudintermedius, 186
limitations and pitfalls, 92 properties, 86 Staphylococcus schleiferi, 186, 192
pigeon fever, 172 mechanism of action, 79 stomatitis, 196–7
placentitis, 178 risk assessment strangles, 165, 169
plague, 201 bottom up, 34 streptomycin, 11, 21, 51, 53, 55–6, 82,
pleuritis, see respiratory infections data requirements and sources, 35–7
pleuromutilin, 102 examples, 37–41 107–109, 114, 121–2, 129, 132–4,
pneumococci, see Streptococcus frameworks, 27–31 136–7, 139, 166, 190, 201
qualitative, 32 Streptococcus, 69, 137, 139, 144, 147, 150,
pneumoniae quantitative, 33 169–72, 175–6, 178, 180, 200
pneumonia, see respiratory infections semi-quantitative, 33 Streptococcus agalactiae, 153–4
Polyanna phenomenon, 84 top down, 34 Streptococcus dysgalactiae, 153
polymixin, 94, 107, 174, 180, 188, 193, 201 risk communication, 28 Streptococcus equi, 163–4, 169, 174,
polypeptides, 4, 54, 70–71, 129–30 risk management, 28 178, 199
Porphyromonas, 196–7 Rocky Mountain spotted fever, 200–201 Streptococcus pneumoniae, 44, 47, 94
post-antimicrobial effect (PAE), 84, 90, 92 Streptococcus suis, 104, 114, 116
post-antimicrobial leucocyte salinomycin, 61, 133 Streptococcus uberis, 153–4
selective pressure, 80 streptogramins, 4, 48, 52, 66, 70–71, 185
enhancement (PALE), 84 Salmonella enterica sulbactam, 51, 189, 202
post-antimicrobial sub-MIC effect sulfadiazine, 53, 82, 87–8, 180, 118, 191,
antimicrobial resistance, 6, 8, 14–15, 193, 195, 212
(PASME), 84 16, 44, 49, 68–9, 81, 83, 87, 90 sulfadimethoxine, 88, 144, 191, 210–11
Potomac Horse Fever (PHF), 162, 171 sulfamerazine, 210
povidone-iodine, 151, 179–80 in cattle, 14, 143–7, 149 sulfamethoxazole, 53, 133, 163, 175,
predicted environmental no effect consequences of antimicrobial 194–5, 210
sulfonamides
concentration (PNEC), 62–3 resistance, 20–23 adverse effects, 130, 187, 195–6
Prevotella, 144, 147–8, 196–7 in horses, 163–4, 170–72 importance in human medicine, 53
probiotics, 140–41 in poultry, 14, 130, 132–4, 137, 140–41 killing action, 82
proliferative enteropathy, 104, 171 in small animals, 19, 197–8 lipid solubility and pharmacokinetics
prostatitis, 195–6 in swine, 103–104, 106–108, 114–15, properties, 86
Proteus, 147, 150, 192–5 mechanism of action, 79
prudent and rational antimicrobial use 119–20 Swann Report, 5
therapy in humans, 51, 52
basic principles, 9–11 zoonotic transmission, 16–19, 40–41 teicoplanin, 51, 134
definition, 3 sarafloxacin, 9, 210, 212 temporohyoid osteoarthritis, 176
history, 5–7 seminal vesiculitis, 178 tetracycline, 1–2, 4, 16–17, 40, 53, 55, 69,
national guidelines, 73–5 sepsis, see bacteraemia
practice guidelines, 11 septicaemia, see bacteraemia 106, 108–114, 121–2, 126, 129,
Pseudomonas aeruginosa, 44, 134, silver sulfadiazine, 180, 188, 193 132–3, 137, 145–6, 156, 169, 185,
sinusitis, 169, 198–9 187, 193–4, 196–7, 201
150, 163–4, 166, 175, 178, skin infections adverse effects, 162
191–2, 210 in cattle, 148, 155 importance in human medicine, 46–8,
pyelonephritis, 143, 174–5, 195–6 in horses, 177, 179–80 53, 55
pyoderma, see skin infections in small animals, 186–92 killing action, 82
pyometra, 151, 195 in swine, 104, 122–3 lipid solubility and pharmacokinetics
spectinomycin, 11, 53, 107, 110–12, properties, 86
quinupristin/dalfopristin, 46, 48–9, 52, mechanism of action, 79
55, 133 120, 129–30, 134, 137–9, thiamphenicol, 106
147–9, 156 thrombophlebitis, 143, 175–6
respiratory infections spiramycin, 4, 51, 61, 126, 129, 137, 139, tiamulin, 105, 110–12, 114, 120–22, 129,
in cattle, 148–50, 155 149, 156, 210 137, 139
in horses, 168–70 Staphylococcus, 133, 139, 169, 172, 175, ticarcillin, 53, 87, 167, 177–8, 188,
in poultry, 136–40 178–80, 200 191, 193
in small animals, 198–200 Staphylococcus aureus
in swine, 104–105, 120–22 antimicrobial resistance, 9, 19, 44–7,
49–50
Rhodococcus equi, 87, 162–4, 168–9,
171–2, 177

Index 223

tigecycline, 46, 55, 185 tylosin, 2, 4, 15, 38, 39, 52, 61, 82, 105, virginiamycin, 4–5, 55, 61, 107, 110, 121,
tilmicosin, 38–9, 82, 92, 105, 107, 110–12, 107, 110–11, 120–22, 126, 129, 126, 133
134, 136–7, 139, 149, 156, 198
114, 122, 137, 139, 144, 147, wound infections, 9
149, 156 tylosin-responsive chronic in horses, 165, 167, 172–3
tobramycin, 18, 51, 82, 174, 193 diarrhea, 198 in small animals, 184, 188,
Treponema, 148 200, 202
triamilide, 79, 82, 86, 92, 107 ulcerative lymphangitis, 197
trimethoprim, 9, 53, 70–71, 82, 84, 87–8, urinary tract infections (UTI) Yersinia pestis, 201
102–103, 106, 108–109, 111–12,
114, 120–22, 129–30, 133, 151, in horses, 174–5 zinc oxide, 120
152, 156, 163, 167–72, 174–80, in small animals, 84, 193–6 zoonotic bacteria
183, 185, 187–8, 195–202, 212
Tris-ethylene diamine tetra acetic acid vaginitis, 178 in poultry, 131–4
(EDTA), 188, 193 valnemulin, 107, 110, 121, 148 in small animals, 184–6
tularemia, 201 vancomycin, 2, 14–15, 44, 46–51, 54, 82, in swine, 114–16
tulathromycin, 82, 92, 107, 121, zoonotic transmission of resistant
149, 156 70, 181, 185, 191
vancomycin-resistant enterococci (VRE), bacteria, 16–23

14, 15, 29, 48, 54, 133, 164