Antimicrobial Therapy in Veterinary Medicine

556 Section IV. Antimicrobial Drug Use in Selected Animal Species

Dose (%) 100
90
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Time (h)

Stomach Upper SI Mid SI Lower SI Colon

Figure 33.2. Pharmacokinetics of non-absorbed drug in the intestinal contents of swine (Burch, 2012, after Clemens et al.,
1975) after a single-dose administration.

the jejunum, ileum or colon, is critical to their effect it is possible to underdose in certain cases, resulting in a
(Figure  33.2). Data following a single oral gavage of a poor clinical response.
non-absorbable substance in the middle of feeding
(Burch, 2012, after Clemens et al., 1975), the drug passes Water intake is frequently based on 10% of body
out of the stomach and flows in a wave in the intestinal weight. Some authors describe this as erroneous
contents down the small intestine and accumulates in (Kyriazakis and Whittemore, 2006) and that it is more
the large intestine. The waves would increase in number likely to be up to 15–20% based on dry feed intake.
but decrease in height with the frequency of feeding; for Environmental temperatures can also have a major
example, on an ad-libitum basis, giving a more steady impact on water intake. When calculating dose rates and
flow of antimicrobial concentration along the intestine inclusion rates in feed or water the total body weight
to inhibit bacterial growth. (kg) times daily dose rate (mg/kg bwt), should be
divided by the amount of food consumed or water drunk
Drug dose and inclusion rate is also critical and the (kg or liter) in a day to give the required inclusion rate in
former depends on feed intake/kg body weight of the parts per million (ppm).
pig. Most pharmacokinetic and efficacy work is carried
out on grower pigs and their feed intake in relation to For example:
body weight is approximately 5% (1 kg feed/20 kg body In feed:
weight). In dry sows, this can fall to 1% and lactating 1000 kg body weight × 10 mg/kg bwt dose rate / 50 kg
sows to 2–2.5%. Even in finishers, on restricted feed feed = 200 ppm (or mg drug/kg feed or g drug/ton of feed)
for controlling fat deposition in castrates, it can fall to
2.5%. On this basis, it is essential to adjust the inclusion In water:
rate to  achieve an effective dose rate. Where dosing is 1000 kg body weight × 10 mg/kg bwt dose rate / 100 liters
based on or limited to a standard inclusion rate in feed, of water = 100 ppm (or mg drug/liter of water).

Chapter 33. Antimicrobial Drug Use in Swine 557

Antimicrobial conc. (μg/ml) 7
Maximum concentration (C max)

6

5
Area under the curve (AUC)

4
Steady state (Css)

3 MIC for bacterium

2

1

0
0 4 8 12 16 20 24

Hours

Injection Water/feed MIC

Figure 33.3. Comparative antimicrobial pharmacokinetic curves following injection or in-feed or in-water medication.

If using a water proportioner set at 1%, then the promoters are not available in the EU and trimetho-
quantity of drug (1000 kg × 10 mg / 1000 = 10 g) would prim/sulfonamide combinations are not approved for
need to be dissolved in 1 liter of water and administered oral use in the United States, but human products may
during the day. be used. The antimicrobial products used in swine are
summarized in Table 33.2.
Water and in-feed medication administered over the
day gives usually a lower but flatter pharmacokinetic Antimicrobial Susceptibility of Porcine
plasma concentration curve than following an injection Isolates
or oral dose. This is still ideal for controlling systemic or
respiratory bacterial infections as many of the antibiotics The antimicrobial susceptibility of a number of key
used are inhibitory, like the tetracyclines, and are time- porcine bacterial pathogens is presented in this
and concentration-dependent in their antibacterial effect section. Susceptibility patterns are very useful to
unlike the fluoroquinolones, which can exert a strong demonstrate the “wild-type” patterns and the selection
concentration-dependent bactericidal effect, especially of  mutants and resistance following the use of
when injected or given as a bolus dose (Figure 33.3). antimicrobials.

Common Bacterial and Mycoplasmal Enteric Pathogens
Infections in Swine
Amoxycillin and amoxycillin + clavulanic acid (beta-
The common bacterial and mycoplasmal infections in lactamase inhibitor) demonstrates the way beta-
pigs are summarized in Table 33.1. lactamase enzymes exert their effect and they can be
blocked or inactivated by inhibitors such as clavulanic
Antimicrobials Used in Swine acid (see Figure 33.4). There are high levels of resistance
to tetracycline in E. coli, as the group is the most widely
A wide variety of antimicrobials are available for use in used antibiotics in pigs for both enteric and respiratory
swine, but the availability of certain formulations is infections (Table 33.3).
often different between countries; for example, growth
In contrast, U.S. E. coli clinical isolates (n = 2144)
from small pigs showed a comparatively high inci-
dence of resistance to neomycin 49.5%, ceftiofur 41.8%,

558 Section IV. Antimicrobial Drug Use in Selected Animal Species

Table 33.1. Common swine bacterial and mycoplasmal pathogens, diseases, and ages affected.

Bacterial spp. Disease Age

Enteric infections Neonatal scours 1–3 days
Escherichia coli Piglet scours 7–14 days
Post-weaning diarrhea 5–14 days after weaning
Clostridium perfringens Mastitis, metritis, agalactia (MMA) syndrome Sows, post-parturient
Salmonella enterica spp. 1–7 days
Type C—necrotic enteritis 10–21 days, weaned pigs
Lawsonia intracellularis Type A—diarrhea Grower pigs—from weaning onward
S. Typhimurium—occasional diarrhea, septicemia, death Grower pigs
Brachyspira hyodysenteriae S. Derby—occasional diarrhea Finishing pigs 12–16 weeks
S. Choleraesuis—septicemia, diarrhea, death Grower pigs
Porcine proliferative enteropathy (ileitis) Grower pigs
Regional/necrotic ileitis Finishing pigs and young adults 16–40 weeks
Porcine haemorrhagic enteropathy Growers and finishers, 6–26 weeks
All ages in primary breakdown
Swine dysentery Grower pigs

Brachyspira pilosicoli Intestinal spirochaetosis “colitis” 1–8 weeks
Nasal distortion lasts for life
Respiratory and systemic infections Grower and finisher pig
Grower and finisher—secondary invader
Pasteurella multocida (D) Progressive atrophic rhinitis Grower and finisher—MDA can last for 10 weeks
1–6 weeks
Bordetella bronchiseptica 2–10 weeks
2–10 weeks
Mycoplasma hyopneumoniae Enzootic pneumonia
16 weeks plus
Pasteurella multocida Mycoplasma-induced respiratory disease (MIRD) 3–10 weeks
Growers, finishers, and sows/boars
Actinobacillus pleuropneumoniae Pleuropneumonia
1–8 weeks
Actinobacillus suis Septicemia, endocarditis, arthritis, and pneumonia 1–24 weeks

Streptococcus suis Meningitis, arthritis

Haemophilus parasuis Glässer’s disease (arthritis, polyserositis, pericarditis,

peritonitis)

Mycoplasma hyosynoviae Mycoplasmal arthritis

Mycoplasma hyorhinis Polyserositis, arthritis, low grade pneumonia

Erysipelas rhusiopathiae Erysipelas (dermatitis, arthritis, endocarditis)

Other Exudative epidermitis “greasy pig disease”
Staphylococcus hyicus Abscesses, often spinal
Arcanobacterium pyogenes

florfenicol 39.3%, gentamicin 31.1% but a low The use of zinc oxide in feed at weaning and the
resistance to trimethoprim/sulfonamide 25.5% and postponement of weaning to 28 days of age in the EU
enrofloxacin 1.7% (Frana et al., 2012). This is some- have made significant contributions to the reduction of
what surprising but may be a reflection on the limited cases of post-weaning diarrhea and a reduction in
availability of  other “front-line” drugs, such as the  use of antibiotics to control E. coli and thereby,
trimethoprim/sulfonamide combinations, which are resistance levels.
used in other countries.
The susceptibility of 197 Salmonella enterica serovar
With regard to enrofloxacin resistance against isolates in Indiana in the United States was reported by
E.  coli, there is an initial “wild-type” pattern, a first Huang et al. (2009). It was also reported on an individ-
stage mutant pattern, which is still susceptible if ual serovar basis (Tables 33.4 and 33.5)
situated in the gut due to its excretory pathway and a
second stage, completely resistant peak at 16 μg/ml Generally the susceptibility patterns are similar
(see Figure 33.5). to  E.  coli but usually they are slightly less resistant.
Interestingly, there is a marked difference between sero-

Chapter 33. Antimicrobial Drug Use in Swine 559

Table 33.2. Antimicrobials used in swine—routes of administration, dosages (mg/kg bodyweight), and target
pathogens.

Route of Administration and Dosage (mg/kg)

Family/Antimicrobial Injection Water Feed Use/Indication

Tetracyclines: 10 (LA 20) 10–30 20 M. hyopneumoniae
Oxytetracycline 4–6 20 10–20 P. multocida
Chlortetracycline 20–40 5 A. pleuropneumoniae
Tetracycline 15 (2.5 + 12.5) 5 H. parasuis
Doxycycline 15 (2.5 + 12.5) L. intracellularis
10 (LA 20) 30 (5 + 25) E. coli (R*)
Diaminopyrimidine/Sulfonamide – − Salmonella spp. (R*)
Trimethoprim /sulfadiazine – 10
7 (LA 15) 10 P. multocida
Penicillins: 7.5 15–20 B. bronchiseptica
Penicillin G +1.75 20 − A. pleuropneumoniae
Penicillin V − − S. suis
7 5 S. hyicus
Synthetic penicillins: 3 (LA 5) − H. parasuis
Amoxycillin 1–2 − − L. intracellularis
Ampicillin − − E. coli
Plus clavulanic acid 2.5 − Salmonella spp.
(beta-lactamase inhibitor) 1.25 −
2 − − S. suis
Cephalosporins: − − P. multocida
Cephalexin (1G) − H. parasuis
Ceftiofur (3G) A. pleuropneumoniae
Cefquinome (4G) A. pyogenes
C. perfringens
Fluoroquinolones: E. rhusiopathiae
Enrofloxacin
Danofloxacin S. suis
Marbofloxacin P. multocida
H. parasuis
A. pleuropneumoniae
A. pyogenes
C. perfringens
E. rhusiopathiae
E. coli
Salmonella spp.

S. suis
P. multocida
H. parasuis
A. pleuropneumoniae
A. pyogenes
C. perfringens
E. rhusiopathiae
E. coli
Salmonella spp.

M. hyopneumoniae
P. multocida
A. pleuropneumoniae
H. parasuis
E. coli
Salmonella spp.

(continued )

Table 33.2. Antimicrobials used in swine—routes of administration, dosages (mg/kg bodyweight), and target
pathogens. (continued)

Route of Administration and Dosage (mg/kg)

Family/Antimicrobial Injection Water Feed Use/Indication

Thiamphenicols: 10−30 − 10 P. multocida
Thiamphenicol 15 (LA 30) 15 15 A. pleuropneumoniae
Florfenicol H. parasuis
25 − − S. suis
Aminoglycosides: − ( NA) 11 11 B. bronchiseptica
Streptomycin − 7.5–12.5 4–8
Neomycin − (NA) Injection
Apramycin − (NA) 10−50 2.2 (+lincomycin) S. aureus
Gentamicin 50,000iu P. multocida
Amikacin − (NA) 25 50,000iu E. coli
Aminocyclitol: 2.125–4.25 Salmonella spp.
Spectinomycin − 15–20+ 3–6 (T) Orally
Polymixin: − 1.2–2.4 (P)
Colistin 2−10 − 2.125–4.25 E. coli
Macrolides: − 4.5 8–16+ Salmonella spp.
Tylosin − −
4+ − E. coli
Tylvalosin 8.8–20+ − Salmonella spp.
Tilmicosin 2.5+
Tildipirosin 5.5–11 (T) M. hyopneumoniae
Triamilide: 10 2.2 (P) L. intracellularis
Tulathromycin 1.1–2.2 B. hyodysenteriae (R*)
Lincosamides: − (+spectinomycin) B. pilosicoli (R*)
Lincomycin 10–15+ +Plus A. pleuropneumoniae
3.75–10 (T) H. parasuis
Pleuromutilins: 1.0–1.5 (P) P. multocida
Valnemulin 5–11 (T)
Tiamulin 1.5–2 (P) S. suis (R*)

Anticoccidials: M. hyopneumoniae
Toltrazuril M. hyosynoviae
L. intracellularis
B. hyodysenteriae
B. pilosicoli

M. hyopneumoniae
M. hyosynoviae
L. intracellularis
B. hyodysenteriae
B. pilosicoli
+Plus A. pleuropneumoniae

Isospora suis

20

Miscellaneous: Inclusion rate Claim
Growth promoters (not EU):
Virginiamycin 5.5–110 ppm GP + Swine dysentery(B. hyo)
Bacitracin MD 4.4–220 ppm GP + B. hyo; C. perfringens
Zinc bacitracin 11–55 ppm GP only
Flavophospholipol 2.2–4.4 ppm GP only
(Bambermycin)
Avilamycin 10–40 ppm GP only
10–50 ppm GP + Swine dysentery;
Carbadox S. Choleraesuis
Salinomycin 15–60 ppm GP only
Metals E. coli
Zinc oxide 3500 ppm (Postweaning diarrhea)

LA = long-acting formulation; NA = not approved; R* = resistance problems; T = treatment; P = prevention; GP = growth promotion; + = plus additional
claims; B. hyo = B. hyodysenteriae.

Chapter 33. Antimicrobial Drug Use in Swine 561

70Number of isolates

60
Resistant isolates

50

40

30 Amoxycillin
Amoxycillin + clavulanate

20

10

0
1 2 4 8 16 32 64 128
MICs (μg/ml)

Figure 33.4. Susceptibility patterns demonstrated by E. coli against amoxycillin and amoxycillin+clavulanic acid
(Klein et al., 2012).

Table 33.3. Antimicrobial susceptibility of 152 isolates of E. coli from the EU (Klein et al., 2012).

Antimicrobial MIC50 (μg/ml) MIC90 (μg/ml) MIC range (μg/ml) Resistance (%)

Amoxycillin 8.0 > 128 1.0– > 128 43
Amoxycillin + clavulanic acid 4.0 8.0 1.0–32 0 (enteric)
Streptomycin 32 > 128 4.0– > 128 44
Neomycin 1.0 32 0.25– > 128 5
Apramycin 4.0 16 1.0–32 0 (enteric)
Gentamicin 0.5 2.0 0.25– > 128 9
Enrofloxacin 0.03 1.0 0.008–16 20 (systemic)
7 (enteric)
Ciprofloxacin 0.015 0.5 0.008–16 20 (systemic)
7 (enteric)
Colistin 0.25 0.25 0.12–8.0 0
Trimethoprim + sulfonamide 0.25 > 16 0.015– > 64 45
Tetracycline > 128 > 128 14– > 128 80

vars with S. Typhimurium showing a higher resistance against B. hyodysenteriae as well as a number of other
pattern than S. Derby and S. Choleraesuis. Brachyspira spp. (Clothier et al., 2011; Table 33.7).

Brachyspira spp. seem to develop resistance more Antimicrobial susceptibility of B. pilosicoli and B. inter-
slowly than E. coli presumably because it is a slow media were generally better than for B. hyodysenteriae
growing microorganism, however, most isolates are now (Clothier et al., 2011) possibly, as they are less frequently
resistant to tylosin but many are still susceptible to the used to treat infections with these bacteria, as they tend
pleuromutilins, tiamulin, and valnemulin. There are to be milder. This was confirmed by Williamson et al.,
intermediate levels of resistance to lincomycin, tylvalo- (2010; Table 33.8).
sin, and doxycycline (Table 33.6). In the United States,
carbadox and salinomycin were also shown to be active Lawsonia intracellularis, the cause of ileitis, is a more
difficult microorganism to work with, as it requires cell

562 Section IV. Antimicrobial Drug Use in Selected Animal Species

100Number of isolates

90 Wild type
80

70

60

50
40 First stage mutants

30
Resistant

20

10

0
0.008 0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16
MICs (μg/ml)

Figure 33.5. Susceptibility pattern demonstrated by E. coli against enrofloxacin (Klein et al., 2012).

Table 33.4. Susceptibility of 197 U.S. isolates of Salmonella Table 33.5. Resistance (%) of different U.S. Salmonella

spp. (Huang et al., 2009). spp. (Huang et al., 2009).

MIC50 MIC90 MIC range Resistance Resistance (%)
(μg/ml) (μg/ml) (μg/ml) (%)
Antibiotic Overall S. Typhimurium S. Derby S. Choleraesuis
> 32 > 32 0.25– > 64 55.8
Ampicillin 8.0 > 32 1.0– > 64 21.8 (n = 197) Var. Copenhagen (n = 30) Var. Kunzendorf
Amoxicillin/
Clavulanic acid 4.0 > 32 1.0– > 64 20.8 Antibiotic (n = 39) (n = 27)
Cephalothin 1 >4 0.06– > 8 19.3
Ceftiofur 0.06 0.12 ≤ 0.03–0.25 0 Ampicillin 55.8 84.6 6.7 81.5
Enrofloxacin 4.0 > 8.0 0.5-– > 16 41.1 Amoxicillin/ 21.8 53.9 6.7 0
Florfenicol 0.5 8 0.12– > 4.1 6.6 Clavulanic acid
Gentamicin 32 > 128 16– > 128 42.6 Cephalothin 20.8 10.3 6.7 0
Spectinomycin > 16 > 16 0.5– > 32 83.8 Ceftiofur 19.3
Tetracycline ≤ 0.5 ≤ 0.5 ≤ 0.5–8.0 8.6 Enrofloxacin 0 7.7 6.7 0
Trimethoprim/ Florfenicol 41.1
Sulfonamide Gentamicin 6.6 00 0
Spectinomycin 42.6
Tetracycline 83.8 82.1 20 0
Trimethoprim/ 8.6
Sulfonamide 10.3 0 0

92.3 46.7 7.4

97.4 89 92.6

7.7 6.7 0

cultures to grow the bacterium. The most comprehensive ated with lincomycin and chlortetracycline but not
intracellular MIC work was reported by Wattanaphansak with the other compounds.
et al. (2009) where he tested 10 isolates of L. intracellu-
laris from EU and U.S. sources and the test was repeated Clostridium spp. are also a cause of increasing inter-
2  times, with slightly different results (Table  33.9). est  especially in young pigs. In some countries like the
The iMIC appears to be the most useful for comparison United  States, both C. perfringens Type C and A, and
with therapeutic concentrations of antimicrobials C.  difficile are associated with severe clinical problems.
in  the ileal contents (Burch, 2005) and as such It is interesting that most of the growth promoters, except
demonstrates there might be some resistance associ-

Chapter 33. Antimicrobial Drug Use in Swine 563

Table 33.6. Antimicrobial susceptibility of B. hyodysenteriae
in 70 UK isolates (Williamson et al., 2010).

Antibiotic MIC50 (μg/ml) MIC90 (μg/ml) MIC range (μg/ml)

Tiamulin 0.125 2.0 ≤ 0.06– > 8.0
Valnemulin ≤ 0.03– > 4.0
Lincomycin ≤ 0.03 4.0 0.5– > 32
Tylosin > 32 > 32 2.0– > 128
Tylvalosin > 128 > 128 0.5– > 32
Doxycycline > 32 > 32 0.5– > 16
1.0 16

Table 33.7. Antimicrobial susceptibility of B. hyodysenteriae in 24 U.S. isolates
(Clothier et al., 2011).

Antibiotic Median MIC (μg/ml) MIC90 (μg/ml) Range (μg/ml)

Tiamulin 0.125 0.5 0.125–4.0
Valnemulin 0.125 0.5 0.125–2.0
Lincomycin 32 64 1.0–64
Salinomycin 0.25 0.5 0.25–0.5
Carbadox 0.015 0.03 0.008–0.06

Table 33.8. Antimicrobial susceptibility of B. pilosicoli in 55 UK isolates
(Williamson et al., 2010).

Antibiotic MIC50 (μg/ml) MIC90 (μg/ml) Range (μg/ml)

Tiamulin 0.125 0.5 ≤ 0.06– > 8.0
Valnemulin ≤ 0.03 0.5 ≤ 0.03– > 4.0
Lincomycin 0.5 32 ≤ 0.25– > 32
Tylosin 8.0 > 128 2.0– > 128
Tylvalosin 1.0 > 32 ≤ 0.25– > 32
Doxycycline 0.25 4.0 0.5–8.0

flavomycin, have a strong activity against C. perfringens except to  ceftiofur, amoxycillin/clavulanic acid, the
(Table 33.10). fluoroquinolones, and florfenicol.

Respiratory and Systemic Pathogens Slightly better susceptibility results were achieved
against Pasteurella multocida, except for tetracyclines,
One of the major respiratory pathogens with potential which are again considered the first line of therapy
to develop antimicrobial resistance is A. pleuropneumo- (Table  33.13). Streptococcus suis, the cause of
niae but generally resistance is much lower than for streptococcal meningitis, still remains remarkably sus-
enteric bacteria such as E. coli (Tables 33.11 and 33.12). ceptible to the penicillins but shows poor susceptibility
The tetracyclines would normally be considered to the tetracyclines and tilmicosin (Table 33.14).
a frontline therapy for A. pleuropneumoniae. However,
in some countries such as Italy, a surprisingly high level A comparative study looking at 30 UK and 30 Spanish
of  resistance has been reported (Vanni et al., 2012), isolates of H. parasuis (Martin de la Fuente et al., 2007)
highlights the difference in susceptibility patterns in

564 Section IV. Antimicrobial Drug Use in Selected Animal Species

Table 33.9. Estimated intracellular MIC (iMIC) for a number of
antimicrobials of 20 results (10 isolates × 2 tests; (Wattanaphansak et al.,
2009) against L. intracellularis.

Antimicrobial iMIC50 (μg/ml) iMIC90 (μg/ml) Range (μg/ml)

Tiamulin 0.125 0.125 0.125–0.5
Valnemulin 0.125 0.125 0.125
Tylosin 2.0 8.0 0.25–32
Lincomycin 64 > 128 8.0– > 128
Chlortetracycline 8.0 64 0.125–64
Carbadox 0.125 0.25 0.125–0.25

Table 33.10. Susceptibility of Clostridium spp. to antibiotics. MIC50 (μg/ml) MIC 90 (μg/ml) MIC range (μg/ml)

Antimicrobial 0.06 0.12 0.03–0.12
0.03 4.0 0.007–16
Clostridium perfringens—Dutte and Devriese, 1980—58 Belgian isolates ≤ 128 ≤ 128 ≤ 128
Bacitracin 0.25 0.5 0.25–2.0
Carbadox 2.0 256 0.12– ≥ 512
Flavomycin 0.12 0.5 0.06–1.0
Virginiamycin 16 32 0.06– ≥ 64
Lincomycin – – 0.25–4.0
Penicillin G
Tetracycline 0.012 0.012 0.012– ≥ 64
Tiamulin
4.0 64 0.125–128
Clostridium perfringens—Devriese et al., 1993—95 Belgian isolates 2.0 4.0 0.25–8.0
Tylosin 0.125 8.0 0.063–32
0.063 0.125 0.016–0.25
Clostridium perfringens—Agnoletti et al., 2010—30 Italian and 38 Danish isolates
Tiamulin (Italian) > 256 > 256 –
Tiamulin (Danish) 0.25 2.0 –
Valnemulin (Italian) 0.25 64 –
Valnemulin (Danish) 0.5 > 256 –
8 32 –
Clostridium difficile—Post and Songer, 2002—80 U.S. isolates 4 8 –
Bacitracin 256 > 256 –
Virginiamycin
Tylosin 8 16 0.125–16
Tilmicosin 0.5 1.0 0.063–1.0
Tetracycline
Tiamulin
Ceftiofur

Clostridium perfringens—Agnoletti et al., 2010—15 Italian and Danish isolates
Tiamulin
Valnemulin

different countries, showing it is important to develop ally antibiotic resistance is low (Table  33.16). It is
local farm and national data (Table 33.15). the precursor of many cases of complicated secondary
bacterial pneumonia, associated with P. multocida,
Mycoplasma hyopneumoniae, the cause of enzootic and  also plays a key role in the porcine respiratory
pneumonia, is also a slow growing organism and gener-

Chapter 33. Antimicrobial Drug Use in Swine 565

Table 33.11. Antimicrobial susceptibility of A. pleuropneumoniae in 129 EU isolates
(Klein et al., 2012).

Antimicrobial MIC50 (μg/ml) MIC90 (μg/ml) MIC range (μg/ml) Resistance (%)

Amoxycillin 0.5 0.5 0.25–32 5
Amoxycillin + clavulanic acid 0.25 0.5 0.06–1.0 0
Cephalexin 2.0 2.0 0.12–4.0 0
Ceftiofur 0.015 0.03 0.008–0.06 0
Enrofloxacin 0.03 0.06 0.008–2.0 1
Florfenicol 0.25 0.5 0.12–0.5 0
Trimethoprim+ sulfonamide 0.06 0.25 0.008–16 5
Tetracycline 1.0 16 0.25–32 15
Tilmicosin 8.0 16 4.0–16 0
Tiamulin 8.0 16 0.25–16 0

Table 33.12. Antimicrobial resistance of Italian A. pleuropneumoniae
isolates from 2009 (Vanni et al., 2012).

Antimicrobial Resistance (%) Antimicrobial Resistance (%)

Penicillin G 72.7 Enrofloxacin 9.6
Amoxycillin
Amoxycillin + 82.6 Marbofloxacin 2
Clavulanate
Cephalexin 8.9 Trimethoprim+ 32.7
Ceftiofur
Tetracycline Sulfonamide
Doxycycline
Florfenicol 21.7 Tilmicosin 51.3

7.7 Tulathromycin 66.7

58.8 Tiamulin 13.5

25 Streptomycin 100

7.7 Gentamicin 63.6

Table 33.13. Antimicrobial susceptibility of P. multocida in 135 EU isolates (Klein et al., 2012).

Antimicrobial MIC50 (μg/ml) MIC90 (μg/ml) MIC range (μg/ml) Resistance (%)

Amoxycillin 0.25 0.25 0.06–128 1
Amoxycillin + clavulanic acid 0.25 0.25 0.12–0.25 0
Cephalexin 2.0 4.0 1.0–8.0 0
Ceftiofur 0.004 0.03 0.002–0.5 0
Enrofloxacin 0.015 0.03 0.008–0.25 0
Florfenicol 0.5 0.5 0.25–1.0 0
Trimethoprim+ 0.06 0.5 0.008–16 3

sulfonamide 0.5 2.0 0.25–32 22
Tetracycline 8.0 16 1.0–16 0
Tilmicosin

disease complex (PRDC), where viruses are also enrofloxacin (5  isolates). Acquired resistance to these
involved. Some antibiotic resistance was demonstrated antimicrobials had not been described in M. hyopneu-
against lincomycin, tylosin and tilmicosin (1 isolate and moniae field isolates previously.

566 Section IV. Antimicrobial Drug Use in Selected Animal Species

Table 33.14. Antimicrobial susceptibility of S. suis in 110 EU isolates (Klein et al., 2012).

Antimicrobial MIC50 (μg/ml) MIC90 (μg/ml) MIC range (μg/ml) Resistance (%)

Amoxycillin ≤ 0.03 ≤ 0.03 0.03–0.25 0
≤ 0.06 ≤ 0.06
Amoxycillin + clavulanic acid 0.12 0.5 0.06–0.25 0
Cephalexin 0.12 0.5 0.06–4.0 0
Ceftiofur 0.5 0.5 0.06–2.0 0
Enrofloxacin 0.5 0.5 0.12–8.0 1
Florfenicol 0.06 1.0 0.25–1.0 0
Trimethoprim + sulfonamide 32 32 0.008–16 7
Tetracycline > 128 > 128 0.25–32 82
Tilmicosin 4.0– > 128 54

Table 33.15. Antimicrobial susceptibility of H. parasuis isolates (30 from UK and 30 from Spain;
Martin de la Fuente et al., 2007).

Antibiotic MIC50 (μg/ml) UK Resistance (%) MIC50 (μg/ml) Spain Resistance (%)

Penicillin ≤ 0.12 MIC90 (μg/ml) 0 8.0 MIC90 (μg/ml) 60
Ampicillin ≤ 0.25 6.7 16 56.7
Ceftiofur ≤ 0.5 0.5 0 ≤ 0.5 > 8.0 6.7
Gentamicin 1.0 2.0 10 8.0 > 16 26.7
Oxytetracycline 0.5 1.0 6.7 4.0 4.0 40
Tilmicosin <4 8.0 0 16 > 8.0 40
Enrofloxacin ≤ 0.12 4.0 0 0.25 > 8.0 20
Florfenicol ≤ 0.25 8 0 0.5 > 32 0
Tiamulin ≤ 4.0 0.25 3.3 16 > 2.0 40
Trimethoprim+ ≤ 0.5/9.5 1.0 10 > 2/38 1.0 53.3
16 > 32
Sulfonamide 2/38 > 2/38

Table 33.16. Antimicrobial susceptibility of M. hyopneumoniae in 21 Belgian field
isolates (Maes et al., 2007)—final MICs, 14 days after inoculation.

Antimicrobial MIC50 (μg/ml) MIC90 (μg/ml) MIC range (μg/ml)

Enrofloxacin 0.06 0.5 0.03- > 1.0
0.12- > 2.0
Oxytetracycline 0.5 2.0 0.12–2.0
Doxycycline 0.5 1.0 ≤ 0.06- > 8.0
Lincomycin ≤ 0.06 0.12 ≤ 0.12–1.0
Spectinomycin 0.5 1.0 ≤ 0.12–1.0
Gentamicin 0.5 1.0 ≤ 0.12–1.0
Florfenicol 0.25 0.5 ≤ 0.015–0.12
Tiamulin 0.03 0.12 ≤ 0.015- > 1.0
Tylosin 0.06 0.12 ≤ 0.25- > 16
Tilmicosin 0.5 0.5

Chapter 33. Antimicrobial Drug Use in Swine 567

Conclusion Burch DGS. 2012. Fellowship thesis—Examination of the
pharmacokinetic/pharmacodynamic (PK/PD) relation-
Apart from some microorganisms such as E. coli, ships of orally administered antimicrobials and their
B.  hyodysenteriae and A. pleuropneumoniae, where on correlation with the therapy of various bacterial and
occasions severe antimicrobial resistance has been mycoplasmal infections in pigs. Royal College of Veterinary
determined, the antimicrobial resistance situation is Surgeons, London, p. 63.
generally not that extensive. However, the difference
does vary from country to country. In most cases, an Clemens ET, et al. 1975. Sites of organic acid production and
infection can be treated using existing approved antimi- pattern of digesta movement in the gastrointestinal tract of
crobials, providing that their availability can be main- swine. J Nutr 105:759.
tained for use in pigs. It is thought that it is unlikely
there will be many new antibiotics in the near future. Clothier KA, et al. 2011. Species characterization and
minimum inhibitory concentration patterns of Brachyspira
Care should be taken to not overuse antimicrobials species isolates from swine with clinical disease. J Vet
and veterinarians should consider reduction of use where Diagn Invest 23:1140.
possible and practical, and address management and
housing issues at the same time. Vaccine alternatives Devriese LA, et al. 1993. In vitro susceptibility of Clostridium
should be considered, where appropriate. Susceptibility perfringens isolated from farm animals to growth-enhancing
testing should become routine. If antibiotics are used antibiotics. J Appl Bacteriol 75:55.
responsibly and sensibly, there is no major reason why
our current armoury should not be sufficient for the fore- Drlica K. 2003. The mutant selection window and antimicro-
seeable future. It must be remembered that most of the bial resistance. J Antimicrob Chemother 52:11.
antimicrobials used in pigs are already over thirty years
old and that the majority of them are still working. Even Dutta GN, Devriese LA. 1980. Susceptibility of Clostridium
the more modern antibiotics such as third- and fourth- perfringens of animal origin to fifteen antimicrobial agents.
generation cephalosporins, if used carefully and not for J Vet Pharmacol Therap 3:227.
widespread prophylaxis, will maintain their efficacy
Fabrizio A, et al. 2010. Pleuromutilin susceptibility of
Overall, antimicrobials are extremely useful and Clostridium perfringens and Clostridium difficile isolates
helpful tools but one of the major challenges in swine from pigs in Italy and Denmark. Proceedings of the 21st
medicine is to overcome the management and produc- International Pig Veterinary Society Congress, Vancouver,
tion issues that have often resulted in the requirement to Canada, p. 3.
use antibiotics in the first place.
Frana T, et al. 2012. Antimicrobial susceptibility patterns
Bibliography associated with virulence factors in swine Escherichia coli
isolates. Proceedings of the 43rd American Association of
Anon. 2009. Scientific report of EFSA—analysis of the base- Swine Practitioners Annual Meeting, Denver, Colorado,
line survey on the prevalence of methicillin-resistant p. 57.
Staphylococcus aureus (MRSA) in holdings with breeding
pigs, in the EU, 2008. Part A: MRSA prevalence estimates. Huang TM, et al. 2009. Serovar distribution and antimicro-
EFSA Journal 7:1376. bial susceptibility of swine Salmonella isolates from clini-
cally ill pigs in diagnostic submissions from Indiana in
Anon. 2011. EFSA Panel on Biological Hazards—scientific the United States. Lett Appl Microbiol 48:331.
opinion on the public health risks of bacterial strains
producing extended-spectrum beta-lactamases and/or Khanna T, et al. 2008. Methicillin resistant Staphylococcus
AmpC beta lactamases in food and food-producing aureus colonization in pigs and farmers. Vet Microbiol
animals. EFSA J 9:2322. 128:298.

Burch DGS. 2005. Pharmacokinetic, pharmacodynamic and Klein U, et al. 2012. Antimicrobial susceptibility monitoring
clinical correlations relating to the therapy of Lawsonia of respiratory and enteric tract pathogens isolated
intracellularis infections, the cause of porcine proliferative from diseased swine across Europe between 2004
enteropathy (“ileitis”) in the pig. Pig J 56:25. and 2006. Proceedings of the 4th European Symposium
of Porcine Health Management, Bruges, Belgium,
p. 197.

Kyriazakis I, Whittemore CT. 2006. Whittemore’s Science and
Practice of Pig Production, 3rd ed. Oxford: Blackwell,
p. 407.

Maes D, et al. 2007. In vitro susceptibilities of Mycoplasma
hyopneumoniae field isolates. Vlaams Diergeneeskundig
Tijdscrift 76:300.

Martin de la Fuente AJ, et al. 2007. Antimicrobial susce-
ptibility patterns of Haemophilus parasuis from pigs in the
United Kingdom and Spain. Vet Microbiol 120:184.

Nielsen P. 1997. The influence of feed on the oral bioavaila-
bility of antibiotics/chemotherapeutics in pigs. J Vet
Pharmacol Therap 20 Suppl 1:30.

568 Section IV. Antimicrobial Drug Use in Selected Animal Species

Post KW, Songer JG. 2002. Antimicrobial susceptibility of Wattanaphansak S, et al. 2009. In vitro antimicrobial activ-
Clostridium difficile isolated from neonatal pigs. ity against 10 North American and European Lawsonia
Proceedings of the 17th International Pig Veterinary intracellularis isolates. Vet Microbiol 133:305.
Society Congress, Ames, IA, p. 2:62.
Williamson S, et al. 2010. Preliminary results for Brachyspira
Vanni M, et al. 2012. Antimicrobial resistance of Actinobacillus MIC assessment of isolates from England. Presentation Pig
pleuropneumoniae isolated from swine. Vet Microbiol 156:172. Veterinary Society, Norwich, Norfolk, UK.

Antimicrobial Drug Use in Poultry 34

Charles L. Hofacre, Jenny A. Fricke, and Tom Inglis

Whether fully integrated or not, the commercial drugs in the therapeutic category are used to treat or
poultry industry is a very intensive animal agriculture cure a clinically detectable disease. Because sick birds
system. One poultry house or barn can contain as may be off feed, therapeutic antimicrobials are
many as 100,000 commercial layers or commercial typically administered via the drinking water; how-
broilers. At the hatchery level, depending on the type ever, certain circumstances or disease conditions may
of equipment in place, one incubator can contain dictate administration in feed instead or concomi-
more than 120,000 eggs or developing embryos. This tantly with water. The preventative or prophylactic
ultimately means that disease prevention, on all levels category includes the antimicrobial drugs that are
of the poultry production continuum, is the major used to prevent disease. Prophylactic antimicrobials
focus for a poultry veterinarian. Antimicrobials are are administered prior to the appearance of clinical
critically important in the prevention and treatment signs of disease in a flock. The route of antimicrobial
of diseases in the poultry industry. Under circum- administration may depend on the timing or age of
stances when husbandry and biosecurity procedures bird when the treatment is applied. In poultry pro-
fail to prevent the introduction of a disease agent, duction, population health begins at the hatchery
appropriate antimicrobial therapy can become neces- where eggs from various flocks are comingled and the
sary to prevent pain and suffering in these birds as disease and microbiological status of individual eggs
well as economic losses to the producer. When the can impact all the other birds hatching at that time.
poultry veterinarian makes a diagnosis and decides When increased bacterial contamination has been
that birds need to be treated with an antimicrobial identified in association with eggs coming from a
drug, they must then determine the appropriate drug particular breeder flock, birds from that flock may be
formulation and route of administration. treated preventatively using in ovo (eggs) or subcuta-
neous (day-old chicks or poults) injection of an anti-
Categories of Antimicrobial Drug Use microbial until the underlying cause for such
in the Poultry Industry contamination is identified and corrected. Other routes
for administration of prophylactic antimicrobials
Antimicrobial drug use in poultry can be divided into include oral administration via drinking water or
three categories of use: therapeutic, preventative/ feed. The  last category of antimicrobial use, growth
prophylactic and growth promoting. Antimicrobial promotion, is the most controversial. Antimicrobials
in the growth promotion category were and are only

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

569

570 Section IV. Antimicrobial Drug Use in Selected Animal Species

administered in feed. Many antimicrobials were first Antimicrobial Drug Use in the Poultry
approved for poultry based on their observed Industries of Canada, The United States,
growth-promoting effects: improved feed efficiency and Europe
and growth rates. The improved production results in
an economic benefit that is greater than the cost of Because of issues involving antimicrobial resistance, not
the antimicrobial drug. Due to increasing concerns all of the categories of antimicrobial use are permitted in
that growth-promoting use of antimicrobials in poul- the different poultry producing countries throughout
try has a negative impact on human health due to the world.
antimicrobial resistance, there has been mandated
and voluntary removal of growth promotors from Approved, Prohibited for Extra-Label Use,
poultry production in many jurisdictions. With the or Banned for Use
bans on such use, it has become evident that much of
the growth promotion effect is due to the control and Antimicrobial use, in animals or humans and in any of
prevention of subclinical enteric disease. In some the previously described categories, has the potential to
cases these antimicrobials may be the same as those select for bacterial strains that are resistant to the
approved for therapeutic use; however, the dose level antimicrobial used (O’Brien, 2002). For this reason,
for growth promotion is generally less than the thera- antimicrobial use in food-producing animals, particu-
peutic dose. In countries such as the United States larly with respect to use for growth promotion or
and Canada, where products have both therapeutic disease prevention (as the line between the two is not
and growth-promoting label claims, these products clear), has been and still is a focus of scientific, political
are rarely used for growth promotion. For example, and consumer debate (Casewell et al., 2003; Phillips
penicillin and tetracyclines are rarely used as growth et  al., 2004; Kelly et al., 2004; Cox and Popken, 2004;
promotants even though there are regulatory approv- Cox, 2005; Phillips, 2007). The association of antimi-
als for this. crobial use in food animals with antimicrobial resist-
ance of concern in human health has resulted in
In considering these broad categories of different approaches to the control of antimicrobial use
antimicrobial use in poultry, the distinction between in Canada, the United States and Europe. The use of
therapeutic, preventative and growth-promoting antimicrobials for growth promotion and/or disease
categories is not always clear. The poultry veterinar- prevention in poultry is currently permitted in the
ian is faced with making a decision regarding United States and Canada. Such use has been banned in
treatment of a population; individual treatment is the countries of the European Union (EU); a process
often not possible or practical. As not all birds in that that started with banning a few products in the 1970s
population will be clinically ill, the antimicrobial but now includes all antimicrobial growth promoters
treatment will be   therapeutic for a portion of the (Dibner and Richards, 2005; Castanon, 2007).
population and preventative for another portion of
the population. To further complicate the matter, Subsequent to the EU bans, a number of reviews and
growth-promoting antimicrobials are known to kill risk assessments on the use of in feed antimicrobials
or inhibit the growth of disease-causing agents, have been conducted (Cox and Popken, 2004; Kelly
including bacteria or coccidia. These products are et al., 2004; Phillips et. al, 2004; Cox, 2005. Thus far no
particularly effective at prevention of necrotic enteri- bans have been implemented in North America.
tis, a condition triggered by enteric overgrowth of Therapeutic antimicrobial uses have not yet been
Clostridium perfringens (Grave, 2006; Smith, 2011). banned in Europe, but have been targeted in the United
While the exact mode of action for growth promotion States. Enrofloxacin and sarfloxcin were approved as
associated with the use of antimicrobials is debatable therapeutic antimicrobials for the control of colibacillo-
(Dibner and Richards, 2005; Neiwald 2007), growth sis in poultry in the United States. In 2005, these
promotion is clearly a “side effect” of disease fluoroquinolones were banned from use in poultry. The
prevention. primary reason for this ban was to allay concerns regard-
ing rising fluoroquinolone resistance rates in human

Chapter 34. Antimicrobial Drug Use in Poultry 571

cases of camplylobacteriosis (FDA, 2005). A more recent growth-promoting antibiotics initially led to significant
prohibition of use in the United States occurred in animal and human health concerns. In the poultry
January 2012 with a ban on the extra-label use of cepha- industry, necrotic enteritis is the disease of primary
losporins. This ban particularly targeted the extra-label concern and is a challenge to manage in the absence of
use of ceftiofur, when administered in ovo for metaphy- the antimicrobial growth promoters (Wierup, 2001;
laxis in cases of known or anticipated E. coli challenge Casewell et al., 2003; Dibner and Richards 2005; Grave
(FDA, 2012). Such use was associated with E. coli et al., 2006). Similar observations have been made in the
isolations from poultry carcasses containing genes that United States when poultry producing companies
rendered them resistant to human third-generation voluntarily removed in-feed antimicrobials in order to
cephalosporins. So while extra-label use is prohibited, produce an “antibiotic-free” product for specific markets
ceftiofur remains approved for subcutaneous adminis- (Smith, 2011). In the EU, control of coccidiosis will
tration to day-old chicks and turkey poults. become a major health issue in poultry production, as
the ionophore antibiotics are scheduled to be banned in
In Canada, there have been no bans on antimicrobials 2013 (Castanon, 2007).
in any of the categories of use. Extra-label drug use in
Canada is not codified like the United States; Canadian Of concern for human health in the EU was the
veterinarians have the privilege of extra-label drug use. increased use of therapeutic antimicrobials in poultry to
The definition of extra-label drug use (ELDU) as defined treat clinical disease; primarily necrotic enteritis but also
by Health Canada is “the use or intended use of a drug other forms of infectious enteritis (Casewell et al., 2003;
approved by Health Canada in an animal in a manner Grave et al., 2006). Unlike the majority of the in-feed
not in accordance with the label or package insert” antimicrobials approved for growth promotion, many of
(Health Canada, 2011). While not recommended by the antimicrobials used for therapy are related to or the
Health Canada, it is possible for Canadian veterinarians same as those used in human medicine (Casewell et al.,
to use the cattle injectable enrofloxacin formulation in 2003; Phillips et al., 2004; Phillips, 2007). Another unin-
poultry, and to use the injectable ceftiofur product tended consequence for human health that was over-
(approved for subcutaneous injection in day-old turkey looked is the importance of the antimicrobial growth
poults) in chicks and administered either in ovo or promoters in modulating and promoting good intestinal
subcutaneously. health. Intestinal integrity in a poultry flock is extremely
important, especially in the slaughter and processing of
Consequences of Antimicrobial Bans birds; the normal poultry intestinal tract contains a
plethora of bacterial organisms, many of which are non-
The consequences of the ban on enrofloxacin and sara- pathogenic to the bird but pathogenic for people.
floxacin use in poultry in the United States are being Inflammation and disease of the intestinal tract weakens
extensively studied. Anecdotally it appears that the rates the gut wall and increases the risk of intestinal breakage
of fluoroquinolone and cephalosporin resistance in bac- and the potential for greater contamination of the final
teria of importance to human health are not changing; product (Russell, 2003). While meat is not sterile, good
however, peer-reviewed publications are not yet availa- intestinal health vital in reducing the bacterial load on
ble. The bans have removed effective treatments of poultry products provided to the consumer.
bacterial disease from the poultry veterinarian’s arma-
mentarium. Veterinarians have valid concerns that anti- The remaining use of antimicrobials in poultry for
microbial bans can cause significant animal welfare growth promotion in countries such as the United States
concerns in the face of an untreatable disease outbreak. and Canada, and the use of antimicrobials considered
In a somewhat extreme example, the potentially difficult critically important in human medicine for therapy of
decision regarding early slaughter of entire flocks may food animals will continue to be scrutinized. The bene-
need to be considered should no approved therapy exist. fits of these products for health, both human and animal,
however, also need to be considered. Consumer and
The outcomes or concerns relating to bans on antimi- retailer pressure in some regions has resulted in removal
crobial use for growth promotion and/or prevention are of these antimicrobials from broiler feeds. Producers
better documented and understood. The EU bans on

572 Section IV. Antimicrobial Drug Use in Selected Animal Species

supplying export markets with poultry products may to treat a “sick flock” of birds means veterinarians will be
also be required to discontinue use of antimicrobial administering antimicrobials not only to the sick birds,
growth promoters if they wish to continue to supply but also to all birds in that flock that have been or will be
certain markets where bans are in place, or where con- exposed to the disease agent. In making this decision to
sumers demand that antimicrobial use is discontinued treat the “sick flock,” the poultry veterinarian must also
(Dibner and Richards, 2005). Overall, the general trend decide, based on clinical judgment, whether the “flock”
for the future is reduced antimicrobial use. This ulti- to be treated includes the entire farm or only the house
mately means that when the question of whether to treat containing the most clinically affected birds. A rapidly
or not to treat a flock is raised for the poultry veterinar- spreading disease may necessitate prophylactic treat-
ian, there are more factors than ever to consider in the ment of all houses on the farm.
decision making process; effectiveness against the dis-
ease agent, pharmacokinetics and pharmacodynamics When considering treatment in the drinking water or
of the medication, withdrawal times, pathology and the feed, the poultry veterinarian must take into account
physiology, economics/cost-benefit, animal welfare, lighting schedules and feed programs, which can also
impact on foodborne pathogens, and impact on the strongly influence both feed and water consumption.
ability to market the final product. Laying hens begin to eat when the lights are turned on
and then consume water after eating. Broiler chickens
Factors Influencing Antimicrobial and turkeys that have continuous light eat and drink
Administration in the Poultry Industry intermittently at 3- to 4-hour intervals. The majority of
water intake in replacement breeders under feed restric-
Husbandry and Economics tion occurs for only a few hours after feeding.

Under current husbandry conditions in the poultry Production Type/Bird Type
industry, segregation and medication of individual sick
birds is not feasible. The low economic value of the Within the poultry industry, integrated or not, there is a
individual bird makes it is cost-prohibitive to individu- continuum or flow of birds and bird types. For example,
ally dose each bird in a house, which eliminates paren- in the chain of production of a commercial broiler
teral administration of drugs such as aminoglycosides (meat-type chicken), the parents of that bird are hatched
and cephalosporins. An additional argument against at a hatchery, reared and brought into egg production.
parental administration is that the stress on birds when Eggs collected from that flock will return to a hatchery
individually handled can result in a more rapid progres- for incubation, to hatch into broiler chickens that will be
sion of the disease. Since sick birds continue to drink, grown and ultimately slaughtered for meat. Prevention
therapeutic antimicrobials labeled for use in drinking of disease at all levels within this continuum is extremely
water are most often used. important; there can be serious downstream conse-
quences if not prevented. The consequences are also
Antimicrobial interventions must be administered impacted by the type of bird and the point in this chain
early in the course of disease. Bacterial infections in of production at which the disease occurs. For example,
birds tend to progress rapidly, and there is frequently a disease in a flock producing hatching eggs can not only
very short time from initial infection to death. In addi- have a severe impact on overall health and productivity
tion, birds are adept at producing inflammatory of that flock, but some bacterial diseases such as
responses, but poor at resolving the products of such Mycoplasma can be vertically transmitted to offspring,
responses. As prey species, poultry tend to hide clinical and if not treated, the spread of disease is amplified
signs of disease. Spotting the prodromal, subtle signs of (Bradbury 2005). Conversely, treatment of flocks in egg
infection in individuals in a flock of 10,000–100,000 production can impact the production or quality of the
birds is both important and problematic. Treatment of eggs depending on the antimicrobial used. The use of
all individuals in contact and at high risk of exposure tetracyclines in flocks in egg production can adversely
(i.e., the entire flock) is the only practical approach to affect the amount of calcium available to the hen for
disease outbreaks in large flocks. Thus the decision eggshell formation as these medications are known to
chelate with divalent cations. Poor shell quality in the

Chapter 34. Antimicrobial Drug Use in Poultry 573

eggs in turn increases the risk of bacterial contamina- temperature increases. This affects dosage calculation
tion of the egg, which when placed in a single incubator and makes it possible for birds to be overdosed when a
with up to 120,000 other eggs, increases the risk of bac- drug is administered in drinking water. This is especially
terial disease for all other embryos as well. Disease in a important with the use of sulfonamides, as the therapeu-
broiler flock, where there is only a short time between tic dose is close to the level that can result in toxic effects
hatching and slaughter, can be challenging from the per- (Goren et al., 1984). Fortunately, bacterial diseases in
spective of medication withdrawal times. When flocks general tend to be less common in hot weather.
approach market age, the number of antimicrobial treat-
ment options available for different diseases diminish Pathology and Disease Etiology
because their administration would result in violative
antimicrobial residues present at the time of slaughter. Escherichia coli is the leading cause of disease-related
Antimicrobial residues could in turn result in condem- economic loss for the poultry industry throughout the
nation of slaughtered birds, or could mean postponing world (Barnes et al., 2003). In most instances, E. coli
slaughter, which is accompanied by other challenges infections are secondary infections following a primary
such as limited space in the barn as the birds will con- viral or environmental insult (Glisson, 1998). Therefore,
tinue to grow. Additionally, postponing slaughter can therapeutic antimicrobials in commercial poultry are
result in oversized birds. It is critically important that almost always used to relieve the suffering of the sick
birds meet slaughter specifications, as oversize birds are birds, control morbidity and mortality, and minimize
a challenge for processing equipment, creating a welfare the financial impact of the disease on bird performance
concern for humane slaughter and a challenge to physi- until the primary insult can be identified and controlled
cally process the slaughtered bird, resulting in carcass or eliminated. The use of therapeutic antimicrobials also
damage and potentially increased risk of microbial con- decreases the public health risk associated with slaugh-
tamination at processing. tering birds from sick flocks. Poultry that are sick eat
greater amounts of bedding material (litter), resulting in
Feed and Water Consumption higher rates of Salmonella and Campylobacter spp. in
their intestinal tracts (Corrier et al., 1999). Also, Russell
Flock treatment is the method of choice, with drinking (2003) found that birds from flocks having higher air
water and feed the primary means of delivering antimi- sacculitis condemnation had higher levels of E. coli and
crobials to commercial poultry (Vermeulen et al., 2002). Campylobacter contamination.
When birds become sick, there is a significant reduction
in consumption of both feed and drinking water. The The choice of therapeutic antimicrobials available to
decline in drinking water consumption is usually less treat respiratory infections caused by E. coli is limited
than that of feed. Therefore, the route of choice for (Glisson and Hofacre, 2004). The tetracyclines, enro-
administering antimicrobials in the early stages of a dis- floxacin, and the sulfonamides are the primary drugs
ease is usually by the birds’ drinking water. If therapy used to treat E. coli airsacculitis. It can be speculated that
lasts more than 5–7 days, then the veterinarian may this limited choice of antimicrobials has, over 30 years,
choose to have the antimicrobial drug added to the resulted in selection pressure on E. coli in the commer-
birds’ feed, if an approved feed-grade product is availa- cial poultry environment, resulting in the high levels of
ble. This change to feed can be based upon the flock sulfonamide (93%) and tetracycline (87%) resistance in
beginning to recover and eating more. In general, feed- clinical E. coli isolates observed in many diagnostic
grade antimicrobials are also less expensive than water laboratories (Zhao et al., 2005).
soluble ones, and are preferred when a suitable drug
with a clinically effective inclusion rate is available. The immune status of the flock must also be taken
into account when deciding which antimicrobial agent
Another consideration when selecting the appropriate to use and the dose rate. For example, chickens experi-
antimicrobial is the ambient temperature, since poultry encing an E. coli air sacculitis outbreak secondary to
have limited means of eliminating body heat. In large immune suppression by infectious bursal disease virus
part, they cool themselves by drinking water; therefore, should be treated with a bacteriocidal drug such
water consumption increases significantly as the ambient as enrofloxacin. However, a bacteriostatic drug such as
oxytetracycline may be more effective in treating E. coli

Table 34.1. Antimicrobial treatment options in poultry.

Antimicrobial

Disease/Bacterial Species Bacitracin
Bambermycins
Ceftiofur
Chlortetracycline
Enrofloxacin
Erythromycin
Gentamicin
Lincomycin
Neomycin
Novobiocin
Oxytetracycline
Penicillin
Spectinomycin
Streptomycin
Sulfonamide
Tylosin
Virginiamycin

Arthritis/ Staphyloccus aureus XX XXXXX

Chronic respiratory disease (CRD)/ X X* XX X

Mycoplasma spp.

Colibacillosis/ XX X XXX

Escherichia coli

Erysipelas/Erysipelothrix X

rusiopathiae

Fowl cholera/ Pasteurella X X* XXXXX

multocida

Fowl coryza/ Haemophilus XX X XXX

paragallinarum

Gangrenous dermatitis/ XX XX X X

Clostridium spp.

Necrotic enteritis/ Clostridium XX XX XXX XX

perfringens

Omphalitis/ Pseudomonas spp. &/ XX X X XXX

or Enterobactericiae

Salmonellosis/ XX X XX

Salmonella spp.

*Extra-label use of enrofloxacin is illegal in the United States.
Information based on published data, clinical experience; use may be extra-label.

Chapter 34. Antimicrobial Drug Use in Poultry 575

airsacculitis that is secondary to respiratory infection by and susceptibility testing. Oral treatment of poultry
an infectious bronchitis virus. requires that the drug be stable and be uniformly
distributed in either feed or water. When a feed-based
Pharmacology antimicrobial is prescribed, the time required for the
medicated feed to be manufactured, transported, and
The success of antimicrobial therapy depends upon delivered through the feeding system at the farm
many interacting factors, including pharmacodynamics must be taken into account.
(drug interaction with the pathogen), pharmacokinetics
(drug absorption, distribution, excretion) and the com- Administering the antimicrobial in the drinking
ponents of the host immune system (chapters 4 and 5). water allows for more rapid treatment. The volume of
The activity of an antimicrobial agent against a particu- water consumed in 24 hours by the birds in the house to
lar microbe is often expressed as the minimal inhibitory be treated must first be determined. Freshly medicated
concentration (MIC; chapter 2). When interpreting solutions should be prepared every day. Drinking water
antimicrobial susceptibility information, the poultry medication is usually administered by either a bulk tank
veterinarian must keep in mind that this is an in vitro or a water proportioner. Bulk tanks contain 500–2000
test that does not take into consideration whether the liters, and all of the medication for a given tank’s volume
drug can reach the site of infection or whether the drug of water is added to it. A water proportioner is a device
is bacteriostatic or bactericidal for the microbe. It should that meters the antimicrobial from a highly concen-
also be remembered that the MIC is usually performed trated stock solution into the drinking water to achieve
by the laboratory on only one isolate, and as was previ- the appropriate concentration.
ously stated, many infections of poultry are secondary,
so a “sick flock” is often affected by multiple isolates that It should be apparent that administering antimi-
can have a wide range of MICs. Also, MIC breakpoint crobials to poultry based solely on concentration of
criteria in veterinary medicine are not uniform world- the active ingredient in the drinking water and ignor-
wide and are often based on standards for human medi- ing the above described physiological, pathological,
cine (chapter 2). Additionally, pharmacokinetic data and husbandry conditions can lead to highly inaccu-
determined in mammals are not always applicable to rate dosing. The most accurate method is to calculate
poultry because birds have higher body temperatures, the dose based upon the total body weight of birds in
higher metabolic rates, and shorter alimentary tracts, the house, and then include that dose in the volume
which often results in shorter elimination half-life times of water or feed the birds are expected to consume
for medications. This frequently leaves the poultry vet- during each dosing interval. Dosing based on water
erinarian with an antimicrobial therapy decision based consumption can result in a toxic overdose if the
upon clinical judgment from previous cases rather than ambient temperature increases, or the amount of
on the uncertain available science. The primary crite- drug consumed may drop below the MIC of the
rion for measuring success of treatment under poultry bacteria being treated if the ambient temperature
industry conditions is reduction of morbidity and mor- declines. Additionally, younger birds consume more
tality. Other important parameters include return to water daily per unit of body weight than older birds.
regular water and feed consumption, normal growth Dosing at a constant rate per liter of drinking water
rate, and normal egg production. can result in overdosing of young chicks or under-
dosing of older birds. In addition, hens producing
Practical Antimicrobial Drug Application eggs will drink more per unit of weight than non-
under Commercial Poultry Conditions laying hens or roosters. Approved daily dosages are
shown in Table 34.2.
Since commercial poultry are food animals, the
choice of antimicrobials to treat the most common In situations where the birds’ water consumption is
bacterial diseases is limited (Table 34.1). The decision limited, a short, intensive treatment with certain
to treat is usually made prior to the results of culture antimicrobials may be administered as a pulse dose
(Charleston et al., 1998). This method should only be
used with bactericidal antimicrobials and those with a
wide margin of safety. Pulse dosing requires that all of

Table 34.2. Antimicrobial Treatment Options.

Canada United States

Antimicrobial Disease/ Approved for Therapeutic Prophylactic Dose(s)/ Withdrawal time(s) Therapeutic Dose(s)/ Prophylactic Dose(s)/ Withdrawal
Amoxicillin Bacterial Species use in Dose(s)/Route = Route = Feed mg/kg Days (unless Route = Feed g/ton Route = Feed g/ton time(s)
of feed (unless units defined) (U.S.) of feed (unless (U.S.) of feed (unless
(bird type) Feed mg/kg Days (unless
of feed (unless defined) units defined) units defined) defined)
units defined)

Colibacillosis Meat Chicken 8–16 – 2 15–20 mg/kg oral – ?
mg/kg
Apramycin Colibacillosis Extra-label Use oral – 18 0.25–0.5 g/l – ?
0.25–0.5 g/l 55–110 CgFARAD oral 4–50 0
Bactitracin zinc Necrotic enteritis Meat Chicken oral 0 100–400 g/ton
Layer Chicken –
Bacitracin methylene Necrotic enteritis Turkey
disacyclate Ulcerative Meat Chicken – 4.4–55* 0 – 4–200* 0
Layer Chicken
Ceftiofur (subcutaneous enteritis 27.5–158 mg/L 100–400 mg/gal
injection of day-old birds (feed only)*
only) Colibacillosis Turkey – Chicken ELDU 21 {21} – 0.08–0.2 mg/chick 0
Yolk sac infection 110–220 0.17 mg/poult 7 0.17–0.5 mg/poult 1
Chlortetracycline (feed only)*
Staph. spp. Others 55–110* 106–264.5 mg/L 50–200
Enrofloxacin CRD/Mycoplasma Chicken 55–220 100–500 g/ton
Colibacillosis Turkey
Erythromycin Fowl cholera Banned from 10–25 mg/kg BW – 12–21 10 mg/kg BW – prohib
Fowl coryza 57.8–115.6 mg/L 220 CgFARAD 1
CRD/Mycoplasma ELDU in U.S. 92.5–185 g/ton 92.5–185
Colibacillosis Meat Chicken 1 115.6–250 mg/L
Fowl cholera Layer Chicken
Staph. spp.
Fowl coryza (feed only)*
Mycoplasma Turkey

Banned from
ELDU in US

Meat Chicken
Turkey

Gentamicin (subcutaneous Colibacillosis Meat Chicken – 0.2 35–63 – 0.2–1.0 mg/chick 35–63
injection of day-old birds Yolk sac infection Turkey mg/chick 0.2 mg/poult
only) Pseudomonas 16 mg/L 1.0 mg/poult 0 2 g/ton 0
Meat Chicken 833 mg/L 3 17 mg/L 2 0
Lincomycin spp. – – 0
(total activity) 3 50–65 mg/lb BW 0–3
Necrotic enteritis – 9.6–19.1 530–833 mg/L 35–80 mg/L* 5
140 + 200– mg/L 3–4
Lincomycin + spectinomycin Necrotic enteritis Meat Chicken 7–14 35–226 g/ton 170 ?
CRD 70 + 100 mg/L 187.5 5–10 mg/lb BW* 50 0–5
Neomycin Mycoplasma Meat Chicken – –
Neomycin + tetracycline Necrotic enteritis Turkey* 385* 7–14 100–200 g/ton 0–1
Nitarsone Meat Chicken – 35–40 mg/L 50
Nifursol Bacterial enteritis Turkey – 50–200* –
Novobiocin CRD Meat Chicken – 55–220* 5– 0–5
Histomoniasis Turkey 50–111* mg/L
Nystatin 4* 200–350 g/ton
Oxytetracycline Histomoniasis Meat Chicken 297,000 Only labeled for use 4–14 mg/lb
Staph. spp. Turkey* IU/l
Penicillin Pasteurellosis Ducks in turkey in CA 50–100 g/ton
Riemerellosis Turkey – – 100–500 g/ton
Penicillin/Streptomycin Candidiasis Layer Chicken* – 0–60* hours egg 26.5–105.8* mg/L
Spectinomycin Staph. spp. Meat Chicken 7 day meat 6.25–200* mg/bird
CRD/Mycoplasma Turkey
Colibacillosis 2.2 1 100 g/ton 50–100
Fowl cholera Meat Chicken 1,500,000 IU/gal
Fowl coryza Turkey
Staph. spp. –– 20,000 IU + 25 mg/ –
Necrotic enteritis –
Eyrsipelas lb BW
Fowl cholera Meat Chicken
Fowl coryza – ELDU 264–530 mg/L 132 mg/L
Staph. spp.
Necrotic enteritis CgFARAD 2.5–10 mg/chick
Staph.spp.
CRD/Mycoplasma
Colibacillosis
Necrotic enteritis
Fowl cholera

(continued )

Table 34.2. Antimicrobial Treatment Options. (continued )

Canada United States

Therapeutic Prophylactic

Dose(s)/ Dose(s)/ Therapeutic Dose(s)/ Prophylactic Dose(s)/ Withdrawal
Route = Feed g/ton Route = Feed g/ton time(s)
Approved for Route = Feed mg/ Route = Feed mg/kg Withdrawal time(s) (U.S.) of feed(unless (U.S.) of feed(unless
use in Days (unless Days (unless
Disease/ kg of feed (unless of feed (unless units defined) units defined) units defined) defined)
Bacterial Species (bird type)
Antimicrobial units defined) defined)
Streptomycin
Staph.spp. Meat Chicken* 85–93 mg/L – 5 meat/egg 66–100* mg/L – 4
Colibacillosis Turkey in combination 10–15* mg/lb BW
Necrotic enteritis Layers with penicillin/
Fowl cholera vitamins
Fowl coryza

Sulfachlorpyridazine Coccidiosis Meat Chicken ELDU ELDU ELDU – 0.03% 4
Sulfachlorpyridazine/ Colibacillosis Poultry 24 mg total 24 mg total ELDU 24 mg total 24 mg total activity/ –
Fowl cholera CgFARAD –
Trimethoprim Colibacillosis Meat Chicken activity/kg BW activity/kg BW ELDU activity/kg BW kg BW
Sulfadiazine/Trimethoprim Fowl cholera 750 ppm – CgFARAD 15 mg total – 5
5
Sulfadimethoxine Colibacillosis Meat Chicken – – ELDU activity/kg BW – 10 wks*
Sulfadimethoxine/ Fowl cholera Turkey ELDU ELDU CgFARAD 300 g total activity/
Colibacillosis Meat Chicken ELDU 10
Ormetoprim Fowl cholera Turkey 1000–2500 mg/L 250 mg/L CgFARAD met ton
Ducks 250–500 mg/L 10–14
Sulfamethazine Colibacillosis Partridge* 380 mg/L 255 mg/L 12
Fowl cholera Meat Chicken* ELDU ELDU 227 + 136.2 g/ton 56.75 + 34.05 to –
Sulfaquinoxaline Riemerellosis Turkey 12 to 113.5 + 68.1
Coccidiosis Ducks 454 + 272
Sulfaquinoxaline / Colibacillosis ELDU g/ton 128–187*
Trimethoprim Fowl cholera Meat Chicken CgFARAD 1000 mg/L mg/kg/day BW
Coccidiosis Turkey* 110–273 mg/kg
Colibacillosis 110–273 mg/kg/day
Fowl cholera Meat Chicken 397 mg/L BW
Turkey 10–45 mg/lb/day
3.5–55* mg/lb/day 3.5–60 mg/lb/day
30 mg total 2.5–100* mg/lb/day

activity/kg –

Sulfathiazole Colibacillosis – – – – 1000 mg/L – –
Sulfamethazine, Fowl cholera – – ELDU 14
sulfamerazine, Meat Chicken 45–100 mg/L 45–100 mg/L CgFARAD 160 + 160 + 80–100 – 4–5
sulfaquinoxaline Colibacillosis Turkey 5 + 100 + 50 mg/L
Tetracycline Fowl cholera 200 mg/kg 11–44 0–5
Coccidiosis Meat Chicken 500 mg/L 0–3 200–1000 mg/gal/ 100–200 mg/L
Tylosin Staph. spp. Turkey 11–22 not approved for day 0
20–50*
Virginiamycin arthritis Layer Chicken* use in Layers 25–50 mg/bird 4–50
CRD/Mycoplasma Meat Chicken intranasal
Fowl cholera Turkey 0 5–20
Fowl coryza 25 mg/lb/day BW

CRD/Mycoplasma 800–1000 g/ton
Necrotic enteritis 530 mg/L
Fowl coryza 15–25 mg/bird

Necrotic enteritis Meat Chicken – intranasal
50–60 mg/lb/day

–

Information based on published data (including Table 35.3 from previous edition of this publication), clinical experience; use may be extra-label; withdrawal times and doses must be confirmed by
the reader based on product labels and government regulations. Extra-label use of enrofloxacin is illegal in United States. Banned = prohibited for use in meat- and egg-producing birds.
ELDU = extra-label drug use. CgFARAD = contact the Canadian Global Food Animal Residue Avoidance Database for withdrawal information. References: CFIA, 2012; FDA, 2012; North American
Compendiums, 2012.

580 Section IV. Antimicrobial Drug Use in Selected Animal Species

the medication to be administered for a 24-hour period poor oral absorption, ceftiofur is only approved for
is mixed into the water the birds will consume in, for subcutaneous injection in day-old chicks (United States)
example, 6 hours. and poults (United States and Canada). It is commonly
administered along with Marek’s disease vaccine to
Pharmacological Characteristics of Poultry day-old chicks (Kinney and Robles, 1994), either subcu-
Antimicrobials taneously or in an extra-label fashion by in ovo injection
at approximately 18 days of incubation. The extra-label
Beta-lactams (Cephalosporins and Penicillins) in ovo administration of ceftiofur in the United States
has recently been banned (FDA, 2012). The need for the
Despite years of use, penicillin G is still an effective use of a third-generation cephalosporin should be
antimicrobial for Gram-positive bacterial infections in assessed against the risk of selecting for resistance to this
poultry. This drug is particularly important for the important group of drugs, including the danger of
therapy of clostridial infections causing necrotic enteri- selection of multidrug-resistant Salmonella carrying the
tis (Gadbois et al., 2008). The one Gram-negative blaCMY2 resistance gene, since such isolates would also be
bacterium routinely treated with penicillin is Pasteurella resistant to ceftriaxone, a drug used to treat salmonel-
multocida. Recent publications continue to indicate losis in people (chapter 8).
susceptibility of this pathogen to penicillin and support
the selection of this medication in the treatment of pas- Polypeptides
teurellosis or Fowl Cholera (Huang et al., 2009; Sellyei
et al., 2009). Pencillin G is formulated for both drinking Bacitracin is the only poultry-approved polypeptide
water and feed administration, with water administra- antimicrobial. Its effect is local, as it essentially not
tion being the preferred initial route of administration. absorbed when administered orally in poultry.
The broader-spectrum beta-lactams, such as ampicillin Bacitracin is a very effective antimicrobial for treatment
and amoxicillin, theoretically are more effective for of Gram-positive enteric infections such as necrotic
Gram-negative infections such as E. coli airsacculitis; enteritis caused by Clostridium perfringens (Hofacre,
however, there is limited data published on the use and 1998). It is available in both drinking water and feed
clinical efficacy of these medications in poultry species. additive formulations, with the feed-grade form com-
The reportedly short half-lives of both amoxicillin and monly used as a preventative for necrotic enteritis.
ampicillin when administered to poultry species is a
desirable characteristic from the perspective of manag- Aminoglycosides and Aminocyclitols
ing withdrawal times in broiler flocks, where this can be
a factor limiting the options available for treatment Three aminoglycosides are used in poultry: gentamicin,
(El-Sooud et al., 2004; Fernandez-Varon et al., 2006). streptomycin, and neomycin. Because aminoglycosides
One potential factor that may limit the use of these are poorly absorbed from the gastrointestinal tract
products is the reportedly poor stability of amoxicillin when administered orally, their primary usage in poul-
in aqueous solution (Jerzselle and Nagy, 2009). While try has been by subcutaneous injection. Gentamicin is
there are no products currently available or approved for the most widely used aminoglycoside, and it is used
such use in the United States, Canada, or EU poultry primarily as a day-old subcutaneous injection or in ovo
industries, concerns regarding increasing bacterial injection in chickens or turkeys (McCapes, 1976;
resistance to amoxicillin and ampicillin have prompted Vernimb, 1977). A dose of 5 mg/kg body weight in
some European researchers to investigate the pharma- broiler chickens has been reported to be a suitable ther-
cokinetics of these antimicrobials in combination with apeutic dose when administered either intravenously,
beta-lactamase inhibitors clavulanic acid and sublactam intramuscularly or subcutaneously. Subcutaneous
in poultry (Fernandez-Varon et al., 2006; Jerzsele et al., administration was associated with the best absolute
2009; Jerzsele et al., 2010). bioavailability (100%), while oral administration had an
absolute bioavailability of zero (Abu-Basha et al., 2007a).
The only cephalosporin used in poultry production is Because gentamicin is a highly basic compound, it can
ceftiofur, a third-generation cephalosporin. Since it has damage cell-associated Marek’s disease vaccine if used
at too high a dose (greater than 0.2 mg/chick) or

Chapter 34. Antimicrobial Drug Use in Poultry 581

improperly mixed with the vaccine (Kinney and Robles, all countries, all are available in formulations for
1994). Streptomycin is partially absorbed from the administration either in the drinking water or the feed.
intestines and therefore can be considered for use to Erythromycin is most frequently used in poultry to
treat systemic E. coli infections. Neomycin is commonly treat Staphylococcus aureus arthritis. Tylosin has been
used to treat enteric infections, administered either in one of the most effective antimicrobials to treat
the feed or water. Interestingly, despite poor absorption mycoplasma infections in laying hens to restore egg
from the gastrointestinal tract there are reports that production, reduce transovarial transmission and
administration of neomycin has resulted in clinical reduce clinical signs (Bradbury et al., 1994; Kleven,
efficacy in the treatment of colibacillosis in poultry, 2008). The macrolides are only bacteriostatic, which
likely due to a local effect (Marrett et al, 2000). may be one reason that their use will not entirely
eliminate Mycoplasma spp. infections from a flock and
Spectinomycin and hygromycin are poultry-approved thus treatment is not considered a long-term solution.
aminocyclitols. Hygromycin is used for its anthelmintic Clinical and subclinical necrotic enteritis in poultry
properties rather than as an antimicrobial and is admin- flocks can also be successfully treated with tylosin
istered in the feed. Spectinomycin is a relatively safe (Brennan et al., 2001a; Collier et al., 2003; Lanckriet
antimicrobial in poultry that when administered once et al., 2010). Tiamulin, a semisynthetic macrolide avail-
orally, at doses of 50–100 mg/kg body weight, has lim- able outside the United States for poultry, has excellent
ited absorption from the gastrointestinal tract with efficacy against Mycoplasma spp. infections (Laber and
absolute bioavailability reported as 11.8% and 26.4%, Schutze, 1977). Additionally, this antimicrobial has
respectively (Abu-Basha et al., 2007b). Similar to neo- proven efficacious in the treatment of avian intestinal
mycin, spectinomycin has been reported to be highly spirochetosis (Stephens and Hampson, 2002; Burch
efficacious for E. coli infections when administered in et al., 2006; Islam et al., 2009). It is important to note,
the drinking water (Goren et al., 1988). This antimicro- however, that with the exception of lasalocid, tiamulin
bial is available commercially alone or in combination is incompatible with the ionophore anticoccidials;
with lincomycin. This combination has also been monensin, salinomycin, narasin, maduramicin, and
reported as efficacious in controlling early chick mortal- semduramicin. Administration of tiamulin with these
ity associated with E. coli and Staphylococcus aureus ionophores results in clinical signs consistent with
when administered subcutaneously (Hamdy et al., 1979) ionophore toxicity, and seems to interfere with metab-
and has been used as an alternative to gentamicin or olism and excretion of these compounds (Islam et al.,
ceftiofur for prophylaxis in some hatcheries. However, 2009). Tilmicosin, like the other antimicrobials in this
rapid development of resistance and higher cost limits family, has proven effective for control mycoplasma
the use of spectinomycin. infections and has also been used to treat Pasteurella
multocida and Ornithobacterium rhinotracheale
Apramycin is another aminocyclitol approved for use bacterial infections (Jordan and Horrocks, 1996; Kempf
in poultry in some European countries and can be used et al., 1997; Jordan et al., 1999, Abu-Basha et al., 2007c;
in an extra-label fashion were permitted. Consistent Warner et al., 2009).
with the observations of other antimicrobials in this
class, oral absorption is poor (Afifi NA, Ramadan A, The only poultry-approved lincosamide is lincomycin.
1997). There are, however, reports that oral administra- Although it is absorbed with oral administration in feed or
tion of apramycin for treatment of E. coli infections has water, lincomycin is primarily used to treat enteric infec-
been associated with a clinical response (reduced mor- tions in poultry such as Clostridium perfringens-induced
tality, improved final body weight and feed conversion) necrotic enteritis or intestinal spirochaetosis (Lanckriet
and reduced intestinal colonization by E. coli (Cracknell et al., 2010; Stephens and Hampson, 2002). As previously
et al., 1986; Leitner et al., 2001). described, this antimicrobial is also available in combina-
tion with spectinomycin and has been used effectively to
Macrolides and Lincosamides control clinical signs and lesions associated with infections
due to mycoplasma species in poultry (Hamdy et al., 1982;
The macrolides commonly used in poultry include Hamdy et al., 1976).
erythromycin, tylosin, tiamulin and tilmicosin. While
the use of these antimicrobials may not be permitted in

582 Section IV. Antimicrobial Drug Use in Selected Animal Species

Florfenicol effective in poultry (Anadon et al., 2008). This may not
be appropriate, as there are several publications docu-
The potential for fatal aplastic anemia in humans menting florfenicol MIC90 data against E. coli to be 8 μg/
resulted in the prohibition of chloramphenicol in ani- ml and 16 μg/ml or higher in turkeys and chickens
mals grown for human consumption throughout most respectively (Salmon and Watts, 2000; Dai et al., 2008).
of the world (chapter 16). However, the closely related There has been one report of severe muscle degenera-
antimicrobial florfenicol lacks the para-nitro group tion in broiler chickens treated concurrently with both
associated with aplastic anemia in humans, and is avail- lasalocid and chloramphenicol (Perelman et al., 1986);
able for use in food-producing animals, including poul- there is no information as to whether or not this may
try, for the treatment of susceptible Gram-positive and/ occur with concurrent use of lasalocid and florfenicol.
or Gram-negative infections. There are several publica-
tions on the pharmacokinetics of florfenicol in poultry Tetracyclines
species, indicating that the oral bioavailability of this
antimicrobial is relatively high; reports vary from 55.3% The tetracyclines are the most widely used antimicrobi-
to 94% (Afifi and El-Sooud, 1997; Shen et al., 2002; Shen als in poultry. This is largely due to their broad spectrum
et al., 2003; Switala et al., 2007). Shen et al. (2003) sug- of activity (Mycoplasma, Gram-positive and Gram-
gest that some of the discrepancy in the numbers negative bacteria) and wide margin of safety. This class
reported may relate to timing of oral administration in of antimicrobials is also one of few with label claims per-
relation to feeding as there have been reports of variable mitting use in egg laying breeds of chickens, at the
bioavailability between fasted and fed animals. specified dosage, with a zero day egg withdrawal. The
Successful clinical response to treatment with florfeni- tetracyclines are available in formulations that can be
col appears to be somewhat inconsistent. The multipli- administered in feed and/or water. Since they are only
cation of E. coli and Ornithobacterium rhinotracheale in slightly soluble in water at pH 7.0, concurrent use of
a dual bacterial infection model, as well as the associated citric acid greatly enhances their absorption from the
clinical signs were significantly reduced in turkeys gastrointestinal tract (Clary et al., 1981). Tetracyclines
treated with 20 mg/kg body weight of florfenicol for 5 are readily chelated in the intestine by divalent cations
days (Marien et al., 2007). In the authors experience such as calcium or magnesium, resulting in reduced
however, the use of florfenicol to treat E. coli infections absorption (chapter 15). Therefore the dosage of tetra-
in broiler chickens has not been successful. There may cyclines to laying hens on a high-calcium diet should be
be several reasons for this observation including incom- increased. After administration is complete, it is recom-
patibility with water administration via a proportioner mended to include additional calcium in the diet to
when water hardness is > 275 ppm (North American improve eggshell thickness and make up for calcium lost
Compendium, 2012). Additionally, suitable therapeutic to tetracycline binding and intestinal excretion during
plasma concentrations for the targeted pathogen may therapy. For this same reason, tetracyclines are also
not be achieved as there is scant information published incompatible with concurrently administered oral
on the florfenicol MIC values for poultry pathogens electrolytes.
such as E. coli. Several publications on the pharmacoki-
netics of florfenicol in poultry concur that plasma con- Three tetracyclines most commonly used in poultry
centrations above 2 μg/ml for 11 hours can be achieved are chlortetracycline, oxytetracycline, and tetracycline.
after a single dose of 30 mg/kg body weight florfenicol It appears that any differences in clinical efficacy of
(Shen et al., 2003; Switala et al., 2007). As the activity of these tetracyclines are primarily because of differences
florfenicol is time-dependent, it is important that plasma in absorption, drug distribution, or rate of excretion,
concentrations can be maintained above the MIC dur- and not because of differences in bacterial susceptibil-
ing treatment. In the absence of MIC data for poultry ity, since there is complete cross-resistance (chapter
pathogens, many have looked to the MIC data for bacte- 15). It should be remembered that E. coli air sacculitis is
ria isolated from other species and have extrapolated a secondary infection and even though the E. coli
these values to conclude that florfenicol should also be isolate selected for susceptibility testing demonstrates
resistance to tetracyclines, therapy of a flock of poultry
with a tetracycline may still be successful in reducing

Chapter 34. Antimicrobial Drug Use in Poultry 583

the clinical signs. This may be because tetracyclines will multocida. The combination of these drugs allows for a
inhibit Mycoplasma that predispose birds to E. coli therapeutic dose at a much lower level of each product,
infection. lessening the risk of overdose toxicity.

Sulfonamides The other major “adverse effect” of administering the
sulfonamides to poultry is the potential for presence of
The sulfonamides are broad-spectrum antimicrobials violative residues in meat or eggs. Poultry are highly
widely used to treat or prevent coccidial infections in coprophagic and the sulfonamides are excreted in the
poultry. There are a wide variety of sulfonamides avail- urine and feces; therefore, recycling by coprophagy can
able for feed and/or water administration. Sulfonamides result in residues of the drug beyond the stated
are more soluble in an alkaline pH (chapter 17). withdrawal time (Gupta and Sud, 1978). A poultry vet-
Therefore when administering sulfonamides in acidic erinarian prescribing a sulfonamide should include an
water, it may be necessary to raise the pH of the water additional withdrawal period to ensure adequate time
with household ammonia if the drug precipitates in the for drug clearance (greater than 7–10 days) prior to
bulk tank or stock solution. Conversely, if the poultry harvest of meat or eggs.
water supply is being acidified, this process should be
discontinued prior to and during treatment. Quinolones and Fluoroquinolones

The use of sulfonamides has been limited in poultry Many of the quinolones, such as naladixic acid or
because of their narrow margin of safety and problems oxolinic acid, have been used in poultry to treat pri-
of tissue residues at slaughter. Toxic effects of sulfona- marily Gram-negative bacterial infections. However,
mides include bone marrow suppression, thrombocyto- when these compounds are used, resistance in the
penia, and depression of the lymphoid and immune bacterial population in these flocks develops quickly
function of birds (chapter 17). This is frequently and can eventually result in more rapid resistance
manifested as pale, almost yellow colored bone marrow developing to the fluoroquinolones (Glisson, 1997).
and petechial or ecchymotic hemorrhages on the breast, Therefore poultry veterinarians should not recom-
thigh, and leg muscles (Daft et al., 1989). The most fre- mend the use of these older quinolones in commer-
quent toxic side effect of sulfonamide therapy in laying cial poultry. While now banned for use in poultry in
hens is a decline in egg production and eggshell quality the United States, fluoroquinolones are available for
(loss of brown pigment). The ambient temperature must therapeutic use in some countries and permitted
be noted when deciding to administer a sulfonamide in for extra-label use in others.
the drinking water because as the birds become warmer,
they will increase their rate of water consumption to The fluoroquinolones are some of the most effec-
cool themselves. This can quickly result in sulfonamide tive antimicrobial compounds developed for use in
toxicity. The combination of sulfonamides with poultry. These compounds are highly effective against
ionophores may also predispose birds to toxic effects. Gram-positive, Gram-negative, and Mycoplasma
The mechanism for this toxicity has not yet been eluci- infections. It was shown that one of the fluoroqui-
dated; however, the effect that the drug combination has nolones, enrofloxacin, eliminated a Mycoplasma
on the cytochrome P450 enzyme system has been gallisepticum infection in laying hens (Stanley et al.,
hypothesized as one possible explanation and is being 2001). However, the fluoroquinolones are ineffective
investigated (Ershov et al., 2001). against anaerobic bacteria, such as Clostridium
perfringens.
There is one potentiated sulfonamide in the United
States (sulfadimethoxine/ormetoprim) approved for use The fluoroquinolones have a wide margin of safety
in feed. In Canada, there are several products (sulfadia- in poultry. They are rapidly absorbed from the gas-
zine/trimethoprim) that are approved for use in salmon trointestinal tract, reaching peak blood levels within
or horses, but are used in an extra-label manner to treat 1–2 hours after ingestion. The long half-life of the
poultry. Outside of their use to treat coccidiosis in poul- fluoroquinolones results in a significant post-
try, the potentiated sulfonamides are also used to treat antibiotic effect. This gives the poultry veterinarian
bacterial infections caused by E. coli and/or Pasteurella the opportunity to administer the fluoroquinolones
by a “pulsed dose” method in the drinking water

584 Section IV. Antimicrobial Drug Use in Selected Animal Species

(Charleston et al., 1998), which takes advantage of Responsible Use of Antimicrobials
concentration-dependent killing to help prevent the in Poultry
emergence of resistance (chapter 18). Rapid develop-
ment of resistance to fluoroquinolones is a significant The responsible use of antimicrobial drugs in poultry
problem (chapter 18), and has resulted in resistance producing meat and eggs for human consumption is
increasing in Campylobacter jejuni. This issue is based upon good professional judgment, laboratory
discussed in chapter 3. results, medical knowledge, and information about the
flock to be treated. Above all, residue avoidance is criti-
The presence of multivalent cations in the intestine or cal to ensure that people are not accidentally exposed to
in the drinking water (water hardness ≥ 1300 ppm) will antimicrobial residues in poultry products. When a
adversely influence the absorption of the fluoroqui- flock of commercial poultry begins to exhibit signs of
nolone (Sumano et al., 2004). Therefore it is not illness, the birds should be physically examined (ante
recommended to concurrently administer electrolytes mortem and post-mortem). If possible, bacterial cul-
with a fluoroquinolone. tures should be performed to confirm the clinical diag-
nosis and to determine the susceptibility of the isolate to
Ionophores the chosen antimicrobial. The potential for rapid spread
of disease on a poultry farm often necessitates empirical
The primary use of ionophore antimicrobials in poultry treatment prior to the results of bacterial culture and
is to prevent coccidial infections. However, they also susceptibility testing. When laboratory results are avail-
have activity against Gram-positive bacteria, especially able, the poultry veterinarian must use clinical judg-
anaerobes such as Clostridium perfringens (Brennan ment to decide between continuing or changing therapy.
et al., 2001b; Lanckriet et al., 2010). Also, a flock will usually have birds in three stages of
disease development when symptoms are first noted:
Since the ionophores function by altering cell perme- clinically ill, incubating with no outward signs of illness,
ability of both prokaryotic and eukaryotic cells, the toxic and unaffected but susceptible. Therefore, the entire
side effects in poultry are reluctance to move and paral- flock is treated instead of just the clinically ill birds. Such
ysis. This is caused by muscle weakness resulting from strategic medication in anticipation of major disease
passive transport of potassium out of the cells, with cal- spread is justifiable under conditions of good husbandry
cium entering. Ionophore toxicity is more severe in practices and animal welfare. Finally, responsible ther-
adult birds and especially turkeys, even at a safe thera- apy also allows sufficient withdrawal time for the anti-
peutic dose for young chickens (Fulton, 2008). microbial to be eliminated from meat or eggs destined
for human consumption. Additional information on
Novobiocin judicious antimicrobial use is available in chapter 7 and
from the American Veterinary Medical Association
Novobiocin is rarely used in commercial poultry. It is (http://www.avma. org/scienact/jtua/default.asp).
primarily used to treat juvenile pullets or hens early in
the laying house for Staphylococcus aureus arthritis.
Novobiocin is poorly water soluble, and so must be
administered in the feed. High cost is a major reason for
its limited use.

Nitrofurans Bibliography

The nitrofuran antimicrobials have been removed from Abu-BashaEA,etal.2007a.Pharmacokineticsand bioavailability
systemic use in poultry in much of the world because of of spectinomycin after i.v., i.m., s.c. and oral administration
their carcinogenic potential. They are broad-spectrum in broiler chickens. J Vet Pharmacol Ther 30:139.
antimicrobials that were at one time commonly added
to poultry starter feed to reduce the effects of egg- Abu-Basha EA, et al. 2007b. Comparative pharmacokinetics
transmitted Salmonella infections in the first 2 weeks of of gentamicin after intravenous, intramuscular, subcuta-
life. In poultry, nitrofuran toxicity results in congestive neous and oral administration in broiler chickens. Vet Res
cardiomyopathy (ascites) or central nervous system Commun 31:765.
signs (Zaman et al., 1995).
Abu-Basha EA, et al. 2007c. Pharmacokinetics of tilmicosin
(provitil powder and pulmotil liquid AC) oral formulations
in chickens. Vet Res Commun 31:477.

Chapter 34. Antimicrobial Drug Use in Poultry 585

Afifi NA, El-Sooud KA. 1997. Tissue concentrations and Daft BM, et al. 1989. Experimental and field sulfaquinoxaline
pharmacokinetics of florfenicol in broiler chickens. Brit toxicosis in leghorn chickens. Avian Dis 33:30.
Poultry Sci 38.425.
Dai L, et al. 2008. Characterization of antimicrobial resist-
Afifi NA, Ramadan A. 1997. Kinetic disposition, systemic ance among Escherichia coli isolates form chickens in
bioavailability and tissue distribution of apramycin in China between 2001 and 2006. FEMS Microbiol Lett
broiler chickens. Res Vet Sci 62:249. 286:178.

Anadon A, et al. 2008. Plasma and tissue depletion of flor- Dibner JJ, Richards JD. 2005. Antibiotic growth promoters in
feincol and florfenicol-amine in chickens. J Agric Food agriculture: history and mode of action. Poult Sci 84:634.
Chem 56:11049.
El-Sooud KA, et al. 2004. Comparative pharmacokinetics
Barnes HJ, et al. 2008. Colibacillosis. In: Saif YM (ed). and bioavailability of amoxicillin in chickens after
Diseases of Poultry, 12th ed. Ames, IA: Blackwell, pp. intravenous, intramuscular and oral administrations. Vet
691–732. Res Commun 28:599.

Blom L. 1975. Residues of drugs in eggs after medication of Ershov E, et al. 2001. The effect of hepatic microsomal
laying hens for eight days. Acta Vet Scand. 16:396. cytochrome P450 monooxygenases on monensin-
sulfadimidine interactions in broilers. J Vet Pharmacol
Bradbury JM. 2005. Poultry mycoplasmas: sophisticated Therap 24:73.
pathogens in simple guise. Brit Poultry Sci 46:125.
FDA. 2005. FDA announces final decision about veterinary
Bradbury JM, et al. 1994. In vitro evaluation of various medicine. FDA news release P05-48. http://www.fda.gov/
antimicrobials against Mycoplasma gallisepticum and NewsEvents/Newsroom/PressAnnouncements/2005/
Mycoplasma synoviae by the microbroth method and com- ucm108467.htm.
parison with a commercially prepared test system. Avian
Pathol 23:105. FDA. 2012. New animal drugs; Cephalosporin drugs;
Extralabel animal drug use; Order of prohibition. Federal
Brennan J, et al. 2001a. Efficacy of in-feed tylosin phosphate Register. http://www.gpo.gov/fdsys/pkg/FR-2012-01-06/
for the treatment of necrotic enteritis in broiler chickens. pdf/2012-35.pdf.
Poult Sci 80:1451.
FDA, Department of Health and Human Services. 2012.
Brennan J, et al. 2001b. Efficacy of narasin in the prevention Cephalosporin order of prohibition goes into effect. http://
of necrotic enteritis in broiler chickens. Avian Dis 45:210. www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/
ucm299054.htm.
Burch DGS, et al. 2006. Treatment of a field case of avian
intestinal spirochaetosis caused by Brachyspica pilosicoli Fernandez-Varon E, et al. 2006. Pharmacokinetics of an
with tiamulin. Avian Pathol 35:211. ampicillin-sublactam (2:1) combination after intravenous
and intramuscular administration to chickens. Vet Res
Casewell M, et al. 2003. The European ban on growth- Commun 30:285
promoting antibiotivs and emerging consequences for
human and animal health. J Antimicrob Chemoth 52:259. Fulton RM. 2008. Other toxins and poisons. In: Saif YM (ed).
Diseases of Poultry, 12th ed. Ames, IA: Blackwell,
Castanon JIR. 2007. History of the use of antibiotic as growth pp. 1231–1258.
promoters in European poultry feeds. Poult Sci 86:2466.
Gadbois P, et al. 2008. The role of penicillin G potassium in
Charleston B, et al. 1998. Comparison of the efficacies of managing Clostridium perfringens in broiler chickens.
three fluoroquinolone antimicrobial agents given as Avian Dis 52:407.
continuous or pulsed water medication, against Escherichia
coli infection in chickens. Antimicrob Ag Chemother Glisson JR. 1997. Correct use of fluroquinolones in the
42:83. poultry industry. Turkey World Mar–Apr, pp. 24–26.

Clary BD, et al. 1981. The potentiation effect of citric acid on Glisson JR. 1998. Bacterial respiratory diseases of poultry.
aureomycin in turkeys. Poult Sci 60:1209. Poult Sci 77:1139.

Collier CT, et al. 2003. Effects of tylosin on bacterial myuco- Glisson JR, et al. 2004. Comparative efficacy of enrofloxacin,
lysis, Clostidium perfringens colonization, and intestinal oxytetracycline, and sulfadimethoxine for the control of
barrier function in a chick model of necrotic enteritis. morbidity and mortality caused by Escherichia coli in
Antimicrob Agents Ch 47:3311. broiler chickens. Avian Dis 48:658.

Corrier DE, et al. 1999. Presence of Salmonella in the crop Goren E, et al. 1984. Some pharmacokinetic aspects of four
and ceca of broiler chickens before and after preslaughter sulphonamides and trimethoprim, and their therapeutic
feed withdrawal. Poult Sci 78:45. efficacy in experimental Escherichia coli infection in poul-
try. Vet Quart 6:134.
Cox LA. 2005. Potential human health benefits of antibiotivs
used in food animals: a case study of virginiamycin. Grave K, et al. 2006. Usage of veterinary therapeutic
Environ Int 31:549. antimicrobials in Demark, Norway and Sweden following
termination of antimicrobial growth promoter use. Prev
Cox LA, Popken DA. 2004. Quantifying human health risks Vet Med 75:123.
from virginiamycin used in chickens. Risk Anal 24:271.
Gupta RC, Sud SC. 1978. Sulphaquinoxaline in the poultry.
Cracknell VC, et al. 1986. An evaluation of apramycin soluble Ind J Anim Res 12:91.
powder for the treatment of naturally acquired Escherchia
coli infections in broilers. J Vet Pharmacol Ther 9:273.

586 Section IV. Antimicrobial Drug Use in Selected Animal Species

Hamdy AH, et al. 1976. Efficacy of linco-spectin water McCapes RH, et al. 1976. Injecting antibiotics into turkey
medication on Mycopasma synoviae airsacculitis in broil- hatching eggs to eliminate Mycoplasma meleagridis
ers. Avian Dis 20:118. infection. Avian Dis 19:506.

Hamdy AH, et al. 1979. Effect of a single injection of Niewold TA. 2007. The nonantibiotic anti-inflammatory
lincomycin, spectinomycin , and linco-spectin on early effect of antimicrobial growth promoters, the real mode of
chick mortality caused by Escherchia coli and Staphylococcus action? A hypothesis. Poult Sci 86:605.
aureus. Avian Dis 23:164.
North American Compendiums. 2012. Nuflor 2.3% concen-
Hamdy AH, et al. 1982. Efficacy of lincomycin-spectinomycin trate solution. In: Compendium of Veterinary Products,
water medication on Mycoplasma meleagridis airsacculitis 12th ed. (Canadian edition).
in commercially reared turkey poults. Avian Dis 26:227.
Perelman B, et al. 1986. Clinical and pathological changes
Health Canada. 2011. Extra-label drug use in animals. caused by the interaction of lasolocid and chlorampheni-
http://www.hc-sc.gc.ca/dhp-mps/vet/label-etiquet/index- col in broiler chickens. Avian Pathol 15:279.
eng.php.
Phillips I. 2007. Withdrawal of growth-promoting antibiotics
Hofacre CL, et al. 1998. Use of Aviguard, virginiamycin or in Europe and its effects in relation to human health. Int J
bacitracin MD in experimental Clostridium perfringens Antimicrob Ag 30:101.
associated necrotizing enteritis. J Appl Poult Res 7:412.
Phillips I, et al. 2004. Does the use of antibiotics in food
Huang TM, et al. 2009. Antimicrobial susceptibility and animals pose a risk to human health? A critical review of
resistance of chicken Escherchia coli, Salmonella spp., and published data. J Antimicrob Chemoth 53:28.
Pasteruella multocida isolates Avian Dis 53:89.
Righter HF, et al. 1970. Tissue-residue depletion of sulfaqui-
Islam KMS, et al. 2009. The activity and compatibility of the naloxaline in poultry. Am J Vet Res. 31:1051.
antibiotic tiamulin with other durgs in poultry medicine—
a review. Poult Sci 88:2353. Righter HF, et al. 1973. Tissue residue depletion of
sulfaquinoxaline in turkey poults. J Agr Food Chem
Jerzselle A, Nagy G. 2009. The stability of amoxicillin 21:412.
trihydrate and potassium clavulanate combination in
aqueous solutions. Acta Vet Hung 57:485. Russell SM. 2003. The effect of airsacculitis on bird weights,
uniformity, fecal contamination, processing errors and
Jordan FT, Horrocks BK. 1996. The minimum inhibitory population of Campylobacter spp. and Escherichia coli.
concentration of tilmicosin and tylosin for Mycoplasma Poult Sci 82:1326.
gallisepticum and Mycoplasma synoviae and a comparison
of their efficacy in the control of Mycoplasma gallispeticum Salmon SA, Watts JL. 2000. Minimum inhibitory concentra-
infection in broiler chicks. Avian Dis 40:326. tion determinations for various antimicrobial agents
against 1570 bacterial isolates from turkey poults. Avian
Jordan FT, et al. 1999. The comparison of an aqueous Dis 44:85.
preparation of tilmicosin with tylosin in the treatment of
Mycopasma gallisepticum infection of turkey poults. Avian Sellyei B, et al. 2009. Antimicrobial susceptibility of
Dis 43:521. Pasteurella multocida isolated from swine and poultry.
Acta Vet Hung 57:357.
Kelly L, et al. 2004. Animal growth promoters:to ban or not to
ban? A risk assessment approach. Int J Antimicrob Ag 24:7. Shen J, et al. 2002. Pharmacokinetics of florfenicol in healthy
and Escherichia coli-infected broiler chickens. Res Vet Sci
Kempf I, et al. 1997. Efficacy of tilmicosin in the control of 73:137.
experimental Mycoplasma gallisepticum infection in
chickens. Avian Dis 41:802. Shen J, et al. 2003. Bioavailability and pharmacokinetics of
florfenicol in broiler chickens. J Vet Pharmacol Ther
Kinney N, Robles A. 1994. The effect of mixing antibiotics 26:337.
with Marek’s disease vaccine. Proc 43rd Western Poultry
Disease Conf, pp. 96–97. Smith JA. 2011. Experiences with drug-free broiler produc-
tion. Poult Sci 90:2670
Kleven SH. 2008. Control of avian mycoplasma infections in
commercial poultry. Avian Dis 52:367. Stanley WA, et al. 2001. Case report—monitoring Mycoplasma
gallisepticum and Mycoplasma synoviae infection in an
Laber G, Schutze E. 1977. Blood level studies in chickens, experimental line of broiler chickens after treatment with
turkey poults, and swine with tiamulin, a new antibiotic. enrofloxacin. Avian Dis 45:534.
J Antibiot 30:1112.
Stephens CP, Hampson DJ. 2002. Evaluation of tiamulin and
Lanckriet A, et al. 2010. The effect of commonly used antico- lincomycin for the treatment of broiler breeders
ccidials and antibiotics in a subclinical necrotic enteritis experimentally infected with the intestinal spirochaete
model. Avian Pathol 39:63. Brachyspira pilosicoli. Avian Pathol 31:299.

Leitner G, et al. 2001. The effect of apramycin on coloniza- Sumano LH, et al. 2004. Influence of hard water on
tion of pathogenic Escherichia coli in the intestinal tract of the  bioavailability of enrofloxacin in broilers. Poult Sci
chickens. Vet Quart 23:62 83:726.

Marrett LE, et al. 2000. Efficacy of neomycin sulfate water Switala M, et al. 2007. Pharmacokinetics of florfenicol,
medication on the control of mortality associated with thiamphenicol and chloramphenicol in turkeys. J Vet
colibacillosis in growing turkeys. Poult Sci 79:12. Pharmacol Ther 30:145.

Chapter 34. Antimicrobial Drug Use in Poultry 587

Vermeulen B. 2002. Drug administration to poultry. Adv animal health, disease prevention, productivity, and usage
Drug Deliver Rev 54:795. of antimicrobials. Microb Drug Resist 7:183.
Zamon Q, et al. 1995. Experimental furazolidone toxicosis in
Vernimb GD, et al. 1977. Effect of gentamicin and early broiler chicks: effect of dosage, duration and age upon clinical
morality and later performance of broiler and leghorn signs and some blood parameters. Acta Vet Hung 43:359.
chickens. Avian Dis 20:706. Zhao S, et al. 2005. Antimicrobial susceptibility and molecu-
lar characterization of avian pathogenic Escherichia coli
Warner K, et al. 2009. Control of Ornithobacterium rhinotra- isolates. Vet Microbiol 107:215.
cheale in poultry. Vet Rec 165:668.

Wierup M. 2001. The Swedish experience of the 1986 year ban
of antimicrobial growth promoters, with special reference to

Antimicrobial Drug Use in 35
Companion Birds

Keven Flammer

Companion birds include members of the orders others. In psittacine birds, Gram-negative bacterial
Psittaciformes (e.g., parakeets, parrots, lories, cockatoos, infections are most common, especially those caused by
and macaws), Passeriformes (e.g., canaries and finches), Escherichia coli, Klebsiella spp., and Pseudomonas
and Columbiformes (e.g., pigeons and doves). Psittacine aeruginosa. Other Gram-negative bacteria include
birds are the most common pet birds in the United States; Bordetella spp., Pasteurella spp., Proteus spp., Salmonella
over 50 species are commonly seen in veterinary practice. spp., Serratia spp., and Yersinia spp. Gram-positive
Microbial diseases are common and use of antimicrobial bacterial pathogens include Staphylococcus aureus and
drugs is an important part of avian practice. Optimal treat- Enterococcus spp. Chlamydophila psittaci is the most
ment regimens can be developed if the principles of rational important intracellular pathogen; Mycobacterium avium
antimicrobial therapy are integrated with the unique and M. genavense are occasionally seen. Anaerobes are
behavioral and physiological characteristics of birds. relatively uncommon, although clostridial infections of
the alimentary tract do occur. Similar pathogens are
The general approach to selecting an avian antimicro- found in canaries and pigeons; Enterococcus faecalis is
bial treatment regimen is similar to other species. The an important cause of respiratory disease in canaries
site and cause of infection should be identified and the and there is a higher incidence of Salmonella spp. and
minimal inhibitory concentrations (MIC) of potentially Streptococcus gallolyticus infections in pigeons.
effective antimicrobial drugs determined. Selection of
the most appropriate drug will then depend on the Mycotic infections are also important (Table  35.1).
severity of illness, site of infection, pharmacokinetic and Yeasts most commonly affect the alimentary tract and
pharmacodynamic properties of the selected drugs, and common pathogens include Candida albicans and
the routes of administration that can be accomplished Macrorhabdus ornithogaster. Hyphal fungi are important
by the owner or veterinary staff. Additional considera- pathogens of the respiratory tract and, occasionally, the
tions are drug side effects, toxicity and cost. eye and skin. Aspergillus fumigatus and A. niger are the
most common isolates; Mucor spp., Penicillium spp.,
Establishing the Cause and Site of Infection Rhizopus spp., and Scedosporium spp. and other opportun-
ist moulds may rarely infect immunocompromised birds.
A wide variety of primary and secondary bacterial
pathogens have been identified in companion birds In companion birds, septicemia and infections of the
(Table  35.1); however, some are more common than alimentary tract, respiratory tract, and liver are the most
common sites of microbial infection. It is important to
note that simply culturing a potential pathogen is not an

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

589

Table 35.1. Antimicrobial drug selection in companion avian infections.

Site or Type of Infection Diagnosis Common Organisms Suggested Drugs Comments

Sick bird—severe illness, Septicemia, multiple Aerobic bacteria, especially E. coli and Enrofloxacin; piperacillin; cefotaxime Use IV, IM, or SQ route.
Klebsiella. Salmonella in pigeons
cause unknown organ infection Ceftazidime or piperacillin ± amikacin; Maintain hydration to avoid toxicity.
Pseudomonas aeruginosa meropenem Limited studies in birds.
Doxycycline Use IV route if severely ill, oral or IM if
Chlamydophila psittaci
Amphotericin B stable.
Aspergillus Use IV route.
Enrofloxacin; trimethoprim-
Sick bird—mild illness, Septicemia, multiple Aerobic bacteria, especially E. coli and sulfamethoxazole; ampicillin- Maintain hydration to avoid toxicity.
clavulanic acid Limited studies in birds.
cause unknown organ infection Klebsiella Use oral, medicated food, or medicated
Ceftazidime or piperacillin ± amikacin;
Pseudomonas aeruginosa meropenem water routes.

Chlamydophila psittaci Doxycycline Dose and efficacy vary among species.
Dose and toxicity vary among species.
Aspergillus Itraconazole; Gently lavage nares/sinus with saline to
terbinafine;
Respiratory tract Rhinitis/sinusitis Aerobic bacteria, especially E. coli and voriconazole remove debris. Treat for at least 1 week
Klebsiella Enrofloxacin; piperacillin; cefotaxime after signs resolve. Chronic cases may
require surgical debridement to remove
Respiratory tract Pseudomonas aeruginosa Ceftazidime or piperacillin ± amikacin; nidus of infection.
meropenem Maintain hydration to avoid toxicity.
Candida albicans Fluconazole Limited studies in birds.
Aspergillus Amphotericin B;
itraconazole Nebulize, nasal flush.
Mycoplasma Enrofloxacin; doxycycline Monitor toxicity.
Chlamydophila psittaci Doxycycline Role in psittacine sinusitis uncertain.
Pnemonitis/airsacculitis Aspergillus; opportunistic fungi Amphotericin B
plus Nebulize 2–3x daily; IV if bird is severely
itraconazole debilitated.
or
terbinafine; Oral administration only. Monitor potential
Voriconazole toxicity, especially in African grey parrots.

Treat for at least 1 month after resolution of
clinical signs.

Combine with itraconazole or substitute
for itraconazole.

Dose and safety vary by species.

Gastrointestinal tract Oral, gastric, intestinal Aerobic bacteria, especially E. coli and Enrofloxacin; piperacillin; cefotaxime Use IV, IM, or SQ route.
candidiasis Klebsiella
Nervous Ceftazidime or piperacillin ± amikacin; Maintain hydration to avoid toxicity.
Ophthalmic Bacterial enteritis Pseudomonas aeruginosa meropenem Limited studies in birds.
Doxycycline
Chlamydophila psittaci Itraconazole + terbinafine Rarely reported.
Scedosporium Fluconazole; Can treat oral lesions with topical
Candida nystatin
Enrofloxacin; amphotericin B.
Opportunistic aerobic bacteria, especially other fluoroquinolones; Use oral route. Treat for 5–7 days.
E. coli and Klebsiella trimethoprim-sulfamethoxazole
Doxycycline Rare in psittacines. Occasionally seen in
Campylobacter finches.

Spore-forming bacteria (probable Clindamycin; Common cause of odiferous droppings.
Clostridium spp.) metronidazole C. perfringens may cause acute mortality.

Macrorhabdus Amphotericin B Give orally. Impossible to clear infection
ornithogaster
in all affected birds.
Bacterial enteritis
Pseudomonas aeruginosa Gentamicin PO if showing mild signs. If ill, Check husbandry for environmental

use amikacin + piperacillin or sources (esp. water sources,

ceftriaxone; contaminated food, etc.)

ciprofloxacin or

enrofloxacin if MIC < 0.5 μg/ml;

meropenem

Cloacitis Opportunistic aerobic and anaerobic Enrofloxacin or beta-lactam + clindamycin Most common in cockatoos. Associated
bacteria
or metronidazole; septicemia may cause severe

topical silver sulfadiazine cream debilitation.

Pharyngitis Spiral bacteria Doxycycline Reported in cockatiels.
Bacterial meningitis/ Opportunistic aerobic pathogens
Cefotaxime; Rare. Treat aggressively. Use high end of
encephalitis
doxycycline; the dosage range. Prognosis poor.

enrofloxacin

Mycoplasma Mycoplasma Doxycycline; enrofloxacin Rare. Prognosis poor.
encephalitis Opportunistic bacteria
Topical bacitracin-neomycin-polymixin B Topical gentamicin and topical tetracycline
Bacterial keratitis—
mild ulceration combination are other options.

(continued )

Table 35.1. Antimicrobial drug selection in companion avian infections. (continued )

Site or Type of Infection Diagnosis Common Organisms Suggested Drugs Comments
Pseudomonas aeruginosa Topical tobramycin; topical amikacin
Bacterial keratitis,
severe

Fungal keratitis Aspergillus and other opportunistic fungi Topical miconazole; natamycin

Manifestation of Chlamydophila psittaci Topical tetracycline Also treat with oral doxycycline.
systemic disease
Skin Opportunistic aerobic bacteria Enrofloxacin; trimethoprim- Must also treat underlying cause. Often find
Dermatitis sulfamethoxazole; beta-lactams multiple classes of organisms.
Reproductive tract Staph. dermatitis Staphylococcus aureus
Peritonitis Topical silver sulfadiazine cream Resistant S. aureus uncommon in birds;
Multiple organs Salpingitis (oviduct) Opportunistic yeast Cephalothin; oxacillin; trimethoprim- MRSA occasionally seen.

Mycobacteriosis Opportunistic hyphal fungi sulfamethoxazole Check for a retained or ruptured egg.
Fluconazole; Resolution may require surgery.
Opportunistic aerobic bacteria, especially topical amphotericin B cream
E. coli and Klebsiella Itraconazole; Consider egg yolk peritonitis if bird is
topical amphotericin B cream female.
Mixed bacterial opportunists, especially Fluoroquinolones; beta-lactams
Gram-negative bacteria M. genavense may be zoonotic. Treatment
Enrofloxacin; piperacillin; cefotaxime is complex.
Mycobacterium avium
Mycobacterium genavense Long-term multiple drug therapy

Otitis media Gram-negative bacteria: E. coli and Fluoroquinolones; beta-lactams Most commonly reported in nestling
Klebsiella macaws. Lavage ear and treat with
Ceftazidime or piperacillin; ciprofloxacin topical amikacin.
Pseudomonas aeruginosa or enrofloxacin if MIC < 0.5 μg/ml;
Difficult to deliver multiple injections to
meropenem juvenile birds. Use oral route if an
effective drug is available.

Chapter 35. Antimicrobial Drug Use in Companion Birds 593

indication for antimicrobial drug treatment. It is not from psittacine birds suggests that resistance to
unusual to culture small numbers of Gram-negative many first-generation antimicrobials (e.g., ampicillin,
bacteria or yeasts from the cloaca and choana of appar- cephalexin, chloramphenicol, penicillin, and tetracy-
ently healthy birds. Treatment may be indicated if the cline) may be common in psittacines (Flammer, 1992).
organism is present in large numbers and there are Because of suspicions of resistance, avian veterinarians
accompanying clinical signs. Physical exam findings, often use fluoroquinolones and advanced-generation
results of clinical laboratory tests, and a Gram stain of beta-lactams for initial treatment in severely ill birds.
material from the suspected site of infection can help The treatment plan can be modified once the bird is
determine if a microbial infection is the cause of illness. stable and results of laboratory testing are available.

Choosing an Antimicrobial Regimen The frequency and route of administration are impor-
tant considerations when choosing a dosage regimen.
To be effective, the pathogen must be susceptible to the Most birds will need to be captured and restrained to
drug at concentrations that are achievable in birds. Some deliver medication, so that treatment regimens with a
microbial agents have known susceptibility (e.g., longer dosage interval are preferred. In sick birds, a par-
Chlamydophila psittaci is invariably susceptible to doxy- enteral route of administration should be used to rapidly
cycline), but most will require a susceptibility test to establish effective drug concentrations. Once a bird is
determine the most effective drugs. Susceptibility tests clinically stable, it may be relinquished to the owner’s
reporting minimal inhibitory concentrations (MIC) are care to complete antimicrobial therapy. Birds can be dif-
quantitative and provide the most useful information to ficult to medicate and the procedure is often stressful for
guide drug selection. Disk diffusion tests can be used, both the bird and bird owner. If oral medication is used,
but it is important to recognize that the designations of low-volume, palatable drug formulations can aid treat-
susceptible, intermediate, and resistant may not corre- ment success. Some avian veterinarians favor use of IM
late with treatment success in birds. These designations injection because bird restraint and drug delivery may
are based on the achievable drug concentrations in be easier with this route. Additional pros and cons of
humans (or in a limited number of animal species) and different routes of administration are discussed below.
it may be difficult to achieve similar concentrations in Regardless of the treatment regimen, it is useful to check
birds. Chapter 2 discusses susceptibility testing. compliance and offer assistance after a few days of
treatment.
Companion birds often hide signs of disease and may
present at an advanced stage of illness. If a bacterial Choosing the dose can be challenging because drug
infection is strongly suspected, it may be necessary to formularies often list a wide range of recommended
start empirical treatment before the results of culture dosages. This is partly because there are sparse data on
and susceptibility tests are available. Table 35.1 provides the pharmacokinetics of antibiotics in many species of
a list of diseases and suggested choices for initiating psittacine birds. Many dosage regimens are empirically
antimicrobial therapy. In companion birds, Gram- derived or extrapolated from other species. Table  35.2
negative bacterial infections are most common, espe- provides suggested doses for selected commonly used
cially those caused by E. coli, Klebsiella spp., and P. antimicrobial drugs. However, even doses based on
aeruginosa. Chlamydiosis most commonly occurs in pharmacokinetic studies often represent only a single-
birds recently obtained from commercial sources (e.g., dose study in a limited number of individuals of a single
pet stores, flea markets and breeders). Salmonella is species. Therefore all treated birds should be monitored
common in pigeons. If these organisms are suspected, a carefully since safety and efficacy have not been
broad-spectrum antibiotic with excellent Gram-negative investigated for widespread use of many of the drug
spectrum is most appropriate for initiating empirical dosages listed.
treatment; doxycycline is preferred if chlamydiosis is
likely. Susceptibility data are sparse; however, one study Basic pharmacodynamic principles should be
of the MIC90 values for Gram-negative bacteria isolated considered when evaluating which dose to use.
Drugs  showing time-dependent efficacy (e.g., beta-
lactams, macrolides, tetracyclines, and trimethoprim-
sulfonamides) must be dosed frequently enough to

Table 35.2. Conventional dosage regimens for antimicrobial drugs in companion birds.a

Drugs Dose Interval Route Studyb/Species Refc Comments
(mg/kg) (h)

Penicillins 150 12–24 IM Kin/pigeons 1 Gram-positive bacteria only.
Ampicillin sodium 25 12–25 PO Kin/pigeons 1 Gram-positives only.
Ampicillin trihydrate 125–175 12–25 PO Kin/pigeons 1
100 4 IM Kin/Amazon parrots 2
Amoxicillin sodium 150–200 8–12 PO Kin/Amazon parrots 2
Amoxicillin trihydrate 50 12–24 IM Kin/pigeons 1 Gram-positives only.
250 12–24 IM Kin/pigeons 1
Amoxicillin + 20 12–24 PO Kin/pigeons 1 Gram-positives only.
clavulanic acid 100 12–24 PO Kin/pigeons 1
150–175 4–8 PO Empirical/psittacines
Piperacillin 50/10 8–12 IM Kin/collared doves 3 Gram-positives only.
Ticarcillin
100/25 8–12 PO Kin/collared doves 3
60–120 8–12 IM Kin/collared doves 3
125–250 8 PO Kin/collared doves 3
125 8 PO Kin/blue fronted Amazon parrots 4
75–100 4–8 IM Kin/blue-fronted Amazon parrots 5
200 6–8 IM Empirical/psittacines
200 2–4 IM Kin/blue-fronted Amazon parrots 6

Cephalosporins 100 6 IM Kin/pigeon 7
Cephalothin 35–50
Cephalexin 10 6 PO Kin/pigeon 7
Ceftiofur 10
75–100 4 IM Kin/cockatiels 8
Cefotaxime 50–100
Ceftazidime 75–100 8 IM Kin/orange-winged Amazon parrots 8
Ceftriaxone
Aminoglycosides 15–40 4–8 IM Kin/blue-fronted Amazon parrots 5
Amikacin
4–8 IM

4–8 IM Kin/blue-fronted Amazon parrots 5

24 IM, IV Kin/cockatiels, blue-fronted Amazon 9 Preferred aminoglycoside; potentially nephrotoxic.

parrots, African grey parrots 6

10

Gentamicin 2.5–10 24 IM Kin/cockatiels, scarlet macaws, rose 9 Nephrotoxic.
Tobramycin 2.5–10
breasted cockatoos. 11

24 IM Empirical Empirical—based on gentamicin studies; used for

Pseudomonas aeruginosa.

Fluoroquinolones 7.5–15 12–24 IM Kin/African grey parrots 12 IM injection causes muscle irritation.
Enrofloxacin 7.5–15 12–24 SC Kin/African grey parrots 13 Inject into subcutaneous fluid pocket containing

15–30 24 PO Kin/African grey 13 lactated Ringer’s solution. Double the dose when
parrots 14 using q 24 h administration.
Marbofloxacin 200 mg/L 15 High oral doses result in plasma concentrations that
2.5–5 24 Water Plasma concentration/parrots may be effective with once daily dosing.
24 PO Kin/blue and gold macaw 16 Achieves low plasma concentrations in psittacines.

Tetracyclines 48–72 IM, SC Kin/Goffin’s cockatoo 1 Chlamydophila psittaci; causes irritation at
Oxytetracycline, long 50–100 1 the site of injection.
acting (LA 200, Zoetis)
17 Chlamydophila psittaci;
Doxycycline 25 12 PO Kin/pigeon dose in birds with access to grit.
18 Chlamydophila psittaci;
7.5 12 PO Kin/pigeon dose in birds with no access to grit.
Chlamydophila psittaci.
35 24 PO Psittacines/empirical Chlamydophila psittaci. Diet = 1:4 mixture of hulled
300 mg/kg food 24 Food Plasma concentration/budgerigars
oat groats and hulled millet; coat seed with
300–500 mg/kg food 24 Food Plasma concentration/cockatiels sunflower oil (~6 ml/kg seed).
Diet = 60:40 mixture of hulled millet and hulled
Doxycycline 300 mg/L 24 Water Plasma concentration/cockatiels 18 sunflower seeds; coat seed with sunflower oil
Doxycycline 400 mg/L 24 Water Plasma concentration/cockatiels 19 (~6 ml/kg seed).
400–800 mg/L 24 Water Plasma concentration/orange-winged 20
May be effective for treating chlamydiosis.
Amazon parrot, African grey parrot, 1 May be effective for treating spiral bacteria.
Goffin’s cockatoo 21
Use lower doses in macaws and cockatoos.
Doxycycline injectable 75–100 5–7 days IM Kin/pigeons
(Vibrovenös, Zoetis) Kin/psittacines Gram-positives and anaerobes.

Macrolides 25 6 IM Kin/pigeons 22 (continued )
Tylosin 25–50 8–12 PO Empirical
Clindamycin

Trimethoprim and
sulfonamides

Trimethoprim 15–20 8 PO Kin/pigeons 1

Table 35.2. Conventional dosage regimens for antimicrobial drugs in companion birds. (continued )

Drugs Dose Interval Route Studyb/Species Ref c Comments
(mg/kg) (h) 1
Trimethoprim- 10/50 PO Kin/pigeons
sulfamethoxazole 12
Trimethoprim- 10/50 PO Kin/pigeons 1
sulfatroxazole 24
Trimethoprim- 20/100 PO Empirical May cause regurgitation, especially in macaws.
sulfamethoxazole 12

Other 20–50 12 PO Empirical Anaerobes.
Metronidazole

Antifungals 1.5 8 IV Empirical 23 Aspergillus and hyphal fungi.
Amphotericin B 1.0 8–12 IT Empirical 24 Aspergillus and hyphal fungi.
1.0 mg/ml 8–12 Neb Empirical Aspergillus and hyphal fungi.
Ketoconazole 100 mg/kg 12 PO Empirical 25 Avian gastric yeast.
Fluconazole 20–30 12 PO Kin/Amazon parrots and cockatoos 26 Yeast ± Aspergillus.
10–20 24 PO Kin/African grey parrots, blue-fronted 27 Yeast. Higher dose may be toxic in African grey
Fluconazole
Itraconazole 75–100 mg/L 24 Water Amazon parrots, Goffin’s cockatoos 28 parrots.
5–10 24 PO Kin/cockatiels 29 Candida.
Voriconazole 6 12 PO Kin/blue-fronted Amazon parrot 30,31 Aspergillus and hyphal fungi.
Voriconazole 2.5–5 24 PO Kin/pigeon Aspergillus and hyphal fungi;
Voriconazole Empirical/African grey parrot itraconazole may be toxic in some African grey
Nystatin
18 12 PO Kin/African grey parrot parrots, even at the low dose indicated here.
18 8 PO Kin/Hispaniolan Amazon parrot New drug, safety unknown.
10 12 PO Kin/Pigeon New drug, safety unknown.
200,000–300,000 IU/kg 8–12 PO Empirical May cause hepatic toxicity.
Yeast; not absorbed from the GI tract; must come in

contact with the yeast.

aAdapted from Dorrestein, 2000.
bKin means dose recommendations based on pharmacokinetic studies in the listed species. Empirical means studies based on anecdotal reports; no published kinetic data available for
pigeons or psittacine birds.
cReferences (see bibliography): 1, Dorrestein, 1986; 2, Ensley, 1981; 3, Dorrestein et al., 1998; 4, Orosz et al., 2000; 5, Flammer, 1990; 6, Schroeder et al., 2001; 7, Bush et al., 1981; 8,
Tell et al. 1998; 9, Ramsay et al., 1993; 10, Gronwall et al., 1989; 11, Flammer et al., 1990a; 12, Flammer et al., 1991; 13, Flammer, 2005; 14, Flammer et al., 2002; 15, Carpenter et al.,
2003; 16, Flammer et al., 1990b; 17, Flammer et al., 2003; 18, Powers et al., 2000; 19, Evans et al., 2008; 20, Flammer et al., 2001; 21, Jakoby and Gylstorff, 1983; 22, Bush et. al., 1982;
23, Kollias et al., 1986; 24, Flammer, 1996; 25, Ratzlaff et al., 2011; 26, Orosz et al., 1996; 27, Lumeij et al., 1995; 28, Flammer, et al., 2008; 29, Sanchez-Migallon et al., 2010; 30,
Beernaert et al., 2009a; 31, Beernaert et al., 2009b.
Disclaimer: As noted in the text, safety and efficacy data for widespread use of drugs in birds is lacking; none of these drug doses are warranted to be either safe or effective.

Chapter 35. Antimicrobial Drug Use in Companion Birds 597

maintain plasma concentrations above the target MIC that surgical debridement, use of lipophilic drugs, and
for most of the dosing interval. Birds rapidly excrete prolonged treatment may be needed to improve the
most beta-lactam drugs, so penicillins and cephalo- success of treatment.
sporins should be dosed at least 3–4 times daily unless
pharmacokinetic data demonstrates less frequent In mammals, gastric emptying and drug dissolution
administration is adequate. Cephalosporins that are often the rate limiting steps for oral drug absorption.
show prolonged activity in other species (e.g., cefo- Companion birds have a crop, and passage of ingesta
vecin in dogs) may have short activity in birds from the crop may delay oral drug absorption. For
(Thuesen et al., 2009). Concentration-dependent example, a lag phase of 20–40 minutes was observed in
antibiotics (e.g., fluoroquinolones and aminoglyco- studies investigating the pharmacology of oral suspen-
sides) can probably be dosed once daily if high peak sions of doxycycline in fasted birds (Flammer, unpub-
concentrations and large area under the curve values lished observation, 2005). There is little absorption from
are achieved. Since these values may depend on the the crop, and its neutral pH may precipitate some drugs
route of administration, parenteral routes may be that are solubilized in acid or base (e.g., chlortetracy-
required to achieve the desired concentration for cline), further delaying absorption (Dorrestein, 1986).
resistant organisms.
Alimentary tract motility in birds also differs from
Controlled studies involving large numbers of differ- mammals (Denbo, 2000). Birds have a two-part stom-
ent avian species are lacking, so that veterinarians ach composed of the proventriculus and ventriculus.
should monitor treatment efficacy and potential toxic- Grit is retained in the ventriculus and may expose orally
ity. This is especially important when using drugs with a administered drugs to high concentrations of calcium
narrow therapeutic range or treating an unfamiliar spe- and magnesium. This can reduce the absorption of
cies. Relevant chapters in this book should be consulted tetracyclines and fluoroquinolones. There is also both
on specific antimicrobial drugs and their potential side normograde and retrograde movement of ingesta
effects and contraindications. through the proventriculus, ventriculus, and small
intestine, which might expose acid-sensitive drugs to
Using broad-spectrum antimicrobials may impact greater degradation by gastric acids. Companion birds
normal intestinal microflora. Psittacine birds have also have a short intestinal tract that may limit drug
predominately Gram-positive gut flora, and reduction absorption, especially when food is present and
of this flora after treatment can render the birds more competes for absorption.
susceptible to secondary infections by yeasts and Gram-
negative opportunist bacteria. This is especially common The lower respiratory system of birds consists of the
when treating nestling birds or when using prolonged lungs and air sacs (Powell, 2000). The air sacs are poorly
antimicrobial therapy in adults such as treatment for vascularized and topical drug delivery via nebulization
chlamydiosis (Flammer, 1994). The incidence of may be needed to augment systemic drug administra-
secondary infections can be reduced by maximizing tion. At rest, birds may ventilate only a small portion of
husbandry during treatment. In addition, birds that their total air sac volume, so that nebulization may be
have sustained long-term treatment should be cultured enhanced by gently stimulating the bird to increase res-
to identify potential opportunistic superinfections. piration and promote greater drug penetration.

Anatomical and Physiological The renal system of birds differs considerably from
Considerations mammals (Goldstein, 2000). Avian kidneys contain
both mammalian and reptilian nephrons and may
Differences in anatomy and physiology may alter drug excrete drugs differently than expected from mamma-
pharmacology in birds as compared to mammals. For lian physiology. Uric acid is the major end product of
example, granuloma formation is a common avian avian nitrogen metabolism and is produced in the liver.
response to infection by many microbial agents. Sulphonamide drugs may be excreted via some of the
Granuloma formation can inhibit drug penetration so same metabolic pathways as uric acid, so that caution
should be used if sulfa drugs are given to uricemic birds
(Quesenberry, 1988). Birds lack a bladder, and waste
from the kidney is transported directly to the cloaca.

598 Section IV. Antimicrobial Drug Use in Selected Animal Species

Cloacal contents can be refluxed into the colon to pro- t Subcutaneous (SC) route: Medications can be given
mote additional water absorption. As a consequence, subcutaneously in the groin, axilla and the dorsal region
avian water balance may be independent of the glomer- between the shoulders. Non-irritating drugs are
ular filtration rate and renally excreted drugs may face preferred. Injectable tetracyclines (e.g., oxytetracycline)
reabsorption in the colon. As a final consideration, birds have been used, but can cause skin sloughs (Flammer et
have a renal portal system. Theoretically, renally al., 1990b). Enrofloxacin can be injected into a SC
excreted drugs could face a first-pass effect before reach- pocket of lactated Ringer’s solution and achieve plasma
ing systemic circulation if injected into the leg muscles. concentrations comparable to IM injection, without
causing severe irritation (Flammer, 2005).
Routes of Administration
t Oral (PO) route: Liquid solutions and suspensions are
The route of administration will depend on the drug, often used. Capsules can be given to pigeons but are
available drug formulation, condition of the bird, and difficult to administer to parrots and small passer-
ability of the owner and/or veterinary staff to deliver the ines. Drugs that are unpalatable or require large
drug. Severely ill birds should be treated using paren- volumes are more difficult to administer. Only
teral routes to quickly establish effective drug concen- non-irritating drugs should be used, as birds may
trations. Achievable plasma concentrations are often aspirate drug into the trachea or pass it rostrally into
route-dependent. As a guideline, concentrations follow the choanal slit. It can be surprisingly difficult to
the following pattern: IV > IM ≥ SC > PO > medicated medicate psittacines via the oral route, so owner com-
food or water (Flammer, 1994). pliance should be verified if this route is chosen. As
an alternative, drugs can be administered via a crop
t Intravenous (IV) route: It is difficult to deliver IV tube; however, this method is technically difficult and
drugs in birds so this method is usually reserved for is usually performed in a veterinary hospital setting.
one-time administration of antimicrobials or emer-
gency drugs. Birds can be catheterized, but it is more t Medicated food: Medications can be added to palata-
difficult to maintain IV catheters in birds than in other ble food vehicles such as mash diets and treat foods. It
small animals. The right jugular and right and left bra- is difficult to monitor food (and therefore drug)
chial veins are the most accessible in psittacines. The consumption, so this route should be reserved for
medial metatarsal vein is accessible in pigeons. treatment of clinically stable birds with proven dosage
regimens. Lower plasma drug concentrations are
t Intraosseous (IO) route: Fluids given via the intraosseus usually achieved than with other routes, so this
route quickly reach systemic circulation (Aguilar et al., method is used only to treat highly susceptible bacte-
1993). Intraosseus catheters can be installed in the distal ria. It is important to use the same diet as is used in
ulna or tibiotarsus. This route is most often used to published methods, since food consumption is largely
administer fluids; however, it is an acceptable route for based on the energy content of the diet (Flammer,
IV antimicrobial drug formulations. Care should be 1994). Medicated food recipes for treating chlamydio-
taken to flush fluid through the IO catheter and bone to sis are available for some species.
avoid leaving concentrated drug in the IO site.
t Medicated water: Delivering medication via this route
t Intramuscular (IM) route: The pectoral muscles are usually establishes low plasma drug concentrations.
the most accessible sites for IM administration in par- This route should be avoided unless there is data
rots and passerines; the leg muscles are sometimes proving therapeutic plasma drug concentrations can
used in racing pigeons. Small needle size (25–30 be achieved. For example, water medicated with enro-
gauge) and small volume of injection are necessary. floxacin at 200 mg/L achieves low, sustained plasma
The author prefers to use injection volumes that are concentrations of 0.05–0.2 μg/ml (Flammer et al.,
less than 1 ml/kg. Irritating drugs (e.g., enrofloxacin 2002). Doxycycline medicated water has been shown
and tetracyclines) should be avoided unless there is a to achieve plasma drug concentrations that are greater
compelling reason to use this route. than 1 μg/ml and should be effective for treating
chlamydiosis and spiral bacteria in cockatiels treated
with 300–400 mg/L (Powers et al., 2000; Evans et al.,

Chapter 35. Antimicrobial Drug Use in Companion Birds 599

2008) and cockatoos and grey parrots treated with Beernaert LA, et al. 2009a. Designing voriconazole treatment
400–800 mg/L (Flammer et al., 2001). Water medicated for racing pigeons: balancing between hepatic enzyme
with fluconazole at 100 mg/L achieved plasma drug auto induction and toxicity. Med Mycol 47:276.
concentrations that should be effective for treating
candidasis in cockatiels (Ratzlaff et al., 2011). Beernaert LA, et al. 2009b. Designing a treatment protocol
t Topical: Topical drugs can be applied to the skin or with voriconazole to eliminate Aspergillus fumigatus from
eye. A minimal amount of topical cream or ointment experimentally inoculated pigeons. Vet Microbiol 139:393.
should be used, as birds may ingest or spread
medications into their feathers when preening. Where Bush M, et al. 1981. Pharmacokinetics of cephalothin and
possible, water-soluble formulations are preferred, as cephalexin in selected avian species. Am J Vet Res 43:1014.
they are easier to wash off if the bird spreads them
into the feathers. Silver sulfadiazine cream is a popular Bush M, et al. 1982. Pharmacokinetics and tissue concentrations
choice for treating avian skin infections because it has of tylosin in selected avian species. Am J Vet Res 42:1807.
broad-spectrum activity and is easy to clean up.
Topical products containing corticosteroids should Carpenter JW, et al. 2003. Pharmacokinetics of marbofloxa-
be avoided since birds may be more susceptible to the cin in the blue and gold macaw. Proc Ann Conf Am Assoc
immunosuppressive effects. Zoo Vet, p. 79.
t Antimicrobials are occasionally injected directly into
the site of infection. Intratracheal injection can be Denbo M. 2000. Gastrointestinal anatomy and physiology.
used to deliver topical amphotericin B (~1 ml/kg) to In: Whittow GC (ed). Sturkie’s Avian Physiology, 5th ed.
treat fungal infections of the trachea. Amphotericin B San Diego: Academic Press, p. 299.
and clotrimazole have been used to topically treat
fungal lesions on the air sacs. Topical antibiotics are Dorrestein GM. 1986. Studies on the pharmacokinetics of
sometimes used to treat upper respiratory infections some antibacterial agents in homing pigeons (Columba
via injection into the nares (nasal flush) or periorbital livia). Thesis, Utrecht University.
sinus (sinus flush).
t Nebulization: Nebulization can be used to deliver Dorrestein GM, et al. 1987. Comparative study of ampicillin
topical medication to portions of the air sacs and and amoxicillin after intravenous, intramuscular and oral
lungs. It is most often used when treating respiratory administration in homing pigeons (Columba livia). Res
fungal infections. A nebulizer that produces particles Vet Sci 42:343.
less than 3 μm in diameter should be used. Birds
ventilate only a small portion of their respiratory tract Dorrestein GM, et al. 1998. Comparative study of Synulox
at rest, so that stimulation or mild exercise during and Augmentin after intravenous, intramuscular and oral
nebulization might increase drug penetration. In administration in collared doves (Streptopelia decaocto).
studies investigating tylosin and oxytetracycline, Proc 11th Symp Avian Dis Munich, p. 42.
nebulization achieved therapeutic local concentra-
tions for approximately 4–6 hours, but did not Dorrestein GM. 2000. Antimicrobial drug use in companion
establish therapeutic plasma concentrations (Locke birds. In: Prescott JF, et al. (eds). Antimicrobial Therapy in
et al., 1984; Dyer et al., 1987). Veterinary Medicine, 3rd ed.Ames, IA: Blackwell, p. 617.

Bibliography Dyer DC, et al. 1987. Antibiotic aerosolization: tissue and
plasma oxytetracycline concentrations in parakeets. Avian
Aguilar RF, et al. 1993. Osseous, venous and central Dis 31:677.
circulatory transit times of technetium-99 m pertechnetate
in anesthetized raptors following intraosseus administra- Ensley PK, et al. 1981. A preliminary study comparing the
tion. J Zoo Wildlife Med 24:488. pharmacokinetics of ampicillin given orally and intramus-
cularly to psittacines: Amazon parrots (Amazona spp.) and
blue-naped parrots (Tanygnathus lucionensis). J Zoo Anim
Med 12:42.

Evans EE, et al. 2008. Administration of doxycycline in
drinking water for treatment of spiral bacterial infection in
cockatiels. J Am Vet Med Assoc 232:389.

Filippich LJ, et al. 1993. Drug trials against megabacteria in
budgerigars. Aust Vet Pract 23:184.

Flammer K. 1990. An update on psittacine antimicrobial
pharmacokinetics. Proc Ann Conf Assoc Avian Vet, p. 218.

Flammer K. 1992. New advances in avian therapeutics. Proc
Ann Conf Assoc Avian Vet, p. 14.

Flammer K. 1994. Antimicrobial therapy. In: Ritchie BW,
et al. (eds). Avian Medicine: Principles and Applications.
Boca Raton, FL: Wingers, p. 434.

Flammer K. 1996. Fluconazole in psittacine birds. Proc Ann
Conf Assoc Avian Vet, p. 203.

Flammer K. 2005. Administration strategies for delivery of
enrofloxacin. Proc Ann Conf Assoc Avian Vet, p. 8.

Flammer K, et al. 1990a. Adverse effects of gentamicin in
scarlet macaws and galahs. Am J Vet Res 51:404.

600 Section IV. Antimicrobial Drug Use in Selected Animal Species

Flammer K, et al. 1990b. Potential use of long-acting Orosz SE, et al. 2000. Pharmacokinetics of amoxicillin plus
injectable oxytetracycline for treatment of chlamydiosis in clavulinic acid in blue-fronted Amazon parrots (Amazona
Goffin’s cockatoos. Avian Dis 34:1017. aestiva aestiva). J Avian Med Surg 14:107.

Flammer K, et al. 1991. Intramuscular and oral disposition of Quesenberry KE. 1998. Avian antimicrobial therapeutics. In:
enrofloxacin in African grey parrots following single and Jacobson ER, Kollias GV (eds). Exotic Animals. New York:
multiple doses. J Vet Pharm Therap 41:359. Churchill Livingstone, p. 177.

Flammer K, et al. 2001. Plasma concentrations of doxycycline Powell FL. 2000. Respiration. In: Whittow GC (ed). Sturkie’s
in selected psittacine birds when administered in water for Avian Physiology, 5th ed. San Diego: Academic Press,
potential treatment of Chlamydophila psittaci infection. p. 233.
J Avian Med Surg 15:276.
Powers LV, et al. 2000. Preliminary investigation of
Flammer K, et al. 2002. Plasma concentrations of enrofloxa- doxycycline plasma concentrations in cockatiels
cin in psittacine birds offered water medicated with (Nymphicus hollandicus) after administration by injection
200 mg/L of the injectable formulation of enrofloxacin. or in water or feed. J Avian Med Surg 14:23.
J Avian Med Surg 16:286.
Ramsay EC, et al. 1993. Pharmacokinetic properties of
Flammer K, et al. 2003. Assessment of plasma concentrations gentamicin and amikacin in the cockatiel. Avian Dis 37:628.
of doxycycline in budgerigars fed medicated seed or water.
J Am Vet Med Assoc 223:993. Ratzlaff K, et al. 2011. Plasma concentrations of fluconazole
after a single oral dose and administration in drinking
Flammer K, et al. 2008. Pharmacokinetics of voriconazole water in cockatiels (Nymphicus hollandicus). J Avian Med
after oral administration of single and multiple doses in Surg 25:23.
African grey parrots (Psittacus erithacus timneh). Am J Vet
Res 69:114. Sanchez-Migallon G, et al. 2010. Pharmacokinetics of
voriconazole after oral administration of single and
Goldstein DL, et al. 2000. Renal and extrarenal regulation of multiple doses in Hispaniolan Amazon parrots (Amazona
body fluid composition. In: Whittow GC (ed). Sturkie’s ventralis). Am J Vet Res 71:460.
Avian Physiology, 5th ed. San Diego: Academic Press,
p. 265. Schroeder EC, et al. 2001. Pharmacokinetics of ticarcillin and
amikacin in blue-fronted Amazon parrots (Amazona
Jakoby JR, Gylstorff I. 1983. Comparative research on the aestiva aestiva). J Avian Med Surg 11:260.
medicated treatment of psittacosis. Berl Munich Tier
Wschr 96:261. Schuetz S, et al. 2001. Pharmacokinetic and clinical studies of
the carbapenem antibiotic, meropenem, in birds. Proc
Kollias GV, et al. 1986. The use of ketoconazole in birds: Ann Conf Assoc Avian Vet, p. 183.
preliminary pharmacokinetics and clinical applications.
Proc Ann Conf Assoc Avian Vet, p. 103. Smith KA, et al. 2010. Compendium of measures to control
Chlamydophila psittaci infection among humans (Psittacosis)
Locke D, et al. 1984. Tylosin aerosol therapy in quail and and pet birds (Avian Chlamydiosis). http://www.nasphv.org/
pigeons. J Zoo An Med 15:67. Documents/Psittacosis.pdf. Accessed May 2012.

Lumeij JT, et al. 1995. Plasma and tissue concentrations of Tell L, et al. 1998. Pharmacokinetics of ceftiofur sodium in
itraconazole in racing pigeons (Columba livia domestica). exotic and domestic avian species. J Vet Pharm Therap
J Avian Med Surg 9:32. 21:85.

Moore RP, et al. 2001. Diagnosis, treatment, and prevention Thuesen LR, et al. 2009. Selected pharmacokinetic parame-
of megabacteriosis in the budgerigar (Melopsittacus ters for cefovecin in hens and green iguanas. J Vet Pharm
undulates). Proc Ann Conf Assoc Avian Vet, p. 161. Therap, 32:613.

Orosz SE, et al. 1996. Pharmacokinetic properties of
itraconazole in blue-fronted Amazon parrots (Amazona
aestiva aestiva). J Avian Med Surg 10:168.

Antimicrobial Drug Use in Rabbits, 36
Rodents, and Ferrets

Colette L. Wheler

Introduction and their intended use must also be taken into
consideration, since the treatment of one patient kept as
Veterinary practitioners who care for small mammal a companion animal will differ significantly from that of
pets, such as rabbits, rodents, and ferrets, face several hundreds being bred for the pet trade, used as labora-
challenges when using antimicrobial medications in tory animals, being farmed for fur, or, in the case of
these species. Some antimicrobials are known to be rabbits, being raised for meat.
toxic to rabbits and some rodents, so careful selection of
the most appropriate drug is critical. In Canada and the Lastly, many conditions requiring antimicrobial
United States, there are very few antimicrobials specifi- therapy are actually secondary to inadequate nutrition
cally approved for treatment of these patients, necessi- or husbandry, so these issues must also be addressed for
tating use of drugs extra-label. An alternative source or a positive therapeutic outcome.
formulation of drug may be needed, which may involve
compounding or importing medications from other The following sections discuss these many challenges
countries (following strict federal regulations) or the use in more detail, and conclude with a series of tables listing
of human drug formulations. Many antimicrobials must some reported dosages of antimicrobials, and common
be reconstituted prior to administration, and subse- conditions in small mammal pets. Some information is
quently have a fairly short shelf-life, even if refrigerated. also included for hedgehogs and sugar gliders, since
Very little of the drug is usually needed to treat the their popularity as pets is increasing in North America,
patient, so the remainder is often frozen in aliquots for and this information can be difficult to find.
economic reasons and to avoid wastage. However, infor-
mation on the stability of these frozen, reconstituted Antimicrobial Toxicity
products is often unavailable or difficult to find.
Most veterinary practitioners are aware that some
Drug dosages are generally based on extrapolation antimicrobials are toxic to rabbits and some rodents,
from other species and/or clinical experience, and many especially when given orally. Disruption of the normal
pharmacokinetic studies performed in these animals are population of intestinal flora occurs, and this dysbiosis
actually models for human trials. In addition, most allows proliferation of clostridial or coliform bacteria,
drugs are not manufactured in a form that is convenient and subsequent release of toxins. Hind-gut fermenters,
for administration to small, easily stressed patients, so such as rabbits, guinea pigs, chinchillas, and hamsters,
unique treatment methods must be developed to ensure are particularly susceptible to this condition, and
owner compliance. The number of animals being treated narrow-spectrum antibiotics, such as beta-lactams,

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

601

602 Section IV. Antimicrobial Drug Use in Selected Animal Species

macrolides, and lincosamides are most responsible. ages for mink would likely be valid in ferrets, since they
Diarrhea usually appears within 24–48 hours following are closely related species. In Canada, antimicrobials
administration of the drug, and most cases are fatal. labeled for use in rabbits and mink include: procaine
Pathogenic conditions and sudden alterations in diet penicillin G (IM use only) for the treatment of rabbits
may also predispose the animal to dysbiosis, and even and mink, chlortetracycline feed premix for the
antimicrobials that are considered safe can sometimes treatment of mink, and neomycin/oxytetracycline
cause problems. Rats, mice, gerbils, and ferrets are less water soluble powder for the treatment of mink. In
vulnerable to this condition. order to provide appropriate care for small mammal
patients, veterinarians are required to use many drugs
Other forms of antimicrobial toxicity can also occur extra-label.
in small mammals. Neuromuscular blockade of skeletal
muscle may occur with high dosages of aminoglyco- In Canada and the United States, extra-label drug use
sides, resulting in an ascending flaccid paralysis, respira- refers to the use of a federally approved drug in a man-
tory arrest, and coma. Anesthesia may be a predisposing ner that is not in accordance with the label or package
factor to this condition. As in other species, these drugs insert. It is the responsibility of the veterinarian to be
are also potentially nephrotoxic and ototoxic to small aware of, and follow, the rules and regulations in their
mammal species. Streptomycin has been reported to be particular jurisdiction. In the United States, further clar-
toxic in gerbils. ification of extra-label drug use was made in 1994 with
the introduction of the Animal Medicinal Drug Use
Although normally safe in rabbits, rodents, and Clarification Act (AMDUCA). This act clearly explains
ferrets, fluoroquinolone antimicrobials (e.g., enro- legitimate extra-label drug use by veterinarians, and
floxacin) may cause arthropathies in young animals. outlines the specific conditions that must be followed
Chloramphenicol is generally safe to use in small mam- for acceptable extra-label drug use (see chapter 26).
mals, and many bacteria infecting these animals are
highly susceptible to this drug. However, chlorampheni- In the United States, extra-label use of medicated
col has occasionally been associated with irreversible feeds was initially excluded from the AMDUCA; how-
aplastic anemia in humans, so appropriate directions for ever, this oversight was rectified when the Food and
prevention of exposure, such as wearing gloves and Drug Administration Center for Veterinary Medicine
hand washing, must be given when this antibiotic is pre- issued a Compliance Policy Guideline on Extra-label
scribed. In addition, chloramphenicol is prohibited for Use of Medicated Feeds for Minor Species in 2001
use in food-producing animals, such as meat rabbits. (www.fda.gov/ICECI/ComplianceManuals/Compliance
PolicyGuidanceManual/ucm074659.htm).
Potential toxicities must always be kept in mind when
selecting an antimicrobial based on culture and sensitiv- Extra-label use of human antimicrobial formulations
ity results, as the most appropriate choice may result in is also fairly common for treatment of small mammal
dysbiosis or other problems in a particular species. patients. Many of these products are single dose vials
Supportive ancillary therapies, such as administration of that have a fairly short shelf-life once reconstituted.
fluids along with aminoglycosides, and good nursing Treatment of the small mammal patient may occur for a
care, as well as provision of adequate nutrition and a longer period than the shelf-life of the drug, or the total
comfortable, stress-free environment will also aid in amount needed may be very small. Rather than discard
successful treatment. the remainder, veterinarians often freeze small aliquots
of the product for future use. The stability of these
Extra-Label Use, Compounding, reconstituted products after freezing is often not easy to
and Importation find; however, some information can be found in the
Handbook of Injectable Drugs by Lawrence Trissel, which
In Canada and the United States, there are a limited is available in hardcopy and electronic format, and
number of drugs labeled for use in rabbits, rodents, and Plumb’s Veterinary Drug Handbook by Donald Plumb, as
ferrets, and very few of these are antimicrobials. Some well as in some package inserts.
antimicrobials are approved for use in mink, and dos-
An alternative source of drug sometimes needs to be
explored by veterinarians for the treatment of small

Chapter 36. Antimicrobial Drug Use in Rabbits, Rodents, and Ferrets 603

mammal patients, such as compounding or importing Metabolic scaling is a method popular in zoological
medications from other countries. Compounding is a medicine, and uses a formula based on body weight; a
type of extra-label drug use whereby the original drug constant based on the energy group of the animal; and
dosage form is manipulated by a veterinarian or phar- the known pharmacokinetic data of the drug in one
macist, or an entirely new product is manufactured species, to calculate the dosage of the drug in other
by  a  compounding pharmacy, to create a customized species.
medication to meet a specific need. This could involve
anything from altering the concentration of a drug by Allometric scaling uses mathematical equations to
diluting it other than according to the package instruc- analyze differences in anatomy, physiology, biochemis-
tions, or mixing a crushed tablet into a liquid, to the cus- try, and pharmacokinetics in animals of different sizes.
tom creation of a medicated tablet or liquid that is Known pharmacokinetic parameters in several species
particularly palatable to the intended species. are used in the equations to estimate the pharmacoki-
netic parameter in an unknown species, and thus pre-
Importation of a more suitable drug or drug dict drug dosage. Allometric scaling is commonly used
formulation from another country is another option for in the pharmaceutical industry to determine the first
veterinarians. For example, a suspension of metronida- dosage in human trials. There are several reports in the
zole is available in some countries that is much more literature validating the use of allometric scaling to pre-
accurate for dosing small patients than the tablet form dict pharamacokinetic parameters in small mammal
available here. Mechanisms exist in both Canada and species for several drugs, including some fluoroqui-
the United States for legal importation of drugs (www. nolone antimicrobials. Tables  36.1–36.3 present drug
hc-sc.gc.ca/dhp-mps/vet/edr-dmu/index-eng.php and dosages for the treatment of common microbial dis-
w w w. f d a . g ov / A n i m a l Ve t e r i n a r y / P r o d u c t s / Imp o r t eases. Tables 36.4–36.11 present clinical signs and sug-
Exports/ucm050077.htm). gested drugs for common bacterial diseases.

Drug Dosages Drug Administration

Although there are many antimicrobial dosages Rabbits and rodents are prey species, and are generally
published for rabbits, rodents, and ferrets, very few less tolerant of handling and other manipulations than
pharmacokinetic studies or clinical trials have been per- predator species such as ferrets, dogs, and cats, espe-
formed specifically for these animals; rather they are cially when debilitated. Administration of antimicrobi-
carried out primarily to establish information for future als in these prey species must be performed in a way that
human trials. Because of this, antimicrobial dosages for allows for the entire dose to be given without unduly
these patients are generally based on extrapolations stressing the patient. The method of administration
from other species and/or clinical experience. Lack of must also be achievable for the client, otherwise frustra-
scientifically derived dosages, combined with the extra- tion and non-compliance may result. Available antimi-
label use of most antimicrobials, are daily challenges of crobial formulations are often too large and/or too
veterinarians who care for small mammal patients. concentrated for small mammals and need to be split up
Clients should be informed of this, and give written con- or diluted for accurate dosing.
sent for treatment of their animals were appropriate.
Routes of antimicrobial administration in rabbits,
Extrapolation of drug dosages from one species to rodents, and ferrets include oral (liquid, pill, or capsule);
another can be done in several ways. Straightforward subcutaneous (usually in the loose skin over the shoul-
linear extrapolations based on body weight alone tend ders); intraperitoneal (generally reserved for very small
to result in overdosing of larger animals and underdos- rodents); intramuscular (generally avoided in very small
ing of smaller ones. This method is only appropriate animals); topical; and less commonly, via intravenous or
with drugs that have large margins of safety and wide intraosseous catheter; nebulization; gavage; nasoesoph-
therapeutic margins, or if the two animals are similar in ageal or esophagostomy tube (rabbits, ferrets); or anti-
taxonomy, body size, and physiology. microbial-impregnated implants. Injections are more

604 Section IV. Antimicrobial Drug Use in Selected Animal Species

Table 36.1. Reported antimicrobial drug dosages in rabbits, guinea pigs, and chinchillas. Caution: Most uses and dosages
are extra-label.

Drug Rabbit* Guinea Pig Chinchilla

Amikacin 2–5 mg/kg q 8–12 h; SC, IM 2–5 mg/kg q 8–12 h; SC, IM 2–5 mg/kg q 8–12 h; SC, IM, IV
Azithromycin 5 mg/kg q 48 h; IM OR 15–30 mg/kg 15–30 mg/kg q 12–24 h; PO 15–30 mg/kg q 24 h; PO

Captan powder q 24 h; PO – 5 ml/475 ml bathing dust
Cephalexin – 50 mg/kg q 24 h; IM –
Chloramphenicol 20–50 mg/kg q 6–12 h; PO, SC, IM, IV
Chlortetracycline 11–22 mg/kg q 8–12 h; SC 30–50 mg/kg q 12 h; PO,SC,IM, IV
Ciprofloxacin 30 mg/kg q 8–12 h; PO, SC, IM, IV** – 50 mg/kg q 12 h; PO
Clindamycin 50 mg/kg q 24 h; PO 5–20 mg/kg q 12 h; PO 5–20 mg/kg q 12 h; PO
Doxycycline 5–20 mg/kg q 12 h; PO 7.5 mg/kg q 12 h; SC; Do not use PO 7.5 mg/kg q 12 h; SC; Do not use PO
Enrofloxacin Do not use 2.5 mg/kg q 12 h; PO 2.5 mg/kg q 12 h; PO
2.5 mg/kg q 12 h; PO 0.05–0.2 mg/mL dw q 24 h OR 5–15 mg/kg 5–15 mg/kg q 12 h; PO, SC, IM
Fenbendazole 5–10 mg/kg q 12 h; PO, SC, IM OR
Fluconazole q 12 h; PO, SC, IM 20–50 mg/kg q 24 h; PO
Gentamicin 200 mg/L dw q 24 h 16 mg/kg q 24 h × 14 d; PO
Griseofulvin 16-20 mg/kg q 24 h × 14 d; PO 2 mg/kg q 12 h; SC, IM, IV
(avoid in pregnant animals) 38 mg/kg q 12 h; PO 2–4 mg/kg q 8–12 h; SC, IM 25 mg/kg q 24 h × 30–60d; PO
Itraconazole 1.5–2.5 mg/kg q 8 h; SC, IM, IV 25–50 mg/kg q 12 h × 14–60d; PO
Ketoconazole 25 mg/kg q 24 h × 30–45d; PO 5 mg/kg q 24 h; PO
Lime sulfur dip OR 1.5% in DMSO for 5–7 d; topically 10–40 mg/kg q 24 h; PO
20–40 mg/kg q 24 h; PO 5–10 mg/kg q 24 h; PO Dilute 1:40 with water, dip q 7d for
Marbofloxacin 10–40 mg/kg q 24 h; PO 10–40 mg/kg q 24 h; PO
Dilute 1:40 with water, dip q 7d for Dilute 1:40 with water, dip q 7d for 4–6 wk
Metronidazole 4 mg/kg q 2 h4; PO, SC
4–6 wk 4–6 wk
Oxytetracycline 2 mg/kg q 24 h; IM, IV OR 5 mg/kg q 4 mg/kg q 24 h; PO, SC 10–20 mg/kg q 12 h; PO;
Penicillin G, benzathine use with caution
Penicillin G, procaine 24 h; PO 25 mg/kg q 12 h; PO 50 mg/kg q 12 h; PO
Sulfadimethoxine 20 mg/kg q 12 h; PO Avoid
Sulfamethazine – Avoid
Sulfaquinoxaline 50mg/kg q 12h; PO OR 1mg/mL dw Toxic 25–50 mg/kg q 24 h × 10–14d; PO
Terbinafine 42,000–60,000 IU/kg q 48 h; SC, IM Toxic 1 mg/mL dw
Tetracycline 42,000–84,000 IU/kg q 24 h; SC, IM 10–15 mg/kg q 12 h; PO
10–15 mg/kg q 12 h × 10d; PO 1 mg/mL dw –
Trimethoprim-sulfa 1 mg/mL dw 1 mg/mL dw 10–30 mg/kg q 24 h × 4–6 wk; PO
Tylosin 1 mg/mL dw 10–40 mg/kg q 24 h × 4–6 wk; PO 0.3–2 mg/mL dw q 24 h OR
100 mg/kg q 12–24 h; PO 10–40 mg/kg q 24 h; PO
50 mg/kg q 8–12 h; PO OR 10–20 mg/kg q 8–12 h; PO
15–30 mg/kg q 12 h; PO, SC 15–30 mg/kg q 12 h; PO, SC
250–1000 mg/L dw q 24 h 10 mg/kg q 24 h; PO, SC; use with caution 10 mg/kg q 24 h; PO, SC
30 mg/kg q 12–24 h; PO, SC, IM
10 mg/kg q 12 h; PO, SC

*Observe correct withdrawal time in meat rabbits.
**Do not use in meat rabbits.
PO, per os; SC, subcutaneous; IM, intramuscular; IV, intravenous; dw, drinking water.

commonly used in clinic than at home; however, some restraint, is the best and least-stressful method of medica-
clients are willing to master the procedure, particularly tion (for both the animal and the administrator). Flavored
if the pet objects excessively to being medicated orally, antimicrobial preparations, such as trimethoprim/sulfa or
or if it has a sore mouth, or tends to nip. chloramphenicol palmitate suspensions, are willingly con-
sumed by some of these patients. Crushed pills, liquids, or
Self-administration, where the animal willingly takes capsule contents can be mixed with small amounts of
the entire dose on its own, preferably with minimal or no

Table 36.2. Reported Antimicrobial Dosages in Hamsters, Gerbils, Rats, and Mice. Caution: Most uses and dosages are extra-label.

Drug Hamster Gerbil Rat Mouse

Amikacin 2–5 mg/kg q 8–12 h; SC 2–5 mg/kg q 8–12 h; SC 10 mg/kg q 12 h; SC 10 mg/kg q 8–12 h; SC
Ampicillin Toxic 6–30 mg/kg q 8 h; PO 20–100 mg/kg q 12 h; PO, SC 20–100 mg/kg q 12 h; PO, SC OR

Azithromycin 30 mg/kg q 24 h; PO 500 mg/L dw
15 mg/kg q 12 h; SC
Cephalexin – 25 mg/kg q 24 h; SC 10–25 mg/kg q 24 h; SC 60 mg/kg q 12 h; PO
30 mg/kg q 12 h; IM 10–25 mg/kg q 24 h; SC
Cephaloridine 10–25 mg/kg q 24 h; SC – 30 mg/kg q 12 h; SC
– 50–200 mg/kg q 8 h; PO 0.5mg/mL dw OR 50–200mg/kg q 8h; PO
Cephalosporin – 50–200 mg/kg q 8 h; PO 30–50 mg/kg q 12 h; SC 30–50 mg/kg q 12 h; SC
20–50 mg/kg q 12 h; SC
Chloramphenicol palmitate 50–200 mg/kg q 8 h; PO
–
Chloramphenicol 20–50 mg/kg q 12 h; SC 7–20 mg/kg q 12 h; PO
2.5–5 mg/kg q 12 h; PO; do not use
succinate
in young or pregnant animals
Chlortetracycline 20 mg/kg q 12 h; PO, SC 0.05–0.2 mg/mL dw × 14d OR – 25 mg/kg q 12 h; PO, SC
7–20 mg/kg q 12 h; PO 7–20 mg/kg q 12 h; PO
Ciprofloxacin 7–20 mg/kg q 12 h; PO 5–10 mg/kg q 12 h; PO, SC 5 mg/kg q 12 h; PO 2.5 –5 mg/kg q 12 h; PO
–
Doxycycline 2.5–5 mg/kg q 12 h; PO; do not use in
2–4 mg/kg q 8 h; SC
young or pregnant animals 25–50 mg/kg q 12 h × 14–60d; PO OR

Enrofloxacin 0.05–0.2 mg/mL dw × 14d OR 1.5% in DMSO for 5–7 d; topically 0.05–0.2 mg/mL dw × 14d OR 0.05–0.2 mg/mL dw × 14d OR 5–10 mg/
10–40 mg/kg q 24 h × 14d; PO
5–10 mg/kg q 12 h; PO, SC 7.5 mg/70–90gm animal q 8 h 5–10 mg/kg q 12 h; PO, SC kg q 12 h; PO, SC

Erythromycin – 20 mg/kg q 12 h; PO 20 mg/kg q 12 h; PO

Gentamicin 5 mg/kg q 24 h; SC 5–10 mg/kg divided q 8–12 h; SC 2–4 mg/kg q 8–12 h; SC

Griseofulvin 25–50 mg/kg q 12 h × 14–60d; PO OR 25–50 mg/kg q 12 h × 14–60d; PO OR 25–50 mg/kg q 12 h × 14–60d; PO OR

(avoid in pregnant animals) 1.5% in DMSO for 5–7 d; topically 1.5% in DMSO for 5–7 d; topically 1.5% in DMSO for 5–7 d; topically

Ketoconazole 10–40 mg/kg q 24 h × 14d; PO 10–40 mg/kg q 24 h × 14d; PO 10–40 mg/kg q 24 h × 14d; PO

Metronidazole 7.5 mg/70–90gm animal q 8 h 10–40 mg/kg q 24 h; PO 2.5 mg/mL dw × 5 d OR 20–60 mg/kg

q 8–12 h; PO

Neomycin 0.5mg/mL dw OR 100mg/kg q 24h; PO 2 g/L dw OR 100 mg/kg q 24 h; PO 2 g/L dw OR 25 mg/kg q 12 h; PO 2 g/L dw
Oxytetracycline 0.25–1 mg/mL dw or 16 mg/kg 0.8 mg/mL dw or 10 mg/kg q 8 h; PO
500 mg/L dw or 10–20 mg/kg q 8 h; PO 500 mg/L dw OR 10–20 mg/kg q 8 h; PO
Sulfadimethoxine q 24 h; SC or 20 mg/kg q 24 h; SC
Sulfamerazine 10–15 mg/kg q 12 h; PO 10–15 mg/kg q 12 h; PO 10–15 mg/kg q 12 h; PO 10–15 mg/kg q 12 h; PO
Sulfamethazine 1 mg/mL dw q 24 h 0.8 mg/mL dw q 24 h 1 mg/mL dw 1 mg/mL dw OR 500 mg/L dw
Sulfaquinoxaline 1 mg/mL dw q 24 h 0.8 mg/mL dw q 24 h 1 mg/mL dw 1 mg/mL dw
Tetracycline 1 mg/ml dw q 24 h 1 mg/ml dw q 24 h
0.4 mg/mL dw q 24 h OR 2–5 mg/mL dw q 24 h OR 10–20 mg/ 2–5 mg/mL dw OR 10–20 mg/kg 2–5 mg/mL dw OR 10–20 mg/kg
Trimethoprim/ q 8 h; PO q 8 h; PO
sulfa 10–20 mg/kg q 8–12 h; PO kg q 8–12 h; PO
15–30 mg/kg q 12–24 h; PO, SC 30 mg/kg q 12–24 h; PO, SC 15–30 mg/kg q 12 h; PO, SC 30 mg/kg q 12 h; PO, SC
Tylosin
2–8 mg/kg q 12 h; SC, PO OR 0.5 mg/mL dw q 24 h OR 10 mg/kg 0.5 mg/mL dw OR 10 mg/kg q 24 h; 0.5 mg/mL dw OR 10 mg/kg q 24 h;
500 mg/mL dw q 24 h; PO, SC PO, SC PO, SC

PO, per os; SC, subcutaneous; IM, intramuscular; dw, drinking water.

606 Section IV. Antimicrobial Drug Use in Selected Animal Species

Table 36.3. Reported antimicrobial dosages in ferrets, hedgehogs, and sugar gliders. Caution: Most uses and dosages are
extra-label.

Drug Ferrets Hedgehogs Sugar Gliders

Amikacin 10–15 mg/kg q 12 h; SC, IM 2–5 mg/kg q 8–12 h; SC, IM 10 mg/kg q 12 h; IM
Amoxicillin 20–30 mg/kg q 8–12 h; PO 15 mg/kg q 12 h; PO, SC 30 mg/kg divided q 12–24 h; PO, SC
Amoxicillin/ 12.5–25 mg/kg q 8–12 h; PO 12.5 mg/kg q 12 h; PO 12.5 mg/kg divided q 12–24 h; PO, SC
clavulanate
Ampicillin 5–30 mg/kg q 8–12 h; SC, IM, IV – –
Azithromycin 5 mg/kg q 24 h; PO – –
Ceftiofur 20 mg/kg q 12–24 h; SC –
Cephalexin – 25 mg/kg q 12 h; PO 30 mg/kg divided q 12–24 h; PO, SC
Chloramphenicol 15–30 mg/kg q 8–12 h; PO 30–50 mg/kg q 6–12 h; PO, SC, IV –
Chlortetracycline 25–50 mg/kg q 12 h; PO, SC, IM 5–20 mg/kg q 12 h; PO –
Ciprofloxacin 5–20 mg/kg q 12 h; PO 10 mg/kg q 12 h; PO
Clarithromycin – 5.5 mg/kg q 12 h; PO –
Clindamycin 5–15 mg/kg q 12 h; PO 5.5–10 mg/kg q 12 h; PO –
Doxycycline 12.5–25 mg/kg q 12 h; PO 2.5–10 mg/kg q 12 h; PO, SC –
Enrofloxacin* 5–10 mg/kg q 12 h; PO 5 mg/kg q 12 h; PO, SC 2.5–5 mg/kg q 12–24 h; PO, SC, IM
Erythromycin 10 mg/kg q 12 h; PO 20 q 12 h;
– PO
Fluconazole 10–20 mg/kg q 12–24 h; PO, SC, IM – –
Griseofulvin 10 mg/kg q 6 h; PO 50 mg/kg q 24 h; PO 20 mg/kg q 24 h; PO
(avoid in pregnant
50 mg/kg q 12 h; PO
animals) 25 mg/kg q 12–24 h; PO
Itraconazole
Ketoconazole 15 mg/kg q 24 h; PO 5–10 mg/kg q 12–24 h; PO 5–10 mg/kg q 12 h; PO
Lincomycin 10–30 mg/kg q 12–24 h; PO 10 mg/kg q 12–24 h; PO –
Metronidazole
Neomycin – – 30 mg/kg divided q 12–24 h; PO, IM
Nystatin 20 mg/kg q 12 h; PO 20 mg/kg q 12 h; PO 25 mg/kg q 24 h; PO
Oxytetracycline 10–20 mg/kg q 6 h; PO
Penicillin G procaine – –
Piperacillin – 30,000 IU/kg q 8–24 h; PO, topical 5,000 IU/kg q 8 h x 3d; PO
Sulfadimethoxine – 25–50 mg/kg q 24 h; PO, in food
Tetracycline 40,000 IU/kg q 24 h; SC 40,000 IU/kg q 24 h; SC, IM –
Trimethoprim/sulfa – 10 mg/kg q 8–12 h; SC 22,000–25,000 IU/kg q 12–24 h; SC, IM
Tylosin – 2–20 mg/kg q 24 h; PO, SC
25 mg/kg q 12 h; PO –
15–30 mg/kg q 12 h; PO, SC, IM – 5–10 mg/kg q 12–24 h; PO, SC
10 mg/kg q 8–12 h; PO, SC 30 mg/kg q 12 h; PO, SC
10 mg/kg q 12 h; PO, SC –
15 mg/kg q 12 h; PO

–

*Dilute if giving by subcutaneous or intramuscular route to avoid tissue necrosis at injection site.
PO, per os; SC, subcutaneous; IM, intramuscular; dw, drinking water.

palatable liquids, gels, or food to encourage consumption. and veterinarians alike, including Cool Whip, maple
Small rodents, such as rats and mice, willingly take vanilla- syrup, V.A.L. syrup, canned pumpkin, cooked sweet
flavored human nutritional supplements, such as Boost or potato, coconut milk, raspberry-flavored gelatin, etc.
Ensure, directly from a syringe or small dish. Hamsters The availability of a suitable vehicle, compatible with
favor rice-based baby cereal, rabbits like bananas, chin- both the antimicrobial and the patient, is limited only by
chillas are partial to raisins, and ferrets enjoy malt-flavored the imagination of the veterinarian.
cat laxatives or pet nutritional supplements such as Nutri-
Cal. The internet abounds with suggestions from clients Manual administration of pills, capsules, and liquids
to rabbits and rodents is made challenging by their