Abstract
This study identified antimicrobial resistance patterns of commonly isolated bacteria at the Equine Hospital of the Université de Montréal between 2007 and 2013, and compared the results with the resistance patterns observed in tests performed in previous decades in the same hospital. A total of 396 antimicrobial susceptibility tests were analyzed by the Kirby-Bauer method during the period 2007 to 2013 and compared to 233 and 255 tests completed in 1986 to 1988 and 1996 to 1998, respectively. The most common bacteria were Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) and Escherichia coli. Except for resistance of coagulase-positive staphylococci to trimethoprim-sulfamethoxazole, there was no overall increase in resistance observed between 1986 to 1988 and 2007 to 2013 for antimicrobials reported for all 3 periods. However, between 1996 to 1998 and 2007 to 2013, there was an increase in in vitro resistance to enrofloxacin for E. coli and Enterobacter spp., and to ceftiofur for Enterobacter spp. and coagulase-positive staphylococci. No increase in resistance was observed for S. zooepidemicus and no isolate was resistant to penicillin.
Résumé
Évolution de l’antibiorésistance in vitro dans un hôpital équin pendant 3 décennies. L’objectif était d’identifier les patrons de résistance aux antimicrobiens des bactéries fréquemment isolées à l’Hôpital Équin de l’Université de Montréal de 2007 à 2013, pour ensuite les comparer aux données observées au cours des dernières décennies dans le même hôpital. Trois cent quatre-vingt-seize antibiogrammes faits à l’aide de la méthode Kirby-Bauer ont été analysés et comparés aux 233 et 255 ayant été effectués en 1986–1988 et 1996–1998, respectivement. Les bactéries les plus fréquentes étaient Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) et Escherichia coli. Pour les antibiotiques testés pendant les 3 périodes de l’étude, il n’y pas eu d’augmentation de la résistance observée entre 1986–1988 et 2007–2013, à exception de celle des staphylocoques à coagulase positive au triméthoprime-sulfaméthoxazole. Cependant, entre 1996–1998 et 2007–2013, une augmentation de la résistance à l’enrofloxacin a été observée pour E. coli et Enterobacter spp., ainsi qu’une augmentation de la résistance au ceftiofur pour Enterobacter spp. et les staphylocoques à coagulase positive. Aucune augmentation de résistance n’a été observée pour S. zooepidemicus et aucun isolat n’était résistant à la pénicilline.
(Traduit par les auteurs)
Introduction
Antimicrobial administration early in the course of severe bacterial infections can increase the likelihood of survival. Selection of the appropriate antimicrobial is based on multiple factors including identification of pathogens, in vitro susceptibility, expected in vivo susceptibility, drug disposition, toxicity, ease of administration, and cost. The risk of increasing resistance among bacteria should also be taken into account during antimicrobial selection, especially when using those critically important to human health (1). These include third and fourth generation cephalosporins, aminoglycosides, fluoroquinolones, and macrolides, including antimicrobials highly relevant to the practice of equine medicine such as ceftiofur, gentamicin, amikacin, enrofloxacin, and erythromycin. The development of resistance against these and other critically important antimicrobials is particularly worrisome and has been documented in human and equine populations (2–4). As recommended by the American College of Veterinary Internal Medicine (ACVIM), decisions on how to treat bacterial infections should preferably be based on the antimicrobial susceptibility of isolated bacteria. When this is not possible, an empirical antimicrobial selection should be based on predictable susceptibility patterns and local resistance profiles (5). In order to provide guidance for these empirical choices, the goal of this study was to determine the resistance patterns of frequently isolated bacteria from the equine population of a referral hospital from 2007 to 2013. Its secondary goal was to identify trends in the variation of resistance by comparing data with previous studies performed in the same hospital over 2 previous decades (6,7).
Materials and methods
Selection of bacterial isolates
The Clinical Bacteriology Laboratory of the Faculty of Veterinary Medicine of the Université de Montréal computer system was searched to identify antimicrobial susceptibility tests performed on aerobic bacterial isolates from patients of the Equine Hospital of the Centre Hospitalier Universitaire Vétérinaire between March 1, 2007 and September 1, 2013. In the event that an isolate was cultured more than once (i.e., the same bacterial species was recovered from two sites in the same patient, or twice from the same site during a hospitalization), only the first isolate was used for analysis. Bacteria, or groups of bacteria with a minimum of 5 isolates were retained for analysis. Actinobacillus spp. included bacteria identified as A. equuli, A. equuli subsp. haemolyticus, and A. suis. Pseudomonas spp. included P. aeruginosa and other Pseudomonas spp. Two groups of Enterobacteriaceae (Escherichia coli and Enterobacter spp.) were analyzed, whereas in the Streptococcus genus, only Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) was analyzed. All coagulase positive staphylococci (including Staphylococcus aureus and Staphylococcus intermedius) were retained for analysis. Similar criteria were used in 2 previous studies by our group, except for one bacterium-antimicrobial pair from 1986 to 1988 that was originally reported with less than 5 isolates (6).
Antimicrobial resistance testing
Following the Clinical and Laboratory Standards Institute (CLSI) guidelines (8), isolates were tested for antimicrobial resistance using the Kirby-Bauer disk diffusion method on Mueller-Hinton medium (Mueller-Hinton with 5% sheep blood for Streptococcus spp.). While the Kirby-Bauer method does not determine minimal inhibitory concentrations, qualitative results of bacterial resistance are obtained based on the inhibition zone diameter. Based on CLSI breakpoints, isolates were deemed susceptible, intermediate, or resistant. Veterinary-specific resistance breakpoints were used when available. For this study, and to be consistent with previous reports, intermediate susceptibility was considered resistant. Quality control antimicrobial resistance of E. coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Streptococcus pneumoniae ATCC 49619 were performed monthly. Resistance was compared to the previously reported profiles by the same laboratory using the same technique (6,7). Ceftiofur and enrofloxacin were added after 1986 to 1988, and tetracycline stopped being included in standard Kirby-Bauer for equine isolates in the 2000s. Additional recorded data included the age of the patients and the sample site.
Statistical analysis
Differences among proportions of resistant isolates across 3 time periods were compared with the exact Chi-square test using commercial software (SAS 9.4; SAS Institute, Cary, North Carolina, USA). Pair-wise comparisons between time periods were only performed if there was an overall difference across time periods. The statistical significance level was set to 0.05.
Results
Patients and sites of sampling
There were 299 samples with bacterial growth on aerobic culture that had a Kirby-Bauer test performed during the period 2007 to 2013. Seventy-nine samples had multiple isolates, for a total of 396 Kirby-Bauer tests performed. Most (35%) of the samples originated from the respiratory system and included tracheal aspirates, nasopharyngeal swabs, and thoracocentesis. Streptococcus zooepidemicus was isolated from 37% of these samples. Other frequent sites included wounds and tissue swabs (13%), blood culture (11%), abscesses (7%), and joint fluid (6%). Patients (n = 272) from which these bacteria were isolated were between 0 and 29 years of age (median: 3 years old). Eighty-five (31%) of them were foals 8 mo old or less.
Resistance over time
The 396 resistance patterns were analyzed and compared to those obtained in 1986 to 1988 (233) and 1996 to 1998 (255). Tables 1, 2, and 3 summarize the resistance of frequently isolated bacteria to commonly used antimicrobials during these 3 periods, and the significant differences between them. For antimicrobials with data available for all 3 periods, there was no overall increase in resistance between 1986 to 1988 and 2007 to 2013, except for resistance of coagulase-positive staphylococci to trimethoprim-sulfamethoxazole (P = 0.04). However, there was a significant increase in resistance of E. coli (P = 0.002) and Enterobacter spp. (P = 0.003) to enrofloxacin, and of Enterobacter spp. (P = 0.03) and coagulase-positive staphylococci (P = 0.02) to ceftiofur between the years 1996 to 1998 and 2007 to 2013. An increase in resistance of Actinobacillus spp. (P = 0.03) and E. coli (P = 0.02) to amikacin was observed between 1996 to 1998 and 2007 to 2013, but resistance from 2007 to 2013 did not differ from that in 1986 to 1988 for E. coli and could not be compared to data from 1986 to 1988 for Actinobacillus spp. The previously observed increase in resistance of coagulase-positive staphylococci to trimethoprim-sulfamethoxazole (TMS) was confirmed, while the increase observed for Actinobacillus was no longer significant (TMS) or had again decreased since the years 1996 to 1998 (penicillin). No increase in resistance was observed for S. zooepidemicus and no isolate was resistant to penicillin. Additional observations were that, among the 7 E. coli isolates resistant to amikacin in the 2007 to 2013 period, 5 were isolated between the end of 2012 and 2013, and 3 were also resistant to fluoroquinolones (enrofloxacin and marbofloxacin). Furthermore, 15% (4 of 26 isolates) of coagulase-positive staphylococci were resistant to cefoxitin, a cephalosporin used to detect methicillin resistance among S. aureus. Among the 4 cefoxitin-resistant isolates, 3 were confirmed to be S. aureus and were isolated from a lymphangitis, an infected castration site and an infected biopsy wound.
Table 1.
Resistance of frequently isolated Gram-negative bacteria from equine patients in 2007 to 2013, compared to previously reported resistance in 1986 to 1988 (6) and 1996 to 1998 (7): Pasteurellaceae and non-lactose fermenters
| Pasteurellaceae Actinobacillus spp.e (including Actinobacillus suis) | Non-lactose fermenters Pseudomonas spp. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||||
| 1986–1988 | 1996–1998 | 2007–2013 | 1986–1988 | 1996–1998 | 2007–2013 | |||||||
|
|
|
|
|
|
|
|||||||
| % | (n) | % | (n) | % | (n) | % | (n) | % | (n) | % | (n) | |
| Amikacin | na | 3a | (36) | 22a | (36) | 0 | (5) | 4 | (26) | 13 | (15) | |
| Ampicillin | 17 | (29) | 17 | (46) | 6 | (36) | 92 | (24) | 85 | (27) | 100 | (15) |
| Ceftiofur | na | 0 | (47) | 0 | (36) | na | 88 | (26) | 100 | (15) | ||
| Chloramphenicol | 25 | (4) | 0 | (19) | 0 | (36) | 87 | (23) | 57 | (14) | 79 | (14) |
| Enrofloxacin | na | 0 | (47) | 0 | (36) | na | 15 | (27) | 40 | (15) | ||
| Erythromycin | 13 | (23) | 33 | (46) | 31 | (26) | Intrinsic resistanced | |||||
| Gentamicin | 7 | (29) | 2 | (47) | 6 | (33) | 16 | (25) | 42 | (26) | 33 | (15) |
| Penicillin | 33a,c | (30) | 73a,b | (26) | 3b,c | (34) | Intrinsic resistanced | |||||
| Tetracycline | 10 | (29) | 6 | (48) | na | 83 | (24) | 63 | (27) | na | ||
| TMS | 0a | (30) | 17a | (46) | 8 | (36) | 96 | (25) | 82 | (22) | 80 | (15) |
spp. — species; % — percentage of isolates resistant; n — number of isolates; na — data not available; TMS — trimethoprim-sulfamethoxazole.
For a given bacterium, percentages with the same superscript are significantly different between time periods (P < 0.05).
Intrinsic resistance — in vitro susceptibility cannot be used to predict treatment outcome (15).
Note — changes in guidelines for Pasteurella did not affect Actinobacillus spp.
Table 2.
Resistance of frequently isolated Gram-negative bacteria from equine patients in 2007 to 2013, compared to previously reported resistance in 1986 to 1988 (6) and 1996 to 1998 (7): Enterobacteriaceae
| Enterobacteriaceae | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
||||||||||||
| Escherichia coli | Enterobacter spp. | |||||||||||
|
|
|
|||||||||||
| 1986–1988 | 1996–1998 | 2007–2013 | 1986–1988 | 1996–1998 | 2007–2013 | |||||||
|
|
|
|
|
|
|
|||||||
| % | (n) | % | (n) | % | (n) | % | (n) | % | (n) | % | (n) | |
| Amikacin | 11 | (9) | 0a | (58) | 12a | (57) | 0 | (5) | 9 | (22) | 34e | (29) |
| Ampicillin | 63a | (46) | 34a | (58) | 53 | (57) | 90 | (20) | 91 | (22) | 97 | (29) |
| Ceftiofur | na | 32 | (56) | 18 | (57) | na | 21a | (24) | 52a | (29) | ||
| Chloramphenicol | 36 | (42) | 26 | (34) | 19 | (57) | 61 | (18) | 50 | (10) | 62 | (29) |
| Enrofloxacin | na | 0a | (58) | 14a | (57) | na | 5a | (22) | 41a | (29) | ||
| Erythromycin | Intrinsic resistanced | Intrinsic resistanced | ||||||||||
| Gentamicin | 13 | (47) | 19 | (58) | 25 | (56) | 53 | (19) | 55 | (22) | 55 | (29) |
| Penicillin | Intrinsic resistanced | Intrinsic resistanced | ||||||||||
| Tetracycline | 62 | (48) | 45 | (58) | na | 70 | (20) | 57 | (21) | na | ||
| TMS | 52 | (48) | 39 | (57) | 46 | (57) | 60 | (20) | 62 | (21) | 55 | (29) |
spp. — species; % — percentage of isolates resistant; n — number of isolates; na — data not available; TMS — trimethoprim-sulfamethoxazole.
For a given bacterium, percentages with the same superscript are significantly different between time periods (P < 0.05).
Intrinsic in vivo resistance, in vitro susceptibility cannot be used to predict treatment outcome (15).
P = 0.05.
Table 3.
Resistance of frequently isolated Gram-positive bacteria from equine patients in 2007 to 2013, compared to previously reported resistance in 1986 to 1988 (6) and 1996 to 1998 (7): Streptococcus equi subsp. zooepidemicus and coagulase-positive staphylococci
| Streptococcus equi subsp. zooepidemicus | Coagulase-positive staphylococci | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||||
| 1986–1988 | 1996–1998 | 2007–2013 | 1986–1988 | 1996–1998 | 2007–2013 | |||||||
|
|
|
|
|
|
|
|||||||
| % | (n) | % | (n) | % | (n) | % | (n) | % | (n) | % | (n) | |
| Amikacin | Low-level intrinsic resistanced | na | 4 | (24) | 0 | (42) | ||||||
| Ampicillin | 8 | (12) | 0 | (6) | 8 | (37) | na | 25 | (20) | 43 | (42) | |
| Ceftiofur | na | 0 | (9) | 2 | (86) | na | 11a | (46) | 40a | (42) | ||
| Chloramphenicol | 0 | (5) | 0 | (5) | 10 | (10) | 0 | (19) | 6 | (16) | 0 | (42) |
| Enrofloxacin | na | 33 | (9) | na | na | 2 | (45) | 2 | (42) | |||
| Erythromycin | 0 | (7) | 22a | (9) | 0a | (60) | 0 | (23) | 11 | (46) | 9 | (34) |
| Gentamicin | Low-level intrinsic resistanced | 4 | (23) | 15 | (46) | 19 | (42) | |||||
| Penicillin | 0 | (18) | 0 | (12) | 0 | (86) | 70 | (23) | 41 | (46) | 41 | (41) |
| Tetracycline | 53 | (17) | 44 | (9) | 86 | (7) | 0a | (22) | 28a | (46) | na | |
| TMS | 18 | (17) | 25 | (12) | 35 | (84) | 0a,b | (24) | 33a | (46) | 17b | (42) |
subsp. — subspecies; % — percentage of isolates resistant; n — number of isolates; na — data not available; TMS — trimethoprim-sulfamethoxazole.
For a given bacteria, percentages with the same superscript are significantly different between time periods (P < 0.05).
Low-level resistance of streptococci to aminoglycosides (17).
Discussion
In this study, when comparing the results from the years 2007 to 2013 with the ones from 1986 to 1988, we did not observe an overall increase in the antimicrobial resistance of the most common bacteria isolated from our hospital, except for coagulase-positive staphylococci’s resistance to trimethoprim-sulfamethoxazole. However, not all antimicrobials had data for all 3 periods, and we observed a significant increase in resistance between the years 1996 to 1998 and 2007 to 2013 for 3 antimicrobials considered to be critically important to human health by the World Health Organization (WHO) (1). In addition to the increase in resistance to ceftiofur (Enterobacter spp.), enrofloxacin (Enterobacter spp. and E. coli), and amikacin (E. coli), there was a trend (P = 0.05) for an increase of Enterobacter spp.’s resistance to amikacin. A similar increase in resistance of Enterobacteriaceae isolated from equine patients to ceftiofur and other antimicrobials was also recently described by others (2,4), and at least 1 other study observed this change for enrofloxacin (9).
The pressure of selection due to the widespread use of antimicrobials in veterinary and human patients is an important cause of acquired bacterial resistance and could have played a role in the observed development of resistance to ceftiofur, enrofloxacin, and amikacin. The former (ceftiofur, enrofloxacin) became available in the late 1980s and 1990s, respectively, and have since become widely used by equine practitioners. Amikacin has been on the market for longer, but its use in the equine population (mainly in neonates) has increased in North America since the 1990s (2). However, since Enterobacteriaceae are not typically species-specific and numerous mobile genetic elements conferring resistance (plasmids, bacteriophages, transposons) can be transferred between bacteria and across species (10), an increase in resistance is not necessarily only a consequence of increased use of antimicrobials in the species of interest. Furthermore, even if resistance appears to be most common to the older antimicrobials such as tetracycline, streptomycin, penicillin, and sulfonamides (5), there are many exceptions and one cannot assume that increased resistance is always correlated with increased use.
This study also confirmed the continuing susceptibility of S. zooepidemicus to penicillin, also reported by others (11). The lack of resistance to penicillin and the few variations observed for other antimicrobials over time is notable because S. zooepidemicus is considered a mucosal commensal of the upper airways of horses and is therefore widely exposed to all antimicrobials used in the equine population. Previously observed increase in resistance between 1986 to 1988 and 1996–1998 for Actinobacillus (penicillin and TMS) was not observed again and there was even a decrease in the resistance to penicillin (7). It can be speculated that this is in part due to a decrease in the use of penicillin in our area in the past decade, but this is certainly not the case for TMS, since its ease of administration and observed rarity of side effects make it a widely used antimicrobial in our area. These fluctuations highlight the importance of long-term studies to evaluate trends over multiple decades.
Drugs designated as critically important antimicrobials by the WHO should be reserved for use after appropriate susceptibility testing or when no alternative is available (1). The ACVIM guidelines recommend that practitioners sort antimicrobials used in their practice into Primary, Secondary, and Tertiary categories, and to favor Primary Use drugs (such as penicillin, tetracycline, potentiated sulfonamides) over Secondary or Tertiary Use drugs when choosing an antimicrobial for first line treatment (5). A similar classification is recommended by the British Equine Veterinary Association Protect ME program (12). Some clinical implications can be drawn from the results of this study, particularly regarding respiratory infections. As previously reported (6), S. zooepidemicus was the most commonly isolated bacterium from respiratory samples. None of these isolates were resistant to penicillin, which confirms that this antimicrobial could be the Primary Use drug of choice for horses with non-life-threatening respiratory tract infections, unless culture and sensitivity testing suggests otherwise. It should be noted that, in addition to the relatively low frequency of in vitro activity of TMS against S. zooepidemicus (65% in 2007 to 2013), this antibiotic is unlikely to have appropriate in vivo activity against S. zooepidemicus, even in the face of apparent susceptibility in vitro, making it a poor choice of Primary Use drug for respiratory infections. Indeed, it was suggested that TMS efficacy decreases in purulent exudates due to low pH and high concentrations of p-aminobenzoic acid (13,14). When treating non-respiratory infections, in the presence of life-threatening infections (respiratory or not), or in cases of poorly responding respiratory infections, it becomes even more important to base therapeutic decisions on culture and sensitivity testing, because the second most commonly isolated bacteria (Enterobacteriaceae) have unpredictable resistance patterns.
Resistance should be interpreted with caution when species and organ-specific breakpoints are not available. Such breakpoints are designed to predict the therapeutic outcome of a bacterial infection based on the expected antimicrobial concentrations that can be achieved in a patient, and ideally in a specific organ, depending on pharmacodynamics and recommended dosages (15). Only a limited number of breakpoints had been determined for equine pathogens at the time of the study and these include the following combinations: gentamicin for Enterobacteriaceae, Pseudomonas aeruginosa, Actinobacillus spp. (no organ specified), and ampicillin and ceftiofur for S. zooepidemicus (respiratory disease) (8). Because of this, while a therapeutic failure can most likely be predicted by the use of an antimicrobial in a patient infected by an organism deemed “resistant,” its “susceptibility” should be interpreted with caution in clinical settings. Another point to consider when interpreting the results of this study is that bacterial isolates obtained in referral centers might not represent infections treated in the field, but rather cases seen for a second opinion, which could have received prior antimicrobial treatment. Referral center cases could also include nosocomial infections, which could falsely increase resistance compared to community-acquired infections or first line cases. In fact, it has been shown that prior administration of antimicrobial drugs and sampling of hospitalized patients after their admission can influence susceptibility patterns (16). Unfortunately, it was not possible to extract from the available data the percentage of cases that had received prior antimicrobial treatment. Finally, tetracycline was removed from our routine susceptibility testing of equine bacterial isolates in the 2000s and data are therefore missing for 2007 to 2013.
In conclusion, the results of this study show little overall increase in resistance of common pathogens encountered in the equine species between the periods of 1986 to 1988 and 2007 to 2013 for antimicrobials with data available for all 3 periods. However, a significant and worrisome increase in resistance was observed for some bacteria to aminoglycosides, fluoroquinolones, and third generation cephalosporins between the periods 1996 to 1998 and 2007 to 2013. Since S. zooepidemicus is the most commonly isolated pathogen from the respiratory tract and it appears to be consistently susceptible to penicillin, this should be the drug of choice for non-life-threatening respiratory infections, unless culture and sensitivity testing suggests otherwise. Since Enterobacteriaceae, Pseudomonas spp., and coagulase-positive staphylococci have unpredictable susceptibility patterns in individual patients, routine culture and susceptibility testing should always be attempted for non-respiratory infections, or respiratory infections responding poorly to penicillin alone. CVJ
Footnotes
Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office (hbroughton@cvma-acmv.org) for additional copies or permission to use this material elsewhere.
References
- 1.World Health Organization. Critically Important Antimicrobials for Human Medicine. 3rd Revision 2011. WHO Document Production Services; Geneva, Switzerland: 2011. [Last accessed May 10, 2016]. Available from: http://apps.who.int/iris/bitstream/10665/77376/1/9789241504485_eng.pdf. [Google Scholar]
- 2.Theelen MJ, Wilson WD, Edman JM, Magdesian KG, Kass PH. Temporal trends in prevalence of bacteria isolated from foals with sepsis: 1979–2010. Equine Vet J. 2014;46:169–173. doi: 10.1111/evj.12131. [DOI] [PubMed] [Google Scholar]
- 3.European Food Safety Authority and European Centre for Disease Prevention and Control. The European Union Summary Report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2012. [Last accessed October 29, 2015]. Available from: http://www.efsa.europa.eu/en/efsajournal/pub/3590. [DOI] [PMC free article] [PubMed]
- 4.Johns IC, Adams EL. Trends in antimicrobial resistance in equine bacterial isolates: 1999–2012. Vet Rec. 2015;176:334. doi: 10.1136/vr.102708. [DOI] [PubMed] [Google Scholar]
- 5.Morley PS, Apley MD, Besser TE, et al. Antimicrobial drug use in veterinary medicine. J Vet Intern Med. 2005;19:617–629. doi: 10.1892/0891-6640(2005)19[617:aduivm]2.0.co;2. [DOI] [PubMed] [Google Scholar]
- 6.Lavoie JP, Couture L, Higgins R, Laverty S. Aerobic bacterial isolates in horses in a university hospital, 1986–1988. Can Vet J. 1991;32:292–294. [PMC free article] [PubMed] [Google Scholar]
- 7.Peyrou M, Higgins R, Lavoie JP. Evolution of bacterial resistance to certain antibacterial agents in horses in a veterinary hospital. Can Vet J. 2003;44:978–981. [PMC free article] [PubMed] [Google Scholar]
- 8.Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals; Approved Standard — 4th ed. CLSI document VET01-A4: Clinical and Laboratory Standards Institute 2013. [Last accessed May 10, 2016]. Available from: http://shop.clsi.org/c.1253739/site/Sample_pdf/VET01A4_sample.pdf.
- 9.Sanchez LC, Giguère S, Lester GD. Factors associated with survival of neonatal foals with bacteremia and racing performance of surviving Thoroughbreds: 423 cases (1982–2007) J Am Vet Med Assoc. 2008;233:1446–1452. doi: 10.2460/javma.233.9.1446. [DOI] [PubMed] [Google Scholar]
- 10.Dahmen S, Haenni M, Chatre P, Madec JY. Characterization of blaCTX-M IncFII plasmids and clones of Escherichia coli from pets in France. J Antimicrob Chemother. 2013;68:2797–2801. doi: 10.1093/jac/dkt291. [DOI] [PubMed] [Google Scholar]
- 11.Erol E, Locke SJ, Donahoe JK, Mackin MA, Carter CN. Beta-hemolytic Streptococcus spp. from horses: A retrospective study (2000–2010) J Vet Diagn Invest. 2012;24:142–147. doi: 10.1177/1040638711434138. [DOI] [PubMed] [Google Scholar]
- 12.British Equine Veterinarians Association. PROTECT ME — Responsible antimicrobial use policy. [Last accessed May 10, 2016]. Available from: http://www.beva.org.uk/_uploads/documents/beva-antimicrobial-policy-template-20121.pdf.
- 13.Ensink JM, Bosch G, van Duijkeren E. Clinical efficacy of prophylactic administration of trimethoprim/sulfadiazine in a Streptococcus equi subsp. zooepidemicus infection model in ponies. J Vet Pharmacol Ther. 2005;28:45–49. doi: 10.1111/j.1365-2885.2004.00624.x. [DOI] [PubMed] [Google Scholar]
- 14.Ensink JM, Smit JA, van Duijkeren E. Clinical efficacy of trimethoprim/sulfadiazine and procaine penicillin G in a Streptococcus equi subsp. zooepidemicus infection model in ponies. J Vet Pharmacol Ther. 2003;26:247–252. doi: 10.1046/j.1365-2885.2003.00483.x. [DOI] [PubMed] [Google Scholar]
- 15.Rubin JE. Antimicrobial susceptibility testing methods and interpretation of results. In: Giguère S, Prescott JF, Dowling T, editors. Antimicrobial Therapy in Veterinary Medicine. 5th ed. Ames, Iowa: John Wiley & Sons; 2013. [Google Scholar]
- 16.Dunowska M, Morley PS, Traub-Dargatz JL, Hyatt DR, Dargatz DA. Impact of hospitalization and antimicrobial drug administration on antimicrobial susceptibility patterns of commensal Escherichia coli isolated from the feces of horses. J Am Vet Med Assoc. 2006;228:1909–1917. doi: 10.2460/javma.228.12.1909. [DOI] [PubMed] [Google Scholar]
- 17.Leclercq R, Canton R, Brown DF, et al. Clin Microbiol Infect. 2013;19:141–160. doi: 10.1111/j.1469-0691.2011.03703.x. [DOI] [PubMed] [Google Scholar]