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Rational Selection of Antimicrobials for Use in Horses

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Rational Selection of Antimicrobials for Use in Horses Reprinted in the IVIS website with the permission of AAEP Close window to return to IVIS IN DEPTH: CURRENT CONCEPTS IN SELECTION AND USE OF ANTIMICROBIALS Rational Selection of Antimicrobials for Use in Horses W. David Wilson, BVMS, MRCVS, MS Author’s address: Department of Medicine and Epidemiology (VM:VME), School of Veterinary Medicine, University of California, Davis, CA 95616, USA. © 2001 AAEP. 1. Introduction following discussion emphasizes important aspects Antibiotics frequently play an important central or of antimicrobial use in horses, including the bacte- adjunctive role in the therapeutic management of rial species likely to be involved in particular disease horses and foals with a variety of illnesses, including syndromes, susceptibility profiles of bacterial iso- those requiring critical care, because diseases lates, and the antimicrobial spectrum, mode of ac- caused by primary or secondary bacterial infection tion, indications, dose, and adverse effects of are commonly encountered and may contribute to selected commonly used antibiotics. Knowledge re- failure of single or multiple organs. However, it garding adverse effects is particularly important be- should be understood that supportive therapy usu- cause the relative sparsity of antimicrobials ally plays a role at least as important as antimicro- approved for parenteral and oral use in horses fre- bials in promoting a positive outcome, and that the quently makes extra-label use necessary. Conse- adverse effects of antimicrobial drugs individually quently, much of the responsibility for adverse or in combination may actually lead to negative events rests with the prescribing clinician. consequences. Antibiotic use should be based on 2. Basic Principles of Antimicrobial Therapy sound rational principles involving thorough patient evaluation, good clinical judgment, overall medical The following principles should serve as a guide for knowledge, information regarding the individual pa- antimicrobial use in horses, but not all can be fol- 1-4 tient and the infecting agent(s), selection of an ap- lowed in the critical care patient. In particular, propriate drug, and formulation of a dosage regimen the identity and susceptibility of the etiologic agent appropriate to the patient and its caretaker after is rarely known when therapy is initiated, extra- assessment of the potential benefits and risks of that label drug use is frequently necessary, and combi- therapy.1 nation therapy with more than one antibiotic is The ultimate aim of antibiotic treatment is to often indicated in critical care patients. inflict an insult on infecting bacteria sufficient to kill the organism or render it susceptible to inactivation ● An infectious agent must be involved in the by natural host defenses or the local microenviron- disease process for antimicrobial therapy to be ment without adversely affecting the patient.1 The effective. NOTES AAEP PROCEEDINGS ր Vol. 47 ր 2001 75 Proceedings of the Annual Convention of the AAEP 2001 Reprinted in the IVIS website with the permission of AAEP Close window to return to IVIS IN DEPTH: CURRENT CONCEPTS IN SELECTION AND USE OF ANTIMICROBIALS ● Antimicrobial therapy is necessary to rid the c. Antibiotics approved for IM use: procaine host of the disease penicillin G, benzathine penicillin G, ceftio- ● The identity of the infecting organism is known fur (Naxcel), ampicillin or at least reasonably suspected d. Antibiotics approved for oral use: trimetho- a. Cytologic examination and culture of appro- prim/sulfadiazine (Tribrissen, Uniprim) priate samples e. Antibiotics approved for intrauterine use: ● The organism(s) is (are) susceptible to the amikacin, gentamicin, ticarcillin drug(s) selected as determined by ● Adverse reactions should be recognized, inves- a. MIC—quantitative susceptibility test (pre- tigated and reported to the manufacturer of ferred because this information is helpful for the drug and, in the US, to the FDA/Center selecting dose) for Veterinary Medicine (1-888-332-8387 or 1- b. Kirby Bauer—qualitative susceptibility test 888-FDA-VETS; www.fda.gov/cvm/), or to the ● Host defense mechanisms must contribute to Veterinary Practitioners’ Reporting Network the patient’s recovery (USPPRN) of the US Pharmacopeia (1-800-487- ● Therapeutic concentrations of the drug will be 7776 or 1-800-4-USPPRN; www.usp.org/). achieved at the site of infection and the micro- environment at this site will support activity of In critical care situations, there is insufficient the drug time to wait for results of culture and susceptibility ● Appropriate dose, dosage interval, administra- testing of samples before initiating antimicrobial tion route, and duration of therapy are used as therapy. The appropriate approach is therefore to dictated by a. Pharmacokinetic, pharmacodynamic, and ● Collect and submit appropriate samples toxic properties of the drug ● Begin treatment based on knowledge of bacte- b. Resolution of disease process as determined ria most likely to be involved in certain syn- by clinical status of the patient and labora- dromes/clinical presentations and their most tory monitoring likely susceptibility patterns ● Concurrent use of more than one antimicrobial ● Adjust therapy (antimicrobial, dose, route, fre- drug is appropriate in limited situations quency) based on initial response, physiologic a. Life threatening conditions (insufficient time status, adverse effects, or results of initial cul- to wait for culture and susceptibility results) ture and susceptibility tests b. Mixed infections—more than one drug is needed to provide appropriate antimicrobial 3. Bacteria Associated with Disease Syndromes 5 spectrum in Horses c. Need for synergistic activity The major pathogens of horses vary by body system, ● Causes of therapeutic failure should be investi- age, use, geographic location, and the type of facility gated on which the horses reside. In referral centers, a. The disease process did not have a bacterial nosocomial infection with resistant bacteria in- etiology cluding Salmonella sp, other enteric species, and b. Ineffective concentrations of antimicrobial at Staphylococcus sp influence the situation and the site of infection antibiotic-associated colitis involving Clostridium c. Infection in an inaccessible location or one sp or Salmonella sp is an ever-present concern. In with a poor blood supply general, the following are the most commonly en- d. Microenvironment at the site of infection is countered pathogens of horses: ␤-hemolytic Strep- not conducive to antimicrobial activity tococcus sp, Actinobacillus sp, Pasteurella sp, e. Pathogens were or have become resistant to Escherichia coli, Klebsiella pneumoniae, Enter- the chosen antimicrobial obacter sp, Pseudomonas aeruginosa, Bordetella f. Changes in the microbial environment at the bronchiseptica, Staphylococcus sp, non-hemolytic site of infection Streptococcus sp, Rhodococcus equi (in foals), and g. Continued contamination of the infection anaerobic bacteria, particularly Bacteroides sp and site Clostridium sp. h. Infection is no longer contributing to the clin- ical signs 4. Empirical Selection of Antimicrobials Based on ● Need for extra-label drug use (drug, dose, route, Bacterial Species and Likely Susceptibility Pattern duration) should be considered and reconsid- Antimicrobial susceptibility profiles for Gram-pos- ered itive and Gram-negative aerobic bacteria isolated a. Few antimicrobial drugs are licensed for par- from horses during 1998 at the Veterinary Medi- enteral administration to horses; therefore cal Teaching Hospital, University of California, extra-label use is often necessary Davis, are shown in Tables 1 and 2. Susceptibil- b. Antimicrobials approved for IV use in ity patterns of bacteria such as ␤-hemolytic Strep- horses: ampicillin, sulfadimethoxine, tri- tococcus sp, Actinobacillus sp, Pasteurella sp and methoprim/sulfadiazine 48% suspension anaerobes, with the exception of Bacteroides sp, 76 2001 ր Vol. 47 ր AAEP PROCEEDINGS Proceedings of the Annual Convention of the AAEP 2001 Reprinted in the IVIS website with the permission of AAEP Close window to return to IVIS Table 1. Susceptibility of Gram-Positive Bacteria Isolated from Horses at the University of California, Davis during 1998 to Antimicrobial Agentsa Percent Susceptible to Antimicrobial Organism (Number tested) PENG AMP OX AMXCLA CEPH CEFTIO CEFOX ERYTH RIF TET TMS GENT AMIK CHLOR ENRO IN DEPTH: CURRENT CONCEPTS IN SELECTION AND USE OF ANTIMICROBIALS MIC breakpoint (␮g/ml) 8 8 2 8 8 2 8 0.5 1 4 2 4 16 8 0.5 for Staphylococcus sp 0.003 4 for Streptococcus sp 0.25 0.25 2 4 Staphylococcus aureus (33) 30 67 88 91 69 36 76 94 36 55 48 94 97 94 Coag. negative Staph (31) 13 77 100 97 77 74 61 97 81 74 74 100 94 96 Strep. zooepidemicus (14) 100 100 100 100 100 100 100 71 100 7 0 100 Rhodococcus equi (8) 39 100 100 63 88 25 100 100 87 63 Enterococcus faecalis (10) 100 100 40 90 90 Enterococcus faecium (10) 90 90 10 70 80 aData compiled by Fitchorn J, Jang S, Hirsh D and reprinted with permission. PENG ϭ Penicillin G; AMP ϭ Ampicillin; OX ϭ Oxacillin; AMXCLA ϭ Amoxicillin/clavulanic acid; TICLA ϭ Ticarcillin/clavulanic acid; CEPH ϭ Cephalothin; CEFTIO ϭ Ceftiofur; CEFOX ϭ Ceftizoxime; ERYTH ϭ Erythromycin; RIF ϭ Rifampin; TET ϭ Tetracycline; TMS ϭ Trimethoprim/sulfonamide; GENT ϭ Gentamicin; AMIK ϭ Amikacin; CHLOR ϭ Chloramphenicol; ENRO ϭ Enrofloxacin. Table 2. Susceptibility of Gram-Negative Bacteria Isolated from Horses at the University of California, Davis during 1998 to Antimicrobial Agentsa Percent Susceptible to Antimicrobial Organism (Number tested) PENG AMP AMXCLA TICLA CEPH CEFTIO CEFOX ERYTH TET TMS GENT AMIK CHLOR ENRO AAEP PROCEEDINGS MIC Breakpoint (␮g/ml) 4 8 8 16 8 2 8 0.5 4 2 4 16 8 0.5/.25 E. coli (74) 68 93 94 73 94 97 71 60 86 100 91 100 Klebsiella pneumoniae (15) 14 79 87 66 100 100 54 67 67 100 80 100 Serratia marcescens (4) 0 0 0 75 100 50 0 0 0 0 100 Actinobacillus suis-like (26) 100 89 100 100 100 100 30 96 96 100 100 100 Actinobacillus equuli (7) 100 100 100 100 100 100 28 86 86 100 100 100 Actinobacillus ligniersii (2) 100 100 100 100 100 100 0 100 100 100 100 100 Pasteurella sp (6) 100 100 100 100 83 83 33 100 100 100 100 100 83 ր Vol.
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