Antimicrobial resistance in food animals—are we encountering untreatable diseases? (Proceedings)


Antimicrobial resistance in food animals—are we encountering untreatable diseases? (Proceedings)

Aug 01, 2011

The short answer is "no" when we look for widespread, peer-reviewed evidence of untreatable infectious disease in food animals due to a microbial pathogen. However, there are some trends which bear watching. The evaluation of "untreatable disease" involves several inputs.

Just what difference do we expect from the use of an antimicrobial?

(See the accompanying presentation on the difference antimicrobials make). For some diseases with narrow response differences due to antimicrobial treatment, it may be difficult to discern the decrease in clinical response outside of a research setting. For diseases with wider demonstrated difference due to treatment, such as bovine respiratory disease, the difference made by antimicrobials is significant enough that a lack of efficacy would be more immediately apparent in clinical practice.

How would we evaluate laboratory data to see if decreasing susceptibility is contributing to a lack of efficacy in the field?

The first thing I do is figure out if the application I am evaluating has an approved CLSI breakpoint. If it does, then I am more likely to equate resistance in the laboratory with lack of efficacy in the field. For those antimicrobial/pathogen combinations without an approved breakpoint, if the MIC is in the higher-MIC group of a biphasic distribution (a group of isolates with lower MICs and a group of isolates with higher MICs), then this is suggestive of the presence of a resistant genetic component, and I assume clinical resistance. When the population distribution is monophasic, or this information is lacking, we are left with assuming (hopefully) that "S is better than R".

The CLSI has approved the following veterinary specific breakpoints. These breakpoints are detailed in CLSI M31-A3, including the specific pathogens associated with these breakpoints.

The following breakpoints are included in CLSI M31-A3 as "generic" breakpoints, where the breakpoint was determined on the basis of published pharmacokinetic parameters in the designated species in combination with available target pathogen susceptibility data.

     • Ampicillin - Horses (respiratory disease) and Dogs (skin and soft tissue infections)
     • Gentamicin - Horses (enterobacteriaceae, Pseudomonas aeruginosa, Actinobacillus spp.)
                              Dogs (enterobacteriaceae, Pseudomonas aeruginosa)
     • Oxytetracycline – Cattle (respiratory disease) and swine (respiratory disease)

For some antimicrobials used in veterinary medicine, the CLSI/VAST Subcommittee has found it necessary to use human-derived breakpoints since no sponsor has brought the information to the subcommittee to develop approved breakpoints. The VAST Subcommittee is working on developing "generic" breakpoints for veterinary labels without approved breakpoints and for extralabel uses. The following antimicrobials have human-derived breakpoint criteria adapted by the NCCLS/VAST Subcommittee. For these antimicrobials, and for extralabel use of antimicrobials with approved veterinary breakpoints, it is necessary to evaluate the susceptibility testing results in light of the MIC breakpoint used and the pharmacokinetics/pharmacodynamics of the animal and pathogen being treated.

     • Aminoglycosides
          o amikacin, gentamicin, kanamycin
     • β-lactams
          o amoxicillin-clavulanic acid, ticarcillin-clavulanic acid
          o ampicillin, oxacillin, penicillin, ticarcillin, , imipenem, cefazolin
     • Others
          o erythromycin, chloramphenicol, trimethoprim-sulfamethoxazole
          o rifampin, sulfisoxazole, tetracyclines, vancomycin