Reasons for antimicrobial treatment failures and predictive value of in-vitro susceptibility testing in veterinary practice: An overview.

The choice of the most suitable antimicrobial agent for the treatment of an animal suffering from a bacterial infection is a complex issue. The results of bacteriological diagnostics and the in-vitro antimicrobial susceptibility testing (AST) provide guidance of potentially suitable antimicrobials. However, harmonized AST methods, veterinary-specific interpretive criteria and quality control ranges, which are essential to conduct AST in-vitro and to evaluate the corresponding results lege artis, are not available for all antimicrobial compounds, bacterial pathogens, animal species and sites of infection of veterinary relevance. Moreover, the clinical benefit of an antimicrobial agent (defined as its in vivo efficacy) is not exclusively dependent on the in-vitro susceptibility of the target pathogen. Apart from the right choice of an antibacterial drug with suitable pharmacokinetic properties and an appropriate pharmaceutical formulation, the success of treatment depends substantially on its adequate use. Even if this is ensured and in-vitro susceptibility confirmed, an insufficient improvement of clinical signs might be caused by biofilm-forming bacteria, persisters, or specific physicochemical conditions at the site of infection, such as pH value, oxygen partial pressure and perfusion rate. This review summarizes relevant aspects that have an impact on the predictive value of in-vitro AST and points out factors, potentially leading to an ineffective outcome of antibacterial treatment in veterinary practice. Knowing the reasons of inadequate beneficial effects can help to understand possible discrepancies between in-vitro susceptibility and in vivo efficacy and aid in undertaking strategies for an avoidance of treatment failures.

Effects of intramuscularly administered enrofloxacin on the susceptibility of commensal intestinal Escherichia coli in pigs (sus scrofa domestica).

BACKGROUND: In the European Union, various fluoroquinolones are authorised for the treatment of food producing animals. Each administration poses an increased risk of development and spread of antimicrobial resistance. The aim of this study was to investigate the impact of parenteral administration of enrofloxacin on the prevalence of enrofloxacin and ciprofloxacin susceptibilities in the commensal intestinal E. coli population. METHODS: E. coli isolates from faeces of twelve healthy pigs were included. Six pigs were administered enrofloxacin on day 1 to 3 and after two weeks for further three days. The other pigs formed the control group. MIC values were determined. Virulence and resistance genes were detected by PCR. Phylogenetic grouping was performed by PCR. Enrofloxacin and ciprofloxacin were analysed in sedimentation samples by HPLC. RESULTS: Susceptibility shifts in commensal E. coli isolates were determined in both groups. Non-wildtype E. coli could be cultivated from two animals of the experimental group for the first time one week after the first administration and from one animal of the control group on day 28. The environmental load with enrofloxacin in sedimentation samples showed the highest amount between days one and five. The repeated parenteral administration of enrofloxacin to pigs resulted in rapidly increased MIC values (day 28: MIC up to 4 mg/L, day 35: MIC ≥ 32mg/L). E. coli populations of the control group in the same stable without direct contact to the experimental group were affected. CONCLUSION: The parenteral administration of enrofloxacin to piglets considerably reduced the number of the susceptible intestinal E. coli population which was replaced by E. coli strains with increased MIC values against enrofloxacin. Subsequently also pigs of the control were affected suggesting a transferability of strains from the experimental group through the environment to the control group especially as we could isolate the same PFGE strains from both pig groups and the environment.

[Antimicrobial susceptibility testing of bacteria isolated from animals: methods for in-vitro susceptibility testing and their suitability with regard to the generation of the most useful data for therapeutic applications]. / Empfindlichkeitsprüfung bakterieller Infektionserreger von Tieren gegenüber antimikrobiellen Wirkstoffen: Methoden zur in-vitro Empfindlichkeitsprüfung und deren Eignung in Hinblick auf die Erarbeitung therapeutisch nutzbarer Ergebnisse.

In-vitro susceptibility testing provides valuable informations for choosing the most suitable antimicrobial agent for the control of bacterial infections in animals. Different diffusion and dilution methods, as conducted according to various approved performance standards, can be used to determine the in-vitro susceptibility of bacterial pathogens. In the present article, problems are discussed which arise from the use of different methods and the difficulty to interpret such results. While most approved performance standards were designed for testing of bacteria from human sources, the NCCLS document M31-A2 exclusively focusses on susceptibility testing of bacteria isolated from animals and--in contrast to all other standards--includes veterinary specific breakpoints for a number of antimicrobial agents used in veterinary medicine. Therefore, performance of in-vitro susceptibility testing of veterinary pathogens should follow the recommendations given in the NCCLS document M31-A2. The microdilution method is recommended as the method of choice for susceptibility testing. The result of a microdilution test is given as the minimum inhibitory concentration (MIC). This value provides a quantitative result which precisely indicates the degree of susceptibility of the tested bacterial strain and in return gives the veterinarian a clear guidance whether therapeutic intervention with the antibiotic in question will be successful.