The OPTAMA programme: utilizing MYSTIC (2002) to predict critical pharmacodynamic target attainment against nosocomial pathogens in Europe

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Abstract
Objectives: The Optimising Pharmacodynamic Target Attainment using the MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Antibiogram (OPTAMA) programme identifies antibiotic regimens with the highest probability of attaining critical pharmacodynamic targets, accounting for the inherent variability in pharmacokinetics, dosages and MIC distributions. Methods: European MIC data were obtained from the MYSTIC programme. Pharmacodynamic target attainment was calculated by Monte Carlo simulation for meropenem, imipenem, ceftazidime, cefepime, piperacillin/tazobactam and ciprofloxacin against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. Results: Significant differences in probability of target attainment were found, with Northern Europe demonstrating the highest probabilities of target attainment and Eastern Europe the lowest. The carbapenems had the highest target attainments and susceptibility levels across all regions and pathogens. The cephalosporins demonstrated high target attainments and susceptibility results against E. coli and K. pneumoniae in Northern and Southern Europe. Piperacillin/tazobactam and ciprofloxacin had the lowest levels for both parameters in all regions. Desirable target attainment was not achieved (except for carbapenems in Northern Europe) for A. baumannii and P. aeruginosa; thus, combination therapy may be appropriate empirical therapy for these pathogens in Southern and Eastern Europe. The closest correlations between target attainment and susceptibility were for meropenem 1 g every 8 h, imipenem 0.5 g every 6 h and ceftazidime 1 g every 8 h. Conclusions: The study highlighted significant overestimations between the probability of target attainment and the reported percentage susceptibility, particularly for piperacillin/tazobactam and ciprofloxacin. The approach of the OPTAMA programme provides a novel tool which complements susceptibility data to help in the selection of appropriate empirical antibiotic therapy.