Comparative pharmacodynamics for intravenous antibiotics against Gram-negative bacteria in Europe between 2002 and...

The Optimizing Pharmacodynamic Target Attainment using the MYSTIC Antibiogram (OPTAMA) Program has been used globally to estimate antimicrobial exposures for either targeted pathogens or disease states. Herein, we utilised this methodology to determine antimicrobial exposures of cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem and piperacillin/tazobactam against European-derived isolates of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa obtained in 2006 and compared these with results from 2002. All regimens, except ciprofloxacin, provided optimal pharmacodynamic exposures against E. coli, whereas more regional differences were noted with K. pneumoniae. For K. pneumoniae, the carbapenems provided the highest likelihood of optimal exposures. Ciprofloxacin exposures were also noted to be low for both P. aeruginosa and A. baumannii. Moreover, for these two organisms higher doses and/or prolonged infusion of the studied beta-lactams was necessary to obtain the desired pharmacodynamic targets. These data reveal regional differences in the probability of pharmacodynamic optimisation as well as the potential utility of employing regimens utilising higher doses and/or prolonged infusion techniques when directing therapy against P. aeruginosa and A. baumannii.