Pseudomonas aeruginosa susceptibility and antimicrobial activity by PK/PD analysis: An 18-years surveillance study

Introduction: To evaluate the adequacy of the antimicrobial therapy against Pseudomonas aeruginosa in admitted patients in a tertiary Spanish Hospital (excluding Intensive Care Unit), the changes in the susceptibility of P. aeruginosa strains to the antimicrobials in an 18 years period (2000-2017) were analyzed. Moreover, the therapy success probability was also estimated by applying a PK/PD modeling approach as a microbiological surveillance tool, by using PK/PD indexes as surrogate markers of efficacy. Methods: The susceptibility was studied considering the CLSI breakpoints. Monte Carlo simulations were conducted to calculate the cumulative fraction of response (CFR). Linear regression analysis was applied to determine the trends in susceptibility and in the CFR. Results: In 2017, the susceptibility to amikacin, penicillins and cephalosporins was >= 85%; tobramycin 76%, meropenem 75% and for gentamicin, imipenem and fluoroquinolones <70%. PK/PD analyses was able to identify changes in antimicrobial activity not detected by simply assessing MICs; meropenem administered as extended infusion attained CFR >90%, ceftazidime, piperacillin/tazobactam and imipenem provided CFRs between 80-90%, all of them administered at the highest doses. Conclusions: Both microbiological surveillance tools, analysis of susceptibility and PK/PD modeling, should be considered together to determine the most appropriate antimicrobial drug and its dose regimen. Empirical antipseudomonal therapy would vary considerably if PK/PD analysis is considered in addition to susceptibility data. PK/PD approach has allowed to preserve the therapeutic value of antimicrobials with low susceptibility values, such as carbapenems, and the selection of the most effective antimicrobials among those with high rates of susceptible isolates. (C) 2019 Elsevier Espafia, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.