Pharmacodynamic evaluation of i.v. antimicrobials against Pseudomonas aeruginosa samples collected from U.S. hospitals

Keel, Rebecca A.; Kuti, Joseph L.; Sahm, Daniel F.; Nicolau, David P.
September 2011
American Journal of Health-System Pharmacy;9/1/2011, Vol. 68 Issue 17, p1619
Academic Journal
Purpose. Selected i.v. antimicrobials were evaluated against Pseudomonas aeruginosa isolates collected from U.S. hospitals to predict the likelihood of achieving maximal bactericidal activity. Methods. The pharmacodynamic profiles of ceftazidime, doripenem, imipenem-cilastatin, levofloxacin, meropenem, and piperacillin.tazobactam were simulated for 5000 adult patients using pharmacokinetic data from infected patients with the minimum inhibitory concentrations of 6142 P. aeruginosa isolates in U.S. hospitals collected during 2009. The probability of achieving bactericidal activity in this population, referred to as the cumulative fraction of response (CFR), was calculated for each antimicrobial. An optimal regimen was defined as achieving a CFR of .90%. Results. The majority of isolates were collected from male inpatients who were not in an intensive care unit (ICU) and were over age 65 years. Standard dosing for all antimicrobials failed to achieve optimal CFRs, regardless of hospital location. While high-dose prolonged infusions improved the CFRs for the β-lactams, optimal exposures were only attained by doripenem (2 g every 8 hours infused over 1 hour; 0.5-2 g every 8 hours infused over 4 hours) and meropenem (2 g every 8 hours infused over 0.5 and 3 hours) for all isolates. Non-ICU isolates had approximately 5-10% higher CFRs compared with those collected in the ICU. Lower-respiratory-tract isolates had a lower predicted CFR than did isolates from the blood and skin or wounds. Conclusion. Simulated pharmacodynamic profiles of i.v. antimicrobials commonly used to treat P. aeruginosa indicated that higher dosages and prolonged infusion times are needed to achieve optimal exposure for bactericidal activity.


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