Tomasz Z. Jodlowski

Selection of Optimal Empiric Antimicrobial Therapy against Pseudomonas aeruginosa  in the Greater New York City Area

Tomasz Z. Jodlowski, College of Pharmacy and Health Sciences, Clinical Pharmacy Practice; Students: Andras Farkas, Yuman Lee, Patricia Saunders-Hao, Karen Avisrur

Abstract

Rapidly spreading antimicrobial resistance and the stagnation in the antibiotic drug pipeline is an emerging public health crisis worldwide. Pseudomonas aeruginosa is a common cause of severe nosocomial infections and despite the use of antimicrobial therapy it is still associated with suboptimal outcomes. In our analysis we used population pharmacokinetic models of anti – pseudomonal agents to establish Probabilities of Target Attainment for optimal empiric coverage of isolates collected from geographically distinct locations in the greater New York City area. 5000 subject Monte Carlo simulations were performed for the mean + SD creatinine clearance values of 60 + 30 ml/min and the MIC range of 0.25 to 128 µg/ml at double dilution intervals. Minimum Inhibitory Concentrations (MIC) for non-duplicate Pseudomonas aeruginosa isolates (n = 1,104) were determined by institution specific automated systems. Bactericidal cumulative fraction of response (CFR) for standard doses of cefepime, imipenem, meropenem, piperacillin and tazobactam, ciprofloxacin, tobramycin, gentamicin and amikacin were calculated. Alternative approach - or extended infusion and high-dose - regimens were also modeled to improve CFRs of select agents. Total of 29 antibiotic dosing strategies were evaluated, and only 2 achieved a CFR > 90%. These were 4 hour infusion of meropenem 2 g q8h, and by the 3 hour infusion of cefepime 2 g q8h. Based on our analysis the use of conventional dosing regimens of all anti-pseudomonal agents studied appears to provide sub-optimal coverage for the treatment of Pseudomonas aeruginosa infections in many parts of the Greater New York City area. Selection of high dose meropenem or cefepime regimens using prolonged infusion strategies may be necessary to obtain desired clinical outcomes.