Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

Abstract

Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal β-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA) of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte Carlo simulation was performed for each regimen to determine PTA. MICs from 272 isolates were included in this analysis. No intermittent infusion regimens achieved PTA ≥90%. Prolonged infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA ≥90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of β-lactam antibiotics as intermittent infusion did not achieve 90% PTA against P. aeruginosa isolated at our institution; however, some prolonged infusions were able to achieve these targets.

Simplifying Piperacillin/Tazobactam Dosing: Pharmacodynamics of Utilizing Only 4.5 or 3.375 g Doses for Patients With Normal and Impaired Renal Function

“…Our findings are also consistent with multiple previous Monte Carlo simulation studies, which showed that extended or continuous infusion of piperacillin/tazobactam is needed to achieve the 50% fT > MIC target at an MIC 16 mg/mL, particularly in patients with normal and augmented renal function. 25,[27][28][29] Of note, the prolonged infusion regimen of 3.375 g every 8 hours as a 4-hour infusion did not achieve optimal PTA in our study. We observed a PTA of 76.8% for patients with CrCl of 41 to 120 mL/min receiving this regimen.…”

Primary Pyomyositis as Unusual Cause of Limp: Three Cases in Immunocompetent Children and Literature Review

“…3 When group A streptococci are isolated, treatment should be changed to benzyl penicillin. 5,12 For gram-negative bacteria, an aminoglycoside (gentamicin) should be considered in addition to cephalosporins. 5,13 In immunocompromised patients, ampicillin/sulbactam or piperacillin/tazobactam may be required.…”

Rethinking urinary antibiotic breakpoints: analysis of urinary antibiotic concentrations to treat multidrug resistant organisms

“…For fluoroquinolones, the PK/PD target was identified as achieving a peak concentration (Cpk) to MIC ratio of at least 10 [ 8 ]. These values were compared and validated with Monte Carlo simulations [ 17 , 21 , 22 ]. Additionally, MIC 50 and MIC 90 were calculated for comparison of results obtained with Etest ® with those from Vitek ® .…”