Background: In this report of the OPTAMA (Optimizing Pharmacodynamic Target Attainment
using the MYSTIC Antibiogram) program, we utilized Monte Carlo simulation to compare
the probabilities of achieving bactericidal time above the minimum inhibitory concentration
(MIC) (%T > MIC) exposures for imipenem-cilastatin 500 mg q6h and 1000 mg q8h,
meropenem 500 mg q6h and 1000 mg q8h and piperacillin/tazobactam 3.375 g q6h and 4.5 g
q8h in the empiric treatment of secondary peritonitis.
Methods: The prevalence of pathogens causing secondary peritonitis was identified from
the primary surgical and infectious diseases literature. Data for these pathogens with respect
to MIC were obtained from the 2003 MYSTIC surveillance study and weighted by
the prevalence of each pathogen. A sensitivity analysis varying the prevalence of P. aeruginosa
was performed with two additional models to determine the robustness of the data.
Pharmacokinetic parameters, obtained from previously published studies in healthy volunteers
were used to simulate the %T > MIC for 10,000 patients receiving imipenem-cilastatin,
meropenem, and piperacillin/tazobactam. The likelihood of obtaining bactericidal
exposure is reported.
Results: Empiric utilization of imipenem-cilastatin and meropenem 500 mg q6h and 1000
mg q8h regimens achieved 99.6%–99.7% likelihood of bactericidal exposure. Piperacillin/
tazobactam 3.375 g q6h and 4.5 g q8h produced bactericidal target attainments of 92.9% and
85.2%, respectively. Models simulating higher prevalence of P. aeruginosa reduced the likelihood
of bactericidal exposure for piperacillin/tazobactam regimens significantly and had little
effect on the carbapenems.
Conclusion: All of the β-lactams used in the current analysis were predicted to achieve high
target attainment consistently for the empiric treatment of secondary peritonitis. However,
imipenem-cilastatin 500 mg q6h and 1000 mg q8h, meropenem 1000 mg q8h and 500 mg q6h,
and piperacillin/tazobactam 3.375 g q6h achieved the highest likelihood. These, in particular,
would be effective choices for the empiric treatment of secondary peritonitis.
