Use of Monte Carlo simulation to optimize antibiotic selection for bloodstream infections caused by Enterobacteriaceae in Shandong Province, China.

The increasing rates of resistance to ß-lactams have made it more challenging for clinicians to select appropriate antibiotic treatment for bloodstream infections (BSIs) caused by suspected Enterobacteriaceae. The objective of this analysis was to determine the optimal dosage regimens of ß-lactams for treatment of BSIs based on analysis of 19,334 Enterobacteriaceae collected from blood specimens. Monte Carlo simulation using pharmacokinetic parameters of infected patients was performed to determine the probability of overall pharmacokinetic/pharmacodynamic (PK/PD) target attainment (OPTA). E. coli, K. pneumoniae, and E. cloacae were the 3 most common species. Nine of the 16 tested regimens had optimal OPTAs (>90%) for Enterobacteriaceae overall (meropenem 2g q8h, 3 h infusion; meropenem 2g q8h, 0.5h; meropenem 1g q8h, 0.5h; piperacillin/tazobactam 4.5g q8h, 3h; ceftazidime 2g q8h, 3h; imipenem 0.5g q6h, 0.5h; imipenem 1g q8h, 0.5h; piperacillin/tazobactam 3.375g q6h, 0.5h; ceftazidime 2g q8h, 0.5h). Four other regimens had sub-optimal OPTAs of 80 to 90% (piperacillin/tazobactam 4.5g q8h, 0.5h; ceftazidime 1g q8h, 0.5h; cefepime 2g q12h, 3h; and cefepime 2g q12h, 0.5h). Although there are high antibiotic MICs among Enterobacteriaceae in Shandong Province, carbapenem- , ceftazidime- and piperacillin/tazobactam- based regimens provide the optimal treatment.

Pharmacokinetic/Pharmacodynamic Modeling of Seven Antimicrobials for Empiric Treatment of Adult Bloodstream Infections with Gram-Negative Bacteria in China.

Objective: Optimal dosing regimens for achieving a positive clinical outcome were simulated for seven antibiotics commonly used to treat bloodstream infections (BSIs) in adults. Methods and Results: Pharmacokinetic/pharmacodynamic (PK/PD) modeling was used to simulate 17 regimens, including meropenem, imipenem, cefepime, ceftazidime, piperacillin-tazobactam, tigecycline, and polymyxin B based on patients' characteristics and the antimicrobial resistance data for the main pathogens isolated from blood specimens in Shandong province (China). A regimen for which the cumulative fraction of response (CFR) was 90% or more was considered optimal. For Escherichia coli and Klebsiella pneumoniae, all carbapenem regimens, ceftazidime (2gq8h, 0.5 hr, and 3hr infusion), and piperacillin/tazobactam (4.5gq8h, 3 hr infusion) achieved CFRs above 90%. The meropenem regimen (2gq8h, 3 hr) achieved CFRs above 90% for both ceftriaxone or cefotaxime-resistant (CRO/CTX-R) E. coli and K. pneumoniae. For Pseudomonas aeruginosa, ceftazidime and meropenem (2gq8h, 0.5 hr, and 3 hr infusion) achieved optimal CFRs. None of the ß-lactam regimens examined achieved a CFR above 80% for Acinetobacter baumannii. For all examined bacteria, polymyxin B (50 mg q12h) led to a CFR above 90%. Conclusion: PK/PD modeling based on local antimicrobial resistance data provides valuable guidance for clinicians for the administration of empirical antibiotic treatments for BSIs.