Cuicui Wang1, Wei Hao2, Yan Jin3, Cuihua Shen1, Bo Wang1. 1. Medical Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China. 2. Pediatric Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China. 3. Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China.
Abstract
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 β-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.
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 β-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.
Entities:
Keywords:
Gram-negative bacteria; Monte Carlo simulation; bloodstream infection; pharmacokinetics/pharmacodynamic