Monte Carlo simulation evaluation of cefoperazone-sulbactam regimens for Acinetobacter baumannii infections
LYU Nan
YUE Baosen
ZHANG Weihua
SUN Dan
CUI Wei
LI Yajing
Abstract：Objective To evaluate the efficacy of different cefoperazone-sulbactam dosing regimens against Acineto-bacter baumannii bloodstream infections using Monte Carlo simulation,comparing traditional infusion therapy(TIT),prolonged infusion therapy(PIT),and optimized two-step infusion therapy(OTIT).Methods The antimicrobial susceptibility testing results of Acinetobacter baumannii to cefoperazone-sulbactam in the Xi'an Hospital of Traditional Chinese Medicine from 2023 to 2024 were collected.Monte Carlo simulation was employed to calculate the probability of target attainment(PTA)and cumu-lative fraction of response(CFR)for various regimens differing in dose,dosing interval,infusion duration,and infusion mode.PTA≥90%and CFR≥90%served as the metrics for optimal targeted and empirical therapy,respectively.Results Shortening the dosing interval,prolonging the infusion duration,and increasing the dosage improved both PTA and CFR.The order of PTA and CFR among the three infusion modes was determined to be OTIT>PIT>TIT.Each regimen had a minimal inhibitory con-centration(MIC)threshold.When the MIC was below this threshold,a PTA>90%could be achieved by prolonging the infusion duration and utilizing the OTIT mode.However,when the MIC exceeded the threshold,none of the optimization strategies could achieve a PTA above 90%.The MIC thresholds were 4/2 mg/L for 3 g q12h regimen,8/4 mg/L for 6 g q12h regimen,16/8 mg/L for both 3 g q8h and 3 g q6h regimen,and 32/16 mg/L for both 6 g q8h and 6 g q6h regimen.For targeted therapy,the maximum approved dose of 6 g q12h was only effective against Acinetobacter baumannii with an MIC≤8/4 mg/L.For Acinetobacter bau-mannii strains with MIC of 16/8-32/16 mg/L,PTA>90%could be achieved by optimizing the regimens to 3 g q8h,3 g q6h,6 g q8h,or 6 g q6h and prolonging the infusion duration based on OTIT framework.For empirical therapy,the CFR for all dosing regimens was below 90%.Conclusion To enhance the efficacy of cefoperazone-sulbactam in the treatment of Acinetobacter baumannii bloodstream infections,optimized dosing strategies should be considered,such as prolonging the infusion duration,shortening the administration interval,increasing the dosage,and adjusting the administration mode.The higher the MIC,the more beneficial these optimization measures are likely to be.
Keywords：monte carlo simulationAcinetobacter baumanniibloodstream infectionscefoperazone-sulbactamdos-ing regimensoptimized two-step infusionprolonged infusion
Publication Date：2026-03-25
Online Publishing Date：2026-04-07(First online date of this platform, not the publication date of the document)
Pages：5( 453-457 )