Application Of PK/PD Modeling And Monte Carlo Simulation To Optimizing Initially Antibacterial Drug Regimens In The ICU Patients With Common Staphylococcal And Pseudomonas Aeruginosa Infection

Objective:To optimize initially antibacterial regimen in the treatment of ICU patients with common staphylococcal and pseudomonas aeruginosa infection.Methods:Based on being collected pharmacokinetic and pharmacodynamic parameters of antibacterial drugs, monitoring reports of hospital ICU antimicrobial resistance from ministry of health national antimicrobial resistance investigation net (Mohnarin) and chinese CHINT resistance net, and CLSI (2013), the minimum inhibitory concentration (MIC) of common staphylococci and pseudomonas aeruginosa were set by using the method of discrete uniform distribution.16 administration schemes and 24 administration schemes were worked out for staphylococci and pseudomonas aeruginosa, respectively. The best initially antimicrobial regimen was optimized by using PK/PD models and Monte Carlo simulations of cumulative fraction of response (CFR) from 10000 "real patients".Results: 1. The alternative regimens of treatments for the infectious bactria were:Linezolid 0.4g q12h and vancomycin 0.75g q12h (for staphylococcus aureus); amikacin 0.6g q24h, linezolid 0.4g q12h, and vancomycin 0.75g q12h (for hemolytic staphylococci and staphylococcus epidermidis); linezolid 0.4g q12h and vancomycin 1.0g q12h (for Methicillin-resistant Staphylococcus aureus); ampicillin/sulbactam 1.5g q6h, cefuroxime 0.75g q6h, amikacin 0.6g q24h, moxifloxacin 0.4g q24h (for methicillin-sensitive staphylococcus aureus).2. The alternative regimens of treatments for pseudomonas aeruginosa infection were as follow:pipercillin/tazobactam 4.5g q6h, cefepime 2.0g q12h, meropenem 1.0g q6h, amikacin 17.5mg/(kg·d), ciprofloxacin 0.4g q8h, and colistin 150mg q12h.Conclusion:1. In the ICU patients, it is recommended that the therapeutic regimen is ampicillin/sulbactam, cefuroxime, amikacin, and moxifloxacin for methicillin-sensitive Staphylococcus aureus infection, and linezolid or vancomycin for possible methicillin-resistant Staphylococcus aureus infection.2. It is recommended that the best initially therapeutic regimens are cefepime, cefepime plus ciprofloxacin, and cefepime plus ciprofloxacin plus colistin for the infections caused by non-muli-drug resistant pseudomonas aeruginosa (NMDR-PA), muli-drug resistant pseudomonas aeruginosa (MDR-PA) infection, and pan drug resistant pseudomonas aeruginosa (PDR-PA), respectively.