| DOI: 10.29090/psa.2023.02.22.368 | Pharm Sci Asia 2023; 50(2), 120-130 |
Optimal dosing regimen of biapenem and fosfomycin sodium combination against multidrug resistant Acinetobacter baumannii infection in pediatric patients using Monte Carlo simulationSuwida Tangtrakultham, Jantana Houngsaitong, Korbtham Sathirakul, Wichit Nosoongnoen, Supatat Chumnumwat, Preecha Montakantikul*
- Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Road, Rajathevi, Bangkok, Thailand
The objective of this study was to determine the optimal dosage regimens of biapenem and fosfomycin combination achieving desirable pharmacodynamic effects against multidrug-resistant Acinetobacter baumannii (MDR-AB) infections in pediatric patients. A total of 120 clinical MDR-AB strains were collected from tertiary hospitals in Thailand. Minimum inhibition concentrations (MICs) of all the isolates were determined by broth
microdilution method. Synergy studies were performed using the checkerboard method. The population pharmacokinetic (PK) parameters of biapenem were obtained from a previously published study. PK parameters of fosfomycin were analyzed by using published plasma concentrations of pediatric patients. Then, these PK parameters and MIC after synergy were used in Monte Carlo simulation to find the exposure time during which drug concentration remains above the MIC. MIC for 50% of the isolates (MIC50) of biapenem before and after synergy with fosfomycin were 16 and 2 mcg/mL, respectively, and MIC50 of fosfomycin before and after synergy with biapenem were 256 and 32 mcg/mL, respectively, for MDR-AB. Biapenem 5 mg/kg q8 h 3-h infusion and fosfomycin 100 mg/kg q8 h 8-h infusion could be used for A. baumannii susceptible to biapenem and fosfomycin. For organisms that are resistant to biapenem and fosfomycin, only biapenem can be used. However, biapenem 5, 10 mg/kg q8 h 3-h infusion and fosfomycin 480-600 mg/kg/day with prolonged infusion provided >80% cumulative fraction of response (CFR). In conclusion, extended biapenem infusion combined with prolonged high-dose fosfomycin infusion would be an option for the treatment of MDR-AB infection in pediatric patients.
Keyword:
Biapenem, Fosfomycin, Monte Carlo simulation, Acinetobacter baumnnii, Pediatric patients
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