Optimization of Fosfomycin Doses for Treating Pseudomonas aeruginosa Infection in Critically Ill Patients by using Monte Carlo Simulation
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Abstract
Objective: To predict fosfomycin dosing regimens against P.aeruginosa infection in critically ill patients. Method: The fosfomycin susceptibilities were evaluated by E-test method. The percentages of a 24 h period where the drug concentration exceeds the MIC (T>MIC) of 70% and 100 % were used as target values. Monte Carlo simulation was used to calculate T>MIC on day 1 and day 5 of treatment. The probability of target attainment (PTA) and cumulative fraction of response (CFR) were calculated. Results: The MICs of fosfomycin were 3 mg/L to > 1024 mg/L. The MIC50, and MIC90 were 64 mg/L and 128 mg/L. On the first day, the PTAs for achieving 70% T>MIC and 100% T>MIC had reached the target in pathogens with a MIC of 64 mg/L and 32 mg/L. Five regimens of fosfomycin covered the pathogen with MIC 128 mg/L at PTAs target of achieving 70% T>MIC. At PTAs target of achieving 100% T>MIC, three regimens of fosfomycin covered the pathogen with MIC 64 mg/L. Using a target CFR of 80%, nine regimens of fosfomycin were determined to be appropriate for fosfomycin in day 1 of treatment with a PK-PD target of 70% T>MIC. Only one regimen achieved a target of 100% T>MIC. Each regimen gave a PTA and CFR above 80% at day 5. Conclusions: Prolonged fosfomycin infusion with high dose regimen is suggested in early phase of treatment in critically ill patients with severe infection. Most of the studied fosfomycin regimens reached the target in day 5.
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ผลการวิจัยและความคิดเห็นที่ปรากฏในบทความถือเป็นความคิดเห็นและอยู่ในความรับผิดชอบของผู้นิพนธ์ มิใช่ความเห็นหรือความรับผิดชอบของกองบรรณาธิการ หรือคณะเภสัชศาสตร์ มหาวิทยาลัยสงขลานครินทร์ ทั้งนี้ไม่รวมความผิดพลาดอันเกิดจากการพิมพ์ บทความที่ได้รับการเผยแพร่โดยวารสารเภสัชกรรมไทยถือเป็นสิทธิ์ของวารสารฯ
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