Optimizing Micafungin Dosing in Patients with Critically Ill Candidemia and Trends of Candida Species Causing Bloodstream Infections in a Tertiary Hospital in Thailand: A Monte Carlo Simulation Approach
Year: 2025
Type: article
Abstract: Jutharat Watcharasuwanseree,1,2 Worawong Chueansuwan,3 Nuntra Suwantarat,4 Wichai Santimaleeworagun,5,6 Piraporn Juntanawiwat,7 Adisak Sangchankoom,8 Weerayuth Saelim5,6 1The College of Pharmacotherapy of Thailand, Nonthaburi, Thailand; 2Department of Pharmaceutical Care, Faculty of Pharmacy, Thammasat University, Pathumthani, Thailand; 3Division of Infectious Diseases, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand; 4Division of Infectious Diseases, Department of Internal Medicine, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand; 5Division of Pharmaceutical Care, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 6Pharmaceutical Initiative for Resistant Bacteria and Infectious Diseases Working Group [PIRBIG], Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 7Department of Clinical Pathology, Division of Microbiology, Phramongkutklao Hospital, Bangkok, Thailand; 8Division of Microbiology, Clinical Laboratory, Udonthani Hospital, Udonthani, ThailandCorrespondence: Weerayuth Saelim, Division of Pharmaceutical Care, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand, Tel +6634 255 800, Fax +6634 255 801, Email [email protected]: This study aimed to determine the optimal micafungin dosage for treating candidemia in critically ill adult patients using Monte Carlo simulation.Patients and Methods: Clinical Candida isolates were obtained from blood cultures collected between September 2023 and December 2024 at Phramongkutklao Hospital, Thammasat University Hospital, and Udonthani Hospital. Susceptibility testing was performed using the Sensititre® YeastOne® system, applying a broth microdilution method in 96-well plates to determine minimum inhibitory concentrations (MICs). Monte Carlo simulations were conducted to identify optimal micafungin dosing regimens, using cumulative fraction of response (CFR) and probability of target attainment (PTA) as key parameters.Results: In total, 128 clinical Candida isolates were identified. Candida tropicalis was the most frequently isolated species (32%), followed by C. albicans (22.7%), C. parapsilosis (16.4%), C. glabrata (Nakaseomyces glabrata) (12.5%), and C. auris (Candidozyma auris) (9.4%). The micafungin MIC ranges were as follows: C. tropicalis, 0.015– 0.25 μg/mL; C. albicans, 0.008– 0.015 μg/mL; C. parapsilosis, 0.5– 2 μg/mL; C. glabrata, 0.015–> 8 μg/mL; and C. auris, 0.12– 0.25 μg/mL. Pan-echinocandin-resistant C. glabrata was also detected. A standard micafungin dose (100 mg/day) may be effective for C. tropicalis infections when MIC is ≤ 0.015 μg/mL. In patients with Sequential Organ Failure Assessment scores > 10 and alanine aminotransferase > 120 U/L, the standard micafungin dose adequate CFR for empirical therapy and PTA for documented treatment at MICs up to 0.03 μg/mL, with the target threshold set at ≥ 90%. However, in the absence of MIC data and with increasing MIC trends, a higher empirical dose (up to 400 mg/day) may be warranted.Conclusion: Non-albicans Candida bloodstream infections are increasing, along with higher MIC trends, signaling emerging resistance. Standard dosing may be insufficient in critically ill patients. Empirical high-dose micafungin could improve treatment efficacy.Keywords: MIC distribution, ICU patient, empirical dosing, invasive candidiasis
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7094976962
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