Title: Micafungin Treatment Failure in Obese Patients: Standard versus Body Mass Index-Adjusted Dosing Regimens
Authors: Helene Gao, Zachary Halbig, Caroline Gresham, Qian Zhong
Piedmont Athens Regional Medical Center - Athens, GA
Background: Obesity (BMI ≥30 kg/m²) affects more than 40% of adults in the United States and is associated with altered pharmacokinetics, creating uncertainty around optimal antifungal dosing. Micafungin, an echinocandin, is commonly used for invasive Candida infections, with standard dosing recommendations of 100-150 mg daily. However, pharmacokinetic and pharmacodynamic studies suggest that higher doses may be necessary in obese patients to achieve adequate drug exposure. Despite these findings, clinical outcome data supporting dose adjustments remain limited. Existing studies have largely been small, model‑based, or lacking comparison groups, leaving the real-world clinical impact of higher micafungin dosing unclear. This study aimed to compare clinical outcomes in obese adults receiving BMI-adjusted micafungin dosing (150-200 mg daily) versus standard dosing, with a primary focus on treatment failure.
Methods: This IRB-exempt, single-center, retrospective study evaluated obese adult patients admitted to Piedmont Athens Regional who received micafungin for ≥3 days as empiric or definitive antifungal therapy. The BMI-dose-adjusted group consisted of 19 randomly selected patients admitted between October 1, 2020, and October 30, 2025, with a cohort of 19 obese patients receiving standard micafungin dosing. Exclusion criteria included outpatient micafungin initiation, missing weight data, dose changes after ≥2 days, or <3 days of therapy. Data collected included demographics, comorbidities,infection‑related risk factors, key laboratory values, and micafungin treatment characteristics. Clinical variables evaluated included critical‑care interventions, hemodynamic support, and the presence of polymicrobial infection. The primary outcome was treatment failure, defined as all‑cause inpatient mortality or transition to comfort care before discharge. Secondary outcomes included micafungin duration, total hospital length of stay, and occurrence of adverse drug events involving hepatic, renal, or hematologic function. Categorical variables were analyzed using Chi‑squared or Fisher’s exact testing as appropriate, and continuous variables were analyzed using the Mann‑Whitney U test. A multivariable logistic regression was performed to adjust for confounders.
Results: Unadjusted outcomes revealed that treatment failure occurred in 36.8% of patients in the BMI-adjusted group and 42.1% in the standard-dose group (OR=1.25, 95% CI=0.34-4.59; p=0.74). The median duration of micafungin therapy was 5 days in the BMI-adjusted group and 7 days in the standard-dose group (p=0.12), while median hospital length of stay was 16 versus 23 days, respectively (p=0.11). Adverse drug reactions occurred in 36.8% of BMI-adjusted patients and 26.3% of standard-dose patients (p = 0.49). After adjusting for confounders, including SOFA score, number of comorbidities, and polymicrobial infection, there was a trend toward fewer treatment failures in the BMI-adjusted dosing group (OR=0.22, 95% CI=0.03-1.58;p=0.13). Within the observed range of SOFA scores, each 1-point increase within 24 hours of micafungin initiation was associated with approximately 40% increased odds of treatment failure (OR=1.40, 95%CI=1.12-2.47; p=0.002). In exploratory subgroup analyses, BMI-adjusted dosing was associated with 45% lower odds of treatment failure in ICU patients (OR=0.55, 95% CI=0.12-2.47; p=0.43) and 44% lower odds in patients with candidiasis (OR=0.56, 95% CI=0.07-4.76; p=0.59).
Conclusions: In obese adults receiving micafungin, BMI-adjusted dosing was not associated with a statistically significant difference in treatment failure compared with standard dosing. However, accounting for confounders, the analysis demonstrated numerically lower odds of treatment failure with BMI-adjusted dosing, with only SOFA score remaining significantly associated with treatment failure. Furthermore, exploratory subgroup analyses showed a consistent directional association favoring BMI-adjusted therapy. Limitations include the retrospective design, small sample size, and limited power to detect differences in outcomes. Larger, prospective studies are warranted to further evaluate the clinical effectiveness and safety of BMI-adjusted micafungin dosing, particularly in ICU patients.
