D325 - Therapeutic and Pharmacokinetic Challenges with Treatment of Nontuberculous Mycobacteria Infection in a Lung Transplant Recipient: A Case Series

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Author Block: R. Jung¹, A. Ali¹, T. Royer², M. Tucker², N. Sinha³, ¹Jefferson Transplant Institute, Thomas Jefferson University Hospital, Philadelphia, PA, ²Division of Infectious Diseases, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, ³Division of Pulmonary, Allergy, and Critical Care, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA
*Purpose: Lung transplant (LTx) recipients are susceptible to pulmonary non-tuberculous mycobacteria (NTM) infections due to pre-transplant colonization and degree of post-transplant immunosuppression. This presents a challenge when managing immunosuppression and infection prophylaxis post-LTx due to drug-drug interactions (DDIs) with antimycobacterial agents.
*Methods: We present a case series of two LTx recipients requiring concomitant rifabutin for NTM treatment and isavuconazole for post-LTx fungal prophylaxis and describe the pharmacokinetic effects of both drugs.
*Results: A 62-year-old male was diagnosed pre-LTx with pulmonary Mycobacterium avium complex (MAC) infection and initiated on rifabutin, azithromycin, and ethambutol. Post-LTx, the patient was initiated on isavuconazole for fungal prophylaxis per institutional protocol. On POD 6, the rifabutin peak level was therapeutic at 0.43 mcg/mL (range 0.3-0.9 mcg/mL). An isavuconazole trough drawn the same day was 1.96 mcg/mL (range ≥1-2 mcg/mL). Acid fast bacilli (AFB) stains and cultures were followed serially with no growth and NTM therapy was continued for 3 months post-LTx. While on rifabutin and isavuconazole, the patient required 5-7 mg/day of tacrolimus (0.09-0.14 mg/kg/day), which decreased to 2-3.5 mg/day (0.04-0.7 mg/kg/day) after rifabutin was discontinued. A 45-year-old female was similarly diagnosed with MAC pre-LTx and was initiated on a triple-drug regimen including rifabutin. The rifabutin level was 0.33 mcg/mL and 0.22 mcg/mL on POD 7 and 14, respectively. Isavuconazole trough levels were 1.33 mcg/mL and 1.04 mcg/mL on POD 7 and 14, respectively. This patient remains on NTM therapy at 2 months post-LTx and has required 9-12 mg/day (0.18-0.24 mg/kg/day) of tacrolimus. Despite DDIs, neither patient required antimicrobial dose adjustments.
*Conclusions: This case series adds to the limited data available describing the pharmacokinetic interaction between isavuconazole and rifabutin in a transplant recipient. Therapeutic drug monitoring with the appropriate timing from initiation of CYP3A4 inducers may be necessary to confirm therapeutic serum concentrations. The effect of interpatient variability in CYP3A4 metabolism on response to enzyme induction or inhibition should be further evaluated.