Therapeutic and Pharmacokinetic Challenges With Treatment of Nontuberculous Mycobacteria Infection in Two Lung Transplant Recipients: Case Report

Lung transplant (LTx) recipients are susceptible to pulmonary nontuberculous mycobacteria (NTM) infections due to pre-transplant colonization and post-transplant immunosuppression. This presents a challenge when managing immunosuppression and infection prophylaxis post-LTx due to drug-drug interactions (DDIs) with antimycobacterial agents. We present two cases of LTx recipients requiring concomitant rifabutin and isavuconazole. A 62-year-old male receiving rifabutin for pre-LTx pulmonary Mycobacterium avium complex (MAC) infection was initiated on isavuconazole for post-LTx fungal prophylaxis. A rifabutin peak level on post-operative day (POD) 6 was 0.43 mcg/mL (range 0.3-0.9 mcg/mL) and an isavuconazole trough was 1.96 mcg/mL (range ≥1 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. The patient developed leukopenia that was managed conservatively without changes to the antimycobacterial regimen. A 45 year-old female was similarly diagnosed with MAC pre-LTx and required a triple-drug regimen including rifabutin. The rifabutin peak levels were 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 18, respectively. This patient experienced severe, prolonged leukopenia, prompting discontinuation of rifabutin. She remained on dual therapy with ethambutol and azithromycin. Despite this adverse reaction, neither patient required antimicrobial dose adjustments due to DDIs. Therapeutic drug monitoring of rifabutin and isavuconazole may be necessary to confirm therapeutic serum concentrations when used concomitantly. The effect of this drug interaction on the incidence or severity of rifabutin-associated leukopenia needs further evaluation.