Mycobacterium avium complex (MAC) Immune Reconstitution Syndrome (IRIS) With Reduced Susceptibility to Ethambutol in an HIV-Infected Patient

Objective: To describe a case of Mycobacterium avium complex (MAC) lymphadenitis complicated by immune reconstitution syndrome (IRIS) and reduced susceptibility to ethambutol. Case Summary: A 24-year-old man was diagnosed in October 2012 with advanced HIV infection upon hospitalization for multiple opportunistic infections (OIs). Within 5 months of starting antiretroviral therapy, the patient developed significant cervical lymphadenopathy concerning for MAC/IRIS. Acid-fast bacilli were detected in the primary lymph node biopsy smear, and culture results confirmed the presence of MAC. Susceptibility testing revealed an organism susceptible to azithromycin, with an elevated minimum inhibitory concentration (MIC) to ethambutol (8 µg/mL). Currently, there is no interpretation for an ethambutol MIC of 8 µg/mL for MAC. A review of the primary literature revealed the possibility of decreased ethambutol susceptibility when the MIC is above 1 µg/mL, and therefore, therapy was replaced by rifabutin in combination with azithromycin. Discussion: Current guidelines recommend a 2-drug regimen for the treatment of MAC, specifically a macrolide plus ethambutol. Guidelines also emphasize MAC susceptibility testing for macrolides only. Susceptibility results from this patient’s biopsy prompted an evaluation of the effectiveness of his antimycobacterial regimen. Conclusions: Reduced ethambutol susceptibility in this patient triggered a search of the primary literature that resulted in the decision to replace ethambutol with rifabutin. Additional clinical trials are needed to define susceptibility breakpoints for ethambutol and other antimycobacterial agents used for MAC infection treatment and to direct clinical decisions when elevated MICs to primary agents are identified.