Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV

N ontuberculous mycobacteria (NTM) cause a broad spectrum of disease, most commonly pulmonary infection, but also cause disseminated infection in immunocompromised patients, posing a major risk for illness and death (1).Treatment involves immune function optimization and prolonged use of combinations of species-specific antimycobacterial drugs but is often complicated by the intrinsic or acquired drug resistance of NTM (2) and adverse effects of the drug combinations; treatment failure is common.Therefore, there is considerable interest in the use of novel drugs (3).Bedaquiline, a novel, oral, diarylquinolone antimycobacterial drug, is used in treatment of infections with multidrug-resistant Mycobacterium tuberculosis (4).However, its role in treatment of disseminated NTM infections remains unclear.We report the successful use of bedaquiline in treatment for 2 HIV-infected patients in London, UK, who had disseminated NTM infections. The StudyCase-patient 1 was a 54-year-old HIV-infected man who had colonic perforation secondary to rectal trauma.He underwent an emergency Hartmann's procedure and showed an uncomplicated immediate recovery.Two months later, he showed development of fevers, breathlessness, and a purulent exudate at the abdominal wound site, which did not improve after receiving antimicrobial drug therapy.Imaging showed pleural effusions and perihepatic collections; mycobacterial liquid culture of effusions, collections, and wound exudate contained M. abscessus, presumed secondary to fecal abdominal cavity contamination.Mycobacterial blood cultures were negative.At diagnosis of his disseminated NTM infection, HIV viral load was undetectable (CD4 count >900 cells/µL).Empirical treatment was begun and then refined after speciation as M. abscessus (Figure 1, panel A).Susceptibility testing subsequently demonstrated extensive drug resistance (Table 1).MIC estimations for bedaquiline showed in vitro susceptibility (MIC <0.0625 mg/L).There was no information on Clinical and Laboratory Standards Institute/European Committee on Antimicrobial Susceptibility Testing for M. abscessus.The MIC breakpoint for this drug with M. tuberculosis was 0.25 mg/L (T.McHugh, University College London, pers.comm., 2020 Jun 29).Compassionate access to bedaquiline was obtained from Janssen-Cilag (https://www.janssen.com).Treatment was initiated (400 mg/d for 2 wks, followed by 200 mg 3×/wk), as per treatment for tuberculosis.Bedaquiline was well tolerated and treatment continued for a year; there was a brief interruption because of a delay in reapproval.During his treatment for NTM, the patient showed adverse effects caused by intravenous amikacin (1 g/d) and mild renal impairment.Therefore,