Implementation of Bedaquiline, Pretomanid, and Linezolid in the United States: Experience Using a Novel All-Oral Treatment Regimen for Treatment of Rifampin-Resistant or Rifampin-Intolerant Tuberculosis Disease.

BACKGROUND: Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. METHODS: Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. RESULTS: Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. CONCLUSIONS: BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.

Outbreak of tuberculosis among Guatemalan immigrants in rural Minnesota, 2008.

OBJECTIVES: We described the outbreak investigation and control measures after the Minnesota Department of Health identified a cluster of tuberculosis (TB) cases among Guatemalan immigrants within three rural Minnesota counties in August 2008. METHODS: TB cases were diagnosed by tuberculin skin test followed by chest radiography and sputum testing for Mycobacterium tuberculosis (M. tuberculosis). We reviewed medical records, interviewed patients, and completed a contact investigation for each infectious case. We used isolate genotyping to confirm epidemiologic links between cases. RESULTS: The index case was a six-month-old U.S.-born male with Guatemalan parents. Although he experienced four months of cough and fever, TB was not considered at two medical visits but was diagnosed upon hospitalization in May 2008. The presumed source of infection was a Guatemalan male aged 25 years who sang in a band that practiced in the infant's house and whose pulmonary TB was diagnosed at hospitalization in June 2008, despite his having sought medical attention for symptoms seven months earlier. Among the 16 identified TB cases, 14 were outbreak-related. Three genetically distinct M. tuberculosis strains circulated. Of 150 contacts of the singer, 62 (41%) had latent TB infection and 13 (9%), including 10 children, had TB disease. CONCLUSIONS: In this outbreak, delayed diagnoses contributed to M. tuberculosis transmission. Isolate genotyping corroborated the social links between outbreak-related patients. More timely diagnosis of TB among immigrants and their children can prevent TB transmission among communities in rural, low-incidence areas that might have limited resources for contact investigations.