Seaworth, Barbara

Abstract 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.

AbstractTransmission of tuberculosis (TB) from a deceased solid organ donor to recipients can result in severe morbidity and mortality. In 2018, four solid organ transplant recipients residing in three states but sharing a common organ donor were diagnosed with TB disease. Two recipients were hospitalized and none died. The organ donor was born in a country with a high incidence of TB and experienced 8 weeks of headache and fever prior to death, but was not tested for TB during multiple hospitalizations or prior to organ procurement. TB isolates of two organ recipients and a close contact of the donor had identical TB genotypes and closely related whole‐genome sequencing results. Donors with risk factors for TB, in particular birth or residence in countries with a higher TB incidence, should be carefully evaluated for TB.

BACKGROUND: To examine the utilization of the Tuberculosis (TB) Centers of Excellence (COE) medical consultation service and evaluate how these services were being employed for patients in relation to multidrug-resistant TB (MDR-TB).METHODS: Medical consults are documented in a secure database. The database was queried for MDR-TB consultations over the period 1 January 2013–31 December 2017. All were analyzed to assess provider type, center, setting, year of call, and type of patient (pediatric vs. adult). A subgroup was randomly selected for thematic analysis.RESULTS: The centers received 1560 MDR-TB consultation requests over this period. Providers requesting consults were primarily physicians (55%). The majority of requests were from public health departments (64%) and for adult patients (80%). Four major topic areas emerged: 1) initial management of MDR-TB, 2) MDR-TB longitudinal treatment and complications, 3) management of persons exposed to MDR-TB, and 4) MDR-TB treatment completion.CONCLUSIONS: Analysis of these consultations provides insight into the type of expert advice about MDR-TB that was provided. These findings highlight topics where increased medical training and education may help to improve MDR-TB-related practices.