Ahmed, Amina

Abstract Introduction Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis (TB). Pediatric data comparing the 2 IGRAs in the United States are very limited. We compared the performance of the 2 IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cutoff values. Methods Children aged 0-15 years with both T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests were identified from a US multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar’s Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results. Results Among 3793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, P < .001). This difference was noted for all age categories except <2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cutoff of 0.35 IU/mL. Conclusions In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cutoffs.

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.