Tuberculosis treatment adherence in the era of COVID-19.

BACKGROUND: In-person directly observed therapy (DOT) is commonly used for tuberculosis (TB) treatment monitoring in the US, with increasing usage of video-DOT (vDOT). We evaluated the impact of COVID-19 on TB treatment adherence, and utilization and effectiveness of vDOT. METHODS: We abstracted routinely collected data on individuals treated for TB disease in Baltimore, Maryland between April 2019 and April 2021. Our primary outcomes were to assess vDOT utilization and treatment adherence, defined as the proportion of prescribed doses (7 days/week) verified by observation (in-person versus video-DOT), comparing individuals in the pre-COVID and COVID (April 2020) periods. RESULTS: Among 52 individuals with TB disease, 24 (46%) received treatment during the COVID-19 pandemic. vDOT utilization significantly increased in the COVID period (18/24[75%]) compared to pre-COVID (12/28[43%], p = 0.02). Overall, median verified adherence was similar pre-COVID and COVID periods (65% versus 68%, respectively, p = 0.96). Adherence was significantly higher overall when using vDOT (median 86% [IQR 70-98%]) compared to DOT (median 59% [IQR 55-64%], p < 0.01); this improved adherence with vDOT was evident in both the pre-COVID (median 98% vs. 58%, p < 0.01) and COVID period (median 80% vs. 62%, p = 0.01). CONCLUSION: vDOT utilization increased during the COVID period and was more effective than in-person DOT at verifying ingestion of prescribed treatment.

The health-system benefits and cost-effectiveness of using Mycobacterium tuberculosis direct nucleic acid amplification testing to diagnose tuberculosis disease in the United States.

BACKGROUND: The utility of Mycobacterium tuberculosis direct nucleic acid amplification testing (MTD) for pulmonary tuberculosis disease diagnosis in the United States has not been well described. METHODS: We analyzed a retrospective cohort of reported patients with suspected active pulmonary tuberculosis in 2008-2010 from Georgia, Hawaii, Maryland, and Massachusetts to assess MTD use, effectiveness, health-system benefits, and cost-effectiveness. RESULTS: Among 2140 patients in whom pulmonary tuberculosis was suspected, 799 (37%) were M. tuberculosis-culture-positive. Eighty percent (680/848) of patients having acid-fast-bacilli-smear-positive specimens had MTD performed; MTD positive-predictive value (PPV) was 98% and negative-predictive value (NPV) was 94%. Nineteen percent (240/1292) of patients having smear-negative specimens had MTD; MTD PPV was 90% and NPV was 88%. Among patients suspected of tuberculosis but not having MTD, smear PPV for lab-confirmed tuberculosis was 77% and NPV 78%. Compared with no MTD, MTD significantly decreased time to diagnosis in patients with smear-positive/MTD-positive specimens, decreased respiratory isolation for patients having smear-positive/MTD-negative/culture-negative specimens, decreased outpatient days of unnecessary tuberculosis medications, and reduced resources expended on contact investigation. While MTD generally cost more than no MTD, incremental cost savings occurred in patients with human immunodeficiency virus (HIV) or homelessness to diagnose or to exclude tuberculosis, and in patients with substance abuse having smear-negative specimens to exclude tuberculosis. CONCLUSIONS: MTD improved diagnostic accuracy and timeliness and reduced unnecessary respiratory isolation, treatment, and contact investigations. It was cost saving in patients with HIV, homelessness, or substance abuse, but not in others.

Tuberculosis treatment adherence in the era of COVID-19.

BACKGROUND In-person directly observed therapy (DOT) is commonly used for tuberculosis (TB) treatment monitoring in the US, with increasing usage of video-DOT (vDOT). We evaluated the impact of COVID-19 on TB treatment adherence, and utilization and effectiveness of vDOT. METHODS We abstracted routinely collected data on individuals treated for TB disease in Baltimore, Maryland between April 2019 and April 2021. Our primary outcomes were to assess vDOT utilization and treatment adherence, defined as the proportion of prescribed doses (7 days/week) verified by observation (in-person versus video-DOT), comparing individuals in the pre- and post-COVID (April 2020) periods. RESULTS Among 52 individuals with TB disease, 24 (46%) received treatment during the COVID-19 pandemic. vDOT utilization significantly increased post-COVID (18/24[75%]) compared to pre-COVID (12/28[43%], p=0.02). Overall, median verified adherence was similar pre- and post-COVID (65% versus 68%, respectively, p=0.96). Adherence was significantly higher overall when using vDOT (median 86% [IQR 70-98%]) compared to DOT (median 59% [IQR 55%-64%], p<0.01); this improved adherence with vDOT was evident in both the pre-COVID (median 98% vs 58%, p<0.01) and post-COVID period (median 80% vs 62%, p=0.01). CONCLUSION vDOT utilization increased post-COVID and was more effective than in-person DOT at verifying ingestion of prescribed treatment.

Programmatic Adoption and Implementation of Video-Observed Therapy in Minnesota: Prospective Observational Cohort Study.

BACKGROUND: In-person directly observed therapy (DOT) is standard of care for tuberculosis (TB) treatment adherence monitoring in the US, with increasing use of video-DOT (vDOT). In Minneapolis, vDOT became available in 2019. OBJECTIVE: In this paper, we aimed to evaluate the use and effectiveness of vDOT in a program setting, including comparison of verified adherence among those receiving vDOT and in-person DOT. We also sought to understand the impact of COVID-19 on TB treatment adherence and technology adoption. METHODS: We abstracted routinely collected data on individuals receiving therapy for TB in Minneapolis, MN, between September 2019 and June 2021. Our primary outcomes were to assess vDOT use and treatment adherence, defined as the proportion of prescribed doses (7 days per week) verified by observation (in person versus video-DOT), and to compare individuals receiving therapy in the pre-COVID-19 (before March 2020), and post-COVID-19 (after March 2020) periods; within the post-COVID-19 period, we evaluated early COVID-19 (March-August 2020), and intra-COVID-19 (after August 2020) periods. RESULTS: Among 49 patients with TB (mean age 41, SD 19; n=27, 55% female and n=47, 96% non-US born), 18 (36.7%) received treatment during the post-COVID-19 period. Overall, verified adherence (proportion of observed doses) was significantly higher when using vDOT (mean 81%, SD 17.4) compared to in-person DOT (mean 54.5%, SD 10.9; P=.001). The adoption of vDOT increased significantly from 35% (11/31) of patients with TB in the pre-COVID-19 period to 67% (12/18) in the post-COVID-19 period (P=.04). Consequently, overall verified (ie, observed) adherence among all patients with TB in the clinic improved across the study periods (56%, 67%, and 79%, P=.001 for the pre-, early, and intra-COVID-19 periods, respectively). CONCLUSIONS: vDOT use increased after the COVID-19 period, was more effective than in-person DOT at verifying ingestion of prescribed treatment, and led to overall increased verified adherence in the clinic despite the onset of the COVID-19 pandemic.

Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis.

RATIONALE: Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data regarding its activity in humans are limited. OBJECTIVES: Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB. METHODS: Adults with sputum smear-positive pulmonary TB were randomly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo, or isoniazid 300 mg plus moxifloxacin placebo, administered 5 days/week for 8 weeks, in addition to rifampin, pyrazinamide, and ethambutol. All doses were directly observed. Sputum was collected for culture every 2 weeks. The primary outcome was negative sputum culture at completion of 8 weeks of treatment. MEASUREMENTS AND MAIN RESULTS: Of 433 participants enrolled, 328 were eligible for the primary efficacy analysis. Of these, 35 (11%) were HIV positive, 248 (76%) had cavitation on baseline chest radiograph, and 213 (65%) were enrolled at African sites. Negative cultures at Week 8 were observed in 90/164 (54.9%) participants in the isoniazid arm, and 99/164 (60.4%) in the moxifloxacin arm (P = 0.37). In multivariate analysis, cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity. The proportion of participants who discontinued assigned treatment was 31/214 (14.5%) for the moxifloxacin group versus 22/205 (10.7%) for the isoniazid group (RR, 1.35; 95% CI, 0.81, 2.25). CONCLUSIONS: Substitution of moxifloxacin for isoniazid resulted in a small but statistically nonsignificant increase in Week-8 culture negativity.

Use of the amplified mycobacterium tuberculosis direct test in a public health laboratory: test performance and impact on clinical care.

BACKGROUND: The Amplified Mycobacterium tuberculosis Direct Test (MTD; Gen-Probe; San Diego, CA) is a nucleic-acid amplification test for rapid pulmonary tuberculosis (PTB) diagnosis. In a routine public health setting, test accuracy and impact on clinical decisions are unknown. METHODS: Retrospectively, we evaluated MTD accuracy and impact on clinical decisions in a public health setting. To estimate MTD accuracy, mycobacterial culture was used as the "gold standard." To evaluate MTD impact on clinical decisions, concordance of clinician presumptive diagnosis (at time of MTD and smear availability) and definitive diagnosis, and duration of nonindicated tuberculosis therapy were determined for smear-positive PTB suspects in a period of MTD availability (MTD group) and a prior period of MTD nonavailability (non-MTD group). RESULTS: A total of 1,151 respiratory specimens from 638 PTB suspects were analyzed. MTD sensitivity, specificity, positive predictive value, and negative predictive value were 91.7%, 98.7%, 96.7%, and 96.5% overall, respectively; and 98.7%, 97.8%, 98.7%, and 97.8% for smear-positive patients; and 62.2%, 98.9%, 85.2%, and 96.1% for smear-negative patients. In the MTD group, concordance between definitive and clinician presumptive diagnoses was 78% (95% confidence interval [CI], 64 to 88%), similar to that for the non-MTD group (79%; 95% CI, 68.4 to 89.6%). However, concordance between definitive diagnosis and the MTD test was 98% (95% CI, 94.1 to 100%). Median duration of nonindicated tuberculosis treatment was 6 days for the MTD group vs 31 days for the non-MTD group (p = 0.002). CONCLUSION: In this public health setting, MTD was accurate and rapidly detected more than half of the smear-negative PTB cases. For smear-positive PTB suspects, MTD had excellent concordance with definitive diagnosis, but clinicians often inappropriately initiated TB therapy despite a negative MTD result.

Risk factors for relapse and acquired rifamycin resistance after directly observed tuberculosis treatment: a comparison by HIV serostatus and rifamycin use.

We sought to determine the risk of acquired rifamycin resistant (ARR) tuberculosis associated with rifampin- versus rifabutin-based directly observed therapy and to assess the risk factors for relapse of tuberculosis. This observational cohort study included patients with culture-confirmed rifamycin-susceptible tuberculosis reported to the Baltimore City Health Department (Baltimore, MD) during the period of January 1993 through December 2001. Of the 407 patients, 108 (27%) were human immunodeficiency virus (HIV) seropositive, 161 (40%) were HIV seronegative, and 138 (34%) had an unknown serostatus. Three (2.8%) of 108 HIV-seropositive persons had ARR tuberculosis, compared with 0 of 299 persons with negative or unknown HIV serostatus (P=.02). Among HIV-seropositive patients, 3 (3.7%) of 81 who were treated with rifampin and 0 of 27 who were treated with rifabutin had ARR tuberculosis (P=.57). Among HIV-seropositive patients, the only risk factor for recurrent tuberculosis was a low median initial CD4+ T lymphocyte count (51 vs. 138 cells/mm3; P=.02). The median CD4+ T lymphocyte count among patients with ARR tuberculosis was 51 cells/mm3. ARR tuberculosis can occur with rifampin-based regimens, but in this study, the risk was not significantly higher than that for a rifabutin-based regimen.