Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. Am J Respir Crit Care Med 161:S221‐S247, 2000). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States. The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta‐analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (eg with low‐quality evidence). These updated 2020 LTBI treatment guidelines include the NTCA‐ and CDC‐recommended treatment regimens that comprise three preferred rifamycin‐based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug‐resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al Treatment of drug‐resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93‐e142). The three rifamycin‐based preferred regimens are 3 months of once‐weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin‐based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin‐based regimens. In summary, sh...

Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.

Background Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation. Objective To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials.gov: NCT01582711) Setting Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa. Participants 1002 adults (aged ≥18 years) recommended for treatment of latent tuberculosis infection. Intervention Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring. Measurements The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication event–monitoring devices for self-administration. The main secondary outcome was adverse events. Results Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U.S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the direct-observation group, 74.0% (CI, 68.9% to 78.6%) in the self-administration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration–with–reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met noninferiority criteria. A few drug-related adverse events occurred and were similar across groups. Limitation Persons with latent tuberculosis infection enrolled in South Africa would not routinely be treated programmatically. Conclusion These results support using self-administered, once-weekly isoniazid and rifapentine to treat latent tuberculosis infection in the United States, and such treatment could be considered in similar settings when direct observation is not feasible. Primary Funding Source Centers for Disease Control and Prevention.