Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020

Abstract

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...

Tuberculosis — United States, 2019

“…Concerns regarding the potential adverse effects of LTBI treatment have been an important barrier to LTBI screening and treatment in the past ( 9 ). To address these concerns, CDC and the National Tuberculosis Controllers Association have released new guidelines that recommend short-course, rifamycin-based regimens, which have less toxicity and better completion rates than does isoniazid monotherapy ( 10 ). CDC will continue to support and encourage public health partners and primary care providers to increase adoption of LTBI testing and treatment guidelines to accelerate progress toward TB elimination.…”

Interferon gamma release assay tests are associated with persistence and completion of latent tuberculosis infection treatment in the United States: Evidence from commercial insurance data

“…We used a previously published algorithm [9] to identify persons initiating a 6 to 9 month daily dose LTBI treatment regimen of isoniazid between July 2011 and March 2014. Such regimens have been the most commonly used treatments for LTBI [10,[33][34][35]. In accordance with the algorithm logic, we required that the data be available to determine if LTBI treatment was completed.…”

Rifampin-divalproex drug-drug interaction in an adult patient: A case report

“…In the currently described case report, switching the patient to a 6- to 9-month isoniazid regimen was undesirable given the preference to quickly initiate biological therapy for RA. 1 The baseline steady-state valproic acid trough concentration was 99.8 mcg/mL with mood stability. Over the 4-month course of rifampin, DVP was increased in both dose (75% increase) and frequency (2 to 3 times daily) to maintain clinical stability by treating breakthrough hypomanic symptoms.…”

“…Short-course rifamycin-based regimens are preferred over a longer course of isoniazid monotherapy due to the lower toxicity risk and higher treatment completion rates. 1 Rifampin is a strong inducer of several drug-metabolizing enzymes, yielding many drug interactions. 2 The suspected mechanism of the interaction between rifampin and divalproex (DVP) is rifampin-mediated induction of DVP metabolism through induction of uridine diphosphate glucuronosyltransferase (UGT) enzymes, CYP2C9, and CYP2C19.…”