Updates in the Treatment of Active and Latent Tuberculosis

Michelle K. Haas, MD; Robert W. Belknap, MD

Disclosures

Semin Respir Crit Care Med. 2018;39(3):297-309. 

In This Article

Abstract and Introduction

Abstract

First-line therapy for active tuberculosis (TB) has remained unchanged for nearly 40 years. Isoniazid, rifampin, pyrazinamide, and ethambutol for the initial two-month phase followed by isoniazid and rifampin for 4 to 7 months is standard treatment for people at low risk for drug-resistant disease. Directly-observed therapy (DOT) remains the standard of care for pulmonary TB. Virtual treatment monitoring using digital technologies is becoming more common as a way to provide a more patient-centered approach to care. Attempts to shorten treatment duration have been unsuccessful based on recent clinical trials evaluating the role of fluoroquinolones. Treatment-shortening trials using higher doses of rifamycins are currently underway. Recently approved medications for TB treatment are recommended only for drug-resistant disease, but novel agents in varying stages of development are being evaluated. Rifamycin-based regimens for latent TB infection (LTBI) have been successful in preventing progression to TB disease. Once-weekly isoniazid and rifapentine for 12 weeks by DOT was shown to be safe and effective compared with 9 months of isoniazid. The same regimen was shown to have acceptable treatment completion when given self-administered. Newer studies are investigating even shorter LTBI treatment with durations of less than 2 months. Treatment of LTBI in people likely infected with multidrug resistant TB is very limited, but one observational study found that fluoroquinolones appear to be effective. The first randomized trials for treating LTBI in contacts to MDR-TB are currently enrolling.

Introduction

Tuberculosis (TB) is the leading cause of death from an infection globally, killing an estimated 1.7 million people in 2016.[1] Despite its prevalence, advances in the diagnosis and treatment of TB have moved at a glacial pace. Operational changes including the scale up of TB treatment, improved access to high-quality medications, and increasing use of rapid diagnostics have facilitated modest improvements in global TB morbidity and mortality.[1] Determining the cascade of care[2] for people with active TB has allowed for the identification of additional gaps from diagnosis to completion of treatment, necessitating the development of strategies to mitigate losses at each stage.[3–5] Ensuring that all people at risk for active TB have access to high-quality diagnostic testing, are rapidly diagnosed, and retained in care is essential to maximize their chances of being cured, prevent future relapse, and reduce the risk of ongoing transmission.

The current standard treatment for active TB was first established in 1979 after the publication of a trial demonstrating the efficacy of a "short-course" regimen lasting 6 months.[6] Subsequent trials have identified risk factors for relapse and evaluated whether certain subgroups could be successfully cured with less than 6 months.[7,8] Other studies have evaluated different combinations of medications to determine if treatment can be shortened further and whether it can be administered intermittently.[9–13] Ongoing research continues to seek shorter, effective regimens for both drug-susceptible and drug-resistant TB.[14,15] New technologies are also being used to support adherence and treatment completion which appear promising as alternatives to in-person DOT.[16,17]

Advances in the treatment of latent TB infection (LTBI) have also occurred. The World Health Organization (WHO) released guidance regarding LTBI treatment in low and middle TB burden settings in 2015 which included an emphasis on short-course regimens lasting 3 to 4 months.[18] The 2018 update of the WHO LTBI guideline highlights the increasing emphasis on TB prevention globally.[19] Current trials are evaluating LTBI regimens of 4 to 6 weeks of duration which, if safe and effective, could improve LTBI treatment acceptance and completion.

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