December 05, 2016
2 min read

First-line drugs result in suboptimal outcomes for patients with isoniazid-resistant TB

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Treating patients with isoniazid-resistant tuberculosis with first-line drugs results in higher levels of failure, relapse and acquired drug resistance than among those infected with drug-susceptible strains of tuberculosis, according to a systematic review and meta-analysis published in Lancet Infectious Diseases.

In 2014, nearly 10% of cases of active TB worldwide were caused by strains resistant to isoniazid but not rifampicin. WHO currently recommends rifampicin, ethambutol and pyrazinamide for 9 months to treat isoniazid-resistant strains, though the effectiveness of the regimen has not been thoroughly evaluated.  In this study, researchers updated a systematic review published in 2008 to review outcomes for this course of treatment.

Dick Menzies, MD, MSc, director of the respiratory epidemiology and clinical research unit at the Montreal Chest Institute, McGill University, and colleagues searched the Cochrane databases of systematic reviews and randomized trials, PubMed, Embase and HealthStar and identified 19 cohort studies and 33 trials published through March 2015, for review. From those studies, they analyzed treatment outcomes for 3,744 patients with bacteriologically confirmed isoniazid-resistant TB as well as 19,012 patients with drug-sensitive strains.

In their analysis, Menzies and colleagues found that the pooled rates of failure or relapse, or both, with all drug regimens was 15% (95% CI, 12-18) among patients with isoniazid-resistant TB, compared with 4% (95% CI, 3-5) among patients with drug-sensitive TB. The pooled rate of acquired drug resistance for isoniazid-resistant strains was 3.6% (95% CI, 2-5), compared with 0.6% (95% CI, 0.3-0.9) for drug-sensitive strains. Furthermore, 96% (95% CI, 93-99) of patients with initial isoniazid-resistant TB had acquired multidrug-resistant disease.

The WHO standard regimen for new patients resulted in an 11% (95% CI, 6-17) rate of treatment failure among patients with isoniazid-resistant TB vs. 2% (95% CI, 1-3) for patients with drug-sensitive strains (P < .0001). Relapse rates were 10% (95% CI, 5-15) for isoniazid-resistant strains vs. 5% (95% CI, 2-7) for drug-sensitive strains, and rates of acquired multidrug resistance were 8% (95% CI, 2-8) for isoniazid-resistant strains vs. 1% (95% CI, 0-2) for drug-sensitive strains (P < .0001 for both comparisons).

The WHO standard regimen for previously treated patients resulted in treatment failure, relapse and acquired multidrug resistance for 6% (95% CI, 2-10), 5% (95% CI, 2-8) and 3% (95% CI, 0-6) of patients with isoniazid-resistant TB, respectively. For patients with drug-sensitive disease, the same standard regimen resulted in failure, relapse and acquired multidrug resistance rates of 1% (95% CI, 0-2), 5% (95% CI, 4-7), and 0.3% (95% CI, 0-0.6), respectively.

Menzies and colleagues noted that these findings have important implications for countries with high rates of initial isoniazid resistance.

“Treatment with the standardized regimen recommended for new patients without drug-susceptibility testing could contribute substantially to the epidemic of multidrug-resistant tuberculosis,” they concluded.

In a related editorial, Lia D'Ambrosio, with the WHO Collaborating Center for TB and Lung Disease, and colleagues noted that Gegia and colleagues’ findings are timely and important. “This study should prompt clinicians to establish fully the drug-resistance pattern before prescribing an anti-tuberculosis regimen, especially in places where the prevalence of resistance to isoniazid is high,” they wrote. – by Sarah Kennedy

Disclosure: The researchers report no relevant financial disclosures.