ArticlesTreatment of isoniazid-resistant tuberculosis with first-line drugs: a systematic review and meta-analysis
Introduction
Between 1994 and 2009, isoniazid resistance was detected in 45% of all strains causing active tuberculosis in eastern Europe, and 14% of all strains causing the disease in all other regions.1 In 2014, among all cases of tuberculosis, the average global frequency of isoniazid resistance without concurrent rifampicin resistance was 9·5% (95% CI 8·0–11·0). In new and previously treated cases, the global averages were 8·1% (6·5–9·7) and 14·0% (11·6–16·3), respectively.2 In a separate survey, 4·8% of all estimated incident tuberculosis cases were multidrug resistant3—suggesting that most cases of isoniazid-resistant tuberculosis are mono-drug or poly-drug resistant.1, 3
Recommendations for treatment of isoniazid-resistant tuberculosis are to use first line tuberculosis drugs. Specifically, WHO recommends rifampicin, ethambutol, and pyrazinamide for 9 months with the addition of a fluoroquinolone if the strain has concomitant resistance to ethambutol or pyrazinamide.4 The American Thoracic Society recommendations are similar: rifampicin, pyrazinamide, and ethambutol for 9–12 months; a fluoroquinolone “may be added”.5 In 2008, we did a systematic review of retreatment, and treatment of isoniazid resistance without multidrug resistance.6 We found no trials and only six cohorts in which WHO's recommended retreatment regimen was assessed, only nine trials focused on isoniazid resistance or retreatment cases, and no two trials made the same pair-wise comparison of regimens, precluding pooling.6 The last trial specifically of patients with isoniazid-resistant tuberculosis was published almost 20 years ago.7
We updated our previous review. Our objective was to review treatment outcomes with use of first-line drugs (including streptomycin) for patients with active pulmonary tuberculosis caused by strains resistant to isoniazid but not to rifampicin.
Section snippets
Search strategy and selection criteria
In our previous systematic review,6 which has already been reported in detail, we searched PubMed, Embase, and the Cochrane Library for articles published between Jan 1, 1948, and June 30, 2008. For this update, we searched the Cochrane database of systematic reviews and randomised trials, PubMed, Embase, and HealthSTAR (using Ovid) with the terms “Tuberculosis” AND “Treatment” or “Therapy” AND “INH” or “isoniazid resistance” (the major difference from the previous review is that in that one we
Results
Our updated search identified 294 titles, of which one trial and nine cohort studies were deemed eligible (figure 1; appendix). We added these newly identified articles to the 32 trials and ten cohorts identified for the previous review. The characteristics of the 33 trials7, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 and 19 cohort studies44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62
Discussion
Overall, failure, relapse, and acquired drug resistance were significantly more common in patients with pre-treatment isoniazid-resistant, rifampicin-susceptible tuberculosis than in those infected with fully drug-susceptible organisms when treated with standardised regimens of first-line tuberculosis drugs. Of particular importance is the finding that the frequency of failure, relapse, and acquired multidrug resistance with the widely used WHO-New regimen were 11% (95% CI 6–17), 10% (5–15),
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