Abstract
BackgroundIsoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes.MethodsA prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Löwenstein-Jensen (LJ) media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment.ResultsOf 1292 patients enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance was present in 24 (2%) patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1–4.1), and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9–47.8). Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01) and death (4/85, 5%, p<0.02). Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%, p<0.01).ConclusionA high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes.
Highlights
Tuberculosis (TB) has been one of the leading infectious agents worldwide throughout the past century, but drug resistance has emerged more recently as a major concern [1,2,3,4]
In the multivariate logistic regression model, isoniazid monoresistance was associated with illicit drug use (adjusted odds ratio = 2.10; 95% confidence interval (CI): 1.1–4.1), and rifampicin mono-resistance was associated with HIV infection
A high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden
Summary
Tuberculosis (TB) has been one of the leading infectious agents worldwide throughout the past century, but drug resistance has emerged more recently as a major concern [1,2,3,4]. The prevalence of mono-resistance to isoniazid, one of the most potent first-line anti-TB agents, has been reported in ranges from 4–12% for all TB cases with a global average of 8.1% for new TB cases [3,4,5]. There is less evidence for rifampicin mono-resistance because it is less studied, but prevalences under 1% for new TB cases have been reported within Europe in 2010 and 3.2% in Zambia [6, 7]. Studies have noted previous TB treatment as isoniazid mono-resistant risk factors [14, 15]. Due to few rifampicin mono-resistant patients, risk factors have not been well characterized; but prior studies have identified prior TB treatment and HIV co-infection [1, 16, 17]. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes
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