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Delayed Sputum Culture Conversion in Tuberculosis-Human Immunodeficiency Virus-Coinfected Patients With Low Isoniazid and Rifampicin Concentrations


Sekaggya-Wiltshire, Christine; von Braun, Amrei; Lamorde, Mohammed; Ledergerber, Bruno; Buzibye, Allan; Henning, Lars; Musaazi, Joseph; Gutteck, Ursula; Denti, Paolo; de Kock, Miné; Jetter, Alexander; Byakika-Kibwika, Pauline; Eberhard, Nadia; Matovu, Joshua; Joloba, Moses; Muller, Daniel; Manabe, Yukari C; Kamya, Moses R; Corti, Natascia; Kambugu, Andrew; Castelnuovo, Barbara; Fehr, Jan S (2018). Delayed Sputum Culture Conversion in Tuberculosis-Human Immunodeficiency Virus-Coinfected Patients With Low Isoniazid and Rifampicin Concentrations. Clinical Infectious Diseases, 67(5):708-716.

Abstract

Background The relationship between concentrations of anti-tuberculosis (TB) drugs, sputum conversion and treatment outcome remains unclear. We sought to determine the association between anti-TB drug concentrations and sputum conversion among TB-HIV co-infected patients on first-line anti-TB drugs. Method We enrolled HIV-infected Ugandans with pulmonary TB. Estimation of first-line anti-TB drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of TB treatment. Serial sputum cultures were performed at each visit. Time-to-event analysis was used to determine factors associated with sputum culture conversion. Results We enrolled 268 HIV-infected patients. Patients with low isoniazid and rifampicin concentrations were less likely to have sputum culture conversion before the end of TB treatment or by the end of follow-up; Hazard ratio (HR) 0.54: 95% confidence interval (CI): 0.37-0.77, P=0.001 and HR: 0.61, 95% CI: 0.44-0.85, P=0.003, respectively. Patients in the highest AUC quartile for rifampicin and isoniazid were approximately two times more likely to experience sputum conversion. Rifampicin and isoniazid concentrations below the thresholds and being in a weight band <55kg were both risk factors for unfavorable TB treatment outcomes. Only 4.4% of the participants had treatment failure. Conclusion Although low anti-TB drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications on TB transmission.

Abstract

Background The relationship between concentrations of anti-tuberculosis (TB) drugs, sputum conversion and treatment outcome remains unclear. We sought to determine the association between anti-TB drug concentrations and sputum conversion among TB-HIV co-infected patients on first-line anti-TB drugs. Method We enrolled HIV-infected Ugandans with pulmonary TB. Estimation of first-line anti-TB drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of TB treatment. Serial sputum cultures were performed at each visit. Time-to-event analysis was used to determine factors associated with sputum culture conversion. Results We enrolled 268 HIV-infected patients. Patients with low isoniazid and rifampicin concentrations were less likely to have sputum culture conversion before the end of TB treatment or by the end of follow-up; Hazard ratio (HR) 0.54: 95% confidence interval (CI): 0.37-0.77, P=0.001 and HR: 0.61, 95% CI: 0.44-0.85, P=0.003, respectively. Patients in the highest AUC quartile for rifampicin and isoniazid were approximately two times more likely to experience sputum conversion. Rifampicin and isoniazid concentrations below the thresholds and being in a weight band <55kg were both risk factors for unfavorable TB treatment outcomes. Only 4.4% of the participants had treatment failure. Conclusion Although low anti-TB drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications on TB transmission.

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Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Microbiology (medical), Infectious Diseases
Language:English
Date:3 March 2018
Deposited On:05 Jun 2018 13:39
Last Modified:24 Sep 2019 23:30
Publisher:Oxford University Press
ISSN:1058-4838
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/cid/ciy179
PubMed ID:29514175

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