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. 2018 Mar 6;18(1):112.
doi: 10.1186/s12879-018-3033-9.

Bacterial risk factors for treatment failure and relapse among patients with isoniazid resistant tuberculosis

Phan Vuong Khac Thai  1 , Dang Thi Minh Ha  1 , Nguyen Thi Hanh  2 , Jeremy Day  2 , Sarah Dunstan  2   3 , Nguyen Thi Quynh Nhu  2 , Vo Sy Kiet  2 , Nguyen Huu Lan  1 , Nguyen Huy Dung  1 , Nguyen Thi Ngoc Lan  1 , Nguyen Thuong Thuong  2 , Nguyen Ngoc Lan  1 , Phạm Thị Thúy Liễu  1 , Nguyễn Thị Hồng  1 , Đào Công Điệp  1 , Nguyễn Thị Kim Thanh  1 , Nguyễn Văn Hội  1 , Nguyễn Văn Nghĩa  1 , Trương Ngọc Đại  1 , Hoàng Quang Minh  1 , Nguyễn Văn Thơm  1 , Jeremy Farrar  2 , Maxine Caws  4   5   6
Affiliations

Bacterial risk factors for treatment failure and relapse among patients with isoniazid resistant tuberculosis

Phan Vuong Khac Thai et al. BMC Infect Dis. .

Abstract

Background: Drug resistant tuberculosis (TB) is increasing in prevalence worldwide. Treatment failure and relapse is known to be high for patients with isoniazid resistant TB treated with standard first line regimens. However, risk factors for unfavourable outcomes and the optimal treatment regimen for isoniazid resistant TB are unknown. This cohort study was conducted when Vietnam used the eight month first line treatment regimen and examined risk factors for failure/relapse among patients with isoniazid resistant TB.

Methods: Between December 2008 and June 2011 2090 consecutive HIV-negative adults (≥18 years of age) with new smear positive pulmonary TB presenting at participating district TB units in Ho Chi Minh City were recruited. Participants with isoniazid resistant TB identified by Microscopic Observation Drug Susceptibility (MODS) had extended follow-up for 2 years with mycobacterial culture to test for relapse. MGIT drug susceptibility testing confirmed 239 participants with isoniazid resistant, rifampicin susceptible TB. Bacterial and demographic factors were analysed for association with treatment failure and relapse.

Results: Using only routine programmatic sputum smear microscopy for assessment, (months 2, 5 and 8) 30/239 (12.6%) had an unfavourable outcome by WHO criteria. Thirty-nine patients were additionally detected with unfavourable outcomes during 2 year follow up, giving a total of 69/239 (28.9%) of isoniazid (INH) resistant cases with unfavourable outcome by 2 years of follow-up. Beijing lineage was the only factor significantly associated with unfavourable outcome among INH-resistant TB cases during 2 years of follow-up. (adjusted OR = 3.16 [1.54-6.47], P = 0.002).

Conclusion: One third of isoniazid resistant TB cases suffered failure/relapse within 2 years under the old eight month regimen. Over half of these cases were not identified by standard WHO recommended treatment monitoring. Intensified research on early identification and optimal regimens for isoniazid resistant TB is needed. Infection with Beijing genotype of TB is a significant risk factor for bacterial persistence on treatment resulting in failure/relapse within 2 years. The underlying mechanism of increased tolerance for standard drug regimens in Beijing genotype strains remains unknown.

Keywords: Isoniazid; Multidrug resistance; Resistance; Treatment; Tuberculosis.

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Institutional Research Board of Pham Ngoc Thach Hospital as the supervisory institution of the district TB Units (DTUs) in southern Vietnam, Ho Chi Minh City Health Services and the Oxford University Tropical Research Ethics Committee (Oxtrec 030–07). Written informed consent was obtained from all patients prior to screening for INH susceptibility and, if resistant by MODS testing, a second written informed consent was obtained for enrolment into the INH study.

Consent for publication

not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Map of geographical location of eight District TB Units in central Ho Chi Minh City participating in the study
See this image and copyright information in PMC

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