Dataset Information

Low Frequency of Acquired Isoniazid and Rifampicin Resistance in Rifampicin-Susceptible Pulmonary Tuberculosis in a Setting of High HIV-1 Infection and Tuberculosis Coprevalence.

ABSTRACT:

Background

We estimated the incidence of acquired isoniazid and rifampicin resistance in rifampicin-susceptible tuberculosis in a setting of high human immunodeficiency virus type 1 (HIV-1) infection and tuberculosis coprevalence.

Methods

GeneXpert MTB/RIF-confirmed patients with rifampicin-susceptible tuberculosis were recruited at antituberculosis treatment initiation in Khayelitsha, South Africa. Liquid culture and adherence assessment were performed at 2 and 5-6 months. MTBDRplus was performed on mycobacteria-positive cultures to ascertain acquired drug resistance (ADR). Spoligotyping and whole-genome sequencing were performed to ascertain homogeneity between baseline isolates and isolates with ADR. Baseline isolates were retrospectively tested for isoniazid monoresistance. An electronic database review was performed to ascertain tuberculosis recurrences.

Results

A total of 306 participants (62% with HIV-1 coinfection, of whom 71% received antiretroviral therapy) were recruited. Ascertainment of outcomes was complete for 284 participants. Five acquired a resistant Mycobacterium tuberculosis strain during or subsequent to treatment. One strain was confirmed to have ADR, 2 were confirmed as causing exogenous reinfection, and 2 were unrecoverable for genotyping. Incident ADR was estimated to have ranged from 0.3% (95% confidence interval [CI], .1%-1.9%; 1 of 284 participants) to 1% (95% CI, .2%-3%; 3 of 284 participants). Seventeen of 279 baseline isolates (6.1%; 95% CI, 3.6%-9.6%) had isoniazid monoresistance (13 of 17 had an inhA promoter mutation), but 0 of 17 had amplified resistance.

Conclusions

Treatment with standardized antituberculosis regimens dosed daily throughout, high uptake of antiretroviral therapy, and low prevalence of isoniazid monoresistance were associated with a low frequency of ADR.

SUBMITTER: Rockwood N

PROVIDER: S-EPMC5815623 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Low Frequency of Acquired Isoniazid and Rifampicin Resistance in Rifampicin-Susceptible Pulmonary Tuberculosis in a Setting of High HIV-1 Infection and Tuberculosis Coprevalence.

Rockwood Neesha N Sirgel Frederick F Streicher Elizabeth E Warren Robin R Meintjes Graeme G Wilkinson Robert J RJ

The Journal of infectious diseases 20170901 6

<h4>Background</h4>We estimated the incidence of acquired isoniazid and rifampicin resistance in rifampicin-susceptible tuberculosis in a setting of high human immunodeficiency virus type 1 (HIV-1) infection and tuberculosis coprevalence.<h4>Methods</h4>GeneXpert MTB/RIF-confirmed patients with rifampicin-susceptible tuberculosis were recruited at antituberculosis treatment initiation in Khayelitsha, South Africa. Liquid culture and adherence assessment were performed at 2 and 5-6 months. MTBDRp ...[more]

PMID: 28934422

Similar Datasets

Project description:BACKGROUND: Rapid new diagnostic methods (including Xpert MTB/RIF assay) use rifampicin resistance as a surrogate marker for multidrug resistant tuberculosis. Patients infected with rifampicin susceptible strains are prescribed first line anti-tuberculosis therapy. The roll out of such methods raises a concern that strains with resistance to other first line anti-tuberculosis drugs including isoniazid will be missed and inappropriate treatment given. To evaluate implications of using such methods review of resistance data from high burden settings such as ours is essential. OBJECTIVE: To determine resistance to first line anti-tuberculosis drugs amongst rifampicin susceptible pulmonary Mycobacterium tuberculosis (MTB) isolates from Pakistan. MATERIALS AND METHODS: Data of pulmonary Mycobacterium tuberculosis strains isolated in Aga Khan University Hospital (AKUH) laboratory (2009-2011) was retrospectively analyzed. Antimicrobial susceptibility profile of rifampicin susceptible isolates was evaluated for resistance to isoniazid, pyrazinamide, ethambutol, and streptomycin. RESULTS: Pulmonary specimens submitted to AKUH from 2009 to 2011 yielded 7738 strains of Mycobacterium tuberculosis. These included 54% (n 4183) rifampicin susceptible and 46% (n: 3555) rifampicin resistant strains. Analysis of rifampicin susceptible strains showed resistance to at least one of the first line drugs in 27% (n:1133) of isolates. Overall isoniazid resistance was 15.5% (n: 649), with an isoniazid mono-resistance rate of 4% (n: 174). Combined resistance to isoniazid, pyrazinamide, and ethambutol was noted in 1% (n: 40), while resistance to isoniazid, pyrazinamide, ethambutol, and streptomycin was observed in 1.7% (n: 70) of strains. CONCLUSIONS: Our data suggests that techniques (including Xpert MTB/RIF assay) relying on rifampicin susceptibility as an indicator for initiating first line therapy will not detect patients infected with MTB strains resistant to other first line drugs (including isoniazid). The roll out of these techniques must therefore be accompanied by strict monitoring ensuring early resistance detection to increase chances of improved patient outcomes.

Project description:BackgroundIntrapulmonary pharmacokinetics may better explain response to tuberculosis (TB) treatment than plasma pharmacokinetics. We explored these relationships by modeling bacillary clearance in sputum in adult patients on first-line treatment in Malawi.MethodsBacillary elimination rates (BER) were estimated using linear mixed-effects modelling of serial time-to-positivity in mycobacterial growth indicator tubes for sputum collected during the intensive phase of treatment (weeks 0-8) for microbiologically confirmed TB. Population pharmacokinetic models used plasma and intrapulmonary drug levels at 8 and 16 weeks. Pharmacokinetic-pharmacodynamic relationships were investigated using individual-level measures of drug exposure (area-under-the-concentration-time-curve [AUC] and Cmax) for rifampicin, isoniazid, pyrazinamide, and ethambutol, in plasma, epithelial lining fluid, and alveolar cells as covariates in the bacillary elimination models.ResultsAmong 157 participants (58% human immunodeficiency virus [HIV] coinfected), drug exposure in plasma or alveolar cells was not associated with sputum bacillary clearance. Higher peak concentrations (Cmax) or exposure (AUC) to rifampicin or isoniazid in epithelial lining fluid was associated with more rapid bacillary elimination and shorter time to sputum negativity. More extensive disease on baseline chest radiograph was associated with slower bacillary elimination. Clinical outcome was captured in 133 participants, with 15 (11%) unfavorable outcomes recorded (recurrent TB, failed treatment, or death). No relationship between BER and late clinical outcome was identified.ConclusionsGreater intrapulmonary drug exposure to rifampicin or isoniazid in the epithelial lining fluid was associated with more rapid bacillary clearance. Higher doses of rifampicin and isoniazid may result in sustained high intrapulmonary drug exposure, rapid bacillary clearance, shorter treatment duration and better treatment outcomes.

Dataset Information

Low Frequency of Acquired Isoniazid and Rifampicin Resistance in Rifampicin-Susceptible Pulmonary Tuberculosis in a Setting of High HIV-1 Infection and Tuberculosis Coprevalence.

Background

Methods

Results

Conclusions

Publications

Low Frequency of Acquired Isoniazid and Rifampicin Resistance in Rifampicin-Susceptible Pulmonary Tuberculosis in a Setting of High HIV-1 Infection and Tuberculosis Coprevalence.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets