Abstract
Introduction
Traditionally, single critical concentrations of drugs are utilized for Mycobacterium tuberculosis (Mtb) drug susceptibility testing (DST); however, the level of drug resistance can impact treatment choices and outcomes. Mutations at the katG gene are the major genetic mutations in multidrug resistant (MDR) Mtb and usually associated with high level resistance. We assessed the minimum inhibitory concentrations (MICs) of MDR or rifampin resistant (RR) and isoniazid (INH) resistant Mtb isolates to determine the quantification of drug resistance among key anti-tuberculosis drugs.
Methods
The study was conducted on stored Mtb isolates collected as part of a national drug resistance survey in Ethiopia. MIC values were determined using Sensititre™ MYCOTB plates. A line probe assay (MTBDRplus) was also performed to identify genetic determinants of resistance for all isolates.
Results
MIC testing was performed on 74 Mtb isolates including 46 MDR, 2 RR and 26 INH phenotypically resistant isolates as determined by the Löwenstein Jensen (LJ) method. Four (15%) INH resistant Mtb isolates were detected as borderline rifampin resistance (MIC = 1 μg/ml) using MYCOTB MIC plates and no rifampin resistance mutations were detected by LPA. Among the 48 MDR/RR TB cases, 9 (19%) were rifabutin susceptible (MIC was between ≤0.25 and 0.5μg/ml). Additionally, the MIC for isoniazid was between 2–4 μg/ml (moderate resistance) for 58% of MDR TB isolates and 95.6% (n = 25) of the isolates had mutations at the katG gene.
Conclusion
Our findings suggest a role for rifabutin treatment in a subset of RR TB patients, thus potentially preserving an important drug class. The high proportion of moderate level INH resistant among MDR Mtb isolates indicates the potential benefit of high dose isoniazid treatment in a high proportion of katG gene harboring MDR Mtb isolates.
Funder
Ethiopian Public Health Institute
National Institutes of Health Fogarty International Center
Publisher
Public Library of Science (PLoS)
Reference39 articles.
1. World Health Organization. Technical manual for drug susceptibility testing of medicines used in the treatment of tuberculosis. 2018.
2. World Health Organization. Implementing tuberculosis diagnostics: policy framework. 2015.
3. Application of quantitative second-line drug susceptibility testing at a multidrug-resistant tuberculosis hospital in Tanzania;SG Mpagama;BMC Infect Dis,2013
4. World Health Organization. Technical manual for drug susceptibility testing of medicines used in the treatment of tuberculosis. 2018.
5. The ins and outs of Mycobacterium tuberculosis drug susceptibility testing;EC Böttger;Clin Microbiol Infect,2011
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献