Fluoroquinolone-resistant tuberculosis: implications in settings with weak healthcare systems

Jabeen, Kauser; Shakoor, Sadia; Hasan, Rumina

doi:10.1016/j.ijid.2015.01.006

Cited by 42 publications

(26 citation statements)

References 87 publications

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“…The rates in countries on other continents are lower, e.g., 4.1% in the United States and Canada (48) and 4.3% in MDR-TB patients in Russia (49). It has been hypothesized that resistance to other anti-TB drugs could potentially influence resistance to FQ (13).…”

Section: Figmentioning

confidence: 99%

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Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

et al. 2016

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h Fluoroquinolones (FQs) are broad-spectrum antibiotics recommended for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients. FQ resistance, caused by mutations in the gyrA and gyrB genes of Mycobacterium tuberculosis, is increasingly reported worldwide; however, information on mutations occurring in strains from the Indian subcontinent is scarce. Hence, in this study, we aimed to characterize mutations in the gyrA and gyrB genes of acid-fast bacillus (AFB) smear-positive sediments or of M. tuberculosis isolates from AFB smear-negative samples from patients in India suspected of having MDR-TB. A total of 152 samples from patients suspected of having MDR-TB were included in the study. One hundred forty-six strains detected in these samples were characterized by sequencing of the gyrA and gyrB genes. The extracted DNA was subjected to successive amplifications using a nested PCR protocol, followed by sequencing. A total of 27 mutations were observed in the gyrA genes of 25 strains, while no mutations were observed in the gyrB genes. The most common mutations occurred at amino acid position 94 (13/27 [48.1%]); of these, the D94G mutation was the most prevalent. The gyrA mutations were significantly associated with patients with rifampin (RIF)-resistant TB. Heterozygosity was seen in 4/27 (14.8%) mutations, suggesting the occurrence of mixed populations with different antimicrobial susceptibilities. A high rate of FQ-resistant mutations (17.1%) was obtained among the isolates of TB patients suspected of having MDR-TB. These observations emphasize the need for accurate and rapid molecular tests for the detection of FQ-resistant mutations at the time of MDR-TB diagnosis.T reatment of multidrug-resistant tuberculosis (MDR-TB) patients, with strains resistant to rifampin (RIF) and isoniazid (INH), is further complicated by the presence of fluoroquinolone (FQ) resistance, due to prolonged, limited, and expensive treatment options (1, 2). A recent meta-analysis of the responses to treatment of 6,724 MDR-TB patients from 26 centers revealed that the frequency of treatment success was 64%, while that for patients with MDR-TB plus FQ resistance was only 48% (3). This clearly indicates the need for routine molecular screening for FQ resistance-associated molecular markers so that the treatment of such patients can be optimized without delay. Many such patients develop extensively drug resistant tuberculosis (XDR-TB), defined as MDR-TB plus resistance to any one FQ and any of the aminoglycosides/cyclic peptides (A-CP) (4). This poses an even more serious threat to TB management, since only 40% of XDR-TB patients have successful treatment outcomes (2). Previous studies have suggested that 5.4% (95% confidence interval [95% CI], 3.4 to 7.5%) of MDR-TB cases may actually be XDR-TB (2).FQs are oral antibacterial agents that have activity against Mycobacterium tuberculosis (5, 6). Hence, FQs are recommended for the treatment of MDR-TB patients and patients with intolerance to RIF (2). FQs are also being evaluated in ...

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Section: Figmentioning

confidence: 99%

“…These procedures usually take several weeks. Thus, a patient harboring a drug-resistant M. tuberculosis strain may continue to spread the infection undetected in the community (13). Molecular methods, however, have decreased the time to the detection of drug resistance, especially for MDR-TB (14).…”

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confidence: 99%

Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

et al. 2016

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“…The performance of MTBDRplus and MTBDRsl has been evaluated and documented in different countries with variable sensitivities and specificities (7)(8)(9)(10). A number of studies report high resistance rates of TB by conventional DST in Pakistan (11); however, limited data on LiPA testing has been published from this region (12)(13)(14)(15)).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Plausibility of MTBDRplus and MTBDRsl Line Probe Assays for Rapid Drug Susceptibility Testing of Drug Resistant Mycobacterium tuberculosis Strains in Pakistan

et al. 2016

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Background: World health organization (WHO) recommends the use of line probe assays (LiPAs) for rapid drug susceptibility testing (DST). However, only a limited number of studies from Pakistan have documented the performance characteristics of line probe assays in testing multi-drug resistant (MDR) strains of Mycobacterium tuberculosis (MTB). Objectives: The objective of this work is to evaluate the diagnostic plausibility of the LiPA tests MTBDRplus and MTBDRsl on MDR MTB isolates from Pakistan. Patients and Methods: This was a cross-sectional study conducted at the Indus hospital, Karachi. LiPA testing was performed on 196 smear-positive samples using BACTEC MGIT 960 as a gold standard. Results: The sensitivity of MTBDRplus for isoniazid and rifampicin was found to be 88.8% and 90.2%, respectively, while sensitivity of MTBDRsl for fluoroquinolones, amikacin/capreomycin, and ethambutol was found to be 72.9%, 81.8%, and 56.6%, respectively. Conclusions: The MTBDRplus and MTBDRsl genotypic testing can serve as useful additional tools for DST in a high-burden country like Pakistan provided it is used in combination with phenotypic testing.

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“…En el caso específico de la tuberculosis, es necesario que se fortalezcan las actividades de vigilancia y se analice periódicamente la información, así como el manejo adecuado de los esquemas de tratamiento en los casos sensibles y resistentes para disminuir las probabilidades de extender la resistencia. Asimismo, es necesario mantener actualizadas las guías y los protocolos de manejo de los pacientes (15,26,27).…”

Section: Discussionunclassified

Prevalence of Mycobacterium tuberculosis resistance to quinolones and injectables in Colombia, 2012-2013

et al. 2017

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Introducción. La tuberculosis es un problema de salud pública a nivel mundial. En 2014, la Organización Mundial de la Salud estimó que se habían presentado 9,6 millones de casos nuevos y 480.000 multirresistentes. La evaluación de la resistencia a fármacos inyectables y a quinolonas se introdujo hace pocos años, por lo cual no se conoce su prevalencia.Objetivo. Determinar la prevalencia de la resistencia a amicacina, kanamicina, capreomicina y ofloxacina en casos de tuberculosis resistente a isoniacida, rifampicina o a ambas, entre 2012 y 2013.Materiales y métodos. Se hizo un estudio de corte transversal con 489 aislamientos resistentes a isoniacida o rifampicina. Las pruebas de sensibilidad se hicieron con la técnica Bactec MGITTM. Para el análisis de la proporción de la resistencia, los casos se agruparon según el antecedente de tratamiento con medicamentos de segunda línea.Resultados. En los 438 casos nuevos, la resistencia global a la kanamicina fue mayor (7,1 %; IC95% 4,6-9,6); en los 51 casos previamente tratados, dicha resistencia fue de 27,5 % (IC95% 14,2-40,7). La resistencia global fue mayor en casos con antecedentes de tratamiento con quinolonas y fármacos inyectables. Se encontraron siete casos de tuberculosis extremadamente resistente.Conclusión. El estudio evidenció la presencia de resistencia a fármacos de segunda línea en personas con tuberculosis farmacorresistente sin tratamiento previo o tratadas previamente con quinolonas o fármacos inyectables, estos últimos con mayor porcentaje de resistencia. En consecuencia, es esencial practicar rutinariamente las pruebas de sensibilidad y el análisis de esta información.

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Fluoroquinolone-resistant tuberculosis: implications in settings with weak healthcare systems

Cited by 42 publications

References 87 publications

Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

Diagnostic Plausibility of MTBDRplus and MTBDRsl Line Probe Assays for Rapid Drug Susceptibility Testing of Drug Resistant Mycobacterium tuberculosis Strains in Pakistan

Prevalence of Mycobacterium tuberculosis resistance to quinolones and injectables in Colombia, 2012-2013

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