Molecular detection of fluoroquinolone-resistance in multi-drug resistant tuberculosis in Cambodia suggests low association with XDR phenotypes

• Main Authors: Murray Alan, Namouchi Amine, Cadet-Daniel Véronique, Pierre-Audigier Catherine, Heng Seiha, Surcouf Corinne, Gicquel Brigitte, Guillard Bertrand
• Format: Article
• Language: English
• Published: BMC 2011-09-01
• Series: BMC Infectious Diseases
• Online Access: http://www.biomedcentral.com/1471-2334/11/255

<p>Abstract</p> <p>Background</p> <p>Drug susceptibility testing (DST) remains an important concern for implementing treatment of MDR tuberculosis patients. Implementation of molecular tests for drug resistance identification would facilitate DST particularly in developing countries where culturing is difficult to perform. We have characterized multidrug resistant strains in Cambodia using MDTDR<it>sl </it>tests, drug target sequencing and phenotypic tests.</p> <p>Methods</p> <p>A total of 65 non-MDR and 101 MDR TB isolates collected between May 2007 and June 2009 were tested for resistance to fluoroquinolones and aminoglycosides/cyclic peptides using the GenoType^®MTBDR<it>sl </it>assay and gene sequencing. Rifampicin resistance (RMP-R) was tested using gene sequencing and genotyping was assessed by spoligotyping.</p> <p>Results</p> <p>A total of 95 of the 101 MDR strains were confirmed to be RMP-R by <it>rpoB </it>gene sequencing. Fourteen of the 101 MDR isolates (14%) carried a <it>gyrA </it>mutation associated with fluoroquinolone-resistance (FQ-R) (detected by the MTBDR<it>sl </it>assay and sequencing) compared with only 1 (1.5%) of the 65 non-MDR strains. Only 1 (1%) of the MDR isolates was found to be XDR TB. The MDR group contained a higher proportion of Beijing or Beijing like strains (58%) than the non MDR group (28%). This percentage is higher in MDR FQ-R strains (71%).</p> <p>Conclusions</p> <p>The new GenoType^®MTBDR<it>sl </it>assay combined with molecular tests to detect RMP-R and isoniazid resistance (INH-R) represents a valuable tool for the detection of XDR TB. In Cambodia there is a low rate of XDR amongst MDR TB including MDR FQ-R TB. This suggests a low association between FQ-R and XDR TB. Strain spoligotyping confirms Beijing strains to be more prone to accumulate antibiotic resistance.</p>