Florence Brossier

The World Health Organization recommends short course regimen (SCR) to treat multidrug resistant tuberculosis for patients with strains susceptible by line-probe assays (LPAs) to second-line drugs. Our retrospective study shows LPAs have suboptimal specificity in predicting eligibility for SCR; a quarter of eligible patients would receive inadequate therapy with SCR.

SETTINGS: Identification of extensively drug-resistant tuberculosis (XDR-TB) may be delayed because of the lack of availability of molecular testing for second-line drugs (SLDs). Early suspicion of XDR-TB is therefore necessary to avoid developing further drug resistance. OBJECTIVE: To identify the characteristics associated with XDR-TB among multidrug-resistant TB (MDR-TB) cases before the availability of second-line drug susceptibility testing (DST) results. METHODS: All MDR-TB cases with available second-line DST results recorded in France from 1998 to 2013 were classified as simple MDR-TB (no resistance to fluoroquinolones [FQs] or second-line injectable drugs [SLIDs]), pre-XDR-TB (resistance to FQs or SLIDs) and XDR-TB cases (resistance to both). RESULTS: A total of 833 MDR-TB cases were analysed, including 168 (20%) pre-XDR and 62 (7%) XDR-TB cases. A previous history of treatment was acknowledged among 41% of the cases; 12% were human immunodeficiency virus-positive. Characteristics independently associated with XDR-TB were foreign birth (OR 9.5), previous anti-tuberculosis treatment (OR 2.6), smear positivity (OR 4.5) and ethambutol (EMB) resistance (OR 9.1). Characteristics independently associated with pre-XDR-TB compared to simple MDR-TB cases were male sex (OR 1.6), birth in Europe (OR 2.6) and EMB resistance (OR 1.9). CONCLUSION: The presence of clinical or bacteriological characteristics associated with XDR-TB should lead to rapid molecular testing for resistance to SLDs before starting tailored treatment.

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International audienceAmong the Mycobacterium tuberculosis clinical isolates collected during the 2003-2014 period at the French National Reference Center for Mycobacteria, 29 showed a remarkable combination of mutations in katG, ethA, and the inhA promoter. The aim of this study was to establish the epidemiologic and molecular features of these isolates

Modification of codon 306 in embB is regarded as the main mechanism leading to ethambutol (ETB) resistance in clinical isolates of Mycobacterium tuberculosis . However, numerous mutations elsewhere in the embCAB locus and in embR , a putative transcriptional activator of this locus, have been reported to be involved in ETB resistance. Here, we investigated the diversity of nucleotide variations observed in embCAB and embR in M. tuberculosis complex isolates from France. These regions were sequenced in 71 ETB-resistant (ETB-R) and 60 ETB-susceptible (ETB-S) clinical isolates of known phylogenetic lineages. The 131 isolates had 12 mutations corresponding to phylogenetic markers. Among the 60 ETB-S isolates, only 3 (5%) had nonsynonymous mutations that were not phylogenetic markers. Among the 71 ETB-R isolates, 98% had mutations in embCAB that likely contribute to ETB resistance: 70% had mutations located in embB codon 306, 406, or 497; 13% had mutations located outside these three positions between codons 296 and 426; and 15% had mutations corresponding to mutations in the embC-embA intergenic region. We found a strong association between resistance to ETB and the presence of mutations in embB and the embC-embA intergenic region ( P < 0.001). In contrast, the mutations detected in embC and embA were not involved in ETB resistance, and no mutation was detected in embR . These results strongly suggest that the sensitivity of diagnostic assays for detecting ETB resistance based on testing of embB codon 306 can be increased by testing of the embB region between codons 296 and 497 and by including the embC-embA intergenic region between positions −8 and −21.

We read with interest the recent paper by Wheat et al. (7) reporting on the long-term stability of Aspergillus galactomannan in bronchoalveolar lavage fluid (BALF) and serum specimens stored at −20°C.…

Fifty-two multidrug-resistant isolates of Mycobacterium tuberculosis representative of the currently predominant lineages in France were analyzed using repetitive-sequence-based PCR (rep-PCR) DiversiLab (DL), spoligotyping, 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat typing (MIRU-VNTR), and restriction fragment length polymorphism of IS 6110 (IS 6110 -RFLP). DL, as opposed to MIRU-VNTR and IS 6110 -RFLP analysis, did not allow discrimination among half of the isolates, an indication of comparatively lower resolving power.