RESUMO
The progression of mycobacterial diseases requires the development of new therapeutics. This study evaluated the efficacy and selectivity of a panel of Cyclophostin and Cyclipostins analogues (CyCs) against various bacteria and mycobacteria. The activity 26 CyCs was first assayed by the agar plate method. Compounds exhibiting 50-100% growth inhibition were then selected to determine their minimum inhibitory concentrations (MICs) by the resazurin microtiter assay (REMA). The best drug candidate was further tested against clinical mycobacterial isolates and bacteria responsible for nosocomial infections, including 6 Gram-negative bacteria, 5 Gram-positive bacteria, 29 rapid-growing mycobacteria belonging to the Mycobacterium chelonae-abscessus clade and 3 slow-growing mycobacteria (Mycobacterium marinum, Mycobacterium bovis BCG and Mycobacterium tuberculosis). Among the 26 CyCs tested, 10 were active and their inhibitory activity was exclusively restricted to mycobacteria. The best candidate (CyC17) was further tested against 26 clinical strains and showed high selectivity for mycobacteria, with MICs (<2-40 µg/mL) comparable with those of most classical antimicrobials used to treat M. abscessus infections. Together, these results support the fact that such CyCs represent a new family of potent and selective inhibitors against mycobacteria. This is of particular interest for future chemotherapeutic developments against mycobacterial-associated infections, especially against M. abscessus, the most drug-resistant mycobacterial species.
Assuntos
Antibacterianos/uso terapêutico , Infecções por Mycobacterium/tratamento farmacológico , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium marinum/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Compostos Organofosforados/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium/microbiologia , Mycobacterium abscessus/isolamento & purificação , Mycobacterium bovis/isolamento & purificação , Mycobacterium marinum/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificaçãoRESUMO
We compared two walk-away molecular diagnostic assays, the GeneXpert MRSA Gen 3 assay and the BD-Max MRSA XT assay. A total of 119 prospective swabs and 36 culture-positive samples were tested. Xpert MRSA Gen 3 had sensitivity of 95.7% and specificity of 100% versus 87.5% and 97.1% for BD-Max. The difference in agreement with the enriched culture results was significantly in favor of the Xpert assay (P < 0.02, McNemar nonparametric text).
