Correlation between resistance to pyrazinamide and resistance to other antituberculosis drugs in Mycobacterium tuberculosis strains isolated at a referral hospital

Submitted by Sandra Infurna ([email protected]) on 2017-04-13T19:21:07Z No. of bitstreams: 1 mariahelena2_saad_etal_IOC_2012.pdf: 154535 bytes, checksum: c126bdad3e98dd164adb743307af589e (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-04-13T19:34:32Z (GMT) No. of bitstreams: 1 mariahelena2_saad_etal_IOC_2012.pdf: 154535 bytes, checksum: c126bdad3e98dd164adb743307af589e (MD5)Made available in DSpace on 2017-04-13T19:34:32Z (GMT). No. of bitstreams: 1 mariahelena2_saad_etal_IOC_2012.pdf: 154535 bytes, checksum: c126bdad3e98dd164adb743307af589e (MD5) Previous issue date: 2012Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Instituto de Microbiologia Paulo de Góes. Laboratório de Micobactérias. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Instituto de Doenças do Tórax. Laboratório de Micobactérias. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Instituto de Doenças do Tórax. Laboratório de Micobactérias. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.A correlação entre a resistência à pirazinamida (PZA) e a resistência a outros fármacos antituberculose de primeira linha foi investigada em 395 cepas de Mycobacterium tuberculosis provenientes de espécimes clínicos, que representavam 14% do total de isolados de M. tuberculosis no período entre 2003 e 2008 no laboratório de um hospital universitário de referência para tuberculose. Uma alta correlação foi encontrada entre resistência a PZA e multirresistência, assim como entre resistência a PZA e resistência a rifampicina, isoniazida e etambutol (p < 0,01 para todos). Esses resultados enfatizam a importância da realização do teste de sensibilidade a PZA antes de prescrever a droga para o tratamento de tuberculose resistente e multirresistente.The correlation between resistance to pyrazinamide (PZA) and resistance to other first-line antituberculosis drugs was investigated in 395 Mycobacterium tuberculosis strains isolated from clinical specimens, representing 14% of the overall number of M. tuberculosis isolates obtained between 2003 and 2008 at the laboratory of a referral university hospital for tuberculosis. A high correlation was found between resistance to PZA and multidrug resistance, as well as between PZA resistance and resistance to rifampin, isoniazid, and ethambutol (p < 0.01 for all). These results highlight the importance of performing PZA susceptibility testing prior to the prescription of this drug in order to treat drug-resistant and multidrug-resistant tuberculosis

Correlação entre a resistência a pirazinamida e a resistência a outros fármacos antituberculose em cepas de Mycobacterium tuberculosis isoladas em um hospital de referência

A correlação entre a resistência à pirazinamida (PZA) e a resistência a outros fármacos antituberculose de primeira linha foi investigada em 395 cepas de Mycobacterium tuberculosis provenientes de espécimes clínicos, que representavam 14% do total de isolados de M. tuberculosis no período entre 2003 e 2008 no laboratório de um hospital universitário de referência para tuberculose. Uma alta correlação foi encontrada entre resistência a PZA e multirresistência, assim como entre resistência a PZA e resistência a rifampicina, isoniazida e etambutol (p < 0,01 para todos). Esses resultados enfatizam a importância da realização do teste de sensibilidade a PZA antes de prescrever a droga para o tratamento de tuberculose resistente e multirresistente

Mycobacterium tuberculosis isolates from Rio de Janeiro reveal unusually low correlation between pyrazinamide resistance and mutations in the pncA gene.

It has been widely accepted, that pyrazinamide (PZA) resistance in Mycobacterium tuberculosis is correlated with mutations in the pncA gene. But since years researchers have been puzzled by the fact that up to 30% of PZA resistant strains do not show any correlation between PZA resistance and mutations in the pncA gene, and thus may vary with geographic area. The objective of the study was to investigate the correlation between PZA susceptibility and mutations in pncA gene in M. tuberculosis isolates from individuals living in a highly endemic area. Therefore we analyzed drug resistant and multidrug resistant (MDR) isolates from patients in Rio de Janeiro, Brazil. From a total of 97 clinical isolates of M. tuberculosis 35 were identified as PZA resistant, 24/35 strains did not show PZase activity and 15/24 (62.5%) strains possess mutation in the pncA gene. This is a low correlation between PZA resistance and PZase activity (68.6%) and even lower correlation between PZA resistance and the presence of mutation in pncA gene (45.7%). Most of the mutations found were conserved near the active site or metal binding site of PZase. The 146A>C mutation was found both in PZA resistant and susceptible isolates, suggesting that this mutation may not fully associated with PZA resistance. Of the mutations found, three have not been previously described. The insertions 192-193 TCCTCGTC and 388-389 AGGTCGATG, although found before, here was found to be a short tandem repeat and in one strain, insertion of the IS6110 was observed 55nt upstream of the gene. All PZA resistant isolates had no mutation in the gene coding ribosomal protein S1 (rpsA), which has recently been proposed as alternate target for pyrazinoic acid (POA). The results show a low association of PZA resistance and pncA gene mutations in a selected patient group from an highly endemic area. Our findings point out that the phenotypic susceptibility testing remains important for the detection of PZA-resistant M. tuberculosis