Polymyxin resistance in Enterobacter cloacae complex in Brazil: phenotypic and molecular characterization.
Bianca Santos da Costa, Renata Stavracakis Peixoto, Orlando Carlos da Concei����o Neto, Leilane da Silva Pontes, Thamirys Rachel Tavares E Oliveira, Camila Bastos Tavares Teixeira, Ivson Cassiano de Oliveira Santos, Melise Chaves Silveira, Daiana Cristina Silva Rodrigues, Bruno Rocha Pribul, Cl��udio Marcos Rocha-de-Souza, Ana Paula D 'Alincourt Carvalho-Assef
Author Information
Bianca Santos da Costa: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil.
Renata Stavracakis Peixoto: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil.
Orlando Carlos da Concei����o Neto: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil.
Leilane da Silva Pontes: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil.
Thamirys Rachel Tavares E Oliveira: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil.
Camila Bastos Tavares Teixeira: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil.
Ivson Cassiano de Oliveira Santos: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil.
Melise Chaves Silveira: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil.
Daiana Cristina Silva Rodrigues: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil.
Bruno Rocha Pribul: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil.
Cl��udio Marcos Rocha-de-Souza: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil. ORCID
Ana Paula D 'Alincourt Carvalho-Assef: Instituto Oswaldo Cruz - Funda����o Oswaldo Cruz, Laborat��rio de Bacteriologia Aplicada a Sa��de ��nica E Resist��ncia Antimicrobiana, Av. Brasil, Rio de Janeiro, RJ, 436521045900, Brazil. anapdca@ioc.fiocruz.br.
Enterobacter cloacae complex isolates have been reported as an important nosocomial multidrug resistance pathogen. In the present study, we investigated antimicrobial susceptibility and the colistin-resistance rates, their genetic determinants and clonality among clinical E. cloacae complex isolates from different Brazilian states. For this, an initial screening was carried out on 94 clinical isolates of E. clocacae complex received between 2016 and 2018 by LAPIH-FIOCRUZ, using EMB plates containing 4 ��g/mL of colistin, followed MIC determination, resulting in the selection of 26 colistin-resistant isolates from the complex. The presence of carbapenemases encoding genes (bla, bla and bla), plasmidial genes for resistance to polymyxins (mcr1-9) and mutations in chromosomal genes (pmrA, pmrB, phoP and phoQ) described as associated with resistance to polymyxin were screened by PCR and DNA sequencing. Finally, the hsp60 gene was sequenced to identify species of the E. cloacae complex and genetic diversity was evaluated by PFGE and MLST. The results have shown that among 94 E. cloacae complex isolates, 19 (20.2%) were colistin-resistant. The resistant strains exhibited MIC ranging from 4 to 128 ��g / mL and E. hormaechei subsp. steigerwaltii was the prevalent species in the complex (31,6%), followed by E. cloacae subsp. cloacae (26,3%). The antimicrobials with the highest susceptibility rate were gentamicin (21%) and tigecycline (26%). Carbapenemases encoding genes (bla n���=���5, bla n���=���1) were detected in 6 isolates and mcr-9 in one. Among the modifications found in PmrA, PmrB, PhoP e PhoQ (two-component regulatory system), only the S175I substitution in PmrB found in E. cloacae subsp cloacae isolates were considered deleterious (according to the prediction of PROVEAN). By PFGE, 13 profiles were found among E. cloacae complex isolates, with EcD the most frequent. Furthermore, by MLST 10 ST's, and 1 new ST, were identified in E. cloacae. In conclusion, no prevalence of clones or association among carbapenemase production and polymyxin resistance was found between the E. cloacae. Thereby, the results suggest that the increased polymyxin-resistance is related to the selective pressure exerted by the indiscriminate use in hospitals. Lastly, this study highlights the urgent need to elucidate the mechanism involved in the resistance to polymyxin in the E. cloacae complex and the development of measures to control and prevent infections caused by these multiresistant bacteria.
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