RESUMO
Carbapenem resistance in Acinetobacter baumannii is a global problem. The purpose of this study was to elucidate current resistance mechanisms of imipenem-resistant A. baumannii (IRAB) in Taiwan and their correlation with patient outcomes. Acinetobacter baumannii clinical isolates from two teaching hospitals in Taiwan were collected in 2009 and were examined by Etest for determination of the minimum inhibitory concentrations (MICs) of imipenem, ceftazidime and ceftriaxone. Primers specific for carbapenemase genes and upstream regions were designed for PCR amplification. Bacterial isolates were genotyped by pulsed-field gel electrophoresis (PFGE). Clinical presentations of patients were analysed retrospectively. Upstream insertion sequence ISAba1 was found in 34 isolates that carried bla(OXA-23), including 28 with transposon Tn2006 (ISAba1-bla(OXA-23)-ISAba1) in an AbaR4-type resistance island and 6 with Tn2008 (ISAba1-bla(OXA-23)), as well as in 8 isolates carrying ISAba1-bla(OXA-51-like). All of these isolates expressed full resistance to imipenem (MIC>32 mg/L). Forty-one different PFGE genotypes were found among 62 isolates. Tn2006 was found in 19 genotypes (46.3%), which is more common than ISAba1-bla(OXA-51-like) (12.2%) (P=0.001). Prior use of carbapenems or extended-spectrum cephalosporins for ≥5 days was the only independent risk factor significantly associated with IRAB infection (odds ratio=361.175). Higher mortality was significantly associated with infection caused by IRAB and ISAba1-bla(OXA-23)-carrying strains compared with infection caused by imipenem-susceptible A. baumannii and ISAba1-bla(OXA-51-like)-carrying strains (P=0.009 and 0.027, respectively). Tn2006 is currently the most common imipenem resistance determinant, which showed a higher ability to spread among A. baumannii and was associated with a higher mortality in IRAB-infected patients.
Assuntos
Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/efeitos dos fármacos , Elementos de DNA Transponíveis , Farmacorresistência Bacteriana , Imipenem/farmacologia , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Técnicas de Tipagem Bacteriana , Ceftazidima/farmacologia , Ceftriaxona/farmacologia , Eletroforese em Gel de Campo Pulsado , Feminino , Genes Bacterianos , Genótipo , Hospitais , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Fatores de Tempo , beta-Lactamases/genética , beta-Lactamases/metabolismoRESUMO
Increasing antimicrobial resistance in nontyphoidal Salmonella (NTS) is a global public health problem that complicates antimicrobial therapy. As an enteric pathogen, Salmonella must endure the presence of bile in the intestinal tract during the course of infection. In this study, we sought to identify Salmonella genes necessary for bile resistance and to investigate their association with antimicrobial resistance. Four genes related to bile resistance were identified, namely rfaP, rfbK, dam and tolC. The first three genes are involved in lipopolysaccharide synthesis, and tolC is associated with an efflux pump. Antimicrobial susceptibility testing showed increased susceptibility to polymyxin B and ciprofloxacin in rfaP and tolC mutants of Salmonella, respectively. Genetic analysis of 45 clinical isolates of NTS revealed that all isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration ≥0.125 mg/L) were associated with point mutations in the quinolone resistance-determining regions of the gyrA and parC genes. The efflux pump also played a role, as evidenced by the reduction in fluoroquinolone resistance when the TolC efflux pump was inhibited by Phe-Arg-ß-naphthylamide, a competitive efflux pump inhibitor. Based on these results, we conclude that an intact membrane structure and the efflux pump system provide mechanisms enabling NTS to resist bile. Caution should be taken when using ciprofloxacin and polymyxin B to treat Salmonella enteric infection, as resistance to these agents involves the same mechanisms. Addition of an efflux pump inhibitor to fluoroquinolones may be an effective strategy to deal with the increasing resistance in NTS.