RESUMO
A clinical Pseudomonas aeruginosa isolate resistant to all ß-lactams, including ceftolozane-tazobactam and carbapenems, was recovered. It belonged to sequence type 235 and produced the extended-spectrum ß-lactamase (ESBL) GES-6 differing from GES-1 by two amino acid substitutions (E104K and G170S). GES-6 possessed an increased hydrolytic activity toward carbapenems and to ceftolozane and a decreased susceptibility to ß-lactamase inhibitors compared to GES-1, except for avibactam. We show here that resistance to ceftolozane-tazobactam may occur through acquisition of a specific ESBL in P. aeruginosa but that ceftazidime-avibactam combination remains an effective alternative.
Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Cefalosporinas/farmacologia , Pseudomonas aeruginosa/genética , Tazobactam/farmacologia , Resistência beta-Lactâmica/genética , beta-Lactamases/genética , Substituição de Aminoácidos , Compostos Azabicíclicos/farmacologia , Ceftazidima/farmacologia , Combinação de Medicamentos , Expressão Gênica , Humanos , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/isolamento & purificação , Resistência beta-Lactâmica/efeitos dos fármacos , beta-Lactamases/metabolismoRESUMO
OBJECTIVES: The objective of this study was to evaluate the accuracy of the CIM test in the detection of carbapenemase activity in 124 strains of Enterobacteriaceae. METHODS: A panel of 124 previously characterized Enterobacteriaceae was tested: 77 strains producing the following carbapenemase families: KPC (n = 14), GES (n = 22), NDM (n = 19), VIM (n = 4), IMP (n = 4) and OXA-48 (n = 14) and 47 non-carbapenemase producers. For the CIM method, an active susceptibility meropenem disc was exposed to a bacterial suspension of a test strain; when a carbapenemase is produced, the antibiotic is inactivated allowing uninhibited growth of an indicator strain after overnight incubation. A clear inhibition zone (≥20 mm) was considered indicative of no-carbapenemase activity. RESULTS: All KPC, NDM, VIM, IMP or OXA-48 producing strains were unequivocally detected with the CIM test. CIM false negative results were obtained with eleven Enterobacter cloacae producing GES-6. Two other E. cloacae not producing carbapenemase (one with SHV-12, one hyperproducing AmpC) were positive by the test. The sensitivity and specificity of the assay compared to those of molecular methods were 85.7% and 95.7%, respectively. CONCLUSIONS: The CIM method proved to be inexpensive and easy to interpret. It provided less than optimal results in the detection of GES-6 activity.