Dissemination of the metallo-β-lactamase gene blaIMP-4 among gram-negative pathogens in a clinical setting in Australia

Background. The clinical utility of carbapenems is under threat because of the emergence of acquired metallo-beta-lactamase (MBL) genes. We describe the first outbreak in Australia of infection and/or colonization with gram-negative pathogens carrying the MBL gene bla(IMP-4). Methods. MBL-producing organisms were identified using susceptibility data in conjunction with MBL screening methods. PCR and sequence analysis were performed to characterize the resistance gene and identify the presence of integrons. DNA profiles were determined by ribotyping. Clinical and epidemiological data were prospectively collected from January - July 2004. Results. A total of 19 isolates were recovered from 16 patients: Serratia marcescens (10 isolates), Klebsiella pneumoniae (4 isolates), Pseudomonas aeruginosa (3 isolates), Escherichia coli (1 isolate), and Enterobacter cloacae (1 isolate). Isolates were resistant to most beta-lactams except aztreonam, and variable resistance to carbapenems was observed ( MIC range, 2 to > 8 mg/L). PCR and sequence analysis identified the bla(IMP-4) gene and a class 1 integrase (IntI1) in all isolates. Of the 16 patients, 12 (75%) had infection; 5 had septicemia, 5 had ventilator- associated pneumonia, 1 had a urinary tract infection, and 1 had a superficial central venous line infection. Six (38%) of the 16 patients died, and 5 of those 6 (31% of the group of 16) had clinical infection with an MBL-producing organism. All except 2 patients had spatio-temporal epidemiological links in the intensive care unit. All K. pneumoniae isolates were of different ribogroups, whereas the S. marcescens and P. aeruginosa isolates were predominately of the same ribogroup. Conclusions. MBL-producing gram-negative organisms have now emerged in Australia. The resistance gene, bla(IMP-4), appears highly mobile; this outbreak involved 5 different gram-negative genera from patients with close epidemiological links.