IMP metallo-β-lactamase-producing clinical isolates of Enterobacter cloacae in the UK.

Sir, Carbapenems, such as imipenem, meropenem and ertapenem, are often the main option for treatment of infections caused by multiresistant Gram-negative bacteria, particularly those that produce extended-spectrum or AmpC b-lactamase enzymes. However, the clinical utility of these antimicrobials is under threat with the emergence and spread of acquired genes coding for carbapenem-hydrolysing b-lactamases. These enzymes are broadly classified as serine carbapenemases (e.g. KPC) or metallo-carbapenemases (e.g. IMP, VIM and NDM), based on the hydrolytic mechanism at the active site. Ertapenem resistance in Enterobacter spp. is not uncommon and is mostly mediated by a combination of AmpC enzyme production and porin loss; imipenem and meropenem resistance is rarer, and more likely to be due to acquired carbapenemases. We report our experience with the first IMP metallo-b-lactamaseproducing Enterobacter cloacae isolated from patients admitted to Addenbrooke’s Hospital. In 2008–09, three isolates of meropenem-resistant E. cloacae were referred to the HPA Microbiology Services, Colindale, for confirmation. Two of three isolates were from blood cultures of haematology patients in an intensive care unit at the same time and one was from the urine of a renal transplant recipient. These isolates were resistant to gentamicin, tobramycin and tigecycline, and retained susceptibility only to amikacin and colistin. At the reference laboratory, the isolates were tested for carbapenem resistance by the BSAC agar dilution method and screened for carbapenemase production by the modified Hodge test. Carbapenemase genes were sought by PCR. PFGE of total DNA, digested with XbaI, was performed for strain comparison. All three meropenem-resistant E. cloacae isolates showed potentiation of the activity of imipenem in the presence of EDTA, indicating that they produced metallo-carbapenemases, and gave positive modified Hodge test results. PCR revealed the carbapenemases to be IMP types. A 651 bp intragenic fragment, from nucleotides 47 to 697 of the 741 bp blaIMP allele, was sequenced from all three isolates. The predicted amino acid sequences were identical to IMP-1 carbapenemase and, hence, different from other known IMP variants. PFGE showed that the three isolates belonged to a single strain; nevertheless, no epidemiological link was identified between the renal and haematology patients, or with hospitals elsewhere in the UK or overseas. This is the first identification of E. cloacae with an IMP carbapenemase in the UK based on submissions to HPA Microbiology Services, Colindale. It is part of a pattern whereby carbapenemase production is becoming more widespread in the Enterobacteriaceae, though, generally, KPC, NDM and VIM enzymes are more frequent than IMP types. – 6 The emergence of carbapenemases, which is often linked, as here, to resistance to multiple other drug classes, is a great public health concern. Producer strains should be actively sought to prevent their transmission among patients.