, 24 patients in intensive care units at Tisch Hospital, New York, N.Y., were infected or colonized by carbapenem-resistant Klebsiella pneumoniae. Pulsed-field gel electrophoresis identified a predominant outbreak strain, but other resistant strains were also recovered. Three representatives of the outbreak strain from separate patients were studied in detail. All were resistant or had reduced susceptibility to imipenem, meropenem, ceftazidime, piperacillin-tazobactam, and gentamicin but remained fully susceptible to tetracycline. PCR amplified a bla KPC allele encoding a novel variant, KPC-3, with a His(272)3Tyr substitution not found in KPC-2; other carbapenemase genes were absent. In the outbreak strain, KPC-3 was encoded by a 75-kb plasmid, which was transferred in vitro by electroporation and conjugation. The isolates lacked the OmpK35 porin but expressed OmpK36, implying reduced permeability as a cofactor in resistance. This is the third KPC carbapenem-hydrolyzing ␤-lactamase variant to have been reported in members of the Enterobacteriaceae, with others reported from the East Coast of the United States. Although producers of these enzymes remain rare, the progress of this enzyme group merits monitoring.

Between 1994 and 1998, 97 imipenem-resistant Acinetobacter isolates were identified at the Prince of Wales Hospital, Hong Kong, China. A bla IMP PCR product was obtained from 23 of 35 viable cultures; 12 isolates belonged to genomic DNA group 3, 8 belonged to group 2 (Acinetobacter baumannii), 2 belonged to group 13TU, and 1 belonged to group 1. The bla IMP homologues were sequenced from two isolates from genomic DNA group 2 and one isolate each from groups 3 and 13TU. The four sequences included an identical 738-bp open reading frame, predicted to encode a polypeptide of 246 amino acids, with 95.6% homology to IMP-1 and 89.3% homology to IMP-2. The new enzyme, designated IMP-4, was partially purified. It had a pI of 8.0 and was strongly active against imipenem and meropenem, with V max values 53 and 8% of that for penicillin G, respectively. Strong activity was also seen against oxyimino-aminothiazolyl cephalosporins but not against aztreonam. Hydrolytic activity was inhibited by EDTA but not by clavulanate or tazobactam. Carbapenem MICs for most bla IMP -positive isolates were 4 to 32 g/ml, but one isolate with the intact gene was susceptible, with imipenem and meropenem MICs of 0.25 and 0.5 g/ml, respectively. The latter isolate did not produce the band with a pI of 8.0, and gene expression was inferred to have been lost. None of the isolates studied in detail contained extrachromosomal DNA, and carbapenem resistance was not transmissible to Escherichia coli. Nevertheless, the presence of bla IMP-4 in different genomic DNA groups implies horizontal transfer, and sequences resembling a GTTRRRY integrase-dependent recombination motif were identified in the flanking regions of bla IMP-4 .

Acinetobacters are important nosocomial opportunists, particularly in intensive care and other specialist units. Common infections include ventilator-associated pneumonias and bacteremias; less frequent sites include burn wounds and the urinary tract (3). Most infections are caused by Acinetobacter baumannii, a species resilient to drying and commonly multiresistant to antibiotics.A. baumannii strains notoriously cause hospital outbreaks, and a few lineages achieve "epidemic" status, reaching multiple hospitals or countries. By convention, these are termed "clones" rather than "strains" when their relatedness is inferred on the basis of DNA profiles, without proven chains of site-to-site transmission. Examples include (i) the European clones I, II, and III, which are widespread in continental Europe (8, 25), (ii) a clone with the VEB-1 cephalosporinase that spread in northeast France and Belgium in late 2003 to 2004 (21), (iii) a clone with OXA-40 (OXA-24) carbapenemase which is prevalent at numerous hospitals in Spain and Portugal (7), and (iv) the southeast (SE) clone prevalent in southern England since 2000 (24). Disturbingly, several successful clones are now also carbapenem resistant and, as noted by the Infectious Disease Society of America, Acinetobacter is "a prime example of the mismatch between unmet medical need and the current antimicrobial research and development pipeline" (22).Among consecutive A. baumannii isolates collected at 54 United Kingdom hospitals in 2000 more than 85% were resistant to cephalosporins, 43% were resistant to gentamicin, and 46% were resistant to quinolones, leaving the carbapenems as the only standard antibiotics active against more than 90% of isolates in vitro (11). However, the SE clone, which began to become prevalent shortly after the study period for this survey

Elements mediating VanA glycopeptide resistance in 106 diverse enterococci from humans and nonhuman sources were compared with the prototype VanA transposon, Tn1546, in Enterococcus faecium BM4147. The isolates included 64 from individual patients at 15 hospitals in the United Kingdom (isolated between 1987 and 1996) and 42 from nonhuman sources in the United Kingdom (27 from raw meat, 7 from animal feces, and 8 from sewage). VanA elements were assigned to 24 groups (designated groups A to X) with primers that amplified 10 overlapping fragments of Tn1546. Ten groups of elements were found only in human enterococci, eight groups of elements were unique to nonhuman strains, and six groups of elements were common in enterococci from all sources. Elements indistinguishable from Tn1546 (group A) were observed more frequently in enterococci from nonhuman sources (34 versus 9%) but were identified in enterococci that caused outbreaks in hospital patients between 1987 and 1995. The most common group found in human enterococci (group H; 33%) was rarely observed in enterococci from other sources (5%). Group H elements differed from Tn1546 in three regions and included a novel insertion sequence, designated IS1542, between orf2 and vanR. The VanA elements of 14 other groups had a similar insertion at this position and/or distinct insertions at other positions. We conclude that VanA elements in enterococci are heterogeneous, although all show regions of homology with Tn1546. Furthermore, the elements most common among the human and nonhuman enterococci studied were different. This approach may be useful for monitoring the evolution of VanA resistance and may also be applicable in local “snapshot” epidemiological studies. However, as transposition events involving insertion sequences accounted for the differences observed between several groups, the stability of the elements must be assessed before their true epidemiological significance can be determined.