Clinically significant carbapenemases: an update.
OBJECTIVE
To provide a brief synopsis of studies which have extended our understanding of carbapenem resistance in clinical isolates in terms of epidemiology, mechanism of action and genetic factors affecting their carriage and spread.


RESULTS
Studies published in the last 18 months continue to confirm that VIM-2 is the dominant metallo-beta-lactamase in Pseudomonas aeruginosa and that it has now moved into the cystic fibrosis P. aeruginosa population. Increased incidences of KPC and Guiana extended-spectrum serine carbapenemase would indicate that these are likely to dominate in Enterobacteriaceae and that KPC-2 has now been isolated from P. aeruginosa. Class D carbapenemases still appear to be confined to Acinetobacter baumannii and, interestingly, it has been proposed that OXA-23 was transferred from the nonpathogenic Acinetobacter radioresistens. Crystal structures of KPC-2, GES-1 and OXA-24 have been reported to enhance our understanding of why these clinically important enzymes can bind and hydrolyse carbapenems, whereas others cannot. Therapeutic options continue to be limited and although tigecycline shows activity against carbapenemase-positive Enterobacteriaceae, antibiotic combinations are required for carbapenemase-positive Acinetobacter and P. aeruginosa.


CONCLUSIONS
Carbapenem resistance continues to increase both in number and into new species/strain types, but our therapeutic options remain woefully inadequate - a dilemma that will not improve in the foreseeable future.
Walsh
Timothy R
TR
Department of Medical Microbiology, School of Medical Sciences, Cardiff University, Heath Park Hospital, Cardiff, UK. WalshTR@Cardiff.ac.uk
D000150:Acinetobacter / Q000187:drug effects / Q000201:enzymology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000145:classification / Q000235:genetics; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology*; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology*; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000737:chemistry / Q000145:classification / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047090:beta-Lactams; D001618:beta-Lactamases; C063912:carbapenemase