Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii: genes, plasmids and clones

Abstract number: S382

Woodford N.

Carbapenems (excluding ertapenem) are treatments of choice for infections caused by multi-resistant A. baumannii so the emergence of carbapenem resistance is a serious problem. As with other Gram-negative species, carbapenem resistance has been attributed to multiple mechanisms, including reduced permeability through loss of outer membrane proteins, altered penicillin-binding proteins and over-expression of weakly carbapenem-hydrolyzing b-lactamases, but the major mechanism is carbapenemase production. Diverse carbapenemases have been reported in A. baumannii, differing in their regional prevalence: isolates with IMP or VIM metallo-enzymes are globally scattered; those with SIM-1 are associated particularly with the Far East, while NDM-1 has been observed only rarely. OXA class D enzymes are the dominant carbapenemases in A. baumannii, with 5 phylogenetically distinct groups identified. OXA-51-like enzymes are intrinsic to the species, and are only associated with carbapenem resistance when up-regulated by an adjacent insertion sequence, usually ISAba1. By contrast, OXA-23-like, OXA-40-like, OXA-58-like and OXA-143 carbapenemases have all been acquired via horizontal gene spread. These enzymes usually confer clinically significant carbapenem resistance, although the MICs for individual isolates are influenced by the particular gene present, its copy number, and presence of accessory mechanisms (e.g. loss of the CarO porin). The blaOXA genes may be located on the chromosome, as part of large resistance islands, or on plasmids. Local outbreaks of carbapenem-resistant A. baumannii typically include a predominant strain, and strains from epidemiologically unlinked sites may show sufficient similarity to be regarded as the same clone. There are two dominant carbapenem-resistant clones in the UK, 'OXA-23 clone 1' has OXA-23 enzyme, and the 'South-east clone' has ISAba1-up-regulated OXA-83 enzyme; both have affected >50 hospitals and belong to sequence group 1 (based on ompA, csuE and blaOXA-51-like alleles), which is European clone II. In other countries there may be greater evidence for horizontal gene spread in addition to strain spread, as observed for OXA-72 (an OXA-40-like enzyme) in a Taiwanese hospital. There are few therapeutic options for infections caused by carbapenem-resistant strains other than a polymyxin or glycylcycline and effective infection control remains essential to control their spread and impact.