Abstract
The emergence and global spread of carbapenemase-producing Enterobacteriaceae is of great concern to health services worldwide. These bacteria are often resistant to all beta-lactam antibiotics and frequently co-resistant to most other antibiotics, leaving very few treatment options. The epidemiology is compounded by the diversity of carbapenem-hydrolysing enzymes and the ability of their genes to spread between different bacterial species. Difficulties are also encountered by laboratories when trying to detect carbapenemase production during routine diagnostic procedures due to an often heterogeneous expression of resistance. Some of the resistance genes are associated with successful clonal lineages which have a selective advantage in those hospitals where antimicrobial use is high and opportunities for transmission exist; others are more often associated with transmissible plasmids. A genetically distinct strain of Klebsiella pneumoniae sequence type (ST) 258 harbouring the K. pneumoniae carbapenemases (KPC) has been causing epidemics of national and international proportions. It follows the pathways of patient referrals, causing hospital outbreaks along the way. Simultaneously, diverse strains harbouring New Delhi metallo-beta-lactamase (NDM-1) are repeatedly being imported into Europe, commonly via patients with prior medical exposure in the Indian subcontinent. Since the nature and scale of carbapenem-non-susceptible Entrobacteriaceae as a threat to hospital patients in Europe remains unclear, a consultation of experts from 31 countries set out to identify the gaps in diagnostic and response capacity, to index the magnitude of carbapenem-non-susceptibility across Europe using a novel five-level staging system, and to provide elements of a strategy to combat this public health issue in a concerted manner
Highlights
Enterobacteriaceae are among the most abundant commensal microorganisms in humans
CLSI: Clinical Laboratory Standards Institute; ECOFF: epidemiological cut-off values; EUCAST: European Committee on Antimicrobial Susceptibility Testing; MIC: minimum inhibitory concentration; ND: no data. a I=intermediate is implied by the values between the S-breakpoint and the R-breakpoint. b ECOFF for E. coli and K. pneumoniae define the top end of the wildtype distribution; bacteria with MICs ≥ ECOFF have acquired some mechanism of resistance. c Values in parentheses indicate the CLSI breakpoints recommended before June 2010
If isolates with lower-level resistance are worth monitoring for infection control and public health purposes a simple laboratory tool is needed for detection - as simple as Etest, or double-disk synergy test (DDST), combination disk tests (CDTs) or an expert rule integrated into automated test systems
Summary
Enterobacteriaceae are among the most abundant commensal microorganisms in humans. They are the most frequent cause of bacterial infections in patients of all ages [1]. A further class of beta-lactam antibiotics, the carbapenems, came into clinical use in 1985 [10] These drugs combine exceptional intrinsic antibacterial activity with stability to most of the prevalent beta-lactamases, including ESBLs and have become the treatment of choice for infections due to the ESBL-producing strains, which are increasingly diagnosed in European hospitals. The need for a European-wide consultation on this matter was recognised during the 2009 annual EARSS meeting, and a workshop of scientists involved in the surveillance of antibiotic resistance in Enterobacteriaceae from 31 European countries was hosted at the Netherlands’ National Institute for Public Health and the Environment (RIVM) on 29 and 30 April 2010 These scientists already participated in the EARSS network and were selected on the basis of their expertise in the epidemiology of carbapenem resistance. They have been described in all four classes of beta-lactamases, but the epidemiologically most relevant carbapenemases fall into three of these [20]: Class B includes the metallo-beta-lactamases
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