Abstract
Carbapenems, once considered the last line of defense against of serious infections with Enterobacteriaceae, are threatened with extinction. The increasing isolation of carbapenem-resistant Gram-negative pathogens is forcing practitioners to rely on uncertain alternatives. As little as 5 years ago, reports of carbapenem resistance in Enterobacteriaceae, common causes of both community and healthcare-associated infections, were sporadic and primarily limited to case reports, tertiary care centers, intensive care units, and outbreak settings. Carbapenem resistance mediated by β-lactamases, or carbapenemases, has become widespread and with the paucity of reliable antimicrobials available or in development, international focus has shifted to early detection and infection control. However, as reports of Klebsiella pneumoniae carbapenemases, New Delhi metallo-β-lactamase-1, and more recently OXA-48 (oxacillinase-48) become more common and with the conveniences of travel, the assumption that infections with highly resistant Gram-negative pathogens are limited to the infirmed and the heavily antibiotic and healthcare exposed are quickly being dispelled. Herein, we provide a status report describing the increasing challenges clinicians are facing and forecast the “stormy waters” ahead.
Highlights
Carbapenems are potent and broad-spectrum β-lactam antibiotics traditionally reserved for the treatment of the most serious infections (El-Gamal and Oh, 2010)
Despite radical efforts in infection control (Schwaber et al, 2011) and improvements in rapid molecular diagnostics (Centers for Disease Control and Prevention, 2009; Nordmann et al, 2012c), carbapenem-resistant Gram-negative bacilli remain a formidable threat as few antimicrobial agents are reliably active and very little is expected to be available in the near future
Clinicians hold that the increasing prevalence of extendedspectrum β-lactamases (ESBLs) among Klebsiella pneumoniae and Escherichia coli in the 1980s and 1990s contributed to the increased consumption of carbapenems
Summary
Non-metallo-carbapenemase-A is a chromosomal carbapenemase originally isolated from Enterobacter cloacae in France (Nordmann et al, 1993). The GES-type β-lactamases are acquired β-lactamases recovered from P. aeruginosa, Enterobacteriaceae, and A. baumannii (Poirel et al, 2000a; Castanheira et al, 2004a) The genes encoding these β-lactamase have often, but not exclusively, been identified within class 1 integrons residing on transferable plasmids (Bonnin et al, 2013; Walther-Rasmussen and Høiby, 2007). Another study analyzing 16 KPC-2 producing K. pneumoniae isolates from different geographic regions demonstrated diverse PFGE patterns and MLST types. 42 variants of IMP have been identified with most cases of IMP-mediated carbapenem resistance being reported from Asia and among P. aeruginosa (Bush and Jacoby, 2010)
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