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Increasing prevalence of carbapenem-resistant Enterobacteriaceae and strategies to avert a looming crisis

Enterobacteriaceae are frequently encountered pathogens that cause both communityand healthcare-associated infections. Unfortunately, they are becoming increasingly resistant to many commonly prescribed antibiotics [1]. Clinicians have responded to this dilemma by increasing the use of carbapenems (i.e., ertapenem, meropenem, doripenem and imipenem), especially for serious or life-threatening infections. Predictably, carbapenemresistant Enterobacteriaceae (CRE) has become increasingly prevalent over the last decade [2]. Carbapenems are often considered ‘drugs of last resort’ and antibiotic resistance to this class is particularly troubling; a major drug in our armamentarium is removed. In the USA, most carbapenem resistance in Enterobacteriaceae occurs through plasma-mediated expression of a Klebsiella pneumoniae carbapenemase (KPC)-type serine carbapenemase [3]. KPC carbapenemase hydrolyzes all classes of β-lactam antibiotics ( including expandedspectrum cephalosporins) and are not inactivated by β-lactamase inhibitors. CRE also spreads easily in healthcare settings and causes infections with high mortality; approximately 40–50% [4]. Moreover, these organisms increase medical costs and length of hospital stay. Thus, the emergence of CRE is widely acknowledged to be a serious threat to global public health. Scope of the problem Carbapenem resistance in Enterobacteri aceae was rare until recently, with KPC first discovered in 2001 [5]. Since then this unwelcome phenotype has spread rapidly throughout the USA and to the rest of the world. Other carba penemases have subsequently emerged in Enterobacteriaceae, including New Delhi metallo-β-lactamase (NDM), Verona integron-encoded metalloβ-lactamase, IMP (active on imipenem) and oxacillinase-48. A recent report from the CDC found that the prevalence of CRE has increased from 1 to 4% during the last decade [6]. Furthermore, 4% of acute-care hospitals and 18% of long-term acute-care hospitals (LTACHs) reported at least one strain of CRE to a national database. Fortunately, reports of CRE spreading into community settings are uncommon, although the potential exists for this dreadful scenario to occur. CRE are particularly a concern in intensive care units due to high rates of transmission and excessive mortality. Dutch investigators found that throughout European intensive care units, strains of multidrug-resistant Escherichia coli and K. pneumoniae with carbapenemases are becoming endemic [7]. Patel et al. reported that risk factors associated with CRE include organ or stem-cell transplantation, receipt of mechanical ventilation, longer length of hospitalization before infection and exposure to cephalosporins Increasing prevalence of carbapenem‐resistant Enterobacteriaceae and strategies to avert a looming crisis