New Delhi metallo-β-lactamase and multidrug resistance: a global SOS?

A case report of a multidrug-resistant (MDR) infection with a strain of Klebsiella pneumoniae carrying a novel metallo-b-lactamase (MBL), the New Delhi MBL (NDM-1), appears in this issue of Clinical Infectious Diseases [1]. Sidjabat and colleagues detail the presentation and susceptibility profile and give us a brief molecular characterization of an isolate of K. pneumoniae carrying blaNDM-1 that was recovered from an 87-year-old Australian woman of Indian origin with a urinary tract infection. What is the significance of these findings? Is this really a ‘‘superbug’’? In gram-negative bacteria, 2 types of b-lactamases are responsible for resistance to carbapenems: those that use serine as the active site amino acid to inactivate the carbapenem (‘‘serine carbapenemases’’), and those that use a Zn ion (‘‘metallo b-lactamases’’ or MBLs) [2]. In the 1980s and 1990s, carbapenems were considered the ‘‘last resort antibiotics’’ used primarily against extended-spectrum b-lactamase (ESBL)– or AmpC-producing gram-negative bacteria. At that time, only a few b-lactamases could inactivate carbapenems, and these were limited to rare strains of Enterobacter cloacae possessing serine carbapenemases called NMC-A (Non Metallo Carbapenmase-A) and IMI-1 (Imipenemase-I), Sme-1 (Serratia marcescens), MBLs BcI and BcII of Bacillus cereus, the MBL L1 of Stenotrophomonas maltophilia, and CcrA of Bacteroides fragilis (another MBL) [3]. In a very short time, serine carbapenemases and MBLs became more frequent. MBLs are now widespread and found in Europe, Asia, Australia, Canada, and South and North America [4–8]. Presently, physicians practicing in tertiary care referral centers, long-term acute care hospitals, and nursing homes in large urban areas of the United States are acutely aware of carbapenemresistant gram-negative bacteria carrying the gene for KPC (Klebsiella pneumoniae carbapenemase, blaKPC) [9–12]. In the United States, KPC-producing gramnegative bacteria (usually found in Klebsiella species, Escherichia coli, Proteus species, Enterobacter species and others) raised significant concern, because mortality rates among patients infected with these bacteria are high, especially in long-term care facilities [11]. Moreover, detection of this resistance determinant in the clinical microbiology laboratory is still challenging [13]. The most widespread MBL in the world (thus far) is VIM-2 (isolated first from a patient in Verona, Italy–hence the name Verona Imipenemase) [2, 6, 14, 15]. Up until now, MBLs have been rarely reported in the United States, save for descriptions of VIM-type b-lactamases found in Texas and Illinois [14, 16]. Many believe that we might never see this problem in the United States. Will NDM-1 be the MBL that changes this? How will we readily distinguish between carbapenemresistant KPC and NDM-1–producing gram-negative bacteria by phenotypic methods? NDM-1 attracts significant attention because the gene encoding this MBL is located in a very mobile genetic element and the pattern of spread is proving to be more complex and, apparently, more unpredictable than the gene encoding KPC [17, 18]. In fact, the number of patients infected or colonized with bacteria possessing blaNDM-1 is growing. The gene has moved from India and Pakistan to the United Kingdom, the United States, Kenya, Japan, Canada, Belgium, the Netherlands, Taiwan, Singapore, the Sultanate of Oman, and Australia [19–25]. A review of the original description of blaNDM-1 by Yong et al [17] sets the background for the Received 28 September 2010; accepted 3 December 2010. Reprints or correspondence: Dr Robert A. Bonomo, Louis Stokes Cleveland Dept of Veterans Affairs Medical Center, 10701 East Blvd, Cleveland, OH 44106 (robert.bonomo@ med.va.gov). Clinical Infectious Diseases 2011;52(4):485–487 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. 1058-4838/2011/524-0001$37.00 DOI: 10.1093/cid/ciq179