International Journal of Antimicrobial Agents 41 (2013) 1–4 Contents lists available at SciVerse ScienceDirect International Journal of Antimicrobial Agents jou rn al h om epa ge: h ttp://www.elsevier.com/locate/ijantimicag Discussion Detection systems for carbapenemase gene identification should include the SME serine carbapenemase Karen Bush a,* , Megan Pannell a,1 , John L. Lock b , Anne Marie Queenan c , James H. Jorgensen d , Ryan M. Lee a,2 , James S. Lewis e , Deidre Jarrett f a Department of Biology, Indiana University Bloomington, Bloomington, IN 47405, USA b St Vincent Hospital, Indianapolis, IN 46260, USA c Janssen Research & Development, 1000 Route 202 South, Raritan, NJ 08869, USA d Department of Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USA e University of Texas Health Science Center San Antonio, Division of Infectious Diseases & University Health System Department of Pharmacy, San Antonio, TX 78229, USA f Mid America Clinical Laboratories, 2560 N. Shadeland Ave., Indianapolis, IN 46219, USA a r t i c l e i n f o Article history: Received 13 August 2012 Accepted 15 August 2012 Keywords: SME Carbapenemase Detection Multiplex PCR Microarray a b s t r a c t Carbapenemase detection has become a major problem in hospitals that encounter outbreaks of infections caused by carbapenem-resistant Gram-negative bacteria. Rapid detection systems have been reported using multiplex PCR analyses and DNA microarray assays. Major carbapenemases that are detected by these systems include the KPC and OXA serine carbapenemases, and the IMP, VIM and NDM families of metallo--lactamases. However, increasing numbers of the SME serine carbapenemase are being reported from Serratia marcescens, especially from North and South America. These organisms differ from many of the other carbapenemase-producing pathogens in that they are generally susceptible to the expanded-spectrum cephalosporins ceftazidime and cefepime while retaining resistance to almost all other -lactam antibiotics. Thus, multiplex PCR assays or DNA microarray testing of carbapenem-resistant S. marcescens isolates should include analyses for production of the SME carbapenemase. Confirmation of the presence of this enzyme may provide reassurance that oxyimino-cephalosporins can be considered for treatment of infections caused by these carbapenem-resistant pathogens. © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. 1. Carbapenemase history Carbapenemases are responsible for a growing proportion of carbapenem resistance in enteric Gram-negative bacteria [1]. These -lactamases can hydrolyse virtually all -lactam antibiotics [2], with the distinction of inactivating carbapenems that are often used as broad-spectrum drugs of choice for serious nosocomial infec- tions. The first carbapenemases identified in the literature were chromosomal in origin and were species-specific. However, since the mid 1990s, plasmid-encoded carbapenemases have spread rapidly among enteric bacteria as well as among non-fermentative organisms [3]. They are usually produced in combination with other * Corresponding author. Present address: Department of Biology, Jordan Hall A311, Indiana University Bloomington, Bloomington, IN 47405, USA. Tel.: +1 812 855 1542; fax: +1 812 333 6192. E-mail address: karbush@indiana.edu (K. Bush). 1 Present address: College of Medicine, University of Kentucky, Lexington, KY 40506, USA. 2 Present address: Dow AgroSciences, 9330 Zionsville Road, Indianapolis, IN 46268, USA. -lactamases, thus making it difficult to identify the enzymes using simple phenotypic tests [2]. Carbapenemase production in Gram-negative bacteria is becoming a major crisis in many hospitals worldwide, resulting in high mortality and dwindling choices of appropriate antibiotic treatment [1]. The transferable elements encoding these enzymes may become endemic within a hospital, such that eradication is almost impossible despite intensive infection control procedures [4]. Thus, detection of these enzymes is considered to be a critical activity in many healthcare centres that are experiencing epidemics of carbapenem-non-susceptible Gram-negative pathogens. Carbapenemases have emerged from two different molecular origins, either as metallo--lactamases (MBLs) containing at least one active-site zinc ion, or as serine -lactamases (SBLs) with an active-site serine required for substrate hydrolysis [1]. The differ- ent structural types make it more difficult to develop phenotypic tests that can identify MBLs inhibited by chelating agents such as ethylene diamine tetra-acetic acid (EDTA) as well as SBLs that are inhibited by serine-interactive compounds such as boronic acid derivatives or clavulanic acid [5,6]. This challenge has been addressed by a number of groups that have developed sophisticated methods for carbapenemase detection. 0924-8579/$ – see front matter © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. http://dx.doi.org/10.1016/j.ijantimicag.2012.08.008