Clinical Education Center

Question 1. What is a carbapenemase?

A carbapenemase is an enzyme that hydrolyzes carbapenem antibiotics such as meropenem. These carbapenemases often hydrolyze other β-lactam agents as well, including penicillins, β-lactam/β-lactamase inhibitor combinations, and cephalosporins. Thus, bacteria with a carbapenemase may be resistant to all β-lactam drugs. Carbapenemases fall into one of three categories: Ambler class A enzymes include KPC, SME, IMI, NMC, and GES; Ambler class B enzymes are also known as metallo- β-lactamases (MBL) and include VIM and IMP; and Ambler class D oxacillin-hydrolyzing enzymes (OXA).¹ Carbapenemases are most often found in Enterobacteriaceae, Acinetobacter spp., and Pseudomonas spp.

Question 2. Why is it important to screen for carbapenemases?

Screening can help guide the selection of appropriate antibiotic therapy for the patients being considered for carbapenem and other β-lactam antibiotics. Alternative therapy should be considered for patients with a positive screen.

Screening can also help guide other aspects of patient management. For example, those harboring carbapenem-resistant Enterobacteriaceae (CRE) should be placed on contact precautions to prevent transmission.

Question 3. What is the importance of the carbapenemases detected by this assay?

KPC

Klebsiella pneumoniaecarbapenemases (KPCs) are plasmid-encoded Amber class A carbapenemases that can be found in K pneumoniae and other Enterobacteriaceae species including Escherichia coli. They were first identified in K pneumoniae isolates in North America in 1996 and are currently the most common type of carbapenemase found in the United States.

MBL

Metallo- β-lactamase (MBL) is a carbapenemase that confers resistance to β-lactams such as cephamycins and carbapenems as well as to clavulanic acid, sulbactam, and tazobactam. Some MBLs also cause resistance to aztreonam.² The New Delhi metallo-β-lactamase-1 (NDM-1) is a type of MBL which was first reported in 2009 when found in a K pneumoniae strain and anE coli strain from a Swedish patient repatriated from a New Delhi hospital. Many other cases have been reported since, indicating rapid spread of these strains. Fortunately, NDM-1 isolates are not common in the U.S.

OXA

The OXA-type carbapenemases demonstrate weaker carbapenemase activity than the other carbapenemases, but when combined with other resistance mechanisms, they may convey carbapenem resistance.³ OXAs can affect efficacy of a wide variety of β-lactams. OXA impact on clavulanic acid efficacy is relatively weak.

Question 4. Which carbapenemases does this assay detect?

This assay detects resistance to all carbapenems, regardless of resistance mechanism. This is because we use a phenotypic culture assay that screens for growth in the presence of a carbapenem.

Question 5. Does this assay differentiate the type of carbapenemase that is present?

No. Quest Diagnostics does not offer molecular characterization of β-lactamase resistance at this time.

1. Swenson JM, Patel JB, Jorgensen JH. Special phenotypic methods for detecting antibacterial resistance. In: Versalovic J, et al, ed. Manual of Clinical Microbiology. 10th ed. Washington DC: ASM Press;2011:1155-1179.
2. Rice LB, Bonomo RA. Mechanisms of resistance to antibacterial agents. In: Versalovic J, et al, ed. Manual of Clinical Microbiology. 10th ed. Washington DC: ASM Press;2011:1082-1114.
3. Walther-Rasmussen J, Hoiby N. OXA-type carbapenemases. J Antimicrob Chemo. 2006;57:373-383.