KPC (blaKPC) in Enterobacteriaceae, Molecular Detection, PCR
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Resistance to carbapenem antibiotics, by means of the enzyme KPC (Klebsiella pneumoniae carbapenemase), produced by Klebsiella pneumoniae and other members of the Enterobacteriaceae family, is becoming more common. The gene blaKPC encodes KPC production.
In addition to KPC production, several other genetic factors can cause resistance to carbapenems including production of other carbapenemases, plasmid-encoded AmpC beta-lactamases, or extended beta-lactamase (ESBL) combined with decreased membrane permeability. It is important to know if an isolate is resistant to carbapenems for proper reporting of antimicrobial susceptibility results and, in turn, determining proper antimicrobial therapy.
Detection of carbapenemases by the conventional phenotypic method (ie, modified Hodge test) may be subjective and is not rapid. Testing for the minimum inhibitory concentration (MIC) determines the level of resistance of the isolate, but not the mechanism causing the resistance. Real-time PCR is a sensitive, specific, and rapid means of detecting of a specific portion of the gene encoding KPC production.
Assessing pure isolates of Klebsiella pneumoniae or other members of the Enterobacteriaceae for carbapenem resistance
A positive KPC (Klebsiella pneumoniae carbapenemase) PCR indicates that the isolate tested carries blaKPC. Carbapenems (doripenem, ertapenem, imipenem, meropenem) should not be used to treat these isolates.
A negative result indicates the absence of detectable DNA, however false negative results may occur due to inhibition of PCR or sequence variability underlying primers and/or probes.
The assay detects the 13 blaKPC genotypes described as of June 2012.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay should only be used for testing of isolates. The use of this assay as a screening test directly from clinical specimens (eg, rectal swabs) has not been evaluated.
There are other mechanisms of carbapenem resistance beyond KPC-type carbapenemases that may confer resistance to carbapenems.
Loss of a plasmid carrying a resistance gene with serial passage and rarely on primary culture or in vivo, may result in non-detection of plasmid-mediated resistance.
The assay detects genes which typically confer carbapenem resistance; lack of phenotypic expression of that gene may result in a positive PCR result in a carbapenem susceptible isolate.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Real-Time PCR Procedure for Detection of Genes Encoding KPC Carbapenemases. Centers for Disease Control and Prevention 2007.(unpublished)
2. CLSI Document M100-S19, Vol 29, No.3, 2009. CLSI, Wayne, PA
3. Anderson KF, Lonsway DR, Rasheed JK, et al: Evaluation of methods to identify the Klebsiella pneumoniae carbapenemase in Enterobacteriaceae. J Clin Microbiol 2007;45(8):2723-2725