How is Carbapenemase-producing Enterobacteriaceae (CPE) tested for?

Testing Methods for Carbapenemase-Producing Enterobacteriaceae (CPE)

Genotypic testing methods are preferred for detecting Carbapenemase-Producing Enterobacteriaceae (CPE), with phenotypic tests serving as valuable alternatives when molecular methods are unavailable. 1

Primary Testing Methods

Genotypic Methods (First-Line)

• PCR-based detection: Highly sensitive (98.0%) and specific (100%) with rapid turnaround time (<3 hours) 1
• Whole Genome Sequencing (WGS): Gold standard for confirmation and epidemiological studies 1
• Loop-mediated isothermal amplification (LAMP): Offers higher positive detection rate than standard PCR with 2-3 hour turnaround time 1

Phenotypic Methods (When Genotypic Testing Unavailable)

• Modified Carbapenem Inactivation Method (mCIM): Highly sensitive and specific (95% compliance with genetic detection) 1
• Combined Disc Test (CDT): 94% compliance with genetic detection; uses meropenem disc plus 3-aminophenylboronic acid or EDTA 1
• Carba NP test: Excellent sensitivity (95.9%) and specificity (100%) with <3 hour turnaround time 1
• Modified Hodge Test (MHT): Traditional method but less reliable with lower sensitivity for metallo-β-lactamases (88%) 2

Specimen Collection

• Rectal or perirectal swabs: Provide highest yield for CPE detection in surveillance screening 3
• Clinical specimens: Urine, blood, wound samples, or other infection sites for diagnostic testing 1

Testing Algorithm

1. Initial screening:

   • Screen isolates for reduced susceptibility to carbapenems (ertapenem MIC ≥0.5 μg/mL shows 98% sensitivity) 4
   • For blood cultures: Apply concentration and hemolysis step before testing 5

2. Confirmatory testing:

   • If molecular testing available: Perform multiplex PCR targeting common carbapenemase genes (bla NDM, bla KPC, bla OXA-48 & variants, bla GES, bla IMP, and bla VIM) 4
   • If molecular testing unavailable: Use phenotypic methods (mCIM/eCIM or Carba NP) 1

3. For epidemiological purposes:

   • Conduct point prevalence surveys in high-risk units when cases are identified 1
   • Perform contact tracing with active surveillance for patients with epidemiologic links to confirmed cases 3

Special Considerations

• Test selection based on local epidemiology: Different tests have varying sensitivities for different carbapenemase types (KPC, NDM, OXA-48, VIM, IMP) 1
• Rapid testing for bloodstream infections: Modified colorimetric assays (β-Carba, bcCarba NP) can provide results in 20 minutes to 3 hours directly from positive blood cultures 5
• Weakly hydrolyzing carbapenemases: OXA-48-like enzymes may be missed by some phenotypic tests; newer methods like β-Carba show improved detection 5

Pitfalls to Avoid

• False negatives with MHT: This test has lower sensitivity for metallo-β-lactamases and should not be used alone 2
• Relying solely on susceptibility testing: Some CPE may appear susceptible to carbapenems despite harboring carbapenemase genes 6
• Delayed recognition: Failure to implement rapid testing can lead to undetected transmission in healthcare settings 3
• Inconsistent methodology: Use standardized protocols to ensure reliable detection 1

Early and accurate detection of CPE is crucial for guiding appropriate antimicrobial therapy and implementing effective infection control measures to prevent further transmission in healthcare settings.