The Challenges of Detecting Carbapenem-resistant Enterobacteriaceae

Antibiotic resistance is a global challenge that requires efforts from across several industrial spectrums—agriculture, microbiology, medicine, public health, etc. Perhaps one of the most difficult aspects to fighting the battle of the resistant bug is identification and surveillance efforts. Although there is no international surveillance process, a recent study compared several clinical methods for detecting one of the deadliest resistant organisms: carbapenem-resistant Enterobacteriaceae (CRE).

CRE is one of the toughest resistant organisms and has been responsible for several deadly outbreaks in hospitals. Not only are infections with CRE difficult to treat, but some studies have shown a mortality rate as high as 50% in patients who are infected. Because carbapenem-resistance is complex and can be challenging for surveillance efforts, the results of this new study may help to strengthen these efforts.

The researchers evaluated 96 Enterobacteriaceae isolates with carbapenemase genes and 29 carbapenem-susceptible Enterobacteriaceae isolates. Detecting the carbapenemase-producing genes is necessary for diagnosis; however, it can often take time or have inaccuracies. The carbapenemases include several classes that have specific enzymes, which have been identified as having a “mobile genetic element”, which poses a concern for the transmission of the resistant genes to other bacteria. The researchers noted that “transmission of carbapenemase-mediated resistance has been detected among the Enterobacteriaceae as well as other Gram-negative rods, in particular Pseudomonas and Acinetobacter species. This horizontal spread contributes to a reservoir of organisms both in clinical and environmental locations. Resistance can be mediated by a single mechanism, or combinations of the above, and when present with other extended-spectrum beta-lactamases (eg, extended-spectrum beta-lactamases and AmpC beta-lactamases), confers widespread resistance to multiple antimicrobics.”

In efforts to strengthen the diagnostic and surveillance capabilities against CRE, the researchers evaluated several different methods: routine minimum inhibitory concentrated testing (MIC), testing with the GNX2F MIC panel, TREK Sensititre, Xpert Carba-R polmymerace chance reaction (PCR), the EPI-CRE assay, and matrix-assisted-laser desorption ionization—time of flight mass spectrometry. They also assessed the sensitivity and specificity of each test. Sensitivity was determined through discrepant results, by which “each assay compared to reference genotype were arbitrated with MIC and/or PCR testing to assess loss of plasmid-mediated resistance.”

The 96 isolates with genes encoding carbapenemases where supplied from Children’s Healthcare of Atlanta and the Centers for Disease Control and Prevention (CDC), which provided isolates from all over the United States. The research team worked to simulate routine clinical lab efforts (ie, using Remel blood agar plates and common discs) to be as true as possible to the every-day environment that hospital microbiology labs utilize.

Through the testing the researchers found that carbapenemase-resistance was confirmed for over 95% of the CRE isolates using MICs, Xpert Carba-R PCR, and MALDI-TOF MS imipenem hydrolysis. The highest performing tests in terms of sensitivity were the MIC (96.8%), Xpert Carba-R (97.6%), and MALDI-TOF (97.9%), while EPI-CRE performed lower (91.7%). Discrepant analysis raised the sensitivity values; however, no assay tested within this research study was able to accurately detected all 96 CRE isolates.

This specific study demonstrated the efficacy of current clinical diagnostic tools being used to find cases of CRE. Unfortunately, no single measure was able to detected all of the CRE isolates. Although it is reassuring that current methods are quite effective, there is still room for improvement. Efforts to strengthen diagnostic capability will only serve to help halt antimicrobial resistance as surveillance and control efforts are directly reliant on diagnostic efforts. This makes these tools vital to the global fight against the resistant bug.