Research Article: Retrospective and prospective evaluation of the Carbapenem inactivation method for the detection of carbapenemase-producing Enterobacteriaceae

Date Published: February 3, 2017

Publisher: Public Library of Science

Author(s): Lauraine Gauthier, Remy A. Bonnin, Laurent Dortet, Thierry Naas, Patrick Butaye.


There is an urgent need for accurate and rapid diagnostic tests to identify carbapenemase producing enterobacteria (CPE). Here, we have evaluated the Carbapenem Inactivation Method (CIM) test to detect CPEs from cultured colonies.

A total of 256 enterobacterial isolates were used to evaluate the performance of the CIM in comparison to Carba NP test and molecular detection used a reference method. Ninety three well-characterized isolates (including 29 non-CPE and 63 CPEs of worldwide origin) with decreased susceptibility to at least one carbapenem were used to (i) evaluate the efficacy of CIM test and (ii) to compare it to the Carba NP test. We also tested different carbapenems to determine the best substrate for this test. Finally, the CIM test was then evaluated prospectively against 164 isolates referred to the French National Reference Center (NRC) for Antimicrobial Resistance from may 2016 to july 2016.

Based on the results of this retrospective study, sensitivity and specificity of the CIM and the Carba NP test were 92.1% and 100%, respectively. We demonstrated that the meropenem was the best substrate to perform the CIM test since sensitivity and specificity were 81.1% and 100% using ertapenem disk, and 100% and 65,6% using imipenem disk, and respectively. Taking in account the results of retrospective and prospective studies, CIM and Carba NP tests have similar sensitivity, specificity, positive predictive value and negative predictive values being 96.3%, 98.9%, 99.0% and 98.4% for the CIM test versus 96.9%, 100%, 100% and 100% for the Carba NP test.

Our results confirm that the CIM test may be a useful tool for the reliable confirmation of carbapenemase-activity in enterobacterial isolates, especially in clinical microbiological laboratories with limited resources, no trained personnel, and no specialized equipment.

Partial Text

Carbapenemase producers are increasingly reported worldwide in Enterobacteriaceae [1]. They are most often resistant to many classes of antimicrobial molecules, and thus represent a major public health concern. Their identification is of primary importance for the choice of appropriate therapeutic schemes and the implementation of proper infection control measures [1,2]. Identification based solely on antibiotic susceptibility testing is not easy and a recently described algorithm, showed that at least 66% of Enterobacteriaceae with a reduced susceptibility at least one carbapenem required confirmatory testing [3]. Thus, reliable and simple confirmatory tests are required.

Overall, our results indicate that the CIM has high sensitivity and specificity for CPE detection, as already reported [6,7]. It has significant advantages shared by the CarbaNP test being low cost and simplicity of implementation. In addition, it is very easy to interpret, the indicator E. coli strain grows directly contact to the meropenem disk (inhibitory diameter = 6 mm) with isolates having a carbapenemase activity, while a clear inhibition zone (most often > 20 mm) is obtained with non-carbapenemase producers. This ease of interpretation is a major advantage over the CarbaNP test, for which the colour change may be difficult to appreciate for non-experienced personal [18–20]. In addition, the CIM was positive for OXA-48 like producing isolates, which gave false-negative results with the Carba NP test. This is a particularly interesting point since these OXA-type carbapenemases may be phenotypically difficult to detect when no other β-lactamases are associated.