Second, we did not determine the MICs of the cultured isolates to the carbapenems, but chose rather to confirm the presence of a carbapenemase gene using the same PCR assay. The purpose of the study was to compare the PCR-based screening assay to culture of CPE, with subsequent determi- nation of the presence of a carbapenemase gene in the cultured isolate. We do not feel that MIC determination is relevant to the comparison since currently a rectal swab pos- itive by PCR is the trigger for IPC measures to be implemented, not the isolation of carbapenem-resistant Enterobacteriaceae for which MIC determination would be relevant. Admittedly, some isolates that were isolated by culture and negative by PCR may have been carbapenem susceptible, possibly sec- ondary to a large inoculum (as discussed above).
Third, our study is limited to the low numbers of specific carbapenemase genes that were detected in patients selected for screening within a specific region. No KPC gene was detected in any samples and the predominant gene detected was VIM; thus, we cannot necessarily extrapolate the comparative findings to all carbapenemase genes and to different settings where CPE carriage may vary. Based on local laboratory and hospital data, KPC-positive isolates are rarely detected within the Gauteng region, and VIM, NDM and OXA-48- like appear to be the most prominent, although sporadic, genes. These data, however, support the notion that routine PCR screening results need to be contextualized with culture findings and an understanding of local hospital epidemiology.
Finally, we had no information as to the exact reason for screening but rather surmised that the majority of screening swabs were done as part of an active surveillance admission protocol, known to be the standard within the hospitals served. There is the possibility that some of the swabs were sent in response to a positive case being identified, although we were not aware of any confirmed outbreaks during the study period.
In summary, we present data on the applicability of sur- veillance screening for CPE using a multiplex PCR assay. From a laboratory perspective, despite the excellent performance characteristics of PCR, its use must be tempered by the objective and clinical utility. The result of a diagnostic assay has a clinical implication, and as a screening tool for CPE that implication is the implementation of resource-intensive IPC measures. The consequence of this is that if the screening test has a positive predictive value of <50% then costly measures are being implemented unnecessarily for half of all patients. In the absence of an epidemiological context and without sup- portive culture-based prevalence data, the clinical value of PCR is diminished. At present, due to the low positive predic- tive value of PCR for detection of CPE, we do not support its use in our setting as a stand-alone surveillance tool, especially outside of an outbreak/endemic setting. Further evaluation of PCR, aided by culture, is necessary to better understand and define its role as a tool for active surveillance. We propose that further studies need to be conducted comparing PCR to culture in terms of duration of CPE carriage, colonization levels, risk factors for CPE carriage and transmission, and effectiveness of active surveillance in curtailing the spread of CPE.
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