Multiplex PCR and diagnosis of sepsis

Just came across a really nice paper in the Journal of Clinical Microbiology by Ephraim Tsalik, Chris Woods and others at Duke and the Durham VA. They tested whether multiplex real-time PCR can be a useful addition to blood culture in patients presenting with suspected sepsis to the ED of their two hospitals. Over an almost 6-year period they enrolled 306 patients with suspected sepsis (43 were eventually excluded for non-infectious etiology). Patients had blood samples taken within ~2-3 hours and a questionnaire administered to determine recent exposures and symptoms. Most of the confirmed etiologies were S. aureus (34%) and E. coli (23%).

Results showed that blood culture had a sensitivity of 25% vs. 20% for PCR, a similar negative predictive value (18% vs. 17%), and an area under the curve of 0.63 vs 0.60. Using blood culture as the gold standard, PCR had a sensitivity of 61%. Both PCR and culture detected organisms in 40 patients (38 were the same organism). As far as individual methods, there were 24 organisms only detected by PCR (largely E. coli and Klebsiella) and 52 only detected by blood culture (E. coli, S. pneumo, S. aureus and a large number of CoNS considered contaminants). Six species detected by culture were not in the PCR menu (e.g Listeria, Salmonella).

I think these results speak for themselves. Neither method is perfectly sensitive at this point suggesting that both methods should be used if possible to improve diagnosis. PCR can be quicker and detect additional organisms, but still missed a significant number. Interestingly, blood culture was more sensitive in detecting organisms from patients who had previously received antibiotics (P = 0.06). This is counter to what I would've suspected.

What I really liked about this paper is that it was completed in a way that was clinically useful since they enrolled patients as they presented to the ED and asked the question in the way a clinician would. This was not some convenient sample study which we so frequently see in diagnostic test comparisons. I also liked how they presented the information, giving the sensitivity/specificity, predictive values and AUC. It will be interesting to see if future studies can document a clinical benefit in terms of reduced mortality and length of stay when PCR is added to our diagnostic battery. Finally, I was impressed that this study was completed at all. Enrolling so many septic patients with questionnaires over such a long period of time is no small feat. The authors should be congratulated.


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