Improved Diagnosis of Peritoneal Dialysis Peritonitis by Calorimetry

Background:

Peritonitis is still considered the most important complication of peritoneal dialysis (PD) associated with high mortality, therapy failure, and healthcare expenses. We have recently demonstrated that peritonitis continuous to be the most common reason for technical failure in PD contributing equally to early and late failure; 12 of 279 patients died as a consequence of PD associated peritonitis. The diagnosis of peritonitis is typically based on clinical symptoms, which reflects an already advanced state of inflammation and disease. Since the implementation of the blood culture system for detection of bacterial growth in PD effluent more than ten years ago, no considerable progress has been made to improve diagnosis of PD associated peritonitis. In our own PD population 36 out of 219 (16%) infectious peritonitis episodes were culture-negative. Usually, detection time of microorganisms requires at least 12 hours and time to pathogen identification more than 48 hours. Rapidly dividing cells such as bacteria produce heat, which can be measured by calorimetry. As recently shown, by our research group, calorimetry allows rapid and accurate diagnosis of bacterial growth in cases of meningitis and in contaminated platelets. In pilot experiments, we could show the potential and the feasibility of calorimetry for early and accurate detection of microorganisms in PD fluid.

Hypothesis and aims:

We hypothesize that calorimetry of PD effluent can significantly improve the diagnosis of PD associated peritonitis by early and accurate detection of pathogens. As compared to traditional culture methods, calorimetry may (i) have a shorter time to positivity and (ii) a higher sensitivity without loss of specificity. Specific aims are to evaluate if calorimetry: (i) is more rapid in detection of microorganisms compared to conventional blood cultures, (ii) is superior, regarding sensitivity and specificity, in detection of PD associated peritonitis compared to the standard blood culture system and (iii) is a valuable tool for pathogen identification by specific heat signal "signatures" received by calorimetry. The Primary endpoint is the time to positivity of bacterial growth by calorimetry and conventional blood cultures. The secondary endpoints are the accuracy (i.e. sensitivity and specificity) of detection rates of microorganism in PD fluid and the rate of consistency of pathogen identification between calorimetry curves and conventional microbiological method.

Research plan: