Evaluation of a Polymerase Chain Reaction Assay for Pathogen Detection in Septic Patients under Routine Condition: An Observational Study

Abstract

BackgroundTreatment of septic shock relies on appropriate antimicrobial therapy. Current culture based methods deliver final results after days, which may delay potentially lifesaving adjustments in antimicrobial therapy. This study was undertaken to compare PCR with blood culture results under routine conditions regarding 1. impact on antimicrobial therapy, and 2. time to result, in patients with presumed sepsis.Methodology/Principal FindingsThis was an observational study in a 50 beds ICU of a university hospital. In 245 patients with suspected sepsis, 311 concomitant blood cultures and blood for multiplex PCR (VYOO®) were obtained. 45 of 311 blood cultures (14.5%) and 94 of 311 PCRs (30.1%) were positive. However, blood culture or microbiological sampling from the presumed site of infection rarely confirmed PCR results and vice versa. Median time to positivity and interquartile range were 24.2 (18.0, 27.5) hours for the PCR and 68 (52.2, 88.5) hours for BC (p<0.01). PCR median time to result was dependent on technician availability (53.5 hours on Saturdays, 7.2 hours under optimal logistic conditions). PCR results showed good correlation with procalcitonin (p<0.001). In 34% of patients with positive PCRs antimicrobial therapy was considered inadequate according to assessment of clinical arbitrators including 5 patients with vancomycin-resistant enterococci (VRE), 3 cases with multiresistant staphylococci, and 4 patients with fungi.ConclusionsThe results of this observational study support the hypothesis that PCR results are available faster, are more frequently positive, and may result in earlier adjustment of antimicrobial therapy. However, shorter time to result can only be fully exploited when the laboratory is adequately staffed for a 24 hour/7 day service, or when point of care/automated assay systems become available.

Value of multiplex PCR using cerebrospinal fluid for the diagnosis of ventriculostomy-related meningitis in neurosurgery patients

“…The mean time for species identification was 54.8 h by BACTEC CSF cultures whereas SF results were, in 94.8% of cases, obtained on the same day. These detection times are in line with a study from Bloos et al who compared SF with BC results from 245 patients with suspected sepsis and found that the median time for positive BC results was 68.8 h and, under optimal logistical conditions, 7.2 h for SF [17]. With the use of MALDI-TOF MS the time to identification could be reduced and in cases with clinically relevant pathogens combined with low TTP, the species identification might be possible in less than 24 h [18].…”

Sepsis biomarkers and pathogen detection methods: State of the art

“…However, these observations challenge recent data on clinical utility of the assay (50). To give a further example, Bloos and colleagues revealed a median time-to-positivity of 24.2 hours for their NAT and 68 hours for BC, also with a lab on-site (51). Depending on technician availability, the NAT median time-to-positivity increased up to 53.5 hours on weekends.…”

Bacterial sepsis

“…In an observational study investigating implementation of multiplex PCR in the clinical routine of an ICU, an influence on treatment course was only observed when a pathogen was detected that was not susceptible to the initial calculated therapy-specifically, MDR (VRE and MRSA) bacteria and Candida species [94]. Only two randomized studies have been published on this topic so far: In one study comparing Aspergillus PCR to standard diagnostic testing in patients with fever and neutropenia, mortality could be significantly reduced by the PCR-directed treatment [95].…”