Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia

Abstract

Background: Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 hours. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. Methods: In this prospective study we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheters (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital; the medical and infectious diseases ICU, the surgical ICU and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotics changes they would have made if the M-PCR results had been available. Results We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 hours (IQR 4.4-5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95%CI, 73-88%) and specificity of 99% (95%CI 99-100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p=0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods. Conclusions: Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics.

Classical and Molecular Techniques to Diagnose HAP/VAP

“…Peiffer-Smadja et al used the Unyvero system and examined 95 BAL or plugged telescoping catheter samples from 85 patients with HAP or VAP. 47 The median turnaround time of the mPCR assay was 4.6 hours and a total of 90/112 bacteria were detected by mPCR with a global sensitivity of 80% (95% CI 73–88%) and specificity of 99% (95% CI 99–100). 47 Moreover, five of eight extended-spectrum β-lactamases (CTX-M gene) and four of four carbapenemase genes (3 NDM, one oxa-48) were detected.…”

“…47 The median turnaround time of the mPCR assay was 4.6 hours and a total of 90/112 bacteria were detected by mPCR with a global sensitivity of 80% (95% CI 73–88%) and specificity of 99% (95% CI 99–100). 47 Moreover, five of eight extended-spectrum β-lactamases (CTX-M gene) and four of four carbapenemase genes (3 NDM, one oxa-48) were detected. The mPCR could have led to the earlier initiation of an effective antibiotic in 20 of 95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one patient receiving inadequate antimicrobial therapy.…”

HAP and VAP after Guidelines

“…It would have led to antibiotic changes in two-thirds of the patients including an earlier adequate therapy in one-fifth of the cases and a shift to a narrower spectrum antibiotic therapy in more than one-third of the cases. 54 55 56 On the opposite, the spectrum of commercialized multiplex polymerase chain reaction or rapid phenotypic FISH test does not cover all the bacteria and resistance mechanisms and leads to a false negative result and inadequate antibiotic decisions. 57…”