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 h. 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 catheter (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 antibiotic 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 h (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.

Impact of rapid multiplex PCR on management of antibiotic therapy in COVID-19-positive patients hospitalized in intensive care unit

“…Indeed, since mPCR results were available 1.5 h after reception of the sample and immediately transmitted, intensivists could wait to introduce antibiotics in less severe patients. For the same reason, we observed only 11% de-escalation, which is lower than the 40% expected in studies simulating the impact of mPCR [ 8 , 17 ]. Waiting for the results before initiating or modifying an antibiotic treatment could not have been observed in the previously published studies, as all of them were conducted by simulating an availability of the results and estimating a potential impact on an antibiotic treatment already introduced.…”

Pulmonary infections complicating ARDS

“…Although false-positive results from proximal colonization are a significant problem, intercurrent use of antibiotics is common in ARDS patients and increases the risk of false-negative culture. This is, increasingly, being addressed by the use of culture-independent molecular technique; however, the utility of the tools available is limited by their restricted range of organisms covered and the risk of over-sensitive detection of irrelevant organisms driving inappropriate use of antimicrobials [ 48 – 50 ]. Physicians should be aware of this particular point and therefore interpret with caution the results of these tests.…”

Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia

“…However, apart from our previous report 19 that demonstrated limited clinical impact due to restricted organism coverage, none of the other reports have included ventilated patients and were restricted to retrospective analysis of stored samples. Commercial multiple-pathogen arrays that include respiratory bacteria have recently become available, however most reports of their use in ventilated patients remain limited to describing diagnostic performance, and reporting 'potential' to change antimicrobial therapy rather than impact on clinical practice 3,37,38 . Concerns have been raised about the risks of over-treatment from molecular diagnostics 16,17,39,40 , whilst conversely promising tests with the potential to change therapy have not always proven this in clinical practice 15,19 .…”

“…Concerns have been raised about the risks of over-treatment from molecular diagnostics 16,17,39,40 , whilst conversely promising tests with the potential to change therapy have not always proven this in clinical practice 15,19 . These commercially available assays lack the broad coverage and customisability of the TAC, with consistent concerns raised around limited organism coverage adversely impacting treatment decisions 3,17,19,37,38 .…”