Multicenter evaluation of a syndromic rapid multiplex PCR test for early adaptation of antimicrobial therapy in adult patients with pneumonia

Abstract

Background: Improving timeliness of pathogen identification is crucial to allow early adaptation of antibiotic therapy and improve prognosis in patients with pneumonia. We evaluated the relevance of a new syndromic rapid multiplex PCR test (rm-PCR) on respiratory samples to guide empirical antimicrobial therapy in adult patients with communityacquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-acquired pneumonia (VAP). Methods: This retrospective multicenter study was conducted in four French university hospitals. Respiratory samples were obtained from patients with clinical and radiological signs of pneumonia and simultaneously tested using conventional microbiological methods and the rm-PCR. A committee composed of an intensivist, a microbiologist, and an infectious diseases specialist retrospectively assessed all medical files and agreed on the most appropriate antimicrobial therapy for each pneumonia episode, according to the results of rm-PCR and blinded to the culture results. The rm-PCR-guided antimicrobial regimen was compared to the empirical treatment routinely administered to the patient in standard care. Results: We included 159 pneumonia episodes. Most patients were hospitalized in intensive care units (n = 129, 81%), and episodes were HAP (n = 68, 43%), CAP (n = 54, 34%), and VAP (n = 37, 23%). Conventional culture isolated ≥ 1 microorganism(s) at significant level in 95 (60%) patients. The syndromic rm-PCR detected at least one bacteria in 132 (83%) episodes. Based on the results of the rm-PCR, the multidisciplinary committee proposed a modification of the empirical therapy in 123 (77%) pneumonia episodes. The modification was a de-escalation in 63 (40%), an escalation in 35 (22%), and undetermined in 25 (16%) patients. In microbiologically documented episodes (n = 95), the rm-PCR increased appropriateness of the empirical therapy to 83 (87%), as compared to 73 (77%) in routine care.

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

“…We observed that the main species identified by mPCR, in our population composed exclusively by ICU patients, were Gram-negative bacilli, especially P. aeruginosa, E. coli, and Klebsiella spp. which is consistent with other studies that have evaluated the same kit in ICU patients [8][9][10].…”

“…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.…”

Multinational evaluation of the BioFire® FilmArray® Pneumonia plus Panel as compared to standard of care testing

“…However, considering the high sensitivity and specificity of BioFire PNplus Panel as demonstrated in the US FDA clinical studies [20], in combination with detection of key gram- [24]. A study by Monard et al demonstrated that a multidisciplinary committee proposed modifications of empiric therapy in 77% of pneumonia episodes, including de-escalation (40%) and escalation (22%), and in microbiologic documented cases, the BioFire PNplus Panel increased appropriateness of therapy in 87% of cases as compared to 77% in routine care [34]. This data provides an early indication that proper use and interpretation of BioFire PNplus Panel could lead to targeted therapy not an increase in inappropriate antimicrobial usage.…”

“…HAP and VAP patients pose a different dilemma since these patients quickly become colonized with S. aureus and various gram-negative bacilli which may lead to pneumonia with multidrug-resistant strains [15,16]. Specimens can contain a diversity of pathogens including bacteria, viruses, and fungi [4,[6][7][8][9][10][34][35][36][37][38]. Time to traditional bacterial detection is 24-72 h and antibiotic susceptibility data takes an additional 24-48 h. Comprehensive viral diagnostics are often not performed aside from influenza A/B testing, may not be performed 24/7, or require referral to a reference laboratory delaying time to results.…”

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

“…Commercial multiple-pathogen arrays that include respiratory bacteria have recently become available. However, most of reports of their use in ventilated patients remain limited to describing diagnostic performance, reporting ‘potential’ to change antimicrobial therapy rather than impact on clinical practice 3,25,26 . Concerns have been raised about the risks of over-treatment from molecular diagnostics 16,27,28 , whilst conversely promising tests with the potential to change therapy have not always proven this in clinical practice 15,18 .…”