key: cord-0801388-27fs1ui5
authors: Novy, Emmanuel; Goury, Antoine; Thivilier, Carine; Guillard, Thomas; Alauzet, Corentine
title: Algorithm for rational use of FilmArray Pneumonia Panel in bacterial coinfections of critically ill ventilated COVID-19 patients
date: 2021-07-23
journal: Diagn Microbiol Infect Dis
DOI: 10.1016/j.diagmicrobio.2021.115507
sha: bd2ebf82380301cf865ca3c6797eea31769d0a37
doc_id: 801388
cord_uid: 27fs1ui5

The FilmArray® Pneumonia Panel has proven to be an effective tool for rapid detection of main respiratory pathogens. However, its rational use needs appropriate knowledge and formation regarding its indication and interpretation. Herein, we provide some advices to help with success of its daily routine use, particularly in critically ill ventilated COVID-19 patients. Clinical Trial registration number: NCT04453540.

Since the start of the pandemic Covid-19 outbreak, molecular respiratory panel such as FilmArray® Pneumonia Panel (FAPP; bioMérieux, France) has been widely used in critically ill patients for bacterial coinfections management. Regarding its performance for pathogens and antimicrobial resistance detection (Suppl. Table 1 ), all authors highlighted FAPP interest for antimicrobial stewardship, especially antibiotic sparing [1] [2] [3] [4] [5] [6] . However, FAPP interpretation could be challenging [4, 5] . Indeed, as evoked by Maataoui et al., one of the reasons of a non-optimal use of FAPP was the "lack of knowledge and confidence in the test" [4] . The present study reports the lessons from the implementation of FAPP during the first COVID-19 outbreak, when a training on "how to use FAPP" could not be performed due to the work overload. This is a multicenter retrospective analysis (clinicalTrial.gov NCT04453540) of all critically ill patients who were admitted to the Nancy and Reims University Hospitals (six ICUs) from March to May 2020, with COVID-19 and respiratory failure requiring invasive mechanical ventilation (IMV). The local institutional ethics committee approved this study (Comité d'éthique du CHRU de Nancy, N°CO-20). Informed consent was obtained from all participants and/or their legal guardians. Presence of SARS-CoV-2 was diagnosed using RT-PCR. All patients with suspicion of bacterial pneumonia were eligible. The decision to prescribe FAPP was at the discretion of the clinician. Only patients with concomitant FAPP, conventional culture (CC) and Gram stain were included. Samples were endotracheal aspirates (ETA) and bronchoalveolar lavages (BAL). Results of the FAPP and Gram stain were available for the intensivists within four hours. A first result of the CC was available after one day with a definitive result within five days. For quantitative culture, only the bacteria above the following threshold were considered: 10 4 CFU/mL for BAL and 10 5 CFU/mL for ETA. Phenotypic drug susceptibility testing was performed according to the recommendations of the antibiogram committee of the French Society for Microbiology (CA-SFM)/European Committee for Antibiotic Susceptibility Testing (EU-CAST). A multidisciplinary expert committee (MEC) composed of intensivists, infectious disease specialists and microbiologists from both centers analyzed retrospectively the contribution of FAPP compared to CC in the treatment decision of pneumonia according to criteria from Weiss et al. [7] . Antibiotics used to treat any concomitant infection were not considered by the MEC. Early bacterial coinfections, represented by community-acquired pneumonia (CAP), were defined as infections occurring during the first 48h of ICU admission. The ventilator-associated pneumonia (VAP) were defined as infections occurring after 48h of IMV. Multiple tests from the same patient were considered independent when performed during distinct infectious episodes. Categorical data were analyzed using chi-square test or Fisher's exact test. Statistical analyses were performed by an independent statistician using SAS 9.4 software (SAS Institute, Inc, Cary, N.C.).

Overall, 344 patients with a positive SARS-CoV-2 RT-PCR were admitted in the participating ICUs of whom 90 fulfilled eligibility criteria. Samples were 74 ETA and 45 BAL. Characteristics and ICU data are presented in Table 1 . Bacteriological results were presented in Tables 2 and 3. The rate of clinically confirmed CAP and VAP were 5.0% and 40.3%, respectively. Bacterial pathogens were detected by FAPP (45.4%) and/or by CC (38.7%) in 41 and 34 ETA and in 13 and 12 BAL, respectively. The adequacy between FAPP and CC in pathogen detection was better (p=0.017) for BAL (95.6%) than for ETA (79.7%). for BAL compared with 69% for ETA (p=0.009). The most contribution of FAPP regarding antibiotic prescription was antibiotic spare ( Table 2) . However, we observed that intensivists considered FAPP for treatment only in 42.0% (50/119) of cases.

These results confirmed the usefulness of FAPP to rapidly diagnose bacterial coinfection.

However, there is a room for improvement of its use and interpretation. Herein, we suggest four tips for a tailored use of FAPP in critically ill ventilated patients:

in the daily routine practice. We believe that an appropriate knowledge about FAPP performance and results interpretation should led to a better antibiotic use. Therefore, a collaboration between microbiologists and intensivists is mandatory.

Lower relevance of FAPP results from ETA compared to BAL for treatment could be explained by detection of not significant bacteria from the tracheobronchial colonization.

However, if BAL could not be performed, ETA could be used with cautious interpretation of FAPP results. In the present study, a FAPP use based on these tips would allow 65.6% of antibiotic spare in bacterial coinfection and a better adequacy of empirical antibiotic treatment. Regarding VAP, FAPP should consider local ecology for optimal interpretation, especially for resistance detection (i.e. P. aeruginosa with non-enzymatic resistance). Based on our results, we propose an algorithm to improve the use of FAPP for antibiotic stewardship at the bedside (Figure 1) . Further studies are now warranted to demonstrate that rational use of FAPP will also improve patient outcome.

The authors declare that they have no conflict of interest pertaining to this study.

Funding. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The sponsor was CHRU de Nancy (Direction de la 2) Data are presented as: n (%) ETA: endotracheal aspirate / BAL: bronchoalveolar lavage / CAP: community-acquired pneumonia (defined as infections occurring during the first 48h of ICU admission) / VAP: ventilator-associated pneumonia / FAPP: FilmArray® Pneumonia Panel / CC: conventional culture / AST: antimicrobial susceptibility testing / MRSA: methicillino-resistant Staphylococcus aureus / 3GC-R: third generation cephalosporins resistance / NA: not applicable (species not detected either by the FAPP or by the CC) / MEC: multidisciplinary expert committee. a The isolation of H. alvei and P. stuartii in CC had no impact on antibiotic therapy as they were covered by the antibiotics administered following the detection of other pathogens detected by FAPP. b Among 3GC-resistant Gram-negative bacilli, 3 CTX-M were detected by both FAPP and CC, 2 CTX-M were detected only by FAPP, 2 ESBL not belonging to CTX-M as well as one 3GC-resistant P. aeruginosa were detected only by CC. c A contribution of FAPP at first intensivist decision was noted in 50 samples (42.0%). d Decrease unnecessary antibiotic use (interruption or de-escalation). e Theoretical contribution of FAPP after MEC analysis of the 119 samples (100.0%). Table 3 . Bacteriological results according to the type of respiratory samples IMV, invasive mechanical ventilation; BAL, bronchoalveolar lavage; FAPP, FilmArray® Pneumonia Panel; ATB, antibiotics; GNB, Gram-negative bacilli. a Endotracheal aspirate samples could be used but need cautious interpretation regarding the risk of over-diagnosis due to tracheobronchial colonization b Septic shock (according to SEPSIS-3) or severe ARDS (according to Berlin criteria)

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