Assessing FilmArray Pneumonia+ Panel dynamics during antibiotic treatment to predict clinical success in ICU patients with ventilated hospital-acquired pneumonia and ventilator-associated pneumonia: a multicenter prospective study 

Assessing FilmArray Pneumonia+ Panel dynamics during antibiotic treatment to predict clinical success in ICU patients with ventilated hospital-acquired pneumonia and ventilator-associated pneumonia: a multicenter prospective study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Assessing FilmArray Pneumonia+ Panel dynamics during antibiotic treatment to predict clinical success in ICU patients with ventilated hospital-acquired pneumonia and ventilator-associated pneumonia: a multicenter prospective study Julien Dessajan, Michaël Thy, Marc Doman, Jules Stern, Antoine Gallet, and 24 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5950504/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Jul, 2025 Read the published version in Critical Care → Version 1 posted 13 You are reading this latest preprint version Abstract Background Accurate microbiological documentation seems central for managing severe pneumonia. While the FilmArray® Pneumonia + panel (FA-PP) offers rapid pathogen identification, its effectiveness during antibiotic treatment and in predicting clinical outcomes remains unclear. Methods We conducted a prospective observational study across four ICUs from April 2022 to June 2024, including patients with ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP). Bacterial loads were monitored on days 0, 1, 3, 7 and 10 and 3 days after stopping antibiotics, using endotracheal aspirates (ETAs) analyzed by FA-PP and standard cultures. The main objective was to assess the correlation between quantitative changes in FA-PP results and clinical success. Quantitative changes over time were analyzed using mixed ordinal logistic regression. Results Of the 93 patients enrolled, 60.2% (n = 56) achieved clinical success, while the ICU mortality rate was 25.8% (n = 24). Although FA-PP and culture quantification results declined over time (p < 0.0001), neither method consistently correlated with clinical success (non-significant for both). At diagnosis, FA-PP showed excellent diagnostic performance compared to culture, with a sensitivity of 94% [95% CI: 87–97] and a specificity of 98% [95% CI: 97–98]. Quantitative concordance improved with higher DNA copies, from 22.9% at the culture threshold at 10⁴ DNA copies/ml in FA-PP to 100% at ≥ 10⁷ DNA copies/ml. Diagnostic performance remained stable during antibiotic treatment with 94% sensitivity and 95% specificity in follow-up ETAs. Conclusions FA-PP provides rapid and accurate diagnostics but does not predict clinical outcomes during treatment, indicating limited utility for repeated testing in patient management. Ventilator-associated pneumonia Multiplex PCR FilmArray pneumonia panel Microbiological outcomes Nosocomial pneumonia Figures Figure 1 Figure 2 Background Appropriate antibiotic therapy, guided by early and accurate microbiological identification, plays a key role in the management of severe pneumonia ( 1 ). Currently, bacterial culture of respiratory samples remains the gold standard for diagnosing healthcare-associated pneumonia. However, these conventional methods are often slow, requiring 24–72 hours to yield results, and they lack sensitivity. During this period, antibiotic treatment is often empirical, which expose patients to potential early therapeutic failure and clinical deterioration ( 2 – 4 ). To address these challenges, new rapid diagnostic tests have been developed to enhance the microbiological documentation of pneumonia ( 5 ). These tests are based on molecular methods such as Multiplex Polymerase Chain Reaction (mPCR), performed directly on clinical samples. Among these, the FilmArray® Pneumonia + panel (FA-PP, BioFire, bioMérieux) stands out for its rapid turnaround time of 75 minutes. This panel can identify 15 bacteria semi-quantitatively (from 10 4 to ≥ 10 7 DNA copies/ml), 3 atypical bacteria, 7 resistance genes, and 8 viruses ( 6 ). In several clinical studies, the FA-PP demonstrated good diagnostic performance and strong correlation with bacterial culture results ( 7 – 9 ). Additionally, its use has been associated with improved appropriateness of initial antibiotic therapy and better antibiotic management ( 10 – 13 ). However, the interpretation of a positive FA-PP result in the context of a negative culture remains delicate. Such results may indicate false positives or the persistence of DNA from non-viable bacteria, particularly if antimicrobial therapy was initiated prior to respiratory sampling. Furthermore, the semi-quantitative results of FA-PP seem to offer limited information, as the quantitative correlation between PCR DNA copy numbers and culture colony-forming units (CFU) is weak (40–56%) ( 14 , 15 ). Consequently, their use in clinical practice is unclear until they can be standardized. When evaluating the efficacy of antimicrobial treatment for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), experts chose not to include microbiological cure in the composite endpoints, as clinical outcomes generally offer a more comprehensive assessment ( 16 ). However, one retrospective study suggested that microbiological failure, even when clinical cure was achieved, could still be associated with an increased risk of recurrent pneumonia or death in patients with bacterial pneumonia ( 17 ). Predicting clinical success in patients with pneumonia undergoing antibiotic treatment could be a potential clinical application of the semi-quantitative results of FA-PP. However, the correlation of FA-PP results over time with clinical outcomes, as well as the correlation between FA-PP results and culture during antibiotic treatment, have not yet been assessed. The main objective of this study was to determine whether a decline in FA-PP semi-quantitative results correlates with clinical success in patients with ventilated hospital-associated pneumonia (vHAP) or VAP. Methods Study design This prospective observational study was conducted in four intensive care units (ICUs) of two French university teaching hospitals. Ethical Considerations This observational study included patients under mechanical ventilation at inclusion. Participation was communicated to their next of kin through a signed "informative letter to relatives," outlining their right to object. Upon discharge, an "informative letter to the patient" was given if they were able to receive it; otherwise, it was mailed. Informative letters are available in the Additional File 1 . No written consent was required per regulations. Data from paper Case Report Forms (CRFs) were transferred to a secure database on the hospital's intranet, managed by OUTCOMEREA with INSERM U1137. The database was registered with Commission Nationale de l’Information et des Libertés (CNIL; No. 999262), and MR003 methodology compliance was declared on March 7, 2019 (No. 2212137 v 0). The study received approval from the Société de Réanimation de Langue Française (SRLF) Ethics Committee on September 20, 2022 (No. 22–041). Definitions Pneumonia, vHAP, VAP and episodes of recurrence, relapse or re-infection were defined as previously described ( 18 , 19 ). According to the multinational expert consensus specified above, a clinical cure was characterized by both clinical and radiographic criteria ( 16 ). Definitions are detailed in the Additional File 1 . Patient Selection All adults with vHAP or VAP microbiologically confirmed by a single invasive distal respiratory sample, such as bronchoalveolar lavage (BAL) or mini-BAL, were eligible for inclusion. Patients were included if their pneumonia episode was confirmed by the detection of at least one bacterium using the FA-PP. Exclusion criteria were a life expectancy of less than 72 hours at the time of inclusion, a decision to withdraw or withhold life support, and opposition to research participation. Data collection All clinical data were collected prospectively by the investigators. The study started on day zero (D0), at the initial suspicion of vHAP or VAP. Pneumonia was confirmed by a single initial sample (BAL or mini-BAL) collected systematically for each patient prior to the initiation of empiric antibiotic therapy. As FA-PP is routinely used in the participating centers, empiric antibiotic therapy was guided by its results. An initial endotracheal aspirate (ETA D0) was collected prior to initiation of antibiotic therapy and analyzed using both FA-PP and conventional culture methods. For quantification analysis, the ETA D0 was considered valid if collected before or within the first six hours of antibiotic initiation. Repeated ETAs were collected using the same two methods on days 1, 3, 7, and 10 after diagnosis, as well as three days after antibiotic discontinuation. Complete sequential ETA follow-up was defined as having an ETA performed on Day 7. In cases where patients were weaned from mechanical ventilation, follow-up ETAs were not performed. Clinicians involved in the study were blinded to all ETA microbiological results throughout the study. In cases of clinical suspicion of vHAP or VAP recurrence, a new distal sample (BAL or mini-BAL) was obtained to confirm the diagnosis as part of standard patient care. Bacterial cultures from respiratory samples were performed by a quantitative method using serial dilutions, in accordance with the French Standard Recommendations in Medical Microbiology (REMIC), as detailed in the Additional File 1 . FA-PP was performed upon the arrival of the respiratory samples, concurrently with the bacterial cultures, in accordance with the manufacturer's recommendations. Outcomes The primary outcome was clinical success, defined as a composite measure including clinical cure during antibiotic treatment or within three days after antibiotic discontinuation, and survival without recurrence within seven days after antibiotic discontinuation, as previously defined ( 16 ). The primary outcome was assessed in all enrolled patients. The greatest changes in semi-quantitative FA-PP and culture results from Day 0 to Day 3 and from Day 0 to Day 7 were monitored, and their correlation with the primary outcome was analyzed. Bacterial load quantification with both techniques was monitored over time, and their relationships with time and clinical success were analyzed. For this purpose, Day 0 ETA results were used if the sample was collected before or within the first six hours after initiation of antibiotic treatment. Late-collected Day 0 ETAs were excluded from the analysis to ensure consistency in monitoring bacterial load. In patients with insufficient secretions or when ETA D0 was collected more than six hours after antibiotic initiation, the BAL or mini-BAL result was used for Day 0 quantification, followed by a Day 1 ETA for Day 1 quantification. The diagnostic performance of FA-PP compared to culture was assessed by evaluating the detection of the 15 typical panel bacteria in initial respiratory samples and follow-up ETAs. In addition, the quantitative concordance between semi-quantitative FA-PP results and culture concentrations was evaluated under both antibiotic-free conditions and during antibiotic treatment. Statistical analysis Data were expressed as medians (interquartile range) or numbers (percentage). To analyze the evolution of semi-quantitative results, data were categorized into five groups ranging from 0 to 4: #0 for negative results; #1 for 10 4 DNA copies/ml for FA-PP, <10 5 CFU/ml for ETA culture, and < 10 4 CFU/ml for mini-BAL and BAL culture; #2 for 10 5 DNA copies/ml for FA-PP, 10 5 CFU/ml for ETA culture, and 10 4 CFU/ml for mini-BAL and BAL culture; #3 for 10 6 DNA copies/ml for FA-PP, 10 6 CFU/ml for ETA culture, and 10 5 CFU/ml for mini-BAL and BAL culture; and #4 for ≥ 10 7 DNA copies/ml for FA-PP, >10 6 CFU/ml for ETA culture, and > 10 5 CFU/ml for mini-BAL and BAL culture. The five classification groups were arbitrarily defined based on sample dilution and their ability to reflect lower respiratory tract infection, as previously suggested by differences in culture positivity thresholds ( 20 ). To account for the ordinal nature of semi-quantitative results, a mixed ordinal logistic regression model was used. This model allowed for the analysis of repeated measures while accounting for within-patient variability. Results were presented as effect estimates with standard errors (SE) and p-values (Pr > [t]). Changes in bacterial load were expressed as logarithmic changes (e.g., + 2 log, + 1 log, -1 log, -2 log ) , indicating the variation in DNA copies/ml or CFU/ml from baseline (Day 0) to Days 3 and 7. To visualize changes in bacterial load, waterfall plots were generated, illustrating individual trajectories stratified by clinical outcomes. P values < 0.05 were considered significant. Statistical analyses were performed using SAS 9.4 (Cary, North Carolina, USA). Results Study population Between April 20, 2022, and June 11, 2024, a total of 93 patients were enrolled in the four participating ICUs. The baseline characteristics of the patients are detailed in Table 1 . Clinical outcomes All patients were followed throughout the study, and the primary outcome was assessed for all enrolled patients. Clinical success was achieved in 56 patients (60.2%), while ICU and in-hospital mortality rates were 25.8% (n = 24/93) and 29% (n = 27/93), respectively. (Table 1 ). During the ICU stay, the overall recurrence rate after inclusion was 32.3% (n = 30/93), comprising 20 episodes of relapse (66.7%) and 10 episodes of re-infection (33.3%). Most patients with recurrence experienced a single episode (n = 26/30; 87%). Table 1 Characteristics of patients and outcomes of 93 vHAP/VAP episodes All patients n = 93 Clinical success n = 56 Clinical failure n = 37 Baseline characteristics Age – years 59 [51; 66] 59 [47; 63] 63 [55; 70] Male 62 (66.7) 37 (66.1) 25 (67.6) Weight – kg 76 [65; 90] 76 [66; 90] 75 [62; 82] BMI – kg/m² 25.4 [22.9; 30.4] 25.6 [23.2; 30.6] 25.2 [22.2; 29.3] Co-morbid conditions Chronic respiratory disease 28 (30.1) 14 ( 25 ) 10 ( 27 ) COPD 12 (12.9) 7 (12.5) 5 (13.5) Asthma 4 (4.3) 1 (1.8) 3 (8.1) Others 12 (12.9) 8 (14.3) 4 (10.8) Immunodepression 32 (34.4) 15 (26.8) 17 (45.9) HIV infection 8 (8.6) 4 (7.1) 4 (10.8) AIDS 4 (4.3) 2 (3.6) 2 (5.4) Solid organ transplant recipient 17 (18.2) 8 (14.3) 9 (24.3) Immunosuppression* 21 (22.6) 10 (17.9) 11 (29.7) Charlson co-morbidity score 2 [0; 4] 2 [0; 3] 1 [0; 4] Characteristics at inclusion Hospital stay prior to ICU admission – days 1 [0; 3] 1 [0; 2] 1 [0; 4] ICU stay prior to inclusion – days 7 [3; 12] 8 [4; 13] 6 [2; 8] Known MDR and/or XDR carriage before inclusion 25 (26.9) 14 ( 25 ) 11 (29.7) ESBL-E carriage 23 (24.7) 12 (21.4) 11 (29.7) Antimicrobial therapy within the 7 days before inclusion 57 (61.3) 31 (55.4) 26 (70.3) Fever (> 38.3°C) or hypothermia (< 35°C) 73 (78.5) 42 (75) 31 (83.8) Hypotension /vasopressor requirement 53 (57) 28 (50) 25 (67.6) Worsening oxygenation 81 (87.1) 49 (87.5) 32 (86.5) PaO2/FiO2, median [IQR] 192 [133; 255] 206 [141; 284] 160 [109; 220] Purulent tracheal secretions 79 (84.9) 46 (82.1) 33 (89.2) WBC count - x 10 9 /L 12 [8.4; 17.6] 11.9 [8.8; 18.6] 12.4 [8.2; 16.5] Neutrophils - x 10 9 /L 10 [6.4; 14.3] 9.9 [6.8; 14.6] 9.7 [5.7; 13.6] Procalcitonin — ng/ml (missing, n = 17) 0.5 [0.2; 2] 0.5 [0.2; 1.5] 0.5 [0.3; 2.2] SAPS II 46 [37; 61] 43 [37; 61] 50 [38; 62] Pneumonia type Ventilated Hospital-acquired 21 ( 23 ) 10 (17.9) 11 (29.7) Ventilator-associated 72 (77) 46 (82.1) 26 (70.3) Initial sampling Sample type Bronchoalveolar lavage (BAL) 51 (54.8) 28 (50) 23 (62.2) Mini-BAL 42 (45.2) 28 (50) 14 (37.8) Positive Gram stain examination: positive 73 (78.5) 45 (80.4) 28 (75.7) Clinical outcomes ICU mortality 24 (25.8) 6 (10.7) 18 (48.6) In-hospital mortality 27 (29) 9 (16.1) 19 (51.4) Decisions of withholding and withdrawal of life sustaining therapies 24 (25.9) 10 (16.1) 15 (40.5) SOFA score 28 days after inclusion (missing, n = 38) 1 [0; 4] 1 [1; 2] 2 [1; 2] ICU length of stay – days (missing, n = 1) 25 [16; 48] 25 [17; 48] 24 [13; 44] Hospital length of stay – days (missing, n = 7) 52 [24; 79] 52 [35; 79] 37 [20; 76] Antibiotics duration – days 7 [5; 8] 7 [6; 8] 6 [4; 9] IMV duration – days (missing, n = 1) 19 [12; 32] 19 [12; 34] 20 [11; 32] Weaning tracheostomy 14 (15.1) 7 (12.5) 7 (18.9) Results are expressed as median [IQR] or number of cases (%). vHAP ventilated hospital-acquired pneumonia, VAP ventilator-associated pneumonia, BMI body mass index, COPD chronic obstructive pulmonary disease, HIV human immunodeficiency virus, AIDS acquired immunodeficiency syndrome, ICU intensive care unit, MDR multidrug resistance, XDR Extensively drug-resistance, ESBL-E extended spectrum beta-lactamase producing Enterobacterales, WBC white blood cells, SAPS simplified acute physiology score, SOFA sequential organ failure assessment, IMV invasive mechanical ventilation. *Immunosuppression was defined as recent (within the last 3 months) or active anticancer chemotherapy, systemic steroids ≥ 10 mg/day for at least 15 days, or other immunosuppressive or immunomodulatory drugs. Samples and bacteriological findings In initial samples (51 BALs and 42 mini-BALs), standard culture identified 134 bacteria, of which 19 (14.2%) were not detected by FA-PP because they were outside the target panel. In parallel, FA-PP detected 138 bacteria. The five most commonly isolated bacteria in culture were Pseudomonas aeruginosa (n = 28/134; 20.9%), Escherichia coli (n = 14/134; 10.4%), Klebsiella pneumoniae (n = 14/134; 10.4%), Staphylococcus aureus (n = 12/134; 9%), and Enterobacter cloacae (n = 10/134; 7.5%), as detailed in Supplementary Table 1, Additional File 1 . On Day 0, 52 ETAs (Day 0 ETA) were collected either prior to or within the first 6 hours of antibiotic initiation, representing 56% of the patients. For late-collected or missed Day 0 ETAs (n = 41; 44%), the BAL or mini-BAL diagnostic results were used for Day 0 quantification. To monitor bacteriological findings during treatment, a total of 196 ETAs were collected. Complete sequential ETA follow-up to at least Day 7 was performed in 47 patients (50.5%). Of the 46 patients who did not undergo ETA on day 7, 27 (58.7%) were weaned from mechanical ventilation, 7 (15.2%) had a recurrence, 7 (15.2%) had a missed sampling, and 5 (10.9%) died or were in the process of withdrawal of life-sustaining therapy prior to day 7. FA-PP and culture dynamics during antibiotic treatment Prior to antibiotic initiation, no association was found between the initial bacterial load and clinical success, whether using FA-PP or conventional culture ( Supplementary Table 2, Additional File 1) . During antibiotic treatment, the semi-quantitative FA-PP results (in DNA copies/ml) showed a median greatest change of 0.0 (IQR [-0.3; 0.0]) from Day 0 to Day 3 among 71 patients and − 0.1 (IQR [-0.3; 0.0]) from Day 0 to Day 7 among 47 patients (Table 2 A). These decreases were not significantly different between patients with clinical success and those without. For culture results (in CFU/ml), the median change was − 0.7 (IQR [-1; 0.0]) from Day 0 to Day 3 among 58 patients and − 0.2 (IQR [-0.4; -0.1]) from Day 0 to Day 7 among 40 patients. These changes in culture results were not correlated with clinical success either (Table 2 A). When analyzing the changes in bacterial load by logarithmic categories, no clear trend was observed across the different change categories (+ 2 log or more, + 1 log, no change, -1 log, -2 log or less), regardless of the clinical outcome. These results were confirmed by the mixed ordinal regression model, which was performed using the semi-quantitative groups and demonstrated a decrease over time in both the number of copies and in bacterial load in culture ( P < 0.001). This decrease was similar in patients with clinical success and those with clinical failure ( P = 0.71 for FA-PP and P = 0.61 for bacterial culture; Table 2 B). Figure 1 A and 1 B illustrate the changes in bacterial load from diagnosis (Day 0) to Day 3 for each patient, and their corresponding clinical outcome, with DNA copies/ml measured by FA-PP and CFU/ml measured by culture, respectively. The greatest change in bacterial load from Day 0 to Day 7 is shown in Supplementary Fig. 1. Table 2 FA-PP and culture quantification follow-up during antibiotic treatment Greatest changes in FA-PP and culture results by clinical outcome All patients (n = 93) Clinical success (n = 56) Clinical failure (n = 36) FA-PP Greatest change in DNA copies/ml from Day 0 to Day 3 n = 71 0.0 [-0.3; 0.0] n = 43 -0.3 [-0.3; 0.0] n = 28 0.0 [-0.3; 0.0] + 2 log or more 6 (6.5) 4 (7.1) 2 (5.6) + 1 log 4 (5.6) 1 (2.3) 3 (10.7) No change 28 (39.4) 16 (37.2) 12 (42.9) − 1 log 21 (29.6) 13 (30.2) 8 (28.6) − 2 log or less 12 (12.9) 9 (16.1) 3 (8.3) Greatest change in DNA copies/ml from Day 0 to Day 7 n = 47 -0.1 [-0.3; 0.0] n = 22 -0.1 [-0.3; 0.0] n = 24 -0.1 [-0.3; 0.0] + 2 log or more 3 (3.2) 2 (3.6) 1 (2.8) + 1 log 5 (10.6) 2 (9.1) 3 (12.5) No change 10 (21.3) 4 (18.2) 5 (20.8) − 1 log 14 (29.8) 7 (31.8) 7 (29.2) − 2 log or less 15 (16.1) 7 (12.5) 8 (22.2) Culture Greatest change in CFU/ml from Day 0 to Day 3 n = 58 -0.7 [-1; 0.0] n = 33 -0.5 [-0.8; 0.0] n = 25 -0.7 [-1; 0.0] + 2 log or more 2 (2.2) 0 2 (5.6) + 1 log 4 (6.9) 3 (9.1) 1 ( 4 ) No change 10 (17.2) 6 (18.2) 4 ( 16 ) − 1 log 10 (17.2) 8 (24.2) 2 ( 8 ) − 2 log or less 32 (34.4) 16 (28.6) 16 (44.4) Greatest change in CFU/ml from Day 0 to Day 7 n = 40* -0.2 [-0.4; -0.1] n = 17 -0.3 [-0.4; -0.1] n = 22 -0.2 [-0.3; -0.1] + 2 log or more 3 (3.2) 1 (1.8) 2 (5.6) + 1 log 1 (2.5) 0 (0) 1 (4.5) No change 3 (7.5) 1 (5.9) 2 (9.1) − 1 log 13 (32.5) 6 (35.3) 6 (27.3) − 2 log or less 20 (21.5) 9 (16.1) 11 (30.6) Quantification follow-up was based on the most abundant bacterium in the Day 0 ETA. In case of a tie, the most pathogenic bacterium was selected. *The seven remaining patients had a negative culture result on Day 0 ETA. Results are expressed as median [IQR] or number of cases (%). FA-PP FilmArray® Pneumonia + panel, CFU colony-forming unit (B) Mixed ordinal regression analysis of quantification over time FA-PP Effect Estimate SE Pr >|t| Time -0.29 0.03 |t| Time -0.29 0.03 < 0.0001 Clinical success 0.14 0.27 0.61 Mixed ordinal regression analysis was performed using the quantification groups (0 to 4). Solution for fixed effects, Model with censoring after day 14. FA-PP FilmArray® Pneumonia + panel, SE standard error Diagnostic performance of FA-PP compared to culture For bacterial detection on initial samples At inclusion, 104 bacterial isolates from the panel were detected by both FA-PP and standard culture in the 93 initial specimens (BAL or mini-BAL). FA-PP identified 34 additional bacteria that were not detected by culture in 26 of these samples ( Supplementary Table 3, Additional File 1 ). These 34 cases were categorized as follows: 17 cases (50%) were classified as false positives, as the microorganisms were never cultured before or after study entry; 15 cases (44.1%) involved samples collected after the initiation of antibiotic therapy; and 2 cases (5.9%) involved bacteria associated with prior episodes of pneumonia. Conversely, seven bacterial isolates identified by culture were not detected by FA-PP, although belonging to the FA-PP panel: five from mini-BAL samples and two from BAL samples ( Supplementary Table 4, Additional File 1 ). Of these samples, only two exceeded the culture threshold ( S. pneumoniae n = 1, E. cloacae n = 1). Overall, the technical sensitivity and specificity (detection of the 15 typical bacteria panel) of the FA-PP compared to culture were 94% [95% CI: 87–97] and 98% [95% CI: 97–98] for diagnostic specimens, respectively (Table 3 ). For bacterial detection during antibiotic treatment For all ETA samples collected during antibiotic treatment, sensitivity was 94% [95% CI: 90–97] and specificity was 95% [95% CI: 94–96] (Table 3 ). For antimicrobial resistance genes on initial samples Nineteen bla CTX-M genes were detected, with 6 resulting in false positives, representing a 31.6% overdiagnosis rate ( Supplementary Table 5, Additional File 1 ). Two cases of the bla NDM gene were detected, including one false positive. For the mecA/C and MREJ genes, three instances were detected, with one false positive and one false negative, resulting in a missed detection rate of 1.1% and an overdiagnosis rate of 33.3%. Table 3 Diagnostic performance of FA-PP compared to culture for the 15 typical bacteria of the panel at diagnosis and during antibiotic treatment Number of samples performed Number of bacteria detected FA-PP+/ culture+, n FA-PP+/ culture-, n FA-PP-/ culture+, n FA-PP-/ culture-, n Se, % (95%CI) Sp, % (95%CI) BAL and mini-BAL: D0 93 104 34 7 1330 94 (87–97) 98 (97–98) BAL: D0 51 62 18 2 747 97 (89–100) 98 (96–99) Mini-BAL: D0 42 42 16 5 583 89 (77–96) 97 (96–98) ETA: D0 52 62 30 4 750 95 (85–98) 96 (95–97) ETA: follow-up 196 170 140 10 2800 94 (90–97) 95 (94–96) FA-PP FilmArray® Pneumonia + panel, Se sensitivity, Sp specificity, CI confidence interval, BAL bronchoalveolar lavage, ETA endotracheal aspirate Quantitative concordance on diagnosis and during antibiotic treatment In diagnostic samples (BAL and mini-BAL), 61.6% of pathogens were detected at or above the culture threshold, compared with only 28.7% in follow-up ETA samples (Table 4 ). The concordance between bacteria detected by FA-PP and those recovered by culture increased with the number of DNA copies identified by FA-PP. In diagnostic samples, when FA-PP identified bacteria at 10 4 DNA copies/ml, only 22.9% (n = 8/35) were detected at or above the culture threshold. Conversely, at ≥ 10 7 DNA copies/ml, 100% of bacteria were detected at or above the culture threshold. During antibiotic treatment, this correlation persisted, with culture positivity increasing from 2.8% at the threshold for a FA-PP result of 10 4 DNA copies/ml to 66.7% for bacteria detected at ≥ 10 7 DNA copies/ml (Table 4 and Fig. 2 ). Table 4 Quantitative concordance between FA-PP and culture for the 15 typical bacteria of the panel at diagnosis and during antibiotic treatment Culture: BAL and mini-BAL D0 Total Culture: BAL D0 Total Culture: mini-BAL D0 Total FA-PP <threshold* ≥threshold* < 10^4 CFU/ml ≥ 10^4 CFU/ml < 10^3 CFU/ml ≥ 10^3 CFU/ml 10^4 DNA copies/ml 27 (77.1) 8 (22.9) 35 16 (94.1) 1 (5.9) 17 11 (61.1) 7 (38.9) 18 10^5 DNA copies/ml 17 (53.1) 15 (46.9) 32 13 (65) 7 (35) 20 4 (33.3) 8 (66.7) 12 10^6 DNA copies/ml 9 ( 25 ) 27 (75) 36 3 (16.7) 15 (83.3) 18 6 (33.3) 12 (66.7) 18 ≥ 10^7 DNA copies/ml 0 (0) 35 (100) 35 0 (0) 25 (100) 25 0 (0) 10 (100) 10 Total 53 (38.4) 85 (61.6) 138 32 (40) 48 (60) 80 21 (36.2) 37 (63.8) 58 Culture: ETA D0 Total Culture: ETA follow-up Total FA-PP < 10^5 CFU/ml ≥ 10^5 CFU/ml < 10^5 CFU/ml ≥ 10^5 CFU/ml 10^4 DNA copies/ml 16 (88.9) 2 (11.1) 18 69 (97.2) 2 (2.8) 71 10^5 DNA copies/ml 16 (76.2) 5 (23.8) 21 78 (88.6) 10 (11.4) 88 10^6 DNA copies/ml 5 (23.8) 16 (76.2) 21 48 (65.8) 25 (34.2) 73 ≥ 10^7 DNA copies/ml 6 (18.8) 26 (81.3) 32 26 (33.3) 52 (66.7) 78 Total 43 (46.7) 49 (53.3) 92 221 (71.3) 89 (28.7) 310 Results are expressed as number of cases (%). *Threshold: ≥10^4 CFU/ml for BAL and ≥ 10^3 CFU/ml for mini-BAL FA-PP FilmArray® Pneumonia + panel, BAL broncho-alveolar lavage, CFU colony-forming unit Discussion This prospective study is, to our knowledge, the first to follow-up on changes in FA-PP results during the course of antibiotic treatment in ICU patients with VAP and vHAP. While both FA-PP and culture quantifications decreased over time, these reductions did not correlate significantly with clinical outcome. This finding suggests that changes in FA-PP and culture semi-quantitative levels alone may not reliably predict clinical success. Although the evolution of FA-PP during treatment has not been previously assessed, the impact of microbiological failure on clinical outcomes has been studied. One study indicated that microbiological failure, as determined by culture, was associated with an increased risk of recurrent pneumonia or death, even when clinical cure was achieved ( 17 ). However, the retrospective design and specific patient population of this study limited its conclusions. Additionally, randomized controlled trials on nosocomial pneumonia have shown differences in microbiological cure rates between treatment groups, despite similar clinical cure and mortality rates ( 21 – 24 ). Due to the lack of a consistent correlation between microbiological cure and patient outcomes, experts have rejected the use of microbiological cure as a reliable criterion for establishing consensus clinical endpoints in HAP and VAP clinical trials ( 16 ). Given the potential of FA-PP to detect DNA of bacteria not able to grow, it might be expected that FA-PP results would show a smaller or slower decline during treatment. However, our findings revealed that FA-PP semi-quantitative levels decreased during treatment regardless of clinical success. Consequently, our results indicate that FA-PP should not be used to predict clinical outcomes in patients with severe hospital-acquired pneumonia. The diagnostic performance of FA-PP compared to standard culture was excellent in our study, consistent with previously published findings. A recent meta-analysis reported sensitivity and specificity of 94% and 98%, respectively ( 9 ). These diagnostic performances remained consistent throughout the antibiotic treatment, with a sensitivity of 94% and a specificity of 95%, despite initial concerns that it might be adversely affected. This suggests that FA-PP detection and culture results decline under antibiotic influence in a comparable manner. We identified a clear correlation between semi-quantitative FA-PP results, expressed in DNA copies/ml, and bacterial inoculum measured in CFU/ml. Rather than focusing solely on the correspondence between these two units, our approach emphasized clinical relevance by prioritizing the identification of samples that met the diagnostic threshold necessary for confirming a positive result. Our data demonstrated that higher DNA copy numbers were associated with an increased likelihood of pathogen detection at the culture threshold. Furthermore, this study is the first to assess this quantitative concordance during antibiotic treatment, and to show that it remained relatively stable throughout the treatment course. Few studies have examined quantitative concordance at diagnosis, aiming to refine the interpretation of semi-quantitative FA-PP results and determine a potential positivity threshold. Comparing bacterial loads using the two techniques, authors reported poor quantitative concordance between FA-PP and culture (43% and 53.6%) ( 14 , 15 ). The FA-PP tended to overestimate bacterial load, likely due to the detection of both live and dead organisms by PCR. Similarly, a British study on community-acquired pneumonia, using mostly sputum samples, found that PCR detected higher bacterial loads in culture-positive samples compared to culture-negative samples, which were often collected after antibiotic initiation ( 25 ). This suggests that mPCR could potentially enable a microbiological diagnosis even when early antibiotic therapy, initiated prior to sampling, results in negative culture outcomes. However, our study did not explore this aspect, emphasizing the need for further research to investigate this issue. Regarding resistance gene detection by FA-PP, we observed a high proportion of bla CTX-M genes (20.4%), the most prevalent gene among ESBL-producing Enterobacterales in Europe. This is likely attributable to the high baseline prevalence of ESBL-E carriers in our study population at inclusion (24.7%). As previously observed, the interpretation of resistance gene results should be considered within the context of clinical pre-test probability to avoid overdiagnosis. Given the high sensitivity of the technique, the overdiagnosis rates we observed ranged between 31.6% and 50%, consistent with recent studies that have raised concerns about this issue ( 5 ). This study has several limitations. First, inconsistent Day 0 sample selection introduced potential bias. In 54.9% of patients, the initial sample for quantification was a Day 0 ETA; however, BAL or mini-BAL samples replaced ETAs when the latter were unavailable or collected more than 6 hours post-antibiotic initiation. This variation may have affected the observed dynamics of quantification under antibiotic treatment. Second, analysis of quantification dynamics was limited to a subset of patients due to missing samples, early mortality, or weaning from mechanical ventilation before Day 7. Finally, although a recent study found limited evidence of significant over-identification in ETA compared with single-site BAL, our use of ETAs for follow-up may introduce bias by potentially overestimating microbial loads ( 1 , 4 , 26 , 27 ). On the other hand, the multicenter design of this study enhances the generalizability of the findings. Furthermore, we selected clinical cure as our primary endpoint, a criterion validated by a previously established expert panel ( 16 ). Lastly, interpreting concordance between the two quantification methods from a clinician’s perspective allows for better applicability for the ICU setting. Conclusions The semi-quantitative FA-PP results in patients with vHAP and VAP undergoing antibiotic treatment decline over time, similarly to bacterial culture quantifications. However, neither FA-PP nor culture dynamics during treatment reliably predict clinical success. Consequently, repeated cultures or FA-PP testing during treatment to assess patient recovery do not appear to be recommended. Quantitative concordance between FA-PP and culture is acceptable prior to treatment, particularly for predicting culture threshold results, and this concordance seems to remain stable during treatment. Further research is needed to refine the interpretation of FA-PP result dynamics and to explore their clinical utility in the management of severe hospital-acquired pneumonia. Abbreviations BAL bronchoalveolar lavage bla CTX-M cefotaximase-munich beta-lactamase gene bla NDM New Delhi metallo-beta-lactamase gene CFU colony-forming unit CI confidence interval CNIL commission nationale de l’information et des libertés CRF case report form DNA deoxyribonucleic acid ESBL-E extended-spectrum beta-lactamase-producing enterobacterales ETA endotracheal aspirate FA-PP FilmArray® Pneumonia+ panel ICU intensive care unit mecA/C methicillin resistance gene a/c mPCR multiplex polymerase chain reaction MREJ methicillin-resistant epidemiological junction REMIC recommendations in medical microbiology Se sensitivity SE standard error Sp specificity SRLF société de réanimation de langue française VAP ventilator-associated pneumonia vHAP ventilated hospital-acquired pneumonia Declarations Ethics approval and consent to participate This study was approved by the Société de Réanimation de Langue Française (SRLF) Ethics Committee on September 20, 2022 (No. 22-041). As this was an observational study, written consent was not required per national regulations. Since this study involved mechanically ventilated patients, participation was communicated to next of kin through an informative letter outlining their right to object. Upon discharge, patients received an informative letter, or it was mailed when necessary. Consent for publication This study does not contain any individual person’s data in any form (such as images, videos, or personal details). Not applicable. Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Data were securely stored in a hospital intranet database, managed by OUTCOMEREA under the oversight of INSERM U1137, and registered with the Commission Nationale de l’Information et des Libertés (CNIL; No. 999262). MR003 methodology compliance was declared on March 7, 2019 (No. 2212137 v 0). Competing interests JD, JFT, and LAL report the provision of mPCR kits free of charge to the study centers by BioMérieux. JD has received honoraria for lectures from BioMérieux. JFT has received consulting fees from Advanz, Menarini, Pfizer, and Merck, as well as honoraria for lectures from BioMérieux, Mundipharma, and Merck. LAL has received consulting fees from Shionogi and Viatris, honoraria for lectures from Advanz, Pfizer, and Shionogi, and has also given lectures without fees from BioMérieux and Qiagen. RS reports receiving grants from LFB and ABpharma outside the submitted work. HDR has received support for meetings from Shionogi. NG has received honoraria for lectures from Viatris and support for meetings from Pfizer. The authors declare no other financial or non-financial competing interests related to this study. Funding The study was funded by an unrestricted investigator-driven grant from BioMérieux (n°IPM 20586). The company had no role in the conceptualization, study design, data collection, analysis, decision to publish, or manuscript preparation. Authors’ contributions JFT, LAL, and JD conceptualized the study. JFT, SR, LAL, and JD developed the methodology. SR conducted the formal analysis and investigation. JD, SR, JS, AG, GF, SC, HDR, SG, and FL were responsible for data curation. JD drafted the original manuscript. MT, LH, JLM, LB, RS, EDM, CP, MD, ME, VB, NG, SL, NM, ER, ERu, FB, and VLG contributed to reviewing and editing the manuscript. JD, JFT, and LAL secured funding for the study. JFT and LAL supervised the project. All authors read and approved the final manuscript. Acknowledgments The authors thank all the staff and research personnel at each participating site for their valuable assistance in conducting this study. The authors have obtained permission from all individuals mentioned in this section. 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Colistin and Rifampicin Compared With Colistin Alone for the Treatment of Serious Infections Due to Extensively Drug-Resistant Acinetobacter baumannii: A Multicenter, Randomized Clinical Trial. Clinical Infectious Diseases. 2013 Aug 1;57(3):349–58. Sirijatuphat R, Thamlikitkul V. Preliminary Study of Colistin versus Colistin plus Fosfomycin for Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections. Antimicrob Agents Chemother. 2014 Sep;58(9):5598–601. Gadsby NJ, Russell CD, McHugh MP, Mark H, Conway Morris A, Laurenson IF, et al. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin Infect Dis. 2016 Apr 1;62(7):817–23. Fernando SM, Tran A, Cheng W, Klompas M, Kyeremanteng K, Mehta S, et al. Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis. Intensive Care Med. 2020 Jun;46(6):1170–9. Bisanti A, Giammatteo V, Bello G, Grieco DL, De Pascale G, Antonelli M. Extent of microbial over-identification of endotracheal aspirate versus bronchoalveolar lavage in the diagnosis of ventilator-associated pneumonia. Crit Care. 2024 May 9;28:155. Additional Declarations Competing interest reported. JD, JFT, and LAL report the provision of mPCR kits free of charge to the study centers by BioMérieux. JD has received honoraria for lectures from BioMérieux. JFT has received consulting fees from Advanz, Menarini, Pfizer, and Merck, as well as honoraria for lectures from BioMérieux, Mundipharma, and Merck. LAL has received consulting fees from Shionogi and Viatris, honoraria for lectures from Advanz, Pfizer, and Shionogi, and has also given lectures without fees from BioMérieux and Qiagen. RS reports receiving grants from LFB and ABpharma outside the submitted work. HDR has received support for meetings from Shionogi. NG has received honoraria for lectures from Viatris and support for meetings from Pfizer. The authors declare no other financial or non-financial competing interests related to this study. 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Hôpitaux de Paris","correspondingAuthor":false,"prefix":"","firstName":"Romain","middleName":"","lastName":"Sonneville","suffix":""},{"id":437088415,"identity":"894d348d-64a6-491a-9442-34a1d8c334cd","order_by":26,"name":"Etienne de Montmollin","email":"","orcid":"","institution":"Paris Cité University- Bichat University Hospital, Assistance Publique - Hôpitaux de Paris","correspondingAuthor":false,"prefix":"","firstName":"Etienne","middleName":"","lastName":"de Montmollin","suffix":""},{"id":437088416,"identity":"27dc90b3-5ad8-41ce-a784-7b31c49a393c","order_by":27,"name":"Laurence Armand-Lefèvre","email":"","orcid":"","institution":"Paris Cité University- Bichat University Hospital, Assistance Publique - Hôpitaux de Paris","correspondingAuthor":false,"prefix":"","firstName":"Laurence","middleName":"","lastName":"Armand-Lefèvre","suffix":""},{"id":437088418,"identity":"d20a0bdf-14ba-43e4-a7f3-13dbd718396b","order_by":28,"name":"Jean-François Timsit","email":"","orcid":"","institution":"Paris Cité University- Bichat University Hospital, Assistance Publique - Hôpitaux de Paris","correspondingAuthor":false,"prefix":"","firstName":"Jean-François","middleName":"","lastName":"Timsit","suffix":""}],"badges":[],"createdAt":"2025-02-03 11:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5950504/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5950504/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13054-025-05503-7","type":"published","date":"2025-07-12T15:56:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79812874,"identity":"38e1c309-8a5f-4f94-b362-c925ec5fd2d6","added_by":"auto","created_at":"2025-04-03 07:07:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":503998,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eWaterfall plot of the greatest change in bacterial load from diagnosis (Day 0) to Day 3 in ICU patients with vHAP/VAP, and their corresponding clinical outcome. (A) Changes in DNA copies/ml quantified by FA-PP in 71 patients. (B) Changes in CFU/ml quantified by conventional culture in 58 patients. Data are derived from Table 2A.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFA-PP\u003c/em\u003e FilmArray® Pneumonia+ panel, \u003cem\u003eCFU\u003c/em\u003e colony-forming unit\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5950504/v1/363eea5177a5ce9b1fc6ea9e.png"},{"id":79814237,"identity":"93ae04ca-368c-4135-8ba8-f789ac070002","added_by":"auto","created_at":"2025-04-03 07:23:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":60654,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProportion of bacteria detected at culture threshold categorized by FA-PP semi-quantitative results (DNA Copies/ml) for initial (Day 0) and follow-up samples.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCulture diagnostic threshold: BAL ≥10^4 CFU/ml, mini-BAL ≥10^3 CFU/ml, ETA ≥10^5 CFU/ml.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFA-PP\u003c/em\u003e FilmArray® Pneumonia+ panel, \u003cem\u003eBAL\u003c/em\u003e broncho-alveolar lavage, \u003cem\u003eCFU\u003c/em\u003e colony-forming unit\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5950504/v1/f7a3f071a06d8992e0ab6c35.png"},{"id":86700185,"identity":"ffb60731-c197-483c-951e-cefe07e82fa8","added_by":"auto","created_at":"2025-07-14 16:11:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2420404,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5950504/v1/7a932cc7-1286-4e47-ae2e-8ef25ef28565.pdf"},{"id":79812873,"identity":"a9f7c193-4bfa-4a0b-b9cf-026e609ff25c","added_by":"auto","created_at":"2025-04-03 07:07:30","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":927900,"visible":true,"origin":"","legend":"","description":"","filename":"MultiCureSupplementalCritCareR.docx","url":"https://assets-eu.researchsquare.com/files/rs-5950504/v1/b358c866a7de969c8d305468.docx"}],"financialInterests":"Competing interest reported. JD, JFT, and LAL report the provision of mPCR kits free of charge to the study centers by BioMérieux. JD has received honoraria for lectures from BioMérieux. JFT has received consulting fees from Advanz, Menarini, Pfizer, and Merck, as well as honoraria for lectures from BioMérieux, Mundipharma, and Merck. LAL has received consulting fees from Shionogi and Viatris, honoraria for lectures from Advanz, Pfizer, and Shionogi, and has also given lectures without fees from BioMérieux and Qiagen. RS reports receiving grants from LFB and ABpharma outside the submitted work. HDR has received support for meetings from Shionogi. NG has received honoraria for lectures from Viatris and support for meetings from Pfizer. The authors declare no other financial or non-financial competing interests related to this study.","formattedTitle":"Assessing FilmArray Pneumonia+ Panel dynamics during antibiotic treatment to predict clinical success in ICU patients with ventilated hospital-acquired pneumonia and ventilator-associated pneumonia: a multicenter prospective study ","fulltext":[{"header":"Background","content":"\u003cp\u003eAppropriate antibiotic therapy, guided by early and accurate microbiological identification, plays a key role in the management of severe pneumonia (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Currently, bacterial culture of respiratory samples remains the gold standard for diagnosing healthcare-associated pneumonia. However, these conventional methods are often slow, requiring 24\u0026ndash;72 hours to yield results, and they lack sensitivity. During this period, antibiotic treatment is often empirical, which expose patients to potential early therapeutic failure and clinical deterioration (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo address these challenges, new rapid diagnostic tests have been developed to enhance the microbiological documentation of pneumonia (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). These tests are based on molecular methods such as Multiplex Polymerase Chain Reaction (mPCR), performed directly on clinical samples. Among these, the FilmArray\u0026reg; Pneumonia\u0026thinsp;+\u0026thinsp;panel (FA-PP, BioFire, bioM\u0026eacute;rieux) stands out for its rapid turnaround time of 75 minutes. This panel can identify 15 bacteria semi-quantitatively (from 10\u003csup\u003e4\u003c/sup\u003e to \u0026ge;\u0026thinsp;10\u003csup\u003e7\u003c/sup\u003e DNA copies/ml), 3 atypical bacteria, 7 resistance genes, and 8 viruses (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn several clinical studies, the FA-PP demonstrated good diagnostic performance and strong correlation with bacterial culture results (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Additionally, its use has been associated with improved appropriateness of initial antibiotic therapy and better antibiotic management (\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). However, the interpretation of a positive FA-PP result in the context of a negative culture remains delicate. Such results may indicate false positives or the persistence of DNA from non-viable bacteria, particularly if antimicrobial therapy was initiated prior to respiratory sampling. Furthermore, the semi-quantitative results of FA-PP seem to offer limited information, as the quantitative correlation between PCR DNA copy numbers and culture colony-forming units (CFU) is weak (40\u0026ndash;56%) (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Consequently, their use in clinical practice is unclear until they can be standardized.\u003c/p\u003e \u003cp\u003eWhen evaluating the efficacy of antimicrobial treatment for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), experts chose not to include microbiological cure in the composite endpoints, as clinical outcomes generally offer a more comprehensive assessment (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). However, one retrospective study suggested that microbiological failure, even when clinical cure was achieved, could still be associated with an increased risk of recurrent pneumonia or death in patients with bacterial pneumonia (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePredicting clinical success in patients with pneumonia undergoing antibiotic treatment could be a potential clinical application of the semi-quantitative results of FA-PP. However, the correlation of FA-PP results over time with clinical outcomes, as well as the correlation between FA-PP results and culture during antibiotic treatment, have not yet been assessed. The main objective of this study was to determine whether a decline in FA-PP semi-quantitative results correlates with clinical success in patients with ventilated hospital-associated pneumonia (vHAP) or VAP.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis prospective observational study was conducted in four intensive care units (ICUs) of two French university teaching hospitals.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEthical Considerations\u003c/h3\u003e\n\u003cp\u003eThis observational study included patients under mechanical ventilation at inclusion. Participation was communicated to their next of kin through a signed \"informative letter to relatives,\" outlining their right to object. Upon discharge, an \"informative letter to the patient\" was given if they were able to receive it; otherwise, it was mailed. Informative letters are available in the \u003cb\u003eAdditional File 1\u003c/b\u003e. No written consent was required per regulations. Data from paper Case Report Forms (CRFs) were transferred to a secure database on the hospital's intranet, managed by OUTCOMEREA with INSERM U1137. The database was registered with Commission Nationale de l\u0026rsquo;Information et des Libert\u0026eacute;s (CNIL; No. 999262), and MR003 methodology compliance was declared on March 7, 2019 (No. 2212137 v 0). The study received approval from the Soci\u0026eacute;t\u0026eacute; de R\u0026eacute;animation de Langue Fran\u0026ccedil;aise (SRLF) Ethics Committee on September 20, 2022 (No. 22\u0026ndash;041).\u003c/p\u003e\n\u003ch3\u003eDefinitions\u003c/h3\u003e\n\u003cp\u003ePneumonia, vHAP, VAP and episodes of recurrence, relapse or re-infection were defined as previously described (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). According to the multinational expert consensus specified above, a clinical cure was characterized by both clinical and radiographic criteria (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Definitions are detailed in the \u003cb\u003eAdditional File 1\u003c/b\u003e.\u003c/p\u003e\n\u003ch3\u003ePatient Selection\u003c/h3\u003e\n\u003cp\u003eAll adults with vHAP or VAP microbiologically confirmed by a single invasive distal respiratory sample, such as bronchoalveolar lavage (BAL) or mini-BAL, were eligible for inclusion. Patients were included if their pneumonia episode was confirmed by the detection of at least one bacterium using the FA-PP. Exclusion criteria were a life expectancy of less than 72 hours at the time of inclusion, a decision to withdraw or withhold life support, and opposition to research participation.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eAll clinical data were collected prospectively by the investigators. The study started on day zero (D0), at the initial suspicion of vHAP or VAP. Pneumonia was confirmed by a single initial sample (BAL or mini-BAL) collected systematically for each patient prior to the initiation of empiric antibiotic therapy. As FA-PP is routinely used in the participating centers, empiric antibiotic therapy was guided by its results. An initial endotracheal aspirate (ETA D0) was collected prior to initiation of antibiotic therapy and analyzed using both FA-PP and conventional culture methods. For quantification analysis, the ETA D0 was considered valid if collected before or within the first six hours of antibiotic initiation. Repeated ETAs were collected using the same two methods on days 1, 3, 7, and 10 after diagnosis, as well as three days after antibiotic discontinuation. Complete sequential ETA follow-up was defined as having an ETA performed on Day 7. In cases where patients were weaned from mechanical ventilation, follow-up ETAs were not performed. Clinicians involved in the study were blinded to all ETA microbiological results throughout the study. In cases of clinical suspicion of vHAP or VAP recurrence, a new distal sample (BAL or mini-BAL) was obtained to confirm the diagnosis as part of standard patient care. Bacterial cultures from respiratory samples were performed by a quantitative method using serial dilutions, in accordance with the French Standard Recommendations in Medical Microbiology (REMIC), as detailed in the \u003cb\u003eAdditional File 1\u003c/b\u003e. FA-PP was performed upon the arrival of the respiratory samples, concurrently with the bacterial cultures, in accordance with the manufacturer's recommendations.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome was clinical success, defined as a composite measure including clinical cure during antibiotic treatment or within three days after antibiotic discontinuation, and survival without recurrence within seven days after antibiotic discontinuation, as previously defined (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The primary outcome was assessed in all enrolled patients. The greatest changes in semi-quantitative FA-PP and culture results from Day 0 to Day 3 and from Day 0 to Day 7 were monitored, and their correlation with the primary outcome was analyzed. Bacterial load quantification with both techniques was monitored over time, and their relationships with time and clinical success were analyzed. For this purpose, Day 0 ETA results were used if the sample was collected before or within the first six hours after initiation of antibiotic treatment. Late-collected Day 0 ETAs were excluded from the analysis to ensure consistency in monitoring bacterial load. In patients with insufficient secretions or when ETA D0 was collected more than six hours after antibiotic initiation, the BAL or mini-BAL result was used for Day 0 quantification, followed by a Day 1 ETA for Day 1 quantification. The diagnostic performance of FA-PP compared to culture was assessed by evaluating the detection of the 15 typical panel bacteria in initial respiratory samples and follow-up ETAs. In addition, the quantitative concordance between semi-quantitative FA-PP results and culture concentrations was evaluated under both antibiotic-free conditions and during antibiotic treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were expressed as medians (interquartile range) or numbers (percentage). To analyze the evolution of semi-quantitative results, data were categorized into five groups ranging from 0 to 4: #0 for negative results; #1 for 10\u003csup\u003e4\u003c/sup\u003e DNA copies/ml for FA-PP, \u0026lt;10\u003csup\u003e5\u003c/sup\u003e CFU/ml for ETA culture, and \u0026lt;\u0026thinsp;10\u003csup\u003e4\u003c/sup\u003e CFU/ml for mini-BAL and BAL culture; #2 for 10\u003csup\u003e5\u003c/sup\u003e DNA copies/ml for FA-PP, 10\u003csup\u003e5\u003c/sup\u003e CFU/ml for ETA culture, and 10\u003csup\u003e4\u003c/sup\u003e CFU/ml for mini-BAL and BAL culture; #3 for 10\u003csup\u003e6\u003c/sup\u003e DNA copies/ml for FA-PP, 10\u003csup\u003e6\u003c/sup\u003e CFU/ml for ETA culture, and 10\u003csup\u003e5\u003c/sup\u003e CFU/ml for mini-BAL and BAL culture; and #4 for \u0026ge;\u0026thinsp;10\u003csup\u003e7\u003c/sup\u003e DNA copies/ml for FA-PP, \u0026gt;10\u003csup\u003e6\u003c/sup\u003e CFU/ml for ETA culture, and \u0026gt;\u0026thinsp;10\u003csup\u003e5\u003c/sup\u003e CFU/ml for mini-BAL and BAL culture. The five classification groups were arbitrarily defined based on sample dilution and their ability to reflect lower respiratory tract infection, as previously suggested by differences in culture positivity thresholds (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). To account for the ordinal nature of semi-quantitative results, a mixed ordinal logistic regression model was used. This model allowed for the analysis of repeated measures while accounting for within-patient variability. Results were presented as effect estimates with standard errors (SE) and p-values (Pr \u0026gt; [t]). Changes in bacterial load were expressed as logarithmic changes (e.g., +\u0026thinsp;2 log, +\u0026thinsp;1 log, -1 log, -2 log\u003cb\u003e)\u003c/b\u003e, indicating the variation in DNA copies/ml or CFU/ml from baseline (Day 0) to Days 3 and 7. To visualize changes in bacterial load, waterfall plots were generated, illustrating individual trajectories stratified by clinical outcomes. \u003cem\u003eP\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered significant. Statistical analyses were performed using SAS 9.4 (Cary, North Carolina, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eBetween April 20, 2022, and June 11, 2024, a total of 93 patients were enrolled in the four participating ICUs. The baseline characteristics of the patients are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eClinical outcomes\u003c/h2\u003e \u003cp\u003e All patients were followed throughout the study, and the primary outcome was assessed for all enrolled patients. Clinical success was achieved in 56 patients (60.2%), while ICU and in-hospital mortality rates were 25.8% (n\u0026thinsp;=\u0026thinsp;24/93) and 29% (n\u0026thinsp;=\u0026thinsp;27/93), respectively. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). During the ICU stay, the overall recurrence rate after inclusion was 32.3% (n\u0026thinsp;=\u0026thinsp;30/93), comprising 20 episodes of relapse (66.7%) and 10 episodes of re-infection (33.3%). Most patients with recurrence experienced a single episode (n\u0026thinsp;=\u0026thinsp;26/30; 87%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients and outcomes of 93 vHAP/VAP episodes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;93\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinical success\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;56\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClinical failure\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;37\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBaseline characteristics\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge \u0026ndash; years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 [51; 66]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 [47; 63]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63 [55; 70]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (66.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (67.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight \u0026ndash; kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 [65; 90]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 [66; 90]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75 [62; 82]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI \u0026ndash; kg/m\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.4 [22.9; 30.4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.6 [23.2; 30.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.2 [22.2; 29.3]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCo-morbid conditions\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic respiratory disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (30.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (13.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (8.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (10.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunodepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (34.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (45.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIV infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (10.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAIDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolid organ transplant recipient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (24.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppression*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (29.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharlson co-morbidity score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 [0; 4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 [0; 3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 [0; 4]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCharacteristics at inclusion\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay prior to ICU admission \u0026ndash; days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 [0; 3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 [0; 2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 [0; 4]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU stay prior to inclusion \u0026ndash; days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 [3; 12]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 [4; 13]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 [2; 8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKnown MDR and/or XDR carriage before inclusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (29.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESBL-E carriage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (24.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (29.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntimicrobial therapy within the 7 days before inclusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (61.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (55.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (70.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever (\u0026gt;\u0026thinsp;38.3\u0026deg;C) or hypothermia (\u0026lt;\u0026thinsp;35\u0026deg;C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 (78.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (83.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypotension /vasopressor requirement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (67.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWorsening oxygenation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81 (87.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (86.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaO2/FiO2, median [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e192 [133; 255]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e206 [141; 284]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e160 [109; 220]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePurulent tracheal secretions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79 (84.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (82.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (89.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC count - x 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 [8.4; 17.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.9 [8.8; 18.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.4 [8.2; 16.5]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils - x 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 [6.4; 14.3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.9 [6.8; 14.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.7 [5.7; 13.6]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProcalcitonin \u0026mdash; ng/ml (missing, n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5 [0.2; 2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5 [0.2; 1.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5 [0.3; 2.2]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSAPS II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 [37; 61]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 [37; 61]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 [38; 62]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePneumonia type\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilated Hospital-acquired\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (29.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilator-associated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (82.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (70.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eInitial sampling\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSample type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBronchoalveolar lavage (BAL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (62.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMini-BAL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (37.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive Gram stain examination: positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 (78.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (80.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (75.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eClinical outcomes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (48.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIn-hospital mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (51.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecisions of withholding and withdrawal of life sustaining therapies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (25.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (40.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA score 28 days after inclusion (missing, n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 [0; 4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 [1; 2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 [1; 2]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU length of stay \u0026ndash; days (missing, n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 [16; 48]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 [17; 48]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 [13; 44]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital length of stay \u0026ndash; days (missing, n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 [24; 79]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 [35; 79]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 [20; 76]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotics duration \u0026ndash; days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 [5; 8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 [6; 8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 [4; 9]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIMV duration \u0026ndash; days (missing, n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 [12; 32]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 [12; 34]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 [11; 32]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeaning tracheostomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (15.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (18.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eResults are expressed as median [IQR] or number of cases (%).\u003c/p\u003e \u003cp\u003e \u003cem\u003evHAP\u003c/em\u003e ventilated hospital-acquired pneumonia, \u003cem\u003eVAP\u003c/em\u003e ventilator-associated pneumonia, \u003cem\u003eBMI\u003c/em\u003e body mass index, \u003cem\u003eCOPD\u003c/em\u003e chronic obstructive pulmonary disease, \u003cem\u003eHIV\u003c/em\u003e human immunodeficiency virus, \u003cem\u003eAIDS\u003c/em\u003e acquired immunodeficiency syndrome, \u003cem\u003eICU\u003c/em\u003e intensive care unit, \u003cem\u003eMDR\u003c/em\u003e multidrug resistance, \u003cem\u003eXDR\u003c/em\u003e Extensively drug-resistance, \u003cem\u003eESBL-E\u003c/em\u003e extended spectrum beta-lactamase producing \u003cem\u003eEnterobacterales, WBC\u003c/em\u003e white blood cells, \u003cem\u003eSAPS\u003c/em\u003e simplified acute physiology score, \u003cem\u003eSOFA\u003c/em\u003e sequential organ failure assessment, \u003cem\u003eIMV\u003c/em\u003e invasive mechanical ventilation.\u003c/p\u003e \u003cp\u003e*Immunosuppression was defined as recent (within the last 3 months) or active anticancer chemotherapy, systemic steroids\u0026thinsp;\u0026ge;\u0026thinsp;10 mg/day for at least 15 days, or other immunosuppressive or immunomodulatory drugs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSamples and bacteriological findings\u003c/h2\u003e \u003cp\u003eIn initial samples (51 BALs and 42 mini-BALs), standard culture identified 134 bacteria, of which 19 (14.2%) were not detected by FA-PP because they were outside the target panel. In parallel, FA-PP detected 138 bacteria. The five most commonly isolated bacteria in culture were \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;28/134; 20.9%), \u003cem\u003eEscherichia coli\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;14/134; 10.4%), \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;14/134; 10.4%), \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;12/134; 9%), and \u003cem\u003eEnterobacter cloacae\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;10/134; 7.5%), as detailed in \u003cb\u003eSupplementary Table\u0026nbsp;1, Additional File 1\u003c/b\u003e. On Day 0, 52 ETAs (Day 0 ETA) were collected either prior to or within the first 6 hours of antibiotic initiation, representing 56% of the patients. For late-collected or missed Day 0 ETAs (n\u0026thinsp;=\u0026thinsp;41; 44%), the BAL or mini-BAL diagnostic results were used for Day 0 quantification. To monitor bacteriological findings during treatment, a total of 196 ETAs were collected. Complete sequential ETA follow-up to at least Day 7 was performed in 47 patients (50.5%). Of the 46 patients who did not undergo ETA on day 7, 27 (58.7%) were weaned from mechanical ventilation, 7 (15.2%) had a recurrence, 7 (15.2%) had a missed sampling, and 5 (10.9%) died or were in the process of withdrawal of life-sustaining therapy prior to day 7.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eFA-PP and culture dynamics during antibiotic treatment\u003c/h2\u003e \u003cp\u003ePrior to antibiotic initiation, no association was found between the initial bacterial load and clinical success, whether using FA-PP or conventional culture (\u003cb\u003eSupplementary Table\u0026nbsp;2, Additional File 1)\u003c/b\u003e. During antibiotic treatment, the semi-quantitative FA-PP results (in DNA copies/ml) showed a median greatest change of 0.0 (IQR [-0.3; 0.0]) from Day 0 to Day 3 among 71 patients and \u0026minus;\u0026thinsp;0.1 (IQR [-0.3; 0.0]) from Day 0 to Day 7 among 47 patients (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). These decreases were not significantly different between patients with clinical success and those without. For culture results (in CFU/ml), the median change was \u0026minus;\u0026thinsp;0.7 (IQR [-1; 0.0]) from Day 0 to Day 3 among 58 patients and \u0026minus;\u0026thinsp;0.2 (IQR [-0.4; -0.1]) from Day 0 to Day 7 among 40 patients. These changes in culture results were not correlated with clinical success either (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). When analyzing the changes in bacterial load by logarithmic categories, no clear trend was observed across the different change categories (+\u0026thinsp;2 log or more, +\u0026thinsp;1 log, no change, -1 log, -2 log or less), regardless of the clinical outcome. These results were confirmed by the mixed ordinal regression model, which was performed using the semi-quantitative groups and demonstrated a decrease over time in both the number of copies and in bacterial load in culture (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This decrease was similar in patients with clinical success and those with clinical failure (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.71 for FA-PP and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.61 for bacterial culture; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB illustrate the changes in bacterial load from diagnosis (Day 0) to Day 3 for each patient, and their corresponding clinical outcome, with DNA copies/ml measured by FA-PP and CFU/ml measured by culture, respectively. The greatest change in bacterial load from Day 0 to Day 7 is shown in \u003cb\u003eSupplementary Fig.\u0026nbsp;1.\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFA-PP and culture quantification follow-up during antibiotic treatment Greatest changes in FA-PP and culture results by clinical outcome\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;93)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinical success\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;56)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClinical failure\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFA-PP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGreatest change in DNA copies/ml from Day 0 to Day 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;71\u003c/p\u003e \u003cp\u003e0.0 [-0.3; 0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;43\u003c/p\u003e \u003cp\u003e-0.3 [-0.3; 0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;28\u003c/p\u003e \u003cp\u003e0.0 [-0.3; 0.0]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ 2 log or more\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ 1 log\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (10.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (37.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (42.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;1 log\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (30.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (28.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;2 log or less\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGreatest change in DNA copies/ml from Day 0 to Day 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;47\u003c/p\u003e \u003cp\u003e-0.1 [-0.3; 0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;22\u003c/p\u003e \u003cp\u003e-0.1 [-0.3; 0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;24\u003c/p\u003e \u003cp\u003e-0.1 [-0.3; 0.0]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ 2 log or more\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ 1 log\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (12.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (21.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (20.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;1 log\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (29.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (29.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;2 log or less\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (22.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCulture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGreatest change in CFU/ml from Day 0 to Day 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;58\u003c/p\u003e \u003cp\u003e-0.7 [-1; 0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;33\u003c/p\u003e \u003cp\u003e-0.5 [-0.8; 0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;25\u003c/p\u003e \u003cp\u003e-0.7 [-1; 0.0]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ 2 log or more\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ 1 log\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;1 log\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (24.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;2 log or less\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (34.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (44.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGreatest change in CFU/ml from Day 0 to Day 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;40*\u003c/p\u003e \u003cp\u003e-0.2 [-0.4; -0.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;17\u003c/p\u003e \u003cp\u003e-0.3 [-0.4; -0.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;22\u003c/p\u003e \u003cp\u003e-0.2 [-0.3; -0.1]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ 2 log or more\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ 1 log\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (9.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;1 log\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (32.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (35.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (27.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;2 log or less\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (21.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (30.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eQuantification follow-up was based on the most abundant bacterium in the Day 0 ETA. In case of a tie, the most pathogenic bacterium was selected. *The seven remaining patients had a negative culture result on Day 0 ETA. Results are expressed as median [IQR] or number of cases (%). \u003cem\u003eFA-PP\u003c/em\u003e FilmArray\u0026reg; Pneumonia\u0026thinsp;+\u0026thinsp;panel, \u003cem\u003eCFU\u003c/em\u003e colony-forming unit\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e(B) Mixed ordinal regression analysis of quantification over time\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eFA-PP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEstimate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eSE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ePr \u0026gt;|t|\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical success\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eCulture\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEstimate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eSE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ePr \u0026gt;|t|\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical success\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMixed ordinal regression analysis was performed using the quantification groups (0 to 4). Solution for fixed effects, Model with censoring after day 14. \u003cem\u003eFA-PP\u003c/em\u003e FilmArray\u0026reg; Pneumonia\u0026thinsp;+\u0026thinsp;panel, \u003cem\u003eSE\u003c/em\u003e standard error\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eDiagnostic performance of FA-PP compared to culture\u003c/h2\u003e \u003cdiv id=\"Sec17\" class=\"Section3\"\u003e \u003ch2\u003eFor bacterial detection on initial samples\u003c/h2\u003e \u003cp\u003eAt inclusion, 104 bacterial isolates from the panel were detected by both FA-PP and standard culture in the 93 initial specimens (BAL or mini-BAL). FA-PP identified 34 additional bacteria that were not detected by culture in 26 of these samples (\u003cb\u003eSupplementary Table\u0026nbsp;3, Additional File 1\u003c/b\u003e). These 34 cases were categorized as follows: 17 cases (50%) were classified as false positives, as the microorganisms were never cultured before or after study entry; 15 cases (44.1%) involved samples collected after the initiation of antibiotic therapy; and 2 cases (5.9%) involved bacteria associated with prior episodes of pneumonia. Conversely, seven bacterial isolates identified by culture were not detected by FA-PP, although belonging to the FA-PP panel: five from mini-BAL samples and two from BAL samples (\u003cb\u003eSupplementary Table\u0026nbsp;4, Additional File 1\u003c/b\u003e). Of these samples, only two exceeded the culture threshold (\u003cem\u003eS. pneumoniae\u003c/em\u003e n\u0026thinsp;=\u0026thinsp;1, \u003cem\u003eE. cloacae\u003c/em\u003e n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e \u003cp\u003eOverall, the technical sensitivity and specificity (detection of the 15 typical bacteria panel) of the FA-PP compared to culture were 94% [95% CI: 87\u0026ndash;97] and 98% [95% CI: 97\u0026ndash;98] for diagnostic specimens, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eFor bacterial detection during antibiotic treatment\u003c/h2\u003e \u003cp\u003eFor all ETA samples collected during antibiotic treatment, sensitivity was 94% [95% CI: 90\u0026ndash;97] and specificity was 95% [95% CI: 94\u0026ndash;96] (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eFor antimicrobial resistance genes on initial samples\u003c/h2\u003e \u003cp\u003eNineteen \u003cem\u003ebla\u003c/em\u003eCTX-M genes were detected, with 6 resulting in false positives, representing a 31.6% overdiagnosis rate (\u003cb\u003eSupplementary Table\u0026nbsp;5, Additional File 1\u003c/b\u003e). Two cases of the \u003cem\u003ebla\u003c/em\u003eNDM gene were detected, including one false positive. For the mecA/C and MREJ genes, three instances were detected, with one false positive and one false negative, resulting in a missed detection rate of 1.1% and an overdiagnosis rate of 33.3%.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDiagnostic performance of FA-PP compared to culture for the 15 typical bacteria of the panel at diagnosis and during antibiotic treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNumber of samples performed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eNumber of\u003c/p\u003e \u003cp\u003ebacteria detected\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eFA-PP+/\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eculture+, n\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eFA-PP+/\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eculture-, n\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eFA-PP-/\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eculture+, n\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eFA-PP-/\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eculture-, n\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eSe, % (95%CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eSp, %\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(95%CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBAL and mini-BAL: D0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1330\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e94 (87\u0026ndash;97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e98 (97\u0026ndash;98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBAL: D0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e747\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e97 (89\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e98 (96\u0026ndash;99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMini-BAL: D0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e583\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e89 (77\u0026ndash;96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e97 (96\u0026ndash;98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eETA: D0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e750\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95 (85\u0026ndash;98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e96 (95\u0026ndash;97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eETA: follow-up\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e196\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2800\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e94 (90\u0026ndash;97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e95 (94\u0026ndash;96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eFA-PP\u003c/em\u003e FilmArray\u0026reg; Pneumonia\u0026thinsp;+\u0026thinsp;panel, \u003cem\u003eSe\u003c/em\u003e sensitivity, \u003cem\u003eSp\u003c/em\u003e specificity, \u003cem\u003eCI\u003c/em\u003e confidence interval, \u003cem\u003eBAL\u003c/em\u003e bronchoalveolar lavage, \u003cem\u003eETA\u003c/em\u003e endotracheal aspirate\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eQuantitative concordance on diagnosis and during antibiotic treatment\u003c/h2\u003e \u003cp\u003eIn diagnostic samples (BAL and mini-BAL), 61.6% of pathogens were detected at or above the culture threshold, compared with only 28.7% in follow-up ETA samples (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe concordance between bacteria detected by FA-PP and those recovered by culture increased with the number of DNA copies identified by FA-PP. In diagnostic samples, when FA-PP identified bacteria at 10\u003csup\u003e4\u003c/sup\u003e DNA copies/ml, only 22.9% (n\u0026thinsp;=\u0026thinsp;8/35) were detected at or above the culture threshold. Conversely, at \u0026ge;\u0026thinsp;10\u003csup\u003e7\u003c/sup\u003e DNA copies/ml, 100% of bacteria were detected at or above the culture threshold.\u003c/p\u003e \u003cp\u003eDuring antibiotic treatment, this correlation persisted, with culture positivity increasing from 2.8% at the threshold for a FA-PP result of 10\u003csup\u003e4\u003c/sup\u003e DNA copies/ml to 66.7% for bacteria detected at \u0026ge;\u0026thinsp;10\u003csup\u003e7\u003c/sup\u003e DNA copies/ml (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eQuantitative concordance between FA-PP and culture for the 15 typical bacteria of the panel at diagnosis and during antibiotic treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCulture: BAL and mini-BAL D0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eCulture: BAL D0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eCulture: mini-BAL D0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFA-PP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;threshold*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;threshold*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;10^4 CFU/ml\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;10^4 CFU/ml\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;10^3 CFU/ml\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;10^3 CFU/ml\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10^4 DNA copies/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (77.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (22.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 (94.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11 (61.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10^5 DNA copies/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (53.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (46.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10^6 DNA copies/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15 (83.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e12 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;10^7 DNA copies/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (38.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85 (61.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e48 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e21 (36.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e37 (63.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCulture: ETA D0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u003cb\u003eCulture: ETA follow-up\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFA-PP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;10^5 CFU/ml\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;10^5 CFU/ml\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;10^5 CFU/ml\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;10^5 CFU/ml\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10^4 DNA copies/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69 (97.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10^5 DNA copies/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (76.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78 (88.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10^6 DNA copies/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (76.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48 (65.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25 (34.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;10^7 DNA copies/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (81.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e52 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (46.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (53.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e221 (71.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e89 (28.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eResults are expressed as number of cases (%).\u003c/p\u003e \u003cp\u003e*Threshold: \u0026ge;10^4 CFU/ml for BAL and \u0026ge;\u0026thinsp;10^3 CFU/ml for mini-BAL\u003c/p\u003e \u003cp\u003e \u003cem\u003eFA-PP\u003c/em\u003e FilmArray\u0026reg; Pneumonia\u0026thinsp;+\u0026thinsp;panel, \u003cem\u003eBAL\u003c/em\u003e broncho-alveolar lavage, \u003cem\u003eCFU\u003c/em\u003e colony-forming unit\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective study is, to our knowledge, the first to follow-up on changes in FA-PP results during the course of antibiotic treatment in ICU patients with VAP and vHAP. While both FA-PP and culture quantifications decreased over time, these reductions did not correlate significantly with clinical outcome. This finding suggests that changes in FA-PP and culture semi-quantitative levels alone may not reliably predict clinical success.\u003c/p\u003e \u003cp\u003eAlthough the evolution of FA-PP during treatment has not been previously assessed, the impact of microbiological failure on clinical outcomes has been studied. One study indicated that microbiological failure, as determined by culture, was associated with an increased risk of recurrent pneumonia or death, even when clinical cure was achieved (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). However, the retrospective design and specific patient population of this study limited its conclusions. Additionally, randomized controlled trials on nosocomial pneumonia have shown differences in microbiological cure rates between treatment groups, despite similar clinical cure and mortality rates (\u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Due to the lack of a consistent correlation between microbiological cure and patient outcomes, experts have rejected the use of microbiological cure as a reliable criterion for establishing consensus clinical endpoints in HAP and VAP clinical trials (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGiven the potential of FA-PP to detect DNA of bacteria not able to grow, it might be expected that FA-PP results would show a smaller or slower decline during treatment. However, our findings revealed that FA-PP semi-quantitative levels decreased during treatment regardless of clinical success. Consequently, our results indicate that FA-PP should not be used to predict clinical outcomes in patients with severe hospital-acquired pneumonia.\u003c/p\u003e \u003cp\u003eThe diagnostic performance of FA-PP compared to standard culture was excellent in our study, consistent with previously published findings. A recent meta-analysis reported sensitivity and specificity of 94% and 98%, respectively (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). These diagnostic performances remained consistent throughout the antibiotic treatment, with a sensitivity of 94% and a specificity of 95%, despite initial concerns that it might be adversely affected. This suggests that FA-PP detection and culture results decline under antibiotic influence in a comparable manner.\u003c/p\u003e \u003cp\u003eWe identified a clear correlation between semi-quantitative FA-PP results, expressed in DNA copies/ml, and bacterial inoculum measured in CFU/ml. Rather than focusing solely on the correspondence between these two units, our approach emphasized clinical relevance by prioritizing the identification of samples that met the diagnostic threshold necessary for confirming a positive result. Our data demonstrated that higher DNA copy numbers were associated with an increased likelihood of pathogen detection at the culture threshold. Furthermore, this study is the first to assess this quantitative concordance during antibiotic treatment, and to show that it remained relatively stable throughout the treatment course.\u003c/p\u003e \u003cp\u003eFew studies have examined quantitative concordance at diagnosis, aiming to refine the interpretation of semi-quantitative FA-PP results and determine a potential positivity threshold. Comparing bacterial loads using the two techniques, authors reported poor quantitative concordance between FA-PP and culture (43% and 53.6%) (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The FA-PP tended to overestimate bacterial load, likely due to the detection of both live and dead organisms by PCR. Similarly, a British study on community-acquired pneumonia, using mostly sputum samples, found that PCR detected higher bacterial loads in culture-positive samples compared to culture-negative samples, which were often collected after antibiotic initiation (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). This suggests that mPCR could potentially enable a microbiological diagnosis even when early antibiotic therapy, initiated prior to sampling, results in negative culture outcomes. However, our study did not explore this aspect, emphasizing the need for further research to investigate this issue.\u003c/p\u003e \u003cp\u003eRegarding resistance gene detection by FA-PP, we observed a high proportion of \u003cem\u003ebla\u003c/em\u003eCTX-M genes (20.4%), the most prevalent gene among ESBL-producing \u003cem\u003eEnterobacterales\u003c/em\u003e in Europe. This is likely attributable to the high baseline prevalence of ESBL-E carriers in our study population at inclusion (24.7%). As previously observed, the interpretation of resistance gene results should be considered within the context of clinical pre-test probability to avoid overdiagnosis. Given the high sensitivity of the technique, the overdiagnosis rates we observed ranged between 31.6% and 50%, consistent with recent studies that have raised concerns about this issue (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, inconsistent Day 0 sample selection introduced potential bias. In 54.9% of patients, the initial sample for quantification was a Day 0 ETA; however, BAL or mini-BAL samples replaced ETAs when the latter were unavailable or collected more than 6 hours post-antibiotic initiation. This variation may have affected the observed dynamics of quantification under antibiotic treatment. Second, analysis of quantification dynamics was limited to a subset of patients due to missing samples, early mortality, or weaning from mechanical ventilation before Day 7. Finally, although a recent study found limited evidence of significant over-identification in ETA compared with single-site BAL, our use of ETAs for follow-up may introduce bias by potentially overestimating microbial loads (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOn the other hand, the multicenter design of this study enhances the generalizability of the findings. Furthermore, we selected clinical cure as our primary endpoint, a criterion validated by a previously established expert panel (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Lastly, interpreting concordance between the two quantification methods from a clinician\u0026rsquo;s perspective allows for better applicability for the ICU setting.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe semi-quantitative FA-PP results in patients with vHAP and VAP undergoing antibiotic treatment decline over time, similarly to bacterial culture quantifications. However, neither FA-PP nor culture dynamics during treatment reliably predict clinical success. Consequently, repeated cultures or FA-PP testing during treatment to assess patient recovery do not appear to be recommended. Quantitative concordance between FA-PP and culture is acceptable prior to treatment, particularly for predicting culture threshold results, and this concordance seems to remain stable during treatment. Further research is needed to refine the interpretation of FA-PP result dynamics and to explore their clinical utility in the management of severe hospital-acquired pneumonia.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eBAL\u0026nbsp;\u003c/strong\u003ebronchoalveolar lavage\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ebla\u003c/em\u003eCTX-M\u0026nbsp;\u003c/strong\u003ecefotaximase-munich beta-lactamase gene\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ebla\u003c/em\u003eNDM\u0026nbsp;\u003c/strong\u003eNew Delhi metallo-beta-lactamase gene\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCFU\u0026nbsp;\u003c/strong\u003ecolony-forming unit\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCI\u0026nbsp;\u003c/strong\u003econfidence interval\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCNIL\u0026nbsp;\u003c/strong\u003ecommission nationale de l\u0026rsquo;information et des libert\u0026eacute;s\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRF\u0026nbsp;\u003c/strong\u003ecase report form\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDNA\u0026nbsp;\u003c/strong\u003edeoxyribonucleic acid\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eESBL-E\u0026nbsp;\u003c/strong\u003eextended-spectrum beta-lactamase-producing enterobacterales\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETA\u0026nbsp;\u003c/strong\u003eendotracheal aspirate\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFA-PP\u0026nbsp;\u003c/strong\u003eFilmArray\u0026reg; Pneumonia+ panel\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eICU\u0026nbsp;\u003c/strong\u003eintensive care unit\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003emecA/C\u0026nbsp;\u003c/strong\u003emethicillin resistance gene a/c\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003emPCR\u0026nbsp;\u003c/strong\u003emultiplex polymerase chain reaction\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMREJ\u003c/strong\u003e \u003cstrong\u003emethicillin-resistant epidemiological junction\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eREMIC\u0026nbsp;\u003c/strong\u003erecommendations in medical microbiology\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSe\u0026nbsp;\u003c/strong\u003esensitivity\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSE\u003c/strong\u003e standard error\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSp\u0026nbsp;\u003c/strong\u003especificity\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSRLF\u0026nbsp;\u003c/strong\u003esoci\u0026eacute;t\u0026eacute; de r\u0026eacute;animation de langue fran\u0026ccedil;aise\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVAP\u0026nbsp;\u003c/strong\u003eventilator-associated pneumonia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003evHAP\u0026nbsp;\u003c/strong\u003eventilated hospital-acquired pneumonia\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Soci\u0026eacute;t\u0026eacute; de R\u0026eacute;animation de Langue Fran\u0026ccedil;aise (SRLF) Ethics Committee on September 20, 2022 (No. 22-041). As this was an observational study, written consent was not required per national regulations. Since this study involved mechanically ventilated patients, participation was communicated to next of kin through an informative letter outlining their right to object. Upon discharge, patients received an informative letter, or it was mailed when necessary.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study does not contain any individual person\u0026rsquo;s data in any form (such as images, videos, or personal details). Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Data were securely stored in a hospital intranet database, managed by OUTCOMEREA under the oversight of INSERM U1137, and registered with the Commission Nationale de l\u0026rsquo;Information et des Libert\u0026eacute;s (CNIL; No. 999262). MR003 methodology compliance was declared on March 7, 2019 (No. 2212137 v 0).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJD, JFT, and LAL report the provision of mPCR kits free of charge to the study centers by BioM\u0026eacute;rieux. JD has received honoraria for lectures from BioM\u0026eacute;rieux. JFT has received consulting fees from Advanz, Menarini, Pfizer, and Merck, as well as honoraria for lectures from BioM\u0026eacute;rieux, Mundipharma, and Merck. LAL has received consulting fees from Shionogi and Viatris, honoraria for lectures from Advanz, Pfizer, and Shionogi, and has also given lectures without fees from BioM\u0026eacute;rieux and Qiagen. RS reports receiving grants from LFB and ABpharma outside the submitted work. HDR has received support for meetings from Shionogi. NG has received honoraria for lectures from Viatris and support for meetings from Pfizer. The authors declare no other financial or non-financial competing interests related to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was funded by an unrestricted investigator-driven grant from BioM\u0026eacute;rieux (n\u0026deg;IPM 20586). The company had no role in the conceptualization, study design, data collection, analysis, decision to publish, or manuscript preparation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJFT, LAL, and JD conceptualized the study. JFT, SR, LAL, and JD developed the methodology. SR conducted the formal analysis and investigation. JD, SR, JS, AG, GF, SC, HDR, SG, and FL were responsible for data curation. JD drafted the original manuscript. MT, LH, JLM, LB, RS, EDM, CP, MD, ME, VB, NG, SL, NM, ER, ERu, FB, and VLG contributed to reviewing and editing the manuscript. JD, JFT, and LAL secured funding for the study. JFT and LAL supervised the project.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all the staff and research personnel at each participating site for their valuable assistance in conducting this study. The authors have obtained permission from all individuals mentioned in this section.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTorres A, Niederman MS, Chastre J, Ewig S, Fernandez-Vandellos P, Hanberger H, et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociaci\u0026oacute;n Latinoamericana del T\u0026oacute;rax (ALAT). Eur Respir J. 2017 Sep;50(3):1700582. \u003c/li\u003e\n\u003cli\u003eBarbier F, Andremont A, Wolff M, Bouadma L. Hospital-acquired pneumonia and ventilator-associated pneumonia: recent advances in epidemiology and management. Current Opinion in Pulmonary Medicine. 2013 May;19(3):216. \u003c/li\u003e\n\u003cli\u003eKoulenti D, Tsigou E, Rello J. Nosocomial pneumonia in 27 ICUs in Europe: perspectives from the EU-VAP/CAP study. Eur J Clin Microbiol Infect Dis. 2017 Nov;36(11):1999\u0026ndash;2006. \u003c/li\u003e\n\u003cli\u003eKalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63(5):e61\u0026ndash;111. \u003c/li\u003e\n\u003cli\u003eDessajan J, Timsit JF. Impact of Multiplex PCR in the Therapeutic Management of Severe Bacterial Pneumonia. Antibiotics (Basel). 2024 Jan 18;13(1):95. \u003c/li\u003e\n\u003cli\u003eKerneis S, Visseaux B, Armand-Lefevre L, Timsit JF. Molecular diagnostic methods for pneumonia: how can they be applied in practice? Current Opinion in Infectious Diseases. 2021 Apr;34(2):118. \u003c/li\u003e\n\u003cli\u003eKlein M, Bacher J, Barth S, Atrzadeh F, Siebenhaller K, Ferreira I, et al. Multicenter Evaluation of the Unyvero Platform for Testing Bronchoalveolar Lavage Fluid. Journal of Clinical Microbiology. 2021 Feb 18;59(3):10.1128/jcm.02497-20. \u003c/li\u003e\n\u003cli\u003eMurphy CN, Fowler R, Balada-Llasat JM, Carroll A, Stone H, Akerele O, et al. Multicenter Evaluation of the BioFire FilmArray Pneumonia/Pneumonia Plus Panel for Detection and Quantification of Agents of Lower Respiratory Tract Infection. Journal of Clinical Microbiology. 2020 Jun 24;58(7):10.1128/jcm.00128-20. \u003c/li\u003e\n\u003cli\u003eMoy AC, Kimmoun A, Merkling T, Ber\u0026ccedil;ot B, Cam\u0026eacute;l\u0026eacute;na F, Poncin T, et al. Performance evaluation of a PCR panel (FilmArray\u0026reg; Pneumonia Plus) for detection of respiratory bacterial pathogens in respiratory specimens: A systematic review and meta-analysis. Anaesthesia Critical Care \u0026amp; Pain Medicine. 2023 Dec 1;42(6):101300. \u003c/li\u003e\n\u003cli\u003ePoole S, Tanner AR, Naidu VV, Borca F, Phan H, Saeed K, et al. Molecular point-of-care testing for lower respiratory tract pathogens improves safe antibiotic de-escalation in patients with pneumonia in the ICU: Results of a randomised controlled trial. Journal of Infection. 2022 Dec 1;85(6):625\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eMaataoui N, Chemali L, Patrier J, Tran Dinh A, Le F\u0026egrave;vre L, Lortat-Jacob B, et al. Impact of rapid multiplex PCR on management of antibiotic therapy in COVID-19-positive patients hospitalized in intensive care unit. Eur J Clin Microbiol Infect Dis. 2021 Mar 17;1\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eMarkussen DL, Serigstad S, Ritz C, Knoop ST, Ebbesen MH, Faurholt-Jepsen D, et al. Diagnostic Stewardship in Community-Acquired Pneumonia With Syndromic Molecular Testing. JAMA Netw Open. 2024 Mar 6;7(3):e240830. \u003c/li\u003e\n\u003cli\u003eCartuliares MB, Rosenvinge FS, Mogensen CB, Skovsted TA, Andersen SL, \u0026Oslash;stergaard C, et al. Evaluation of point-of-care multiplex polymerase chain reaction in guiding antibiotic treatment of patients acutely admitted with suspected community-acquired pneumonia in Denmark: A multicentre randomised controlled trial. PLOS Medicine. 2023 Nov 28;20(11):e1004314. \u003c/li\u003e\n\u003cli\u003eGastli N, Loubinoux J, Daragon M, Lavigne JP, Saint-Sardos P, Pailhori\u0026egrave;s H, et al. Multicentric evaluation of BioFire FilmArray Pneumonia Panel for rapid bacteriological documentation of pneumonia. Clin Microbiol Infect. 2021 Sep;27(9):1308\u0026ndash;14. \u003c/li\u003e\n\u003cli\u003eLee SH, Ruan SY, Pan SC, Lee TF, Chien JY, Hsueh PR. Performance of a multiplex PCR pneumonia panel for the identification of respiratory pathogens and the main determinants of resistance from the lower respiratory tract specimens of adult patients in intensive care units. J Microbiol Immunol Infect. 2019 Dec;52(6):920\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eWeiss E, Zahar JR, Alder J, Asehnoune K, Bassetti M, Bonten MJM, et al. Elaboration of Consensus Clinical Endpoints to Evaluate Antimicrobial Treatment Efficacy in Future Hospital-acquired/Ventilator-associated Bacterial Pneumonia Clinical Trials. Clin Infect Dis. 2019 Nov 13;69(11):1912\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eAlbin OR, Henig O, Patel TS, Valley TS, Pogue JM, Petty LA, et al. Clinical Implications of Microbiologic Treatment Failure in the Setting of Clinical Cure of Bacterial Pneumonia. Clinical Infectious Diseases. 2020 Dec 15;71(12):3033\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003ePlachouras D, Lepape A, Suetens C. ECDC definitions and methods for the surveillance of healthcare-associated infections in intensive care units. Intensive Care Med. 2018;44(12):2216\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eSaied WI, Martin-Loeches I, Timsit JF. What is new in non-ventilated ICU-acquired pneumonia. Intensive Care Med. 2020 Mar 1;46(3):488\u0026ndash;91. \u003c/li\u003e\n\u003cli\u003eIoanas M, Ferrer R, Angrill J, Ferrer M, Torres A. Microbial investigation in ventilator-associated pneumonia. European Respiratory Journal. 2001 Apr 1;17(4):791\u0026ndash;801. \u003c/li\u003e\n\u003cli\u003eKollef MH, Ricard JD, Roux D, Francois B, Ischaki E, Rozgonyi Z, et al. A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia: IASIS Trial. Chest. 2017 Jun 1;151(6):1239\u0026ndash;46. \u003c/li\u003e\n\u003cli\u003eParchem NL, Bauer KA, Cook CH, Mangino JE, Jones CD, Porter K, et al. Colistin combination therapy improves microbiologic cure in critically ill patients with multi-drug resistant gram-negative pneumonia. Eur J Clin Microbiol Infect Dis. 2016 Sep 1;35(9):1433\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eDurante-Mangoni E, Signoriello G, Andini R, Mattei A, De Cristoforo M, Murino P, et al. Colistin and Rifampicin Compared With Colistin Alone for the Treatment of Serious Infections Due to Extensively Drug-Resistant Acinetobacter baumannii: A Multicenter, Randomized Clinical Trial. Clinical Infectious Diseases. 2013 Aug 1;57(3):349\u0026ndash;58. \u003c/li\u003e\n\u003cli\u003eSirijatuphat R, Thamlikitkul V. Preliminary Study of Colistin versus Colistin plus Fosfomycin for Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections. Antimicrob Agents Chemother. 2014 Sep;58(9):5598\u0026ndash;601. \u003c/li\u003e\n\u003cli\u003eGadsby NJ, Russell CD, McHugh MP, Mark H, Conway Morris A, Laurenson IF, et al. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin Infect Dis. 2016 Apr 1;62(7):817\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eFernando SM, Tran A, Cheng W, Klompas M, Kyeremanteng K, Mehta S, et al. Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis. Intensive Care Med. 2020 Jun;46(6):1170\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eBisanti A, Giammatteo V, Bello G, Grieco DL, De Pascale G, Antonelli M. Extent of microbial over-identification of endotracheal aspirate versus bronchoalveolar lavage in the diagnosis of ventilator-associated pneumonia. Crit Care. 2024 May 9;28:155. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cric","sideBox":"Learn more about [Critical Care](http://ccforum.biomedcentral.com/)","snPcode":"13054","submissionUrl":"https://submission.nature.com/new-submission/13054/3","title":"Critical Care","twitterHandle":"@Crit_Care","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ventilator-associated pneumonia, Multiplex PCR, FilmArray pneumonia panel, Microbiological outcomes, Nosocomial pneumonia","lastPublishedDoi":"10.21203/rs.3.rs-5950504/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5950504/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAccurate microbiological documentation seems central for managing severe pneumonia. While the FilmArray\u0026reg; Pneumonia\u0026thinsp;+\u0026thinsp;panel (FA-PP) offers rapid pathogen identification, its effectiveness during antibiotic treatment and in predicting clinical outcomes remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a prospective observational study across four ICUs from April 2022 to June 2024, including patients with ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP). Bacterial loads were monitored on days 0, 1, 3, 7 and 10 and 3 days after stopping antibiotics, using endotracheal aspirates (ETAs) analyzed by FA-PP and standard cultures. The main objective was to assess the correlation between quantitative changes in FA-PP results and clinical success. Quantitative changes over time were analyzed using mixed ordinal logistic regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 93 patients enrolled, 60.2% (n\u0026thinsp;=\u0026thinsp;56) achieved clinical success, while the ICU mortality rate was 25.8% (n\u0026thinsp;=\u0026thinsp;24). Although FA-PP and culture quantification results declined over time (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), neither method consistently correlated with clinical success (non-significant for both). At diagnosis, FA-PP showed excellent diagnostic performance compared to culture, with a sensitivity of 94% [95% CI: 87\u0026ndash;97] and a specificity of 98% [95% CI: 97\u0026ndash;98]. Quantitative concordance improved with higher DNA copies, from 22.9% at the culture threshold at 10⁴ DNA copies/ml in FA-PP to 100% at \u0026ge;\u0026thinsp;10⁷ DNA copies/ml. Diagnostic performance remained stable during antibiotic treatment with 94% sensitivity and 95% specificity in follow-up ETAs.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eFA-PP provides rapid and accurate diagnostics but does not predict clinical outcomes during treatment, indicating limited utility for repeated testing in patient management.\u003c/p\u003e","manuscriptTitle":"Assessing FilmArray Pneumonia+ Panel dynamics during antibiotic treatment to predict clinical success in ICU patients with ventilated hospital-acquired pneumonia and ventilator-associated pneumonia: a multicenter prospective study ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-03 07:07:26","doi":"10.21203/rs.3.rs-5950504/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-24T17:37:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-14T15:19:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-13T08:10:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"181856540232203295365611398988864373402","date":"2025-04-07T16:03:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-07T12:32:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"196758170204629051006127643748721498709","date":"2025-04-07T04:46:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"153001056671516826382601964957316620406","date":"2025-04-04T07:15:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"333400846401154441441604480806195834396","date":"2025-04-02T06:54:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-02T00:09:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"315360009987013146632542005311227883537","date":"2025-04-01T22:02:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-01T20:45:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-31T04:56:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Critical Care","date":"2025-03-29T20:57:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cric","sideBox":"Learn more about [Critical Care](http://ccforum.biomedcentral.com/)","snPcode":"13054","submissionUrl":"https://submission.nature.com/new-submission/13054/3","title":"Critical Care","twitterHandle":"@Crit_Care","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"85188da0-2df6-440e-9d62-be78038009f8","owner":[],"postedDate":"April 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-14T16:10:27+00:00","versionOfRecord":{"articleIdentity":"rs-5950504","link":"https://doi.org/10.1186/s13054-025-05503-7","journal":{"identity":"critical-care","isVorOnly":false,"title":"Critical Care"},"publishedOn":"2025-07-12 15:56:59","publishedOnDateReadable":"July 12th, 2025"},"versionCreatedAt":"2025-04-03 07:07:26","video":"","vorDoi":"10.1186/s13054-025-05503-7","vorDoiUrl":"https://doi.org/10.1186/s13054-025-05503-7","workflowStages":[]},"version":"v1","identity":"rs-5950504","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5950504","identity":"rs-5950504","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}