Evaluation of the clinical relevance of the Biofire© FilmArray pneumonia panel among hospitalized patients.

PURPOSE: Panel PCR tests provide rapid pathogen identification. However, their diagnostic performance is unclear. We assessed the performance of the Biofire© FilmArray pneumonia (PN)-panel against standard culture in broncho-alveolar lavage (BAL) samples. METHODS: Setting: University Hospital Basel (February 2019 to July 2020), including hospitalized patients with a BAL (± pneumonia). We determined sensitivity and specificity of the PN-panel against standard culture. Using univariate logistic regression, we calculated odds ratios (OR) for pneumonia according to PN-panel and culture status, stratifying by chronic pulmonary disease. We calculated ORs for pneumonia for different pathogens to estimate the clinical relevance. RESULTS: We included 840 adult patients, 60% were males, median age was 68 years, 35% had chronic pulmonary disease, 21% had pneumonia, and 36% had recent antibiotic use. In 1078 BAL samples, bacterial pathogens were detected in 36% and 16% with PN-panel and culture, respectively. The overall sensitivity and specificity of the PN-panel was high, whereas the positive predictive value was low. The OR of pneumonia was 1.1 (95% CI 0.7-1.6) for PN-panel-positive only; 2.6 (95% CI 1.3-5.3) for culture-positive only, and 1.6 (95% CI 1.0-2.4) for PN-panel and culture-positive. The detection rate of Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis in the PN-panel was high but not associated with pneumonia. CONCLUSION: While sensitivity and specificity of PN-panel are high compared to culture, pathogen detection did not correlate well with a pneumonia diagnosis. Patients with culture-positive BAL had the highest OR for pneumonia-thus the impact of the PN-panel on clinical management needs further evaluation in randomized controlled trials.

Evaluation and clinical practice of pathogens and antimicrobial resistance genes of BioFire FilmArray Pneumonia panel in lower respiratory tract infections.

BACKGROUND: Existing panels for lower respiratory tract infections (LRTIs) are slow and lack quantification of important pathogens and antimicrobial resistance, which are not solely responsible for their complex etiology and antibiotic resistance. BioFire FilmArray Pneumonia (PN) panels may provide rapid information on their etiology. METHODS: The bronchoalveolar lavage fluid of 187 patients with LRTIs was simultaneously analyzed using a PN panel and cultivation, and the impact of the PN panel on clinical practice was assessed. The primary endpoint was to compare the consistency between the PN panel and conventional microbiology in terms of etiology and drug resistance, as well as to explore the clinical significance of the PN panel. The secondary endpoint was pathogen detection using the PN panel in patients with community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). RESULTS: Fifty-seven patients with HAP and 130 with CAP were included. The most common pathogens of HAP were Acinetobacter baumannii and Klebsiella pneumoniae, with the most prevalent antimicrobial resistance (AMR) genes being CTX-M and KPC. For CAP, the most common pathogens were Haemophilus influenzae and Staphylococcus aureus, with the most frequent AMR genes being CTX-M and VIM. Compared with routine bacterial culture, the PN panel demonstrated an 85% combined positive percent agreement (PPA) and 92% negative percent agreement (NPA) for the qualitative identification of 13 bacterial targets. PN detection of bacteria with higher levels of semi-quantitative bacteria was associated with more positive bacterial cultures. Positive concordance between phenotypic resistance and the presence of corresponding AMR determinants was 85%, with 90% positive agreement between CTX-M-type extended-spectrum beta-lactamase gene type and phenotype and 100% agreement for mecA/C and MREJ. The clinical benefit of the PN panel increased by 25.97% compared with traditional cultural tests. CONCLUSION: The bacterial pathogens and AMR identified by the PN panel were in good agreement with conventional cultivation, and the clinical benefit of the PN panel increased by 25.97% compared with traditional detection. Therefore, the PN panel is recommended for patients with CAP or HAP who require prompt pathogen diagnosis and resistance identification.

Precautionary findings on the utilization of FilmArray® to detect human astroviruses in fecal and sewage samples.

The FilmArray® Gastrointestinal (GI) Panel is a modern, sensitive, and comprehensive stool testing technique for identifying common gastrointestinal pathogens, including viruses, bacteria, and parasites. Its increasing demand is due to ease of operation and automation. Pathogens, particularly viruses, undergo constant genetic evolution. For instance, human astrovirus (HAstV), which causes gastroenteritis in children, the elderly, and immune-compromised individuals, can be identified by the GI Panel. HAstV has evolved into several clades, including the classic (HAstV1-8), novel Melbourne (MLB1-3), and Virginia (VA1-5) clades. This study investigated whether the GI Panel accurately detects all HAstV clades. A total of 12 stool and three sewage water (SW) samples were selected post-confirmation of distinct HAstV strains using conventional RT-PCR and sequence-based genotyping for reassessment by the GI Panel. The GI Panel accurately detected the classic HAstV in stool and SW samples. However, our results confirm the GI Panel's inability to detect the novel MLB (MLB1-3) and VA (VA2) clades in fecal samples, raising the possibility of false-negative results in HAstV testing. Although the GI Panel is useful for identifying a variety of gastrointestinal pathogens in stool and SW samples in a single test, our findings highlight the need to exercise caution when interpreting HAstV results from the GI Panel.

[Detection of microorganisms and resistance genes from positive blood cultures using the FilmArray® BCID2 panel: Experience in a pediatric hospital]. / Detección de microorganismos y genes de resistencia en hemocultivos positivos mediante FilmArray® panel BCID2: experiencia en un hospital pediátrico.

The rapid identification of microorganisms that cause bacteremia and their possible resistance markers are extremely important for the timely initiation of effective antibiotic therapy. The FilmArray® panel BCID2 (an automated rapid multiplex PCR assay) detects microorganisms and resistance genes from positive blood cultures within one hour. The aim of this study was to compare the results obtained from the FilmArray® Panel BCID2 and conventional culture in pediatric patients, as well as the reporting times of both methods. Sixty (60) FilmArray® results were included in the analysis. BCID2 showed high agreement with culture in the identification of microorganisms in monomicrobial bacteremias. However, in polymicrobial blood cultures, BCID2 detected a greater number of microorganisms compared to conventional culture, specifically,1 Staphylococcus aureus, 3 Staphylococcus epidermidis, 1 Enterococcus faecium, 2 Klebsiella oxytoca, 1 Acinetobacter calcoaceticus-baumannii complex, 1 Bacteroides fragilis and 1 Haemophilus influenzae. Furthermore, 88.3% (95%CI: 78.7-94.8) of the FilmArray® results coincided with conventional culture, while in polymicrobial bacteremias, BCID2 detected a greater number of microorganisms with respect to conventional culture [70% (95%CI: 39.3-91.5)]. The agreement of resistance genes was good with a few exceptions (one ESBL was not detected by FilmArray® and one S. aureus strain was characterized as methicillin-resistant by BCID2 and methicillin-sensitive by culture). When comparing the time elapsing since the blood culture was reported as positive up to the results were obtained, BCID2 had a median of 2h 50min (IQR of 1 h 58min to 9h 27min) while the conventional culture had a median of 45h 20min (IQR of 24h 57min to 63h 50min).

Clinical Manifestations and Stool Load of Atypical Enteropathogenic Escherichia coli Infections in United States Children and Adults.

BACKGROUND & AIMS: There is debate whether atypical enteropathogenic Escherichia coli (aEPEC) causes disease in adults. aEPEC is commonly detected in symptomatic and asymptomatic individuals. aEPEC, in contrast to typical EPEC, lacks bundle-forming pili, altering its pathogenicity. Here, we define for the first time the clinical manifestations of sporadic aEPEC infection in United States children and adults and determine whether EPEC load correlates with disease. METHODS: This is a retrospective case-control study of 380 inpatients/outpatients of all ages. EPEC load in stools was determined by quantitative polymerase chain reaction. RESULTS: Diarrhea, vomiting, abdominal pain, and fever were more prevalent in EPEC-positive cases than in EPEC-negative controls. aEPEC infection caused mostly acute, mild diarrhea lasting for 6 to 13 days. However, some had severe diarrhea with 10 to 40 bowel movements per day or had persistent/chronic diarrhea. Fever, vomiting, and abnormal serum sodium levels were more common in children. Adults more often reported abdominal pain and longer duration of diarrhea. Symptomatic aEPEC infection was associated with leukocytosis in 24% of patients. EPEC load >0.1% was associated with symptomatic infection; however, loads varied greatly. Co-infecting pathogens did not alter diarrhea severity or EPEC load. Longitudinal data reveal that some are colonized for months to years or are repeatedly infected. CONCLUSIONS: aEPEC is associated with a wide array of symptoms in adults, ranging from asymptomatic carriage to severe diarrhea. Higher EPEC loads are associated with presence of symptoms, but bacterial load does not predict disease or severity. Future studies are needed to understand bacterial and host factors that contribute to aEPEC pathogenicity to improve diagnostic tools and clinical care.

Performance and Hypothetical Impact on Joint Infection Management of the BioFire Joint Infection Panel: a Retrospective Analysis.

Pathogen identification is key in septic arthritis. Culture-based techniques are challenging, especially when patients have been pretreated with antibiotics or when difficult-to-culture bacteria are encountered. The BioFire joint infection assay (BJA) is a multiplex PCR panel which detects 31 of the most prevalent bacterial and fungal pathogens causing septic arthritis. Here, 123 cryoconserved contemporary synovial fluid samples from 120 patients underwent BJA analysis. Results were compared to those of culture-based diagnostics (standard of care [SOC]). Clinical data were collected, and the possible impact of the molecular diagnostic application on patient management was evaluated. Fifteen of 123 synovial fluid cultures grew bacterial pathogens. All on-panel pathogens (9/15) were correctly identified by the BJA. The BJA identified four additional bacterial pathogens in four SOC-negative cases. BJA sensitivity and specificity were 100% (95% confidence interval [CI], 69.2% to 100%) and 100% (95% CI, 96.8% to 100%), respectively. Compared to the SOC, the BJA would have resulted in faster provision of species identification and molecular susceptibility data by 49 h and 99 h, respectively. Clinical data analysis indicates that in BJA-positive cases, faster species ID could have led to timelier optimization of antibiotic therapy. This retrospective study demonstrates high sensitivity and specificity of the BJA to detect on-panel organisms in bacterial arthritis. The usefulness of the BJA in prosthetic-joint infections is limited, as important pathogens (i.e., coagulase negative staphylococci and Cutibacterium acnes) are not covered. Evidence from patient data analysis suggests that the assay might prove valuable for optimizing patient management in acute arthritis related to fastidious organisms or for patients who received antibiotics prior to specimen collection.

Diagnostic utility of oropharyngeal swabs as an alternative to lower respiratory tract samples for PCR-based syndromic testing in patients with community-acquired pneumonia.

Syndromic PCR-based analysis of lower respiratory tract (LRT) samples in patients with community-acquired pneumonia (CAP) improves the bacterial yield and time-to-results compared to culture-based methods. However, obtaining adequate sputum samples can be challenging and is frequently not prioritized in the emergency department (ED). In this study, we assess the concordance of microbiological detections between oropharyngeal- (OP) and LRT samples from patients presenting to the ED with CAP using a syndromic PCR-based respiratory panel [Biofire FilmArray Pneumonia plus (FAP plus)]. Paired OP- and high-quality LRT samples were collected from 103 patients with confirmed CAP, who had been included in a randomized controlled trial (NCT04660084) or a subsequent observational study at Haukeland University Hospital, and analyzed using the FAP plus. The LRT samples were obtained mainly by sputum induction (88%). Using the LRT samples as a reference standard, the positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement for the most common bacterial pathogens in CAP, Streptococcus pneumoniae and Haemophilus influenzae, were 85%, 99% and 95%, and 86%, 98% and 93%, respectively. For Moraxella catarrhalis, the PPA was lower (74%), while the NPA was 100%. For bacteria that are less likely causes of uncomplicated CAP (e.g., Staphylococcus aureus and Enterobacterales) the results were more divergent. In conclusion, the FAP plus detects the most common CAP pathogens S. pneumoniae and H. influenzae from OP samples with high PPAs and excellent NPAs when compared with LRT samples. For these pathogens, the PPAs for OP samples were higher than previous reports for nasopharyngeal samples. This suggests that analysis of OP samples with syndromic PCR panels could represent an alternative approach for rapid microbiological testing in the ED, especially in patients where LRT samples are difficult to obtain. Divergent results for bacteria that are less likely to cause uncomplicated CAP do, however, emphasize the need for clinical evaluation of positive test results.

Primary septic arthritis of the knee caused by Neisseria meningitidis serogroup B in an elderly patient. Case report and review of the literature.

PURPOSE: Primary meningococcal arthritis (PMA) represents an uncommon clinical presentation of meningococcal infection, mainly reported among young people. Herein, a case of PMA of the knee in an elderly patient is described. CASE PRESENTATION: On January 2022, an 87-year-old patient arrived at hospital with continuous fever persisting for three days and a picture of pain, swelling, redness, and warmth of her left knee. An arthrocentesis was promptly performed and the inoculated synovial fluid turned positive with numerous Gram-negative diplococci at the microscopic examination. The identification of bacteria was done in 48 h using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) MS systems (VITEK®MS-bioMérieux) and standard microbiological procedures (VITEK®2 NH ID card-bioMérieux). Both methods identified the strain as N. meningitidis. The meningococcal isolate belonged to the serogroup B (MenB), Sequence type (ST)-162/clonal complex (cc)162. Two grams of ceftriaxone twice a day were administered for 21 days; than cefditoren pivoxil 400 mg twice a day for further 6 weeks after discharge. In Italy, from 2018 to January 2022, among 135 MenB, 31 MenB/cc162 were identified, of which only the case here reported was associated with an atypical clinical presentation. REVIEW OF THE LITERATURE: A total of 41 cases of PMA caused by N. meningitidis was reported in the literature, but only four occurred in elderly. To our knowledgements, no cases of PMA caused by MenB were previously reported among patients of more than 65 years of age.

Diagnostic accuracy of the BioFire® FilmArray® pneumonia panel in COVID-19 patients with ventilator-associated pneumonia.

BACKGROUND: Ventilator-Associated pneumonia (VAP) is one of the leading causes of morbidity and mortality in critically ill COVID-19 patients in lower-and-middle-income settings, where timely access to emergency care and accurate diagnostic testing is not widely available. Therefore, rapid microbiological diagnosis is essential to improve effective therapy delivery to affected individuals, preventing adverse outcomes and reducing antimicrobial resistance. METHODS: We conducted a cross-sectional study of patients with suspected VAP and COVID-19, evaluating the diagnostic performance of the BioFire® FilmArray® Pneumonia Panel (FA-PP). Respiratory secretion samples underwent standard microbiological culture and FA-PP assays, and the results were compared. RESULTS: We included 252 samples. The traditional culture method detected 141 microorganisms, and FA-PP detected 277, resulting in a sensitivity of 95% and specificity of 60%, with a positive predictive value of 68% and negative predictive value of 93%. In samples with high levels of genetic material (> 10^5 copies/mL), the panel had a sensitivity of 94% and specificity of 86%. In addition, 40% of the culture-negative samples had positive FA-PP® results, of which 35% had > 10^5 copies/mL of genetic material. The most prevalent bacteria were Gram-negative bacilli, followed by Gram-positive cocci. The panel identified 98 genes associated with antimicrobial resistance, predominantly extended-spectrum beta-lactamases (28%). CONCLUSION: The FA-PP is a sensitive assay for identifying bacteria causing VAP in patients with COVID-19, with a greater capacity to detect bacteria than the conventional method. The timely microbiological recognition offered by this panel could lead to optimized decision-making processes, earlier tailored treatment initiation, and improved antibiotic stewardship practices.

Comparison of bacterial culture with BioFire® FilmArray® multiplex PCR screening of archived cerebrospinal fluid specimens from children with suspected bacterial meningitis in Nigeria.

BACKGROUND: Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis. METHODS: Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens were frozen and later tested by BioFire ME Panel. RESULTS: A total of 400 samples were analyzed. Thirty-two [32/400 (8%)] of the specimens were culture positive, consisting of; three Salmonella spp. (2 Typhi and 1 non-typhi), three alpha hemolytic Streptococcus, one Staphylococcus aureus, six Neisseria meningitidis, seven Hemophilus influenzae, 11 Streptococcus pneumoniae and 368 were culture negative. Of the 368 culture-negative specimens, the BioFire ME Panel detected at least one bacterial pathogen in 90 (24.5%) samples, consisting of S. pneumoniae, N. meningitidis and H. influenzae, predominantly. All culture positive specimens for H. influenzae, N. meningitidis and S. pneumoniae also tested positive with the BioFire ME Panel. In addition, 12 specimens had mixed bacterial pathogens identified. For the first time in this setting, we have data on the viral agents associated with meningitis. Single viral agents were detected in 11 (2.8%) samples while co-detections with bacterial agents or other viruses occurred in 23 (5.8%) of the samples. CONCLUSIONS: The BioFire® ME Panel was more sensitive and rapid than culture for detecting bacterial pathogens in CSF. The BioFire® ME Panel also provided for the first time, the diagnosis of viral etiologic agents that are associated with meningoencephalitis in this setting. Institution of PCR diagnostics is recommended as a routine test for suspected cases of ABM to enhance early diagnosis and optimal treatment.

Identification of microorganisms by a rapid PCR panel from positive blood cultures leads to faster optimal antimicrobial therapy - a before-after study.

BACKGROUND: The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) - a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification. METHODS: In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions. RESULTS: Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0-31.2) hours with BF-FA-BCIP compared to 45.7 (37.7-51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes. CONCLUSIONS: Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04156633, registered on November 5, 2019.

The usefulness of a nasopharyngeal multiplex polymerase chain reaction system to screen pediatric patients with preoperative fever.

BACKGROUND: When children have a preoperative fever, anesthesiologists must help determine whether to postpone or proceed with surgery, as fever may be a sign of upper respiratory tract infection (URTI). Such infections are a known risk factor for perioperative respiratory adverse events (PRAEs), which are still one of the prime causes of anesthetic mortality and morbidity in pediatric patients. Since the COVID-19 pandemic, preoperative assessments have become drastically more complex as hospitals strive to balance practicality and safety. In our facility, if pediatric patients presented with preoperative fever, we used the FilmArray® Respiratory Panel 2.1 to determine whether to postpone or proceed with surgery. METHODS: This is a single-center retrospective observational study evaluating the efficacy of the FilmArray® Respiratory Panel 2.1 as a preoperative screening test. This study included pediatric patients scheduled for elective surgeries between March 2021 and February 2022. FilmArray was used if a patient had a preoperative fever (determined by axillary temperature, ≥38°C for <1-year-old, ≥37.5°C for ≥1-year-old) between hospital admission and before surgery. We excluded patients if they had apparent symptoms of URTI. RESULTS: In the FilmArray positive group, 11 of 25 (44%) cases developed subsequent symptoms after surgery was canceled. No patients in the negative group developed symptoms. The proportion of the development of subsequent symptoms between the FilmArray positive and negative groups was statistically significant (p < .001, odds ratio: 29.6, 95% confidence interval: [3.80-1356.01]). CONCLUSIONS: Our retrospective observational study revealed that 44% of the FilmArray positive group subsequently developed symptoms, and no PRAEs were observed in the FilmArray negative group. We suggest that FilmArray could be useful as a screening test for pediatric patients with preoperative fever.

Usefulness of the FilmArray blood culture identification panel for identifying causative pathogens of bone and joint infections.

As bone and joint infections (BJIs) require long-term treatment, identifying their causative pathogens is vital. However, the detection rate of conventional culturing remains inadequate. This study aimed to evaluate the usefulness of the FilmArray blood culture identification (BCID) panel for identifying causative pathogens in patients with BJIs. We tested a BCID panel using collected samples, in addition to conventional cultures. The primary outcome was to evaluate the diagnostic performance of the BCID panel, calculated using conventional culturing methods. A total of 44 patients who underwent BJI-related specimen collection were enrolled. Of the 44 patients, 22 were diagnosed with a BJI. Conventional culture identified 15 of 22 organisms (68.2%), whereas the BCID panel identified 14 of 22 organisms (63.4%). The overall sensitivity and specificity of the BCID panel were 73.3% and 57.1%, respectively, compared to those of the conventional culture. However, the sensitivity reached 100% when only pathogens included in the BCID panel were considered. In seven culture-negative cases, the BCID panel identified three organisms (42.9%). The BCID panel also indicated the appropriate therapy against a BJI caused by methicillin-resistant Staphylococcus aureus by detecting the mecA gene. This study demonstrated that the BCID panel has the potential for early and accurate diagnosis of the causative organism of BJI using specimens such as joint fluid and bone tissue. Our results suggest that BCID panels, in addition to routine culture, may improve our ability to diagnose the causative microorganisms of BJI in clinical practice, thereby contributing to the selection of appropriate antimicrobial agents.

Clinical influence of multiplex polymerase chain reaction routine uses in urgent pediatric admissions.

BACKGROUND: The coronavirus disease 2019 outbreak has prompted some hospitals to implement screening tests upon admission since 2020. FilmArray® Respiratory 2.1 Panel (FilmArray) is a multiplex polymerase chain reaction (PCR) test with high sensitivity and specificity for detecting respiratory pathogens. We aimed to assess the clinical influence of the routine use of FilmArray for pediatric patients, including those without symptoms suggestive of an infection. METHODS: We conducted a single-center retrospective observational study, which investigated patients aged ≤15 years who underwent FilmArray on admission in 2021. We collected the patients' epidemiological information, symptoms, and FilmArray results from their electronic health records. RESULTS: A positive result was observed in 58.6% of patients admitted to the general ward or intensive care unit (ICU) but only in 1.5% of patients in the neonatal ward. Among the patients admitted to the general ward or ICU who tested positive, 93.3% had symptoms suggestive of infections, 44.6% had a sick contact before admission, and 70.5% had siblings. However, 62 (28.2%) out of 220 patients without the four (fever, respiratory, gastrointestinal, and dermal) symptoms also had positive results. Among them, 18 patients with adenovirus and three with respiratory syncytial virus were isolated to private rooms. However, 12 (57.1%) patients were discharged without symptoms suggestive of viral infection. CONCLUSION: Multiplex PCR routine use for all inpatients may lead to excessive management of positive cases because FilmArray cannot quantify microorganisms. Thus, targets for testing should be considered carefully based on patients' symptoms and histories of sick contacts.

Impact of the multiplex molecular FilmArray Respiratory Panel on antibiotic prescription and clinical management of immunocompromised adults with suspected acute respiratory tract infections: A retrospective before-after study.

This study aimed to assess the impact of the implementation of a rapid multiplex molecular FilmArray Respiratory Panel (FRP) on the medical management of immunocompromised patients from a community general hospital. We conducted a single-center, retrospective, and before-after study. Two periods were evaluated: before the implementation of the FRP (pre-FRP) from April 2017 to May 2018 and after the implementation of the FRP (post-FRP) from January to July 2019. The inclusion criteria were immunocompromised patients over 18 years of age with suspected acute respiratory illness tested by conventional diagnostic methods (pre-FRP) or the FilmArray™ Respiratory Panel v1.7 (post-FRP). A total of 142 patients were included, 64 patients in the pre-FRP and 78 patients in the post-FRP. The positive detection rate was significantly higher in the post-FRP (63% vs. 10%, p<0.01). There were more patients receiving antimicrobial treatment in the pre-FRP compared with the post-FRP period (94% vs. 68%, p<0.01). A decrease in beta-lactam (89% vs. 61%, p<0.01) and macrolide (44% vs. 13%, p<0.01) prescriptions were observed in the post-FRP. No differences were observed in oseltamivir use (22% vs. 13%, p=0.14), changes in antimicrobial treatment, hospital admission rate, days-reduction in droplet isolation precautions, hospital length of stay (LOS), admission to intensive care unit (ICU), LOS in ICU, treatment failure and 30-day mortality. The implementation of the FRP impacted patient care by improving diagnostic yield and optimizing antimicrobial treatment in immunocompromised adult patients.

Type-I Interferon assessment in 45 minutes using the FilmArray® PCR platform in SARS-CoV-2 and other viral infections.

Low concentrations of type-I interferon (IFN) in blood seem to be associated with more severe forms of Coronavirus disease 2019 (COVID-19). However, following the type-I interferon response (IR) in early stage disease is a major challenge. We evaluated detection of a molecular interferon signature on a FilmArray® system, which includes PCR assays for four interferon stimulated genes. We analyzed three types of patient populations: (i) children admitted to a pediatric emergency unit for fever and suspected infection, (ii) ICU-admitted patients with severe COVID-19, and (iii) healthcare workers with mild COVID-19. The results were compared to the reference tools, that is, molecular signature assessed with Nanostring® and IFN-α2 quantification by SIMOA® (Single MOlecule Array). A strong correlation was observed between the IR measured by the FilmArray®, Nanostring®, and SIMOA® platforms (r-Spearman 0.996 and 0.838, respectively). The FilmArray® panel could be used in the COVID-19 pandemic to evaluate the IR in 45-min with 2 min hand-on-time at hospitalization and to monitor the IR in future clinical trials.

Direct comparison of Xpert Xpress, FilmArray Respiratory Panel, Lumipulse antigen test, and RT-qPCR in 165 nasopharyngeal swabs.

BACKGROUND: The nucleic acid amplification test (NAAT) and antigen test are approved diagnostic tests for COVID-19. In this study, we aimed to investigate the assay performance of two NAATs (Xpert Xpress SARS-CoV-2 and FilmArray Respiratory Panel) and a quantitative antigen test (Lumipulse). METHODS: One hundred and sixty-five nasopharyngeal swabs were subjected to Xpert, FilmArray, Lumipulse, and RT-qPCR assays. RESULTS: Of 165 samples, RT-qPCR showed 100 positives and 65 negatives. The Xpert had an overall agreement of 99.4% (95% confidence interval [CI]: 96.7-99.4%), sensitivity of 99% (95% CI: 96.8-99%), and specificity of 100% (95% CI: 96.6-100%). FilmArray had an overall agreement of 98.8% (95% CI: 95.9-98.8%), sensitivity of 98% (95% CI: 95.6-98%), and specificity of 100% (95% CI: 96.3-100%). Lumipulse had an overall agreement of 95.5% (95% CI: 91.8-95.5%), sensitivity of 92.3% (95% CI: 89.2-92.3%), and specificity of 100% (95% CI: 95.5-100%). The κ coefficient showed excellent agreement between each test and RT-qPCR. There was a high correlation between Xpert Ct values, RT-qPCR Ct values, viral loads and antigen level. CONCLUSIONS: Xpert Xpress and FilmArray Respiratory Panel exhibited an equivalent performance. The Lumipulse antigen test was slightly less sensitive than the NAATs, but showed high assay performance except for samples with low viral load. The Xpert Xpress, FilmArray Respiratory Panel and Lumipulse antigen tests offer rapid sample-to-answer data, allowing random access detection on automated devices.

The changing spectrum of microbial aetiology of respiratory tract infections in hospitalized patients before and during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic was met with strict containment measures. We hypothesized that societal infection control measures would impact the number of hospital admissions for respiratory tract infections, as well as, the spectrum of pathogens detected in patients with suspected community acquired pneumonia (CAP). METHODS: This study is based on aggregated surveillance data from electronic health records of patients admitted to the hospitals in Bergen Hospital Trust from January 2017 through June 2021, as well as, two prospective studies of patients with suspected CAP conducted prior to and during the COVID-19 pandemic (pre-COVID cohort versus COVID cohort, respectively). In the prospective cohorts, microbiological detections were ascertained by comprehensive PCR-testing in lower respiratory tract specimens. Mann-Whitney's U test was used to analyse continuous variables. Fisher's exact test was used for analysing categorical data. The number of admissions before and during the outbreak of SARS-CoV-2 was compared using two-sample t-tests on logarithmic transformed values. RESULTS: Admissions for respiratory tract infections declined after the outbreak of SARS-CoV-2 (p < 0.001). The pre-COVID and the COVID cohorts comprised 96 and 80 patients, respectively. The proportion of viruses detected in the COVID cohort was significantly lower compared with the pre-COVID cohort [21% vs 36%, difference of 14%, 95% CI 4% to 26%; p = 0.012], and the proportion of bacterial- and viral co-detections was less than half in the COVID cohort compared with the pre-COVID cohort (19% vs 45%, difference of 26%, 95% CI 13% to 41%; p < 0.001). The proportion of bacteria detected was similar (p = 0.162), however, a difference in the bacterial spectrum was observed in the two cohorts. Haemophilus influenzae was the most frequent bacterial detection in both cohorts, followed by Streptococcus pneumoniae in the pre-COVID and Staphylococcus aureus in the COVID cohort. CONCLUSION: During the first year of the COVID-19 pandemic, the number of admissions with pneumonia and the microbiological detections in patients with suspected CAP, differed from the preceding year. This suggests that infection control measures related to COVID-19 restrictions have an overall and specific impact on respiratory tract infections, beyond reducing the spread of SARS-CoV-2.

Diagnostic concordance between BioFire® FilmArray® Pneumonia Panel and culture in patients with COVID-19 pneumonia admitted to intensive care units: the experience of the third wave in eight hospitals in Colombia.

BACKGROUND: The detection of coinfections is important to initiate appropriate antimicrobial therapy. Molecular diagnostic testing identifies pathogens at a greater rate than conventional microbiology. We assessed both bacterial coinfections identified via culture or the BioFire® FilmArray® Pneumonia Panel (FA-PNEU) in patients infected with SARS-CoV-2 in the ICU and the concordance between these techniques. METHODS: This was a prospective study of patients with SARS-CoV-2 who were hospitalized for no more than 48 h and on mechanical ventilation for no longer than 24 h in 8 ICUs in Medellín, Colombia. We studied mini-bronchoalveolar lavage or endotracheal aspirate samples processed via conventional culture and the FA-PNEU. Coinfection was defined as the identification of a respiratory pathogen using the FA-PNEU or cultures. Serum samples of leukocytes, C-reactive protein, and procalcitonin were taken on the first day of intubation. We analyzed the empirical antibiotics and the changes in antibiotic management according to the results of the FA-PNEUM and cultures. RESULTS: Of 110 patients whose samples underwent both methods, FA-PNEU- and culture-positive samples comprised 24.54% versus 17.27%, respectively. Eighteen samples were positive in both techniques, 82 were negative, 1 was culture-positive with a negative FA-PNEU result, and 9 were FA-PNEU-positive with negative culture. The two bacteria most frequently detected by the FA-PNEU were Staphylococcus aureus (37.5%) and Streptococcus agalactiae (20%), and those detected by culture were Staphylococcus aureus (34.78%) and Klebsiella pneumoniae (26.08%). The overall concordance was 90.1%, and when stratified by microorganism, it was between 92.7 and 100%. The positive predictive value (PPV) was between 50 and 100% and were lower for Enterobacter cloacae and Staphylococcus aureus. The negative predictive value (NPV) was high (between 99.1 and 100%); MecA/C/MREJ had a specificity of 94.55% and an NPV of 100%. The inflammatory response tests showed no significant differences between patients whose samples were positive and negative for both techniques. Sixty-one patients (55.45%) received at least one dose of empirical antibiotics. CONCLUSIONS: The overall concordance was 90.1%, and it was between 92.7% and 100% when stratified by microorganisms. The positive predictive value was between 50 and 100%, with a very high NPV.

Usefulness of the FilmArray Meningitis/Encephalitis Panel in diagnosis of central nervous system infection after allogeneic hematopoietic stem cell transplantation.

PURPOSE: The BioFire FilmArray® Meningitis/Encephalitis Panel (FAMEP) is designed to rapidly and accurately detect common multiple pathogens that cause central nervous system (CNS) infection, including viruses, bacteria, and yeast. The FAMEP's usefulness in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) has not been fully evaluated. This retrospective study evaluated the usefulness of the FAMEP in the screening for CNS infection after allogeneic HSCT. METHODS: Cerebrospinal fluid (CSF) was obtained from 12 patients to evaluate the causes of CNS disorders after allogeneic HSCT, and the FAMEP was applied. RESULTS: The median day of the FAMEP evaluations was 27 days post-transplant (range, 0-390). Human herpesvirus 6 (HHV-6) was detected in three patients and cytomegalovirus was detected in one patient, leading to the diagnosis of encephalitis/myelitis. In three patients (HHV-6, n = 2; CMV, n = 1), the presence of the viruses was confirmed by conventional real-time polymerase chain reaction (PCR). However, in the remaining patient with HHV-6 detected by the AMEP, HHV-6 was not detected by real-time PCR at the onset but was detected 7 days later. The treatments for the detected viruses improved the clinical conditions in the four patients. CONCLUSIONS: Our results suggest that the FAMEP can be a useful sensitive assay in the screening and diagnosis of CNS viral infections after allogeneic HSCT.