Multicenter evaluation of the BIOFIRE Joint Infection Panel for the detection of bacteria, yeast, and AMR genes in synovial fluid samples.

The bioMérieux BIOFIRE Joint Infection (JI) Panel is a multiplex in vitro diagnostic test for the simultaneous and rapid (~1 h) detection of 39 potential pathogens and antimicrobial resistance (AMR) genes directly from synovial fluid (SF) samples. Thirty-one species or groups of microorganisms are included in the kit, as well as several AMR genes. This study, performed to evaluate the BIOFIRE JI Panel for regulatory clearance, provides data from a multicenter evaluation of 1,544 prospectively collected residual SF samples with performance compared to standard-of-care (SOC) culture for organisms or polymerase chain reaction (PCR) and sequencing for AMR genes. The BIOFIRE JI Panel demonstrated a sensitivity of 90.9% or greater for all but six organisms and a positive percent agreement (PPA) of 100% for all AMR genes. The BIOFIRE JI Panel demonstrated a specificity of 98.5% or greater for detection of all organisms and a negative percent agreement (NPA) of 95.7% or greater for all AMR genes. The BIOFIRE JI Panel provides an improvement over SOC culture, with a substantially shorter time to result for both organisms and AMR genes with excellent sensitivity/PPA and specificity/NPA, and is anticipated to provide timely and actionable diagnostic information for joint infections in a variety of clinical scenarios.

Detection of human herpesvirus 6 in pediatric CSF samples: causing disease or incidental distraction?

Interpretation of human herpesvirus type 6 (HHV6) detection in the cerebrospinal fluid (CSF) of children can be complex; the virus can cause acute infection, reactivation, or can be inherited chromosomally integrated (iciHHV6). Our objectives were to determine the prevalence of HHV6 including iciHHV6 in CSF and compare the clinical and laboratory characteristics with and without iciHHV6 in our patient population. Overall, the prevalence of HHV6 and iciHHV6 was 2.4% and 0.85%, respectively. Children with iciHHV6 were significantly younger and less likely to present with fever. Septic infants (≤60 days) accounted for 65.2% (15/23) of the iciHHV6 patients. Patients with iciHHV6 had higher viral loads in CSF and whole blood. Twenty-one (91.3%) patients with iciHHV6 and 12 (33.3%) without ici-HHV6 were determined to have an incidental detection of HHV6 not associated with presenting symptoms. Molecular detection of HHV6 in CSF is not always associated with HHV6 infection and may represent iciHHV6 particularly in infants evaluated for sepsis.

Performance comparison of three commercial tests for the detection of SARS-CoV-2 antibodies in a common set of pediatric samples.

BACKGROUND: Serologic testing for SARS CoV-2 is useful for detection of past infection and assisting in diagnosis of post-COVID-19 syndromes such as MIS-C. Immune responses to SARS-CoV-2 infection in children differ from adults but most antibody performance studies are limited to adults. OBJECTIVE: The objective of this study was to compare three commercial SARS-CoV-2 antibody kits in a common set of children being evaluated for SARS-CoV-2 infection. METHODS: Three SARS-CoV-2 antibody tests: Abbott anti-nucleocapsid (N) IgG (AA), Epitope Diagnostics anti-N IgG (EDI) and EUROIMMUN anti-S1 Spike IgG (EU) were compared against two references: 1) RT-PCR and 2) consensus IgG (consIgG). RESULTS: All three tests had a sensitivity <53% compared to RT-PCR, with EU outperforming EDI (p = 0.03). When all samples were compared to consIgG, positive percent agreement was comparable (AA-90%, EU- 98% and EDI- 88%) but EDI had significantly better negative percent agreement than EU (p = 0.009). No difference in test performance was observed using either reference when samples were collected ≥15 days post-symptom onset (PSO). CONCLUSIONS: Our findings suggest good performance of commercial SARS-CoV-2 IgG assays in pediatric patients with samples collected ≥15 days PSO. Additional studies investigating antibody response and assay performance in children are warranted.

Multicenter Evaluation of the BIOFIRE Blood Culture Identification 2 Panel for Detection of Bacteria, Yeasts, and Antimicrobial Resistance Genes in Positive Blood Culture Samples.

Diagnostic tools that can rapidly identify and characterize microbes growing in blood cultures are important components of clinical microbiology practice because they help to provide timely information that can be used to optimize patient management. This publication describes the bioMérieux BIOFIRE Blood Culture Identification 2 (BCID2) Panel clinical study that was submitted to the U.S. Food & Drug Administration. Results obtained with the BIOFIRE BCID2 Panel were compared to standard-of-care (SoC) results, sequencing results, PCR results, and reference laboratory antimicrobial susceptibility testing results to evaluate the accuracy of its performance. Results for 1,093 retrospectively and prospectively collected positive blood culture samples were initially enrolled, and 1,074 samples met the study criteria and were included in the final analyses. The BIOFIRE BCID2 Panel demonstrated an overall sensitivity of 98.9% (1,712/1,731) and an overall specificity of 99.6% (33,592/33,711) for Gram-positive bacteria, Gram-negative bacteria and yeast targets which the panel is designed to detect. One hundred eighteen off-panel organisms, which the BIOFIRE BCID2 Panel is not designed to detect, were identified by SoC in 10.6% (114/1,074) of samples. The BIOFIRE BCID2 Panel also demonstrated an overall positive percent agreement (PPA) of 97.9% (325/332) and an overall negative percent agreement (NPA) of 99.9% (2,465/2,767) for antimicrobial resistance determinants which the panel is designed to detect. The presence or absence of resistance markers in Enterobacterales correlated closely with phenotypic susceptibility and resistance. We conclude that the BIOFIRE BCID2 Panel produced accurate results in this clinical trial.

SARS-CoV-2 Reinfection With Different SARS-CoV-2 Variants in Children, Ohio, United States.

BACKGROUND: Beginning in late 2021, we observed a significant increase in SARS-CoV-2 reinfections in pediatric patients evaluated at our institution. We aimed to characterize the children with SARS-CoV-2 reinfection, determine the number of SARS-CoV-2 reinfections, and characterize the intervals between two infections in our patient population. METHODS: From March 2020 to September 2022, we identified children ≤21 years old who had ≥2 SARS-CoV-2 infections using laboratory reports. We then defined the type of SARS-CoV-2 variant in the first and subsequent infections by mutation-specific typing or local epidemiology data. Clinical outcomes and the intervals between SARS-CoV-2 infections were assessed. RESULTS: We identified 541 children with ≥2 SARS-CoV-2 infections. The median interval between two infections was 229 days. The hospitalization rate was lower in the second infection. Reinfection counts were higher during the periods that Omicron variants predominated. Reinfection occurred more rapidly when Omicron variants were circulating with some occurring in less than 90 days. CONCLUSIONS: As SARS-CoV-2 continues to evolve, there is a need for ongoing surveillance to identify the frequency and time interval between reinfections and to re-evaluate the definition of SARS-CoV-2 reinfections.

A Hypothesis-Generating Prospective Longitudinal Study to Assess the Relative Contribution of Common Respiratory Viruses to Severe Lower Respiratory Infections in Young Children.

BACKGROUND: Respiratory viruses such as respiratory syncytial virus (RSV), influenza, parainfluenza and human metapneumovirus are well-established etiologies of acute lower respiratory tract infections (ALRIs; LRI-viruses). In contrast, adenovirus (AdV), rhinovirus/enterovirus (RV/EV) and seasonal human coronaviruses (CoV), collectively termed AdV/RV/CoV, are detected both in healthy children and children with ALRI. METHODS: The methods include a prospective longitudinal case-control study, assessing the prevalence of LRI-viruses versus AdV/RV/CoV in ALRI [community-acquired alveolar pneumonia (CAAP) and bronchiolitis] during hospitalization (visit 1), 7-14 days (visit 2) and 28-35 days (visit 3) in 2-17-month-old children. Controls were 2-27-month-old children hospitalized for elective surgery during the same respiratory seasons. RESULTS: We enrolled 99 infants (37 CAAP, 38 bronchiolitis and 24 controls) and obtained 211 nasopharyngeal swabs. Overall, 163 (77%) had greater than or equal to 1 viruses detected; RV/EV (n = 94; 45%) and RSV (n = 71; 34%) were the most frequently detected viruses. In CAAP, the overall LRI-virus prevalence was 78.4%, 32.4% and 5.4% in visits 1, 2 and 3, respectively; the respective rates in bronchiolitis were 73.7%, 34.5% and 8.0%. In controls, no LRI-viruses were detected. In contrast, the overall AdV/RV/CoV prevalence was high among controls (70.8%) and similar among CAAP (48.6%, 40.5% and 40.5%) and bronchiolitis (47.4, 58.6% and 64.0%) across visits. CONCLUSIONS: Among ALRI cases, LRI-viruses dominated during the acute disease, with prevalence declining within 28-35 days, suggesting their causative role. In contrast, AdV/RV/CoV prevalence was similar during all 3 visits and in controls, suggesting that carriage of these viruses is common during the viral respiratory season. The current study is relatively small and of short duration; however, the findings are supported by other recent studies.

Clinical Characteristics and Etiology of Community-acquired Pneumonia in US Children, 2015-2018.

BACKGROUND: Pneumonia has a major impact on childhood health and health care costs. This study was designed to obtain contemporary information on the clinical characteristics and etiology of community-acquired pneumonia (CAP) in children from both inpatient and outpatient settings in the USA. METHODS: We conducted a prospective, multicenter, observational study of CAP among previously healthy children 2 months to 18 years of age in 6 children's hospitals in Ohio from 2015 to 2018. For pathogen detection, nasopharyngeal swabs were collected from all subjects. Blood and pleural fluid cultures were available per standard of care. RESULTS: We enrolled a convenience sample of 441 patients: 380 hospitalized and 61 outpatients. Tachypnea and radiologic findings of consolidation and pleural effusion were more frequent among inpatients than outpatients. A pathogen was detected in 64.6% of patients: viruses in 55.6%, atypical bacteria in 8.8% and pyogenic bacteria in 4.3%. Eighteen (4.1%) patients had both viruses and bacteria detected. Rhinovirus/enterovirus (RV; 18.6%) and respiratory syncytial virus (RSV; 16.8%) were the viruses most frequently detected, and Mycoplasma pneumoniae (8.2%) and Streptococcus pneumoniae (2.3%) were the most common bacteria. Except for S. pneumoniae, which was identified more frequently in inpatients, there were no significant differences between inpatients and outpatients in the proportions of children with specific pathogens detected. CONCLUSIONS: Rhinovirus/enterovirus and RSV among viruses and M. pneumoniae and S. pneumoniae among bacteria were the most common pathogens detected in children with CAP. Tachypnea and chest radiographs with consolidation and/or pleural effusion were associated with hospitalization.

Corrigendum to: 204. Mucosal Cytokine Profiles in Children with COVID-19.

[This corrects the article DOI: 10.1093/ofid/ofab466.000.].

Macrolide-Resistant Mycoplasma pneumoniae Infections in Children, Ohio, USA.

Emergence of macrolide-resistant Mycoplasma pneumoniae (MRMp) challenges empiric macrolide therapy. Our goal was to determine MRMp rates and define characteristics of children infected with macrolide-sensitive M. pneumoniae (MSMp) versus MRMp in Ohio, USA. We cultured PCR-positive M. pneumoniae specimens and sequenced M. pneumoniae-positive cultures to detect macrolide resistance mutations. We reviewed medical records to compare characteristics of both groups. We identified 14 (2.8%) MRMp and 485 (97.2%) MSMp samples. Patients in these groups had similar demographics and clinical characteristics, but patients with MRMp had longer hospitalizations, were more likely to have received previous macrolides, and were more likely to have switched to alternative antimicrobial drugs. MRMp-infected patients also had ≈5-fold greater odds of pediatric intensive care unit admission. Rates of MRMp infections in children in central Ohio are low, but clinicians should remain aware of the risk for severe illness caused by these pathogens.

Multicenter Evaluation of the BioFire FilmArray Pneumonia/Pneumonia Plus Panel for Detection and Quantification of Agents of Lower Respiratory Tract Infection.

The ability to provide timely identification of the causative agents of lower respiratory tract infections can promote better patient outcomes and support antimicrobial stewardship efforts. Current diagnostic testing options include culture, molecular testing, and antigen detection. These methods may require collection of various specimens, involve extensive sample treatment, and can suffer from low sensitivity and long turnaround times. This study assessed the performance of the BioFire FilmArray Pneumonia Panel (PN panel) and Pneumonia Plus Panel (PNplus panel), an FDA-cleared sample-to-answer assay that enables the detection of viruses, atypical bacteria, bacteria, and antimicrobial resistance marker genes from lower respiratory tract specimens (sputum and bronchoalveolar lavage [BAL] fluid). Semiquantitative results are also provided for the bacterial targets. This paper describes selected analytical and clinical studies that were conducted to evaluate performance of the panel for regulatory clearance. Prospectively collected respiratory specimens (846 BAL and 836 sputum specimens) evaluated with the PN panel were also tested by quantitative reference culture and molecular methods for comparison. The PN panel showed a sensitivity of 100% for 15/22 etiologic targets using BAL specimens and for 10/24 using sputum specimens. All other targets had sensitivities of ≥75% or were unable to be calculated due to low prevalence in the study population. Specificity for all targets was ≥87.2%, with many false-positive results compared to culture that were confirmed by alternative molecular methods. Appropriate adoption of this test could provide actionable diagnostic information that is anticipated to impact patient care and antimicrobial stewardship decisions.

Practical Comparison of the BioFire FilmArray Pneumonia Panel to Routine Diagnostic Methods and Potential Impact on Antimicrobial Stewardship in Adult Hospitalized Patients with Lower Respiratory Tract Infections.

Lower respiratory tract infections, including hospital-acquired and ventilator-associated pneumonia, are common in hospitalized patient populations. Standard methods frequently fail to identify the infectious etiology due to the polymicrobial nature of respiratory specimens and the necessity of ordering specific tests to identify viral agents. The potential severity of these infections combined with a failure to clearly identify the causative pathogen results in administration of empirical antibiotic agents based on clinical presentation and other risk factors. We examined the impact of the multiplexed, semiquantitative BioFire FilmArray Pneumonia panel (PN panel) test on laboratory reporting for 259 adult inpatients submitting bronchoalveolar lavage (BAL) specimens for laboratory analysis. The PN panel demonstrated a combined 96.2% positive percent agreement (PPA) and 98.1% negative percent agreement (NPA) for the qualitative identification of 15 bacterial targets compared to routine bacterial culture. Semiquantitative values reported by the PN panel were frequently higher than values reported by culture, resulting in semiquantitative agreement (within the same log10 value) of 43.6% between the PN panel and culture; however, all bacterial targets reported as >105 CFU/ml in culture were reported as ≥105 genomic copies/ml by the PN panel. Viral targets were identified by the PN panel in 17.7% of specimens tested, of which 39.1% were detected in conjunction with a bacterial target. A review of patient medical records, including clinically prescribed antibiotics, revealed the potential for antibiotic adjustment in 70.7% of patients based on the PN panel result, including discontinuation or de-escalation in 48.2% of patients, resulting in an average savings of 6.2 antibiotic days/patient.

Multicenter Evaluation of BioFire FilmArray Respiratory Panel 2 for Detection of Viruses and Bacteria in Nasopharyngeal Swab Samples.

The FilmArray Respiratory Panel 2 (RP2) is a multiplex in vitro diagnostic test for the simultaneous and rapid (∼45-min) detection of 22 pathogens directly from nasopharyngeal swab (NPS) samples. It contains updated (and in some instances redesigned) assays that improve upon the FilmArray Respiratory Panel (RP; version 1.7), with a faster run time. The organisms identified are adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human metapneumovirus, human rhinovirus/enterovirus, influenza virus A, influenza virus A H1, influenza virus A H1-2009, influenza virus A H3, influenza virus B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, respiratory syncytial virus, Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae Two new targets are included in the FilmArray RP2: Middle East respiratory syndrome coronavirus and Bordetella parapertussis This study provides data from a multicenter evaluation of 1,612 prospectively collected NPS samples, with performance compared to that of the FilmArray RP or PCR and sequencing. The overall percent agreement between the FilmArray RP2 and the comparator testing was 99.2%. The RP2 demonstrated a positive percent agreement of 91.7% or greater for detection of all but three analytes: coronavirus OC43, B. parapertussis, and B. pertussis The FilmArray RP2 also demonstrated a negative percent agreement of ≥93.8% for all analytes. Of note, the adenovirus assay detects all genotypes, with a demonstrated increase in sensitivity. The FilmArray RP2 represents a significant improvement over the FilmArray RP, with a substantially shorter run time that could aid in the diagnosis of respiratory infections in a variety of clinical scenarios.

Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens.

Rapid diagnosis and treatment of infectious meningitis and encephalitis are critical to minimize morbidity and mortality. Comprehensive testing of cerebrospinal fluid (CSF) often includes Gram stain, culture, antigen detection, and molecular methods, paired with chemical and cellular analyses. These methods may lack sensitivity or specificity, can take several days, and require significant volume for complete analysis. The FilmArray Meningitis/Encephalitis (ME) Panel is a multiplexed in vitro diagnostic test for the simultaneous, rapid (∼1-h) detection of 14 pathogens directly from CSF specimens: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus agalactiae, cytomegalovirus, enterovirus, herpes simplex virus 1 and 2, human herpesvirus 6, human parechovirus, varicella-zoster virus, and Cryptococcus neoformans/Cryptococcus gattii We describe a multicenter evaluation of 1,560 prospectively collected CSF specimens with performance compared to culture (bacterial analytes) and PCR (all other analytes). The FilmArray ME Panel demonstrated a sensitivity or positive percentage of agreement of 100% for 9 of 14 analytes. Enterovirus and human herpesvirus type 6 had agreements of 95.7% and 85.7%, and L. monocytogenes and N. meningitidis were not observed in the study. For S. agalactiae, there was a single false-positive and false-negative result each, for a sensitivity and specificity of 0 and 99.9%, respectively. The specificity or negative percentage of agreement was 99.2% or greater for all other analytes. The FilmArray ME Panel is a sensitive and specific test to aid in diagnosis of ME. With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship are anticipated.