Abstract Background Aztreonam–avibactam (AZA) is a recently approved agent active against metallo-β-lactamase-producing Enterobacterales. However, independent evaluations of commercially available antimicrobial susceptibility testing (AST) products remain limited. Methods We evaluated 56 carbapenem-resistant Enterobacterales isolates using four newly available AZA AST products, including two gradient diffusion (bioMérieux Etest; Liofilchem MIC Test Strip) and two disk diffusion (Hardy, Liofilchem) tests across three Mueller–Hinton agar manufacturers at two independent clinical laboratories. A diverse isolate collection enriched for nonsusceptible and breakpoint-adjacent MICs was used to rigorously assess categorical agreement. Broth microdilution (BMD) was used as the reference method. Essential agreement (EA), categorical agreement (CA), error rates, and reproducibility were analyzed. Results All four commercial AST products demonstrated acceptable analytical performance compared with reference BMD. Gradient diffusion demonstrated high EA (bioMérieux 94.3%, Liofilchem 90.5%), whereas CA ranged from 83.3% to 89.0% across all four products. Minor errors accounted for all categorical discrepancies, and occurred almost exclusively among breakpoint-adjacent isolates. Media-related variability was modest, and quality control performance was generally high, with strong within-site precision and consistent performance across laboratories. Conclusions This study provides the first comprehensive head-to-head comparison of commercial AZA susceptibility testing products and supports their implementation in clinical microbiology laboratories.

ABSTRACT The Burkholderia cepacia complex (BCC) is comprised of 24 species of Gram-negative bacteria that cause opportunistic infections. While antimicrobial susceptibility testing (AST) has historically been used to guide treatment for BCC infections, recent work highlighting problems with AST for these organisms led the Clinical and Laboratory Sciences Institute (CLSI) to remove disk diffusion (DD) and minimal inhibitory concentration (MIC) breakpoints for BCC from its M100 standards document. Epidemiological cut-off values (ECVs) may be helpful to clinicians in the absence of breakpoints, as they may be used to determine whether an isolate has a wild-type or non-wild-type phenotype. Here we present an analysis of BCC ECVs for ceftazidime (CAZ), levofloxacin (LVX), meropenem (MEM), minocycline (MIN), and trimethoprim-sulfamethoxazole (TMP-SMX). ECVs were calculated using MIC data from 3 previous studies and 3 independent laboratories for 1,896 BCC isolates. ECVs were 16 μg/ml for CAZ, 8 μg/ml for LVX, 16 μg/ml for MEM, and 8 μg/ml for MIN. The ECV for TMP-SMX varied depending on the analysis from 2 μg/ml, 8 μg/ml, and 16 μg/ml and therefore could not be reliably established. Challenges with establishing ECVs for BCC include limitations with the pooled MIC dataset, broad MIC distributions, and high ECVs that are above the obsolete susceptible MIC breakpoints. These challenges limit the clinical utility of ECVs for these organisms and supported removal of ECVs from the CLSI M100 standards document. IMPORTANCE The Burkholderia cepacia complex is a group of bacterial species that cause difficult-to-treat opportunistic infections. Recently, clinical breakpoints, which are used to determine whether organisms are susceptible to certain antimicrobials, were removed from Clinical and Laboratory Standards Institute (CLSI) standards for these organisms due to problems with antimicrobial susceptibility testing performance. Clinicians are now faced with the challenge of how to treat these complex infections without clinical breakpoints. Here we determine epidemiological cut-off values (ECVs) for relevant antimicrobials for the B. cepacia complex. While we established ECVs for four antimicrobials, we encountered significant challenges in our analyses, including limitations with data for these organisms and high ECVs that are not clinically useful. These challenges limit the practical use of these ECVs in helping guide clinicians on treatment and supported the eventual removal of ECVs from the CLSI M100 standards document.

Blood cultures (BC) are a critical resource to diagnose bloodstream infections. However, over-ordering may lead to antibiotic overuse and increased hospital cost, length of stay, and contamination rates. A national blood culture bottle shortage prompted diagnostic stewardship of follow-up blood cultures (FUBC) in patients monitored for clearance of a prior positive BC, or with new/worsening symptoms after initial negative BC. We aimed to reduce the use of paired-set FUBC and increase single-set FUBC. This study was performed from 2/18/2024 to 11/23/2024 at a network of 8 academic and community hospitals in New York. Prior to stewardship interventions, clinicians were free to order any number of FUBC at a time. In August 2024 we implemented a series of iterative PDSA (PlanDoStudyAct) cycles to guide clinicians toward appropriate ordering of FUBC including educational memos, limiting the ability to order more than one BC at a time, an electronic best practice advisory to limit BC orders with a prior negative within 72 hours, and a new order panel for BC that defaulted FUBC to a single set. Our goal was a >10% reduction in paired FUBC. QI methodology assessed special cause, descriptive statistics were used to compare pre- and post-intervention characteristics and balancing measures, and data were analyzed using R software. Over the study period 168,779 BC were ordered, of which 11% were from community hospitals. Demographic characteristics were similar before and after intervention. Prior to our QI project, 29% of BC were FUBC, of which 59% were paired sets. After the series of PDSA cycles there was a 39% increase in single FUBC, a 36% reduction in paired FUBC, and an overall 3.3% reduction in total blood culture bottle use (p = 0.002). There were no differences in the length of stay, in-hospital mortality, or 30-day readmission. Reduced paired FUBC usage was also seen in S. aureus bacteremia (44%) and candidemia (45%) (p < 0.001). We exceeded our goal of reducing paired FUBC through targeted clinical decision support while successfully increasing single-set FUBC. Outside of a blood culture bottle shortage, future iterative changes are needed to support the use of FUBC in S. aureus bacteremia and candidemia. Lars Westblade, PhD, Elements Materials Technology: Grant/Research Support|Hardy Diagnostics: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Selux Diagnostics: Grant/Research Support|Shionogi: Advisor/Consultant|SNIPRBIOME: Grant/Research Support

Background Pastuerella multicoda is a gram-negative coccobacillus commonly found in the oral flora of many animals, most commonly in cats and implicated in zoonotic infections, commonly cellulitis secondary to cat bites and scratches. Here we describe a teenager with CHARGE syndrome who developed an infection of her cochlear implant secondary to P multicoda. Case Presentation An 18-year-old female with CHARGE syndrome developed headache, ear pain and cellulitis at the site of her cochlear implant and was found to have osteomyelitis and transient bacteremia secondary to P. multicoda . She required both surgical and medical management, including removal of her cochlear implant and four weeks of antibiotic therapy. Exposure history included numerous excoriations from her new kitten at home. Conclusion This case highlights the importance of obtaining thorough exposure history as part of the evaluation of any pediatric patient with headache, ear pain and cellulitis with complicating factors such as presence of cochlear implant to include zoonotic infections on the differential diagnosis. Additionally, this case highlights the importance of a multidisciplinary team for care of patients with complex medical and surgical history.

In a recent article in ASM Case Reports, G. P. Higerd-Rusli, A. Karan, S. A. Hoffman, I. E. A. Morante, et al. (ASM Case Rep 2:e00165-25, 2025, https://doi.org/10.1128/asmcr.00165-25) describe one confirmed and one probable case of influenza A(H5N1) detected through universal subtyping of influenza A-positive specimens, including cases without known animal exposure. These findings highlight the limitations of exposure-based testing strategies and raise important questions about early detection of emerging pathogens. Drawing on lessons from prior pandemics, this commentary examines the tradeoffs between targeted and expanded surveillance and emphasizes the need for adaptive, flexible approaches to laboratory preparedness.

OBJECTIVE:Default settings in electronic medical records (EMRs) can drive overordering of diagnostic tests. After transitioning to Epic, our hospital network noted a sharp rise in acid-fast bacilli (AFB) and fungal culture orders from operating rooms (ORs), likely due to 1-click ordering tools ("quick buttons") in the Epic OpTime module. We assessed the impact of removing these buttons on test utilization. METHODS:This multicenter study included 8 medical centers and compared two 9-month periods: preintervention (January to September 2023) and postintervention (December 2023 to August 2024). The AFB and fungal cultures remained orderable via manual entry. Order volumes, positivity rates, and turnaround times (TATs) were extracted from the Laboratory Information System. RESULTS:Postintervention, AFB orders decreased by nearly 50% (P < .001) while positivity doubled (1.74% to 3.64%, P < .001). Median AFB TAT improved by more than 2 hours (P < .001). Fungal culture orders declined 35% (P < .001), with no significant change in positivity (6.37% vs 6.25%, P = .83). Median fungal TAT improved by more than 1 hour (P < .001). CONCLUSIONS:Removing OR quick buttons significantly reduced unnecessary AFB and fungal culture orders and improved TAT without reducing detection of clinically important infections. This is the first study to evaluate the impact of EMR quick buttons on -microbiology utilization.

INTRODUCTION:Bronchiolitis, a viral lower respiratory tract infection, is the leading cause of hospitalisation for infants, with healthcare utilisation highest among young infants (aged ≤90 days). Clinical models to predict respiratory deterioration in infants with bronchiolitis have been developed for a broad age group that includes children up to 2 years old, not focusing specifically on young infants. These models have also been limited by exclusion of viral aetiology and by use of vital signs measured at a single time point during clinical evaluation, overlooking the variable and dynamic course of bronchiolitis. This study aims to combine clinical history and examination factors with viral aetiology (primary aim) and continuous physiological data from bedside monitors (secondary aim) to develop accurate prediction models to identify young infants at low risk of respiratory deterioration and enable safe discharge to home. METHODS AND ANALYSIS:We are conducting a single-centre, prospective cohort study of young infants with bronchiolitis presenting to the paediatric emergency department (ED) of a tertiary care children's hospital. Enrolment began in November 2021 and will end in April 2027. Young infants with a clinical diagnosis of bronchiolitis are included. Infants with hospitalisation within 1 week of the index ED visit or baseline (home) use of supplemental oxygen or respiratory support are excluded. We are collecting clinical, laboratory, imaging and treatment data from the ED and hospitalisation, if admitted. All patients have a standardised initial examination as well as a repeat examination at 2-4 hours if still physically located in the ED. We are also obtaining swabs from the anterior nares and the nasopharynx. Continuous physiological data are collected through pulse oximetry and 5-lead ECG. We will contact parents or guardians at 7, 14 and 21 days for follow-up of symptom resolution and unplanned visits to a healthcare provider. The primary outcome is the development of respiratory deterioration within 24 hours of ED presentation. Respiratory deterioration is defined as new use of non-invasive or invasive respiratory support within 24 hours of ED arrival. For the primary aim, regression and recursive partitioning techniques will create the low-risk model. For the secondary aim, we will use machine learning models such as Lasso regression and support vector machines. ETHICS AND DISSEMINATION:Ethics approval was obtained through the Columbia University Institutional Review Board (IRB-AAAT8528). Written informed consent will be obtained for all patients. Results will be disseminated through academic conferences, peer-reviewed publications and appropriate free open-access medical education.

BACKGROUND:Obtaining urine cultures (UCx) in the absence of symptoms and inflammation can result in misdiagnosis of urinary tract infections (UTIs) and inappropriate use of antibiotics. Reflex UCx is a diagnostic stewardship strategy in which a UCx is performed only if a urinalysis (UA) meets UTI criteria. We retrospectively applied a reflex UCx algorithm to assess its performance and safety in children. METHOD:From November 1, 2020, to July 23, 2023, we studied children aged >24 months to <18 years with paired UA and UCx, ie, a UTI evaluation, in emergency departments or inpatient units at our 8-hospital network. We assessed the diagnostic performance of pyuria of ≥10 white blood cells (WBC)/high power field (hpf) using a positive UCx as the reference standard; assessed reflex UCx exclusion criteria; and reviewed medical records of children with <10 WBC/hpf and positive UCx for signs and symptoms consistent with clinical UTI. RESULTS:Of 79 960 UA and UCx, 10 226 UTI evaluations were eligible for inclusion. Of the 8.7% (890/10 226) positive UCx, 81.5% (725/890) had UA with ≥10 WBC/hpf, and 18.5% (165/890) had UA with <10 WBC/hpf. The sensitivity of ≥10 WBC/hpf was 81% and the negative predictive value (NPV) was 98%. Of 165 UTI evaluations with positive UCx and <10 WBC/hpf, 26% (43/165) met reflex UCx exclusion criteria, 58 (35%) met neither exclusion criteria nor clinical UTI definition, and 39% (64/165) not meeting exclusion criteria fulfilled the clinical UTI definition, representing 0.6% (64/10 226) of all UTI evaluations. CONCLUSIONS:Retrospective application of a reflex UCx algorithm demonstrated high NPV and sensitivity, suggesting the algorithm had low risk for missing clinical UTIs and could have avoided unnecessary UCx.

An accurate and timely diagnosis of pharyngitis caused by group A streptococcus (GAS) is essential for ensuring appropriate antibiotic therapy. Early detection through point-of-care (POC) testing is valuable in initiating effective treatment. This study aimed at evaluating the analytical sensitivity of the molecular ID NOW™ Strep A 2 POC test as compared to 3 POC lateral flow assays: BD Veritor™ Plus System, Sofia® Strep A+ Fluorescent Immunoassay, and Sekisui Diagnostic OSOM® Strep A test for GAS detection. Two Streptococcus pyogenes bacterial American Type Culture Collection (ATCC) isolates and one clinical isolate from a throat swab sample were used to evaluate the limit of detection (LoD) of each assay. Ten-fold serial dilutions of the isolates starting from 107 colony factor units (CFU)/mL were prepared, and each dilution was tested in triplicate for all 4 assays simultaneously. All tests were performed as per manufacturers' instructions. The LoD was defined as the last dilution that yielded positive results for all 3 replicates. CFU per swab was also calculated. For the 3 isolates evaluated, LoDs of ID NOW Strep A 2 ranged from 3.125 × 103 to 2.5 × 104 CFU/mL; for Quidel Sofia the range was 1 × 106 to 1 × 107 CFU/mL; for BD Veritor the range was 1 × 107 to 1.5 × 107 CFU/mL; and for Sekisui OSOM the LoD was 1 × 107 CFU/mL for all 3 isolates. Compared to antigen-based lateral flow assays (LFAs), the molecular ID Now Strep A 2 assay demonstrated a lower LoD, which translates into higher sensitivity. In a clinical setting, this could enable detection of samples with a lower bacterial load that could be missed by low-sensitivity LFAs.

ABSTRACT The Burkholderia cepacia complex (BCC) is a group of Gram-negative bacteria that cause opportunistic infections, most notably in people with cystic fibrosis (CF), and have been associated with outbreaks caused by contaminated medical products. Antimicrobial susceptibility testing (AST) is often used to guide treatment for BCC infections, perhaps most importantly in people with CF who are being considered for lung transplant. However, recent studies have highlighted problems with AST methods. Here, we address limitations from previous studies to further evaluate BCC AST methods. We assessed the performance of reference broth microdilution (BMD), disk diffusion (DD) using Mueller-Hinton agar (MHA) from three manufacturers, agar dilution (AD), and gradient diffusion (ETEST) for ceftazidime (CAZ), levofloxacin (LVX), meropenem (MEM), minocycline (MIN), and trimethoprim-sulfamethoxazole (TMP-SMX) on a set of 205 BCC isolates. The isolate set included 100 isolates from people with CF and 105 isolates from people without CF from a variety of sources, which enabled us to systematically evaluate whether specimen source impacts AST performance. For all BCC isolates, BMD reproducibility was 93%, 98%, 99%, 98%, and 96% for CAZ, LVX, MEM, MIN, and TMP-SMX, respectively. Using BMD as the comparator method, we show that DD, AD, and ETEST perform poorly, with neither MHA manufacturer nor specimen source significantly impacting method performance. Based on our data, we recommend that routine AST should not be performed for BCC isolates. If a provider requests AST, clinical microbiology laboratories should perform Clinical and Laboratory Standards Institute reference methodology for BMD (stored frozen) and report MIC only. IMPORTANCE Antimicrobial susceptibility testing for the Burkholderia cepacia complex (BCC) is often used to determine eligibility for lung transplant in people with cystic fibrosis. However, problems with method performance have been reported. Here, we systematically evaluate the performance of reference broth microdilution, disk diffusion, agar dilution, and gradient diffusion (ETEST) for BCC organisms isolated from people with and without cystic fibrosis. We show that broth microdilution reproducibility is acceptable for levofloxacin, meropenem, minocycline, and trimethoprim-sulfamethoxazole, while ceftazidime was just below the acceptability cut-off. Regardless of specimen source, the results from disk diffusion, agar dilution, and ETEST do not correlate with broth microdilution. Based on these findings, we recommend that antimicrobial susceptibility testing should not be routinely performed for BCC, and if requested by the provider, only broth microdilution following Clinical and Laboratory Standards Institute guidelines should be used. Providers should be aware of the significant limitations of antimicrobial susceptibility testing methods for BCC.

The use of gastrointestinal disease multiplex polymerase chain reaction (GI PCR) testing has become common for suspected gastrointestinal infection. Patients often test positive for multiple pathogens simultaneously through GI PCR, although the clinical significance of this is uncertain. This retrospective cohort study investigated risk factors and clinical outcomes associated with detection of multiple (as opposed to single) pathogens on GI PCR. We included adult patients who underwent GI PCR testing from 2020 to 2023 and had one or more pathogens detected. We compared patients with multiple versus those with single pathogens and hypothesized that immunosuppression would be a risk factor for detection of multiple pathogens. We further hypothesized that, during the 90 days after GI PCR testing, patients with multiple pathogens would have worse clinical outcomes such as increased rates of emergency department (ED) visits, death, hospitalization, or ambulatory care visits. GI PCR was positive in 1341 (29

BACKGROUND:Evaluation of suspected neonatal sepsis rarely considers diagnostic workup for vector-borne illnesses, as these are generally infrequent etiologies in the febrile neonate. Babesiosis -- a zoonosis caused by apicomplexan parasites of the genus Babesia and spread to humans by the Ixodes scapularis tick -- can either be clinically silent, or symptomatic with fever, constitutional symptoms, as well as anemia and thrombocytopenia. We report here a rare case of neonatal babesiosis that was incidentally identified during routine workup for neonatal sepsis. CASE PRESENTATION:A full-term male neonate with fever was admitted to the hospital for sepsis evaluation. On routine complete blood count with manual differential blood smear, parasites were incidentally detected, later identified as Babesia microti. On review of maternal history, there was antenatal history of unexplained thrombocytopenia and anemia, and post-hoc review of peripartum maternal blood smear showed rare intra-erythrocytic parasites, which were confirmed as B. microti by PCR testing of maternal blood. Ultimately, the infant was successfully treated with azithromycin and atovaquone, received a red blood cell transfusion for symptomatic anemia, and remained well at his outpatient follow-up visit. CONCLUSION:This unusual case highlights the importance of including neonatal babesiosis in the differential diagnosis for neonatal sepsis in endemic regions, including careful review of maternal antenatal exposure history and labs, and consideration of peripheral blood smear in suggestive cases.

OBJECTIVE: To assess the impact of active surveillance and decolonization strategies on methicillin-resistant Staphylococcus aureus (MRSA) infection rates in a NICU. STUDY DESIGN: MRSA infection rates were compared before (2014-2016) and during (2017-2022) an active surveillance program. Eligible infants were decolonized with chlorohexidine gluconate (CHG) bathing and/or topical mupirocin. Successful decolonization and rates of recolonization were assessed. RESULTS: Fifty-two (0.57%) of 9 100 hospitalized infants had invasive MRSA infections from 2014 to 2022; infection rates declined non-significantly. During the 6-year surveillance program, the risk of infection was 16.9-times [CI95 8.4, 34.1] higher in colonized infants than uncolonized infants. Those colonized with mupirocin-susceptible MRSA were more likely successfully decolonized (aOR 9.7 [CI95 4.2, 22.5]). Of 57 infants successfully decolonized who remained hospitalized, 34 (60%) became recolonized. CONCLUSIONS: MRSA infection rates did not significantly decline in association with an active surveillance and decolonization program. Alternatives to mupirocin and CHG are needed to facilitate decolonization.

Background Microbiome restitution therapies are being developed to prevent gut pathogen colonization among patients in the intensive care unit (ICU) and in other select populations. If preventive therapies are to be effective, they must be administered prior to pathogen acquisition. The timing and risk factors for early acquisition of gut pathogen colonization (within 72 h) are currently unknown and could be helpful to guide ICU trial design. Methods This was a prospective cohort study. Patients in the ICU had deep rectal swabs performed within 4 h of ICU admission and exactly 72 h later. Early gut pathogen colonization was classified as the new presence (based on culture of rectal swabs) of one or more of the following organisms of interest: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant (VRE), and Gram-negative bacteria that showed multidrug resistance (MDR) or third generation Cephalosporin resistance (Ceph-R). Clinical risk factors for early acquisition of gut pathogen colonization were captured using the Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scoring system. Findings Among 131 patients who were swabbed at ICU admission and 72 h later, the rates of gut pathogen colonization at ICU admission were 11.4%, 10.6%, 38.6%, and 8.3% for MRSA, VRE, MDR and Ceph-R Gram-negatives respectively. Among the patients who were negative for a given pathogen at ICU admission, the rates of early acquisition of gut pathogen colonization were 7.8% for MRSA (95% CI 3.6 to 14.2%), 7.7% for VRE (95% CI 3.6 to 14.1%), 11.3% for MDR Gram-negatives (95% CI 4.4 to 18.8%), and 4.2% for Ceph-R Gram-negatives (95% CI 1.4 to 9.5%). There were no clinical risk factors which independently predicted early acquisition of gut pathogen colonization. Interpretation Early gut pathogen colonization was common in the ICU, but our single-center study could not identify any clinical risk factors which were significantly associated with acquisition of gut pathogens.

Mycolicibacter kumamotonensis is a slowly growing, non-chromogenic non-tuberculous mycobacteria (NTM) that was initially distinguished from the M. terrae complex in 2006. Since then it has been rarely reported as the cause of pulmonary and soft-tissue infections in both immunocompromised and immunocompetent patients. We present a case of severe pulmonary disease due to Mycolicibacter kumamotonensis in a 57-year-old male who was immunocompetent at time of diagnosis, with a history of interstitial lung disease and a prior diagnosis of tuberculosis (TB). After initial treatment for TB in 2017, his condition stabilized until a recurrence in September 2021, leading to an evaluation for lung transplant in the setting of pulmonary fibrosis and emphysema which led to the identification of Mycolicibacter kumamotonensis. A lung transplant was completed, and the patient was successfully treated with a combination of Ethambutol, Azithromycin, and Rifabutin. This represents the first case reported of M. kumamotonensis in a patient undergoing lung transplant, and the first case with rapid culture growth during identification of the organism (4 days). This report highlights the need for consideration of M. kumamotonensis as a pathogen in humans, with the potential for rapid growth in liquid media, and the importance of early identification to inform empiric therapy.

Introduction In the Northeast US, respiratory viruses such as influenza and respiratory syncytial virus (RSV), which were largely suppressed by COVID-19-related social distancing, made an unprecedented resurgence during 2022, leading to a substantial rise in viral co-infections. However, the relative rates of co-infection with seasonal respiratory viruses over this period have not been assessed. Methods Here we reviewed multiplex respiratory viral PCR data (BioFire FilmArray™ Respiratory Panel v2.1 [RPP]) from patients with respiratory symptoms presenting to our medical center in New York City to assess co-infection rates of respiratory viruses, which were baselined to total rates of infection for each virus. We examined trends in monthly RPP data from adults and children during November 2021 through December 2022 to capture the full seasonal dynamics of respiratory viruses across periods of low and high prevalence. Results Of 50,022 RPPs performed for 34,610 patients, 44% were positive for at least one target, and 67% of these were from children. The overwhelming majority of co-infections (93%) were seen among children, for whom 21% of positive RPPs had two or more viruses detected, as compared to just 4% in adults. Relative to children for whom RPPs were ordered, children with co-infections were younger (3.0 vs 4.5 years) and more likely to be seen in the ED or outpatient settings than inpatient and ICU settings. In children, most viral co-infections were found at significantly reduced rates relative to that expected from the incidence of each virus, especially those involving SARS-CoV-2 and influenza. SARS-CoV-2 positive children had an 85%, 65% and 58% reduced rate of co-infection with influenza, RSV, and Rhino/enteroviruses, respectively, after compensating for the incidence of infection with each virus (p< 0.001). Discussion Our results demonstrate that most respiratory viruses peaked in different months and present in co-infections less than would be expected based on overall rates of infection, suggesting a viral exclusionary effect between most seasonal respiratory viruses, including SARS-CoV-2, influenza and RSV. We also demonstrate the significant burden of respiratory viral co-infections among children. Further work is necessary to understand what predisposes certain patients for viral co-infection despite this exclusionary effect.

Respiratory tract infections represent a global health concern. More than 1 pathogenic organism in the respiratory tract has been widely recognized owing to the availability of molecular detection technologies. However, the association between the occurrence of multiple-pathogen infections and clinical disease severity remains unclear. Multiple infections fall into two broad categories: Coinfection occurs when a person is found to be infected by two or more micro-organisms, but which infection was established first cannot be clearly determined, while superinfection is an infection arising when one or more infections is already present. This review presents an overview of the prevalence and clinical disease severity of respiratory co-infections and superinfections and discusses possible mechanisms of the interactions between viral infections.

Mutations in the viral genome of SARS-CoV-2 can impact the performance of molecular diagnostic assays. In some cases, such as S gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here we describe partial ORF1ab gene target failure (pOGTF) on the cobas ® SARS-CoV-2 assays, defined by a ≥2 thermocycles delay in detection of the ORF1ab gene compared to the E gene. We demonstrate that pOGTF is 97% sensitive and 99% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may impact transmission, infectivity, and/or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.

CONTEXT.—:The FilmArray Meningitis/Encephalitis (ME) panel is the first US Food and Drug Administration-cleared multiplex polymerase chain reaction panel for the detection of central nervous system infections. While the assay's performance characteristics have been described, the real-world significance of positive results has not been fully characterized. OBJECTIVE.—:To evaluate the clinical significance of positive ME panel results in a tertiary care medical center in New York, New York. DESIGN.—:Four physicians independently performed retrospective clinical assessments of all positive ME panel results at Columbia University Irving Medical Center, including the Children's Hospital of New York, during an 18-month period. Each reviewer determined the likelihood of central nervous system infection for all cases and whether cases fit Brighton diagnostic criteria for meningitis, encephalitis, or meningoencephalitis. RESULTS.—:Among 119 cases, there was 75% positive agreement (95% CI, 54%-89%) between ME panel results and clinical consensus, which varied among panel targets. CONCLUSIONS.—:The ME panel showed good agreement with expert clinical consensus for patients presenting with acute meningitis/encephalitis. Factors contributing to clinically insignificant ME positive results included low pretest probability, traumatic lumbar puncture, specimen contamination, and detection of incidental viral targets such as human herpesvirus 6. Notably, the ME panel detected more than twice the number of cases of bacterial meningitis detected by culture alone, particularly among patients receiving empiric antimicrobial therapy before lumbar puncture. Appropriate test use and contextual interpretation of results are critical to leveraging the advantages of the platform while avoiding potential pitfalls.

Diagnostic stewardship aims to improve diagnostic test utilization through evidence-based practices to improve care, quality, safety, and costs. Diagnostic stewardship is a collaborative effort that brings together multidisciplinary groups that have a common interest in promoting and ensuring best testing practices. For infectious disease testing, clinical microbiology laboratories are perhaps best positioned within their health care systems to lead these efforts, as they are not only diagnostic experts, but also directly oversee many of the tools and choices available to improve test performance and utilization. While some interventions may not fall under the direct purview of clinical microbiology laboratories, their expertise is nevertheless essential to inform these efforts, as well. Multiple stewardship strategies have been evaluated, providing laboratories with several opportunities to implement evidence-based practice changes to improve quality and outcomes. Further research is needed to continue advancing practice for well-established and emerging tests alike.