Lower respiratory tract infections (LRTI) are still burdened by considerable morbidity and mortality. Rapid and appropriate treatment imply knowledge of the underlying causative pathogen; while it is tempting to offer broad spectrum antibiotics, Antimicrobial Stewardship Practices invite a judicious use of the latter, especially when bacteria are not the cause. However, the epidemiology shifts to multidrug resistant (MDR) pathogens that require optimization of molecules in order to provide optimal treatment. Novel methods requiring direct sample result testing such as the Biofire Pneumonia (PN) panel have recently been made available on the market. Syndromic testing may hence provide support in the diagnosis of LRTI. There is paucity of data concerning experiences in high MDR settings, and even less concerning the performance of these panels in pediatric settings with moderate MDR prevalence. Our study highlights the optimal sensitivity and importance of support from such methods in settings burdened by MDR presence and where fast and appropriate therapy is mandatory.

BACKGROUND: The FilmArray Meningitis/Encephalitis(FA/ME) panel brings benefits in clinical practice, but its diagnostic test accuracy (DTA) remains unclear. We aimed to determine the DTA of FA/ME for the aetiological diagnostic in patients with suspected central nervous system(CNS) infection.
METHODS: We performed a systematic review with DTA meta-analysis (PROSPERO: CRD42020139285). We searched Embase, Medline (Ovid), and Web of Science from inception until September 1st, 2021. We assessed the study-level risk of bias with the QUADAS-2 tool and applied the GRADE approach to assess the certainty of the synthesised evidence. We included studies that simultaneously measured the reference test (CSF/blood culture for bacteria, and specific polymerase chain reaction for viruses) and the FA/ME in patients with suspected CNS infection. We performed random-effects bivariate meta-analysis models of combined sensitivity and specificity using CSF/blood cultures(reference test 1) and a final diagnosis adjudication based on clinical/laboratory criteria (reference test 2).
RESULTS: We included 19 studies (11,351 participants). For all bacteria with reference test 1 (16 studies/6183 patients) sensitivity was estimated at 89·5% (95%CI 81·1-94·4), and specificity at 97·4% (95%CI 94-98·9). With reference test 2 (15 studies/5,524 patients), sensitivity was estimated at 92·1%(95%CI 86·8-95·3) and specificity at 99.2(95%CI 98·3-99·6) For herpes simplex virus-2(HSV-2), enteroviruses, and Varicella-Zoster virus (VZV), we obtained sensitivities between 75·5 and 93·8%, and specificities above 99% (reference test 1). Certainty of the evidence was low.
CONCLUSIONS: FA/ME may have acceptable-to-high sensitivities and high specificities for identifying bacteria, especially for S.pneumoniae, and viruses, especially for HSV-2, and enteroviruses. Sensitivities for L.monocytogenes, H.influenzae, E.coli, and HSV-1 were suboptimal.
BACKGROUND: None.

Cryptococcus neoformans is generally observed with immunosuppressive conditions. Rarely, it may be seen in immunocompetent individuals and presented with non-specific conditions. We described an immunocompetent case of cryptococcal meningitis presented with multiple cerebral infarcts. Despite the late diagnosis and emergence of hydrocephalus during treatment, the patient was recovered without any sequelae. In immunocompetent patients, the conventional diagnostics tests may be negative because of the low fungal load. If it is available, the Biofire FilmArray meningitis panel has high sensitivity and specificity for diagnosis.

The COVID-19 pandemic has raised concerns over secondary infections because it has limited treatment options and empiric antimicrobial treatment poses serious risks of aggravating antimicrobial resistance (AMR). Studies have shown that COVID-19 patients are predisposed to develop secondary infections. This study was conducted to ascertain the prevalence and profiles of co- & secondary infections in patients at the COVID-19 facility in North India.
We studied the profile of pathogens isolated from 290 clinical samples. Bacterial and fungal pathogens were identified, and antimicrobial susceptibility was determined by the Vitek2® system. Additionally, respiratory samples were tested for any viral/atypical bacterial co-infections and the presence of AMR genes by FilmArray test. The clinical and outcome data of these patients were also recorded for demographic and outcome measures analyses.
A total of 151 (13%) patients had secondary infections, and most got infected within the first 14 days of hospital admission. Patients aged >50 years developed severe symptoms (p = 0.0004) and/or had a fatal outcome (p = 0.0005). In-hospital mortality was 33%.K.pneumoniae (33.3%) was the predominant pathogen, followed by A. baumannii (27.1%). The overall resistance was up to 84%.Majority of the organisms were multidrug-resistant (MDR) harbouring MDR genes.
A high rate of secondary infections with resistant pathogens in COVID-19 patients highlights the importance of antimicrobial stewardship programs focussing on supporting the optimal selection of empiric treatment and rapid-de-escalation, based on culture reports.

Objective: The aim of this study was to examine the prevalence of bandemia in confirmed respiratory viral infections in febrile infants and children presenting to the emergency department. Methods: An observational retrospective study from January 1, 2016, through December 31, 2016, was conducted in patients between the ages of ≥ 1 month and ≤ 5 years presenting to the emergency room with fever and who had a complete blood cell count performed. Patients were separated into seven groups based on the type of respiratory viral infection. Inclusion criteria strictly counted children with viral infections and absence of clinical and laboratory evidence of a bacterial coinfection. Results: A total of 419 patients had a documented viral infection. A significant proportion of these children were found to have bandemia; children with adenovirus (17%), respiratory syncytial virus (RSV) (14.9%), human metapneumovirus (hMPV) (13%), and parainfluenza virus (7.9%) had the highest prevalence when the cutoff for bandemia was set at 10%. The prevalence increased to 35.3, 30.9, 40.3, and 15.8% for adenovirus, RSV, hMPV, and parainfluenza virus, respectively, when this cutoff was lowered further to 5%. Conclusion: Band neutrophils are detected frequently in confirmed respiratory viral infections particularly during early stages.

BACKGROUND: The FilmArray® meningitis/encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption.
OBJECTIVE: The aim was to evaluate the ME panel in a diagnostic test accuracy review.
METHODS: The PubMed and EMBASE databases were systematically searched through May 2019.
METHODS: Eligible studies were those providing sensitivity and specificity data for the ME panel compared with a reference standard. Studies providing details on false positive and false negative results of the panel as well as further investigation (adjudication) of the discordant results between the panel and comparator assays were included and assessed separately.
METHODS: Patients with suspected ME for whom a panel was ordered were included.
METHODS: The ME panel was compared to reference standard methods for diagnosing community-acquired ME. We performed a meta-analysis and calculated the summary sensitivity and specificity of the ME panel. Moreover, we evaluated the false positive and false negative results of the panel.
RESULTS: Thirteen studies (3764 patients) were included in the review and 8 of them (3059 patients) were pooled in a meta-analysis. The summary estimates of sensitivity and specificity with 95% confidence intervals (CI) was 90% (95% CI 86-93%) and 97% (95% CI 94-99%), respectively. When we looked specifically at studies that assessed further the false positive and false negative results, false positive detections were 11.4% and 4% before and after adjudication, respectively. The highest proportion of false positive was observed for Streptococcus pneumoniae followed by Streptococcus agalactiae. False negative isolates were 2.2% and 1.5% before and after adjudication, respectively. Herpes simplex virus 1 and 2, enterovirus and Cryptococcus neoformans/gattii had the highest proportions of false negative determinations. False negative C. neoformans/gattii were mostly patients with positive antigen titres, on treatment or cleared disease.
CONCLUSIONS: The currently available literature suggests that the ME panel has high diagnostic accuracy. However, the decision for implementation should be individualized based on the needs of the patient population, the capabilities of the laboratory, and the knowledge of the healthcare providers that will utilize the test.

Rapid diagnostic tests (RDTs) have revolutionized the management of Gram-negative bacteremia by allowing antimicrobial stewardship teams the ability to escalate therapy and improve patient outcomes through timely organism identification and detection of certain resistance determinants. However, given the complex nature of Gram-negative resistance, stewardship teams are left without clear direction for how to respond when resistance determinants are absent, as the safety of de-escalation in this setting is unknown. The primary purpose of this analysis was to determine the negative predictive values (NPVs) of resistance marker absence for predicting susceptibility in target bug-drug scenarios at two geographically distinct institutions. A total of 1,046 Gram-negative bloodstream isolates that were analyzed with the Verigene BC-GN platform were assessed. Except for Pseudomonas aeruginosa, the absence of resistance determinants as reported by the RDT largely predicted susceptibility to target antibiotics at both institutions. NPVs for ceftriaxone susceptibility in Escherichia coli and Klebsiella pneumoniae in the absence of either CTX-M or a carbapenemase gene were 98% and 93 to 94%, respectively. Similar results were seen with other target bug-drug scenarios, with NPVs of 94 to 100% demonstrated at both institutions, with the exception of P. aeruginosa, for which NPVs were poor, likely due to the more complex nature of resistance in this pathogen. The results of this study show that clinicians at both institutions should have confidence in de-escalation in the absence of resistance determinant detection by Verigene BC-GN testing, and the methodology described within this article can serve as a blueprint for other stewardship programs to employ at their institutions to optimize management of Gram-negative bacteremia.

INTRODUCTIONSyndromic panels were first FDA cleared for detection of respiratory pathogens in 2008. Since then, other panels have been approved by the FDA, and most recently, the FilmArray meningitis/encephalitis panel (BioFire, Salt Lake City, UT) has become available. This assay detects 14 targets within 1 h and includes pathogens that typically cause different manifestations of infection, although they infect the same organ system. Several studies have reported both false-positive and false-negative results with this test, and all agree that the cost is significant. As with other panels, health care systems have adopted different strategies for offering this assay. Some have implemented strategies to limit the use of the test to certain patient populations, others have elected not to offer the test, and others have elected not to offer the test and instead request that providers order specific PCRs for the pathogens that best fit the patient\'s symptoms. In this Point-Counterpoint, Jennifer Dien Bard of the Department of Pathology and Laboratory Medicine, Children\'s Hospital Los Angeles, and of the Keck School of Medicine at the University of Southern California explains why laboratories should offer these assays without restriction. Kevin Alby of the University of Pennsylvania explains the concerns about the use of these assays as first-line tests and why some limitations on their use might be appropriate.