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Introduction The epidemiology of severe lower respiratory tract infections (LRTI) is constantly changing. We aimed to describe it using the BioFire® FilmArray® Pneumonia plus (PNplus) Panel. Methods In a sub-study of the PROGRESS trial, sputum samples of 90 patients with sepsis and LRTI were retrospectively studied. The primary endpoint was the comparative detection rate of pathogens between conventional microbiology and PNplus Panel; secondary endpoints were microbiology and the association with the inflammatory host response. Results Fifty-six patients with community-acquired pneumonia without risk factors for multidrug-resistant (MDR) pathogens and another 34 patients with risk factors for MDR were studied; median pneumonia severity index (PSI) was 113 (88–135). PNplus detection rate was 72.2% compared to 10% by conventional microbiology (p

Study designWhether or not to administer antibiotics is a common and challenging clinical decision in patients with suspected infections presenting to the emergency department (ED). We prospectively validate InSep, a 29-mRNA blood-based host response test for the prediction of bacterial and viral infections.MethodsThe PROMPT trial is a prospective, non-interventional, multi-center randomized, controlled clinical trial that enrolled 397 adult patients presenting to the ED with signs of acute infection and at least one vital sign change. The infection status was adjudicated using chart review (including a syndromic molecular respiratory panel, procalcitonin and C-reactive protein) by three infectious disease physicians blinded to InSep results. InSep (version BVN-2) was performed using PAXgene Blood RNA processed and quantified on NanoString nCounter SPRINT. InSep results (likelihood of bacterial and viral infection) were compared to the adjudicated infection status.ResultsSubject mean age was 64 years, comorbidities were significant for diabetes (17.1%), chronic obstructive pulmonary disease (13.6%), and severe neurological disease (6.8%); 16.9% of subjects were immunocompromised. Infections were adjudicated as bacterial (14.1%), viral (11.3%) and noninfected (0.25%): 74.1% of subjects were adjudicated as indeterminate. InSep distinguished bacterial vs. viral/noninfected patients and viral vs. bacterial/noninfected patients using consensus adjudication with AUROCs of 0.94 (95% CI 0.90-0.99) and 0.90 (95% CI 0.83-0.96), respectively. AUROCs for bacterial vs. viral/noninfected patients were 0.88 (95%CI 0.79-0.96) for PCT, 0.80 (95% CI 0.72-89) for CRP and 0.78 (95% CI 0.69-0.87) for white blood cell counts (of note, the latter biomarkers were provided as part of clinical adjudication). To enable clinical actionability, InSep incorporates score cutoffs to allocate patients into interpretation bands. The Very Likely (rule in) InSep bacterial band showed a specificity of 98% compared to 94% for the corresponding PCT band (>0.5 ug/L); the Very Unlikely (rule-out) band showed a sensitivity of 95% for InSep compared to 86% for PCT. For the detection of viral infections, InSep demonstrated a specificity of 93% for the Very Likely band (rule in) and a sensitivity of 96% for the Very Unlikely band (rule out).ConclusionInSep demonstrated high accuracy for predicting the presence of both bacterial and viral infections in ED patients with suspected acute infections or suspected sepsis. When translated into a rapid, point-of-care test, InSep will provide ED physicians with actionable results supporting early informed treatment decisions to improve patient outcomes while upholding antimicrobial stewardship.Take-home messageInSep host response test is a point-of-care test providing with accuracy the likelihood for bacterial or viral infection for patients admitted at the emergencies InSep provided information on the likelihood of bacterial co-infection among patients with COVID-19.

Controversies in outcomes with the parenteral administration of antioxidants as adjuvant therapies led to the measurement of malondialdehyde (MDA), a product of lipid peroxidation, in serum collected from 120 patients with primary Gram-negative bacteremia during the first 24 h from sepsis onset. MDA was measured by the thiobarbiturate assay, followed by high-performance liquid chromatography (HPLC) analysis. After receiver operator characteristic (ROC) curve analysis, patients were divided into those with high levels of MDA and low levels of MDA. The primary endpoint was the association of the level of MDA with septic shock. The level of MDA as an index of neutrophil function and associations with outcome and with infections by carbapenem-resistant Klebsiella pneumoniae were the secondary endpoints. In total, 63 patients had high and 57 had low MDA levels; 27% and 49.1%, respectively, had septic shock (p = 0.015). The rate of the concentration of MDA to the total neutrophil count was used as an expression of neutrophil function; this was lower among patients with septic shock. The odds ratio (OR) for death among patients without septic shock and low level of MDA was 4.00; this was 0.48 for patients with septic shock (p = 0.020 between the two ORs). The OR for resistance to carbapenems among patients with bacteremia by K. pneumoniae and low level of MDA was 7.50 (p = 0.011 compared to patients with bacteremia by other pathogens). Low level of circulating MDA is associated with susceptibility to septic shock and infections by carbapenem-resistant K. pneumoniae.

In the present study, we challenged the concept that levofloxacin should not be used for the management of ventilator-associated pneumonia (VAP) when minimum inhibitory concentrations (MICs) exceed 2 μg/ml. Multidrug-resistant (MDR) and genetically distinct isolates of Pseudomonas aeruginosa (n = 49) and Acinetobacter baumannii (n = 29) from patients with VAP were exposed over time to levofloxacin, imipenem, colistin and their combinations. Synergy between levofloxacin and imipenem was found in 55.3 % and between levofloxacin and colistin in 90.9 % of isolates of P. aeruginosa within the first 4 h of growth. Synergy with imipenem but not with colistin was dependent of the MIC. Synergy between levofloxacin and imipenem was found in 58.6 % of isolates of A. baumannii after 24 h of growth. Considerable synergy was found between levofloxacin and colistin, reaching 84.8 % of isolates of A.baumannii after 6 h of growth. Synergy was independent from the MIC. These results create hopes that levofloxacin can be used as combination therapy for infections by MDR bacteria.