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Respiratory syncytial virus‐associated acute respiratory infection (RSV‐ARI) constitutes an emerging cause of morbidity in the adult population. The present retrospective study was aimed at identifying factors predictive of poor outcome that may be assessed at the first evaluation in the Emergency Department (ED). We included 275 adult patients with laboratory‐confirmed RSV‐ARI that required hospital admission from the ED between January 2018 and December 2019. Poor outcome (composite of progression to high‐flow oxygen therapy, non‐invasive or invasive mechanical ventilation, or intensive care unit admission, and/or 30‐day all‐cause mortality) occurred in 31 patients (11.2%). Immunosuppression was present in 59 patients (21.5%). Although bacterial co‐infection was rare, antibiotic therapy was commonly initiated. Ribavirin was administered in 10 patients. Cognitive impairment (odds ratio [OR]: 2.452; 95% confidence interval [CI]: 0.990–6.072), concurrent oral anticoagulation (OR: 3.099; 95 CI: 1.287–7.464) and a pulse oximetry oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) ratio <382 at ED admission (OR: 3.013; 95 CI: 1.306–6.950) were independent risk factors for poor outcome, whereas influenza vaccination in the current season was protective (OR: 0.324; 95% CI: 0.138–0.763). Various factors easily available at the ED are useful for early risk stratification in adult patients with RSV‐ARI. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) can lead to a massive cytokine release. The use of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6‐point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6‐point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon‐β (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06‐0.94; P =.041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06‐0.99; P =.048) were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C‐reactive protein levels dropped by day 2. There were no TCZ‐attributable adverse events. In this observational single‐center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID‐19 pneumonia. Highlights: COVID‐19 can lead to a hyperinflammatory state that mirrors the cytokine release syndrome.The off‐labeluse of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab has been proposed to abrogate this deleterious inflammatory response, although the supporting evidence is scarce.In the present single‐centre study comprising 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous tocilizumab between March 16 and 27, 2020, the rates of clinical improvement (defined by discharge to home and/or a decrease of = 2 points on a six‐point ordinal scale) were 44.3% (39/88) and 73.9% (65/88) by days 7 and 14, respectively.The previous or concomitant use of interferon‐β and baseline serum lactate dehydrogenase levels >450 U/L were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8%, with no tocilizumab‐attributable adverse events. [ABSTRACT FROM AUTHOR]

Objectives: We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [b-D-glucan (BDG) or Candida albicans germtube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), whomay benefit frommaintaining antifungal therapy. Methods: Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at !2 and !4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome). Results: Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA [3/14 (21.4%) versus 8/35 (22.9%), P"1] and BDG [8/14 (57.1%) versus 17/35 (48.6%), P"0.75] results were similar in poor- and good-outcome patients. Conversely, a positive T2MR was associated with a higher risk of poor outcome [5/14 (35.7%) versus 0/35 (0.0%) P"0.0001]. Specificity and positive predictive value of a positive T2MR for predicting poor outcome were both 100%, with a negative predictive value of 79.6%. After testing the combinations of biomarkers/standard cultures and T2MR/standard cultures, the combination of T2MR/standard cultures showed a high capacity to discriminate patients with poor outcome fromthose with good clinical evolution. Conclusions: T2MR may be of significant utility to identify patients who may benefit frommaintaining antifungal therapy. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosis of complicated candidaemia represents a challenge for clinicians since early clinical manifestations may be non-specific and difficult to identify, thus precluding an appropriate treatment. Patients and methods: This was a multicentre prospective study for predicting complicated episodes in patients with bloodstream infection caused by Candida species, while assessing the value of follow-up blood cultures (BCs) and the persistence of positive results for T2Candida MR (T2MR) and blood β-D-glucan (BDG) tests. Immediately after the first positive BC yielding Candida species, samples were obtained on days 0, +2, +4, +7 and +14, to simultaneously perform follow-up BC, T2MR and BDG. An episode of candidaemia was defined as 'complicated' when (i) it caused septic metastasis; and/or (ii) it was the cause of the patient's death. Results: From January to June 2017, 30 patients were enrolled in the study. Of these, nine (30%) had complicated candidaemia. Values of persistently positive samples for the prediction of complicated episodes for BCs, T2MR and BDG, respectively, were as follows: sensitivity (44.4%, 100%, 100%); specificity (76.1%, 76.1%, 38.9%); positive predictive value (PPV) (44.4%, 64.2%, 40.9%) and negative predictive value (NPV) (76.1%, 100%, 100%). In multivariate analysis, having a positive T2MR within the first 5 days was associated with an almost 37-fold higher risk of developing complicated candidaemia. Conclusions: The T2MR test performed in patients with proven candidaemia may be a better marker of complicated infection than follow-up BCs or BDG. It is possible that this test may change current clinical practice, influencing the length and type of antifungal therapy in this population. [ABSTRACT FROM AUTHOR]

Background and aims Cardiovascular disease (CVD) is a leading cause of mortality after kidney transplantation (KT). The potential role of the complement system in the pathogenesis of post-transplant CVD remains unexplored. Methods Serum complement (C3 and C4) levels were measured at baseline and post-transplant months 1 and 6 in 447 kT recipients. The study outcome was post-transplant atherothrombotic event (PAE), a composite of acute coronary syndrome, critical peripheral arterial disease, stroke and/or transient ischemic attack. Results After a median follow-up of 4.2 years, 48 PAEs occurred in 43 patients (cumulative incidence: 9.6%; incidence rate: 2.6 events per 100 transplant-years). No differences were found in C3 and C4 levels at baseline or month 1 between patients with or without PAE. However, C3 levels at month 6 were significantly lower in patients developing PAE beyond that point (i.e., late PAE) (96.9 ± 22.3 vs. 109.6 ± 24.0 mg/dL; p  = 0.013). The presence of C3 hypocomplementemia at month 6 was associated with a lower PAE-free survival ( p  = 0.002). After adjusting for conventional CVD risk factors and acute graft rejection, C3 hypocomplementemia at month 6 remained as an independent risk factor for late PAE in all the exploratory models (minimum hazard ratio: 3.24; p  = 0.011). With respect to a model exclusively based on clinical variables, the inclusion of C3 levels at month 6 improved predictive capacity (areas under ROC curves: 0.788 and 0.812, respectively). Conclusions Post-transplant monitoring of serum C3 levels might be useful to identify KT recipients at increased risk of CVD. [ABSTRACT FROM AUTHOR]

Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR]: 1.1 - 10.5). Most episodes (96.4% [132/137]) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum β-lactamase-producing Enterobacterales [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [95%CI]: 31.9 - 48.9) for the whole cohort and 42.3% (95%CI: 31.2 - 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR]: 2.42; 95%CI: 1.11 - 5.29; P -value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 - 41.35; P -value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens., (Copyright © 2021 American Society for Microbiology.)

OBJECTIVETo compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypesMETHODSAs part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression.RESULTSThe study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction amplification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia >14 days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4%; odds ratio, 1.64; P=.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non-CTX-M ESBLs were detected.CONCLUSIONSClinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected.CLINICAL TRIALS IDENTIFIERClinicalTrials.gov. Identifier: NCT01764490.Infect Control Hosp Epidemiol 2018;39:660-667.

Objectives: Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E., Methods: A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality., Results: The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P = 0.06) in the ETC and 89.8% and 82.6% (P = 0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P = 0.01) in the ETC and 9.3% and 17.1% (P = 0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24-20.08; P = 0.58) and 1.04 (0.44-2.50; P = 0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43-3.29; P = 0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43-2.03; P = 0.86) and for the propensity-matched cohorts it was 1.05 (0.46-2.44; P = 0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems., Conclusions: Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)