Clinical sub-phenotypes of Staphylococcus aureus bacteraemia.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) is a clinically heterogeneous disease. The ability to identify sub-groups of patients with shared traits (sub-phenotypes) is an unmet need that could allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically-relevant sub-phenotypes can be reproducibly identified amongst patients with SAB. METHODS: We studied three cohorts of hospitalised adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n=458), the UK ARREST randomised trial (n=758), and the Spanish SAFO randomised trial (n=214). Latent class analysis was used to identify sub-phenotypes using routinely-collected clinical data, without considering outcomes. Mortality and microbiologic outcomes were then compared between sub-phenotypes. RESULTS: Included patients had predominantly methicillin-susceptible SAB (1366/1430,95.5%). We identified five distinct, reproducible clinical sub-phenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the sub-phenotypes. 84-day mortality was highest in sub-phenotype A, and lowest in B and E. Microbiologic outcomes were worse in sub-phenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased 84-day mortality in sub-phenotype B and improved microbiologic outcomes in sub-phenotype C. CONCLUSIONS: We have identified reproducible and clinically-relevant sub-phenotypes within SAB, and provide proof-of-principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these sub-phenotypes could contribute to a personalised medicine approach to SAB.

Impact of Intermediate Susceptibility to Penicillin on Antimicrobial Treatment and Outcomes of Endocarditis Caused by Viridans and Gallolyticus Group Streptococci.

BACKGROUND: Evidence supporting combination treatment with a beta-lactam plus an aminoglycoside (C-BA) for endocarditis caused by viridans and gallolyticus group streptococci (VGS-GGS) with intermediate susceptibility to penicillin (PENI-I) is lacking. We assessed the clinical characteristics and outcomes of PEN-I VGS-GGS endocarditis and compared the effectiveness and safety of C-BA with third-generation cephalosporin monotherapy. METHODS: Retrospective analysis of prospectively collected data of a cohort of definite endocarditis caused by penicillin-susceptible and PENI-I VGS-GGS (penicillin minimum inhibitory concentration ranging from 0.25 to 2 mg/L) between 2008 and 2018 in 40 Spanish hospitals. We compared cases treated with monotherapy or with C-BA and performed multivariable analyses of risk factors for in-hospital and 1-year mortality. RESULTS: A total of 914 consecutive cases of definite endocarditis caused by VGS-GGS with complete or intermediate susceptibility to penicillin were included. A total of 688 (75.3%) were susceptible to penicillin and 226 (24.7%) were PENI-I. Monotherapy was used in 415 (45.4%) cases (cephalosporin in 331 cases) and 499 (54.6%) cases received C-BA. In-hospital mortality was 11.9%, and 190 (20.9%) patients developed acute kidney injury. Heart failure (odds ratio [OR]: 6.06; 95% confidence interval [CI]: 1.37-26.87; P = .018), central nervous system emboli (OR: 9.83; 95% CI: 2.17-44.49; P = .003) and intracardiac abscess (OR: 13.47; 95% CI: 2.24-81.08; P = .004) were independently associated with in-hospital mortality among PEN-I VGS-GGS cases, while monotherapy was not (OR: 1.01; 95% CI: .26-3.96; P = .982). CONCLUSIONS: Our findings support the use of cephalosporin monotherapy in PEN-I VGS-GGS endocarditis in order to avoid nephrotoxicity without adversely affecting patient outcomes.

Impact of a prospective audit and feedback antimicrobial stewardship programme on carbapenem consumption: a quasi-experimental study (IPANEMA study).

OBJECTIVES: To test the hypothesis that a prospective audit and feedback (PAF) intervention combined with electronic tools will reduce carbapenem use without negatively affecting patient outcomes. METHODS: A quasi-experimental, pre-intervention and intervention study was performed conducted in the urology department of a university hospital. The intervention involved implementing a PAF within an antimicrobial stewardship programme with the aid of an electronic tool. The primary outcome was carbapenem use, assessed by DDD/100 patient-days (PD). Secondary outcomes included evaluating the effect of the intervention on overall antibiotic use measured by DDD/100 PD and days of therapy (DOT)/100 PD, as well as patient safety. The chi-squared test or t-test was used, and the Poisson model was employed to assess the association between the intervention and outcomes. RESULTS: A 9% decrease in carbapenem DDD/100 PD was observed during the intervention period (IR = 0.91; 95% CI = 0.85-0.97, P = 0.007). The proportion of patients who received carbapenem treatment dropped from 17.8% to 16.5% [incidence ratio (IR) = 0.95; 95% CI = 0.86-2.05, P = 0.31]. Carbapenem DOT/100 PD decreased from 12.4 to 11.0 (IR = 0.89; 95% CI = 0.83-0.94, P < 0.001). Overall antibiotic DDD/100 PD decreased by 3% (IR = 0.97; 95% CI = 0.94-0.99, P = 0.001) and DOT/100 PD by 7% (IR = 0.93; 95% CI = 0.91-0.95, P < 0.001). The incidence of infections caused by carbapenemase-producing microorganisms, Enterococcus faecium bacteraemia and Clostridioides difficile-associated diarrhoea episodes was similar in the pre-intervention and intervention periods. ESBL incidence rate decreased, but the differences were not statistically significant (3.94/1000 PD versus 2.88/1000 PD, P = 0.111). Length of hospital stay, in-hospital all-cause mortality, and 30 day readmission incidence remained unchanged. CONCLUSIONS: The implementation of PAF combined with an electronic tool was an effective and safe intervention for reducing carbapenem use.

Time from symptoms onset to remdesivir is associated with the risk of ICU admission: a multicentric analyses.

BACKGROUND: Shorter duration of symptoms before remdesivir has been associated with better outcomes. Our goal was to evaluate variables associated with the need of ICU admission in a cohort of hospitalized patients for COVID-19 under remdesivir including the period from symptoms onset to remdesivir. METHODS: We conducted a retrospective multicentric study analysing all patients admitted with COVID-19 in 9 Spanish hospitals who received treatment with remdesivir in October 2020. The main outcome was the need of ICU admission after 24 h of the first dose of remdesivir. RESULTS: In our cohort of 497 patients, the median of days from symptom onset to remdesivir was 5 days, and 70 of them (14.1%) were later admitted into ICU. The clinical outcomes associated with ICU admission were days from symptoms onset (5 vs. 6; p = 0.023), clinical signs of severe disease (respiratory rate, neutrophil count, ferritin levels and very-high mortality rate in SEIMC-Score) and the use of corticosteroids and anti-inflammatory drugs before ICU. The only variable significatively associated with risk reduction in the Cox-regression analyses was ≤ 5 days from symptoms onset to RDV (HR: 0.54, CI95%: 0.31-0.92; p = 0.024). CONCLUSION: For patients admitted to the hospital with COVID-19, the prescription of remdesivir within 5 days from symptoms onset diminishes the need of ICU admission.

Executive summary - Diagnosis, treatment and prophylaxis of influenza virus infection - Consensus statement of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Pediatric Infectious Diseases (SEIP), the Spanish Association of Vaccinology (AEV), the Spanish Society of Family and Community Medicine (SEMFYC) and the Spanish Society of Preventive Medicine, Public Health and Health Management (SEMPSPGS).

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.

Impact of Empirical Antibiotic Regimens on Mortality in Neutropenic Patients with Bloodstream Infection Presenting with Septic Shock.

We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. A multicenter retrospective study (2010 to 2019) of two prospective cohorts compared BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Of 1,563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% versus 15%, P < 0.001). Gram-negative bacilli caused 81% of episodes with septic shock, Gram-positive cocci caused 22%, and Candida species caused 5%. Inappropriate empirical antibiotic treatment (IEAT) was administered in 17.5% of septic shock episodes. Empirical ß-lactam combined with other active antibiotics was associated with the lowest mortality observed. When amikacin was the only active antibiotic, mortality was 90%. Addition of empirical specific Gram-positive coverage had no impact on mortality. Mortality was higher when IEAT was administered (76% versus 51%, P = 0.002). Age of >70 years (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2 to 4.7), IEAT for Candida spp. or Gram-negative bacilli (OR, 3.8; 95% CI, 1.3 to 11.1), acute kidney injury (OR, 2.6; 95% CI, 1.4 to 4.9), and amikacin as the only active antibiotic (OR, 15.2; 95% CI, 1.7 to 134.5) were independent risk factors for mortality, while the combination of ß-lactam and amikacin was protective (OR, 0.32; 95% CI, 0.18 to 0.57). Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active ß-lactam and amikacin results in the best outcomes.

Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial.

OBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumonia after treatment with tocilizumab, an anti-interleukin-6 receptor antibody, using data from the COVACTA trial in patients hospitalized with severe coronavirus disease 2019 pneumonia. DESIGN: Exploratory analysis from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. SETTING: Hospitals in North America and Europe. PATIENTS: Adults hospitalized with severe coronavirus disease 2019 pneumonia receiving standard care. INTERVENTION: Randomly assigned 2:1 to IV tocilizumab 8 mg/kg or placebo. MEASUREMENTS AND MAIN RESULTS: Candidate biomarkers were measured in 295 patients in the tocilizumab arm and 142 patients in the placebo arm. Efficacy outcomes assessed were clinical status on a seven-category ordinal scale (1, discharge; 7, death), mortality, time to hospital discharge, and mechanical ventilation (if not receiving it at randomization) through day 28. Prognostic and predictive biomarkers were evaluated continuously with proportional odds, binomial or Fine-Gray models, and additional sensitivity analyses. Modeling in the placebo arm showed all candidate biomarkers except lactate dehydrogenase and d-dimer were strongly prognostic for day 28 clinical outcomes of mortality, mechanical ventilation, clinical status, and time to hospital discharge. Modeling in the tocilizumab arm showed a predictive value of ferritin for day 28 clinical outcomes of mortality (predictive interaction, p = 0.03), mechanical ventilation (predictive interaction, p = 0.01), and clinical status (predictive interaction, p = 0.02) compared with placebo. CONCLUSIONS: Multiple biomarkers prognostic for clinical outcomes were confirmed in COVACTA. Ferritin was identified as a predictive biomarker for the effects of tocilizumab in the COVACTA patient population; high ferritin levels were associated with better clinical outcomes for tocilizumab compared with placebo at day 28.

Impact of ceftazidime/avibactam versus best available therapy on mortality from infections caused by carbapenemase-producing Enterobacterales (CAVICOR study).

BACKGROUND: Infections caused by carbapenemase-producing Enterobacterales (CPE) are not well represented in pivotal trials with ceftazidime/avibactam. The best strategy for the treatment of these infections is unknown. METHODS: We conducted a multicentre retrospective observational study of patients who received ≥48 h of ceftazidime/avibactam or best available therapy (BAT) for documented CPE infections. The primary outcome was 30 day crude mortality. Secondary outcomes were 21 day clinical response and microbiological response. A multivariate logistic regression model was used to identify factors predictive of 30 day crude mortality. A propensity score to receive treatment with ceftazidime/avibactam was used as a covariate in the analysis. RESULTS: The cohort included 339 patients with CPE infections. Ceftazidime/avibactam treatment was used in 189 (55.8%) patients and 150 (44.2%) received BAT at a median of 2 days after diagnosis of infection. In multivariate analysis, ceftazidime/avibactam treatment was associated with survival (OR 0.41, 95% CI 0.20-0.80; P = 0.01), whereas INCREMENT-CPE scores of >7 points (OR 2.57, 95% CI 1.18-1.5.58; P = 0.01) and SOFA score (OR 1.20, 95% CI 1.08-1.34; P = 0.001) were associated with higher mortality. In patients with INCREMENT-CPE scores of >7 points, ceftazidime/avibactam treatment was associated with lower mortality compared with BAT (16/73, 21.9% versus 23/49, 46.9%; P = 0.004). Ceftazidime/avibactam was also an independent factor of 21 day clinical response (OR 2.43, 95% CI 1.16-5.12; P = 0.02) and microbiological eradication (OR 0.40, 95% CI 0.18-0.85; P = 0.02). CONCLUSIONS: Ceftazidime/avibactam is an effective alternative for the treatment of CPE infections, especially in patients with INCREMENT-CPE scores of >7 points. A randomized controlled trial should confirm these findings.

Cytokine response as a biomarker for early diagnosis and outcome prediction of stem cell transplant recipients and acute leukemia patients with invasive aspergillosis.

We aimed to determine the role of serum cytokine expression in invasive aspergillosis (IA) diagnosis and outcome prediction in hematologic patients. In this multicenter study, serum cytokines (IL6, IL10, INF-gamma, IL12, IL4, TNF-alpha, IL17, and IL23) were prospectively recruited from all consecutive patients with hematologic malignances at IA diagnosis and compared to control patients matched by center, age, baseline disease, and therapeutic regimen. We included 36 patients with IA and 36 controls. Serum levels of IL6 and IL10 cytokines on day 0 were significantly increased in patients with IA when compared to controls (P = 0.001 and P = 0.025, respectively), even in those who were neutropenic. No differences were observed for the other cytokines. IL6 and IL10 predicted IA with an area under the ROC curve of 0.74 (95% CI 0.62-0.86) and 0.64 (95% CI 0.51-0.77), respectively. The best cutoff point in predicting IA was 20.85 pg/ml for IL6 (sensitivity 72.2%; specificity 77.8%; PPV 76.5% and NPV 73.7%), and 0.045 pg/ml for IL10 (sensitivity 62.9%; specificity 63.9%; PPV 62.9% and NPV 63.9%). IL6 levels were associated with increased mortality, with the best cutoff value being 65.59 pg/ml in mortality prediction. In conclusion, in addition to current tests in place, IL6 and IL10 levels-as measured in plasma-may help clinicians diagnose IA. High levels of IL6 at IA diagnosis are related with worse outcomes. LAY SUMMARY: We evaluated the role of serum cytokine expression in invasive aspergillosis (IA) diagnosis and outcome. Serum levels of IL6 and IL10 are increased in patients with IA compared to controls, and IL6 levels are associated with mortality.

Infective Endocarditis: New Challenges in a Classic Disease.

Infective endocarditis is a relatively rare, but deadly infection, with an overall mortality of around 20% in most series. Clinical manifestations have evolved in response to significant epidemiological shifts in industrialized nations, with a move toward a nosocomial or health-care-related pattern, in older patients, with more episodes associated with prostheses and/or intravascular electronic devices and a predominance of staphylococcal and enterococcal etiology.Diagnosis is often challenging and is based on the conjunction of clinical, microbiological, and imaging information, with notable progress in recent years in the accuracy of echocardiographic data, coupled with the recent emergence of other useful imaging techniques such as cardiac computed tomography (CT) and nuclear medicine tools, particularly 18F-fluorodeoxyglucose positron emission/CT.The choice of an appropriate treatment for each specific case is complex, both in terms of the selection of the appropriate agent and doses and durations of therapy as well as the possibility of using combined bactericidal antibiotic regimens in the initial phase and finalizing treatment at home in patients with good evolution with outpatient oral or parenteral antimicrobial therapies programs. A relevant proportion of patients will also require valve surgery during the active phase of treatment, the timing of which is extremely difficult to define. For all the above, the management of infective endocarditis requires a close collaboration of multidisciplinary endocarditis teams.

Ceftolozane/tazobactam for difficult-to-treat Gram-negative infections: A real-world tertiary hospital experience.

OBJECTIVE: To evaluate the real-world clinical efficacy of ceftolozane/tazobactam (C/T) in difficult-to-treat infections caused by multi-drug resistant Gram-negative microorganisms, including carbapenem-resistant Pseudomonas aeruginosa. METHODS: Retrospective cohort study of adult patients treated with C/T for at least 48 hours for infections caused by multi-drug resistant Gram-negative bacteria in a tertiary hospital from May 2016 until August 2019. The primary outcome analysed was clinical failure, defined as a composite of symptomatology persistence after 7 days of C/T treatment, infection recurrence, and/or all-cause mortality within 30 days of follow-up. RESULTS AND DISCUSSION: 96 episodes of C/T treatment were included, mostly consisting of targeted treatments (83.9%) for the following sources of infection: intra-abdominal (22.6%), urinary tract (25.8%), skin and soft tissue (19.4%), hospital-acquired pneumonia (14%), and other (6.4%). The most frequently isolated bacteria were carbapenem-resistant (88, 94.6%). Clinical failure rate was 30.1%, due to persistent infection at day 7 (4.3%), recurrence of the initial infection (16.1%), or 30-day all-cause mortality (8.6%). Adverse events most frequently reported were Clostridium difficile infection (9%) and cholestasis (8%). WHAT IS NEW AND CONCLUSION: C/T showed a favourable clinical profile for difficult-to-treat multidrug-resistant and carbapenem-resistant Gram-negative infections, regardless of the source of infection.

A Care Bundle Intervention to Prevent Surgical Site Infections After a Craniotomy.

BACKGROUND: Although surgical site infections after a craniotomy (SSI-CRANs) are a serious problem that involves significant morbidity and costs, information on their prevention is scarce. We aimed to determine whether the implementation of a care bundle was effective in preventing SSI-CRANs. METHODS: A historical control study was used to evaluate the care bundle, which included a preoperative shower with 4% chlorhexidine soap, appropriate hair removal, adequate preoperative systemic antibiotic prophylaxis, the administration of 1 g of vancomycin powder into the subgaleal space before closing, and a postoperative dressing of the incisional surgical wound with a sterile absorbent cover. Patients were divided into 2 groups: preintervention (January 2013 to December 2015) and intervention (January 2016 to December 2017). The primary study end point was the incidence of SSI-CRANs within 1 year postsurgery. Propensity score matching was performed, and differences between the 2 study periods were assessed using Cox regression models. RESULTS: A total of 595 and 422 patients were included in the preintervention and intervention periods, respectively. The incidence of SSI-CRANs was lower in the intervention period (15.3% vs 3.5%; P < .001). Using a propensity score model, 421 pairs of patients were matched. The care bundle intervention was independently associated with a reduced incidence of SSI-CRANs (adjusted odds ratio, 0.23; 95% confidence interval, .13-.40; P < .001). CONCLUSIONS: The care bundle intervention was effective in reducing SSI-CRAN rates. The implementation of this multimodal preventive strategy should be considered in centers with high SSI-CRAN incidences.

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial.

BACKGROUND: We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. METHODS: A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. RESULTS: Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). CONCLUSIONS: Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. CLINICAL TRIALS REGISTRATION: NCT01898338.

Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Development and validation of a prediction model for 30-day mortality in hospitalised patients with COVID-19: the COVID-19 SEIMC score.

OBJECTIVE: To develop and validate a prediction model of mortality in patients with COVID-19 attending hospital emergency rooms. DESIGN: Multivariable prognostic prediction model. SETTING: 127 Spanish hospitals. PARTICIPANTS: Derivation (DC) and external validation (VC) cohorts were obtained from multicentre and single-centre databases, including 4035 and 2126 patients with confirmed COVID-19, respectively. INTERVENTIONS: Prognostic variables were identified using multivariable logistic regression. MAIN OUTCOME MEASURES: 30-day mortality. RESULTS: Patients' characteristics in the DC and VC were median age 70 and 61 years, male sex 61.0% and 47.9%, median time from onset of symptoms to admission 5 and 8 days, and 30-day mortality 26.6% and 15.5%, respectively. Age, low age-adjusted saturation of oxygen, neutrophil-to-lymphocyte ratio, estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, dyspnoea and sex were the strongest predictors of mortality. Calibration and discrimination were satisfactory with an area under the receiver operating characteristic curve with a 95% CI for prediction of 30-day mortality of 0.822 (0.806-0.837) in the DC and 0.845 (0.819-0.870) in the VC. A simplified score system ranging from 0 to 30 to predict 30-day mortality was also developed. The risk was considered to be low with 0-2 points (0%-2.1%), moderate with 3-5 (4.7%-6.3%), high with 6-8 (10.6%-19.5%) and very high with 9-30 (27.7%-100%). CONCLUSIONS: A simple prediction score, based on readily available clinical and laboratory data, provides a useful tool to predict 30-day mortality probability with a high degree of accuracy among hospitalised patients with COVID-19.

Effects of age and comorbidities on serum levels of inflammatory markers in community-acquired pneumonia.

INTRODUCTION: Studies have suggested that an inappropriate inflammatory response is a major cause of treatment failure and mortality in patients with community-acquired pneumonia (CAP). We aimed to determine the effect of age and comorbidities on serum inflammatory markers in CAP. METHODS: We performed a prospective cohort study of adults hospitalized with CAP. For the purposes of this study, we compared patients according to comorbidities and age. Inflammatory markers were measured at hospital admission, focusing on acute phase proteins, cytokines and monocyte human leucocyte antigen DR (mHLA-DR) expression. RESULTS: In patients with chronic pulmonary disease (COPD), serum cytokines had significantly decreased levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and mHLA-DR expression, as well as the C-reactive protein (CRP), compared with patients who had no comorbidities. Similarly, patients with chronic heart disease had a significantly reduced CRP levels and mHLA-DR expression, whereas patients with chronic kidney disease had significantly higher serum levels of procalcitonin and TNF-α. Lower procalcitonin, IL-6 and IL-10 levels, as well as mHLA-DR expression, were documented in older patients, but with no significant differences compared to younger patients. Multimorbidity in older patients was associated with significant lower levels of CRP and mHLA-DR expression. CONCLUSIONS: The circulating inflammatory markers to CAP have profiles that differ with age and underlying comorbidities. Multimorbidity in the elderly is also associated with lower serum levels of some inflammatory markers. Our findings suggest that inflammatory markers in CAP should be interpreted after considering age and comorbid conditions.

Risk factors for enterococcal urinary tract infections: a multinational, retrospective cohort study.

Complicated urinary tract infection (cUTI) is a frequent cause of morbidity. In this multinational retrospective cohort study, we aimed to demonstrate risk factors for enterococcal UTI. Univariate and multivariate analyses of risk factors for enterococcal infection were performed. Among 791 hospitalized patients with cUTI, enterococci accounted for approximately 10% of cases (78/791). Risk factors for enterococcal UTI in multivariable analysis were male gender, age range of 55-75 years, catheter-associated UTI, and urinary retention. This information may assist treating physicians in their decision-making on prescribing empiric anti-enterococcus treatment to hospitalized patients presenting with cUTI and thus improve clinical outcomes.

Efficacy of ß-lactam/ß-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

BACKGROUND: Whether active therapy with ß-lactam/ß-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/µL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

Inappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug Resistance.

BACKGROUND: We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality. METHODS: This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006-2017). Episodes receiving IEAT were compared with episodes receiving appropriate empirical therapy. Adherence to Infectious Diseases Society of America (IDSA) recommendations was evaluated. Multivariate analysis was performed to identify independent risk factors for mortality in Pseudomonas aeruginosa episodes. RESULTS: Of 1615 episodes, including Escherichia coli (24%), coagulase-negative staphylococci (21%), and P. aeruginosa (16%), 394 (24%) received IEAT despite IDSA recommendations being followed in 87% of cases. Patients with multidrug-resistant gram-negative bacilli (MDR-GNB), accounting for 221 (14%) of all isolates, were more likely to receive IEAT (39% vs 7%, P < .001). Overall mortality was higher in patients with GNB BSI who received IEAT (36% vs 24%, P = .004); when considering individual microorganisms, only patients with infection caused by P. aeruginosa experienced a significant increase in mortality when receiving IEAT (48% vs 31%, P = .027). Independent risk factors for mortality in PA BSI (odds ratio [95% confidence interval] were IEAT (2.41 [1.19-4.91]), shock at onset (4.62 [2.49-8.56]), and pneumonia (3.01 [1.55-5.83]). CONCLUSIONS: IEAT is frequent in high-risk patients with FN and BSI, despite high adherence to guidelines. This inappropriate treatment primarily impacts patients with P. aeruginosa-related BSI mortality and in turn is the only modifiable factor to improve outcomes.