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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.

Background Surgical site infections after craniotomy (SSI-CRAN) significantly impact patient outcomes and healthcare costs by increasing length of stay and readmission and reoperation rates. However, to our knowledge, no study has yet analysed the economic impact of a surgical care bundle for preventing SSI-CRAN. The aim is to analyse the hospital cost saving after implementation of a care bundle for the prevention of SSI-CRAN. Methods A retrospective cost-analysis was performed, considering two periods: pre-care bundle (2013–2015) and care bundle (2016–2017). A bottom-up approach was used to calculate the costs associated with infection in patients who developed a SSI-CRAN in comparison to those who did not, in both periods and on a patient-by-patient basis. The derived cost of SSI-CRAN was calculated considering: (1) cost of the antibiotic treatment, (2) cost of length of stay in the neurosurgery ward within the 1-year follow up period, (3) cost of the re-intervention, and (4) cost of the implant for cranial reconstruction, when necessary. Results A total of 595 patients were included in the pre-care bundle period and 422 in the care bundle period. Mean cost of a craniotomy procedure was approximately €8000, rising to €24,000 in the case of SSI-CRAN. Mean yearly hospital costs fell by €502,857 in the care bundle period (€714,886 vs. €212,029). Extra costs between periods were mainly due to increased length of hospital stay (€573,555.3 vs. €183,958.9; difference: €389,596.4), followed by the cost of implant for cranial reconstruction (€69,803.4 vs. €9,936; difference: €59,867.4). Overall, implementation of the care bundle saved the hospital €500,844.3/year. Conclusion The implementation of a care bundle for SSI-CRAN had a significant economic impact. Hospitals should consider the deployment of this multimodal preventive strategy to reduce their SSI-CRAN rates, and also their costs.

INTRODUCTION In a large cohort of patients with Staphylococcus aureus bloodstream infection (SABSI), we aimed to analyze the incidence and risk factors for infective endocarditis (IE) among patients with active cancer (PAC) in comparison with those without cancer (PWC). METHODS Multicenter cohort study of patients with SABSI admitted to two tertiary care hospitals, from 2011 to 2019. PAC were defined as those with an active solid organ cancer or hematological malignancies. SABSI and S. aureus IE were compared between PAC and PWC. RESULTS Among 978 episodes of SABSI, 217 (22.2%) occurred in PAC. PAC were younger, had fewer comorbidities, carried cardiac devices less often, and had less community-acquired SABSI than PWC. Compared to PWC, PAC more frequently had catheter-related SABSI, less IE (2.8% vs 10.9%, p

Hospital readmissions following severe infections are a major economic burden on the health care system and have a negative influence on patients' quality of life. Understanding the risk factors for readmission, particularly the extent to which they could be prevented, is of a great importance. In this study we evaluated potentially preventable risk factors for 60-day readmission in patients surviving hospitalization for complicated urinary tract infection (cUTI). This was a multinational, multicentre retrospective cohort study conducted in Europe and the Middle East. Our cohort included survivors of hospitalization due to cUTI during the years 2013–2014. The primary outcome was 60-day readmission following index hospitalization. Patient characteristics that could have influenced readmission: demographics, infection presentation and management, microbiological and clinical data; were collected via computerized medical records from infection onset up to 60 days after hospital discharge. Overall, 742 patients were included. The cohort median age was 68 years (interquartile range, (IQR) 55–80) and 43.3% (321/742) of patients were males. The all-cause 60-day readmission rate was 20.1% (149/742) and more than half were readmitted for infection [57.1%, (80/140)]. Recurrent cUTI was the most frequent cause for readmission [46.4% (65/140)]. Statistically significant risk factors associated with 60-day readmission in multivariable analysis were: older age (odds ratio (OR) 1.02 for an one-year increment, confidence interval (CI) 1.005–1.03), diabetes mellitus (OR 1.63, 95% CI 1.04–2.55), cancer (OR 1.7, 95% CI 1.05–2.77), previous urinary tract infection (UTI) in the last year (OR 1.8, 95% CI: 1.14–2.83), insertion of an indwelling bladder catheter (OR 1.62, 95% CI 1.07–2.45) and insertion of percutaneous nephrostomy (OR 3.68, 95% CI 1.67–8.13). In conclusion, patients surviving hospitalization for cUTI are frequently re-hospitalized, mostly for recurrent urinary infections associated with a medical condition that necessitated urinary interventions. Interventions to avoid re-admissions should target these patients.

© 2020 The Author(s)., [Objectives]: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters., [Methods]: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs)., [Results]: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001)., [Conclusions]: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation., IJ has received honoraria for participating in an advisory board from Gilead Sciences, and for educational activities from ViiV. JB has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV, and honoraria for being a speaker or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. JRA received fees for participating in an advisory board, being a speaker, and research grant support from Viiv, Janssen, Gilead, MSD, Teva, Alexa and Serono. PR is involved as speaker or advisory board participant for Gilead Sciences, AbbVie and ViiV. JR-B, JP, JC and MY have no conflicts of interest to declare. SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, “Investing in your future”) and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas received funding for research from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades – co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP).

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

[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., This work was supported by the Spanish Ministry of Science, Innovation and Universities (PI12/01907); Spanish Network for Research in Infectious Diseases (RD16/0016/0005); Instituto de Salud Carlos III (ISCIII); and Spanish Ministry of Economy, Industry and Competitiveness. This work was also supported by the European Development Regional Fund “A way to achieve Europe,” Operational Programme Intelligent Growth 2014–2020; Spanish Clinical Research Network (SCReN), co-financed by the Plan Nacional de I+D and ISCIII, Subdirección General de Evaluación y Fomento de la Investigación (PT13/0002/0007); and the Grupo de Estudio de la Infección Relacionada con la Asistencia Sanitaria. J. M.-M. received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques Agust Pi i Sunyer, Barcelona, Spain, during 2017–2021.

Spanish Network for Research in Infectious Diseases/Enterobacter spp. Bacteriemia Project Group., [Objectives] The genus Enterobacter is a common cause of nosocomial infections. Historically, the most frequent Enterobacter species were those of Enterobacter cloacae complex and Enterobacter aerogenes. In 2019, E. aerogenes was re-classified as Klebsiella aerogenes owing to its higher genotypic similarity with the genus Klebsiella. Our objective was to characterise and compare the clinical profiles of bacteraemia caused by E. cloacae and K. aerogenes., [Methods] This 3-year multicentre, prospective cohort study enrolled consecutive patients with bacteraemia by E. cloacae or K. aerogenes. Baseline characteristics, bacteraemia features (source, severity, treatment), antibiotic susceptibility, resistance mechanisms and mortality were analysed. bacteraemia had received more antibiotics., [Results] The study included 285 patients with bacteraemia [196 (68.8%) E. cloacae and 89 (31.2%) K. aerogenes]. The groups showed no differences in age, sex, previous use of invasive devices, place of acquisition, sources or severity at onset. The Charlson score was higher among patients with E. cloacae bacteraemia [2 (1–4) vs. 1 (0.5–3); P = 0.018], and previous antibiotic therapy was more common in patients with K. aerogenes bacteraemia (57.3% vs. 41.3%; P = 0.01). Mortality was 19.4% for E. cloacae and 20.2% for K. aerogenes (P = 0.869). Antibiotic susceptibility was similar for both species, and the incidence of multidrug resistance or ESBL production was low (6% and 5.3%, respectively), with no differences between species., [Conclusion] Bacteraemias caused by E. cloacae and K. aerogenes share similar patient profiles, presentation and prognosis. Patients with E. cloacae bacteraemia had more co-morbidities and those with K. aerogenes bacteraemia had received more antibiotics., This work was supported by the Instituto Carlos III [grant PS09/00916], Ministerio de Ciencia e Innovación, the Plan Nacional I+D+i 2013–2016 and Instituto Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases [REIPI, RD16/0016/0001; RD16/0016/0005; RD16/0016/0007; RD16/0016/0008; RD16/0016/0009], co-financed by the European Regional Development Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020.

PRAISE network: Maaike S. M. van Mourik, Stephanie M.van Rooden, Mohamed Abbas, Olov Aspevall, Pascal Astagneau, Marc J. M. Bonten, Elena Carrara, Aina Gomila-Grange, Sabine C. de Greeff , Sophie Gubbels, Wendy Harrison, Hilary Humphreys, Anders Johansson, Mayke B. G. Koek, Brian Kristensen, Alain Lepape, Jean-Christophe Lucet, Siddharth Mookerjee, Pontus Naucler, Zaira R. Palacios-Baena, Elisabeth Presterl, Miquel Pujol, Jacqui Reilly, Christopher Roberts, Evelina Tacconelli, Daniel Teixeira, Thomas Tängdén, John Karlsson Valik, Michael Behnke, PetraGastmeier., [Introduction] Healthcare-associated infections (HAI) are a major public health concern. Monitoring of HAI rates, with feedback, is a core component of infection prevention and control programmes. Digitalization of healthcare data has created novel opportunities for automating the HAI surveillance process to varying degrees. However, methods are not standardized and vary widely between different healthcare facilities. Most current automated surveillance (AS) systems have been confined to local settings, and practical guidance on how to implement large-scale AS is needed., [Methods] This document was written by a task force formed in March 2019 within the PRAISE network (Providing a Roadmap for Automated Infection Surveillance in Europe), gathering experts in HAI surveillance from ten European countries., [Results] The document provides an overview of the key e-health aspects of implementing an AS system of HAI in a clinical environment to support both the infection prevention and control team and information technology (IT) departments. The focus is on understanding the basic principles of storage and structure of healthcare data, as well as the general organization of IT infrastructure in surveillance networks and participating healthcare facilities. The fundamentals of data standardization, interoperability and algorithms in relation to HAI surveillance are covered. Finally, technical aspects and practical examples of accessing, storing and sharing healthcare data within a HAI surveillance network, as well as maintenance and quality control of such a system, are discussed., [Conclusions] With the guidance given in this document, along with the PRAISE roadmap and governance documents, readers will find comprehensive support to implement large-scale AS in a surveillance network., This network has been supported under the 7th transnational call within the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), Network Call on Surveillance (2018) and was thereby funded by ZonMw (grant 549007001). This project also received support from the COMBACTE MAGNET EPI-Net project funded by the Innovative Medicines Initiative Joint Undertaking under grant agreement 115523 | 115620 | 115737 | 777362, resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. J.K.V. was supported by grants from Region Stockholm and Vinnova.

[Background] Staphylococcus aureus bloodstream infection (SABSI) arising from a urinary tract source (UTS) is poorly understood., [Methods] We conducted a retrospective analysis in 3 major teaching hospitals in Spain of prospectively collected data of hospitalized patients with SABSI. SABSI-UTS was diagnosed in patients with urinary tract symptoms and/or signs, no evidence of an extra-urinary source of infection, and a urinary S. aureus count of ≥105 cfu/mL. Susceptibility of S. aureus strains and patient mortality were compared between SABSI from UTS (SABSI-UTS) and other sources (SABSI-other)., [Results] Of 4181 episodes of SABSI, we identified 132 (3.16%) cases of SABSI-UTS that occurred predominantly in patients who were male, had high Charlson comorbidity scores, were dependent for daily life activities, and who had undergone urinary catheterization and/or urinary manipulation before the infection. SABSI-UTS was more often caused by MRSA strains compared with SABSI-other (40.9% vs 17.5%; P < .001). Patients with SABSI-UTS caused by MRSA more often received inadequate empirical treatment compared with those caused by susceptible strains (59.7% vs 23.1%; P < .001). The 30-day case fatality rate was lower in patients with SABSI-UTS than in those with SABSI-other (14.4% vs 23.8%; P = .02). Factors independently associated with mortality were dependence for daily activities (aOR, 3.877; 95% CI, 1.08–13.8; P = .037) and persistent bacteremia (aOR, 7.88; 95% CI, 1.57–39.46; P = .012)., [Conclusions] SABSI-UTS occurs predominantly in patients with severe underlying conditions and in those who have undergone urinary tract manipulation. Moreover, it is frequently due to MRSA strains and causes significant mortality., This work was supported by Plan Nacional de I+D+i 2017–2021 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005, RD16/0016/0002, RD16/0016/0001) and was co-financed by the European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014–2020.

This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.

Introduction International travelers have grown significantly over last years, as well as imported diseases from tropical areas. Information in pediatric population is scarce. We describe demographic and clinical characteristics of febrile children coming from the tropics. Methods Retrospective review of patients under 18 years old, presenting at a tertiary hospital and surrounding primary health care centers between July 2002 and July 2018 with a stay in a tropical region during the previous year. Patients were selected from microbiological charts of thick smears for malaria or dengue serologies. Results 188 patients were studied: 52.7% were born in Spain with a median age of 3.0 years old (IQR 1.5–8.0). Main regions of stay were Sub-Saharan Africa (54.8%) and Latin America (29.8%), mostly for visiting their friends and relatives (56.3%), followed by recent arrival migrants (32.4%). Only 34% of travelers attended pre-travel consultation. More than 80% of these febrile children attended directly the Emergency Room. The most frequent diagnoses were febrile syndrome without source (56.4%), respiratory condition (15.4%) and acute diarrhea (11.7%). Around a half (52.1%) were managed as outpatients, but 46.2% were hospitalized and 7.4% were admitted to Intensive Care Unit. No specific diagnosis was achieved in 24% of cases. However, 29.7% were diagnosed with malaria. Conclusion Children with fever coming from tropical areas were at risk of severe infectious diseases. Malaria was diagnosed in one out of four and 7% required admission in PICU. This information emphasizes the need of reinforcing training about tropical diseases among first line physicians.

Objective:Automated surveillance of healthcare-associated infections reduces workload and improves standardization, but it has not yet been adopted widely. In this study, we assessed the performance and feasibility of an easy implementable framework to develop algorithms for semiautomated surveillance of deep incisional and organ-space surgical site infections (SSIs) after orthopedic, cardiac, and colon surgeries.Design:Retrospective cohort study in multiple countries.Methods:European hospitals were recruited and selected based on the availability of manual SSI surveillance data from 2012 onward (reference standard) and on the ability to extract relevant data from electronic health records. A questionnaire on local manual surveillance and clinical practices was administered to participating hospitals, and the information collected was used to pre-emptively design semiautomated surveillance algorithms standardized for multiple hospitals and for center-specific application. Algorithm sensitivity, positive predictive value, and reduction of manual charts requiring review were calculated. Reasons for misclassification were explored using discrepancy analyses.Results:The study included 3 hospitals, in the Netherlands, France, and Spain. Classification algorithms were developed to indicate procedures with a high probability of SSI. Components concerned microbiology, prolonged length of stay or readmission, and reinterventions. Antibiotics and radiology ordering were optional. In total, 4,770 orthopedic procedures, 5,047 cardiac procedures, and 3,906 colon procedures were analyzed. Across hospitals, standardized algorithm sensitivity ranged between 82% and 100% for orthopedic surgery, between 67% and 100% for cardiac surgery, and between 84% and 100% for colon surgery, with 72%–98% workload reduction. Center-specific algorithms had lower sensitivity.Conclusions:Using this framework, algorithms for semiautomated surveillance of SSI can be successfully developed. The high performance of standardized algorithms holds promise for large-scale standardization.

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.

Spanish Network for Research in Infectious Diseases/Enterobacter spp. Bacteriemia Project group., [Background] Enterobacter is among the main etiologies of hospital-acquired infections. This study aims to identify the risk factors of acquisition and attributable mortality of Enterobacter bacteremia., [Results] The study included 285 cases and 570 controls. E. cloacae was isolated in 198(68.8%) cases and E. aerogenes in 89(31.2%). Invasive procedures (hemodialysis, nasogastric tube, mechanical ventilation, surgical drainage tube) and previous antibiotics or corticosteroids were independently associated with Enterobacter bacteremia. Its attributable mortality was 7.8%(CI95%2.7–13.4%), being dissimilar according to a McCabe index: non-fatal=3.2%, ultimately fatal=12.9% and rapidly fatal=0.12%. Enterobacter bacteremia remained an independent risk factor for mortality among cases with severe sepsis or septic shock (OR 5.75 [CI95%2.57–12.87], p, [Conclusions] Invasive procedures, previous antibiotics and corticosteroids predispose to acquire Enterobacter bacteremia. This entity increases mortality among fragile patients and those with severe infections. Antibiotic resistances did not affect the outcome., This study was supported by the Instituto Carlos III, grant PS09/00916, Ministerio de Ciencia e Innovación, and the Plan Nacional I+D+i 2013-2016 and Instituto Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI, RD 16/0016/0001; RD 16/0016/0005; RD 16/0016/0007; RD 16/0016/0008; RD 16/0016/0009) – co – financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014-2020.

Summary Background Short-term peripheral venous catheters are a significant source of healthcare-acquired bloodstream infections and a preventable cause of death. Aim To assess the effectiveness of interventions applied to reduce the incidence and mortality associated with short-term peripheral venous catheter-related bloodstream infections (PVCR-BSIs). Methods The intervention included continuous PVCR-BSI surveillance, implementation of preventive measures related to catheter insertion and maintenance in accordance with evidence-based recommendations and the hospital's own data, front-line staff educational campaigns, and assessment of adherence to hospital guidelines by ward rounds. A Poisson regression model was used to estimate the trend of rate per year. Findings From January 2003 to December 2016, 227 episodes of PVCR-BSI were identified among hospitalized patients at a university hospital. The mean age of patients was 67 years (standard deviation 14 years), 69% were male and the median Charlson score was 3 (interquartile range 2–5). Staphylococcus aureus caused 115 (50.7%) episodes. Thirty-day mortality was 13.2%. After implementation of the intervention, the incidence of PVCR-BSIs decreased significantly from 30 episodes in 2003 (1.17 episodes/10,000 patient-days) to eight episodes in 2016 (0.36/10,000 patient-days). The number of episodes caused by S. aureus decreased from 18 episodes in 2003 (0.70/10,000 patient-days) to three episodes in 2016 (0.14/10,000 patient-day), and mortality decreased from seven cases in 2003 (0.27/10,000 patient-days) to zero cases in 2016 (0.00/10,000 patient-days). Conclusions Surveillance, implementation of a multi-modal strategy and periodical assessment of healthcare workers' adherence to hospital guidelines led to a sustained reduction in PVCR-BSIs. This reduction had a major impact on S. aureus BSI rates and associated mortality.

FOSIMI Investigators., This work was supported by the Ministerio de Sanidad y Consumo of Spain (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Madrid, Spain, Grant #EC0800190). JMP received a “Rio Hortega” Research Grant (CM14/00135; 2015-16) from Instituto de Salud Carlos III and the Ministerio de Economia and Competitividad, Madrid (Spain) and the ESCMID/FEMS Research Fellowship 2016. JMM received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–19.

Surgical site infections (SSIs) are the leading cause of healthcare-associated infections in acute care hospitals in Europe. However, the risk factors for the development of early-onset (EO) and late-onset (LO) SSI have not been elucidated.This study investigated the predictive factors for EO-SSI and LO-SSI in a large cohort of patients undergoing colorectal surgery.We prospectively followed-up adult patients undergoing elective colorectal surgery in 10 hospitals (2011-2014). Patients were divided into three groups: EO-SSI, LO-SSI, or no infection (no-SSI). The cut-off defining EO-SSI and LO-SSI was seven days (median time to SSI development). Different predictive factors for EO-SSI and LO-SSI were analysed, comparing each group with the no-SSI patients.Of 3701 patients, 320 (8.6%) and 349 (9.4%) developed EO-SSI and LO-SSI, respectively. The rest had no-SSI. Patients with EO-SSI were mostly males, had colon surgery and developed organ-space SSI whereas LO-SSI patients frequently received chemotherapy or radiotherapy and had incisional SSI. Male sex (odds ratio (OR): 1.92; P 0.001), American Society of Anesthesiologists' physical status2 (OR: 1.51; P = 0.01), administration of mechanical bowel preparation (OR: 0.7; P = 0.03) and stoma creation (OR: 1.95; P 0.001) predicted EO-SSI whereas rectal surgery (OR: 1.43; P = 0.03), prolonged surgery (OR: 1.4; P = 0.03) and previous chemotherapy (OR: 1.8; P = 0.03) predicted LO-SSI.We found distinctive predictive factors for the development of SSI before and after seven days following elective colorectal surgery. These factors could help establish specific preventive measures in each group.

Summary Background Contaminated handwashing sinks have been identified as reservoirs that can facilitate colonization/infection of patients with multidrug-resistant (MDR) Gram-negative bacteria (GNB) in intensive care units (ICUs). Aim To assess the impact of removing patients' sinks and implementing other water-safe strategies on the annual rates of ICU-acquired MDR-GNB. Methods This six-year quasi-experimental study was conducted from January 2011 to December 2016. The intervention was carried out in August 2014 in two adult ICU wards with 12 rooms each. To assess the changes in annual MDR-GNB rates before and after the intervention, we used segmented regression analysis of an interrupted time-series. Crude relative risk (RR) rates were also calculated. Findings The incidence rates of MDR-GNB were 9.15 and 2.20 per 1000 patient-days in the pre- and post-intervention periods, respectively. This yielded a crude RR of acquiring MDR-GNB of 0.24 (95% confidence interval: 0.17–0.34). A significant change in level was observed between the MDR-GNB rate at the first point of the post-intervention period and the rate predicted by the pre-intervention time trend. Conclusion The implementation of a new water-safe policy, which included the removal of sinks from all patient rooms, successfully improved the control of MDR-GNB spread in an ICU with endemic infection. Our results support the contribution of sink use with the incidence of MDR-GNB in endemic environments.

Colorectal surgery; Mechanical bowel preparation; Oral antibiotic prophylaxis Cirugía colorrectal; Preparación mecánica del intestino; Profilaxis antibiótica oral Cirurgia colorrectal; Preparació mecànica de l'intestí; Profilaxi antibiòtica oral Background: The role of oral antibiotic prophylaxis (OAP) and mechanical bowel preparation (MBP) in the prevention of surgical site infection (SSI) after colorectal surgery is still controversial. The aim of this study was to analyze the effect of a bundle including both measures in a National Infection Surveillance Network in Catalonia. Methods: Pragmatic cohort study to assess the effect of OAP and MBP in reducing SSI rate in 65 hospitals, comparing baseline phase (BP: 2007-2015) with implementation phase (IP: 2016-2019). To compare the results, a logistic regression model was established. Results: Out of 34,421 colorectal operations, 5180 had SSIs (15.05%). Overall SSI rate decreased from 18.81% to 11.10% in BP and IP, respectively (OR 0.539, CI95 0.507-0.573, p < 0.0001). Information about bundle implementation was complete in 61.7% of cases. In a univariate analysis, OAP and MBP were independent factors in decreasing overall SSI, with OR 0.555, CI95 0.483-0.638, and OR 0.686, CI95 0.589-0.798, respectively; and similarly, organ/space SSI (O/S-SSI) (OR 0.592, CI95 0.494-0.710, and OR 0.771, CI95 0.630-0.944, respectively). However, only OAP retained its protective effect at both levels at multivariate analyses. Conclusions: oral antibiotic prophylaxis decreased the rates of SSI and O/S-SSI in a large series of elective colorectal surgery.

Introduction Methicillin-susceptibleStaphylococcus aureus(MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin againstS. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods We will perform a superiority, randomised, open-label, phase IV–III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. Trial registration number The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier:NCT03959345; Pre-results.

To determine current outcomes and predictors of treatment failure among patients with surgical site infection (SSI) after colorectal surgery.A multicentre observational prospective cohort study of adults undergoing elective colorectal surgery in 10 Spanish hospitals (2011-2014). Treatment failure was defined as persistence of signs/symptoms of SSI or death at 30 days post-surgery.Of 3701 patients, 669 (18.1%) developed SSI; 336 (9.1%) were organ-space infections. Among patients with organ-space SSI, 81.2% required source control: 60.4% reoperation and 20.8% percutaneous/transrectal drainage. Overall treatment failure rate was 21.7%: 9% in incisional SSIs and 34.2% in organ-space SSIs (p 0.001). Median length of stay was 15 days (IQR 9-22) for incisional SSIs and 24 days (IQR 17-35) for organ-space SSIs (p 0.001). One hundred and twenty-seven patients (19%) required readmission and 35 patients died (5.2%). Risk factors for treatment failure among patients with organ-space SSI were age ≥65 years (OR 1.83, 95% CI: 1.07-1.83), laparoscopy (OR 1.7, 95% CI: 1.06-2.77), and reoperation (OR 2.8, 95% CI: 1.7-4.6).Rates of SSI and treatment failure in organ-space SSI after elective colorectal surgery are notably high. Careful attention should be paid to older patients with previous laparoscopy requiring reoperation for organ-space SSI, so that treatment failure can be identified early.

Background Organ-space surgical site infections (SSI) are the most serious and costly infections after colorectal surgery. Most previous studies of risk factors for SSI have analysed colon and rectal procedures together. The aim of the study was to determine whether colon and rectal procedures have different risk factors and outcomes for organ-space SSI. Methods A multicentre observational prospective cohort study of adults undergoing elective colon and rectal procedures at 10 Spanish hospitals from 2011 to 2014. Patients were followed up until 30 days post-surgery. Surgical site infection was defined according to the Centers for Disease Control and Prevention criteria. Oral antibiotic prophylaxis (OAP) was considered as the administration of oral antibiotics the day before surgery combined with systemic intravenous antibiotic prophylaxis. Results Of 3,701 patients, 2,518 (68%) underwent colon surgery and 1,183 (32%) rectal surgery. In colon surgery, the overall SSI rate was 16.4% and the organ-space SSI rate was 7.9%, while in rectal surgery the rates were 21.6% and 11.5% respectively (p

Background: Short peripheral venous catheters are one of the most frequently used devices in hospitals. Peripheral venous catheter failure, defined as the unscheduled dysfunction of peripheral venous catheter, is common and frequently entails a new invasive procedure. Flushing the catheter maintains patency and could prolong peripheral venous catheter dwell time. The introduction of pre-filled saline flushing syringes as compared to manually filled saline flushing syringes could facilitate the frequency of catheter flushing, and subsequently it could reduce peripheral venous catheter failure rate. Objective: To demonstrate differences in overall peripheral venous catheter failure rates before and after the introduction of pre-filled saline flushing syringes and to assess the risk factors for peripheral venous catheter failure. Methods: Quasi-experimental design, before-and-after intervention study. Intervention: introduction of pre-filled saline syringes for flushing. Multicenter study conducted in medical and surgical wards of three European hospitals during a 9-month period (4 months pre-intervention, 5 months intervention). A multivariate Cox proportional model was used to identify factors associated with the occurrence of peripheral venous catheter failure. Results: Data from 3853 peripheral venous catheters in 1915 patients were analyzed. Compared to pre-intervention period, a significant decrease in peripheral venous catheter failure rate was observed in the intervention period (57% vs 43.4%, p Conclusion: The use of pre-filled saline syringes significantly reduced peripheral venous catheter failure and increased catheter dwell time. Thus, it is important to reinforce the use of the pre-filled syringes for flushing to reduce the incidence of peripheral venous catheters’ failure.

Background Although catheter-associated urinary tract infection (CA-UTI) is a major healthcare-related problem worldwide, there is a scarcity of current data from countries with high antimicrobial resistance rates. We aimed to determine the clinical outcomes of patients with CA-UTI compared to those of patients with other sources of complicated urinary tract infection (cUTI), and to assess the impact of antimicrobial resistance. We also aimed to identify the factors influencing 30-day mortality among patients with CA-UTI. Methods This was a multicentre, multinational retrospective cohort study including hospitalised adults with cUTI between January 2013 and December 2014 in twenty hospitals from eight countries from southern Europe, Turkey and Israel. The primary endpoint was 30-day mortality. The secondary endpoints were length of hospital stay, symptom improvement after 7 days’ treatment, symptom recurrence at 30 days and readmission 60 days after hospital discharge. Results Of the 807 cUTI episodes, 341 (42.2%) were CA-UTIs. The time from catheter insertion to cUTI diagnosis was less than 2 weeks in 44.6% of cases. Overall, 74.5% of cases had hospital or healthcare-acquired CA-UTI. Compared to patients with other cUTI aetiologies, those with CA-UTI had the following characteristics: they were more frequently males, older, admitted for a reason other than cUTI and admitted from a long-term care facility; had higher Charlson’s comorbidity index; and more frequently had polymicrobial infections and multidrug-resistant Gram-negative bacteria (MDR-GNB). Patients with CA-UTI also had significantly higher 30-day mortality rates (15.2% vs 6%) and longer hospital stay (median 14 [interquartile range -IQR- 7-27] days vs 8 [IQR 5–14] days) than patients with cUTI of other sources. After adjusting for confounders, CA-UTI was not independently associated with an increased risk of mortality (odds ratio, 1.40; 95% confidence interval, 0.77–2.54), and neither was the presence of MDR-GNB. Conclusions CA-UTI was the most frequent source of cUTI, affecting mainly frail patients. The mortality of patients with CA-UTI was high, though this was not directly related to the infection.

Summary Background Surveillance of surgical site infections (SSIs) is a core component of effective infection control practices, though its impact has not been quantified on a large scale. Aim To determine the time-trend of SSI rates in surveillance networks. Methods SSI surveillance networks provided procedure-specific data on numbers of SSIs and operations, stratified by hospitals' year of participation in the surveillance, to capture length of participation as an exposure. Pooled and procedure-specific random-effects Poisson regression was performed to obtain yearly rate ratios (RRs) with 95% confidence intervals (CIs), and including surveillance network as random intercept. Findings Of 36 invited networks, 17 networks from 15 high-income countries across Asia, Australia and Europe participated in the study. Aggregated data on 17 surgical procedures (cardiovascular, digestive, gynaecological-obstetrical, neurosurgical, and orthopaedic) were collected, resulting in data concerning 5,831,737 operations and 113,166 SSIs. There was a significant decrease in overall SSI rates over surveillance time, resulting in a 35% reduction at the ninth (final) included year of surveillance (RR: 0.65; 95% CI: 0.63–0.67). There were large variations across procedure-specific trends, but strong consistent decreases were observed for colorectal surgery, herniorrhaphy, caesarean section, hip prosthesis, and knee prosthesis. Conclusion In this large, international cohort study, pooled SSI rates were associated with a stable and sustainable decrease after joining an SSI surveillance network; a causal relationship is possible, although unproven. There was heterogeneity in procedure-specific trends. These findings support the pivotal role of surveillance in reducing infection rates and call for widespread implementation of hospital-based SSI surveillance in high-income countries.

Background Although surgical site infection after craniotomy (SSI-CRAN) is a serious complication, risk factors for its development have not been well defined. We aim to identify the risk factors for developing SSI-CRAN in a large prospective cohort of adult patients undergoing craniotomy. Methods A series of consecutive patients who underwent craniotomy at a university hospital from January 2013 to December 2015 were prospectively assessed. Demographic, epidemiological, surgical, clinical and microbiological data were collected. Patients were followed up in an active post-discharge surveillance programm e for up to one year after surgery. Multivariate analysis was carried out to identify independent risk factors for SSI-CRAN. Results Among the 595 patients who underwent craniotomy, 91 (15.3%) episodes of SSI-CRAN were recorded, 67 (73.6%) of which were organ/space. Baseline demographic characteristics were similar among patients who developed SSI-CRAN and those who did not. The most frequent causative Gram-positive organisms were Cutibacterium acnes (23.1%) and Staphylococcus epidermidis (23.1%), whereas Enterobacter cloacae (12.1%) was the most commonly isolated Gram-negative agent. In the univariate analysis the factors associated with SSI-CRAN were ASA score > 2 (48.4% vs. 35.5% in SSI-CRAN and no SSI-CRAN respectively, p = 0.025), extrinsic tumour (28.6% vs. 19.2%, p = 0.05), and re-intervention (4.4% vs. 1.4%, p = 2 (AOR: 2.26, 95% CI: 1.32–3.87; p = .003) and re-intervention (OR: 8.93, 95% CI: 5.33–14.96; p

Surgical site infections (SSIs) are among the most common healthcare-associated infections, and contribute significantly to patient morbidity and healthcare costs. Staphylococcus aureus is the most common microbial cause. The epidemiology of S. aureus is changing with the dissemination of newer clones and the emergence of mupirocin resistance. The prevention and control of SSIs is multi-modal, and this article reviews the evidence on the value of screening for nasal carriage of S. aureus and subsequent decolonization of positive patients pre-operatively. Pre-operative screening, using culture- or molecular-based methods, and subsequent decolonization of patients who are positive for meticillin-susceptible S. aureus and meticillin-resistant S. aureus (MRSA) reduces SSIs and hospital stay. This applies especially to major clean surgery, such as cardiothoracic and orthopaedic, involving the insertion of implanted devices. However, it requires a multi-disciplinary approach coupled with patient education. Universal decolonization pre-operatively without screening for S. aureus may compromise the capacity to monitor for the emergence of new clones of S. aureus, contribute to mupirocin resistance, and prevent the adjustment of surgical prophylaxis for MRSA (i.e. replacement of a beta-lactam agent with a glycopeptide or alternative).

Background Mortality rates from Staphylococcus aureus bacteremia are high and have only modestly improved in recent decades. We compared the efficacies of a β-lactam in combination with daptomycin (BL/D-C) and β-lactam monotherapy (BL-M) in improving clinical outcomes in methicillin-susceptible S. aureus (MSSA) bacteremia. Methods A retrospective cohort study of MSSA bacteremia was performed in a tertiary hospital from January 2011 to December 2017. Patients receiving BL/D-C and BL-M were compared to assess 7-, 30-, and 90-day mortality rates. A 1:2 propensity score matching analysis was performed. Differences were assessed using Cox regression models. Results Of the 514 patients with MSSA bacteremia, 164 were excluded as they had received combination therapies other than BL/D-C, had pneumonia, or died within 48 hours of admission. Of the remaining 350 patients, 136 and 214 received BL/D-C and BL-M, respectively. BL/D-C patients had higher Pitt scores and persistent bacteremia more often than BL-M patients. In the raw analysis, there were no differences in mortality rates between groups. After propensity score matching, there were no significant differences between the BL/D-C (110 patients) and BL-M (168 patients) groups for all-cause mortality rates at 7 days (8.18% vs 7.74%; P = 1.000), 30 days (17.3% vs 16.1%; P = .922), and 90 days (22.7% vs 23.2%; P = 1.000), even in a subanalysis of patients with high-risk source of infection and in a subgroup excluding catheter-related bacteremia. Conclusions BL/D-C failed to reduce mortality rates in patients with MSSA bacteremia. Treatment strategies to improve survival in MSSA bacteremia are urgently needed.

Background The purpose of this study was to analyze the secular trends of infective endocarditis in a teaching hospital between January 1996 and December 2015. Methods We report on a single-center retrospective study of patients with left-side valve infective endocarditis. We performed an analysis of secular trends in the main epidemiological and etiological aspects, as well as clinical outcomes, in 5 successive 4-year periods (P1 to P5). Results In total, 595 episodes of infective endocarditis were included, of which 76% were community-acquired and 31.3% involved prosthetic valves. Among the cases, 70% occurred in men, and the mean age (SD) was 64.1 (14.3) years. A significant increase in older patients (age ≥70 years) between P1 (15.332%) and P5 (51.9%; P < .001) was observed. The rate of infective endocarditis on biological prostheses also increased in the prosthetic group, accounting for 30% in P1 and 67.3% in P5 (P < .001). By contrast, there were significant decreases in vascular and immunological phenomena over the study period, with decreases in the presence of moderate to severe valvular insufficiency (75.9% in P1 to 52.6% in P5; P < .001) and valvular surgery (43% in P1 vs 29.6% in P5; P = .006). Finally, overall mortality was 23.9%, and although it was highest in P1, it subsequently remained stable through P2 to P5 (38% in P1 to 20% in P5; P = .004). Conclusions There has been a significant increase in infective endocarditis in older patients. The decrease in moderate to severe valve regurgitation at diagnosis could explain the stable mortality despite the increase in the mean age of patients over time.

Aina Gomila,1,2 JCarratalà,1–3 N Eliakim-Raz,4 E Shaw,1,2 I Wiegand,5 LVallejo-Torres,6 A Gorostiza,2 JM Vigo,7 S Morris,6 M Stoddart,8 S Grier,8 C Vank,5 N Cuperus,9 L Van den Heuvel,9 C Vuong,5 A MacGowan,8 L Leibovici,4 I Addy,5 M Pujol1,2 On behalf of COMBACTE MAGNET WP5 RESCUING Study Group and Study Sites 1Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut Català de la Salut (ICS-HUB), Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; 2Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain; 3Infectious Diseases Department, University of Barcelona, Barcelona, Spain; 4Department of Medicine E, Beilinson Hospital, Rabin Medical Center, Petah-Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Israel; 5AiCuris Anti-infective Cures, Wuppertal, Germany; 6UCL Department of Applied Health Research, University College London, London, UK; 7Informatics Unit, Fundació Institut Català de Farmacologia, Barcelona, Spain; 8Department of Medical Microbiology, Southmead Hospital, North Bristol NHS Trust, Bristol, UK; 9Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands Purpose: Complicated urinary tract infections (cUTIs) are among the most frequent health-care-associated infections. In patients with cUTI, Pseudomonas aeruginosa deserves special attention, since it can affect patients with serious underlying conditions. Our aim was to gain insight into the risk factors and prognosis of P. aeruginosa cUTIs in a scenario of increasing multidrug resistance (MDR). Methods: This was a multinational, retrospective, observational study at 20 hospitals in south and southeastern Europe, Turkey, and Israel including consecutive patients with cUTI hospitalized between January 2013 and December 2014. A mixed-effect logistic regression model was performed to assess risk factors for P. aeruginosa and MDR P. aeruginosa cUTI.Results: Of 1,007 episodes of cUTI, 97 (9.6%) were due to P. aeruginosa. Resistance rates of P. aeruginosa were: antipseudomonal cephalosporins 35 of 97 (36.1%), aminoglycosides 30 of 97 (30.9%), piperacillin–tazobactam 21 of 97 (21.6%), fluoroquinolones 43 of 97 (44.3%), and carbapenems 28 of 97 (28.8%). The MDR rate was 28 of 97 (28.8%). Independent risk factors for P. aeruginosa cUTI were male sex (OR 2.61, 95% CI 1.60–4.27), steroid therapy (OR 2.40, 95% CI 1.10–5.27), bedridden functional status (OR 1.79, 95% CI 0.99–3.25), antibiotic treatment within the previous 30 days (OR 2.34, 95% CI 1.38–3.94), indwelling urinary catheter (OR 2.41, 95% CI 1.43–4.08), and procedures that anatomically modified the urinary tract (OR 2.01, 95% CI 1.04–3.87). Independent risk factors for MDR P. aeruginosa cUTI were age (OR 0.96, 95% CI 0.93–0.99) and anatomical urinary tract modification (OR 4.75, 95% CI 1.06–21.26). Readmission was higher in P. aeruginosa cUTI patients than in other etiologies (23 of 97 [23.7%] vs 144 of 910 [15.8%], P=0.04), while 30-day mortality was not significantly different (seven of 97 [7.2%] vs 77 of 910 [8.5%], P=0.6).Conclusion: Patients with P. aeruginosa cUTI had characteristically a serious baseline condition and manipulation of the urinary tract, although their mortality was not higher than that of patients with cUTI caused by other etiologies. Keywords: health care-associated infections, complicated urinary tract infections, Pseudomonas aeruginosa, multidrug-resistance

Summary Background Accounting for time-dependency and competing events are strongly recommended to estimate excess length of stay (LOS) and risk of death associated with healthcare-associated infections. Aim To assess the effect of organ/space (OS) surgical site infection (SSI) on excess LOS and in-hospital mortality in patients undergoing elective colorectal surgery (ECS). Methods A multicentre prospective adult cohort undergoing ECS, January 2012 to December 2014, at 10 Spanish hospitals was used. SSI was considered the time-varying exposure and defined as incisional (superficial and deep) or OS. Discharge alive and death were the study endpoints. The mean excess LOS was estimated using a multistate model which provided a weighted average based on the states patients passed through. Multivariate Cox regression models were used to assess the effect of OS-SSI on risk of discharge alive or in-hospital mortality. Findings Of 2778 patients, 343 (12.3%) developed SSI: 194 (7%) OS-SSI and 149 (5.3%) incisional SSI. Compared to incisional SSI or no infection, OS-SSI prolonged LOS by 4.2 days (95% confidence interval (CI): 4.1–4.3) and 9 days (8.9–9.1), respectively, reduced the risk of discharge alive (adjusted hazard ratio (aHR): 0.36 (95% CI: 0.28–0.47) and aHR: 0.17 (0.14–0.21), respectively), and increased the risk of in-hospital mortality (aHR: 8.02 (1.03–62.9) and aHR: 10.7 (3.7–30.9), respectively). Conclusion OS-SSI substantially extended LOS and increased risk of death in patients undergoing ECS. These results reinforce OS-SSI as the SSI with the highest health burden in ECS.

Objective Complicated urinary tract infections (cUTIs) impose a high burden on healthcare systems and are a frequent cause of hospitalisation. The aims of this paper are to estimate the cost per episode of patients hospitalised due to cUTI and to explore the factors associated with cUTI-related healthcare costs in eight countries with high prevalence of multidrug resistance (MDR). Design This is a multinational observational, retrospective study. The mean cost per episode was computed by multiplying the volume of healthcare use for each patient by the unit cost of each item of care and summing across all components. Costs were measured from the hospital perspective. Patient-level regression analyses were used to identify the factors explaining variation in cUTI-related costs. Setting The study was conducted in 20 hospitals in eight countries with high prevalence of multidrug resistant Gram-negative bacteria (Bulgaria, Greece, Hungary, Israel, Italy, Romania, Spain and Turkey). Participants Data were obtained from 644 episodes of patients hospitalised due to cUTI. Results The mean cost per case was €5700, with considerable variation between countries (largest value €7740 in Turkey; lowest value €4028 in Israel), mainly due to differences in length of hospital stay. Factors associated with higher costs per patient were: type of admission, infection source, infection severity, the Charlson comorbidity index and presence of MDR. Conclusions The mean cost per hospitalised case of cUTI was substantial and varied significantly between countries. A better knowledge of the reasons for variations in length of stays could facilitate a better standardised quality of care for patients with cUTI and allow a more efficient allocation of healthcare resources. Urgent admissions, infections due to an indwelling urinary catheterisation, resulting in septic shock or severe sepsis, in patients with comorbidities and presenting MDR were related to a higher cost.

We investigated whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to perform in vitro time-kill studies using standard (10 6 ) and high (10 8 ) inocula. Combined therapy was compared to daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied, and the equivalents of cloxacillin at 2 g/4 h, fosfomycin at 2 g/6 h, and daptomycin at 6 to 10 mg/kg/day were administered intravenously. A combination of daptomycin and either fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 μg/ml) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/day in terms of both the proportion of sterile vegetations (100% versus 72%, P = 0.046) and the decrease in the density of bacteria within the vegetations ( P = 0.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/day (100% versus 93%, P = 1.00) and had activity similar to that of daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/day (100% versus 88%, P = 0.48). Daptomycin nonsusceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.

Case-fatality rates for Staphylococcus aureus bacteremia (SAB) remain unacceptably high and have improved only modestly in recent decades. Treatment of SAB is still a clinical challenge, especially if methicillin-resistant strains are involved. New drugs with anti-staphylococcal activity are currently available, and their role as alternatives to standard therapies is being investigated. Areas covered: In this review, we give an update of the current available antibiotics for the treatment of SAB. We provide information regarding the pharmacological characteristics, the accepted indications, and the most important adverse events of the old and new anti-staphylococcal agents, as well as the existing evidence on their use for the treatment of SAB. Expert opinion: The management of patients with SAB is very complex and needs a multidisciplinary approach. There are currently new available options for the treatment of methicillin-resistant SAB. However, more data from clinical trials are needed to assign specific roles to each antibiotic and to include them in the new antibacterial armamentarium. The role of combination therapy for the treatment of increasingly complex patients with SAB deserves thorough investigation.

Summary Background Vascular catheter-related bloodstream infections (CRBSIs) are highly preventable hospital-acquired infections and a major threat to patient safety. While there is significant information regarding CRBSI outcome among intensive care unit (ICU) patients, data regarding non-ICU patients are scarce. Aim To determine the risk factors associated with 30-day mortality among non-ICU patients with nosocomial CRBSIs. Methods Prospective cohort study of non-ICU patients with nosocomial CRBSIs in a tertiary care centre between January 2004 and December 2014. The primary outcome was 30-day mortality, defined as death from any cause within 30 days of CRBSI. Follow-up was performed 30 days after CRBSI onset. Time until death was the dependent variable in Cox regression analysis. Findings In total, 546 cases of CRBSI were identified. The mean age of patients was 64.5 years [interquartile range (IQR) 55–75 years], 66% were male, and the mean Charlson score was 3.59 (IQR 2–5). Of the 546 cases, 58.4% resulted from central venous catheters and 41.6% from peripheral venous catheters. The causative agents were Gram-positive cocci (70.1% of cases), Gram-negative bacilli (31.1%) and Candida spp. (1%). Mortality within 30 days was 13.9%, with no significant changes over the study period. Independent risk factors for 30-day mortality were Charlson score ≥4 [hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.19–2.73], Staphylococcus aureus infection (HR 2.67, 95% CI 1.61–4.43) and Candida spp. infection (HR 6.1, 95% CI 2.08–18.04). Age; area of admission; type, use and site of vascular catheter; and administration of appropriate empirical antibiotic treatment were not independent risk factors for 30-day mortality. Conclusion Nosocomial CRBSIs outside ICUs are associated with high risk of mortality, particularly among patients with a higher Charlson score and bloodstream infections caused by Staphylococcus aureus and Candida spp.

Even with appropriate clinical management, complicated methicillin-susceptible Staphylococcus aureus (MSSA) catheter-related bacteremia (CRB) is frequent. We investigated the influence of molecular characteristics of MSSA strains on the risk of complicated bacteremia (CB) in MSSA-CRB. A multicenter prospective study was conducted in Spain between 2011 and 2014 on MSSA-CRB. Optimized protocol-guided clinical management was required. CB included endocarditis, septic thrombophlebitis, persistent bacteremia and/or end-organ hematogenous spread. Molecular typing, agr functionality and DNA microarray analysis of virulence factors were performed in all MSSA isolates. Out of 83 MSSA-CRB episodes included, 26 (31.3%) developed CB. MSSA isolates belonged to 16 clonal complexes (CCs), with CC30 (32.5%), CC5 (15.7%) and CC45 (13.3) being the most common. Comparison between MSSA isolates in episodes with or without CB revealed no differences regarding agr type and functionality. However, our results showed that CC15 and the presence of genes like cna, chp and cap8 were associated with the development of CB. The multivariate analysis highlighted that the presence of cna (Hazard ratio 2.9; 95% CI 1.14-7.6) was associated with the development of CB. Our results suggest that particular CCs and specific genes may influence the outcome of MSSA-CRB.

Results: One hundred and one patients were included in the analysis; 68 (67.3%) received MT and 33 (32.7%) received CT. Pneumonia was the most common infection (50.5%), 68.6% of cases being associated with mechanical ventilation. Colistin (67.6%) and carbapenems (14.7%) were the most common drugs used in MT; colistin plus tigecycline (27.3%) and carbapenem plus tigecycline (12.1%) were the most frequent combinations. Crude 30 day mortality was 23.5% and 24.2% for the MT and CT groups, respectively (RR ¼ 1.03; 95% CI 0.49 – 2.16; P ¼ 0.94). Multivariate analysis of 30 day survival showed no trend towards reduced 30 day mortality with CT (HR ¼1.35; 95% CI 0.53–3.44; P ¼ 0.53). Subgroup analysis showed similar results. Conclusions: Our data do not support an association of CT with reduced mortality in MDRAB infections. More data for specific types of infection and combinations are needed.

Infections related to the health-care system are those associated with health care practices in hospitalized patients as well as in out-patients with health-care contact. Nosocomial infections affect 5% of in-patients, and carry a high morbidity, mortality and economic cost. The main types of nosocomial infections are related to invasive procedures, and include respiratory tract infection, surgical site infections, urinary tract infections, and vascular catheter bacteremia. It has been shown that the application of checklists and a bundle of measures are useful in preventing these infections. Epidemiological surveillance, defined as the gathering of information to take actions, is the basis of infection control programs. These have evolved from a global surveillance targeted at processes and indicators of nosocomial infection. The comparison of these indicators can be useful in establishing preventive measures.

The prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa has increased over the past decade and a significant rise in these isolates in ventilator-associated pneumonia (VAP) has been observed. However, the impact of MDR on VAP outcome has not been analysed in depth. We investigated the risk factors for early and crude mortality in a retrospective study of microbiologically and clinically documented VAP. Ninety-one VAP episodes in 83 patients were included, 31 caused by susceptible P. aeruginosa and 60 by MDR strains, of which 42 (70 %) were extensively drug-resistant (XDR) P. aeruginosa. Thirteen episodes concomitantly presented P. aeruginosa bacteraemia, in seven of which the origin was the respiratory tract. Whereas susceptible P. aeruginosa episodes were more likely than MDR episodes to receive adequate empirical (68 % vs. 30 %; p

Patients infected with these bacteria were more likely to have local endovascular complications., We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011–June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2–5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1–5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications.

In the 1950s an unusually virulent and transmissible penicillin-resistant Staphylococcus aureus clone harbouring Panton-Valentine leukocidin (PVL) genes, known as phage type 80/81 and subsequently identified as multilocus sequence type (ST) 30, emerged and caused serious infections in hospitals and the community. We describe an outbreak of skin infections caused by a PVL-positive, methicillin-susceptible S. aureus (MSSA) strain of ST1472, related to phage type 80/81, in three associated occupational centres. After identification of the first patient an active case-finding strategy was initiated among the three centres. Epidemiological and clinical features were indistinguishable from outbreaks currently caused by community-acquired methicillin-resistant S. aureus. The S. aureus was cultured and identified from nasal swabs and skin lesions by conventional methods; PVL was detected using a PCR assay. Pulsed-field gel electrophoresis and DNA-array-based genotyping were applied to MSSA isolates. MSSA was identified in nasal swabs from 49 of 133 individuals (37%). A single pulsed-field gel electrophoresis pattern, belonging to ST1472 (CC30) and PVL positivity, were detected in 20 individuals, including eight of 18 skin cultures, i.e. 15% of the screened individuals were colonized by the epidemic strain. Nasal and cutaneous decontamination with 5% nasal mupirocin ointment and 2% aqueous chlorhexidine was implemented for all individuals. Patients with active skin infections were treated with a first-generation cephalosporin. General recommendations were made to prevent cross-transmission. No new cases were reported over the following 90 days.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of healthcare-related infection. Surveillance and prevention of MRSA is a priority in infection control programs. The aim of this study was to describe rates and trends of MRSA colonization or infection in 40 hospitals participating in the VINCat Program from 2008 to 2010. The study included all patients treated in acute care areas of participating hospitals. Hospitals were stratified into 3 groups based on size. The following annual indicators were reported: Methicillin-resistance rate, incidence density of new cases of MRSA and incidence density of MRSA bacteremia. Between 2008 and 2010, the yearly mean rate of resistance to methicillin remained stable for the study period (24%–25%), while the mean incidence of new cases of MRSA decreased from 0.65 to 0.54 cases per 1000 patient-days (p=NS) and the mean incidence of MRSA bacteremia decreased from 0.06 to 0.05 cases per 1,000 patient-days (p=NS). The implementation of a MRSA surveillance system in hospitals that participated in the VINCat Program provides information on the situation of each institution and facilitated interhospital comparisons in order to establish appropriate preventive measures.

The VINCat Program is a standardized surveillance program of healthcare infections in Catalonia, Spain. This program includes monitoring of surgical site infections (SSI) of elective colorectal surgery. The aim of this study was to define SSI rates in colorectal surgery among VINCat hospitals over a period of 4 years. We included consecutive elective colorectal interventions performed in VINCat hospitals from 2007 to 2010. Follow-up visits were performed 30 days after surgery. Prospective monitoring of SSI in colorectal surgery was performed according to standardized VINCat methodology. SSI was defined according to the Centers for Disease Control (CDC) and surgical risk factors according to the National Healthcare Safety Network (NHSN) classification. From 2007 to 2010, 49 centers performed 10,104 surgical procedures. The cumulative incidence of SSI was 20.8% (95% CI: 20.03-21.63). The annual cumulative SSI incidence rate did not vary significantly over the study period; however, there were significant differences among hospital infection rates. The relative frequency of organ-space infection increased from 25% in 2007 to 40% in 2010 (p

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) is a cause of concern in health systems all over the world, due to the high incidence rates and the associated undesirable outcomes. In our tertiary 900-bed university hospital, all episodes of MRSA-BSI have been prospectively followed up since the identification of the first episode in 1990. We conducted the current study to report changes in the epidemiology of MRSA-BSI over the 19-year period between 1990 and 2008, comparing 4 periods (1990-1994, 1995-1999, 2000-2004, and 2005-2008). Overall, 524 patients developed MRSA-BSI. Cumulative incidence was 10.0 episodes/100,000 patient days (range, 1.3-17.4). Although no trend in the incidence rate was observed between the 4 consecutive periods, significant upward trends in patient age and comorbidities, health care acquisition, and non-intravascular catheter source were all identified (p < 0.05). While the Iberian clone (ST247/SCCmecI) was dominant during the first and second periods, almost all the strains isolated in the subsequent periods belonged to Clonal Complex 5 (ST125/SCCmecIV and ST228/SCCmecI). A significant downward trend in vancomycin geometric minimum inhibitory concentration (MIC) was also observed from 2.04 mg/L to 0.88 mg/L, coinciding with the clonal replacement and the reduction in the hospital vancomycin prescription. Therefore, no MRSA vancomycin MIC creep was observed since higher MICs were associated with strains belonging to the Iberian clone. Glycopeptides were the most frequently used antibiotics for MRSA-BSI during all 4 periods. No differences in MRSA-BSI outcomes were found, and the mortality rate at 30 days was close to 29% in each of the 4 periods. In conclusion, we identified significant changes in demographic and clinical characteristics and in the molecular epidemiology of MRSA-BSI during the study period, but found no significant trends in cumulative incidence or in overall mortality rate.