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Objectives To determine the health status, exercise capacity, and health related quality of life (HRQoL) of COVID-19 associated acute respiratory distress syndrome (ARDS) survivors, 8 months after diagnosis. Methods All eligible patients were interviewed and underwent a physical examination, chest X-ray, and 6 min walk test (6MWT). Scales to evaluate post-traumatic stress disorder, depression, anxiety, and HRQoL were applied. Results Of 1295 patients, 365 suffered ARDS and 166 survived to hospital discharge. Five died after discharge and 48 were lost to follow-up. Of the 113 remaining patients, 81% had persistent symptoms. More than 50% of patients completed less than 80% of the theoretical distance on the 6MWT, 50% had an abnormal X-ray and 93% of patients developed psychiatric disorders. Mean SF-36 scores were worse than in the general population. After multivariate regression analysis, female sex, non-Caucasian race, and Charlson index>2 were independent risk factors for a worse mental health component summary score on the SF-36, and age was associated with a better prognosis. Female sex and chronic obstructive pulmonary disease were independently associated with a worse physical component summary score. Conclusion COVID-19 associated ARDS survivors have long-term consequences in health status, exercise capacity, and HRQoL. Strategies addressed to prevent these sequelae are needed.

We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB22TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD81 T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-g) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2-TB1 value.0.6 IU.ml(-1) was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB2-TB1 result of >0.6 IU.ml(-1) and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2-TB1 difference of.0.6 IU.ml(-1) was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection. IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-gamma) release assay, a difference in IFN-gamma production between the two antigen tubes (TB2 minus TB1) of.0.6 IU.ml(-1) could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN- g in TB1 and TB2 tubes that were higher than 0.6 IU.ml(-1). QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing. Funding Agencies|Department of Clinical Sciences of the University of Barcelona

The clinical value of transanal total mesorectal excision is debated.This study aimed to compare short- and medium-term effects of transanal versus anterior total mesorectal excision for rectal cancer.This was a multicenter retrospective cohort study.The study included all Catalonian public hospitals.All patients receiving transanal or anterior total mesorectal excision (open or laparoscopic) for nonmetastatic primary rectal cancer in 2015 to 2016 were included.Data on vital status were collected to March 2019. Between-group differences were minimized by applying propensity score matching to baseline patient characteristics. Competing risk models were used to assess systemic and local recurrence along with death at 2 years, and multivariable Cox regression was used to assess 2-year disease-free survival. Results are expressed with their 95% CIs.The final subsample was 537 patients receiving total mesorectal excision (transanal approach: n = 145; anterior approach: n = 392). Median follow-up was 39.2 months (interquartile range, 33.0-45.8). Accounting for death as a competing event, there was no association between transanal total mesorectal excision and local recurrence (matched subhazard ratio 1.28, 95% CI 0.55-2.96). There were no statistical differences in the comparative rate of local recurrence (transanal: 1.77 per 100 person-years, 95% CI 0.76-3.34; anterior: 1.37 per 100 person-years, 95% CI 0.8-2.15) or mortality (transanal: 3.98 per 100 person-years, 95% CI 2.36-6.16; anterior: 2.99 per 100 person-years, 95% CI 2.1-4.07). Groups presented similar 2-year cumulative incidence of local recurrence (4.83% versus 3.57%) and disease-free survival (HR, 1.33; 95% CI 0.92-1.92).We used data only from the public system, the study is retrospective, and data on individual surgeons are not reported.These population-based results support the use of either the transanal, open, or laparoscopic approach for rectal cancer in Catalonia. See Video Abstract at http://links.lww.com/DCR/B744.ESCISIÓN MESORRECTAL TOTAL TRANSANAL VERSUS ESCISIÓN MESORRECTAL TOTAL ANTERIOR PARA EL CÁNCER DE RECTO: UN ESTUDIO POBLACIONAL CON EMPAREJAMIENTO DE PUNTAJE DE PROPENSIÓN EN CATALUÑA, ESPAÑA.Se debate el valor clínico de la escisión mesorrectal total transanal.Comparar los efectos a corto y mediano plazo de la escisión mesorrectal total transanal versus anterior para el cáncer de recto.Este fue un estudio de cohorte retrospectivo multicéntrico.El estudio incluyó a todos los hospitales públicos de Cataluña.Todos los pacientes no metastásicos que recibieron escisión mesorrectal total anterior o transanal (abierta o laparoscópica) por cáncer de recto primario en 2015-16.Los datos sobre el estado vital se recopilaron hasta marzo de 2019. Las diferencias entre los grupos se minimizaron aplicando el emparejamiento de puntajes de propensión a las características iniciales del paciente. Se utilizaron modelos de riesgo competitivo para evaluar la recurrencia sistémica y local junto con la muerte a los dos años, y la regresión de Cox multivariable para evaluar la supervivencia libre de enfermedad a dos años. Los resultados se expresan con sus intervalos de confianza del 95%.La submuestra final fue de 537 pacientes que recibieron escisión mesorrectal total (abordaje transanal: n = 145; abordaje anterior: n = 392). La mediana de seguimiento fue de 39,2 meses (rango intercuartílico 33,0-45,8). Teniendo en cuenta la muerte como un evento competitivo, no hubo asociación entre la escisión mesorrectal total transanal y la recurrencia local (cociente de subriesgo apareado 1,28, 0,55-2,96). No hubo diferencias estadísticas en la tasa comparativa de recurrencia local (transanal: 1,77 por 100 personas-año, 0,76-3,34; anterior: 1,37 por 100 personas-año, 0,8-2,15) o mortalidad (transanal: 3,98 por 100 personas-año, 2,36-6,16; anterior: 2,99 por 100 personas-año, 2,1-4,07). Los grupos presentaron una incidencia acumulada de dos años similar de recidiva local (4,83% frente a 3,57%, respectivamente) y supervivencia libre de enfermedad (índice de riesgo 1,33, 0,92-1,92).Utilizamos datos solo del sistema público, el estudio es retrospectivo y no se informan datos sobre cirujanos individuales.Estos resultados poblacionales apoyan el uso del abordaje transanal, abierto o laparoscópico para el cáncer de recto en Cataluña. Consulte. Video Resumen en http://links.lww.com/DCR/B744. (Traducción- Dr. Francisco M. Abarca-Rendon).

Outcomes of kidney transplantation (KT) after controlled circulatory death (cDCD) with highly expanded criteria donors (ECD) and recipients have not been thoroughly evaluated. We analyzed in a multicenter cohort of 1161 consecutive KT, granular baseline donor and recipient factors predicting transplant outcomes, selected by bootstrapping and Cox proportional hazards, and were validated in a contemporaneous European KT cohort (n = 1585). 74.3% were DBD and 25.7% cDCD-KT. ECD-KT showed the poorest graft survival rates, irrespective of cDCD or DBD (log-rank

IntroductionAntibiotic overuse is directly related to antibiotic resistance, and primary care is one of the main reasons for this overuse. This study aims to demonstrate that including experts on infectious diseases (ID) within the antimicrobial stewardship (AMS) programme team in primary care settings achieves higher reductions in overall antibiotic consumption and increases the quality of prescription.Methods and analysisA multicentre, cluster-randomised, blinded clinical trial will be conducted between 2021 and 2023. Six primary care centres will be randomly assigned to an advanced or a standard AMS programme. The advanced AMS programme will consist of a standard AMS programme combined with the possibility that general practitioners (GP) will discuss patients’ therapies with ID experts telephonically during working days and biweekly meetings. The main endpoint will be overall antibiotic consumption, defined as daily defined dose per 1000 inhabitants per day (DHD). Secondary end-points will be: (1) unnecessary antibiotic prescriptions in patients diagnosed with upper respiratory tract or urinary tract infection, (2) adequacy of antibiotic prescription, (3) reattendance to GP or emergency room within 30 days after the initial GP visit and (4) hospital admissions for any reason within 30 days after the GP visit. Two secondary endpoints (unnecessary antibiotic therapy and adequacy of therapy) will be evaluated by blinded investigators.We will select three clusters (centres) per arm (coverage of 147 644 inhabitants) which will allow the rejection of the null hypothesis of equal consumption with a power of 80%, assuming a moderate intracluster correlation of 0.2, an intracluster variance of 4 and a mean difference of 1 DHD. The type I error will be set at 5%.Ethics and disseminationThe protocol was reviewed and approved by local ethics committees. The results of this study will be published in peer-reviewed journals and presented at medical conferences.Trial registration numberNCT04848883

Bisphosphonates are the first-line treatment for preventing fractures in osteoporosis patients. However, their use is contraindicated or to be used with caution in chronic kidney disease (CKD) patients, primarily because of a lack of information about their safety and effectiveness. We aimed to investigate the safety of oral bisphosphonates in patients with moderate to severe CKD, using primary-care electronic records from two cohorts, CPRD GOLD (1997-2016) and SIDIAP (2007-2015) in the UK and Catalonia, respectively. Both databases were linked to hospital records. SIDIAP was also linked to end-stage renal disease registry data. Patients with CKD stages 3b to 5, based on two or more estimated glomerular filtration rate measurements less than 45 mL/min/1.73 m2 , aged 40 years or older were identified. New bisphosphonate users were propensity score-matched with up to five non-users to minimize confounding within this population. Our primary outcome was CKD stage worsening (estimated glomerular filtration rate [eGFR] decline or renal replacement therapy). Secondary outcomes were acute kidney injury, gastrointestinal bleeding/ulcers, and severe hypocalcemia. Hazard ratios (HRs) were estimated using Cox regression and Fine and Gray sub-HRs were calculated for competing risks. We matched 2447 bisphosphonate users with 8931 non-users from CPRD and 1399 users with 6547 non-users from SIDIAP. Bisphosphonate use was associated with greater risk of CKD progression in CPRD (sub-HR [95% CI]: 1.14 [1.04, 1.26]) and SIDIAP (sub-HR: 1.15 [1.04, 1.27]). No risk differences were found for acute kidney injury, gastrointestinal bleeding/ulcers, or hypocalcemia. Hence, we can conclude a modest (15%) increased risk of CKD progression was identified in association with bisphosphonate use. No other safety concerns were identified. Our findings should be considered before prescribing bisphosphonates to patients with moderate to severe CKD. © 2020 American Society for Bone and Mineral Research (ASBMR).

Peri-implant fractures occur in association with an implant, used to treat a previous injury that is still attached to the bone. We recently published a proposal for a classification system for peri-implant femoral fractures [Videla-Cés, Injury,2019].To assess the agreement of our classification system for peri-implant femoral fractures among a group of future users of said classification system.A prospective, multicentre, international agreement pilot study was conducted among a group of independent traumatologists/orthopaedic surgeons (evaluators): senior (a minimum of 10 years' experience) and junior (in fourth or fifth training year). A set of 30 radiographs of peri-implant femoral fractures were selected (stratified into 3 levels of difficulty: low, medium and high). Each evaluator interpreted the radiographs on 2 different occasions separated by a period of one month and in a different order each time. The level of difficulty was masked from the evaluators and they had one week to classify the radiographs each time. Logistic regression and Cohen's kappa coefficient (κ) and its 95% confidence interval (95%CI) were used to assess the accuracy and agreement, both intra- and inter-evaluator. Between senior and junior surgeons was performed an exploratory analysis.35 traumatologists/orthopaedic surgeons (17 senior and 18 junior) from 16 tertiary hospitals from 4 countries acted as evaluators. The accuracy, percentage of correct classifications (2 digits and 3 letters), in the first and second evaluation was: 56% (95%CI: 53-59%) and 55% (95%CI: 51-57%), respectively. (insert space) Negligible differences were found between junior and senior evaluators (first evaluation, OR: 1.46, 95%CI: 0.82-2.61, p-value: 0.199; second evaluation, OR: 1.06, 95%CI: 0.56-2.00, p-value: 0.860). (insert space) Both medium and low radiograph difficulty were associated with a lower probability of an incorrect classification compared with those of high difficulty (first evaluation, OR: 7.60, 95%CI: 5.24-11.05, p-value:0.001; OR: 14.15, 95%CI: 9.12-21.96, p-value:0.001, respectively; second evaluation, OR: 7.11, 95%CI: 4.88-10.38, p-value:0.001, OR: 15.28, 95%CI: 9.77-23.89, p-value:0.001). (insert space) The kappa for intra-observer agreement between the first and second evaluation was: 0.66, 95%CI: 0.63, 0.69. The kappa for inter-observer agreement considering all 30 radiographs was: 0.40, 95%CI: 0.40, 0.41 in the first evaluation and 0.39, 95%CI: 0.39, 0.40 in the second evaluation.The proposed classification for peri-implant femoral fractures may be useful and user-friendly. Future studies are needed to assess the how clinically useful this classification system may be (the third phase in the validation process).

Background Acute cardiac events (ACEs) are increasingly being recognized as a major complication in pneumococcal community-acquired pneumonia (CAP). Information regarding host- and pathogen-related factors for ACEs, including pneumococcal serotypes and clonal complexes, is scarce. Methods A retrospective study was conducted of a prospective cohort of patients hospitalized for CAP between 1996 and 2019. Logistic regression and funnel plot analyses were performed to determine host- and pathogen-related factors for ACEs. Results Of 1739 episodes of pneumococcal CAP, 1 or more ACEs occurred in 304 (17.5%) patients, the most frequent being arrhythmia (n = 207), heart failure (n = 135), and myocardial infarction (n = 23). The majority of ACEs (73.4%) occurred within 48 hours of admission. Factors independently associated with ACEs were older age, preexisting heart conditions, pneumococcal bacteremia, septic shock at admission, and high-risk pneumonia. Among 983 pneumococcal isolates, 872 (88.7%) were serotyped and 742 (75.5%) genotyped. The funnel plot analyses did not find any statistically significant association between serotypes or clonal complexes with ACEs. Nevertheless, there was a trend toward an association between CC230 and these complications. ACEs were independently associated with 30-day mortality (adjusted odds ratio, 1.88; 95% CI, 1.11–3.13). Conclusions ACEs are frequent in pneumococcal pneumonia and are associated with increased mortality. The risk factors defined in this study may help identify patients who must undergo close follow-up, including heart rhythm monitoring, and special care to avoid fluid overload, particularly during the first 48 hours of admission. These high-risk patients should be the target for preventive intervention strategies.

Background: Lung transplantation is the ultimate treatment for end stage lung disease. There is paucity of data on the impact of surgical incision and analgesia on clinically relevant outcomes. Methods: A single centre retrospective study was performed between July 2007 and August 2017 of patients undergoing single or double lung transplantation. Gender, age, indication for lung transplantation, and the three types of surgical access (Thoracotomy (T), Sternotomy (S) and Clamshell (C)) were used, as well as two analgesic techniques: epidural and intravenous opioids. Outcome variables of the study were: Pain scores; Postoperative hemorrhage in the first 24 hours, duration of mechanical ventilation and length of stay at ICU. Results: 341 patients were identified. Thoracotomy was associated with higher pain scores than Sternotomy (OR 1.66, 95% CI: 1.01;2.74, p: 0.045) and no differences were found between Clamshell and Sternotomy incision.The median blood loss was 800 ml [IQR: 500; 1238], thoracotomy patients had 500 ml [325;818] (p < 0.001). Median duration of mechanical ventilation in Thoracotomy, Sternotomy and Clamshell groups were 19 [11; 37] hours, 34 [IQR 16; 57.5] hours and 27 [IQR 15; 50.5] hours respectively. Thoracotomy group were discharged earlier from ICU (p

There is paucity of data on the impact of surgical incision and analgesia on relevant outcomes. A retrospective STROBE-compliant cohort study was performed between July 2007 and August 2017 of patients undergoing lung transplantation. Gender, age, indication for lung transplantation, and the 3 types of surgical access (Thoracotomy (T), Sternotomy (S), and Clamshell (C)) were used, as well as 2 analgesic techniques: epidural and intravenous opioids. Outcome variables were: pain scores; postoperative hemorrhage in the first 24 hours, duration of mechanical ventilation, and length of stay at intensive care unit (ICU). Three hundred forty-one patients were identified. Thoracotomy was associated with higher pain scores than Sternotomy (OR 1.66, 95% CI: 1.01; 2.74, P: .045) and no differences were found between Clamshell and Sternotomy incision. The median blood loss was 800 mL [interquartile range (IQR): 500; 1238], thoracotomy patients had 500 mL [325; 818] (P

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.

Oral bisphosphonates (oBPs) have been associated with reduced fractures and mortality. However, their risks and benefits are unclear in patients with moderate–severe CKD. This study examined the association between oBPs and all-cause mortality in G3B-5D CKD. This is a population-based cohort study including all subjects with an estimated glomerular filtration rate (eGFR) 2 (G3B: eGFR 2 G4: eGFR 15–29/mL/min/1.73 m 2 G5: eGFR 2 G5D: hemodialysis) aged 40+ years from the UK Clinical Practice Research Datalink (CPRD) and the Catalan Information System for Research in Primary Care (SIDIAP). Previous and current users of other anti-osteoporosis drugs were excluded. oBP use was modeled as a time-varying exposure to avoid immortal time bias. Treatment episodes in oBP users were created by concatenating prescriptions until patients switched or stopped therapy or were censored or died. A washout period of 180 days was added to (date of last prescription +180 days). Propensity scores (PSs) were calculated using prespecified predictors of mortality including age, gender, baseline eGFR, socioeconomic status, comorbidities, previous fracture, co-medications, and number of hospital admissions in the previous year. Cox models were used for PS adjustment before and after PS trimming (the first and last quintiles). In the CPRD, of 19,351 oBP users and 210,954 non-oBP users, 5234 (27%) and 85,105 (40%) deaths were recorded over 45,690 and 915,867 person-years of follow-up, respectively. oBP users had 8% lower mortality risk compared to non-oBP users (hazard ratio [HR] 0.92; 95% CI, 0.89 to 0.95). Following PS trimming, this became nonsignificant (HR 0.98; 95% CI, 0.94 to 1.04). In the SIDIAP, of 4146 oBP users and 86,127 non-oBP users, 1330 (32%) and 36,513 (42%) died, respectively. oBPs were not associated with mortality in PS adjustment and trimming (HR 1.04; 95% CI, 0.99 to 1.1 and HR 0.95; 95% CI, 0.89 to 1.01). In this observational, patient-based cohort study, oBPs were not associated with increased mortality among patients with moderate–severe CKD. However, further studies are needed on other effects of oBPs in CKD patients.

Background: Although contraindicated in patients with severe chronic kidney disease (CKD) due to a lack of safety data, bisphosphonates are commonly used to prevent or treat bone fragility in these patients. We studied the safety of bisphosphonates in patients with moderate-to-severe CKD. Methods: Patients with stage 3b+ CKD based on 2+ estimated glomerular filtration rate (eGFR) measures were identified in two primary-care records databases, the UK CPRD GOLD during 1997-2016 and the Catalan (Spain) SIDIAP during 2007-2015. New bisphosphonate users were propensity-scorematched with up to five non-users to minimise confounding, and followed until treatment discontinuation, switching, dropout, death, or 10 years. The primary outcome was CKD stage worsening (eGFR decline or renal replacement therapy). Secondary outcomes included hospitalised acute kidney injury (AKI), gastrointestinal bleeding/ulcers (GIE), and hypocalcaemia. Hazard ratios (HRs) were estimated using Cox regression for SIDIAP participants, and sub-HRs (sHRs) calculated using Fine-Gray models for CPRD. Findings: We matched 2,447 bisphosphonate users with 8,931 non-users from CPRD, and 1,399 users with 6,547 non-users from SIDIAP. Bisphosphonate use was associated with greater risk of CKD progression in both CPRD (HR [95% CI]: 1·14 [1·04, 1·26]) and SIDIAP (HR: 1·16 [1·04, 1·29]). No statistically significant risk differences were found for AKI, GIE, or hypocalcaemia. Interpretation: A modest (10%-15%) increased risk of CKD progression was identified in association with bisphosphonate use amongst patients with moderate-severe disease. No other safety concerns were identified. Our findings should be considered in combination with effectiveness data before prescribing bisphosphonates to patients with moderate-severe CKD. Funding Statement: Funding was provided by the National Institute of Health Research Health Technology Assessment project number 14/36/02. The project was partially funded by CIBERFES, Instituto Carlos III, Spain. JP and MJP-S are supported by PI16/00619 (Spanish Ministry of Health ISCIII FIS-FEDER) and RD16/0009/0013 (ISCIII FEDER RedinRen). Declaration of Interests: B Abrahamsen reports research grants from UCB and Novartis. NK Arden reports personal fees from Flexion, Freshfields, Janssen, Merck, and Regeneron. C Cooper reports lecture fees and honoraria from the Alliance for Better Bone Health Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda, and UCB. A Judge is a subpanel member of the NIHR PGfAR, has received consultancy fees from Freshfields Bruckhaus Deringer, and has held advisory board positions (which involved receipt of fees) at Anthera Pharmaceuticals, INC. MK Javaid reports research support and speaker fees from Amgen. D Prieto-Alhambra reports research grants from UCB, Amgen, and Les Laboratoires Servier, and departmental (not personal) speaker and consultancy fees from UCB and Amgen. D Prieto-Alhambra is a member of the NIHR HTA CET panel since November 2017. DE Robinson, MS Ali, VY Strauss, L Elhussein, Y Ben-Shlomo, F Caskey, D Dedman, and A Delmestri have nothing to disclose. Ethics Approval Statement: This study was approved by the CPRD Independent Scientific Advisory Committee (protocol number 15_ 53R2A).

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 Daptomycin plus fosfomycin combination has demonstrated synergistic and bactericidal effect in animal models of methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), but there is lack of data in humans. Method A randomized (1:1), open-label, clinical trial involving adults with MRSAB was conducted at 18 medical centers in Spain. Patients were assigned to receive daptomycin, 10 mg/kg IV daily plus fosfomycin, 2 g IV/6 hour (combination therapy) or to receive daptomycin 10 mg/kg/24 h IV (monotherapy) during 10 up to 14 days for uncomplicated bacteremia and 28 up to 42 days for complicated bacteremia. The primary efficacy endpoints were: (a) treatment success at Test-of-Cure visit (ToC: 6 weeks after end of therapy) and (b) treatment success at 7 days (defined as alive at day 7 and clearance of bacteremia without relapse from 8 to 90 days after randomization), according with the proposed primary endpoints for use in clinical trials in bloodstream infections in adults. Result Between December 2013 and November 2017, 674 patients with MRSAB were evaluated and 155 patients were randomized: 74 received combination therapy and 81 monotherapy. In intention-to-treat analysis, (a) at ToC visit successful outcome was achieved in 40 of 74 patients (54,1%) who received combination therapy as compared with 34 of 81 patients (42%) who were given monotherapy (54.1% vs. 42.0%; absolute difference, 12.1%; 95% confidence interval, 0%-27.0%); (b) at 7 days after starting the therapy: a successful outcome was achieved in 69 of 74 patients who received combination therapy as compared with 62 out of 81 patients who received monotherapy (93.2% vs. 76.5%; absolute difference, 16.7%; 95% confidence interval, 5.4%–27.7%). Combination therapy was associated with lower rates of microbiologic failure than monotherapy at ToC visit (0 vs. 9 patients, P = 0.009). Combination therapy, as compared with daptomycin monotherapy, was associated with a nonsignificantly higher rate of adverse events due to study medication leading to treatment failure and discontinuation of therapy: 6/74 (8.1%) vs. 3/81 (3.7%) (P = 0.31). Conclusion The combination of daptomycin plus fosfomycin was more effective than daptomycin alone for treating MRSAB (NCT01898338). Disclosures All authors: No reported disclosures.