Antimicrobial stewardship programs in acute-care hospitals: A multicenter assessment of structure, process, and outcome indicators in Italy and Spain.

BACKGROUND: Antimicrobial stewardship (AMS) programs have been differently implemented across Europe. This study primarily aimed to compare AMS in two European regions. Secondarily, the study explored the COVID-19 pandemic impact on surrogate outcome indicators of AMS. METHODS: A retrospective observational study was conducted in Piedmont (Italy) and Catalonia (Spain). AMS programs were compared through structure and process indicators in 2021. Changes in surrogate outcome indicators (antimicrobial usage; alcohol-based sanitizer consumption; antimicrobial resistance, AMR) from 2017 to 2021 described the pandemic impact. RESULTS: Seventy-eight facilities provided structure and process indicators. Catalonia showed better structure scores (p < 0.001) and less dispersion in both indicators. The greatest areas to improve were accountability (Piedmont) and diversification of strategies (Catalonia). Overall, the regions reported consistent changes in outcome indicators. Antimicrobial usage decreased in 2020, returning to near-pre-pandemic levels in 2021. Alcohol-based sanitizer consumption surged in 2020, then dipped remaining above pre-pandemic levels. AMR trends were minimally affected. CONCLUSIONS: The centralized approach of Catalonia ensured consistent attainment of quality objectives across all facilities, but it may limit facility-specific strategies. In Piedmont, accountability remain one of the most critical factors as in previous years. The pandemic did not substantially disrupt surrogate outcome measures of AMS. However, the data on AMR suggest that maintaining vigilance against this issue remains paramount.

Impact of an antimicrobial stewardship program indicator on the appropriateness of the empiric antibiotic treatment of urinary source Escherichia coli bacteraemia.

A prospective multicentre study was carried out between 2017 and 2021 to assess (1) the appropriateness of the empirical treatment to the local guidelines of urinary source Escherichia coli bacteraemia, (2) the appropriateness of empirical treatment to antibiotic sensitivity results and (3) the degree of error in the local guidelines regarding the antibiotic sensitivity reported in acute care hospitals enrolled in the vigilància de les infeccions relacionades amb l'atenció sanitària de Catalunya program. During the study period, 79.0% of the empirical treatments analysed complied with the guidelines and 88.1% were appropriate in view of the in vitro activity of the isolated strain. The rate of appropriateness rose from 73.8% in 2017 to 81.0% in 2021 (P < 0.001). The degree of error in the recommendations regarding the in vitro activity of the isolated strains was 5.9% and remained stable during the study period. Antibiotic families correctly prescribed according to the guidelines were third-generation cephalosporins (54.9%), carbapenems (16.8%) and combinations of penicillins and beta-lactamase inhibitors (16.4%). Of the 8009 E. coli strains, 19.0% were extended-spectrum beta-lactamases producers, 36.8% were resistant to quinolones and 0.5% were resistant to carbapenems. The broad implementation of an antimicrobial stewardship program with quality indicators of antibiotic use improved compliance to local guidelines in the empiric treatment of urinary tract E. coli bacteraemia. The degree of error in local guidelines was low but higher in more complex hospitals and in healthcare-associated infections. Guidelines need to be constantly updated with the use of epidemiological data, rapid diagnostic tests and the analysis of patient risk factors specific to each geographical area.

Quality check: concordance between two monitoring systems for postoperative organ/space-surgical site infections in rectal cancer surgery. Linkage of data from the Catalan Cancer Plan and the VINCat infection surveillance programme.

BACKGROUND: The Catalan Cancer Plan (CCP) undertakes periodic audits of cancer treatment outcomes, including organ/space surgical site infections (O/S-SSI) rates, while the Catalan Healthcare-associated Infections Surveillance Programme (VINCat) carries out standardized prospective surveillance of surgical site infections (SSI) in colorectal surgery. This cohort study aimed to assess the concordance between these two monitoring systems for O/S-SSI following primary rectal cancer surgery. METHODS: The study compared O/S-SSI incidence data from CCP clinical audits versus the VINCat Programme in patients undergoing surgery for primary rectal cancer, in 2011-12 and 2015-16, in publicly funded centres in Spain. The main outcome variable was the incidence of O/S-SSI in the first 30 days after surgery. Concordance between the two registers was analysed using Cohen's kappa. Discordant cases were reviewed by an expert, and the main reasons for discrepancies evaluated. RESULTS: Pooling data from both databases generated a sample of 2867 patients. Of these, O/S-SSI was detected in 414 patients-235 were common to both registry systems, with satisfactory concordance (κ = 0.69, 95% confidence interval 0.65-0.73). The rate of discordance from the CCP (positive cases in VINCat and negative in CCP) was 2.7%, and from VINCat (positive in CCP and negative in VINCat) was 3.6%. External review confirmed O/S-SSI in 66.2% of the cases in the CCP registry and 52.9% in VINCat. CONCLUSIONS: This type of synergy shows the potential of pooling data from two different information sources with a satisfactory level of agreement as a means to improving O/S-SSI detection. CLINICALTRIALS: gov Identifier: NCT06104579. Registered 30 November 2023.

Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial.

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Reducing the duration of antibiotic therapy in surgical patients through a specific nationwide antimicrobial stewardship program. A prospective, interventional cohort study.

BACKGROUND: Guidelines recommend 5-7 days of antibiotic treatment in patients with surgical infection and adequate source control. This nationwide stewardship intervention aimed to reduce the duration of treatments in surgical patients to <7 days. METHODS: Prospective cohort study evaluating surgical patients receiving antibiotics ≥7 days in 32 hospitals. Indication for treatment, quality of source control, type of recommendations issued, and adherence to the recommendations were analysed. Temporal trends in the percentages of patients with treatment >7 days were evaluated using a linear regression model and Pearson's correlation coefficients. RESULTS: A total of 32 499 patients were included. Of these, 13.7% had treatments ≥7 days. In all, 3912 stewardship interventions were performed, primarily in general surgery (90.7%) and urology (8.1%). The main types of infection were intra-abdominal (73.4%), skin/soft tissues (9.8%) and urinary (9.2%). The septic focus was considered controlled in 59.9% of cases. Out of 5458 antibiotic prescriptions, the most frequently analysed drugs were piperacillin/tazobactam (21.7%), metronidazole (11.2%), amoxicillin/clavulanate (10.3%), meropenem (10.7%), ceftriaxone (9.3%) and ciprofloxacin (6.7%). The main recommendations issued were: treatment discontinuation (35.0%), maintenance (40.0%) or de-escalation (15.5%), and the overall adherence rate was 91.5%. With adequate source control, the most frequent recommendation was to terminate treatment (51.2%). Throughout the study period, a significant decrease in the percentage of prolonged treatments was observed (Pc=-0.69;P < 0.001). CONCLUSIONS: This stewardship programme reduced the duration of treatments in surgical departments. Preference was given to general surgery services, intra-abdominal infection, and beta-lactam antibiotics, including carbapenems. Adherence to the issued recommendations was high.

Best practice in the use of peripheral venous catheters: A scoping review and expert consensus.

Background: Peripheral intravenous catheters (PIVCs) are the most commonly used invasive medical device in health care with an overall failure rate of 35-50%. Most complications are non-infectious, but local site and bloodstream infections can also occur. Even if PIVC-related infections are rare, the total number of affected patients and the preponderance of Staphylococcus aureus as related pathogen due to the frequent use of these devices are relevant arguments to implement preventive strategies. The aim of this document is to raise awareness that infections caused by PIVCs are a relevant problem that can be reduced by practice change. Methods: A panel of experts discussed this topic based on evidence and proposed practice points by consensus. Discussion: Despite published evidence-based guidelines, current practice concerning aseptic techniques during insertion and care of PIVCs often are substandard. These devices have become commonplace and tend to be perceived as safe. An overall lack of awareness about the true risks associated with the use of PIVCs results in limited surveillance and prevention efforts. Conclusion: Successful insertion and maintenance bundles in central venous lines are a blueprint to the implementation of adapted bundle strategies in the prevention of PIVC-associated infections. There is a need for studies to specifically investigate infection prevention in PIVCs and to agree on effective and implementable bundles.

Leveraging a nationwide infection surveillance program to implement a colorectal surgical site infection reduction bundle: a pragmatic, prospective, and multicenter cohort study.

BACKGROUND: Bundled interventions usually reduce surgical site infection (SSI) when implemented at single hospitals, but the feasibility of their implementation at the nationwide level and their clinical results are not well established. MATERIALS AND METHODS: Pragmatic interventional study to analyze the implementation and outcomes of a colorectal surgery care bundle within a nationwide quality improvement program. The bundle consisted of antibiotic prophylaxis, oral antibiotic prophylaxis (OAP), mechanical bowel preparation, laparoscopy, normothermia, and a wound retractor. Control group (CG) and Intervention group (IG) were compared. Overall SSI, superficial (S-SSI), deep (D-SSI), and organ/space (O/S-SSI) rates were analyzed. Secondary endpoints included microbiology, 30-day mortality, and length of hospital stay. RESULTS: A total of 37 849 procedures were included, 19 655 in the CG and 18 194 in the IG. In all, 5462 SSIs (14.43%) were detected: 1767 S-SSI (4.67%), 847 D-SSI (2.24%), and 2838 O/S-SSI (7.5%). Overall SSI fell from 18.38% (CG) to 10.17% (IG), odds ratio (OR) of 0.503 [0.473-0.524]. O/S-SSI rates were 9.15% (CG) and 5.72% (IG), OR of 0.602 [0.556-0.652]. The overall SSI rate was 16.71% when no measure was applied and 6.23% when all six were used. Bundle implementation reduced the probability of overall SSI (OR: 0.331; CI 95 : 0.242-0.453), and also O/S-SSI rate (OR: 0.643; CI 95 : 0.416-0.919). In the univariate analysis, all measures except normothermia were associated with a reduction in overall SSI, while only laparoscopy, OAP, and mechanical bowel preparation were related to a decrease in O/S-SSI. Laparoscopy, wound retractor, and OAP decreased overall SSI and O/S-SSI in the multivariate analysis. CONCLUSIONS: In this cohort study, the application of a specific care bundle within a nationwide nosocomial infection surveillance system proved feasible and resulted in a significant reduction in overall and O/S-SSI rates in the elective colon and rectal surgery. The OR for SSI fell between 1.5 and 3 times after the implementation of the bundle.

Molecular Epidemiology, Antimicrobial Susceptibility, and Clinical Features of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections over 30 Years in Barcelona, Spain (1990-2019).

Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSI) are a significant cause of mortality. We analysed the evolution of the molecular and clinical epidemiology of MRSA-BSI (n = 784) in adult patients (Barcelona, 1990−2019). Isolates were tested for antimicrobial susceptibility and genotyped (PFGE), and a selection was sequenced (WGS) to characterise the pangenome and mechanisms underlying antimicrobial resistance. Increases in patient age (60 to 71 years), comorbidities (Charlson's index > 2, 10% to 94%), community-onset healthcare-associated acquisition (9% to 60%), and 30-day mortality (28% to 36%) were observed during the 1990−1995 and 2014−2019 periods. The proportion of catheter-related BSIs fell from 57% to 20%. Current MRSA-BSIs are caused by CC5-IV and an upward trend of CC8-IV and CC22-IV clones. CC5 and CC8 had the lowest core genome proportions. Antimicrobial resistance rates fell, and only ciprofloxacin, tobramycin, and erythromycin remained high (>50%) due to GyrA/GrlA changes, the presence of aminoglycoside-modifying enzymes (AAC(6')-Ie-APH(2″)-Ia and ANT(4')-Ia), and mph(C)/msr(A) or erm (C) genes. Two CC22-IV strains showed daptomycin resistance (MprF substitutions). MRSA-BSI has become healthcare-associated, affecting elderly patients with comorbidities and causing high mortality rates. Clonal replacement with CC5-IV and CC8-IV clones resulted in lower antimicrobial resistance rates. The increased frequency of the successful CC22-IV, associated with daptomycin resistance, should be monitored.

Effects of the COVID-19 Pandemic on Incidence and Epidemiology of Catheter-Related Bacteremia, Spain.

We compared hospital-acquired catheter-related bacteremia (CRB) episodes diagnosed at acute care hospitals in Catalonia, Spain, during the COVID-19 pandemic in 2020 with those detected during 2007-2019. We compared the annual observed and predicted CRB rates by using the negative binomial regression model and calculated stratified annual root mean squared errors. A total of 10,030 episodes were diagnosed during 2007-2020. During 2020, the observed CRB incidence rate was 0.29/103 patient-days, whereas the predicted CRB rate was 0.14/103 patient-days. The root mean squared error was 0.153. Thus, a substantial increase in hospital-acquired CRB cases was observed during the COVID-19 pandemic in 2020 compared with the rate predicted from 2007-2019. The incidence rate was expected to increase by 1.07 (95% CI 1-1.15) for every 1,000 COVID-19-related hospital admissions. We recommend maintaining all CRB prevention efforts regardless of the coexistence of other challenges, such as the COVID-19 pandemic.

Clostridioides difficile infection recurrence in the VINCat hospitals: a prospective observational cohort study.

Background: The 2016 cumulative incidence of Clostridioides difficile infection (CDI) in Spain was reported by the European Center for Disease Control to be above the mean of other European countries. The aim of this multicenter prospective observational cohort study was to examine the risk factors that determine 90-day CDI recurrence in Catalonia, Spain. Methods: The study included 558 consecutive adults admitted to hospital who had a symptomatic, first positive CDI diagnosis. Sociodemographic, clinical and epidemiological variables were recorded. The primary outcome was 90-day CDI recurrence. Results: In this Catalan population, having received more than one course of antibiotics in the 30 days prior to CDI diagnosis (odds ratio: 2.459; 95% CI: 1.195-5.060; p = 0.015) and active chemotherapy (odds ratio: 4.859; 95% CI: 1.495-15.792; p = 0.009) are significant predictors of 90-day CDI recurrence. Conclusion: The identification of independent risk factors of 90-day CDI recurrence will enable the optimization of preventive measures in at-risk populations.

The Effectiveness of Combination Therapy for Treating Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Systematic Literature Review and a Meta-Analysis.

BACKGROUND: This meta-analysis aims to evaluate the effectiveness of combination therapy for treating MSSA bacteremia. METHODS: We searched Ovid MEDLINE, EMBASE, Cochrane CENTRAL, and clinicaltrials.gov for studies including adults with MSSA bacteremia. The monotherapy group used a first-line antibiotic active against MSSA and the combination group used a first-line antibiotic plus additional antibiotic/s. The primary outcome was all-cause mortality. Secondary outcomes included persistent bacteremia, duration of bacteremia, relapse, and adverse events. Random-effects models with inverse variance weighting were used to estimate pooled risk ratios (pRR). Heterogeneity was assessed using the I2 value and the Cochrane's Q statistic. RESULTS: A total of 12 studies (6 randomized controlled trials [RCTs]) were included. Combination therapy did not significantly reduce 30-day mortality (pRR 0.92, 95% CI, 0.70-1.20), 90-day mortality (pRR 0.89, 95% CI, 0.74-1.06), or any-time mortality (pRR 0.91, 95% CI, 0.76-1.08). Among patients with deep-seated infections, adjunctive rifampicin may reduce 90-day mortality (3 studies with moderate-high risk of bias; pRR 0.62, 95% CI, 0.42-0.92). For secondary outcomes, combination therapy decreased the risk of relapse (pRR 0.38, 95% CI, 0.22-0.66), but this benefit was not maintained when pooling RCTs (pRR 0.54, 95% CI, 0.12-2.51). Combination therapy was associated with an increased risk of adverse events (pRR 1.74, 95% CI, 1.31-2.31). CONCLUSIONS: Combination therapy not only did not decrease mortality in patients with MSSA bacteremia, but also increased the risk of adverse events. Combination therapy may reduce the risk of relapse, but additional high-quality studies are needed.

Trends in the epidemiology of catheter-related bloodstream infections; towards a paradigm shift, Spain, 2007 to 2019.

BackgroundCatheter-related bloodstream infections (CRBSI) are frequent healthcare-associated infections and an important cause of death.AimTo analyse changes in CRBSI epidemiology observed by the Infection Control Catalan Programme (VINCat).MethodsA cohort study including all hospital-acquired CRBSI episodes diagnosed at 55 hospitals (2007-2019) in Catalonia, Spain, was prospectively conducted. CRBSI incidence rates were adjusted per 1,000 patient days. To assess the CRBSI rate trend per year, negative binomial models were used, with the number of events as the dependent variable, and the year as the main independent variable. From each model, the annual rate of CRBSI diagnosed per 1,000 patient days and the incidence rate ratio (IRR) with its 95% confidence intervals (CI) were reported.ResultsDuring the study, 9,290 CRBSI episodes were diagnosed (mean annual incidence rate: 0.20 episodes/1,000 patient days). Patients' median age was 64.1 years; 36.6% (3,403/9,290) were female. In total, 73.7% (n = 6,845) of CRBSI occurred in non-intensive care unit (ICU) wards, 62.7% (n = 5,822) were related to central venous catheter (CVC), 24.1% (n = 2,236) to peripheral venous catheters (PVC) and 13.3% (n = 1,232) to peripherally-inserted central venous catheters (PICVC). Incidence rate fell over the study period (IRR: 0.94; 95%CI: 0.93-0.96), especially in the ICU (IRR: 0.88; 95%CI: 0.87-0.89). As a whole, while episodes of CVC CRBSI fell significantly (IRR: 0.88; 95%CI: 0.87-0.91), peripherally-inserted catheter CRBSI (PVC and PICVC) rose, especially in medical wards (IRR PICVC: 1.08; 95%CI: 1.05-1.11; IRR PVC: 1.03; 95% 1.00-1.05).ConclusionsOver the study, CRBSIs associated with CVC and diagnosed in ICUs decreased while episodes in conventional wards involving peripherally-inserted catheters increased. Hospitals should implement preventive measures in conventional wards.

An interventional nationwide surveillance program lowers postoperative infection rates in elective colorectal surgery. A cohort study (2008-2019).

BACKGROUND: Colorectal surgery is associated with the highest rate of surgical site infection (SSI). This study analyses the effectiveness of an interventional surveillance program on SSI rates after elective colorectal surgery. MATERIAL AND METHODS: Cohort study showing temporal trends of SSI rates and Standardized Infection Ratio (SIR) in elective colorectal surgery over a 12-year period. Prospectively collected data of a national SSI surveillance program was analysed and the effect of specific interventions was evaluated. Patient and procedure characteristics, as well as SIR and SSI rates were stratified by risk categories and type of SSI analysed using stepwise multivariate logistic regression models. RESULTS: In a cohort of 42,330 operations, overall cumulative SSI incidence was 16.31%, and organ-space SSI (O/S-SSI) was 8.59%. There was a 61.63% relative decrease in SSI rates (rho = -0.95804). The intervention which achieved the greatest SSI reduction was a bundle of 6 measures. SSI in pre-bundle period was 19.73% vs. 11.10% in post-bundle period (OR 1.969; IC 95% 1.860-2.085; p < 0.0001). O/S-SSI were 9.08% vs. 6.06%, respectively (OR 1.547; IC 95% 1.433-1.670; p < 0.0001). Median length of stay was 7 days, with a significant decrease over the studied period (rho = -0.98414). Mortality of the series was 1.08%, ranging from 0.35% to 2.0%, but a highly significant decrease was observed (rho = -0.67133). CONCLUSIONS: Detailed analysis of risk factors and postoperative infection in colorectal surgery allows strategies for reducing SSI incidence to be designed. An interventional surveillance program has been effective in decreasing SIR and SSI rates.

Bloodstream Infection and Endocarditis Caused by Staphylococcus aureus in Patients with Cancer: A Multicenter Cohort Study.

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 < 0.001) and osteoarticular infection (2.3% vs 14.3%, p < 0.001). Independent risk factors for IE were cardiopathy (aOR 4.392, 95% CI 2.719-7.094) and persistent bacteremia (aOR 3.545, 95% CI 2.159-5.820). Thirty-day mortality was high, and similar between groups (24.2% vs 25.5%, p = 0.282). CONCLUSIONS: PAC with SABSI developed IE less frequently than PWC did. This finding seems related to the differences in baseline characteristics and may have significant clinical implications, such as transesophageal echocardiography in PAC without cardiopathy or persistent bacteremia.

Oral Antibiotic Prophylaxis Lowers Surgical Site Infection in Elective Colorectal Surgery: Results of a Pragmatic Cohort Study in Catalonia.

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.

Economic impact of a care bundle to prevent surgical site infection after craniotomy: a cost-analysis study.

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.

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial.

INTRODUCTION: Methicillin-susceptible Staphylococcus 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 against S. 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.

PRAISE: providing a roadmap for automated infection surveillance in Europe.

INTRODUCTION: Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance - manual chart review - is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care. METHODS: The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts. RESULTS: This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS. CONCLUSIONS: Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists.

Risk factors for hospital readmission following complicated urinary tract infection.

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.