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Background: Staphylococcus aureus bacteremia (SAB) is a clinically heterogeneous disease. The ability to identify subgroups of patients with shared traits (subphenotypes) is an unmet need to allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically relevant subphenotypes can be reproducibly identified among patients with SAB., Methods: We studied 3 cohorts of adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n = 458), the UK ARREST trial (n = 758), and the Spanish SAFO trial (n = 214). Latent class analysis was used to identify subphenotypes using routinely collected clinical data without considering outcomes. Mortality and microbiologic outcomes were then compared between subphenotypes., Results: Included patients had predominantly methicillin-susceptible SAB (1366 of 1430, 95.5%). We identified 5 distinct, reproducible clinical subphenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the subphenotypes. Mortality was highest in subphenotype A and lowest in subphenotypes B and E. Microbiologic outcomes were worse in subphenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased mortality in subphenotype B and improved microbiologic outcomes in subphenotype C., Conclusions: We have identified reproducible and clinically relevant subphenotypes within SAB and provide proof of principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these subphenotypes could contribute to a personalized medicine approach to SAB., Competing Interests: Potential conflicts of interest . C. T. reports speaker fees from Gedeon Richter. V. G. F. reports grants/research support from Astra Zeneca, MedImmune, Merck, ContraFect, Karius, Genentech, Regeneron, and Basilea; serving as a paid consultant for Astra Zeneca, GSK, Armata, Debiopharm, Genentech, Basilea Affinergy, Janssen, ContraFect, and Destiny; and royalties from UpToDate. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Although a significant number of cases of Staphylococcus aureus bacteraemia (SAB) are managed at non-referral community hospitals, the impact of a bundle-of-care intervention in this setting has not yet been explored., Methods: We performed a quasi-experimental before-after study with the implementation of a bundle of care for the management of SAB at five non-referral community hospitals and a tertiary care university hospital. Structured recommendations for the five indicators selected to assess quality of care were provided to investigators before the implementation of the bundle and monthly thereafter. Primary endpoints were adherence to the bundle intervention and treatment failure, defined as death or relapse at 90 days of follow-up., Results: One hundred and seventy patients were included in the pre-intervention period and 103 in the intervention period. Patient characteristics were similar in both periods. Multivariate analysis controlling for potential confounders showed that performance of echocardiography was the only factor associated with improved adherence to the bundle in the intervention period (adjusted OR 2.13; 95% CI 1.13-4.02). Adherence to the bundle, performance of follow-up blood cultures, and adequate duration of antibiotic therapy for complicated SAB presented non-significant improvements. The intervention was not associated with a lower rate of 90 day treatment failure (OR 1.11; 95% CI 0.70-1.77)., Conclusions: A bundle-of-care intervention for the management of SAB at non-referral community hospitals increased adherence to quality indicators, but did not significantly reduce rates of 90 day mortality or relapse., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

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 ., (© 2023. The Author(s).)

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 0.29/10 3 patient-days, whereas the predicted CRB rate was 0.14/10 3 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.

Background: The incidence of catheter-related bloodstream infections (CRBSIs) has fallen over the last decade, especially in intensive care units (ICUs)., Aim: To assess the existence of concomitant trends in outcomes and to analyse the current risk factors for mortality., Methods: A multicentre retrospective cohort study was conducted at 24 Catalan hospitals participating in the Surveillance of healthcare-associated infections in Catalonia (VINCat). All hospital-acquired CRBSI episodes diagnosed from January 2010 to December 2019 were included. A common protocol including epidemiological, clinical, and microbiological data was prospectively completed. Mortality at 30 days after bacteraemia onset was analysed using the Cox regression model., Findings: Over the study period, 4795 episodes of CRBSI were diagnosed. Among them, 75% were acquired in conventional wards and central venous catheters were the most frequently involved (61%). The 30-day mortality rate was 13.8%, presenting a significant downward trend over the study period: from 17.9% in 2010 to 10.6% in 2019 (hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.92-0.98). The multivariate analysis identified age (HR: 1.03; 95% CI: 1.02-1.04), femoral catheter (1.78; 1.33-2.38), medical ward acquisition (2.07; 1.62-2.65), ICU acquisition (3.45; 2.7-4.41), S. aureus (1.59; 1.27-1.99) and Candida sp. (2.19; 1.64-2.94) as risk factors for mortality, whereas the mortality rate associated with episodes originating in peripheral catheters was significantly lower (0.69; 0.54-0.88)., Conclusion: Mortality associated with CRBSI has fallen in recent years but remains high. Intervention programmes should focus especially on ICUs and medical wards, where incidence and mortality rates are highest., (Copyright © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

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.

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., Competing Interests: Competing interests: GH received a research grant from ERN (19PNJ145)., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

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., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: 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.

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.

Background: It has been suggested that there is an increased risk of treatment failure in episodes of MRSA bloodstream infection (BSI) caused by strains with high vancomycin MICs. However, it is unknown if this phenomenon may also act as a risk factor for the development of infective endocarditis (IE)., Methods: We analysed 207 episodes of catheter-related (CR)-BSI recruited from June 2008 to December 2009 within a prospective study on MRSA BSI in 21 Spanish hospitals. Vancomycin susceptibility was centrally tested. The impact of high vancomycin MIC values (≥1.5 mg/L by Etest) on the subsequent development of IE was investigated by Cox regression., Results: High vancomycin MIC values were observed in 46.9% of the isolates. Initial therapy consisted of vancomycin [99 episodes (44.7%)], daptomycin [25 (12.1%)], linezolid [18 (8.7%)] and other antistaphylococcal agents [16 (7.7%)]. Haematogenous complications occurred in 41 patients (19.8%), including 10 episodes complicated by IE. Early (48 h) and late (30 day) all-cause mortality were 3.4% and 25.1%, respectively. High vancomycin MIC isolates were more common among patients that developed IE compared with those free from this complication [90.9% (9/10) versus 44.7% (88/197); P  = 0.007]. This association remained significant after adjusting for multiple confounders (including initial antibiotic therapy and catheter removal) in different models (minimum hazard ratio: 9.18; 95% CI: 1.16-72.78; P  = 0.036). There were no differences in mortality according to vancomycin MIC values., Conclusions: Decreased susceptibility to vancomycin acted as a predictor of the development of IE complicating MRSA CR-BSI., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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.

Objectives: To compare clinical and microbiological characteristics, treatment and outcomes of MRSA bacteraemia among elderly and younger patients., Material and Methods: Prospective study conducted at 21 Spanish hospitals including patients with MRSA bacteraemia diagnosed between June/2008 and December/2009. Episodes diagnosed in patients aged 75 or more years old (≥75) were compared with the rest of them (<75)., Results: Out of 579 episodes of MRSA bacteraemia, 231 (39.9%) occurred in patients ≥75. Comorbidity was significantly higher in older patients (Charlson score ≥4: 52.8 vs. 44%; p = .037) as was the severity of the underlying disease (McCabe ≥1: 61.9 vs. 43.4%; p < .001). In this group the acquisition was more frequently health-care related (43.3 vs. 33.9%, p = .023), mostly from long-term care centers (12.1 vs. 3.7%, p < .001). An unknown focus was more frequent among ≥75 (19.9 vs. 13.8%; p = .050) while severity at presentation was similar between groups (Pitt score ≥3: 31.2 vs. 27.6%; p = .352). The prevalence of vancomycin resistant isolates was similar between groups, as was the appropriateness of empirical antibiotic therapy. Early (EM) and overall mortality (OM) were significantly more frequent in the ≥75 group (EM: 12.1 vs. 6%; p = .010 OM: 42.9 vs. 23%; p < .001). In multivariate analysis age ≥75 was an independent risk factor for overall mortality (aOR: 2.47, CI: 1.63-3.74; p < .001)., Conclusion: MRSA bacteraemia was frequent in patients aged ≥75 of our cohort. This group had higher comorbidity rates and the source of infection was more likely to be unknown. Although no differences were seen in severity or adequacy of empiric therapy, elderly patients showed a higher overall mortality., (Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Bacteremia and infective endocarditis caused by Staphylococcus aureus are common and severe diseases. Optimization of treatment is fundamental in the prognosis of these infections. The high rates of treatment failure and the increasing interest in the influence of vancomycin susceptibility in the outcome of infections caused by both methicillin-susceptible and -resistant isolates have led to research on novel therapeutic schemes. The interest in the new antimicrobials with activity against methicillin-resistant staphylococci has been extended to susceptible strains, which still carry the most important burden of infection. New combinations of antimicrobials have been investigated in experimental and clinical studies, but their role is still being debated. Also, the appropriateness of the initial empirical therapy has acquired relevance in recent years. The aim of this guideline is to update the 2009 guidelines and to provide an ensemble of recommendations in order to improve the treatment of staphylococcal bacteremia and infective endocarditis, in accordance with the latest published evidence., (Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Both bacteremia and infective endocarditis caused by Staphylococcus aureus are common and severe diseases. The prognosis may darken not infrequently, especially in the presence of intracardiac devices or methicillin-resistance. Indeed, the optimization of the antimicrobial therapy is a key step in the outcome of these infections. The high rates of treatment failure and the increasing interest in the influence of vancomycin susceptibility in the outcome of infections caused by both methicillin-susceptible and -resistant isolates has led to the research of novel therapeutic schemes. Specifically, the interest raised in recent years on the new antimicrobials with activity against methicillin-resistant staphylococci has been also extended to infections caused by susceptible strains, which still carry the most important burden of infection. Recent clinical and experimental research has focused in the activity of new combinations of antimicrobials, their indication and role still being debatable. Also, the impact of an appropriate empirical antimicrobial treatment has acquired relevance in recent years. Finally, it is noteworthy the impact of the implementation of a systematic bundle of measures for improving the outcome. The aim of this clinical guideline is to provide an ensemble of recommendations in order to improve the treatment and prognosis of bacteremia and infective endocarditis caused by S. aureus, in accordance to the latest evidence published., (Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Background: The aim of the study was to determine clinical and microbiological differences between patients with methicillin-resistant Staphylococcus aureus (MRSA) catheter-related bacteraemia (CRB) undergoing or not undergoing haemodialysis, and to compare outcomes., Methods: Prospective multicentre study conducted at 21 Spanish hospitals of patients with MRSA bacteraemia diagnosed between June 2008 and December 2009. Patients with MRSA-CRB were selected. Data of patients on haemodialysis (HD-CRB) and those not on haemodialysis (non-HD-CRB) were compared., Results: Among 579 episodes of MRSA bacteraemia, 218 (37.7%) were CRB. Thirty-four (15.6%) were HD-CRB and 184 (84.4%) non-HD-CRB. All HD-CRB patients acquired the infection at dialysis centres, while in 85.3% of the non-HD-CRB group the infection was nosocomial (p < .001). There were no differences in age, gender or severity of bacteraemia (Pitt score); comorbidities (Charlson score ≥ 4) were higher in the HD-CRB group than in the non-HD-CRB group (73.5% vs. 46.2%, p = .003). Although there were no differences in VAN-MIC ≥ 1.5 mg/L according to microdilution, using the E-test a higher rate of VAN-MIC ≥ 1.5 mg/L was observed in HD-CRB than in non-HD-CRB patients (63.3% vs. 44.1%, p = .051). Vancomycin was more frequently administered in the HD-CRB group than in the non-HD-CRB group (82.3% vs. 42.4%, p = <.001) and therefore the appropriate empirical therapy was significantly higher in HD-CRB group (91.2% vs. 73.9%, p = .029). There were no differences with regard to catheter removal (79.4% vs. 84.2%, p = .555, respectively). No significant differences in mortality rate were observed between both groups (Overall mortality: 11.8% vs. 27.2%, p = .081, respectively), but there was a trend towards a higher recurrence rate in HD-CRB group (8.8% vs. 2.2%, p = .076)., Conclusions: In our multicentre study, ambulatory patients in chronic haemodialysis represented a significant proportion of cases of MRSA catheter-related bacteraemia. Although haemodialysis patients with MRSA catheter-related bacteraemia had significantly more comorbidities and higher proportion of strains with reduced vancomycin susceptibility than non-haemodialysis patients, overall mortality between both groups was similar.

Introduction: Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone., Methods and Analysis: A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis., Ethics and Dissemination: The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study., Trial Registration Number: NCT01898338., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

There is increasing concern regarding the association between certain methicillin-resistant Staphylococcus aureus (MRSA) genotypes and poor clinical outcome. To assess this issue, a large cohort of 579 subjects with MRSA bacteraemia was prospectively followed from June 2008 to December 2009, in 21 hospitals in Spain. Epidemiology, clinical data, therapy, and outcome were recorded. All MRSA strains were analysed in a central laboratory. Presence of a haematogenous seeding infection was the dependent variable in an adjusted logistic regression model. Of the 579 patients included in the study, 84 (15%) had haematogenous seeding infections. Microdilution vancomycin median MIC (IQR) was 0.73 (0.38-3) mg/L. Most MRSA isolates (n = 371; 67%) belonged to Clonal Complex 5 (CC5) and carried an SCCmec element type IV and agr type 2. Isolates belonging to ST8-agr1-SCCmecIV, ST22-agr1-SCCmecIV and ST228-agr2-SCCmecI--a single locus variant of ST5--accounted for 8%, 9% and 9% of the isolates, respectively. After adjusting by clinical variables, any of the clones was associated with increased risk of haematogenous seeding infections. Higher vancomycin MIC was not identified as an independent risk factor, either. In contrast, persistent bacteraemia (OR 4.2; 2.3-7.8) and non-nosocomial acquisition (3.0; 1.7-5.6) were associated with increased risk., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Mortality related to methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) remains high, despite changes in the epidemiology. To analyze the current predictive factors for mortality we conducted a prospective study in a large cohort of patients with MRSA-BSI from 21 Spanish hospitals. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed, including susceptibility to antibiotics and molecular characterization. Vancomycin MICs (V-MIC) were tested by the E-test and microdilution methods. Time until death was the dependent variable in a Cox regression analysis. Overall, 579 episodes were included. Acquisition was nosocomial in 59% and vascular catheter was the most frequent source (38%). A dominant PFGE genotype was found in 368 (67%) isolates, which belonged to Clonal Complex (CC)5 and carried SCCmecIV and agr2. Microdilution V-MIC50 and V-MIC90 were 0.7 and 1.0 mg/L, respectively. Initial therapy was appropriate in 66% of episodes. Overall mortality was observed in 179 (32%) episodes. The Cox-regression analysis identified age >70 years (HR 1.88), previous fatal disease (HR 2.16), Pitt score >1 (HR 3.45), high-risk source (HR 1.85) and inappropriate initial treatment (HR 1.39) as independent predictive factors for mortality. CC5 and CC22 (HR 0.52 and 0.45) were associated with significantly lower mortality rates than CC8. V-MIC ≥1.5 did not have a significant impact on mortality, regardless of the method used to assess it., (© 2012 The Authors Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

To determine the impact of a multimodal intervention designed to reduce the incidence of catheter-related bloodstream infections (CRBSIs) outside the ICU, we conducted a prospective, quasi-experimental, before-after intervention study in 11 hospitals participating in the VINCat programme in Catalonia, Spain. The intervention consists of: (i) an evidence-based bundle of practices relating to catheter insertion and maintenance; (ii) a training programme for healthcare workers; (iii) four point-prevalence surveys to track the status of the catheters; and (iv) feedback reports to the staff involved. The study included both central (CVC) and peripheral venous catheters (PVCs). Rates of CRBSI per 1000 patient-days were prospectively measured in 2009 (pre-intervention period) and 2010 (post-intervention period). The analysis included 1 191 843 patient-days in 2009 and 1 173 672 patient-days in 2010. The overall incidence of CRBSI decreased from 0.19 to 0.15 (p 0.04) and the incidence of CRBSI associated with a CVC decreased from 0.14 to 0.10 (p 0.004) after the intervention. The incidence in PVCs remained unchanged. There was a statistically significant improvement in the adequate maintenance of both CVCs and PVCs. Among the CRBSIs originating in PVCs, 61.8% appeared more than 72 h every insertion. There was a lower infection rate in the hospitals with a higher adherence to the recommendation to replace PVCs after 72 h. Our findings suggest that the implementation of intervention programmes similar to ours could have a major impact on patient safety by reducing the incidence of CRBSIs, and that routine replacement of PVCs might additionally prevent a significant number of bloodstream infections., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

Objectives: A high proportion of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia die within a few days of the onset of infection. However, predictive factors for early mortality (EM) have barely been examined. The aim of this study was to determine the predictive factors for EM in patients with MRSA bacteraemia., Methods: All episodes of MRSA bacteraemia were prospectively followed in 21 Spanish hospitals from June 2008 to December 2009. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed in a central laboratory. Mortality was defined as death from any cause occurring in the 30 days after the onset of MRSA bacteraemia. EM was defined as patients who died within the first 2 days, and late mortality (LM) for patients who died after this period. Multivariate analyses were performed by using logistic regression models., Results: A total of 579 episodes were recorded. Mortality was observed in 179 patients (31%): it was early in 49 (8.5%) patients and late in 130 (22.5%). Independent risk factors for EM were [OR (95% CI)] initial Pitt score >3 [3.99 (1.72-3.24)], previous rapid fatal disease [3.67 (1.32-10.24)], source of infection lower respiratory tract or unknown [3.76 (1.31-10.83) and 2.83 (1.11-7.21)], non-nosocomial acquisition [2.59 (1.16-5.77)] and inappropriate initial antibiotic therapy [3.59 (1.63-7.89)]. When predictive factors for EM and LM were compared, inappropriate initial antibiotic therapy was the only distinctive predictor of EM, while endocarditis and lower respiratory tract sources both predicted LM., Conclusions: In our large cohort of patients several factors were related to EM, but the only distinctive predictor of EM was inappropriate initial antibiotic therapy.

Several studies have suggested that resistance determinants usually reduce virulence. However, their contribution to decrease bloodstream infections is unclear. Our aim was to identify risk factors of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) bacteremia and to assess the prevalence of XDR-PA bacteremia. A retrospective study of PA bloodstream infections in our patient population with at least one clinical sample isolate due to PA (2006-2007) was carried out. A total of 2,131 patients with PA clinical samples were detected. Among 1,657 patients with susceptible-PA isolates, 95 developed PA-susceptible bacteremia. Concomitantly, among 474 patients with multidrug-resistant (MDR)-PA isolates, 265 with XDR-PA, and 209 with non-XDR MDR-PA, 43 developed XDR-PA bacteremia and 13 non-XDR MDR-PA bacteremia, respectively. Pulsed-field gel electrophoresis (PFGE) revealed the clonal nature of the two predominant XDR-PA phenotypes and genetic heterogeneity in non-XDR MDR-PA phenotypes. The proportion of XDR-PA bacteremia was higher than the proportion of bacteremia in the susceptible-PA population (16 % vs. 6 %; p < 0.001). A logistic regression model identified prior exposure to fluoroquinolones [odds ratio (OR) 2.80; 95 % confidence interval (CI) 1.02 to 7.70] as the independent variable associated with XDR-PA bacteremia. Our study suggests that XDR-PA strains have a greater ability to develop bacteremia. It remains unclear as to whether this invasive capacity depends on clonal traits or on other virulence determinants.

Objective: Catheter-related bloodstream infections (CR-BSI) are an increasing problem in the management of critically ill patients. Our objective was to analyze the incidence and epidemiology of CR-BSI in arterial catheters (AC) in a population of critically ill patients., Methods: We conducted a two-year, prospective, non-randomized study of patients admitted for > 24 h in a 24-bed medical-surgical major teaching ICU. We analyzed the arterial catheters and differentiated between femoral and radial locations. Difference testing between groups was performed using the two-tailed t-test and chi-square test as appropriate. Multivariate logistic regression analyses were conducted to identify independent predictors of CR-BSI occurrence and type of micro-organism responsible., Results: The study included 1456 patients requiring AC placement for ≥ 24 h. A total of 1543 AC were inserted for 14,437 catheter days. The incidence of AC-related bloodstream infections (ACR-BSI) was 3.53 episodes per 1000 catheter days. In the same period the incidence of central venous catheter (CVC)-related bloodstream infections was 4.98 episodes per 1000 catheter days. Logistic regression analysis showed that days of insertion (OR: 1.118 95% confidence interval (CI) 1.026-1.219) and length of ICU stay (OR: 1.052 95% CI: 1.025-1.079) were associated with a higher risk of ACR-BSI. Comparing 705 arterial catheters in femoral location with 838 in radial location, no significant differences in infection rates were found, although there was a trend toward a higher rate among femoral catheters (4.13 vs. 3.36 episodes per 1000 catheter days) (p = 0.72). Among patients with ACR-BSI, Gram-negative bacteria were isolated in 16 episodes (61.5%) in the femoral location and seven (28%) in radial location (OR: 2.586; 95% CI: 1.051-6.363)., Conclusions: We concluded that as has been reported for venous catheters ACR-BSI plays an important role in critically ill patients. Days of insertion and length of ICU stay increase the risk of ACR-BSI. The femoral site increases the risk for Gram-negative infection., (Copyright © 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objective: We aimed to study the influence of carbapenem resistance on attributable mortality in a cohort of patients with Pseudomonas aeruginosa bacteremia., Methods: Data on 121 episodes of P. aeruginosa bacteremia occurring between January and December 2005 were retrospectively analyzed., Results: Thirty-three episodes were caused by carbapenem-resistant P. aeruginosa (CRPA) strains and 88 by carbapenem-susceptible P. aeruginosa (CSPA) strains. There was no significant difference in mortality between the groups (33% in CRPA vs. 30% in CSPA; p = 0.69). However, a Kaplan-Meier survival analysis showed that in the first 48h after the onset of bacteremia, there was a lower cumulative mortality proportion in the CRPA group than in the CSPA group (13% vs. 50%; p = 0.026). The independent risk factors associated with death in P. aeruginosa bacteremia were clinical presentation with severe sepsis (odds ratio (OR) 38, 95% confidence interval (CI) 10.2-142.2) and bacteremia of high-risk origin (OR 6.6, 95% CI 1.6-26.9)., Conclusions: According to our data, carbapenem resistance was not associated with higher mortality in patients with P. aeruginosa bacteremia. The slower initial mortality in the CRPA group might have implications in the design of the optimal antibiotic policy strategy., (Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Community-onset infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are increasing. However, there is little information about community-onset bacteremia (CB) due to MRSA in Spain. The objectives of this study were to evaluate the prevalence, clinical and molecular epidemiology, clinical features, and prognosis of CB due to MRSA in comparison with nosocomial bacteremia (NB)., Methods: Prospective multicenter cohort study; all new cases of bacteremia due to MRSA occurring during June 2003 in 59 Spanish hospitals were included. Episodes diagnosed during the first 48 hours of admission were considered CB, and otherwise, NB. Isolates were typed by pulsed field electrophoresis and multilocus sequence typing. Staphylococcal cassete chromosome mec types and Panton-Valentine leukocidin genes were studied by polymerase chain reaction., Results: Sixty-four cases were included; 21 (33%) were classified as CB. In all CB cases, a relation was found with health care, or the isolate proved to be clonally related to nosocomial isolates. There were no significant differences between the groups in terms of demographic data, underlying conditions, prognosis, or characteristics of the isolates. Regarding the source of bacteremia, catheter-related cases were more frequent in NB than CB (39.5% vs 5%, P=0.005), whereas a urinary source was more frequent in CB than NB (25% vs 0%, P=0.001). Most isolates belonged to 2 clones related to the pandemic "pediatric" clone., Conclusion: MRSA should be considered in empiric treatment for certain infectious syndromes in patients with healthcare-associated community-onset sepsis., (Copyright 2009 Elsevier España, S.L. All rights reserved.)

Introduction: Catheter-related bloodstream infection (CR-BSI) is a cause of morbidity and mortality in intensive care units, and the optimal approach for preventing these infections is not well defined. Comparison of CR-BSI rates with those provided by programs such as the National Nosocomial Infection Surveillance System (NNISS) from the USA and the Spanish National Nosocomial Infection Surveillance Study (ENVIN), enable determination of the need to implement control measures. In 2000, we found that the CR-BSI rates in UCIs of our hospital were much higher than the data reported by ENVIN., Objective: To assess the impact of implementing a protocol for proper use of intravascular catheters on CR-BSI rates in the intensive care unit (ICU) of a tertiary hospital., Methods: Prospective study of patients admitted to the ICUs of a tertiary hospital in the months of May and June, from 2000 to 2004. In 2001, a CR-BSI prevention program including aspects related to catheter insertion and maintenance in ICU patients was implemented. We calculated infection rates per 1000 days of catheter use in all the 2-month periods studied, and compared the 2000 and 2004 results by analysis of the odds ratios and confidence intervals., Results: A total of 923 patients were included. Mean age was 58.7 years (SD: 15.4), mean ICU stay was 11.6 days (SD: 11.4), mean SAPSII was 28.2 (SD: 15.9), and mortality was 20.5%. There was a significant reduction in CR-BSI rates from 13.3 episodes per 1000 days of catheter use in the first period to 3.21 in the last period (OR=3.53, 95% CI: 2.36-5.31)., Conclusions: Application of a prevention program for CR-BSI and a system for monitoring BSI rates led to a significant, sustained reduction in these infections.

Objectives: To describe the incidence and clinical characteristics of imipenem-resistant (IR) Pseudomonas aeruginosa bacteraemia., Methods: We performed a retrospective study including all episodes of IR P. aeruginosa bacteraemia seen from January 2003 to December 2005 in a tertiary teaching hospital., Results: There were 108 episodes of IR P. aeruginosa bacteraemia, which represented an incidence of 0.14 episodes per 1000 patient-days in 2003 and 0.11 episodes per 1000 patient-days in 2005. 83 of the episodes (77%) were nosocomially acquired. Most of patients had at least one underlying disease and had previously received antimicrobial treatment. The most frequent source was the urinary tract (31%), followed by unknown origin (22%). A total of 23 (21%) episodes were polymicrobial and 51 (47%) were caused by multidrug-resistant strains. The independent risk factors for mortality from IR P. aeruginosa bloodstream infection were a high-risk source of the bacteraemia (OR: 4.6; 95% CI 1.7-12.4; p=0.01), and presentation with severe sepsis (OR: 2.8; 95% CI 1-7.8; p=0.05)., Conclusions: Our study shows that the rates of IR P. aeruginosa bacteraemia remained stable throughout the study period. The source of bacteraemia and the clinical presentation with severe sepsis were the main determinants of the prognosis.

Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and clinically important. The rise in MRSA bacteremia and endocarditis is related with the increasing use of venous catheters and other vascular procedures. Glycopeptides have been the reference drugs for treating these infections. Unfortunately their activity is not completely satisfactory, particularly against MRSA strains with MICs > 1 microg/mL. The development of new antibiotics, such as linezolid and daptomycin, and the promise of future compounds (dalvabancin, ceftobiprole and telavancin) may change the expectatives in this field.The principal aim of this consensus document was to formulate several recommendations to improve the outcome of MRSA bacteremia and endocarditis, based on the latest reported scientific evidence. This document specifically analyzes the approach for three clinical situations: venous catheter-related bacteremia, persistent bacteremia, and infective endocarditis due to MRSA.

Objective: To assess the risk factors associated with CR-BSI development in critically ill patients with non-tunneled, non-cuffed central venous catheters (CVC) and the prognosis of the episodes of CR-BSI. Design and setting; prospective, observational, multicenter study in nine Spanish Hospitals., Patients: All subjects admitted to the participating ICUs from October 2004 to June 2005 with a CVC., Interventions: None., Measurement and Results: Overall, 1,366 patients were enrolled and 2,101 catheters were analyzed. Sixty-six episodes of CR-BSI were diagnosed. The incidence of CR-BSI was significantly higher in CVC compared with peripherically inserted central venous catheters (PICVC) without significant differences among the three locations of CVC. In the multivariate analysis, duration of catheterization and change over a guidewire were the independent variables associated with the development of CR-BSI whereas the use of a PICVC was a protective factor. Excluding PICVC, 1,598 conventional CVC were analyzed. In this subset, duration of catheterization, tracheostomy and change over a guidewire were independent risk factors for CR-BSI. A multivariate analysis of predictors for mortality among 66 patients with CRSI showed that early removal of the catheter was a protective factor and APACHE II score at the admission was a strong determinant of in-hospital mortality., Conclusions: Peripherically inserted central venous catheters is associated with a lower incidence of CR-BSI in critically ill patients. Exchange over a guidewire of CVC and duration of catheterization are strong contributors to CR-BSI. Our results reinforce the importance of early catheter removal in critically ill patients with CR-BSI.

Bloodstream infections (BSIs) related to central venous catheters (CVCs) and arterial catheters (ACs) are an increasing problem in the management of critically ill patients. Our objective was to assess the efficacy of a needle-free valve connection system (SmartSite), Alaris Medical Systems, San Diego, CA, USA) in the prevention of catheter-related bloodstream infection (CR-BSI). Patients admitted to an intensive care unit were prospectively assigned to have a CVC and AC connected with either a needle-free valve connection system (NFVCS) or a three-way stopcock connection (3WSC). The characteristics of the patients were similar in the two groups. Before manipulation, the NFVCS was disinfected with chlorhexidine digluconate 0.5% alcoholic solution. The 3WSC was not disinfected between use but it was covered with a protection cap. A total of 799 patients requiring the insertion of a multilumen CVC or AC for >48h from 1 April 2002 to 31 December 2003 were included. CR-BSI rates were 4.61 per 1000 days of catheter use in the disinfected NFVCS group and 4.11 per 1000 days of catheter use in the 3WSC group (P=0.59). When CVC-BSIs and AC-BSIs were analysed separately, the rate of CVC-BSI was 4.26 per 1000 days of catheter use in the NFVCS group, compared with 5.27 in the 3WSC group (P=0.4). The incidence rate of AC-BSI was 5.00 per 1000 days of catheter use in the NFVCS group, compared with 2.83 in the 3WSC group (P=0.08). The use of NFVCS does not reduce the incidence of catheter-related bacteraemia. The arterial catheter (AC) is a significant source of infection in critically ill patients.

Despite enormous clinical experience of using peripheral vascular catheters, there is still controversy over the incidence and clinical relevance of bloodstream infections caused by these devices and the measures for preventing them. We performed a prospective study to determine the clinical epidemiology and outcomes of nosocomial bloodstream infections caused by short- and mid-line peripheral venous catheters among a group of non-intensive care unit patients. Cases of peripheral venous catheter-related bloodstream infections (PVC-BSIs) were compared to cases of central venous catheter-related bloodstream infections (CVC-BSIs). From October 2001 to March 2003, 150 cases of vascular catheter-related bloodstream infections were identified among 147 patients. Seventy-seven episodes (0.19 cases/1000 patient-days) were PVC-BSIs and 73 episodes (0.18 cases/1000 patient-days) were CVC-BSIs. Compared with CVC-BSIs, patients with PVC-BSIs more often had the catheter inserted in the emergency department (0 vs 42%), had a shorter duration from catheter insertion to bacteraemia (mean: 15.4 vs 4.9 days) and had Staphylococcus aureus (33 vs 53%) more frequently as the causative pathogen. Among patients with PVC-BSIs, catheters inserted in the emergency department had a significantly shorter duration in situ compared with those inserted on hospital wards (mean: 3.7 vs 5.7 days). Patients with PVC-BSIs caused by S. aureus had a higher rate of complicated bacteraemia (7%) and higher overall mortality (27%) than patients with PVC-BSIs caused by other pathogens (0 and 11%, respectively). Bloodstream infections remain underestimated and potentially serious complications of peripheral vascular catheterisation. Targeted interventions should be introduced to minimise this complication.

Meticillin-resistant Staphylococcus aureus (MRSA) is prevalent throughout the healthcare system in Spain, particularly in long-term care facilities (LTCF) and the incidence of MRSA bloodstream infection (MRSA-BSI) at hospital admission is increasing. This study aimed to determine factors that predict meticillin resistance among patients who require hospitalization for S. aureus BSI. We performed a case-control study comparing patients with S. aureus at hospital admission from January 1991 to December 2003. Case patients with MRSA-BSI at hospital admission (N=50) were compared with control patients with meticillin-susceptible S. aureus bloodstream infection (MSSA-BSI) at hospital admission (N=98). The incidence of MRSA-BSI at hospital admission increased significantly from 0.08 cases/1000 hospital admissions in 1991 to 0.37 cases in 2003 (P<0.001). Univariate analysis comparing patients with MRSA- and MSSA-BSI found a significant association between meticillin resistance and age >60 years, female sex, prior MRSA isolation and healthcare-related BSI. No differences were found in underlying conditions such as diabetes, haemodialysis, immunosuppression, source of infection or mortality between the two groups. Multivariate analyses identified prior MRSA isolation [odds ratio (OR): 41; 95% confidence interval (CI): 4-350] and admission from long-term care facilities (OR: 37; 95% CI: 4.5-316) as independent risk factors for MRSA-BSI.

We describe a case of bacteremia due to an as yet unclassified Acinetobacter genomic species 17-like strain. The recognition of this microorganism as non-Acinetobacter baumannii may have important epidemiological implications, as it relieves the hospital of the implementation of barrier precautions for patients infected or colonized as may be necessary with a multiresistant A. baumannii epidemic.

A retrospective analysis of data from January 1996 to June 2004 was performed to evaluate the transmission of bacterial infections from organ donors to recipients. Donors were classified according to blood culture results: group 1 with negative blood culture (n = 216), and group 2 with positive blood cultures (n = 52). The age, cause of death, temperature, leukocytes, and number of organs procured were similar in both groups. Donors of group 2 had significantly more days in the intensive care unit (ICU): group 1 (3.14 +/- 3) versus group 2 (4.39 +/- 3.38 days P = .038). Fifty-one percent of group 1 and 52% of group 2 received antibiotic treatment, in most cases because of the suspected presence of a respiratory infection. In 22 donors the organisms that yielded in the blood culture were considered potentially pathogenic/contaminants (subgroup 2A) and in 30 donors the organisms were considered pathogenic (subgroup 2B). The demographic profiles of these two subgroups were similar. During the first month after transplantation, kidney and liver recipients were closely monitored. Recipients received wide-spectrum antimicrobial prophylaxis. Ten of 61 renal recipients developed infectious diseases. In nine cases (four in subgroup 2A and five in subgroup 2B) there were urinary infections. One recipient of subgroup 2B developed prostatitis. Six of 34 hepatic recipients developed infectious diseases. Four of the six cases (four in group 2A and five in group 2B) developed catheter infections and two cases of peritoneal infections. We could not find any case where a bacterial blood isolate from a donor matched a positive culture in the corresponding recipient. A longer stay of a donor in the ICU resulted in the more pronounced growth of organisms in blood cultures, as expected. In our experience, organs obtained from a donor with a positive blood culture may be transplanted safely, probably due to the low virulence of the organisms as well as the polymicrobial therapy routinely given to the recipients.

This study describes the clinical outcome of an outbreak of extended-spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-KP) bacteraemia. Ninety-two episodes of hospital-acquired K. pneumoniae bacteraemia were studied, 49 ESBL-KP and 43 non-ESBL-KP, from May 1993 to June 1995. Of these, 44 (90%) episodes of ESBL-KP vs. 20 (46%) episodes of non-ESBL-KP occurred in intensive care unit (ICU) patients. The incidence of K. pneumoniae bacteraemia (mainly due to ESBL-KP) increased in the ICU during the outbreak. A significant association was found between intravascular catheter-related bacteraemia and isolation of ESBL-KP [27 (56%) in the ESBL-KP group vs. 13 (30%) in the non-ESBL-KP group;P= 0.01]. The worst prognostic features were identified as age > 65 years (P= 0.02), septic shock (P< 0.001) and secondary bacteraemia (P= 0.04). High rates of resistance to beta-lactam/beta-lactamase inhibitors observed in our ESBL-KP isolates, as well as variable activity of aminoglycosides, restricts the empirical use of these antibiotics. Carbapenems should be the treatment of choice since they are uniformly active against these strains. Our study shows that ESBL-KP bacteraemia occurring in an epidemic ICU setting is mainly catheter-related. We did not find ESBL strains to be associated with a significantly poor outcome., (Copyright 2001 The Hospital Infection Society.)

Objectives: To determine the relevance of nasal carriage of Staphylococcus aureus, either methicillin-sensitive (MSSA) or methicillin-resistant (MRSA), as a risk factor for the development of nosocomial S aureus bacteremia during an MRSA outbreak., Patients and Methods: In this prospective cohort study, 488 patients admitted to an intensive care unit (ICU) during a 1-year period were screened with nasal swabs within 48 hours of admission and weekly thereafter in order to identify nasal S aureus carriage. Nasal staphylococcal carriers were observed until development of S aureus bacteremia, ICU discharge, or death., Results: One hundred forty-seven (30.1%) of 488 patients were nasal S aureus carriers; 84 patients (17.2%) harbored methicillin-sensitive S aureus; and 63 patients (12.9%) methicillin-resistant S aureus. Nosocomial S aureus bacteremia was diagnosed in 38 (7.7%) of 488 patients. Rates of bacteremia were 24 (38%) of the MRSA carriers, eight (9.5%) of the MSSA carriers, and six (1.7%) of noncarriers. After adjusting for other predictors of bacteremia by means of a Cox proportional hazard regression model, the relative risk for S aureus bacteremia was 3.9 (95% confidence interval, 1.6-9.8; P = 0.002) for MRSA carriers compared with MSSA carriers., Conclusions: Among ICU patients, nasal carriers of S aureus are at higher risk for S aureus bacteremia than are noncarriers; in the setting of an MRSA outbreak, colonization by methicillin-resistant strains represents a greater risk than does colonization by MSSA and strongly predicts the occurrence of MRSA bacteremia.

From 1988 to 1992, 27 of 855 cases of Escherichia coli bacteremia in nonneutropenic adult patients observed at our hospital were due to ciprofloxacin-resistant (CIPRO-R) strains. Eighteen episodes (67%) were community acquired, and nine (33%) were nosocomially acquired. Overall, the rates of E. coli bacteremia caused by CIPRO-R strains increased steadily from 0% in 1988 to 7.5% in 1992 (P < 0.01). There was a statistically significant correlation between the incidence of CIPRO-R E. coli bacteremia and the upward trend in fluoroquinolone (norfloxacin and ciprofloxacin) use in the community (r = 0.974; P = 0.005) as well as in the hospital (r = 0.975; P = 0.005). When we compared the 27 case patients with 54 simultaneous control patients who had ciprofloxacin-susceptible E. coli bacteremia, the case patients more frequently had chronic underlying diseases (71 versus 37%; P = 0.004), urinary tract infection (74 versus 50%; P = 0.03), prior surgery (22 versus 6%; P = 0.02), and prior fluoroquinolone use (63 versus 4%; P < 0.001). A logistic regression analysis identified prior quinolone use as the only independent risk factor for CIPRO-R E. coli bacteremia. In conclusion, our study shows a significant correlation between ciprofloxacin resistance and fluoroquinolone use and indicates that prior fluoroquinolone use seems to be the most important risk factor for CIPRO-R E. coli bacteremia.

In a prospective surveillance study (February 1990-December 1991) performed at a 1000-bed teaching hospital to identify risk factors for nosocomial methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, 309 patients were found to be colonized (n = 103; 33%) or infected (n = 206; 67%) by MRSA. Sixty-three of them developed bacteremia. Compared with 114 patients who had nosocomial bacteremia caused by methicillin-sensitive Staphylococcus aureus during the same period of time, MRSA bacteremic patients had more severe underlying diseases (p < 0.01), were more often in intensive care units (p < 0.01) and had received prior antibiotic therapy more frequently (p < 0.01). To further identify risk factors for MRSA bacteremia, univariate and multivariate analyses of this series of 309 patients were performed using the occurrence of MRSA bacteremia as the dependent variable. Among 14 variables analyzed, intravascular catheterization, defined as one or more intravascular catheters in place for more than 48 h, was the only variable selected by a logistic regression model as an independent risk factor (OR = 2.7, CI = 1.1-6.6). The results of this study reinforce the concept that recent antibiotic therapy may predispose patients to MRSA infection and suggest that among patients colonized or infected by MRSA, those with intravascular catheters are at high risk of developing MRSA bacteremia.

Background: The aim of this study was to establish the clinical and epidemiologic features of nosocomial bacteremia by Enterobacter spp. and to analyse its prognostic factors., Methods: A prospective study of the episodes of nosocomial bacteremia by Enterobacter spp. with clinical significance, detected in a third level university hospital from January 1984 to December 1990 was performed., Results: During the study period, 226 episodes of bacteremia by Enterobacter spp., of which 184 (81%) were of nosocomial origin (8.1% of all the nosocomial bacteremias), while 14% were polymicrobial. An increasing trend was observed in the number of episodes (1984 vs 1990) from 0.9 vs 1.8 episodes per 1,000 admissions, respectively. The mean age was 57 years and the male/female relation was 2.4/1. The most frequent focus of origin was infection of the vascular catheter (43%), followed by intraabdominal catheter (21%), urinary tract (14%), and other foci (17%). Fifty-four percent of the patients had received antibiotics prior to the episode of bacteremia. Most of the cases were detected in the Intensive Care Units (ICU) (41%) and in the gastrointestinal surgery area (24%). Global mortality was 23%. Logistic regression analysis selected an entry site other than infection of the vascular catheter (odds ratio 6.1; CI [95%)] 2.0-18.4), shock (odds ratio, 6; CI [95%], 1.6-21.9) and immunosuppressive treatment (odds ratio, 5; CI [95%], 1.5-16.2) as independent variables of bad prognosis., Conclusions: Enterobacter spp. is an important nosocomial pathogen taking fourth place in the ranking of nosocomial bacteremia by gram negative bacilli. It predominantly affects a population of patients admitted in the ICU and surgery. The intravascular catheter is a frequent entry site for nosocomial bacteremia by Enterobacter spp.

Background: Nosocomial enterococcal infections have increased in various institutions, and patients with these infections had often been treated with cephalosporins during the previous weeks. The objective of this study was to determine whether the use of second- and third-generation cephalosporins is a risk factor for nosocomial enterococcal bacteremia (NEB), by means of a matched case-control study design., Methods: Two hundred seven cases of NEB were studied. A control was matched to each case by sex, age (+/- 10 years), date of admission (+/- 2 years), hospital service, days of hospitalization, primary diagnosis, and operative procedures., Results: One hundred fifty-six cases had an appropriate matched control. The univariate analysis of unmatched variables showed that the presence of a urinary catheter (odds ratio [OR], 3.8), mechanical ventilation (OR = 2.6), and cephalosporin use (OR = 5.1) were associated with NEB. Using a conditional logistic regression model, cephalosporin use (adjusted OR = 4.8, 95% confidence interval, 2.3 to 9.8) and urinary catheter use (adjusted OR = 3.6, 95% confidence interval, 1.7 to 7.4) remained significantly associated with NEB after controlling for other unmatched variables., Conclusions: These data show that the use of second- and third-generation cephalosporins may be a major risk factor for NEB. It may explain, at least partially, the steadily increasing number of enterococcal infections observed in some hospitals.

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 < 0.001) and definitive antimicrobial therapy (96 % vs. 50 %; p < 0.001), susceptible P. aeruginosa VAP presented a trend towards early mortality (29 % vs. 15 %; p = 0.06). A logistic regression model with early mortality as the dependent variable identified multiorgan dysfunction syndrome (MODS) [odds ratio (OR) 10.4; 95 % confidence interval (CI) 1.7-63.5; p = 0.01] and inadequate antibiotic therapy (OR 4.27; 95 % CI 0.98-18.4; p = 0.052) as independent risk factors for early mortality. A similar analysis identified MODS (OR 4.31; 95 % CI 1.14-16.2; p = 0.03) as the only independent predictor of crude mortality. The severity of acute illness clinical presentation was the main predictor of mortality. Despite adequate antibiotic therapy, susceptible P. aeruginosa seems to cause major early mortality. Although adequate therapy is essential to treat VAP, the severity of acute illness is a more important factor than drug resistance. [ABSTRACT FROM AUTHOR]