Search

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

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

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

Long-term care facilities (LTCFs) have become receptors of patients with a high risk of healthcare-associated infections (HAIs).To determine the prevalence of HAIs in LTCFs.During the period 2011-2014 2 annual prevalence studies were performed according to Healthcare-associated infections in long-term-care facilities (HALT) study definitions and methodology.A total of 28,360 patients were included in the study. The overall prevalence rate of HAIs was 10.2%. Subacute units and palliative care units showed the highest rates, 22.3% and 18.7%, respectively. Main infections were respiratory tract infection (35.8%) and urinary tract infection (35.8%).These results were higher than other similar experiences, a fact that suggests the need to extend the specific strategies and programs to LTCFs, and ensuring a sufficient number of specialised staff in infection control.

Resumen Introduccion Los centros sanitarios de cuidados prolongados (CSCP) se han convertido en receptores de enfermos con un alto riesgo de aparicion de infecciones relacionadas con la asistencia sanitaria (IRAS). Objetivo Determinar la prevalencia de las IRAS en los CSCP de nuestro medio. Metodo Durante el periodo 2011-2014 se realizaron 2 estudios anuales de prevalencia siguiendo las definiciones y metodologia del estudio Healthcare-associated infections in long-term-care facilities (HALT). Resultados La muestra final fue de 28.360 pacientes. La prevalencia de IRAS en los datos agregados fue de 10,2%. Las unidades de subagudos, con un 22,3%, y paliativos, con un 18,7%, fueron las que presentaron un mayor porcentaje de infecciones. Las infecciones mas frecuentes fueron las respiratorias (35,8%) y las urinarias (35,8%). Conclusion La prevalencia de infeccion en nuestros CSCP fue muy superior a la publicada en el estudio HALT. Nuestros resultados muestran la necesidad de desarrollar programas preventivos especificos en estos centros, garantizando un numero suficiente de personal especializado en el control de las infecciones.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

REIPI/GEIH Study Group: A. Jover, F. Barcenilla, M. García (Hospital ‘Arnau de Vilanova’, Lleida, Spain); M. Pujol, O. Gasch, M.A. Domínguez, M. Camoez (Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain); C. Dueñas, E. Ojeda (Hospital Universitario de Burgos, Burgos, Spain); J. A. Martinez, F. Marco (Hospital Clinic, Barcelona, Spain); F. Chaves, M. Fernández-Ruiz, M. Lagarde, F. López-Medrano, J. M. Aguado (Hospital Universitario ‘12 de Octubre’, Madrid, Spain); J. M. Montejo, E. Bereciartua, J. L. Hernández (Hospital de Cruces, Barakaldo, Spain); M. A. Von Wichmann, A. Goenaga, J. M. García-Arenzana (Hospital de Donostia, Donostia, Spain); B. Padilla, C. Padilla, E. Cercenado (Hospital General Universitario ‘Gregorio Marañón’, Madrid, Spain); G. García-Pardo, J. Tapiol (Hospital Universitari ‘Joan XXIII’, Tarragona, Spain); J. P. Horcajada, M. Montero, M. Salvadó (Hospital Universitari del Mar, Barcelona, Spain); A. Arnáiz, C. Fernández (Hospital Universitario ‘Marqués de Valdecilla’, Santander, Spain); E. Calbo, M. Xercavins (Hospital Universitari Mútua de Terrassa, Terrassa, Spain); A. Granados, D. Fontanals (Corporació Sanitària Parc Taulí, Sabadell, Spain); V. Pintado, E. Loza (Hospital Universitario ‘Ramón y Cajal’, Madrid, Spain); J. Torre-Cisneros, R. Lara, F. Rodríguez-López, M. Rodríguez, C. Natera (Hospital Universitario ‘Reina Sofía’, Córdoba, Spain); J. R. Blanco, I. Olarte (Hospital Universitario ‘San Pedro’, Logroño, Spain); N. Benito, B. Mirelis (Hospital Universitari de la Santa Creu i Sant Pau, Barcelona, Spain); J. Murillas, E. Ruiz de Gopegui (Hospital Universitari Son Dureta, Palma de Mallorca, Spain); H. Espejo, M. A. Morera (Hospiyal de Terrassa, Terrassa, Spain); J. Rodríguez-Baño, E. López, A. Pascual (Hospital Universitario ‘Virgen Macarena’, Sevilla, Spain); C. Martín, J. A. Lepe, J. Molina (Hospital Universitario ‘Virgen del Rocío’, Sevilla, Spain); R. Sordé, B. Almirante, N. Larrosa (Hospital Universitari Vall d’Hebrón, Barcelona, Spain)., [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., This study was co-funded by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa [co-financed by the European Development Regional Fund (ERDF) ‘A way to achieve Europe’] and by the Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). M. F. R. holds a clinical research contract ‘Juan Rodés’ (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III.

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

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

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

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

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

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

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

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

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

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.

Resumen Introduccion Las infecciones de presentacion comunitaria por Staphylococcus aureus resistente a meticilina (SARM) son un fenomeno creciente. Sin embargo, existe escasa informacion acerca de las bacteriemias de presentacion comunitaria (BPC) por SARM en nuestro medio. Los objetivos de este estudio son evaluar la frecuencia, la epidemiologia clinica y molecular, las caracteristicas clinicas y las caracteristicas pronosticas de las BPC por SARM con respecto a las bacteriemias nosocomiales (BN). Metodos Estudio de cohorte prospectivo y multicentrico; se incluyeron todos los casos incidentes de bacteriemia por SARM en 59 hospitales espanoles durante el mes de junio de 2003. Se considero BPC a aquella que se diagnostico en las primeras 48 h de ingreso del paciente, y BN cuando se realizo posteriormente. Las cepas se tiparon mediante electroforesis en campo pulsante y multilocus sequence typing ; los tipos de casete cromosomico estafilococico mec y produccion de leucocidina de Panton-Valentine se estudiaron por reaccion en cadena de la polimerasa. Resultados Se incluyeron 64 bacteriemias; 21 (33%) de ellas se consideraron como BPC. En todos estos casos se encontro relacion con la atencion sanitaria o bien se detecto una cepa genotipicamente relacionada con las nosocomiales. No se observaron diferencias significativas entre los 2 grupos en cuanto a los datos demograficos, las caracteristicas intrinsecas, el pronostico o las caracteristicas de las cepas. En relacion con el foco de origen, las originadas en un cateter vascular fueron mas frecuentes en las BN (el 39,5 versus el 5%; p = 0,005) y las originadas en el aparato urinario fueron mas frecuentes en las BPC (el 25 versus el 0%; p = 0,001). La mayoria de las cepas pertenecio a 2 clones relacionados con el clon pandemico denominado “pediatrico”. Conclusion Es necesario considerar SARM en el tratamiento empirico de determinados sindromes infecciosos de pacientes con sepsis de presentacion comunitaria y relacion previa con los cuidados sanitarios.

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.

Cefepime (FEP) and ceftazidime (CAZ) are broad-spectrum cephalosporins that display similar MICs for wild-type Pseudomonas aeruginosa strains. Recently, P. aeruginosa isolates showing a discordance in susceptibility to CAZ and FEP have been noted at the Hospital de Bellvitge in Barcelona, Spain, and a clustering was suspected. During the study period (March to December 2007), 51 patients, particularly those in an intensive care units (ICUs) ( n = 29 [57%]), infected or colonized with at least one P. aeruginosa non-FEP-susceptible and CAZ-susceptible (Fep ns Caz s ) phenotype strain were detected. Twenty-three (45%) patients were infected, and the respiratory tract was the most frequent site of infection. Changes in the consumption of antimicrobials in the ICUs were observed over time: a progressive reduction in the levels of consumption of carbapenems (247 defined daily doses [DDD]/1,000 patient days to 66 DDD/1,000 patient days; P = 0.008), after restriction of its use in 2006, and an expected increase in the rate of piperacillin-tazobactam use (42 DDD/1,000 patient days in 2004 to 200 DDD/1,000 patient days in 2007; P < 0.001). Throughout the whole study period, only a single clone of a P. aeruginosa Fep ns Caz s phenotype strain was identified by pulsed-field gel electrophoresis analysis to be associated with the hyperexpression of MexXY-OprM and the production of an integron-borne PSE-1 ß-lactamase. In conclusion, we identified an epidemic P. aeruginosa clone of an Fep ns Caz s phenotype strain involving 51 patients, in particular, ICU patients. The combination of the overexpression of an efflux pump and PSE-1 ß-lactamase production is associated with the multidrug-resistant phenotype. The dominant use of a single class of antibiotics could have provided the selective pressure required for the emergence and spread of this P. aeruginosa strain.

Summary Objectives We investigated the influence of empirical therapy on the mortality of patients with health care-associated (HCA) sepsis caused by methicillin-resistant Staphylococcus aureus (MRSA) infections in a multicenter cohort, and the variables associated with inappropriate empirical therapy. Methods All new cases of infection caused by HCA-MRSA presenting with sepsis syndrome in 59 Spanish hospitals during June 2003 were prospectively followed. The main outcome variable was mortality at day 30. Predictors of mortality and of inappropriate empirical therapy were studied using multivariate logistic regression. Results We included 209 cases. Crude mortality was 23%. After controlling for severity of the underlying condition, ICU stay, presentation with severe sepsis or shock, and site of infection, inappropriate empirical therapy was associated with an increased odds of mortality (OR=3.0; 95% CI: 1.01–9.0; p =0.04). Only 21.1% of the patients received appropriate empirical therapy. Variables independently associated with appropriate therapy were recent surgery, central venous catheter and certain sites of infection (primary bacteraemia, intraabdominal infections, and respiratory tract infections). Cancer patients were at an increased risk of receiving inappropriate therapy. Conclusions Inappropriate empirical therapy was independently associated with increased mortality in this multicenter cohort. Clinicians should be aware of the need to consider coverage against MRSA more frequently.

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.

Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) strains are no longer limited to acute-care hospitals but have now spread to other healthcare settings such as long-term-care facilities (LTCFs), in most of which they are endemic. In Europe, few studies have addressed the MRSA situation in LTCFs. A cross-sectional study to determine MRSA prevalence and factors associated with S. aureus carriage in community LTCF residents is reported here. Nasal and decubitus ulcer cultures were performed for residents of nine community LTCFs. Residents were classified as MRSA carriers, methicillin-susceptible S. aureus carriers and non-carriers. Overall, 1377 nasal swabs and 82 decubitus ulcer cultures were performed. MRSA was isolated from 15.5% and 59.0% of the former and latter, respectively. The prevalence of MRSA colonization was 16.8% (95% CI 14.9–18.8), varying from 6.7% to 35.8% (p

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. All subjects admitted to the participating ICUs from October 2004 to June 2005 with a CVC. None. 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. 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.

La infecciones producidas por Staphylococcus aureus resistentes a la meticilina (SARM) son un motivo de creciente preocupacion en los centros de larga estancia (CLE). Los estudios epidemiologicos practicados en nuestro ambito han mostrado unas tasas de colonizacion por SARM en la poblacion geriatrica que pueden ser muy elevadas en determinados centros. Sin embargo, la repercusion clinica que tiene esa colonizacion suele ser escasa. Con los conocimientos que tenemos hasta la actualidad, la prevencion de la transmision del SARM en los CLE pasa por la aplicacion de medidas de prevencion sencillas pero de demostrada eficacia, como el lavado de manos, la cobertura adecuada de heridas infectadas, el uso adecuado de los antibioticos, sin limitar las actividades de los residentes colonizados ni realizar tareas de vigilancia activa.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen, both in-hospital and in the community. Although there are several guidelines with recommendations for the control of this microorganism, the measures proposed are not uniformly implemented in Spanish hospitals. The objective of this document is to provide evidence-based recommendations that are applicable to Spanish hospitals, with the aim of reducing transmission of MRSA in our health care centers. The recommendations are divided into the following groups: surveillance, active detection of colonization in patients and health care workers, control measures for colonized or infected patients, decolonization therapy, environmental cleaning and disinfection, antimicrobial consumption, measures for non-hospitalized patients, and others. The main measures recommended include appropriate surveillance, hand hygiene, and implementation of active surveillance, contact precautions, and environmental cleaning.

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.

Enterobacter cloacae has been associated with several outbreaks, usually involving strains that overproduce chromosomal β-lactamase or, uncommonly, strains expressing extended-spectrum β-lactamases (ESBL). Only sporadic cases of ESBL-producing E. cloacae have been identified in our hospital in recent years. We describe the epidemiology and clinical and microbiological characteristics of an outbreak caused by ESBL-producing E. cloacae in a cardiothoracic intensive care unit (CT-ICU). Prospective surveillance of patients with infection or colonization by ESBL-producing E. cloacae among patients admitted to the CT-ICU was performed during the outbreak. Production of ESBL was determined by decreased susceptibility to expanded-spectrum cephalosporins and a positive double-disk test result. Clone relatedness was determined by pulsed-field gel electrophoresis (PFGE). From July to September 2005, seven patients in the CT-ICU with ESBL-producing E. cloacae were identified (four males; median age, 73 years; range, 45 to 76 years); six patients had cardiac surgery. Four patients developed infections; three had primary bacteremia, one had ventilator-associated pneumonia, and one had tracheobronchitis. ESBL-producing E. cloacae showed resistance to quinolones and aminoglycosides. PFGE revealed two patterns. Five isolates belonged to clone A; two carried a single ESBL (pI 8.2 and a positive PCR result for the SHV type), and three carried two ESBLs (pIs 8.1 and 8.2 and positive PCR results for the SHV and CTX-M-9 types). Isolates belonging to clone B carried a single ESBL (pI 5.4 and a positive PCR result for the TEM type). Review of antibiotic consumption showed increased use of cefepime and quinolones during June and July 2005. The outbreak was stopped by the implementation of barrier measures and cephalosporin restriction. ESBL production could be increasingly common in nosocomial pathogens other than Escherichia coli or Klebsiella pneumoniae .

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 (P0.001). Univariate analysis comparing patients with MRSA- and MSSA-BSI found a significant association between meticillin resistance and age60 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.

To determine the epidemiology and risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR-PA) digestive tract colonization, weekly rectal and pharyngeal swabs were obtained in two serial incidence surveys (266 patients). Forty-two (16%) patients were CR-PA colonized (12 [29%] on admission and 30 [71%] in intensive care units). Pulsed-field gel electrophoresis showed extensive clonal diversity, although one specific clone (type B) was isolated from 11 patients. The presence of similar genotypes of CR-PA colonizing 30% of the CR-PA-colonized patients suggests the occurrence of cross-colonization; in addition, 10 pairs of carbapenem-susceptible P. aeruginosa (CS-PA) and subsequent CR-PA strains isolated from the same patients were found to be clonally identical and were considered to have been endogenously acquired (33%). All endogenously acquired CR-PA strains were isolated after exposure to a carbapenem, and 80% showed a phenotype of imipenem resistance (IR pattern) alone, while 67% of the CR-PA strains acquired by cross-transmission exhibited a multiresistant (MR) phenotype, with previous carbapenem exposure in 44%. Logistic regression analysis identified severity of acute illness (odds ratio [OR], 1.0; 95% confidence interval [CI], 1.0 to 1.1), prior carbapenem use (OR, 7.8; 95% CI, 1.7 to 35.3), and prior use of fluoroquinolones (OR, 11.0; 95% CI, 1.7 to 67.9) as independent risk factors for CR-PA digestive tract colonization. Overall, the local epidemiology of CR-PA digestive tract colonization was characterized by polyclonal endemicity with phenotype patterns of IR and MR divided evenly between patients. Restricting the use of particular agents, such as carbapenems and fluoroquinolones, should be considered advisable to minimize the problem of this antibiotic resistance. However, the possible risk for development of collateral unexpected bacterial resistance patterns should be accurately monitored.

To compare clinical and microbiological characteristics, treatment and outcomes of MRSA bacteraemia among elderly and younger patients.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).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).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.

Background Our institution experienced an endemic situation with extensively drug-resistant (XDR) Acinetobacter baumannii in the intensive care units (ICUs). Here, we describe the long-term results of the implementation of a screening and cohorting policy and new cleaning techniques based on a procedure that we call the 1 room, 1 wipe approach. Methods We conducted a 4-year quasi-experimental study in the ICUs of an 800-bed teaching hospital. The main actions implemented were active surveillance of XDR A baumannii and cohorting of carriers and introducing new cleaning techniques intended to avoid sharing wipes between rooms. Results XDR A baumannii significantly decreased from 132 cases in 2011 to 8 cases in 2014 and from 10.78 cases per 1,000 patient days in 2011 to 0.69 cases per 1,000 patient days in 2014. Segmented regression analysis showed that after implementing the measures, the monthly rates presented a sustained negative slope, with a significant change of −0.623 ( P = .002). Conclusions The prompt identification and isolation of patients and adequate environmental cleaning are effective measures for reducing XDR A baumannii in ICUs. The 1 wipe, 1 room approach should be considered a standard measure for cleaning hospital facilities to avoid cross-transmission as a result of reusable cleaning wipes.

Background: Colonization by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been found to be markedly more common in HIV-infected individuals in the USA. Studies evaluating the prevalence MRSA colonization in HIV-infected populations in Europe are scarce. The aim of this study was to investigate the prevalence of MRSA colonization in a cohort of HIV-infected patients in Barcelona, Spain. Methods: Nasal and pharyngeal S. aureus carriage was assessed in a random sample of 190 patients from an outpatient HIV clinic. Nasal and pharyngeal swab specimens were obtained for staphylococcal culture from 190 and 110 patients respectively. All MRSA isolates were screened for Panton-Valentine leukocidin (PVL) genes by PCR. Molecular characterization of MRSA isolates was performed by multilocus sequence typing. Data related to HIV infection, healthcare exposure, and previously described risk factors for MRSA were collected from medical records and a questionnaire administered to each patient. Results: The patients' characteristics were as follows: male, 83 %; median (IQR) age, 45 (39-49) years; intravenous drug users, 39 %; men who have sex with men, 32 %; heterosexual, 26 %; CD4 count, 528/μL (IQR 351-740); on antiretroviral therapy, 96 %; and undetectable plasma viral load, 80 %. Sixty-five patients (34 %) were colonized by S. aureus. MRSA colonization was found in 1 % and 2 % of nasal and pharyngeal samples respectively. No PVL positive MRSA strains were detected and all the MRSA isolates belonged to typical hospital-acquired clones. Conclusions: Our data suggest that CA-MRSA colonization is not currently a problem in HIV-infected individuals in our area.