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Objective: To assess the performance of differential time to positivity (DTP) for the diagnosis of catheter-related bloodstream infections (CRBSI)., Methods: From all episodes of bloodstream infections (BSI) diagnosed during a 15-year period (2003-17) those in which a paired set of blood cultures drawn from a catheter and a peripheral vein were positive for the same microorganism and had a clinically and/or microbiologically defined source were selected. To assess diagnostic discrimination ability and accuracy of DTP for CRBSI, area under the receiver operating characteristic curves (AUC) and performance characteristics of a DTP ≥2 h were computed., Results: A total of 512 BSI were included, of which 302 (59%) were CRBSI. Discrimination ability of DTP was low for Staphylococcus aureus (AUC 0.656 ± 0.06), coagulase-negative staphylococci (AUC 0.618 ± 0.081), enterococci (AUC 0.554 ± 0.117) and non-AmpC-producing Enterobacteriaceae (AUC 0.653 ± 0.053); moderate for Pseudomonas aeruginosa (AUC 0.841 ± 0.073), and high for AmpC-producing Enterobacteriaceae (AUC 0.944 ± 0.039). For the entire sample, DTP had a low-to-moderate discrimination ability (AUC 0.698 ± 0.024). A DTP ≥2 h has a low sensitivity for coagulase-negative staphylococci (60%) and very low for S. aureus (34%), enterococci (40%) and non-AmpC-producing Enterobacteriaceae (42%). A DTP cut-off of 1 h improved sensitivity (90%) for AmpC-producing Enterobacteriaceae., Conclusions: Differential time to positivity performs well for diagnosing CRBSI only when AmpC-producing Enterobacteriaceae and P. aeruginosa are involved. Performance is low for common Gram-positive organisms and non-AmpC-producing enteric bacilli; a negative test should not be used to rule out CRBSI due to these microorganisms. A DTP ≥1 h may improve accuracy for AmpC-producing Enterobacteriaceae, particularly Enterobacter spp., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: Tropheryma whipplei has been detected in 3.5% of the blood culture-negative cases of endocarditis in Spain. Experience in the management of T. whipplei endocarditis is limited. Here we report the long-term outcome of the treatment of previously reported patients who were diagnosed with infective endocarditis (IE) caused by T. whipplei from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) and discuss potential options for antimicrobial therapy for IE caused by T. whipplei., Patients and Methods: Seventeen patients with T. whipplei endocarditis were recruited between 2008 and 2014 in 25 Spanish hospitals. Patients were classified according to the therapeutic regimen: ceftriaxone and trimethoprim/sulfamethoxazole, doxycycline + hydroxychloroquine and other treatment options., Results: Follow-up data were obtained from 14 patients. The median follow-up was 46.5 months. All patients completed the antibiotic treatment prescribed, with a median duration of 13 months. Six patients were treated with ceftriaxone and trimethoprim/sulfamethoxazole (median duration 13 months), four with doxycycline + hydroxychloroquine (median duration 13.8 months) and four with other treatment options (median duration 22.3 months). The follow-up after the end of the treatments was between 5 and 84 months (median 24 months)., Conclusions: All treatment lines were effective and well tolerated. Therapeutic failures were not detected during the treatment. None of the patients died or experienced a relapse during the follow-up. Only six patients received antibiotic treatment in accordance with guidelines. These data suggest that shorter antimicrobial treatments could be effective., (© The Author(s) 2019. 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.)

Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality., Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk., Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality., Conclusion: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group., (Copyright © 2019. Published by Elsevier B.V.)

Background: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS., Methods: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol., Results: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species., Conclusions: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.

Objective: To assess the current clinical features and determinants of outcome of Candida tropicalis bloodstream infection (BSI)., Methods: A population-based surveillance on Candida BSI was conducted from May 2010 to April 2011 in 29 Spanish hospitals. Antifungal susceptibility testing (EUCAST methodology) was centrally performed. The characteristics and outcome of C. tropicalis BSI episodes were compared with those due to other species., Results: Fifty-nine out of 752 episodes (7.8%) were due to C. tropicalis (annual incidence: 0.62 cases per 100,000 population). Resistance to fluconazole and voriconazole was found in 23.2% and 26.8% of isolates. Breakthrough BSI occurred in 10.5% of episodes. Risk factors for C. tropicalis BSI were age (odds ratio [OR]: 1.01; P-value = 0.05), underlying leukaemia (OR: 4.77; P-value = 0.001) and chronic lung disease (OR: 2.62; P-value = 0.002). There were no differences in clinical failure (persistent BSI for ≥72 h after initiation of therapy and/or 30-day all-cause mortality) between C. tropicalis (39.6%) and non-C. tropicalis groups (45.6%). The appropriateness of antifungal therapy or the fluconazole MIC values had no significant impact on outcome, whereas early central venous catheter removal exerted a protective effect., Conclusions: C. tropicalis BSI was associated with advanced age, haematological malignancy and respiratory comorbidity. We found no correlation between the unexpectedly high resistance rate to azoles observed and outcome., (Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

This study describes coagulase-negative staphylococcal (CoNS) infective endocarditis (IE) epidemiology at our institution, the antibiotic susceptibility profile, and the influence of vancomycin minimum inhibitory concentration (MIC) on patient outcomes. One hundred and three adults with definite IE admitted to an 850-bed tertiary care hospital in Barcelona from 1995-2008 were prospectively included in the cohort. We observed that CoNS IE was an important cause of community-acquired and healthcare-associated IE; one-third of patients involved native valves. Staphylococcus epidermidis was the most frequent species, methicillin-resistant in 52% of patients. CoNS frozen isolates were available in 88 patients. Vancomycin MICs of 2.0 μg/mL were common; almost all cases were found among S. epidermidis isolates and did not increase over time. Eighty-five patients were treated either with cloxacillin or vancomycin: 38 patients (Group 1) were treated with cloxacillin, and 47 received vancomycin; of these 47, 27 had CoNS isolates with a vancomycin MIC <2.0 μg/mL (Group 2), 20 had isolates with a vancomycin MIC ≥ 2.0 μg/mL (Group 3). One-year mortality was 21%, 48%, and 65% in Groups 1, 2, and 3, respectively (P = 0.003). After adjusting for confounders and taking Group 2 as a reference, methicillin-susceptibility was associated with lower 1-year mortality (OR 0.12, 95% CI 0.02-0.55), and vancomycin MIC ≥ 2.0 μg/mL showed a trend to higher 1-year mortality (OR 3.7, 95% CI 0.9-15.2; P=0.069). Other independent variables associated with 1-year mortality were heart failure (OR 6.2, 95% CI 1.5-25.2) and pacemaker lead IE (OR 0.1, 95%CI 0.02-0.51). In conclusion, methicillin-resistant S.epidermidis was the leading cause of CoNS IE, and patients receiving vancomycin had higher mortality rates than those receiving cloxacillin; mortality was higher among patients having isolates with vancomycin MICs ≥ 2.0 μg/mL.

The aim of this study was to assess changes in antibiotic resistance, epidemiology and outcome among patients with Enterococcus faecalis infective endocarditis (EFIE) and to compare the efficacy and safety of the combination of ampicillin and gentamicin (A+G) with that of ampicillin plus ceftriaxone (A+C). The study was a retrospective analysis of a prospective cohort of EFIE patients treated in our centre from 1997 to 2011. Thirty patients were initially treated with A+G (ampicillin 2 g/4 h and gentamicin 3 mg/kg/day) and 39 with A+C (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) for 4-6 weeks. Increased rates of high-level aminoglycoside resistance (HLAR; gentamicin MIC ≥512 mg/L, streptomycin MIC ≥1024 mg/L or both) were observed in recent years (24% in 1997-2006 and 49% in 2007-2011; p 0.03). The use of A+C increased over time: 1997-2001, 4/18 (22%); 2002-2006, 5/16 (31%); 2007-2011, 30/35 (86%) (p <0.001). Renal failure developed in 65% of the A+G group and in 34% of the A+C group (p 0.014). Thirteen patients (43%) in the A+G group had to discontinue treatment, whereas only one patient (3%) treated with A+C had to discontinue treatment (p <0.001). Only development of heart failure and previous chronic renal failure were independently associated with 1-year mortality, while the individual antibiotic regimen (A+C vs. A+G) did not affect outcome (OR, 0.7; 95% CI, 0.2-2.2; p 0.549). Our study shows that the prevalence of HLAR EFIE has increased significantly in recent years and that alternative treatment with A+C is safer than A+G, with similar clinical outcomes, although the sample size is too small to draw firm conclusions. Randomized controlled studies are needed to confirm these results., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Data on the incidence, associated factors, and prognosis of pericardial effusion (PE) in patients with infective endocarditis (IE) are scarce. Patients with native valve IE were prospectively followed in our center from 1990 to 2007. A logistic regression analysis was performed to identify independent variables associated with PE and mortality. We included 479 episodes of IE from 459 patients (70% men, mean age 51 years). Small-to-moderate PE was observed in 109 episodes (23%) and large-to-very large PE was observed in 9 episodes (2%). Patients with small-to-moderate PE had a greater prevalence of intravenous drug use (38% vs 23%) and more frequent right-sided IE than patients without PE (33% vs 17%). Patients with large-to-very large PE had a higher rate of systemic emboli (22% vs 18%) and periannular abscess (22% vs 6%) than patients without PE. Renal failure was associated with a higher risk of PE (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.3); age was associated with a lower risk of PE (OR 0.98, 95% CI 0.97 to 0.99). One-year mortality of patients with IE with large-to-very large PE was higher than that of patients with small-to-moderate and absence of PE (56%, 18%, and 24%, respectively, p = 0.033). Large-to-very large PE increases the 1-year mortality of IE (OR 3.0, 95% CI 1.2 to 7.9). In conclusion, renal failure and younger age are associated with a higher risk of PE. Large-to-very large PE was associated with an increase in 1-year mortality., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Testosterone (T) is thought to play a key role in male-male competition and courtship in many vertebrates, but its precise effects are unclear. We explored whether courtship behaviour in humans is modulated and preceded by changes in T. Pairs of healthy male students first competed in a non-physical contest in which their T levels became elevated. Each participant then had a short, informal interaction with either an unfamiliar man or woman. The sex of the stimulus person did not affect the participants' behaviour overall. However, in interactions with women, those men who had experienced a greater T increase during the contest subsequently showed more interest in the woman, engaged in more self-presentation, smiled more and made more eye contact. No such effects were seen in interactions with other men. This is the first study to provide direct evidence that elevating T during male-male competition is followed by increased affiliative behaviour towards women.

This field study investigated the release of testosterone and cortisol of a vicarious winning experience in Spanish fans watching the finals between Spain and the Netherlands in the 2010 FIFA World Cup Soccer. Spanish fans (n = 50) watched the match with friends or family in a public place or at home and also participated in a control condition. Consistent with hypotheses, results revealed that testosterone and cortisol levels were higher when watching the match than on a control day. However, neither testosterone nor cortisol levels increased after the victory of the Spanish team. Moreover, the increase in testosterone secretion was not related to participants' sex, age or soccer fandom, but the increase in total cortisol secretion during the match was higher among men than among women and among fans that were younger. Also, increases in cortisol secretion were greater to the degree that people were a stronger fan of soccer. Level of fandom further appeared to account for the sex effect, but not for the age effect. Generally, the testosterone data from this study are in line with the challenge hypothesis, as testosterone levels of watchers increased to prepare their organism to defend or enhance their social status. The cortisol data from this study are in line with social self-preservation theory, as higher cortisol secretion among young and greater soccer fans suggests that especially they perceived that a negative outcome of the match would threaten their own social esteem.

Objectives: Gram-positive microorganisms have been the predominant pathogens in central venous catheter-related bloodstream infections (CRBSIs). Recent guidelines recommend empirical therapy according to this and restrict coverage for Gram-negatives to specific circumstances. This study aimed to analyse the epidemiological changes in CRBSIs over the 1991-2008 period and to analyse predictors of Gram-negative CRBSIs., Patients and Methods: A prospectively collected cohort of patients with confirmed CRBSIs was analysed. Strains isolated and antimicrobial susceptibility, as well as clinical and demographic variables were recorded. Differences observed during the study period were analysed by means of a χ² trend test and factors associated with Gram-negative CRBSIs by means of multivariable analysis., Results: Between 1991 and 2008, 1129 episodes of monomicrobial CRBSIs were recorded. There was an increase in the incidence of CRBSIs, from 0.10 (1991-92) to 0.31 (2007-08) episodes/1000 patient-days. A significant increase in the number of Gram-negative strains among the total isolates was also found, from 3 (4.7%) in 1991-92 to 70 (40.23%) in 2007-08, with a parallel decrease in the percentage of Gram-positives. Solid organ transplantation, prior use of penicillins and hospital stay longer than 11 days were independently associated with a significantly higher risk of Gram-negative CRBSIs, while cirrhosis, diabetes and use of quinolones were associated with a higher risk of Gram-positives., Conclusions: Gram-negative strains are an increasing cause of CRBSIs, reaching a prevalence of 40% in the 2007-08 period in our hospital. If this trend is confirmed in other centres, a broad-spectrum empirical therapy should be considered in managing these infections.

Infection is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). This study was aimed at characterizing bloodstream infections in these patients and analysing factors associated with long term outcome. For this purpose, episodes of significant bacteraemia diagnosed from January 1991 to December 2006 among patients with SLE at a single centre were identified through a central database and clinical and analytical variables were recorded regarding short- and long-term follow-up. Univariate and multivariable analysis were performed to identify factors associated with long-term outcome. Thirty-eight SLE patients had 48 episodes of significant bacteraemia, with a 30-day mortality rate of 6.25%. Escherichia coli and Staphylococcus aureus were the leading Gram-negative and Gram-positive pathogens, respectively. After a median follow-up of 25 months, eight of these 38 patients (21.1%) had a further episode of bacteraemia and 13 of them (34.21%) died. Community-acquired bacteraemia and C reactive protein levels lower than 8 mg/dl during episodes were factors associated with lower long-term mortality. These results reinforce previous findings suggesting that lupus patients with bacteraemia episodes have poor long-term outcomes.

Candidaemia remains a major cause of morbidity and mortality in the healthcare setting. Candida spp. bloodstream infection episodes prospectively recorded through a blood culture surveillance programme in a single institution from 1991 to 2008 were included in the study. Data regarding candidaemia episodes were analysed, including specific fungal species and patient survival at 30 days after diagnosis. There were 529 candidaemia episodes during the study period (495 were nosocomial infections). The incidence of candidaemia caused by non-Candida albicans Candida spp. (52%) was higher than the incidence of candidaemia caused by C. albicans (48%). The overall crude 30 day mortality rate was 32%. Patients with Candida parapsilosis candidaemia had the lowest mortality rate (23%). Candida krusei candidaemia was most commonly associated with haematological malignancy (61%; P < 0.001), stem cell transplantation (22%; P = 0.004), neutropenia (57%; P = 0.001) and prior use of antifungal azole agents (26%; P < 0.001). Patients with C. krusei candidaemia had the highest crude 30 day mortality in this series (39%). Epidemiological studies are important to define clinical and microbiological candidaemia characteristics and to guide empirical treatment in every setting., (Copyright © 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: the aim of our study was to review the epidemiology and clinical manifestations of infections due to Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus (PVL-MRSA)., Material and Methods: Medical history of patients infected by MRSA-PVL admitted to our hospital from January 2007 to July 2009 was reviewed. PVL and the type of cromosomic cassette were determined in all strains by PCR., Results: A total of 37 cases were included. Seventy percent were males and the median age was 39 years. Sixtytwo percent were Spanish, 14 (37.8%) were HIV-positive and 11 (29.7%) were homosexual. The source of the infection was the skin and soft tissue in 36 cases and pneumonia in 1. Sixteen patients were hospitalized, 5 had bacteremia and 5 developed septic metastasis. The relapse rate was 24% (9 cases). The prevalence during the study period was 11.2% of all MRSA isolated (37 out of 329). All the strains had a cromosomic cassette type IV and were susceptible to cotrimoxazole, rifampin, vancomyin, daptomycin and linezolid. The MIC of vancomycin, measured by E-test, was ≥ 1.5 mg/L in 28 out of 34 cases (82.3%)., Conclusions: Eleven percent of the MRSA strains isolated in our hospital are PVL positive. In general, skin and soft tissue infections are the most common and bacteremia or septic metastasis are frequent. In contrast to previous Spanish studies, more cases are observed in patients born in Spain and the infections are more severe.

Extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC) is an increasing cause of community and nosocomial infections worldwide. However, there is scarce clinical information about nosocomial bloodstream infections (BSIs) caused by these pathogens. We performed a study to investigate the risk factors for and prognosis of nosocomial BSIs due to ESBLEC in 13 Spanish hospitals. Risk factors were assessed by using a case-control-control study; 96 cases (2 to 16% of all nosocomial BSIs due to E. coli in the participating centers) were included; the most frequent ESBL was CTX-M-14 (48% of the isolates). We found CTX-M-15 in 10% of the isolates, which means that this enzyme is emerging as a cause of invasive infections in Spain. By repetitive extragenic palindromic sequence-PCR, most isolates were found to be clonally unrelated. By multivariate analysis, the risk factors for nosocomial BSIs due to ESBLEC were found to be organ transplant (odds ratio [OR]=4.8; 95% confidence interval [CI]=1.4 to 15.7), the previous use of oxyimino-beta-lactams (OR=6.0; 95% CI=3.0 to 11.8), and unknown BSI source (protective; OR=0.4; 95% CI=0.2 to 0.9), and duration of hospital stay (OR=1.02; 95% CI=1.00 to 1.03). The variables independently associated with mortality were a Pitt score of >1 (OR=3.9; 95% CI=1.2 to 12.9), a high-risk source (OR=5.5; 95% CI=1.4 to 21.9), and resistance to more than three antibiotics, apart from penicillins and cephalosporins (OR=6.5; 95% CI=1.4 to 30.0). Inappropriate empirical therapy was not associated with mortality. We conclude that ESBLEC is an important cause of nosocomial BSIs. The previous use of oxyimino-beta-lactams was the only modifiable risk factor found. Resistance to drugs other than penicillins and cephalosporins was associated with increased mortality.

Background: There is little clinical information about community-onset bloodstream infections (COBSIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC). We investigated the prevalence and risk factors for COBSI due to ESBLEC, and described their clinical features and the impact of COBSI caused by ESBLEC on 14-day mortality., Methods: Risk factors were assessed using a multicenter case-control-control study. Influence of ESBL production on mortality was studied in all patients with COBSI due to E. coli. Isolates and ESBLs were microbiologically characterized. Statistical analysis was performed using multivariate logistic regression. Thirteen tertiary care Spanish hospitals participated in the study., Results: We included 95 case patients with COBSI due to ESBLEC, which accounted for 7.3% of all COBSI due to E. coli. The ESBL in 83 of these (87%) belonged to the CTX-M family of ESBL, and most were clonally unrelated. Comparison with both control groups disclosed association with health care (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.8), urinary catheter use (OR, 3.1; 95% CI, 1.5-6.5), and previous antimicrobial use (OR, 2.7; 95% CI, 1.5-4.9) as independent risk factors for COBSI due to ESBLEC. Mortality among patients with COBSI due to ESBLEC was lower among patients who received empirical therapy with beta-lactam/beta-lactam inhibitor combinations or carbapenems (8%-12%) than among those receiving cephalosporins or fluoroquinolones (24% and 29%, respectively). Mortality among patients with COBSI due to E. coli was associated with inappropriate empirical therapy irrespective of ESBL production., Conclusions: ESBLEC is an important cause of COBSI due to E. coli. Clinicians should consider adequate empirical therapy with coverage of these pathogens for patients with risk factors.

Objective: Bloodstream infections (BSI) are a major cause of morbidity and mortality after solid organ transplantation. Our aim was to analyze early BSI after solid organ transplantation., Materials and Methods: A prospective cohort study included patients undergoing a kidney, simultaneous kidney-pancreas (SPK), or orthotopic liver transplantation (OLT) from 2003-2007. We prospectively collected demographic variables, underlying chronic diseases, transplantation procedures, and posttransplant complications. Recorded cases of BSI were defined as significant according to CDC criteria. Early BSIs were considered to be those appearing within 30 days posttransplantation., Results: During the study period, we performed 902 transplantations: 474 renal, 340 liver, and 88 pancreas. Seventy episodes of early BSI were diagnosed in 67 patients (7.4%). The incidences of BSI according to the type of transplantation were: 4.8% in renal, 4.5% in SPK, and 12% in OLT (P < .001). Sixty-three percent of the bacteria isolated were gram-negative, the most frequent being Escherichia coli, of which 18 (54%) were extended-spectrum beta-lactamase-producing (ESBL), and Pseudomonas aeruginosa, of which 18 (31%) were multidrug-resistant. The most frequent gram-positive bacteria were coagulase-negative staphylococci (20%). The urinary tract was a frequent source of BSI (27%), followed by a catheter (18%). Two patients (3%) died, both liver recipients, but neither death was related to the BSI., Conclusions: In our setting, the incidence of early BSI among solid organ transplant recipients was high, especially liver recipients, but with low associated mortality. The most frequent sources of infection were urinary tract and catheter. Gram-negative BSI showed a high rate of multidrug resistance.

We conducted this study to determine the associated factors and outcomes of community-acquired primary bacteremia (PB), to describe the most frequently isolated microorganisms, the antibiotic resistance pattern, and to guide the most appropriate antibiotic treatment. A total of 1,640 community-acquired bacteremia cases in nonneutropenic adults were consecutively enrolled from January 2003 to May 2006 and prospectively followed up. Nonconditional logistic regression methods were used with PB and death as dependent variables. Secondary bacteremia (SB) was present in 1,440 patients, and 200 (12%) cases were PB. The independent factors associated with PB were male sex (OR 1.69, 95%CI 1.27-2.25, P = 0.001) and an ultimately or rapidly fatal prognosis for an underlying disease (OR 2.48, 95%CI 1.84-3.34, P = 0.001). The most frequently isolated microorganisms in PB were E. coli and other enterobacteria (26 and 22%, respectively) and S. aureus (15%). There were 28 and 37% ciprofloxacin-resistant E. coli strains in SB and PB, respectively (P = 0.2). Mortality was significantly higher in PB cases (13 vs 8%, P = 0.04). The independent factors associated with mortality in PB were ultimately or rapidly fatal prognosis of underlying disease (OR 2.1, 95%CI 1.41-3.13, P = 0.001), lack of fever at the moment of bacteremia (OR 2.38, 95%CI 1.18-4.76, P = 0.02) and incorrect empirical antibiotic therapy (OR 2.01, 95%CI 1.22-3.33, P = 0.006). The initial empiric antibiotic treatment was more frequently incorrect in PB than in SB, and this was a predictive factor for mortality in PB. The resistance pattern of E. coli, other enterobacteria and S. aureus in every setting should guide the most appropriate empirical treatment for PB.

Candida parapsilosis has emerged as an important yeast species causing fungemia. We describe the incidence and epidemiology of C. parapsilosis fungemia. Data from active population-based surveillance in Barcelona, Spain, from January 2002 to December 2003 were analyzed. We focused on 78 episodes of C. parapsilosis fungemia, and we compared them with 175 Candida albicans controls. C. parapsilosis accounted for 23% of all fungemias. The annual incidences were 1 episode per 10(5) patients, 1.2 episodes per 10(4) discharges, and 1.7 episodes per 10(5) patient days. All isolates but one (99%) were fluconazole susceptible. Seventy-two isolates (92%) were inpatient candidemias. Forty-two episodes (51%) were considered catheter-related fungemia, 35 (45%) were considered primary fungemia, and 3 (4%) were considered secondary fungemia. Risk factors for candidemia were vascular catheterization (97%), prior antibiotic therapy (91%), parenteral nutrition (54%), prior surgery (46%), prior immunosuppressive therapy (38%), malignancy (27%), prior antifungal infection (26%), transplant recipient (16%), neutropenia (12%), and prior colonization (11%). Multivariate analysis of the differential characteristics showed that the factors that independently predicted the presence of C. parapsilosis fungemia were neonate patients (odds ratio [OR], 7.5; 95% confidence interval [CI], 2.1 to 26.8; P = 0.002), transplant recipients (OR, 9.2; 95% CI, 1.9 to 43.3; P = 0.005), patients with a history of prior antifungal therapy (OR, 5.4; 95% CI, 1.8 to 15.9; P = 0.002), and patients who received parenteral nutrition (OR, 2.2; 95% CI, 1.09 to 4.6; P = 0.028). The overall mortality rate was lower than that associated with C. albicans candidemia (23% versus 43%; P < 0.01). In summary, C. parapsilosis was responsible for 23% of all candidemias and was more frequent in neonates, in transplant recipients, and in patients who received parenteral nutrition or previous antifungal therapy, mainly fluconazole. The mortality rate was lower than that associated with C. albicans fungemia.

An unexplained resurgence of Group A streptococci (GAS) infections has been observed since the mid-1980s in the United States and Europe, particularly among intravenous drug users (IDUs). Several risk factors have been identified. Mutations in the capsule synthesis regulator genes (csrRS) have been associated with an increase in virulence. From January 1998 to December 2003, we conducted a prospective and retrospective descriptive analysis of invasive GAS soft-tissue infections in IDUs in Barcelona, Spain. Clinical features were collected, and we conducted a surveillance study to identify risk factors associated with GAS soft-tissue infections. We analyzed chromosomal DNA by low cleavage restriction enzymes and used pulsed-field gel electrophoresis (PFGE) and variable gene sequence typing (VGST) of the emm gene to disclose the epidemiologic relationship between the strains. We analyzed the influence of clonality (M-type) and mutations in csrRS genes of these strains on clinical features. We identified 44 cases, all of which were grouped in 3 clusters: fall 2000, fall 2002, and fall 2003. Cellulitis with or without abscesses (75%) and fever (90.9%) were the most common clinical manifestations. Distant septic complications were infrequent (18.2%). Although all patients had severe infections (mainly bacteremic needle abscesses), their outcome with antibiotic therapy, usually beta-lactam, was successful in all cases. However, surgery was needed in 40.9% of patients. Through the surveillance study we found that infected patients had a higher number of drug injections per day (odds ratio [OR], 18.84; 95% confidence interval [CI], 4.83-79.4; p<0.00001), shared paraphernalia for drug use more frequently (OR, 11.11; 95% CI, 3.24-39.04; p<0.0001), were in a higher proportion both currently unemployed and homeless (OR, 4.22; 95% CI, 1.5-12.15; p<0.0001), were not in a methadone maintenance program (OR, 0.03; 95% CI, 0-0.19; p<0.00001), and more often bought drugs at a specific site (OR, 33.92; 95% CI, 7.44-174.93; p<0.00001) and from a specific dealer (OR, 72; 95% CI, 8-3090; p<0.00001), compared with patients not infected. The fall 2000 cluster was polyclonal, whereas the other 2 clusters were mainly due to the same strain of GAS (emm 25.2), and were defined as epidemic outbreaks. Clinically, the cases due to the clonal strain presented abscesses and needed surgery more frequently (p<0.001 and p=0.005, respectively). On the other hand, mutations in the csrRS genes were not associated with invasive GAS soft-tissue infection. There has been an increase in the number of cases of invasive GAS soft-tissue infections in IDUs in Barcelona, which seems to be related to drug users' habits and their socioeconomic status. Clonality (emm 25.2) but not mutations in the csrRS genes was associated with more severe GAS soft-tissue infections.

In order to gather more data on the use of teicoplanin for reducing MRSA infections in high-risk populations, the present study was conducted. At a hospital in Barcelona, Spain, there was a high prevalence of MRSA infections among patients who underwent surgery for femoral neck fracture during the first 5 months of 2002 (period A) when cefuroxime was the antibiotic prophylaxis. During the following 12 months (period B) 600 mg of teicoplanin was added to cefuroxime. The rates of overall and MRSA infection during period A were 5.07 and 2.73%, respectively. Pulsed-field gel electrophoresis demonstrated there was no clonal relationship among MRSA strains. No nasal carriers of MRSA were detected among health workers. During period B the rates of overall and MRSA infection were 2.36 and 0.19%, respectively. Both rates were statistically significantly lower than those in period A (p<0.05). These results suggest teicoplanin may be useful in patients undergoing orthopedic surgery when the prevalence of MRSA is high.

Background: Few data are available on the clinical features of patients who develop breakthrough bacteraemia, understood as positive blood cultures despite appropriate antibiotic therapy., Objectives: To determine the clinical significance and outcome of a large series of breakthrough bacteraemia., Design: Retrospective analysis of a prospectively collected database., Setting: Two university-affiliated hospitals in Catalonia, Spain., Subjects: A total of 392 individuals who suffered an episode of breakthrough bacteraemia recorded between 1997 and 2002., Interventions: Demographic characteristics, underlying diseases, origin of infection, sources of infection, microorganisms isolated, McCabe and Jackson prognostic criteria, and mortality were analysed., Results: Breakthrough bacteraemia was detected in 392 of 6324 (6.1%) episodes of bacteraemia. Eighty per cent of episodes were nosocomial. The most frequent source of infection in breakthrough bacteraemia was endovascular (70%). Coagulase-negative staphylococci, Staphylococcus aureus, and Pseudomonas aeruginosa were the most significant microorganisms involved. Nosocomial acquisition together with selected sources (central venous catheter, endocarditis and other endovascular foci), underlying conditions (neutropenia, polytraumatism, allogenic bone marrow and kidney transplantation), and particular microbial aetiologies (S. aureus, P. aeruginosa and polymicrobial) were independently associated with increased risk for developing breakthrough bacteraemia. Crude mortality rate was greater in patients with breakthrough bacteraemia (16% vs. 12.3%; P<0.05), and this condition was an independent predictor of death (OR 1.4, 95% CI, 1-1.9; P=0.04)., Conclusions: In view of a case of breakthrough bacteraemia it is mandatory to search for an endovascular focus. Empiric treatment should be directed to cover S. aureus, coagulase-negative staphylococci and nonfermentative Gram-negative bacilli. Breakthrough bacteraemia is an independent predictor of death.

We conducted population-based surveillance for Candida bloodstream infections in Spain to determine its incidence, the extent of antifungal resistance, and risk factors for mortality. A case was defined as the first positive blood culture for any Candida spp. in a resident of Barcelona, from 1 January 2002 to 31 December 2003. We defined early mortality as occurring between days 3 to 7 after candidemia and late mortality as occurring between days 8 to 30. We detected 345 cases of candidemia, for an average annual incidence of 4.3 cases/100,000 population, 0.53 cases/1,000 hospital discharges, and 0.73 cases/10,000 patient-days. Outpatients comprised 11% of the cases, and 89% had a central venous catheter (CVC) at diagnosis. Overall mortality was 44%. Candida albicans was the most frequent species (51% of cases), followed by Candida parapsilosis (23%), Candida tropicalis (10%), Candida glabrata (8%), Candida krusei (4%), and other species (3%). Twenty-four isolates (7%) had decreased susceptibility to fluconazole (MIC > or = 16 microg/ml). On multivariable analysis, early death was independently associated with hematological malignancy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.1 to 10.4). Treatment with antifungals (OR, 0.05; 95% CI, 0.01 to 0.2) and removal of CVCs (OR, 0.3; 95% CI, 0.1 to 0.9) were protective factors for early death. Receiving adequate treatment, defined as having CVCs removed and administration of an antifungal medication (OR, 0.2; 95% CI, 0.08 to 0.8), was associated with lower odds of late mortality; intubation (OR, 7.5; 95% CI, 2.6 to 21.1) was associated with higher odds. The incidence of candidemia and prevalence of fluconazole resistance are similar to other European countries, indicating that routine antifungal susceptibility testing is not warranted. Antifungal medication and catheter removal are critical in preventing mortality.

Objectives: The antifungal drug susceptibilities of 351 isolates of Candida species, obtained through active laboratory-based surveillance in the period January 2002-December 2003, were determined (Candida albicans 51%, Candida parapsilosis 23%, Candida tropicalis 10%, Candida glabrata 9%, Candida krusei 4%)., Methods: The MICs of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and caspofungin were established by means of the broth microdilution reference procedure of the European Committee on Antibiotic Susceptibility Testing., Results and Conclusions: Amphotericin B and flucytosine were active in vitro against all strains. A total of 24 isolates (6.8%) showed decreased susceptibility to fluconazole (MIC > or = 16 mg/L) and 43 (12.3%) showed decreased susceptibility to itraconazole (MIC > or = 0.25 mg/L). Voriconazole and caspofungin were active in vitro against the majority of isolates, even those that were resistant to fluconazole.

The frequency of isolation and antifungal susceptibility patterns to established and two new antifungal agents were determined for 218 Candida spp isolates causing bloodstream infection from 1996 to 2001. Overall, 41.7% of the candidemias were due to C. albicans, followed by C. parapsilosis (22%), C. tropicalis (16.1%), C. glabrata (11.9%), C. krusei (6%) and miscellaneous Candida spp (2.3%). Isolates of C. albicans C. parapsilosis and C. tropicalis (80% of isolates) were highly susceptible to fluconazole (94 to 100% at /= 32 microg/ml).

Objectives: We aimed to assess the incidence, demographic data, clinical features, and outcome of peritoneal infections due to Listeria monocytogenes in individuals with cirrhosis., Methods: During a 10-yr study period, 153 cases of invasive listeriosis were recorded in a prospective population-based surveillance project carried out in Barcelona, Spain., Results: Thirteen cases were of spontaneous bacterial peritonitis by L. monocytogenes. Ages of the patients ranged between 29 and 85 yr. In addition to cirrhosis, underlying conditions included diabetes mellitus in four and malignancy in three. Bacteremia was present in six cases (46%). Only one patient with bacteremia developed meningitis. Analysis of the peritoneal fluid showed a mean (SD) protein content of 21.5 (9.6) g/L and leukocyte count of 7,273 (9,171) cells/ml. L. monocytogenes serotype 4b was the serogroup predominantly isolated (61%). The mortality rate was 30.7%. Eight patients received empirical antibiotic treatment with cephalosporins., Conclusions: In geographical areas with a high incidence of listeriosis, L. monocytogenes should be suspected as a causative pathogen of spontaneous bacterial peritonitis in cirrhosis. Early adjustment of antibiotic therapy is essential to reduce mortality.

The in vitro activity of 22 antimicrobial agents against 82 human Listeria monocytogenes strains isolated in Barcelona from 1994 to 1998 was determined. Ampicillin and gentamicin showed good in vitro activity against all strains (MIC90: 1 and < or = 0.25 microg/ml, respectively). No resistance to rifampin or co-trimoxazole was detected and only one strain was resistant to tetracycline. Of the nine fluoroquinolones tested, clinafloxacin and gemifloxacin were the most active compounds (MIC90: 0.12 and 0.25 microg/ml, respectively). No increasing MICs values were observed during the five-year period.

To assess whether methicillin resistance is a microbial characteristic associated with deleterious clinical outcome, we performed a cohort study on 908 consecutive episodes of Staphylococcus aureus bacteremia and a case-control study involving 163 pairs of patients matched for preexisting comorbidities, prognosis of the underlying disease, length of hospitalization, and age. Of 908 bacteremic episodes, 225 (24.8%) were due to methicillin-resistant S. aureus (MRSA). Multivariate analysis did not reveal that methicillin resistance was an independent predictor for mortality when shock, source of bacteremia, presence of an ultimately or rapidly fatal underlying disease, acquisition of the infection in an intensive care unit (ICU), inappropriate empirical therapy, female sex, and age were taken into account. Nonetheless, methicillin resistance was an independent predictor for shock. The case-control study could not confirm that shock was linked to MRSA when prior antimicrobial therapy, inappropriate treatment, ICU residence, and female sex were considered. Our data suggest that cohort studies tend to magnify the relationship of MRSA with clinical markers of microbial pathogenicity and that this effect is a shortcoming of these kind of studies that is caused by inadequate control for underlying diseases.

A prospective analysis of 43 episodes of Pseudomonas aeruginosa bacteremia in HIV-1-infected subjects was performed and the results compared with the incidence and outcome of Pseudomonas aeruginosa bacteremia in other high-risk patients, such as transplant recipients, leukemia patients, or patients hospitalized in the intensive care unit. The incidence of bacteremia/fungemia as a whole and of gram-negative and Pseudomonas aeruginosa bacteremia in particular was greater in HIV-1-infected subjects than in the unselected general population admitted. In contrast, the incidence of Pseudomonas aeruginosa bacteremia in HIV-1-infected patients did not differ from that in patients with other high-risk conditions. In patients with HIV-1 infection, independent risk factors for presenting Pseudomonas aeruginosa bacteremia were nosocomial origin (OR, 2.7; 95% CI, 1.3-5.7), neutropenia (OR, 2.7; 95% CI, 1.07-6.8), previous treatment with cephalosporins (OR, 3.6; 95% CI, 1.1-11.6), and a CD4+ cell count lower than 50 cells/mm3 (OR, 3.1; 95% CI, 1.7-8.6). Primary bacteremia and pneumonia were the most common forms of presentation. Fourteen (33%) patients died as a consequence of the bacteremia. The presence of severe sepsis (OR, 17.5; 95% CI, 3.2-68) and the institution of inappropriate definitive antibiotic therapy (OR, 2.7; 95% CI, 1.1-13) were independently associated with a poor outcome. One year after the development of bacteremia, only eight (19%) patients remained alive.

Background: Patients who have prosthetic heart valves, previous history of endocarditis, and surgically constructed systemic-pulmonary shunts or conduits should receive prophylactic antibiotics before colonoscopy. The usefulness of this approach in cirrhotic patients remains unknown. The present study prospectively assesses the incidence of bacteremia in these patients., Methods: Lower intestinal endoscopy was performed in 58 cirrhotic patients. Two blood samples were obtained from every patient (just before endoscopy and within 5 minutes of withdrawal of the endoscope) and were incubated for 7 days and examined daily for growth of bacteria. Patients were closely monitored for 72 hours after endoscopy to detect the development of infectious complications., Results: Only 6 cultures from 6 patients were positive. Four were obtained post-endoscopy and the remaining 2 before colonoscopy but the corresponding post-endoscopy samples were negative. All organisms recovered were normal skin flora. All patients, including those with positive cultures, remained asymptomatic during the 72 hours after the procedure., Conclusions: Our findings indicate that lower intestinal endoscopy does not induce bacteremia in cirrhotic patients with or without ascites in the absence of gastrointestinal bleeding and do not support the routine use of prophylactic antibiotics in these patients.

The aim off this study was to describe the incidence, epidemiology, clinical presentation, and outcome of perinatal listeriosis for a 7-year period (1990-1996) based on data of an active population-based surveillance project implemented in the city of Barcelona, Spain. There were 30 cases (20.8%) associated with pregnancy (15 pregnant women, 13 neonates, and 2 fetal deaths). The incidence of perinatal listeriosis varied from 4.1 to 0 per 10,000 live births. The proportion of perinatal cases in relation to the total number of cases of listeriosis varied between 0 and 42%. Early-onset neonatal sepsis accounted for 12 of 13 live births. The mean age of infected pregnant women with listeriosis was 30.1+/-2.0 years. Chorioamnionitis was the predominant clinical form (86.7%). Only two mothers had primary bacteremia by L. monocytogenes in the second trimester of pregnancy. Both infants were born healthy, without signs of infection. One of these mothers was infected with the human immunodeficiency virus (HIV). Since January 1994, 12 strains were available for serotyping and phagotyping; 9 belonged to serovar 4b, 2 to serovar 1/2b, and 1 to serovar 1/2a. No outbreaks of L. monocytogenes infection occurred during the study period. The overall neonatal mortality rate was 7.7% among infected live births. All pregnant women were treated with ampicillin and none died. Early antenatal treatment with ampicillin improves neonatal outcome and can result in the birth of healthy babies.

Background: To get better knowledge about clinical and bacteriological features in Campylobacter spp. bacteremia., Patients and Methods: Over a period of 8 years (1987-1994) we prospectively analyzed underlying diseases, predisposing factors, clinical manifestations, complications and outcome of patients with Campylobacter spp. bacteremia. The study took place in an urban third-level teaching hospital. Antibiogram was tested in all the strains isolated., Results: We identified 30 cases of Campylobacter spp. bacteremia (26 due to C. jejuni and 4 due to C. fetus). Seventy-three percent of the patients were male and the mean age +/- SD of all the patients was 52 +/- 19 years. Ninety percent of patients had some kind of immunodepression related to immunosuppressive therapy or to underlying diseases, especially liver cirrhosis and HIV infection. All patients had fever and 40% complained of intestinal symptoms before bacteremia. Mortality rate in patients with C. jejuni bacteremia was 30.8% (8 patients) during the admission, the death was directly related to bacteremia in 11.5% (3 patients). In all the fatal cases C. jejuni was resistant to empirical antibiotherapy instituted. In contrast, none of the patients with C. fetus bacteremia died. We detected an increasing ciproflaxin resistance in C. jejuni strains during this period which reached to 75% in the last years. Antimicrobial susceptibility to erythromycin and aminoglucosids was kept in all the strains., Conclusions: Campylobacter spp. bacteremia has a remarkable mortality rate, probably related to immunosuppressive underlying diseases in affective patients. In our institution we detected an increasing fluoroquinolone resistance over the years while susceptibility to erythromycin and aminoglucosids was maintained.

Background: The aim of this study was to determine the incidence of human listeriosis in Barcelona in addition to its clinical form of presentation, seasonability, risk groups and evolution., Methods: A prospective study of the cases of listeriosis registered in the city of Barcelona, Spain (population of 1,643,542 inhabitants) over the period from January 1, 1990 to December 31, 1991 was carried out., Results: Fifty-five cases were reviewed with a global rate of incidence of listeriosis of 9.4 per one million inhabitants per year with predominance being observed in the summer months (39% in 1990, 42% in 1991). Ninety-one percent of the cases were observed in non pregnant adults, with 86% of the patients being immunosuppressed. Nosocomial listeriosis, diagnosed in 23 patients (42%), was predominant in the group with immunosuppressive treatment (p = 0.0005). The main site of isolation was blood in 45 cases (82%), in the form of primary listeriosis (p < 0.0005). Global mortality was 49%, being greater in the group of patients with nosocomial infection (p = 0.01) and with primary bacteremia (p < 0.001). No patients without known risk factors or pertaining to the perinatal group have died., Conclusions: The use of an active system of registration of listeriosis facilitates better knowledge of its incidence, distribution and infection pattern thus allowing the early detection of epidemic outbreaks with the aim of controlling such an infection, given the social implications and morbidity of this disease.

A population-based register of cases of listeriosis admitted to acute-care hospitals has been established in Barcelona, Spain, in order to estimate the basal incidence of sporadic cases and to facilitate epidemiological surveillance of potential epidemics. Eleven acute-care hospitals reported all cases of listeriosis to a central unit following a standardized protocol. During 1990, 31 patients with listeriosis were identified, 18 of whom were residents of the city, resulting in an annual incidence of 10.95 cases per million inhabitants. Twelve of the 31 cases occurred in the period from July to September 1990, ten of them being community-acquired. The incidence of listeriosis was higher in elderly (> or = 65 years) and immunosuppressed persons. Forty-two percent of the cases were considered to be nosocomial infections. The overall mortality rate was 51.6%. The incidence of listeriosis in the present study is one of the highest reported in the literature. A high sensitivity of the reporting system with good case identification techniques, or demographic and environmental characteristics related to Listeria monocytogenes infection in our area, might be possible reasons for this geographic variation.

Five hundred forty-three episodes of nosocomial bacteremia were prospectively followed in a large Spanish university hospital. The commonest isolates were Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida species. The most frequent sources of infection were intravenous lines, urinary tract, and lower respiratory tract. Overall mortality was 18%. A step-forward logistic regression analysis defined eight variables independently influencing the outcome: shock, underlying rapidly fatal disease, high-risk source of bacteremia (intraabdominal, lower respiratory tract, or not identified), age more than 70 years, hospitalization in intensive care or medical units, inappropriate antibiotic treatment, infection due to a high-risk microorganism (P. aeruginosa, Serratia marcescens, Klebsiella, Bacteroides, or Candida), and development of septic metastasis. The identification of those factors independently influencing the outcome and their possible modification may represent a further step in the control of nosocomial bacteremia by improving its prognosis.