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The objective of this study was to evaluate the efficacy and safety of fidaxomicin in the real-life clinical setting. This was a retrospective cohort of patients with Clostridium difficile infection (CDI) treated with fidaxomicin in 20 Spanish hospitals between July 2013 and July 2014. Clinical cure, 30-day recurrence, 30-day mortality, sustained cure, and factors associated with the failure to achieve sustained cure were analyzed. Of the 72 patients in the cohort 41 (56.9 %) had a fatal underlying disease. There were 44 (61.1 %) recurrent episodes and 26 cases (36.1 %) with a history of multiple recurrences. Most episodes were severe (26, 36 %) or severe-complicated (14, 19.4 %). Clinical cure rate was 90.3 %, recurrence rate was 16.7 % and three patients (4.2 %) died during the follow-up period. Sustained cure was achieved in 52 cases (72.2 %). Adverse events were reported in five cases (6.9 %). Factors associated with the lack of sustained cure were cardiovascular comorbidity (OR 11.4; 95 %CI 1.9-67.8), acute kidney failure (OR 7.4; 95 %CI 1.3-43.1), concomitant systemic antibiotic treatment (OR 6.2; 95 %CI 1.1-36.8), and C-reactive protein value at diagnosis (OR 1.2 for each 1 mg/dl increase; 95 %CI 1.03-1.3). Fidaxomicin is an effective and well tolerable treatment for severe CDI and for cases with elevated recurrence risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18: 1134-1142 Abstract The aim of this study was to evaluate the clinical characteristics, predictors and outcomes of pneumococcal pneumonia developing pulmonary complications and the distribution of pneumococcal serotypes. It was a prospective study including all adult patients admitted to the Hospital Clinic of Barcelona, Spain (2001-2009) with the diagnosis of pneumococcal pneumonia. Microbiological investigation was systematically performed, including antimicrobial susceptibility and serotype distribution (only invasive strains isolated during 2006-2009). Complicated pneumonia was defined as the presence of one or more pulmonary complications: pleural effusion, empyema, or multilobar infiltrates. We included 626 patients, and 235 (38%) had the following pulmonary complications: pleural effusion, 122 (52%); empyema, 18 (8%); and multilobar infiltration, 151 (64%). Forty-six (20%) patients had more than one complication. Patients with pulmonary complications showed a higher rate of intensive-care unit admission (34% vs. 13%, p <0.001), a higher rate of shock (16% vs. 7%, p <0.001), a longer length of stay (9 days vs. 6 days, p <0.001), and a lower rate of penicillin resistance (14% vs. 25%, p 0.013), but similar mortality (9% vs. 8%). No significant differences were observed in the serotype distribution between complicated and uncomplicated pneumonia. Chronic obstructive pulmonary disease (COPD) (OR 0.38, 95% CI 0.23-0.63; p <0.001) was a protective factor against pulmonary complications, whereas chronic liver disease (OR 3.60, 95% CI 1.71-7.60; p 0.001), admission C-reactive protein level ≥18 mg/dL (OR 2.77, 95% CI 1.91-4.00; p <0.001) and admission creatinine level >1.5 mg/dL (OR 2.01, 95% CI 1.31-3.08; p 0.001) were risk factors for pulmonary complications. Complicated pneumonia was characterized by a more severe clinical presentation, but was not associated with increased mortality. Resistance to antibiotics was lower in complicated cases. No significant differences were observed in the serotype distribution between complicated and uncomplicated pneumonia. In the multivariate analysis, COPD was a protective factor against pulmonary complications. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2010; 16: 1676-1682 Although Candida albicans (CA) is the most common cause of Candida bloodstream infections (BSIs), recent studies have observed an increasing percentage of candidaemias caused by non- albicans Candida species (NAC). In the present study, we attempted to identify the predictors of candidaemia due to NAC compared to CA. We analyzed data from an active population-based surveillance in Barcelona (Spain) from January 2002 to December 2003. Factors associated with NAC fungaemia were determined by multivariate analysis. A total of 339 episodes of Candida BSI, in 336 patients (median age 63 years, interquartile range: 41-72 years), were included. CA was the most commonly isolated (52%), followed by Candida parapsilosis (23%), Candida tropicalis (10%), Candida glabrata (8.6%), Candida krusei (3.4%) and other NAC spp. (3%).Overall, 48% of cases were due to NAC spp. Multivariate logistic regression analysis identified factors associated with a risk of BSI due to NAC spp.: having received a haematologic transplant (OR 10.8; 95% CI 1.31-90.01; p 0.027), previous fluconazole exposure (OR 4.47; 95% CI 2.12-9.43; p <0.001) and neonatal age (OR 4.42; 95% CI 1.63-12.04; p 0.004). Conversely, previous CA colonization (OR 0.33; 95% CI 0.19-0.57; p 0.001) and previous antibiotic use (OR 0.42; 95% CI 0.21-0.85; p 0.017) were associated with CA fungaemia compared to NAC. In conclusion, NAC candidaemia comprised 48% of cases in our series. Predictors of NAC include having received a haematologic transplant, neonatal age and previous fluconazole use. [ABSTRACT FROM AUTHOR]

Removal of central venous catheters (CVCs) from candidaemic patients is considered the reference standard of care, although this practice is not always possible. The impact of prompt catheter removal on outcome was investigated by analysing data from an active population-based surveillance study in Barcelona, Spain. Patients with candidaemia and a CVC were identified between January 2002 and December 2003. Cases with CVC removal within 2 days were classified as having early CVC removal. Outcome, defined as in-hospital mortality 2–30 days after diagnosis of candidaemia, was determined among hospitalised adults using univariate, Kaplan–Meier and multivariate logistic regression analysis. Outpatients, paediatric patients and those who died or were discharged within 2 days were excluded. The study identified 265 patients with candidaemia and a CVC. Median time from diagnosis of candidaemia to catheter removal was 1 day (range 0–29 days). Overall, 172 patients met the criteria for inclusion in the outcome study. Patients with early CVC removal differed significantly from those with delayed CVC removal. According to univariate, Kaplan–Meier and multivariate analysis, the marker most predictive of in-hospital mortality among candidaemic patients with CVCs was severity of illness. These data suggest that timing of CVC removal may best be determined after carefully considering the risks and benefits to individual patients. [ABSTRACT FROM AUTHOR]

Clinical Decision Support Systems (CDSS) are computer-based tools that leverage the analysis of large volumes of health data to assist healthcare professionals in making clinical decisions, whether preventive, diagnostic, or therapeutic. This review examines the impact of CDSS on clinical practice, highlighting both their potential benefits and their limitations and challenges. We detail the experience of clinical medical professionals in the development of a virtual control center for COVID-19 patients (C3 COVID-19) in Spain during the SARS-CoV-2 pandemic. This tool enabled real-time monitoring of clinical data for hospitalized COVID-19 patients, optimizing personalized and informed medical decision-making. CDSS can offer significant advantages, such as improving the quality of inpatient care, promoting evidence-based clinical and therapeutic decision-making, facilitating treatment personalization, and enhancing healthcare system efficiency and productivity. However, the implementation of CDSS presents challenges, including the need for physicians to become familiar with the systems and software, and the necessity for ongoing updates and technical support of the systems., (©The Author 2024. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: We aimed to describe the epidemiology of catheter-related bloodstream infections (CRBSIs) in onco-hematological neutropenic patients during a 25-year study period, to evaluate the risk factors for Gram-negative bacilli (GNB) CRBSI, as well as rates of inappropriate empirical antibiotic treatments (IEAT) and mortality., Materials/methods: All consecutive episodes of CRBSIs were prospectively collected (1994-2018). Changing epidemiology was evaluated comparing five-year time spans. A multivariate regression model was built to evaluate risk factors for GNB CRBSIs., Results: 482 monomicrobial CRBSIs were documented. The proportion of CRBSIs among all BSIs decreased over time from 41.2% to 15.8% (p<0.001). CRBSIs epidemiology has been changing: the rate of GNB increased over time (from 11.9% to 29.4%; p<0.001), as well as the absolute number and rate of multidrug-resistant (MDR) GNB (from 9.5% to 40.0%; p = 0.039). P. aeruginosa increased and comprised up to 40% of all GNB. Independent factors related with GNB-CRBSIs were: longer duration of in-situ catheter (OR 1.007; 95%CI 1.004-1.011), older age (OR 1.016; 95%CI 1.001-1.033), prior antibiotic treatment with penicillins (OR 2.716; 95%CI 1.306-5.403), and current antibiotic treatment with glycopeptides (OR 1.931; 95%CI 1.001-3.306). IEATs were administered to 30.7% of patients, with the highest percentage among MDR P. aeruginosa (76.9%) and S. maltophillia (92.9%). Mortality rate was greater among GNB than GPC-CRBSI (14.4% vs 5.4%; p = 0.002), with mortality increasing over time (from 4.5% to 11.2%; p = 0.003)., Conclusion: A significant shift towards GNB-CRBSIs was observed. Secondarily, and coinciding with an increasing number of GNB-MDR infections, mortality increased over time., Competing Interests: CG-V has received honoraria for talks on behalf of Gilead Science, Merck Sharp and Dohme, Pfizer, Jannsen, Novartis, Lilly and a grant support from Gilead Science and Merck Sharp and Dohme. AS has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, Angellini, and grant support from Pfizer. JM has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, and Angellini. PP-A has received honoraria for talks on behalf of Pfizer. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Controversial results on remdesivir efficacy have been reported. We aimed to report our real-life experience with the use of remdesivir from its availability in Spain., Methods: We performed a descriptive study of all patients admitted for ≥48 hours with confirmed COVID-19 who received remdesivir between the 1st of July and the 30th of September 2020., Results: A total of 123 patients out of 242 admitted with COVID-19 at our hospital (50.8%) received remdesivir. Median age was 58 years, 61% were males and 56.9 % received at least one anti-inflammatory treatment. No adverse events requiring remdesivir discontinuation were reported. The need of intensive care unit admission, mechanical ventilation and 30-days mortality were 19.5%, 7.3% and 4.1%, respectively., Conclusions: In our real-life experience, the use of remdesivir in hospitalized patients with COVID-19 was associated with a low mortality rate and good safety profile., (©The Author 2021. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Objectives: To describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19)., Methods: We performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records., Results: Of a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes., Conclusions: Co-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again., (©The Author 2020. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Objectives: To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients., Methods: Single-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004-2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk., Results: Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15-9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32-18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74-7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64-28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04-5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15-15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87-17.67), haematological malignancy (OR 3.44; 95% CI 1.07-10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42-10.22) and quinolones (OR 3.97; 95% CI 1.37-11.48), corticosteroids (OR 2.92; 95% CI 1.15-7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58-15.05) and β-lactam other than ertapenem (OR 4.51; 95% CI 1.45-14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI., Conclusions: A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Pseudomonas aeruginosa is characterized by a notable intrinsic resistance to antibiotics, mainly mediated by the expression of inducible chromosomic β-lactamases and the production of constitutive or inducible efflux pumps. Apart from this intrinsic resistance, P. aeruginosa possess an extraordinary ability to develop resistance to nearly all available antimicrobials through selection of mutations. The progressive increase in resistance rates in P. aeruginosa has led to the emergence of strains which, based on their degree of resistance to common antibiotics, have been defined as multidrug resistant, extended-resistant and panresistant strains. These strains are increasingly disseminated worldwide, progressively complicating the treatment of P. aeruginosa infections. In this scenario, the objective of the present guidelines was to review and update published evidence for the treatment of patients with acute, invasive and severe infections caused by P. aeruginosa. To this end, mechanisms of intrinsic resistance, factors favoring development of resistance during antibiotic exposure, prevalence of resistance in Spain, classical and recently appeared new antibiotics active against P. aeruginosa, pharmacodynamic principles predicting efficacy, clinical experience with monotherapy and combination therapy, and principles for antibiotic treatment were reviewed to elaborate recommendations by the panel of experts for empirical and directed treatment of P. aeruginosa invasive infections., (© The Author 2018. Published by Sociedad Española de Quimioterapia.)

The aim of the study was to analyse the epidemiology and prognosis of candidaemia in elderly patients. We performed a comparison of clinical presentation of candidaemia according to age and a study of hazard factors within a prospective programme performed in 29 hospitals. One hundred and seventy-six episodes occurred in elderly patients (>75 years), 227 episodes in middle-aged patients (61-75 years) and 232 episodes in younger patients (16-60 years). Central venous catheter, parenteral nutrition, neutropenia, immunosuppressive therapy and candidaemia caused by Candida parapsilosis were less frequent in elderly patients. These patients received inadequate antifungal therapy (57.3%) more frequently than middle-aged and younger patients (40.5% P < .001). Mortality during the first week (20%) and 30 days (42%) was higher in elderly patients. The variables independently associated with mortality in elderly patients during the first 7 days were acute renal failure (OR: 2.64), Pitt score (OR: 1.57) and appropriate antifungal therapy (OR: 0.132). Primary candidaemia (OR: 2.93), acute renal failure (OR: 3.68), Pitt score (OR: 1.38), appropriate antifungal therapy (OR: 0.3) and early removal of the central catheter (OR: 0.47) were independently associated with 30-day mortality.In conclussion, inadequate antifungal treatment is frequently prescribed to elderly patients with candidaemia and is related with early and late mortality., (© 2017 Blackwell Verlag GmbH.)

The sensitivity of blood cultures in the diagnosis of bacteraemia for community-acquired pneumonia is low. Recommendations, by guidelines, to perform blood cultures are discordant. We aimed to determine the incidence, microbial aetiology, risk factors and outcomes of bacteraemic patients with community-acquired pneumonia, including cases with antibiotic-resistant pathogens (ARP). A prospective, observational study was undertaken on consecutive adult patients admitted to the Hospital Clinic of Barcelona (Barcelona, Spain) with community-acquired pneumonia and blood cultures were obtained. Of the 2892 patients included, bacteraemia was present in 297 (10%) patients; 30 (10%) of whom had ARP (multidrug-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and an extended spectrum of beta-lactamase producing Enterobacteriaceae). In multivariate analyses, pleuritic pain, C-reactive protein ≥21.6 mg·dL(-1) and intensive care unit admissions were independently associated with bacteraemia, while prior antibiotic treatment and pneumococcal vaccine were protective factors. The risk factors for ARP bacteraemia were previous antibiotics and C-reactive protein <22.2 mg·dL(-1), while pleuritic pain was the only protective factor in the multivariate analysis. Bacteraemia (excluding ARP), appropriate empiric treatment, neurological disease, arterial oxygen tension/inspiratory oxygen fraction <250, pneumonia severity index risk classes IV and V, and intensive care unit admission were independently associated with a 30-day hospital mortality in the multivariate analysis. Inappropriate therapy was more frequent in ARP bacteraemia, compared with other bacteraemias (27% versus 3%, respectively, p<0.001). Antibiotic therapy protected against bacteraemia, but increased specifically the risk of bacteraemia from ARP due to the inappropriate coverage of these pathogens. Identifying patients at risk of ARP bacteraemia would help in deciding appropriate empiric antimicrobial therapy. The results from this study provide evidence concerning community-acquired pneumonia patients in whom blood cultures should not be performed., (Copyright ©ERS 2015.)

Background: Prolonged life expectancy has currently increased the proportion of the very elderly among patients with community-acquired pneumonia (CAP). The aim of this study was to determine the influence of age and comorbidity on microbial patterns in patients over 65 years of age with CAP., Methods: This study was a prospective observational study of adult patients with CAP (excluding those in nursing homes) over a 12-year period. We compared patients aged 65 to 74 years, 75 to 84 years, and > 85 years for potential differences in clinical presentation, comorbidities, severity on admission, microbial investigations, causes, antimicrobial treatment, and outcomes., Results: We studied a total of 2,149 patients: 759 patients (35.3%) aged 65 to 74 years, 941 patients (43.7%) aged 75 to 84 years, and 449 patients (20.8%) aged > 85 years. At least one comorbidity was present in 1,710 patients (79.6%). Streptococcus pneumoniae was the most frequent pathogen in all age groups, regardless of comorbidity. Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa accounted for 9.1% of isolates, and Haemophilus influenzae, 6.4%. All these pathogens were isolated only in patients with at least one comorbidity. Mortality increased with age (65-74 years, 6.9%; 75-84 years, 8.9%; > 85 years, 17.1%; P < .001) and was associated with increased comorbidities (neurologic; OR, 2.1; 95% CI, 1.5-2.1), Pneumonia Severity Index IV or V (OR, 3.2; 95% CI, 1.8-6.0), bacteremia (OR, 1.7; 95% CI, 1.1-2.7), the presence of a potential multidrug-resistant (MDR) pathogen (S. aureus, P. aeruginosa, Enterobacteriaceae; OR, 2.4; 95% CI, 1.3-4.3), and ICU admission (OR, 4.2; 95% CI, 2.9-6.1) on multivariate analysis., Conclusions: Age does not influence microbial cause itself, whereas comorbidities are associated with specific causes such as H. influenzae and potential MDR pathogens. Mortality in the elderly is mainly driven by the presence of comorbidities and potential MDR pathogens.

Rationale: Previous use of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease has been associated with increased risk of community-acquired pneumonia. However, ICS have been associated with fewer pneumonia complications and decreased risk of pneumonia-related mortality., Objectives: The objective of the study was to assess the influence of previous use of ICS on the incidence of parapneumonic effusion in patients with different baseline respiratory disorders., Methods: We conducted a single-center cohort study of 3,612 consecutively collected patients diagnosed with community-acquired pneumonia. We assessed clinical, radiographic, and pleural-fluid chemistry and microbiologic variables. Patients were classified according to whether or not they received prior ICS treatment., Measurements and Main Results: A total of 633 patients (17%) were treated with corticosteroids before the diagnosis of pneumonia (chronic obstructive pulmonary disease, 54%; asthma, 13%). Incidence of parapneumonic effusion was lower in patients with ICS use compared with non-ICS patients (5% vs. 12%; P < 0.001). After matching according to propensity scores (n = 640), prior treatment with corticosteroids was still significantly associated with a lower incidence of parapneumonic effusion (odds ratio, 0.40; 95% confidence interval, 0.23-0.69; P = 0.001) compared with patients without ICS treatment. Prior ICS treatment was associated with higher levels of glucose (P = 0.003) and pH (P = 0.02), and lower levels of protein (P = 0.01) and lactic acid dehydrogenase (P = 0.007) in the pleural fluid., Conclusions: Prior treatment with ICS in a population of patients with different respiratory chronic disorders who develop pneumonia is associated with lower incidence of parapneumonic effusion.

Objective: To elaborate practical recommendations based on scientific evidence, when available, or on expert opinions for the diagnosis, treatment and prevention of fungal respiratory infections in the critically ill patient, including solid organ transplant recipients., Methods: Twelve experts from two scientific societies (The Spanish Society for Chemotherapy and The Spanish Society of Intensive Care and Coronary Units) reviewed in a meeting held in March 2012 epidemiological issues and risk factors as basis for a document about prevention, diagnosis and treatment of respiratory fungal infections caused by Candida spp., Aspergillus spp or Zygomycetes., Results: Despite the frequent isolation of Candida spp. from respiratory tract samples, antifungal treatment is not recommended since pneumonia by this fungal species is exceptional in non-neutropenic patients. In the case of Aspergillus spp., approximately 50% isolates from the ICU represent colonization, and the remaining 50% cases are linked to invasive pulmonary aspergillosis (IPA), an infection of high mortality. Main risk factors for invasive disease in the ICU are previous treatment with steroids and chronic obstructive pulmonary disease (COPD). Collection of BAL sample is recommended for culture and galactomannan determination. Voriconazole and liposomal amphotericin B have the indication as primary therapy while caspofungin has the indication as salvage therapy. Although there is no solid data supporting scientific evidence, the group of experts recommends combination therapy in the critically ill patient with sepsis or severe respiratory failure. Zygomycetes cause respiratory infection mainly in neutropenic patients, and liposomal amphotericin B is the elective therapy., Conclusions: Presence of fungi in respiratory samples from critically ill patients drives to different diagnostic and clinical management approaches. IPA is the most frequent infection and with high mortality.

Unlabelled: Epidemiology, risk factors, and clinical effect of infections by multiresistant bacteria in cirrhosis are poorly known. This work was a prospective evaluation in two series of cirrhotic patients admitted with infection or developing infection during hospitalization. The first series was studied between 2005 and 2007 (507 bacterial infections in 223 patients) and the second between 2010 and 2011 (162 bacterial infections in 110 patients). In the first series, 32% of infections were community acquired (CA), 32% healthcare associated (HCA), and 36% nosocomial. Multiresistant bacteria (92 infections; 18%) were isolated in 4%, 14%, and 35% of these infections, respectively (P < 0.001). Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E; n = 43) was the main multiresistant organism identified, followed by Pseudomonas aeruginosa (n = 17), methicillin-resistant Staphylococcus aureus (n = 14), and Enterococcus faecium (n = 14). The efficacy of currently recommended empirical antibiotic therapy was very low in nosocomial infections (40%), compared to HCA and CA episodes (73% and 83%, respectively; P < 0.0001), particularly in spontaneous bacterial peritonitis, urinary tract infection, and pneumonia (26%, 29%, and 44%, respectively). Septic shock (26% versus 10%; P < 0.0001) and mortality rate (25% versus 12%; P = 0.001) were significantly higher in infections caused by multiresistant strains. Nosocomial origin of infection (hazard ratio [HR], 4.43), long-term norfloxacin prophylaxis (HR, 2.69), recent infection by multiresistant bacteria (HR, 2.45), and recent use of β-lactams (HR, 2.39) were independently associated with the development of multiresistant infections. Results in the second series were similar to those observed in the first series., Conclusions: Multiresistant bacteria, especially ESBL-producing Enterobacteriaceae, are frequently isolated in nosocomial and, to a lesser extent, HCA infections in cirrhosis, rendering third-generation cephalosporins clinically ineffective. New antibiotic strategies tailored according to the local epidemiological patterns are needed for the empirical treatment of nosocomial infections in cirrhosis., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Background: From the beginning of the influenza pandemic until the time the outbreak described here was detected, 77,201 cases of pandemic influenza A(H1N1) with 332 deaths had been reported worldwide, mostly in the United States and Mexico. All of the cases reported in Spain until then had a recent history of travel to Mexico, the Dominican Republic, or Chile. We describe an outbreak of influenza among medical students who traveled from Spain to the Dominican Republic in June 2009., Methods: We collected diagnostic samples and clinical histories from consenting medical students who had traveled to the Dominican Republic and from their household contacts after their return to Spain., Results: Of 113 students on the trip, 62 (55%) developed symptoms; 39 (45%) of 86 students tested had laboratory evidence of influenza A(H1N1) infection. Most students developed symptoms either just before departure from the Dominican Republic or within days of returning to Spain. The estimated secondary attack rate of influenza-like illness among residential contacts of ill students after return to Spain was 2.1%., Conclusions: The attack rate of influenza A(H1N1) can vary widely depending on the circumstances of exposure. We report a high attack rate among a group of traveling medical students but a much lower secondary attack rate among their contacts after return from the trip. These findings may aid the development of recommendations to prevent influenza., (© 2011 International Society of Travel Medicine.)

Purposes: To review patients with a hematogenous and early post-surgical prosthetic joint infection (PJI) due to S. aureus treated with debridement and retention of the implant and to compare their clinical characteristics and outcome., Methods: From January 2000 all patients with a prosthetic joint infection treated in a single-center were prospectively registered and followed-up. All potentially variables associated with outcome were recorded. For the present study, cases with a hematogenous or early post-surgical PJI due to S. aureus treated with debridement and at least 2 years of follow-up were reviewed. Cox regression model to identify factors associated with outcome were applied., Results: 12 hematogenous and 53 early post-surgical PJI due to S. aureus were included. Number of patients presenting with fever, leucocyte count, C-reactive protein concentration, and the number of bacteremic patients were significantly higher in hematogenous infections while the number of polymicrobial infections was lower in hematogenous than in early post-surgical infections. The global failure rate in hematogenous and early post-surgical PJI was 58.7% and 24.5%, respectively (p=0.02). The Cox regression model identified hematogenous infections (OR: 2.57, CI95%: 1.02-6.51, p=0.04) and the need of a second debridement (OR: 4.61, CI95%: 1.86-11.4, p=0.001) as independent predictors of failure., Conclusion: Hematogenous infections were monomicrobial and had more severe symptoms and signs of infection than early post-surgical PJI. Hematogenous PJI due to S. aureus, using debridement with implant retention, had a worse outcome than early post-surgical infections.

Purpose: To evaluate the relationship between intraoperative cultures during hip arthroplasty, the different patient characteristics, and the risk of developing a prosthetic joint infection (PJI)., Methods: A prospective observational study was performed. Patients who underwent elective THA from March 2007 to March of 2011 were included. Three samples were taken just after arthrotomy: synovial fluid inoculated into blood culture flasks (SF), a tissue sample (TS), and a swab of peri- prosthetic tissue (S). Patients received standard antibiotic prophylaxis. The PJI rate within the first 3 months after arthroplasty was recorded., Results: 402 prostheses were included in the study. Contamination rate of synovial fluid was 10.2%. The most frequent isolated microorganism was coagulase-negative staphylococci (CoNS) (32 out of 41). Body mass index (BMI) was the only host characteristic associated with positive intraoperative culture (p=0.009). The PJI rate was 3.7%. Variables associated with PJI in the univariate and multivariate analysis were: age =67 years (p=0.012 OR: 5.35 (1.45-19.81); CI95%) and a BMI =35 (p=0.002, OR: 7.7 (2.12-27.85) CI95%). PJI rate among patients with BMI<35 with negative and positive intraoperative cultures was 3% and 2.7%, respectively, however, the rate among patients with BMI = 35 was 15% and 25%, respectively., Conclusion: A BMI =35 was associated with a higher risk of positive intraoperative culture during hip arthroplasty. In addition, a BMI ≥35 was independently associated with a high risk of PJI and the highest rate was documented among obese patients with positive intraoperative cultures.

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.

Background: The distribution of the microbial aetiology and mortality of community-acquired pneumonia (CAP) was investigated in relation to the clinical setting and severity scores (pneumonia severity index (PSI) and confusion, blood urea nitrogen, respiratory rate, blood pressure, age (CURB-65))., Methods: 3523 patients with CAP were included (15% outpatients, 85% inpatients). The distribution of the microbial aetiology in relation to the clinical setting and severity scores (PSI, CURB-65) and the relative mortality of different aetiologies across the severity scores were analysed., Results: The aetiology was established in 1463 patients (42%), of whom 257 died (7%). The ranking of aetiologies varied according to site of care, with increasing frequency of Streptococcus pneumoniae and mixed aetiologies and decreasing frequency of atypical pathogens in hospitalised patients and those in ICUs. The distribution of aetiologies according to severity scores showed corresponding patterns; however, the severity scores were more sensitive to Gram-negative enteric bacilli (GNEB) and Pseudomonas aeruginosa and less sensitive in identifying mixed aetiologies as moderate- and high-risk conditions. Mortality rates according to aetiology and severity scoring showed increasing mortality rates for all pathogens except atypical pathogens. S pneumoniae had the highest number of deaths while GNEB, P aeruginosa, Staphylococcus aureus and mixed aetiologies had the highest mortality rates. Legionella pneumophila was similarly distributed according to site of care and prognostic scores., Conclusions: CAP due to atypical bacterial pathogens is recognised both clinically and by severity scoring as a low-risk condition. Severity scores are more sensitive in identifying patients with GNEB and P aeruginosa as moderate- and high-risk aetiologies whereas mixed aetiologies may be underestimated.

The objective of our study was to study which is the most accurate specimen for histological diagnosis of prosthetic joint infections (pseudocapsule or interface membrane). This is a prospective study including hip revision arthroplasties performed from January 2007 to June 2009. Specimens from pseudocapsule and from interface membrane were obtained from each patient. The histology was considered positive for infection when ≥5 neutrophils per high-power field ( × 40) were found. Definitive diagnosis of infection was considered when ≥2 cultures were positive for the same microorganism. According to the definition of infection, patients were classified in two groups: (A) patients with aseptic loosening in whom cultures obtained during surgery were negative and (B) patients with prosthetic joint infection. A total of 69 revisions were included in the study; 57 were classified in group A and 12 in group B. In group B, the percentage of positive interface membrane histology was significantly higher than the percentage of positive pseudocapsule histology (83 vs 42%, P=0.04, Fisher's exact test). The results suggest that periprosthetic interface membrane is the best specimen for the histological diagnosis of prosthetic joint infection.

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.)

The mortality rate of severe sepsis and septic shock remains still high. Within the last years a better knowledge of its physiopathology and the implementation of a group of measures addressed to a fast identification and early treatment of the septic patients have proved to reduce mortality rate. Likewise, it continues being investigated in modulating the inflammatory response and limiting the harmful action of the bacterial products on the immune system. As a result of this research some endotoxin adsorber devices have been designed to control one of the most important targets that start the inflammatory cascade when gram negative microorganisms are involved.The usefulness that these endotoxin removal devices might have as adjuvant treatment in the Septic Syndrome and its applicability are reviewed in this paper. Likewise a profile of patient that might be to the benefit of this therapy is suggested according to the current knowledge.

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.

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.

We describe an outbreak of multidrug-resistant Serratia marcescens infection and colonization involving adults admitted to a surgical intensive care unit. Examination of the outbreak revealed epidemiological evidence that consumption of tap water from a contaminated faucet during receipt of oral medication was the mechanism of S. marcescens acquisition.

The role of mixed community-acquired pneumonia (CAP) is controversial. The aim of the present study was to determine the incidence, principal microbial patterns, clinical predictors and course of mixed CAP. The current study included 1,511 consecutive hospitalised patients with CAP. Of these, 610 (40%) patients had an established aetiology. One pathogen was demonstrated in 528 patients and 82 (13%) patients had mixed pneumonia. Cases including CAP, by a pyogenic bacteria and a complete paired serology for "atypicals", revealed that 82 (13%) patients had definite single pyogenic pneumonia and 28 patients (5%) had mixed pyogenic pneumonia. In patients with mixed CAP, Streptococcus pneumoniae was the most prevalent microorganism (44 out of 82; 54%). The most frequent combination was S. pneumoniae with Haemophilus influenzae (17 out of 82; 21%). Influenza virus A and S. pneumoniae (five out of 28; 18%) was the most frequent association in the mixed pyogenic pneumonia group. No clinical predictors for mixed pneumonias could be identified. Patients with mixed pyogenic pneumonia more frequently developed shock when compared with patients with single pyogenic pneumonia (18 versus 4%). In conclusion, mixed pneumonia occurs in >10% of cases with community-acquired pneumonia requiring hospitalisation.

The lectin pathway of the complement system is activated when mannan-binding lectin (MBL) in complex with MBL-associated serine protease 2 (MASP-2) binds to carbohydrate structures on microorganisms. Structural gene mutations and promoter polymorphisms in the MBL2 gene responsible for low-MBL serum levels are present in all human populations and associate with increased risk of infection. Recently, investigations on Danes revealed the existence of a mutation on the MASP2 gene, which introduces an amino acid substitution in the CUB1 domain (Asp105Gly; numbering refers to the mature protein), and is associated with reduction in the level of MASP-2 in serum. Here, we present the results of a sequence-based typing analysis of the MBL2 and MASP2 gene polymorphisms in a group of 65 Africans (50 North Africans and 15 Sub-Saharan) and of 104 Spaniards. The analysis identified three novel exon 3 MASP2 variants introducing amino acid substitutions at positions 84 (Arg-->Gln), 103 (Arg-->Cys) and 111 (Pro-->Leu) in the CUB1 domain. None of these variants were identified in Spaniards. The Arg84Gln was detected in four of the 15 Sub-Saharans. The Arg103Cys and Pro111Leu variants were detected only among North Africans (two and four individuals, respectively). The Asp105Gly variant was similarly represented among Spaniards and North Africans (three and two individuals, respectively), which appears to be a lower frequency than that reported for Danes (5.5%). As reported for MBL2, the marked geographic distribution of the new MASP2 variants may represent an evolutionary adaptation to different environments.

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).

To evaluate the incidence of vancomycin tolerance among Streptococcus pneumoniae isolates, we performed killing curve studies with 633 isolates. The penicillin MIC was > or = 0.12 mg/liter for 481 (76%) of the isolates. All strains were susceptible to vancomycin. Killing curve studies were performed with a vancomycin concentration of 2.5 mg/liter. The Tupelo strain was used for quality control. No vancomycin-tolerant strain was detected.

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.

The aim of the study was to determine risk factors for severe community-acquired pneumonia (CAP) as well as to compare microbial patterns of severe CAP to a previous study from our respiratory intensive care unit (ICU) originating from 1984 to 1987. Patients admitted to the ICU according to clinical judgment were defined as having severe CAP. For the study of risk factors, a hospital-based case-control design was used, matching each patient with severe CAP to a patient hospitalized with CAP but not requiring ICU admission. Microbial investigation included noninvasive and invasive techniques. Overall, 89 patients with severe CAP were successfully matched to a control patient. The presence of an alcohol ingestion of >/= 80 g/d (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.4 to 10.6, p = 0.008) was found to be an independent risk factor for severe CAP and prior ambulatory antimicrobial treatment (OR 0.37, 95% CI 0.17 to 0.79, p = 0.009) to be protective. Streptococcus pneumoniae (24%) continued to be the most frequent pathogen; however, 48% of strains were drug-resistant. "Atypical" bacterial pathogens were significantly more common (17% versus 6%, p = 0.006) and Legionella spp. less common (2% versus 14%, p = 0.004) than in our previous study, whereas gram-negative enteric bacilli (GNEB) and Pseudomonas aeruginosa continued to represent important pathogens (6% and 5%, respectively). Our findings provide additional evidence for the importance of the initiation of early empiric antimicrobial treatment for a favorable outcome of CAP. Variations of microbial patterns are only in part due to different epidemiological settings. Therefore, initial empiric antimicrobial treatment will also have to take into account local trends of changing microbial patterns.

The aim of this study was to determine the etiology of community-acquired pneumonia (CAP) and the impact of age, comorbidity, and severity on microbial etiologies of such pneumonia. Overall, 395 consecutive patients with CAP were studied prospectively during a 15-mo period. Regular microbial investigation included examination of sputum, blood culture, and serology. Sampling of pleural fluid, transthoracic puncture, tracheobronchial aspiration, and protected specimen brush (PSB) sampling were performed in selected patients. The microbial etiology was determined in 182 of 395 (46%) cases, and 227 pathogens were detected. The five most frequent pathogens were Streptococcus pneumoniae (65 patients [29%]), Haemophilus influenzae (25 patients [11%]), Influenza virus A and B (23 patients [10%]), Legionella sp. (17 patients [8%]), and Chlamydia pneumoniae (15 patients [7%]). Gram-negative enteric bacilli (GNEB) accounted for 13 cases (6%) and Pseudomonas aeruginosa for 12 cases of pneumonia (5%). Patients aged < 60 yr were at risk for an "atypical" bacterial etiology (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.2 to 4.5), especially Mycoplasma pneumoniae (OR: 5.3; 95% CI: 1.7 to 16.8). Comorbid pulmonary, hepatic, and central nervous illnesses, as well as current cigarette smoking and alcohol abuse, were all associated with distinct etiologic patterns. Pneumonia requiring admission to the intensive care unit was independently associated with the pathogens S. pneumoniae (OR: 2.5; 95% CI: 1.3 to 4.7), gram-negative enteric bacilli, and P. aeruginosa (OR: 2.5; 95% CI: 0.99 to 6.5). Clinical and radiographic features of "typical" pneumonia were neither sensitive nor specific for the differentiation of pneumococcal and nonpneumococcal etiologies. These results support a management approach based on the associations between etiology and age, comorbidity, and severity, instead of the traditional syndromic approach to CAP.

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.

The purpose of the study was to validate the criteria used in the guidelines of the American Thoracic Society (ATS) for severe community-acquired pneumonia (CAP). Severe pneumonia was defined as admission to the intensive care unit (ICU). Overall 331 nonsevere (84%) and 64 severe cases (16%) of CAP were prospectively studied. Mortality was 19 of 395 (5%) and 19 of 64 (30%), respectively. Single severity criteria as well as the ATS definition of severe pneumonia were assessed calculating the operative indices. A modified prediction rule including minor (baseline) and major (baseline or evolutionary) criteria was derived. Single minor criteria at admission had a low sensitivity and positive predictive value. Defining severe pneumonia according to the ATS guidelines had a high sensitivity (98%). However, specificity and positive predictive value were low (32% and 24%, respectively). A modified prediction rule (presence of two or three minor criteria [systolic blood pressure < 90 mm Hg, multilobar involvement, PaO2/FIO2 < 250] or one of two major criteria [requirement of mechanical ventilation, presence of septic shock]) had a sensitivity of 78%, a specificity of 94%, a positive predictive value of 75%, and a negative predictive value of 95%. The ATS definition of severe pneumonia was highly sensitive but insufficiently specific and had a low positive predictive value. Our suggested modified rule had a more balanced performance and, if validated in an independent population, may represent a more accurate definition of severe CAP.

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.

Four hundred and fourty-five adult patients suffering acute gastroenteritis (AG) seen at the emergency ward of two hospitals in Barcelona, have been studied. The aim of this work was to analyze the cause of AG in our community and to evaluate the utility of the biologic and clinical criteria chosen as indicators of bacteremia or of AG produced by invasive microorganisms. Stool culture was positive in 157 patients (35%) of which 140 were Salmonella sp. The most frequently isolated serotype was S. enteritidis. Eight patients (7.8%) presented Salmonella sp. bacteremia. Presence of an underlying disease, dehydration, shivers, fever, presence of occult blood in stools, septic hemogram and the history of AG in other family members were more common in patients with a positive stool culture (p less than 0.05). Patients with bacteremia presented dehydration with a significantly higher frequency than nonbacteremics. The rest of the parameters studied were similar in both groups. We conclude that Salmonella sp. is the most frequently encountered microorganisms responsible for adult AG in our community. It is possible to identify patients with AG due to Salmonella sp. based on clinical and biological parameters. On the contrary, it is necessary to perform a wider study in order to determine the parameters that may allow the identification of patients with bacteremia.

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.

In February and March 1989 a community-acquired outbreak of legionnaires' disease developed in Barcelona, involving at least 56 patients (48 males and 8 females) with a mean age of 60 years (range 22-87). 70% were smokers, 20% alcohol abusers, 50% had chronic bronchitis and 20% were immunologically depressed. The most common signs and symptoms were: fever (100%), features of lung condensation (77%), cough (51%), stupor (27%), diarrhea (18%), thoracic pain (18%, hyponatremia (53%), increased serum level of hepatic enzymes (44%) or CK (37%), and renal failure (21%). Radiological involvement was bilateral in 30% of cases. In most patients the diagnosis was made by seroconversion (70%). Late seroconversion (between 4 and 14 weeks) was seen in 20 patients, whose age was significantly higher than that of patients with early seroconversion (p less than 0.02). All cases were caused by Legionella pneumophila serogroup 1. Forty-six patients (81%) were admitted to the hospital and 10 (18%) required tracheal intubation. Although all received erythromycin, seven patients died. Hypoxemia, leukopenia, hyponatremia and renal failure were associated with a higher mortality rate. However, after multivariate analysis renal failure appeared as the only independent prognostic variable. Finally, it was concluded that in the community-acquired outbreaks of pneumonia Legionella pneumophila infection should be ruled out.

To test the hypothesis that HIV infection can modify the clinical characteristics of tuberculosis, 65 consecutive cases of tuberculosis in HIV-seropositive patients diagnosed in Barcelona (Spain) were compared with 65 HIV-seronegative controls matched for age and sex. Thirty of the 65 cases were accepted as AIDS cases (August 1987 Centers for Disease Control criteria) only because of the tuberculosis. Among the cases 54 (83%) were parenteral drug addicts and 88% were males. The tuberculosis was pulmonary or pleural in 62 controls (96%) but in only 25 cases (39%; P less than 0.0001). Lymph nodes were involved in 25 cases (39%) and in none of the controls (P less than 0.0001). Disseminated forms of tuberculosis were present in seven cases (11%) and in no controls (P less than 0.007). Bone, joints and central nervous system involvement were also significantly (P less than 0.05) more frequent in cases. The treatment (isoniazid and rifampin for 6 months plus ethambutol and pyrazinamide during the first 2 months) was always effective. One relapse was detected after a median follow-up of 55 months in cases and none in controls after a median follow-up of 43 months. Twenty-five cases (39%) and 14 controls (22%) developed mild or severe side effects related to the treatment (P less than 0.004). In conclusion, most of the HIV-infected patients with tuberculosis were drug addicts with extrapulmonary or disseminated forms. A short course of treatment (6 or 9 months) may be enough but side effects were frequent.