M. Almela

Epidemiology and Predictors of Mortality in Cases of Candida Bloodstream Infection: Results from Population-Based Surveillance, Barcelona, Spain, from 2002 to 2003

ABSTRACT 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 ≥ 16 μg/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.

Addition of a Macrolide to a β-Lactam-Based Empirical Antibiotic Regimen Is Associated with Lower In-Hospital Mortality for Patients with Bacteremic Pneumococcal Pneumonia

To assess the association between inclusion of a macrolide in a beta-lactam-based empirical antibiotic regimen and mortality among patients with bacteremic pneumococcal pneumonia, 10 years of data from a database were analyzed. The total available set of putative prognostic factors was subjected to stepwise logistic regression, with in-hospital death as the dependent variable. Of the 409 patients analyzed, 238 (58%) received a beta-lactam plus a macrolide and 171 (42%) received a beta-lactam without a macrolide. Multivariate analysis revealed 4 variables to be independently associated with death: shock (P<.0001), age of >or=65 years (P=.02), infections with pathogens that have resistance to both penicillin and erythromycin (P=.04), and no inclusion of a macrolide in the initial antibiotic regimen (P=.03). For patients with bacteremic pneumococcal pneumonia, not adding a macrolide to a beta-lactam-based initial antibiotic regimen is an independent predictor of in-hospital mortality. However, only a randomized study can definitively determine whether this association is due to a real effect of macrolides.

Pathogenic significance of methicillin resistance for patients with Staphylococcus aureus bacteremia

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.

Community-Onset Bacteremia Due to Extended-Spectrum β-Lactamase-Producing Escherichia coli: Risk Factors and Prognosis

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.

Analysis of 4758 Escherichia coli bacteraemia episodes: predictive factors for isolation of an antibiotic-resistant strain and their impact on the outcome.

OBJECTIVES To describe the predictive factors for the isolation of fluoroquinolone-resistant or extended- spectrum beta-lactamase (ESBL)-producing Escherichia coli and their impact on bacteraemia outcome. METHODS Analysis of E. coli bacteraemia episodes prospectively collected through a blood culture surveillance programme from January 1991 to December 2007. RESULTS Out of 18 080 episodes, 4758 (26%) E. coli bacteraemias were reported in the period of study. Mortality was noted in 440 cases (9%). Fluoroquinolone-resistant strains were reported in 1300 (27%) cases and ESBL-producing strains in 211 cases (4%). One hundred and seventy-eight strains out of 211 (84%) ESBL-producing E. coli were isolated since 2001. The two main independent risk factors for mortality were shock (OR: 10.28, P < 0.001) and inappropriate empirical therapy (OR: 4.83, P < 0.001). Inappropriate empirical therapy was significantly more frequent for infections caused by fluoroquinolone-resistant strains (n = 203, 16%, P < 0.001) and ESBL-producing strains (n = 110, 52%, P < 0.001). Independent factors associated with the isolation of a fluoroquinolone-resistant strain were: nosocomial origin (OR: 1.61, P < 0.001); urinary catheterization (OR: 2.44, P < 0.001); and previous therapy with a fluoroquinolone (OR: 7.41, P < 0.001). The independent risk factors associated with the isolation of an ESBL-producing strain were: nosocomial origin (OR: 1.68, P = 0.03); urinary catheterization (OR: 1.88, P = 0.001); and previous beta-lactam antibiotic therapy (OR: 2.81, P < 0.001). CONCLUSIONS Inappropriate empirical therapy was the strongest independent factor that we could modify to improve mortality in E. coli bacteraemia and was more frequent in cases caused by fluoroquinolone-resistant or ESBL-producing strains. Nosocomial acquisition, urinary catheterization and previous therapy with a fluoroquinolone or beta-lactam were predictive factors for infection with an antibiotic-resistant strain.

Staphylococcus lugdunensis infective endocarditis: description of 10 cases and analysis of native valve, prosthetic valve, and pacemaker lead endocarditis clinical profiles

Objective: To evaluate the incidence and the clinical and echocardiographic features of infective endocarditis (IE) caused by Staphylococcus lugdunensis and to identify the prognostic factors of surgery and mortality in this disease. Design: Prospective cohort study. Setting: Study at two centres (a tertiary care centre and a community hospital). Patients: 10 patients with IE caused by S lugdunensis in 912 consecutive patients with IE between 1990 and 2003. Methods: Prospective study of consecutive patients carried out by the multidisciplinary team for diagnosis and treatment of IE from the study institutions. English, French, and Spanish literature was searched by computer under the terms “endocarditis” and “Staphylococcus lugdunensis” published between 1989 and December 2003. Main outcome measures: Patient characteristics, echocardiographic findings, required surgery, and prognostic factors of mortality in left sided cases of IE. Results: 10 cases of IE caused by S lugdunensis were identified at our institutions, representing 0.8% (four of 467), 1.5% (two of 135), and 7.8% (four of 51) of cases of native valve, prosthetic valve, and pacemaker lead endocarditis in the non-drug misusers. Native valve IE was present in four patients (two aortic, one mitral, and one pulmonary), prosthetic valve aortic IE in two patients, and pacemaker lead IE in the other four patients. All patients with left sided IE had serious complications (heart failure, periannular abscess formation, or shock) requiring surgery in 60% (three of five patients) of cases with an overall mortality rate of 80% (four of five patients). All patients with pacemaker IE underwent combined medical treatment and surgery, and mortality was 25% (one patient). In total 59 cases of IE caused by S lugdunensis were identified in a review of the literature. The combined analysis of these 69 cases showed that native valve IE (53 patients, 77%) is characterised by mitral valve involvement and frequent complications such as heart failure, abscess formation, and embolism. Surgery was needed in 51% of cases and mortality was 42%. Prosthetic valve endocarditis (nine of 60, 13%) predominated in the aortic position and was associated with abscess formation, required surgery, and high mortality (78%). Pacemaker lead IE (seven of 69, 10%) is associated with a better prognosis when antibiotic treatment is combined with surgery. Conclusions:S lugdunensis IE is an uncommon cause of IE, involving mainly native left sided valves, and it is characterised by an aggressive clinical course. Mortality in left sided native valve IE is high but the prognosis has improved in recent years. Surgery has improved survival in left sided IE and, therefore, early surgery should always be considered. Prosthetic valve S lugdunensis IE carries an ominous prognosis.

Risk Factors and Prognosis of Nosocomial Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Escherichia coli

ABSTRACT Extended-spectrum-β-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-β-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-β-lactams was the only modifiable risk factor found. Resistance to drugs other than penicillins and cephalosporins was associated with increased mortality.

Candida species bloodstream infection: epidemiology and outcome in a single institution from 1991 to 2008.

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.

Early Bacteremia After Solid Organ Transplantation

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.

Influence of Empiric Therapy with a β-Lactam Alone or Combined with an Aminoglycoside on Prognosis of Bacteremia Due to Gram-Negative Microorganisms

ABSTRACT Evidence supporting the combination of aminoglycosides with β-lactams for Gram-negative bacteremia is inconclusive. We have explored the influence on survival of empirical therapy with a β-lactam alone versus that with a β-lactam-aminoglycoside combination by retrospectively analyzing a series of bacteremic episodes due to aerobic or facultative Gram-negative microorganisms treated with single or combination therapy. The outcome variable was a 30-day mortality. Prognostic factors were selected by regression logistic analysis. A total of 4,863 episodes were assessed, of which 678 (14%) received combination therapy and 467 (10%) were fatal. Factors independently associated with mortality included age greater than 65 (odds ratio [OR], 2; 95% confidence interval [CI], 1.6 to 2.6), hospital acquisition (OR, 1.5; 95% CI, 1.2 to 1.9), a rapidly or ultimately fatal underlying disease (OR, 2.5; 95% CI, 2 to 3.2), cirrhosis (OR, 1.9; 95% CI, 1.4 to 2.6), prior corticosteroids (OR, 1.5; 95% CI, 1.1 to 2), shock on presentation (OR, 8.8; 95% CI, 7 to 11), pneumonia (OR, 2.8; 95% CI, 1.9 to 4), and inappropriate empirical therapy (OR, 1.8; 95% CI, 1.3 to 2.5). Subgroup analysis revealed that combination therapy was an independent protective factor in episodes presenting shock (OR, 0.6; 95% CI, 0.4 to 0.9) or neutropenia (OR, 0.5; 95% CI, 0.3 to 0.9). Combination therapy improved the appropriateness of empirical therapy in episodes due to extended-spectrum β-lactamase (ESBL)- or AmpC-producing Enterobacteriaceae and Pseudomonas aeruginosa. In patients with Gram-negative bacteremia, we could not find an overall association between empirical β-lactam-aminoglycoside combination therapy and prognosis. However, a survival advantage cannot be discarded for episodes presenting shock or neutropenia, hence in these situations the use of combination therapy may still be justified. Combination therapy also should be considered for patients at risk of being infected with resistant organisms, if only to increase the appropriateness of empirical therapy.