Manel Almela

Epidemiology, risk factors, and prognosis of Candida parapsilosis bloodstream infections: case-control population-based surveillance study of patients in Barcelona, Spain, from 2002 to 2003.

ABSTRACT Candida parapsilosis has emerged as an important yeast species causing fungemia. We describe the incidence and epidemiology of C. parapsilosis fungemia. Data from active population-based surveillance in Barcelona, Spain, from January 2002 to December 2003 were analyzed. We focused on 78 episodes of C. parapsilosis fungemia, and we compared them with 175 Candida albicans controls. C. parapsilosis accounted for 23% of all fungemias. The annual incidences were 1 episode per 105 patients, 1.2 episodes per 104 discharges, and 1.7 episodes per 105 patient days. All isolates but one (99%) were fluconazole susceptible. Seventy-two isolates (92%) were inpatient candidemias. Forty-two episodes (51%) were considered catheter-related fungemia, 35 (45%) were considered primary fungemia, and 3 (4%) were considered secondary fungemia. Risk factors for candidemia were vascular catheterization (97%), prior antibiotic therapy (91%), parenteral nutrition (54%), prior surgery (46%), prior immunosuppressive therapy (38%), malignancy (27%), prior antifungal infection (26%), transplant recipient (16%), neutropenia (12%), and prior colonization (11%). Multivariate analysis of the differential characteristics showed that the factors that independently predicted the presence of C. parapsilosis fungemia were neonate patients (odds ratio [OR], 7.5; 95% confidence interval [CI], 2.1 to 26.8; P = 0.002), transplant recipients (OR, 9.2; 95% CI, 1.9 to 43.3; P = 0.005), patients with a history of prior antifungal therapy (OR, 5.4; 95% CI, 1.8 to 15.9; P = 0.002), and patients who received parenteral nutrition (OR, 2.2; 95% CI, 1.09 to 4.6; P = 0.028). The overall mortality rate was lower than that associated with C. albicans candidemia (23% versus 43%; P < 0.01). In summary, C. parapsilosis was responsible for 23% of all candidemias and was more frequent in neonates, in transplant recipients, and in patients who received parenteral nutrition or previous antifungal therapy, mainly fluconazole. The mortality rate was lower than that associated with C. albicans fungemia.

Blood Cultures for Women with Uncomplicated Acute Pyelonephritis: Are They Necessary?

To assess the utility of blood cultures in the management of uncomplicated pyelonephritis in women, we prospectively collected data from 583 cases. Discordant cases were defined as those for which the pathogens isolated from urine and from blood were different. We found that 97.6% of cases were nondiscordant. Clinical and microbiological evolution of infection did not differ between the 2 groups, and no changes of antibiotic therapy were required on the basis of blood culture results. Blood culture may not be routinely required for the evaluation of uncomplicated pyelonephritis in women.

Bacterial and fungal bloodstream isolates from 796 hematopoietic stem cell transplant recipients between 1991 and 2000

To examine shifts in the etiology, incidence, evolution, susceptibility, and patient mortality of bacterial and fungal bloodstream isolates (BSIs) from hematopoietic stem cell transplantation (HSCT) recipients, we reviewed the BSIs of 796 patients who underwent an HSCT in our institution during a 10-year period. Four hundred eighty-nine episodes of bacterial and fungal BSI were detected in 330 patients (41%). Three hundred ten isolates (63%) were gram-positive bacteria, 142 (29%) were gram-negative, and 18 and 19 isolates were different species of anaerobic organism and Candida spp. (both 4%). Coagulase-negative staphylococci (CoNS), with 210 isolates, were the organism most frequently isolated in each year of study and during the three phases of immune recovery after HSCT. The ratio of gram-positive to gram-negative has declined from 3.3 (1991–1992) to 1.8 (1999–2000). Crude mortality occurred in 47 cases of 489 BSI episodes (10%). Mortality according to groups was gram-negative, 7%; gram-positive, 9%; and anaerobic bacteria, 11%. Candida spp. was the group that accounted for the highest crude mortality, with 42%. Gram-positive microorganisms were isolated more often than gram-negative organisms, but the trend is reversing. CoNS were the leading pathogen during the 10 years of study and during the three phases of immune recovery after HSCT. Crude mortality of HSCT patients with BSI was low except for infections caused by Candida spp.

Influence of Multidrug Resistance and Appropriate Empirical Therapy on the 30-Day Mortality Rate of Pseudomonas aeruginosa Bacteremia

ABSTRACT Infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa are increasing. The aim of our study was to evaluate the influences of appropriate empirical antibiotic therapy and multidrug resistance on mortality in patients with bacteremia due to P. aeruginosa (PAB). Episodes of PAB were prospectively registered from 2000 to 2008. MDR was considered when the strain was resistant to ≥3 antipseudomonal antibiotics. Univariate and multivariate analyses were performed. A total of 709 episodes of PAB were studied. MDR PAB (n = 127 [17.9%]) was more frequently nosocomial and associated with longer hospitalization, bladder catheter use, steroid and antibiotic therapy, receipt of inappropriate empirical antibiotic therapy, and a higher mortality. Factors independently associated with mortality were age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.002 to 1.033), shock (OR, 6.6; 95% CI, 4 to 10.8), cirrhosis (OR, 3.3; 95% CI, 1.4 to 7.6), intermediate-risk sources (OR, 2.5; 95% CI, 1.4 to 4.3) or high-risk sources (OR, 7.3; 95% CI, 4.1 to 12.9), and inappropriate empirical therapy (OR, 2.1; 95% CI, 1.3 to 3.5). To analyze the interaction between empirical therapy and MDR, a variable combining both was introduced in the multivariate analysis. Inappropriate therapy was significantly associated with higher mortality regardless of the susceptibility pattern, and there was a trend toward higher mortality in patients receiving appropriate therapy for MDR than in those appropriately treated for non-MDR strains (OR, 2.2; 95% CI, 0.9 to 5.4). In 47.9% of MDR PAB episodes, appropriate therapy consisted of monotherapy with amikacin. In conclusion, MDR PAB is associated with a higher mortality than non-MDR PAB. This may be related to a higher rate of inappropriate empirical therapy and probably also to amikacin as frequently the only appropriate empirical therapy given to patients with MDR PAB.

New rapid antigen test for diagnosis of pneumococcal meningitis

Conventional diagnostic methods for bacterial meningitis are frequently not rapid or sensitive enough to guide initial antimicrobial therapy. Streptococcus pneumoniae is the most frequent and severe cause of community-acquired bacterial meningitis and treatment is complicated by the increasing prevalence of antimicrobial resistance to third-generation cephalosporins. We used a new rapid antigen test in the cerebrospinal fluid and urine of patients with suspected bacterial meningitis, and found it to be highly sensitive and specific for the detection of pneumococci. This test might help guide initial therapy for bacterial meningitis according to the local rates of pneumococcal antimicrobial resistance.

Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study

BACKGROUND The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. METHODS In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0-7 [low mortality score] vs 8-15 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. FINDINGS Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38·5%] of 343 patients died vs 57 [60·6%] of 94; absolute difference 22·1% [95% CI 11·0-33·3]; adjusted hazard ratio [HR] 0·45 [95% CI 0·33-0·62]; p<0·0001). Among those receiving appropriate therapy, 135 (39%) received combination therapy and 208 (61%) received monotherapy. Overall mortality was not different between those receiving combination therapy or monotherapy (47 [35%] of 135 vs 85 [41%] of 208; adjusted HR 1·63 [95% CI 0·67-3·91]; p=0·28). However, combination therapy was associated with lower mortality than was monotherapy in the high-mortality-score stratum (30 [48%] of 63 vs 64 [62%] of 103; adjusted HR 0·56 [0·34-0·91]; p=0·02), but not in the low-mortality-score stratum (17 [24%] of 72 vs 21 [20%] of 105; adjusted odds ratio 1·21 [0·56-2·56]; p=0·62). INTERPRETATION Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to CPE. Combination therapy was associated with improved survival only in patients with a high mortality score. Patients with BSIs due to CPE should receive active therapy as soon as they are diagnosed, and monotherapy should be considered for those in the low-mortality-score stratum. FUNDING Spanish Network for Research in Infectious Diseases, European Development Regional Fund, Instituto de Salud Carlos III, and Innovative Medicines Initiative.

Relationship of Phylogenetic Background, Biofilm Production, and Time to Detection of Growth in Blood Culture Vials with Clinical Variables and Prognosis Associated with Escherichia coli Bacteremia

ABSTRACT In patients with Escherichia coli bacteremia, data on the relationship of phylogenetic background, biofilm production, and degree of bacteremia with clinical variables and prognosis are scarce. During a 1-year period, all adults with bacteremia due to Escherichia coli diagnosed at a university center were enrolled. Determination of phylogenetic background, biofilm production, and genotyping was performed with all strains, and the time to positivity of blood culture vials was recorded. A total of 185 episodes of diverse-source E. coli bacteremia was analyzed. Strains of phylogroup D were predominant (52%). Phylogroup A isolates were associated with pneumonia and prior antibiotic intake, B1 with an abdominal source of infection, B2 with the absence of urological abnormalities, and D with urological abnormalities and age below 65 years. Resistance to antibiotics and no biofilm production were concentrated in phylogroup A strains. Biofilm production was not associated with any clinical variable. An immunocompromising condition (odds ratio [OR] = 5.01, 95% confidence interval [CI] = 1.4 to 17.9), peritonitis (OR = 17, 95% CI = 3.32 to 87), pneumonia (OR = 9.97, 95% CI = 1.96 to 50.6), and ≤7 h to bacteremia detection (OR = 4.37, 95% CI = 1.38 to 13.8) were the best predictors of a fatal outcome. Results from this study suggest that the distribution of phylogenetic backgrounds among E. coli strains involved in diverse-source bacteremia may be subject to geographical variation and that, in afflicted individuals, some high-risk sources, the patients underlying condition, and the degree of bacteremia are more important than microbial factors in determining the outcome. Time to positivity of blood culture vials may be a variable of potential clinical impact.

A Multinational, Preregistered Cohort Study of β-Lactam/β-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae

ABSTRACT The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)

Initial Use of Echinocandins Does Not Negatively Influence Outcome in Candida parapsilosis Bloodstream Infection: A Propensity Score Analysis

BACKGROUND Concerns have arisen regarding the optimal antifungal regimen for Candida parapsilosis bloodstream infection (BSI) in view of its reduced susceptibility to echinocandins. METHODS The Prospective Population Study on Candidemia in Spain (CANDIPOP) is a prospective multicenter, population-based surveillance program on Candida BSI conducted through a 12-month period in 29 Spanish hospitals. Clinical isolates were identified by DNA sequencing, and antifungal susceptibility testing was performed by the European Committee on Antimicrobial Susceptibility Testing methodology. Predictors for clinical failure (all-cause mortality between days 3 to 30, or persistent candidemia for ≥72 hours after initiation of therapy) in episodes of C. parapsilosis species complex BSI were assessed by logistic regression analysis. We further analyzed the impact of echinocandin-based regimen as the initial antifungal therapy (within the first 72 hours) by using a propensity score approach. RESULTS Among 752 episodes of Candida BSI identified, 200 (26.6%) were due to C. parapsilosis species complex. We finally analyzed 194 episodes occurring in 190 patients. Clinical failure occurred in 58 of 177 (32.8%) of evaluable episodes. Orotracheal intubation (adjusted odds ratio [AOR], 2.81; P = .018) and septic shock (AOR, 2.91; P = .081) emerged as risk factors for clinical failure, whereas early central venous catheter removal was protective (AOR, 0.43; P = .040). Neither univariate nor multivariate analysis revealed that the initial use of an echinocandin-based regimen had any impact on the risk of clinical failure. Incorporation of the propensity score into the model did not change this finding. CONCLUSIONS The initial use of an echinocandin-based regimen does not seem to negatively influence outcome in C. parapsilosis BSI.

Changing epidemiology of central venous catheter-related bloodstream infections: increasing prevalence of Gram-negative pathogens

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.