Mar Ortega

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.

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.

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.

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.

Cerebrospinal fluid HIV-1 RNA levels in asymptomatic patients with early stage chronic HIV-1 infection: support for the hypothesis of local virus replication.

OBJECTIVE To assess HIV-1 RNA levels in cerebrospinal fluid (CSF) and their potential correlation with plasma viral load and central nervous system (CNS) HIV-1 infection markers in stable asymptomatic patients with a CD4 T cell count >500x10(6) cells/l. PATIENTS AND METHODS Consecutive patients screened for two trials were eligible for lumbar puncture assessment. At day 0, simultaneous samples of CSF and plasma were obtained and levels of total proteins, albumin, IgG, antibodies against HIV-1 p24 antigen, HIV-1 RNA (using the polymerase chain technique) and white cells were measured. RESULTS The integrity of the blood-brain barrier was preserved (albumin index > or =7) in 59 out of 70 patients (84%). Intrathecal production of antibodies against HIV-1 p24 antigen was demonstrated in 55 out of 70 individuals (78%). Viral load in CSF was significantly lower than plasma values (3.13+/-0.95 versus 4.53+/-0.53, P = 0.0001). HIV-1 RNA was not detected in CSF in only three of the 70 patients (4%). Overall, there was a significant correlation between plasma and CSF HIV-1 RNA levels (r = 0.43, P = 0.0001); however, in 29 patients (41%) there were significant differences (>1.5 log10 copies/ml) between the viral loads in plasma and CSF. In the multivariate analysis, a high level of protein and white cells in CSF, but not the HIV-1 RNA plasma level, were factors independently associated with a higher level of HIV-1 RNA in CSF (P = 0.0001). CONCLUSIONS HIV-1 RNA can be detected almost always in CSF of asymptomatic patients in early stages of HIV-1 infection including those with a preserved integrity of the blood-brain barrier. The important discrepancies between plasma and CSF viral load, and the independent association between CSF abnormalities and CSF viral load, support the hypothesis of local production of HIV-1.

Comparative Study of the Effects of Pyridoxine, Rifampin, and Renal Function on Hematological Adverse Events Induced by Linezolid

ABSTRACT Hematological disturbances that develop during linezolid treatment are a major concern when linezolid is administered for prolonged periods of time. The aim of this study was to evaluate the influences of pyridoxine, rifampin, and renal function on hematological adverse events. From January 2002 to April 2006, 52 patients received a long-term course of linezolid. Blood cell counts were monitored weekly. Thrombocytopenia was defined as a decrease to <75% of the baseline platelet count, and anemia was defined when the hemoglobin concentration decreased by ≥2 g/liter from the baseline value. Twenty-four patients received linezolid alone, and 28 patients received linezolid plus 200 mg of pyridoxine. The Kaplan-Meier survival method, followed by the log-rank test, was used to estimate the cumulative probability of adverse events, and Cox regression analysis was performed to evaluate the independent predictors of toxicity. The baseline characteristics of the patients in both groups were similar. The cumulative probability of thrombocytopenia and anemia in patients who received pyridoxine was not different from that in patients who did not receive it. Hematological adverse events were less frequent in patients taking rifampin and were more frequent in patients with renal failure. However; the Cox regression analysis showed that rifampin was the only independent predictor associated with a lower risk of thrombocytopenia (hazard ratio, 0.37; 95% confidence interval, 0.14 to 0.98; P = 0.045). In conclusion, pyridoxine did not prevent linezolid-related hematological adverse events, and the coadministration of rifampin was associated with a lower risk of thrombocytopenia.

Community-acquired pneumonia in outpatients: aetiology and outcomes

The purpose of this study was to establish the microbial aetiology and outcomes of patients with community-acquired pneumonia (CAP) treated as outpatients after presenting to a hospital emergency care unit. A prospective observational study was carried out in the Hospital Clinic of Barcelona (Barcelona, Spain). All consecutive cases of CAP treated as outpatients were included. 568 adult outpatients with CAP were studied (mean±sd age 47.2±17.6 yrs; 110 (19.4%) were aged ≥65 yrs). Aetiological diagnoses were established in 188 (33.1%) cases. Streptococcus pneumoniae was the most frequent pathogen followed by Mycoplasma pneumoniae and respiratory viruses. Legionella was detected in 13 (2.3%) cases. More than one causative agent was found in 17 (9.0%) patients. Mortality was low (three (0.5%) patients died) and other adverse events were rare (30 (5.2%) patients had complications, 13 (2.3%) were re-admitted and treatment failed in 13 (2.3%)). Complications were mostly related to pleural effusion and empyema, and re-admissions and treatment failures to comorbidities. Outpatients with CAP have a characteristic microbial pattern. Regular antipneumococcal coverage remains mandatory. Treatment failures and re-admissions are rare and may be reduced by increased attention to patients requiring short-term observation in the emergency care unit and in the presence of pleural effusion and comorbidities.

Prospective evaluation of procalcitonin in adults with febrile neutropenia after haematopoietic stem cell transplantation

Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin (n = 51), microbiological (n = 26) or clinical (n = 5) documented infection and non‐infectious febrile episodes (n = 10). On first day of fever, mean (±SD) PCT level was 0·3 ng/ml (0·2) in neutropenic fever of unknown origin, 0·5 ng/ml (0·7) in microbiologically confirmed infections, 0·2 ng/ml (0·2) in clinically documented infections and 1·7 (4·2) in non‐infectious fever (P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10·1 ng/ml (6·7)] than all remaining groups (P = 0·027; Kruskal–Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values ≥3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis.

Candida spp. bloodstream infection: influence of antifungal treatment on outcome

OBJECTIVES To assess the influence of new antifungal treatments on candidaemia outcome. METHODS Candidaemia episodes prospectively collected through a blood culture surveillance programme in a single institution. The study was divided into two periods of time, 1994-2003 (A) and 2004-2008 (B), according to the introduction of echinocandin treatment. Non-conditional logistic regression methods with mortality as the dependent variable were used. RESULTS Four hundred and thirty-three (3%) candidaemias out of 15 628 bloodstream infection episodes were analysed. Candida albicans was the most frequent species (211; 49%). Mortality was noted in 132 cases (30%). A total of 262 and 171 candidaemias were reported in period A and B, respectively. There were 94 deaths in period A (36%) and 38 in period B (22%, P = 0.03). Treatment in period A was amphotericin B in 89 patients (41 dead, 46%) and fluconazole in 151 (41 dead, 27%, P = 0.003). In period B, 113 patients received a triazole (26 dead, 23%), 30 an echinocandin (3 dead, 10%, P = 0.08) and 9 (0 dead) were treated with combined therapy (echinocandin and triazole). Mortality was higher in period A (94 dead, 36%) than in period B (38 dead, 27%), P = 0.03. Independent risk factors associated with mortality in period B were: age, chronic renal failure, ultimately or rapidly fatal prognosis of underlying disease and shock. Echinocandin alone or in combination therapy was associated with better outcome (odds ratio = 0.22, 95% confidence interval = 0.06-0.81, P = 0.02). CONCLUSIONS In patients with candidaemia, echinocandin therapy results in a better outcome.

Bloodstream infections among human immunodeficiency virus-infected adult patients: epidemiology and risk factors for mortality

This study was undertaken to describe the epidemiology and sensitivity pattern of pathogens causing community-acquired (CA) and nosocomial (N) bloodstream infection (BSI) in adult HIV-infected patients and to establish risk factors for mortality. The type of study was a retrospective analysis of BSI episodes prospectively collected through a blood culture surveillance program from January 1991 to December 2006. We used non-conditional logistic regression methods with death as a dependent variable. One thousand and seventy-seven episodes of BSI (6%) occurred in HIV-infected patients out of 16,946 episodes during the period of study. CA and N BSI were 634 (59%) and 443 (41%) respectively. S. pneumoniae and S. aureus were the most frequent pathogens (n = 279, 44%) in CA BSI. Coagulase-negative staphylococci and S. aureus were the most frequent micro-organisms isolated in N cases (n = 169, 38%). Cotrimoxazole resistance was common in CA and N BSI and was caused by gram-negative bacilli (50% and 61% respectively). However, resistance rates to ceftriaxone were low (3%). Crude mortality accounted for 140 cases (13%). The independent risk factors associated with mortality were: liver cirrhosis (OR: 2.90, p = 0.001), corticosteroids treatment (OR: 3.51, p < 0.001), neutropenia (OR: 2.21, p = 0.02), inappropriate empirical therapy (OR: 2.44, p = 0.006), and isolate of C. albicans (OR: 7.58, p = 0.010). BSI in adult HIV-infected patients was often caused by gram-positive pathogens in both CA and N settings. Inappropriate empirical therapy and the presence of other immunosuppressive factors were independent risk factors for mortality. Ceftriaxone could be used as the initial empiric therapy for HIV-infected patients with suspected CA BSI.