Variability of intestinal colonization with third-generation cephalosporin-resistant Enterobacteriaceae and antibiotic use in intensive care units.

OBJECTIVES: Healthcare-associated infections due to third-generation cephalosporin-resistant Enterobacteriaceae (CRE) have become a major public health threat, especially in intensive care units (ICUs). We assessed and compared ß-lactam use, the prevalence of colonization with CRE at admission and the incidence of CRE acquisition across ICUs. PATIENTS AND METHODS: A cohort study was conducted in 10 ICUs of the Paris (France) metropolitan area between November 2005 and February 2006. Antibiotic use was recorded prospectively in all patients admitted during the study period. Rectal swabs were collected at admission, twice weekly thereafter, before ß-lactam prescription and before discharge. RESULTS: A total of 893 patients provided 3453 rectal swabs; 793 of the patients were newly admitted, mostly for medical reasons (80.7%). On admission, 74 patients (9.6%) were colonized with CRE, including 32 with an extended-spectrum ß-lactamase (ESBL)-producing strain. Among the remaining 694 naive patients, 94 acquired CRE during their follow-up, including 31 with an ESBL-producing strain. Incidence rates of colonization ranged from 8.8 to 21.0/1000 patient-days for all CRE, and from 1.4 to 10.9/1000 patient-days for ESBL producers. A majority of patients (68.3%) were prescribed ß-lactams during their ICU stay, with defined daily doses ranging from 428 to 985/1000 patient-days. Across ICUs, prescriptions of all antibiotics, ß-lactams and carbapenems were significantly correlated to incidence rates of colonization with ESBL-producing CRE. CONCLUSIONS: The standardized and systematic follow-up of patients in 10 ICUs revealed great heterogeneity in the rates of colonization with ESBL- and non-ESBL-producing CRE, as well as in antimicrobial prescription practices.

Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006).

OBJECTIVE: To describe the evolving epidemiology, management, and risk factors for death of invasive Candida infections in intensive care units (ICUs). DESIGN: Prospective, observational, national, multicenter study. SETTING: One hundred eighty ICUs in France. PATIENTS: Between October 2005 and May 2006, 300 adult patients with proven invasive Candida infection who received systemic antifungal therapy were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred seven patients (39.5%) with isolated candidemia, 87 (32.1%) with invasive candidiasis without documented candidemia, and 77 (28.4%) with invasive candidiasis and candidemia were eligible. In 37% of the cases, candidemia occurred within the first 5 days after ICU admission. C. albicans accounted for 57.0% of the isolates, followed by C. glabrata (16.7%), C. parapsilosis (7.5%), C. krusei (5.2%), and C. tropicalis (4.9%). In 17.1% of the isolates, the causative Candida was less susceptible or resistant to fluconazole. Fluconazole was the empirical treatment most commonly introduced (65.7%), followed by caspofungin (18.1%), voriconazole (5.5%), and amphotericin B (3.7%). After identification of the causative species and susceptibility testing results, treatment was modified in 86 patients (31.7%). The case fatality ratio in ICU was 45.9% and did not differ significantly according to the type of episode. Multivariate analysis showed that factors independently associated with death in ICU were type 1 diabetes mellitus (odds ratio [OR] 4.51; 95% confidence interval [CI] 1.72-11.79; p = 0.002), immunosuppression (OR 2.63; 95% CI 1.35-5.11; p = 0.0045), mechanical ventilation (OR 2.54; 95% CI 1.33-4.82; p = 0.0045), and body temperature >38.2 degrees C (reference, 36.5-38.2 degrees C; OR 0.36; 95% CI 0.17-0.77; p = 0.008). CONCLUSIONS: More than two thirds of patients with invasive candidiasis in ICU present with candidemia. Non-albicans Candida species reach almost half of the Candida isolates. Reduced susceptibility to fluconazole is observed in 17.1% of Candida isolates. Mortality of invasive candidiasis in ICU remains high.

Evaluation of the Binax NOW Streptococcus pneumoniae urinary antigen assay in intensive care patients hospitalized for pneumonia.

OBJECTIVE: To evaluate the diagnostic performance of Binax Now S. pneumoniae urinary antigen rapid immunochromatographic membrane test (ICT) for patients with suspicion of community-acquired pneumonia hospitalized in intensive care and to assess the impact of prior antibiotics on its diagnostic performance. DESIGN AND SETTING: Retrospective study in a medicosurgical ICU in a 700-bed general hospital. PATIENTS: Charts of patients with ICT performed (result blinded) were reviewed between May 2002 and July 2004. ICT has been performed in 140 of the 1,006 patients hospitalized in the unit; two-thirds had received antibiotics prior to admission. MEASUREMENTS AND RESULTS: Diagnosis of pneumonia was made according to usual criteria. All patients had at least one microbiological test. Pneumonia diagnosis confirmed in 108 patients including 32 pneumococcal. ICT was positive in 23 of 32 patients with pneumococcal pneumonia, in 11 of 108 without, and in none of the 32 patients without pneumonia, resulting in sensitivity, specificity, and positive and negative predictive values of, respectively: 72%, 90%, 68% and 92%. Positive likelihood ratios were comparable among patients with or without prior antibiotics (respectively 6 and 12 for 7 in the overall population). CONCLUSIONS: This first clinical evaluation of ICT in intensive care patients hospitalized for suspicion of community-acquired pneumonia, demonstrated performance in accordance with published data even in the case of prior antibiotics. Its clinical interest and impact on antibiotics policy remain to be refined.

Respiratory tract infections: at-risk patients, who are they? Implications for their management with levofloxacin.

At this symposium, the bacterial aetiologies of community-acquired pneumonia and acute exacerbations of chronic bronchitis were evaluated. By reviewing the clinical criteria for the identification of at-risk patients and the recommendations for antimicrobial drug selection in treatment guidelines, the role of levofloxacin in clinical practice was explored. In addition, consideration was also given to the economic impact of using levofloxacin in at-risk patients.

Severe community-acquired pneumonia as a cause of severe sepsis: data from the PROWESS study.

OBJECTIVE: To investigate community-acquired pneumonia (CAP) as a cause of severe sepsis in the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial and to evaluate the effect of drotrecogin alfa (activated) (DrotAA) in this subgroup. DESIGN: Retrospective analysis of the severe CAP subgroup in the PROWESS trial. SETTING: Tertiary care institutions in 11 countries. INTERVENTIONS: DrotAA (n = 850), 24 microg.kg.hr for 96 hrs, or placebo (n = 840). PARTICIPANTS: The 1,690 patients with severe sepsis enrolled in the PROWESS trial. MEASUREMENTS AND MAIN RESULTS: Patients were classified as having CAP if lung was the primary site of infection and if they were enrolled directly from home (private residence) with /=25, Pneumonia Severity Index score of >/=4, or CURB-65 (confusion, urea, respiratory rate, blood pressure, age) score of >/=3. CONCLUSIONS: CAP associated with a high Pneumonia Severity Index score, bacteremia, or an intense coagulation and inflammatory response requiring intensive care unit care were indicators of a high risk of death from severe sepsis. In patients with severe sepsis resulting from CAP, a readily identifiable disease, DrotAA, improved survival compared with placebo.

Prevention of intravascular catheter-related infection with newer chlorhexidine-silver sulfadiazine-coated catheters: a randomized controlled trial.

BACKGROUND: The indication of antiseptic-coated catheters remains debated. OBJECTIVE: To test the ability of the new generation of chlorhexidine-silver and sulfadiazine-coated catheters, with enhanced antiseptic coating, to reduce the risk of central venous catheter (CVC)-related infection in ICU patients. DESIGN: Multicentre randomized double-blind trial. PATIENTS AND SETTING: A total of 397 patients from 14 ICUs of university hospitals in France. INTERVENTION: Patients were randomized to receive an antiseptic-coated catheter (ACC) or a standard non-coated catheter (NCC). MEASUREMENTS: Incidence of CVC-related infection. RESULTS: Of 367 patients having a successful catheter insertion, 363 were analysed (175 NCC and 188 ACC). Patients had one (NCC=162, ACC=180) or more (NCC=13, ACC=11) CVC inserted. The two groups were similar for insertion site [subclavian (64 vs 69)] or jugular (36 vs 31%)], and type of catheters (single-lumen 18 vs 18%; double-lumen 82 vs 82%), and mean (median) duration of catheterisation [12.0+/-11.7 (9) vs 10.5+/-8.8 (8) days in the NCC and ACC groups, respectively]. Significant colonisation of the catheter occurred in 23 (13.1%) and 7 (3.7%) patients, respectively, in the NCC and ACC groups (11 vs 3.6 per 1000 catheter-days; p=0.01); CVC-related infection (bloodstream infection) occurred in 10 (5) and 4 (3) patients in the NCC and CC groups, respectively (5.2 vs 2 per 1000 catheter days; p=0.10). CONCLUSIONS: In the context of a low baseline infection rate, ACC were associated with a significant reduction of catheter colonisation and a trend to reduction of infection episodes, but not of bloodstream infection.

The clinical evaluation committee in a large multicenter phase 3 trial of drotrecogin alfa (activated) in patients with severe sepsis (PROWESS): role, methodology, and results.

OBJECTIVE: In the multinational PROWESS trial, drotrecogin alfa (activated) significantly reduced mortality rate in patients with severe sepsis compared with placebo. The use of large multiple-center trials can potentially complicate interpretation of results in severe sepsis populations because of variability in medical attitudes and practices and the frequency of confounding events such as protocol violations. The objective of this study was to perform a blinded, critical, integrated review of data from the 1,690 severe sepsis patients from 164 medical centers enrolled in the PROWESS trial using a Clinical Evaluation Committee. DESIGN: Blinded, critical, integrated review of data. SETTING: Participating sites. PATIENTS: The 1,690 severe sepsis patients from 164 medical centers enrolled in the PROWESS trial. INTERVENTIONS: We performed analyses of the optimal cohort, defined as patients who had full compliance with the protocol, had evidence of an infection, and received adequate anti-infective therapy. We also performed other analyses, including significant underlying disorders, life support measures, and causes of death. MEASUREMENTS AND MAIN RESULTS: The optimal cohort of 81.4% of the intention-to-treat population [drotrecogin alfa (activated), n = 695; placebo, n = 680] had similar baseline severity of illness between the two groups, a similar pharmacodynamic effect, and a relative risk of death estimate consistent with that observed in the overall PROWESS trial (0.83, 95% confidence interval 0.69-0.99 vs. 0.806, 95% confidence interval 0.69-0.94). A beneficial effect of drotrecogin alfa (activated) similarly was observed in patients with significant underlying disorders (0.73, 95% confidence interval 0.57-0.93) who were more severely ill and had a higher percentage of patients forgoing life-sustaining therapy. In contrast with the original investigator determinations, a benefit associated with drotrecogin alfa (activated) treatment in urinary tract infection adjudicated by the Clinical Evaluation Committee was observed. CONCLUSIONS: The survival benefit associated with drotrecogin alfa (activated) use was consistent with the results of the overall trial regardless of whether patients met criteria of the optimal cohort or had a significant underlying disorder.

Selecting patients with severe sepsis for drotrecogin alfa (activated) therapy.

Selecting patients for drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN) therapy outside of a clinical trial setting requires knowledge of the rationale that led the Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) investigators to select the various entry criteria for the trial. Enrollment criteria for the study included a known or suspected infection, presence of at least 3 systemic inflammatory response syndrome (SIRS) criteria, and dysfunction of > or =1 organ or system. The infection criteria used in PROWESS were designed to be straightforward and were based on common clinical and radiological data. Although previous definitions of sepsis required only 2 SIRS criteria, the PROWESS trial investigators required the presence of > or =3 SIRS criteria to improve the sensitivity and specificity of these criteria for the diagnosis of sepsis. Acute organ dysfunction, the diagnostic criterion for severe sepsis, was used to define the study population because it identifies patients at significant risk of death. Characteristics of drotrecogin alfa (activated)-treated patients, including infection, modified SIRS criteria, and organ dysfunction, were similar to those of the placebo group and the general sepsis population. Proper clinical judgment and use of the these inclusion criteria as a guide will help clinicians select and treat sepsis patients with drotrecogin alfa (activated).