Benoit Misset

Continuous versus Intermittent Infusion of Vancomycin in Severe Staphylococcal Infections: Prospective Multicenter Randomized Study

ABSTRACT A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections. A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%). Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar. CIV patients reached the targeted concentrations faster (36 ± 31 versus 51 ± 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 ± 2.2 versus 11.8 ± 3.9 per treatment, P < 0.0001). The variability between patients in both the area under the serum concentration-time curve (AUC24h) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg2/liter2/h2[P = 0.026] and 414 versus 818 g2[P = 0.057], respectively). The 10-day treatment cost per patient was

Femoral vs Jugular Venous Catheterization and Risk of Nosocomial Events in Adults Requiring Acute Renal Replacement Therapy : A Randomized Controlled Trial

454 ± 137 in the IIV group and was 23% lower in the CIV group (

Outcome, functional autonomy, and quality of life of elderly patients with a long-term intensive care unit stay

321 ± 81: P < 0.0001). In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV.

Circulating interleukin-8 concentrations in patients with multiple organ failure of septic and nonseptic origin.

CONTEXT Based on concerns about the risk of infection, the jugular site is often preferred over the femoral site for short-term dialysis vascular access. OBJECTIVE To determine whether jugular catheterization decreases the risk of nosocomial complications compared with femoral catheterization. DESIGN, SETTING, AND PATIENTS A concealed, randomized, multicenter, evaluator-blinded, parallel-group trial (the Cathedia Study) of 750 patients from a network of 9 tertiary care university medical centers and 3 general hospitals in France conducted between May 2004 and May 2007. The severely ill, bed-bound adults had a body mass index (BMI) of less than 45 and required a first catheter insertion for renal replacement therapy. INTERVENTION Patients were randomized to receive jugular or femoral vein catheterization by operators experienced in placement at both sites. MAIN OUTCOME MEASURES Rates of infectious complications, defined as catheter colonization on removal (primary end point), and catheter-related bloodstream infection. RESULTS Patient and catheter characteristics, including duration of catheterization, were similar in both groups. More hematomas occurred in the jugular group than in the femoral group (13/366 patients [3.6%] vs 4/370 patients [1.1%], respectively; P = .03). The risk of catheter colonization at removal did not differ significantly between the femoral and jugular groups (incidence of 40.8 vs 35.7 per 1000 catheter-days; hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.62-1.16; P = .31). A prespecified subgroup analysis demonstrated significant qualitative heterogeneity by BMI (P for the interaction term < .001). Jugular catheterization significantly increased incidence of catheter colonization vs femoral catheterization (45.4 vs 23.7 per 1000 catheter-days; HR, 2.10; 95% CI, 1.13-3.91; P = .017) in the lowest tercile (BMI <24.2), whereas jugular catheterization significantly decreased this incidence (24.5 vs 50.9 per 1000 catheter-days; HR, 0.40; 95% CI, 0.23-0.69; P < .001) in the highest tercile (BMI >28.4). The rate of catheter-related bloodstream infection was similar in both groups (2.3 vs 1.5 per 1000 catheter-days, respectively; P = .42). CONCLUSION Jugular venous catheterization access does not appear to reduce the risk of infection compared with femoral access, except among adults with a high BMI, and may have a higher risk of hematoma. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00277888.

Guidelines for management of intra-abdominal infections.

ObjectiveTo examine the outcome, functional autonomy, and quality of life of elderly patients (≥70 yrs old) hospitalized for >30 days in an intensive care unit (ICU). DesignProspective cohort study. SettingA ten-bed, medical-surgical ICU in a 460-bed, acute care, tertiary, university hospital. PatientsA consecutive cohort of 75 patients, >70 yrs old, admitted to the ICU from January 1, 1993, to August 1, 1998, for >30 days. InterventionsNone. Measurements and Main ResultsSeverity at admission and of the underlying disease was estimated according to the Simplified Acute Physiologic Score (SAPS II), the Organ Dysfunction and/or Infection (ODIN) score, the McCabe score, and the Knaus classification. Therapeutic intensity was measured through the French Omega scoring system. All patients were mechanically ventilated during their ICU stay. Outcome measurements were made by two cross-sectional studies using telephone interviews on the first week of September 1996 and 1998 with a questionnaire including measures of functional capacity by Katz’s Activities of Daily Living, modified Patrick’s Perceived Quality of Life score, and the Nottingham Health Profile. The survival rate was 67% in the ICU and 47% in the hospital. A total of 30 patients were alive and able to participate in at least one of the cross-sectional studies. Independence in activities of daily living was decreased significantly after the ICU stay, except for feeding. However, most of the 30 patients remained independent (class A of the Activities of Daily Living index) with the possibility of going home. Perceived Quality of Life scores remained good, even if the patients estimated a decrease in their quality of life for health and memory. Return to society appeared promising regarding patient self respect and happiness with life. The estimated cost by survivor was of 55,272 EUR (

Excess Risk of Death from Intensive Care Unit—Acquired Nosocomial Bloodstream Infections: A Reappraisal

60,246 US). ConclusionsThis study suggests that persistent high levels of ICU therapeutic intensity were associated with a reasonable hospital survival in elderly patients experiencing prolonged mechanical ventilatory support. These patients presented a moderate disability that influenced somewhat their perceived quality of life. These results are sufficient to justify prolonged ICU stays for elderly patients.

A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients.

ObjectivesInterleukin (IL)-8, a pro-inflammatory cytokine, is a potent chemoattractant factor and an activator of neutrophils produced by many cell types after stimulation by IL-1, tumor necrosis factor (TNF), or microbial products such as endotoxins. We investigated whether the presence of measurable IL-8 in plasma was associated with the clinical status of severely ill septic or nonseptic patients susceptible to the development of multiple organ failure. DesignCohort study. SettingA collaborative study between an intensive care unit and a research laboratory. SubjectsCirculating IL-8 concentrations were measured in the plasma of 27 patients with sepsis syndrome and in 16 patients with noninfectious shock because these two conditions put patients at risk for the development of multiple organ failure. Sixteen of 27 patients with severe infection and 13 of 16 patients with noninfectious pathologies developed multiple organ failure. Measurements and Main ResultsA specific enzyme-linked immunosorbent assay (ELISA) for IL-8 was set up with a monoclonal and a rabbit polyclonal antihuman IL-8 using a sandwich technique. High concentrations of circulating IL-8 were found in the plasma of patients with sepsis syndrome. Among septic patients, a significant difference was observed between concentrations of IL-8 in survivors (n = 16) and nonsurvivors (n = 11) (81 pL 13 pg/mL vs. 3326 pL 1219 pg/mL, respectively; p = .001). A correlation was noticed between plasma IL-8 and IL-6 concentrations (r2 = .42; p = .001), while no correlation was observed between IL-8 and TNF-aP values, or between IL-8 and IL-1β. Although the mortality rate of nonseptic, multiple organ failure patients was 92%, low plasma concentrations of IL-8 were found (78 pL 34 pg/mL), while high plasma concentrations were measured in septic, multiple organ failure patients (mortality rate 69%) who were sampled at a similar stage. By contrast, increased IL-6 values were observed in both septic and nonseptic, multiple organ failure patients. ConclusionsIn septic patients, high amounts of circulating IL-8 concentrations correlate with fatal outcome, whereas only low plasma concentrations of IL-8 are present in patients with nonseptic, multiple organ failure. This finding suggests that the signals involved in the exacerbation of IL-8 production are different, depending on infectious or noninfectious etiology. (Crit Care Med 1994; 22:673–679)

Colonization With Methicillin-Resistant Staphylococcus aureus in ICU Patients Morbidity, Mortality, and Glycopeptide Use

Intra-abdominal infections are one of the most common gastrointestinal emergencies and a leading cause of septic shock. A consensus conference on the management of community-acquired peritonitis was published in 2000. A new consensus as well as new guidelines for less common situations such as peritonitis in paediatrics and healthcare-associated infections had become necessary. The objectives of these Clinical Practice Guidelines (CPGs) were therefore to define the medical and surgical management of community-acquired intra-abdominal infections, define the specificities of intra-abdominal infections in children and describe the management of healthcare-associated infections. The literature review was divided into six main themes: diagnostic approach, infection source control, microbiological data, paediatric specificities, medical treatment of peritonitis, and management of complications. The GRADE(®) methodology was applied to determine the level of evidence and the strength of recommendations. After summarising the work of the experts and application of the GRADE(®) method, 62 recommendations were formally defined by the organisation committee. Recommendations were then submitted to and amended by a review committee. After 2 rounds of Delphi scoring and various amendments, a strong agreement was obtained for 44 (100%) recommendations. The CPGs for peritonitis are therefore based on a consensus between the various disciplines involved in the management of these patients concerning a number of themes such as: diagnostic strategy and the place of imaging; time to management; the place of microbiological specimens; targets of empirical anti-infective therapy; duration of anti-infective therapy. The CPGs also specified the value and the place of certain practices such as: the place of laparoscopy; the indications for image-guided percutaneous drainage; indications for the treatment of enterococci and fungi. The CPGs also confirmed the futility of certain practices such as: the use of diagnostic biomarkers; systematic relaparotomies; prolonged anti-infective therapy, especially in children.

Impact of an intensive care unit diary on psychological distress in patients and relatives

BACKGROUND Overall rates of bloodstream infection (BSI) are often used as quality indicators in intensive care units (ICUs). We investigated whether ICU-acquired BSI increased mortality (by > or = 10%) after adjustment for severity of infection at ICU admission and during the pre-BSI stay. METHODS We conducted a matched, risk-adjusted (1:n), exposed-unexposed study of patients with stays longer than 72 h in 12 ICUs randomly selected from the Outcomerea database. RESULTS Patients with BSI after the third ICU day (exposed group) were matched on the basis of risk-exposure time and mortality predicted at admission using the Three-Day Recalibrated ICU Outcome (TRIO) score to patients without BSI (unexposed group). Severity was assessed daily using the Logistic Organ Dysfunction (LOD) score. Of 3247 patients with ICU stays of >3 days, 232 experienced BSI by day 30 (incidence, 6.8 cases per 100 admissions); among them, 226 patients were matched to 1023 unexposed patients. Crude hospital mortality was 61.5% among exposed and 36.7% among unexposed patients (P<.0001). Attributable mortality was 24.8%. The only variable associated with both BSI and hospital mortality was the LOD score determined 4 days before onset of BSI (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.03-1.16; P = .0025). The adjusted OR for hospital mortality among exposed patients (OR, 3.20; 95% CI, 2.30-4.43) decreased when the LOD score determined 4 days before onset of BSI was taken into account (OR, 3.02; 95% CI, 2.17-4.22; P<.0001). The estimated risk of death from BSI varied considerably according to the source and resistance of organisms, time to onset, and appropriateness of treatment. CONCLUSIONS When adjusted for risk-exposure time and severity at admission and during the ICU stay, BSI was associated with a 3-fold increase in mortality, but considerable variation occurred across BSI subgroups. Focusing on BSI subgroups may be valuable for assessing quality of care in ICUs.

Perceptions of a 24-hour visiting policy in the intensive care unit.

RATIONALE The clinical relevance of Aspergillus-positive endotracheal aspirates in critically ill patients is difficult to assess. OBJECTIVES We externally validate a clinical algorithm to discriminate Aspergillus colonization from putative invasive pulmonary aspergillosis in this patient group. METHODS We performed a multicenter (n = 30) observational study including critically ill patients with one or more Aspergillus-positive endotracheal aspirate cultures (n = 524). The diagnostic accuracy of this algorithm was evaluated using 115 patients with histopathologic data, considered the gold standard. Subsequently, the diagnostic workout of the algorithm was compared on the total cohort (n = 524), with the categorization based on the diagnostic criteria of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group. MEASUREMENTS AND MAIN RESULTS Among 115 histopathology-controlled patients, 79 had proven aspergillosis. The algorithm judged 86 of 115 cases to have putative aspergillosis. This diagnosis was confirmed in 72 and rejected in 14 patients. The algorithm judged 29 patients to have Aspergillus colonization. This was confirmed in 22 and rejected in 7 patients. The algorithm had a specificity of 61% and a sensitivity of 92%. The positive and negative predictive values were 61 and 92%, respectively. In the total cohort (n = 524), 79 patients had proven invasive pulmonary aspergillosis (15.1%). According to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 32 patients had probable aspergillosis (6.1%) and 413 patients were not classifiable (78.8%). The algorithm judged 199 patients to have putative aspergillosis (38.0%) and 246 to have Aspergillus colonization (46.9%). CONCLUSIONS The algorithm demonstrated favorable operating characteristics to discriminate Aspergillus respiratory tract colonization from invasive pulmonary aspergillosis in critically ill patients.