Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment

International audiencePurposeThe optimal treatment duration for ventilator-associated pneumonia is based on one study dealing with late-onset of the condition. Shortening the length of antibiotic treatment remains a major prevention factor for the emergence of multiresistant bacteria.ObjectiveTo demonstrate that 2 different antibiotic treatment durations (8 versus 15 days) are equivalent in terms of clinical cure for early-onset ventilator-associated pneumonia.MethodsRandomized, prospective, open, multicenter trial carried out from 1998 to 2002.MeasurementsThe primary endpoint was the clinical cure rate at day 21. The mortality rate was evaluated on days 21 and 90.Results225 patients were included in 13 centers. 191 (84.9%) patients were cured: 92 out of 109 (84.4%) in the 15 day cohort and 99 out of 116 (85.3%) in the 8 day cohort (difference = 0.9%, odds ratio = 0.929). 95% two-sided confidence intervals for difference and odds ratio were [−8.4% to 10.3%] and [0.448 to 1.928] respectively. Taking into account the limits of equivalence (10% for difference and 2.25 for odds ratio), the objective of demonstrative equivalence between the 2 treatment durations was fulfilled. Although the rate of secondary infection was greater in the 8 day than the 15 day cohort, the number of days of antibiotic treatment remained lower in the 8 day cohort. There was no difference in mortality rate between the 2 groups on days 21 and 90.ConclusionOur results suggest that an 8-day course of antibiotic therapy is safe for early-onset ventilator-associated pneumonia in intubated patients

Predictors of intensive care unit refusal in French intensive care units: a multiple-center study.

OBJECTIVE: To identify factors associated with granting or refusing intensive care unit (ICU) admission, to analyze ICU characteristics and triage decisions, and to describe mortality in admitted and refused patients. DESIGN: Observational, prospective, multiple-center study. SETTING: Four university hospitals and seven primary-care hospitals in France. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age, underlying diseases (McCabe score and Knaus class), dependency, hospital mortality, and ICU characteristics were recorded. The crude ICU refusal rate was 23.8% (137/574), with variations from 7.1% to 63.1%. The reasons for refusal were too well to benefit (76/137, 55.4%), too sick to benefit (51/137, 37.2%), unit too busy (9/137, 6.5%), and refusal by the family (1/137). In logistic regression analyses, two patient-related factors were associated with ICU refusal: dependency (odds ratio [OR], 14.20; 95% confidence interval [CI], 5.27-38.25; p < .0001) and metastatic cancer (OR, 5.82; 95% CI, 2.22-15.28). Other risk factors were organizational, namely, full unit (OR, 3.16; 95% CI, 1.88-5.31), center (OR, 3.81; 95% CI, 2.27-6.39), phone admission (OR, 0.23; 95% CI, 0.14-0.40), and daytime admission (OR, 0.52; 95% CI, 0.32-0.84). The Standardized Mortality Ratio was 1.41 (95% CI, 1.19-1.69) for immediately admitted patients, 1.75 (95% CI, 1.60-1.84) for refused patients, and 1.03 (95% CI, 0.28-1.75) for later-admitted patients. CONCLUSIONS: ICU refusal rates varied greatly across ICUs and were dependent on both patient and organizational factors. Efforts to define ethically optimal ICU admission policies might lead to greater homogeneity in refusal rates, although case-mix variations would be expected to leave an irreducible amount of variation across ICUs

Microbiology of secondary infections.

*<p>CSF,</p>‡<p>pleural fluid,</p>**<p>chest drain,</p>§<p>ESBL (Extended-Spectrum Beta-Lactamase),</p><p>CAZ-S^† (sensitive to ceftazidime),</p><p>CAZ-R^†† (resistant to ceftazidime),</p>‡‡<p>Reduced sensitivity to beta-lactams and high-level aminoglycoside resistance,</p>§§<p>Sensitive to chloramphenicol, cyclins, vancomycin, teicoplanin.</p

Definition of secondary infections requiring the initiation of antibiotic treatment for more than 48 hours.

<p>Definition of secondary infections requiring the initiation of antibiotic treatment for more than 48 hours.</p

Data regarding number of patients included, treated according to protocol and followed up at 21 and 90 days.

<p>Data regarding number of patients included, treated according to protocol and followed up at 21 and 90 days.</p

Treatments authorized in the study.

*<p>Aminoglycosides were administered in a single dose with a loading dose on the first day of treatment. The dose was adapted in the event of renal failure.</p

Indications for antibiotic treatment before bacteriology results.

<p>Indications for antibiotic treatment before bacteriology results.</p

Patients with documented secondary infections.

<p>Abbreviations:</p>*<p>sensitive,</p>†<p>resistant,</p>**<p>Fischer exact test.</p

Admission characteristics of the study patients according to the duration of antibiotic treatment.

<p>Abbreviations:</p>*<p>RTA: road traffic accident;</p>†<p>SAPS: simplified acute physiological score;</p>‡<p>ICU: intensive care unit;</p>§<p>BAL: bronchoalveolar lavage;</p>**<p>3GC: third generation cephalosporin.</p