Research from JAMA — International Study of the Prevalence and Outcomes of Infection in Intensive Care Units

Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome. Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f T_>MIC) and 100% (100% f T_>MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome. Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48–73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14–24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f T_>MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50% f T_>MIC and 100% f T_>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status. Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.

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.

To determine whether continuous subglottic aspiration prevents nosocomial pneumonia in mechanically ventilated patients. A randomized, controlled, blinded study. Medical-surgical intensive care unit. 190 patients who were admitted to the intensive care unit during a 33-month period and whose condition suggested the need for prolonged intubation (> 3 days). 76 patients were randomly allocated to receive continuous aspiration of subglottic secretions, and 77 control patients were allocated to receive usual care. The numbers of cases of ventilator-associated pneumonia, ventilated days, days in intensive care unit, and deaths were recorded. The amount of subglottic secretions aspirated daily and surveillance cultures in the subglottic secretions were also obtained periodically. Etiologic diagnosis was based on the quantitative culture of secretions obtained by protected specimen brush or bronchoalveolar lavage. The incidence rate of ventilator-associated pneumonia was 19.9 episodes/1000 ventilator days in the patients receiving continuous aspiration of subglottic secretions and 39.6 episodes/1000 ventilator days in the control patients (relative risk, 1.98; 95% CI, 1.03 to 3.82). This difference was due to a significant (P < 0.03) reduction in the number of gram-positive cocci and Haemophilus influenzae organisms in the patients receiving continuous aspiration. However, no differences were observed in the number of Pseudomonas aeruginosa or Enterobacteriaceae organisms. Episodes of ventilator-associated pneumonia occurred later in patients receiving continuous aspiration (12.0 +/- 7.1 days) than in the control patients (5.9 +/- 2.1 days) (P = 0.003). The same microorganisms isolated from protected specimen brush or bronchoalveolar lavage cultures in patients with ventilator-associated pneumonia were previously isolated from cultures of subglottic secretions in 85% of cases. No significant differences in outcome were found. The incidence of nosocomial pneumonia in mechanically ventilated patients can be significantly reduced by using a simple method that decreases the chronic microaspirations through the cuff of endotracheal tubes.