ICU-acquired pneumonia with or without etiologic diagnosis: a comparison of outcomes.

OBJECTIVES: The impact of ICU-acquired pneumonia without etiologic diagnosis on patients' outcomes is largely unknown. We compared the clinical characteristics, inflammatory response, and outcomes between patients with and without microbiologically confirmed ICU-acquired pneumonia. DESIGN: Prospective observational study. SETTING: ICUs of a university teaching hospital. PATIENTS: We prospectively collected 270 consecutive patients with ICU-acquired pneumonia. Patients were clustered according to positive or negative microbiologic results. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared the characteristics and outcomes between both groups. Negative microbiology was found in 82 patients (30%). Both groups had similar baseline severity scores. Patients with negative microbiology presented more frequently chronic renal failure (15 [18%] vs 11 [6%]; p=0.003), chronic heart disorders (35 [43%] vs 55 [29%]; p=0.044), less frequently previous intubation (44 [54%] vs 135 [72%]; p=0.006), more severe hypoxemia (PaO2/FIO2: 165±73 mm Hg vs 199±79 mm Hg; p=0.001), and shorter ICU stay before the onset of pneumonia (5±5 days vs 7±9 days; p=0.001) compared with patients with positive microbiology. The systemic inflammatory response was similar between both groups. Negative microbiology resulted in less changes of empiric treatment (33 [40%] vs 112 [60%]; p=0.005) and shorter total duration of antimicrobials (13±6 days vs 17±12 days; p=0.006) than positive microbiology. Following adjustment for potential confounders, patients with positive microbiology had higher hospital mortality (adjusted odds ratio 2.96, 95% confidence interval 1.24-7.04, p=0.014) and lower 90-day survival (adjusted hazard ratio 0.50, 95% confidence interval 0.27-0.94, p=0.031), with a nonsignificant lower 28-day survival. CONCLUSIONS: Although the possible influence of previous intubation in mortality of both groups is not completely discarded, negative microbiologic findings in clinically suspected ICU-acquired pneumonia are associated with less frequent previous intubation, shorter duration of antimicrobial treatment, and better survival. Future studies should corroborate the presence of pneumonia in patients with suspected ICU-acquired pneumonia and negative microbiology.

Validation of predictors of adverse outcomes in hospital-acquired pneumonia in the ICU.

OBJECTIVE: To validate a set of predictors of adverse outcomes in patients with ICU-acquired pneumonia in relation to clinically relevant assessment at 28 days. DESIGN: Prospective, observational study. SETTING: Six medical and surgical ICUs of a university hospital. PATIENTS: Three hundred thirty-five patients with ICU-acquired pneumonia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Development of predictors of adverse outcomes was defined when at least one of the following criteria was present at an evaluation made 72-96 hours after starting treatment: no improvement of PaO2/FIO2, need for intubation due to pneumonia, persistence of fever or hypothermia with purulent respiratory secretions, greater than or equal to 50% increase in radiographic infiltrates, or occurrence of septic shock or multiple organ dysfunction syndrome. We also assessed the inflammatory response by different serum biomarkers. The presence of predictors of adverse outcomes was related to mortality and ventilator-free days at day 28. Sequential Organ Failure Assessment score was evaluated and related to mortality at day 28.One hundred eighty-four (55%) patients had at least one predictor of adverse outcomes. The 28-day mortality was higher for those with versus those without predictors of adverse outcomes (45% vs 19%, p<0.001), and ventilator-free days were lower (median [interquartile range], 0 [0-17] vs 22 [0-28]) for patients with versus patients without predictors of adverse outcomes (p<0.001). The lack of improvement of PaO2/FIO2 and lack of improvement in Sequential Organ Failure Assessment score from day 1 to day 5 were independently associated with 28-day mortality and fewer ventilator-free days. The marginal structural analysis showed an odds ratio of death 2.042 (95% CI, 1.01-4.13; p=0.047) in patients with predictors of adverse outcomes. Patients with predictors of adverse outcomes had higher serum inflammatory response accordingly to biomarkers evaluated. CONCLUSIONS: The presence of any predictors of adverse outcomes was associated with mortality and decreased ventilator-free days at day 28. The lack of improvement in the PaO2/FIO2 and Sequential Organ Failure Assessment score was independently associated with mortality in the multivariate analysis.

Linezolid limits burden of methicillin-resistant Staphylococcus aureus in biofilm of tracheal tubes.

OBJECTIVE: To evaluate the effects of systemic treatment with linezolid compared with vancomycin on biofilm formation in mechanically ventilated pigs with severe methicillin-resistant Staphylococcus aureus-induced pneumonia. DESIGN: Prospective randomized animal study. SETTING: Departments of Pneumology, Microbiology, and Pharmacy of the Hospital Clínic, Barcelona, and Scientific and Technological Services of the University of Barcelona. SUBJECTS: We prospectively analyzed 70 endotracheal tube samples. Endotracheal tubes were obtained from pigs either untreated (controls, n=20), or treated with vancomycin (n=32) or linezolid (n=18). INTERVENTIONS: The endotracheal tubes were obtained from a previous randomized study in tracheally intubated pigs with methicillin-resistant Staphylococcus aureus severe pneumonia, and mechanically ventilated for 69±16 hrs. MEASUREMENTS AND MAIN RESULTS: Distal and medial hemisections of the endotracheal tube were assessed to quantify methicillin-resistant Staphylococcus aureus burden, antibiotic biofilm concentration by high-performance liquid chromatography or bioassay, and biofilm thickness through scanning electron microscopy. We found a trend toward a significant variation in biofilm methicillin-resistant Staphylococcus aureus burden (log colony-forming unit/mL) among groups (p=.057), and the lowest bacterial burden was found in endotracheal tubes treated with linezolid (1.98±1.68) in comparison with untreated endotracheal tubes (3.72±2.20, p=.045) or those treated with vancomycin (2.97±2.43, p=.286). Biofilm linezolid concentration was 19-fold above the linezolid minimum inhibitory concentration, whereas biofilm vancomycin concentration (1.60±0.91 µg/mL) was consistently below or close to the vancomycin minimum inhibitory concentration. Biofilm was thicker in the vancomycin group (p=.077). CONCLUSIONS: Systemic treatment with linezolid limits endotracheal tube biofilm development and methicillin-resistant Staphylococcus aureus burden. The potential clinical usefulness of linezolid in decreasing the risk of biofilm-related respiratory infections during prolonged tracheal intubation requires further investigation.

Nosocomial pneumonia in the intensive care unit acquired by mechanically ventilated versus nonventilated patients.

RATIONALE: Most current information on hospital-acquired pneumonia (HAP) is extrapolated from patients with ventilator-associated pneumonia (VAP). No studies have evaluated HAP in the intensive care unit (ICU) in nonventilated patients. OBJECTIVES: To compare pneumonia acquired in the ICU by mechanically ventilated versus nonventilated patients. METHODS: We prospectively collected 315 episodes of ICU-acquired pneumonia. We compared clinical and microbiologic characteristics of patients with VAP (n = 164; 52%) and nonventilator ICU-acquired pneumonia (NV-ICUAP; n = 151; 48%). Among NV-ICUAP patients, 79 (52%) needed subsequent intubation. MEASUREMENTS AND MAIN RESULTS: Compared with NV-ICUAP, patients with VAP were more severe (APACHE-II 17 ± 6 vs. 15 ± 5; P < 0.001) and pneumonia occurred later in the ICU (8 ± 8 vs. 5 ± 6 d; P < 0.001). Etiologic diagnosis (117, 71% vs. 64, 42%; P < 0.001), nonfermenting (28% vs. 15%; P = 0.009) and enteric gram-negative bacilli (26% vs. 13%; P = 0.006), and methicillin-sensitive Staphylococcus aureus (14% vs. 6%; P = 0.031) were more frequent in VAP, likely caused by more patients with lower respiratory tract samples cultured (100% vs. 84%; P < 0.001). However, in patients with defined etiology only, the proportion of pathogens was similar between groups, except for a higher proportion of Streptococcus pneumoniae in NV-ICUAP (P = 0.045). The hospital mortality also was similar. CONCLUSIONS: Despite a lower proportion of pathogens in NV-ICUAP compared with VAP, the type of isolates and outcomes are similar regardless of whether pneumonia is acquired or not during ventilation, indicating they may depend on patients' underlying severity rather than previous intubation. With the diagnostic techniques currently recommended by guidelines, both types of patients might receive similar empiric antibiotic treatment.