Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies.

BACKGROUND: Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention. METHODS: We identified relevant studies through systematic review. We analysed individual patient data in a one-stage meta-analytical approach (in which we defined attributable mortality as the ratio between the relative risk reductions [RRR] of mortality and ventilator-associated pneumonia) and in competing risk analyses. Predefined subgroups included surgical, trauma, and medical patients, and patients with different categories of severity of illness scores. FINDINGS: Individual patient data were available for 6284 patients from 24 trials. The overall attributable mortality was 13%, with higher mortality rates in surgical patients and patients with mid-range severity scores at admission (ie, acute physiology and chronic health evaluation score [APACHE] 20-29 and simplified acute physiology score [SAPS 2] 35-58). Attributable mortality was close to zero in trauma, medical patients, and patients with low or high severity of illness scores. Competing risk analyses could be done for 5162 patients from 19 studies, and the overall daily hazard for intensive care unit (ICU) mortality after ventilator-associated pneumonia was 1·13 (95% CI 0·98-1·31). The overall daily risk of discharge after ventilator-associated pneumonia was 0·74 (0·68-0·80), leading to an overall cumulative risk for dying in the ICU of 2·20 (1·91-2·54). Highest cumulative risks for dying from ventilator-associated pneumonia were noted for surgical patients (2·97, 95% CI 2·24-3·94) and patients with mid-range severity scores at admission (ie, cumulative risks of 2·49 [1·81-3·44] for patients with APACHE scores of 20-29 and 2·72 [1·95-3·78] for those with SAPS 2 scores of 35-58). INTERPRETATION: The overall attributable mortality of ventilator-associated pneumonia is 13%, with higher rates for surgical patients and patients with a mid-range severity score at admission. Attributable mortality is mainly caused by prolonged exposure to the risk of dying due to increased length of ICU stay. FUNDING: None.

Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies.

OBJECTIVE: To assess the attributable mortality of ventilator-associated pneumonia using results from randomized controlled trials on ventilator-associated pneumonia prevention. DATA SOURCES: A systematic search was performed in PubMed, Embase, Web of Science, and Cochrane Library from their inception until July 2010. In addition, a reference and related article search was performed. STUDY SELECTION: Randomized ventilator-associated pneumonia prevention studies in which all patients were mechanically ventilated and from which ventilator-associated pneumonia and mortality rates of intervention and control group could be extracted were included. DATA EXTRACTION/SYNTHESIS: Fifty-three papers were identified describing 58 comparisons. Statistical significant reductions in ventilator-associated pneumonia incidences were reported in 20 of the 58 comparisons, whereas none of these trials reported a significant reduction of mortality. Pooled estimates of the relative risk reductions of both ventilator-associated pneumonia and mortality were calculated and the attributable mortality was estimated as the ratio between the relative risk reductions of mortality and ventilator-associated pneumonia. Effects of study quality, diagnostic methods used, and effectiveness of preventing ventilator-associated pneumonia on the mortality rate of ventilator-associated pneumonia were assessed in subgroup analyses. The overall attributable mortality of ventilator-associated pneumonia was estimated as 9%. In subgroup analyses, the attributable mortality varied between 3% and 17%. CONCLUSION: Based on the results of 58 randomized studies on ventilator-associated pneumonia prevention, the attributable mortality rate of ventilator-associated pneumonia was estimated to be 9% and ranged between 3% and 17% in subgroup analyses. Together with the results of other recent studies, there is cumulative evidence that the attributable mortality resulting from ventilator-associated pneumonia is approximately 10%.

Ventilator-associated pneumonia and mortality: a systematic review of observational studies.

OBJECTIVE: To determine the attributable mortality of ventilator-associated pneumonia in a systematic review and meta-analysis of observational studies. Ventilator-associated pneumonia is generally believed to increase the mortality of patients. This notion is predominantly based on the results of observational studies. DATA SOURCE: We performed a systematic search strategy using PubMed, Web of Science, and Embase from their inception through February 2007. In addition, a reference and related article search was performed. STUDY SELECTION: Studies were included if they reported mortality rates of patients with and without ventilator-associated pneumonia. DATA EXTRACTION AND SYNTHESIS: Fifty-two studies with a total of 17,347 patients met the inclusion criteria. Pooling of all studies resulted in relative risk of 1.27 (95% Confidence Interval = 1.15-1.39), but heterogeneity was considerable (I2 statistic = 69%). The origin of heterogeneity could not be explained by differences in study design, study quality, and diagnostic approach. However, heterogeneity was limited for studies investigating only trauma patients (I2 = 1.3%) or patients with acute respiratory distress syndrome (I2 = 0%), with estimated relative risk of 1.09 (95% Confidence Interval = 0.87-1.37) among trauma patients and 0.86 (95% Confidence Interval = 0.72-1.04) among patients with acute respiratory distress syndrome. CONCLUSIONS: There is no evidence of attributable mortality due to ventilator-associated pneumonia in patients with trauma or acute respiratory distress syndrome. However, in other nonspecified patient groups, there is evidence for attributable mortality due to ventilator-associated pneumonia, but this could not be quantified due to heterogeneity in study results. More detailed studies, allowing subgroup analyses, are needed to determine the attributable mortality of ventilator-associated pneumonia in these patient populations.

Effects of systemic antibiotic therapy on bacterial persistence in the respiratory tract of mechanically ventilated patients.

OBJECTIVE: Bacterial respiratory tract colonization predisposes critically ill patients to intensive care unit (ICU)-acquired infections. It is unclear to what extent systemic antibiotics affect colonization persistence. Persistence of respiratory tract colonization, and the effects of systemic antibiotics hereon, were determined in a cohort of ICU patients. DESIGN: Clinical and microbiological data were collected from 715 admitted mechanically ventilated ICU patients with bacterial growth documented in respiratory tract samples. First day of colonization, persistence of colonization and antibiotic effects hereon were analyzed for six groups of pathogens: Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae, Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae. Systemic antibiotics were grouped into 'effective' and 'ineffective' antibiotics, based on in-vitro susceptibility data for the relevant bacteria. The effects of antibiotics were quantified as relative risk (RR) of bacterial persistence in the absence of effective antibiotics. MEASUREMENTS AND RESULTS: Persistence of colonization differed significantly between pathogens, ranging from 4 days (median) for H. influenzae and Strep. pneumoniae to 8 days for P. aeruginosa. Systemic antibiotics were administered on 7,102 (61%) of patient days. Antibiotic use was associated with non-persistence for all pathogens, except Acinetobacter species and P. aeruginosa. RR for non-persistence (as compared to ineffective or no antibiotics) ranged from 3.1 (95% CI 1.4-6.6) for H. influenzae to 0.5 (0.3-1.0) for Acinetobacter species. CONCLUSIONS: In mechanically ventilated patients, persistence dynamics of bacterial respiratory tract colonization, and the effects of (in-vitro) effective antibiotics hereon, are pathogen-specific.