Attributable Mortality of Ventilator-associated Pneumonia Replicating Findings, Revisiting Methods

Rationale: Estimating the impact of ventilator-associated pneumonia (VAP) from routinely collected intensive care unit (ICU) data is methodologically challenging. Objectives: We aim to replicate earlier findings of limited VAP-attributable ICU mortality in an independent cohort. By refining statistical analyses, we gradually tackle different sources of bias. Methods: Records of 2,720 adult patients admitted to Ghent University Hospital ICUs (2013-2017) and receiving mechanical ventilation within 48 hours after admission were extracted from linked Intensive Care Information System and Computerbased Surveillance and Alerting of Nosocomial Infections, Antimicrobial Resistance, and Antibiotic Consumption in the ICU databases. The VAP-attributable fraction of ICU mortality was estimated using a competing risk analysis that is restricted to VAP-free patients (approach 1), accounts for VAP onset by treating it as either a competing (approach 2) or censoring event approach 3), or additionally adjusts for time-dependent confounding via inverse probability weighting (approach 4). Results: A total of 210 patients (7.7%) acquired VAP. Based on benchmark approach 4, we estimated that (compared with current preventive measures) hypothetical eradication of VAP would lead to a relative ICU mortality reduction of 1.7% (95% confidence interval, 21.3 to 4.6) by Day 10 and of 3.6% (95% confidence interval, 0.7 to 6.5) by Day 60. Approaches 1-3 produced estimates ranging from 20.7% to 2.5% by Day 10 and from 5.2% to 5.5% by Day 60. Conclusions: In line with previous studies using appropriate methodology, we found limited VAP-attributable ICU mortality given current state-of-the-art VAP prevention measures. Our study illustrates that inappropriate accounting of the time dependency of exposure and confounding of its effects may misleadingly suggest protective effects of early-onset VAP and systematically overestimate attributable mortality.