BACKGROUND: Ventilator-associated pneumonia (VAP) rates are higher in low- and middle-income countries (LMICs) than in high-income countries (HICs). RESEARCH QUESTION: Could differences in ventilator bundle adherence, ventilation practices, and critical care staffing be driving variations in VAP risk between LMICs and HICs? STUDY DESIGN AND METHODS: This secondary analysis of the multicenter, international Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN) study included mechanically ventilated patients at risk for VAP from 11 LMICs and 5 HICs. We included oral care, head-of-bed elevation, spontaneous breathing assessments, and sedation breaks in the ventilator bundle. Staffing was assessed by the number of physicians and nurses per bed. Multivariable analyses were adjusted for severity, baseline characteristics, and checklist implementation. The primary outcome was VAP development. RESULTS: Among 2,253 patients, 1,755 were from LMICs and 498 from HICs. Compared with HICs, patients from LMICs were younger, had lower comorbidity burden, and were less severely ill. Lower country income level was independently associated with VAP development (adjusted OR [aOR], 2.11
95% CI, 1.37-3.24). Ventilator bundle adherence was not significantly associated with VAP. Increased total duration of ventilation was associated with an increased risk of VAP (aOR, 1.04
95% CI, 1.03-1.05), whereas higher nursing (aOR, 0.88
95% CI, 0.79-0.98) and physician staffing ratios (aOR, 0.69
95% CI, 0.50-0.87) were associated with lower VAP rates. INTERPRETATION: Patients in LMICs have a 2-fold higher risk of VAP, independent of bundle adherence. Prolonged mechanical ventilation was an independent predictor of VAP, whereas higher staffing ratios were associated with decreased risk for VAP development. Unmeasured factors (eg, infrastructure, infection control practices) may explain the higher VAP rates in LMICs.