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ObjectivesTo evaluate whether the performance of the modified Clinical Pulmonary Infection Score (CPIS) for diagnosis of ventilator-associated pneumonia (VAP) could be improved by incorporating procalcitonin (PCT), lactate and a standardised lung ultrasound score (LUS).DesignProspective observational study.SettingInternal medicine and respiratory intensive care units (ICUs) of a tertiary care centre in India over 18 months.Participants97 adult patients receiving invasive mechanical ventilation for 48 hours or more with suspected VAP.Primary and secondary outcome measuresThe primary outcome was the diagnostic accuracy (area under the receiver operating characteristic curve (AUC)) of the integrated score compared with a reference standard of quantitative bronchoalveolar lavage culture (>104 CFU/mL). Secondary outcomes included ICU length of stay and 14-day mortality.ResultsOf the 97 patients, 70 (72.2%) were culture positive. The modified CPIS alone demonstrated limited diagnostic utility (AUC 0.686). In contrast, the novel 4-point Lactate-Lung Ultrasound-Procalcitonin-Clinical Pulmonary Infection Score (LPCPIS) score (integrating CPIS >5, lactate >2.15 mmol/L, PCT >1.3 ng/mL and LUS >14) achieved excellent discriminatory ability (AUC 0.919, 95% CI 0.844 to 0.976). At a cut-off of ≥2, the score yielded 95.7% sensitivity and 77.8% specificity. Crucially, a 4-point LPCPIS bedside score of ≤1 was associated with a highly diminished probability of VAP, yielding a negative predictive value of 100% in this cohort. In comparison, a score ≥3 strongly indicated a high likelihood of VAP, with a positive predictive value of 96.5% and specificity of 92.6%, pending definitive microbiological confirmation.ConclusionsThe novel 4-point LPCPIS bedside score demonstrates significant diagnostic superiority over the traditional modified CPIS (AUC 0.919 vs 0.686). By integrating bedside lung ultrasound with biomarkers, this simplified pragmatic tool provides impressive discriminatory power, allowing clinicians in resource-limited settings to reliably assess probability of VAP and guide early antimicrobial decision-making while awaiting definitive microbiological cultures.