Suppression of microbial burden to reduce pneumonia in critical illness: the SMURF feasibility pilot study

Nasal antimicrobial photodynamic therapy (aPDT) is a non-antibiotic decolonization strategy with potential to reduce ICU-acquired infections without contributing to antimicrobial resistance. We conducted a feasibility pilot to evaluate implementation of intranasal aPDT in critically ill adults and to generate preliminary estimates of microbiologic and clinical outcomes to inform a future definitive trial. Prospective, single-center, non-randomized feasibility pilot study with sequential control and intervention phases. Adult mixed medical–surgical intensive care units at a tertiary academic hospital. Adults ≥ 19 years with an expected ICU stay > 48 h. During the intervention phase, patients received intranasal aPDT every 48 h until ICU discharge. Control-phase patients received standard ICU care without nasal decolonization. Nasal swabs were obtained at ICU admission and every four days. Recruitment rate, protocol adherence, safety, data completeness, and ability to adjudicate pneumonia events using blinded, rule-based criteria aligned with CDC/NHSN definitions. A total of 227 patients were analyzed (126 control, 101 intervention). Recruitment targets were met. Adherence to scheduled nasal swab collection was 97.7%. During the intervention phase, 57.8% of scheduled aPDT treatments were delivered in full and 12.0% partially delivered. No intervention-related serious adverse events were observed. Pneumonia adjudication was completed with high inter-system concordance and minimal missing data, supporting adequacy of data capture tools. Exploratory analyses demonstrated significantly lower early cumulative nasal pathogen burden in the intervention group (p < 0.01). The incidence of adjudicated VAP/HAP was 9.0 per 1,000 ICU patient-days during the intervention phase compared with 14.9 per 1,000 ICU patient-days during the control phase (incidence rate ratio 0.61, 95% CI 0.31–1.17, a difference that was not statistically significant). A hierarchical composite endpoint incorporating pneumonia, microbiologic clearance, and cumulative pathogen burden yielded a win ratio of 1.29 (95% CI 0.74–2.31) favoring treatment. Implementation of nasal aPDT in the ICU was feasible and safe, with high sampling adherence and successful blinded adjudication. Exploratory signals of reduced pathogen burden and lower though not statistically significant, pneumonia incidence provide preliminary support for progression to a multicenter randomized trial powered for clinical endpoints. NCT06867458 clinicaltrials.gov, Registration date March 6, 2025.