Structural equation modeling the "control of gut overgrowth" in the prevention of ICU-acquired Gram-negative infection

Abstract

Background: Conceptually, the "control of gut overgrowth" (COGO) is key in mediating prevention against infection with Gram-negative bacilli by topical antibiotic prophylaxis, a common constituent of selective digestive decontamination (SDD) regimens. However, the relative importance of the other SDD components, enteral and protocolized parenteral antibiotic prophylaxis, versus other methods of infection prevention and versus other contextual exposures cannot be resolved within individual studies. Methods: Seven candidate generalized structural equation models founded on COGO concepts were confronted with Pseudomonas and Acinetobacter bacteremia as well as ventilator-associated pneumonia data derived from > 200 infection prevention studies. The following group-level exposures were included in the models: use and mode of antibiotic prophylaxis, anti-septic and non-decontamination methods of infection prevention; proportion receiving mechanical ventilation; trauma ICU; mean length of ICU stay; and concurrency versus non-concurrency of topical antibiotic prophylaxis study control groups. Results: In modeling Pseudomonas and Acinetobacter gut overgrowth as latent variables, anti-septic interventions had the strongest negative effect against Pseudomonas gut overgrowth but no intervention was significantly negative against Acinetobacter gut overgrowth. Strikingly, protocolized parenteral antibiotic prophylaxis and concurrency each have positive effects in the model, enteral antibiotic prophylaxis is neutral, and Acinetobacter bacteremia incidences are high within topical antibiotic prophylaxis studies, moreso with protocolized parenteral antibiotic prophylaxis exposure. Paradoxically, topical antibiotic prophylaxis (moreso with protocolized parenteral antibiotic prophylaxis) appears to provide the strongest summary prevention effects against overall bacteremia and overall VAP. Conclusions: Structural equation modeling of published Gram-negative bacillus infection data enables a test of the COGO concept. Paradoxically, Acinetobacter and Pseudomonas bacteremia incidences are unusually high among studies of topical antibiotic prophylaxis.