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Structural equation modelling the relationship between anti-fungal prophylaxis and Pseudomonas bacteremia in ICU
1Melbourne Medical School, University of Melbourne, Melbourne, Australia. jamesh@bhs.org.au.
Purpose:
Animal models implicate candida colonization facilitating invasive bacterial infections. The clinical relevance of this microbial interaction remains undefined and difficult to study directly. Observations from studies of anti-septic, antibiotic, anti-fungal, and non-decontamination-based interventions to prevent ICU acquired infection collectively serve as a natural experiment.
Methods:
Three candidate generalized structural equation models (GSEM), with Candida and Pseudomonas colonization as latent variables, were confronted with blood culture and respiratory tract isolate data derived from 464 groups from 279 studies including studies of combined antibiotic and antifungal exposures within selective digestive decontamination (SDD) interventions.
Results:
Introducing an interaction term between Candida colonization and Pseudomonas colonization substantially improved GSEM model fit. Model derived coefficients for singular exposure to anti-septic agents (- 1.23; - 2.1 to - 0.32), amphotericin (- 1.78; - 2.79 to - 0.78) and topical antibiotic prophylaxis (TAP; + 1.02; + 0.11 to + 1.93) versus Candida colonization were similar in magnitude but contrary in direction. By contrast, the model-derived coefficients for singular exposure to TAP, as with anti-septic agents, versus Pseudomonas colonization were weaker or non-significant. Singular exposure to amphotericin would be predicted to more than halve candidemia and Pseudomonas bacteremia incidences versus literature benchmarks for absolute differences of approximately one percentage point or less.
Conclusion:
GSEM modelling of published data supports the postulated interaction between Candida and Pseudomonas colonization towards promoting bacteremia among ICU patients. This would be difficult to detect without GSEM modelling. The model indicates that anti-fungal agents have greater impact in preventing Pseudomonas bacteremia than TAP, which has no impact.
Insights
Candida and Pseudomonas colonization interact to increase bacteremia risk in ICUs. Antifungal agents effectively reduce Pseudomonas bacteremia, unlike topical antibiotic prophylaxis (TAP).
Area of Science:
- Medical Microbiology
- Infectious Diseases
- Intensive Care Medicine
Background:
- Animal models suggest Candida colonization facilitates invasive bacterial infections.
- The clinical significance of this interaction in intensive care unit (ICU) patients is unclear.
- Interventions to prevent ICU-acquired infections offer a natural experiment to study microbial interactions.
Purpose of the Study:
- To investigate the clinical relevance of Candida colonization in facilitating invasive bacterial infections, specifically bacteremia, in ICU patients.
- To explore the interaction between Candida and Pseudomonas colonization using generalized structural equation modeling (GSEM).
Main Methods:
- Utilized data from 464 patient groups across 279 studies, including those with selective digestive decontamination (SDD) interventions.
- Developed three candidate generalized structural equation models (GSEM) with Candida and Pseudomonas colonization as latent variables.
- Analyzed blood culture and respiratory tract isolate data to assess the impact of antiseptic, antibiotic, and antifungal exposures.
Main Results:
- A GSEM incorporating an interaction term between Candida and Pseudomonas colonization significantly improved model fit.
- Antifungal agents (amphotericin) and antiseptics were associated with reduced Candida colonization, while topical antibiotic prophylaxis (TAP) showed a complex association.
- Antifungal exposure was predicted to significantly reduce both candidemia and Pseudomonas bacteremia, whereas TAP showed no significant impact on Pseudomonas bacteremia.
Conclusions:
- GSEM modeling of published data supports a significant interaction between Candida and Pseudomonas colonization in promoting bacteremia in ICU patients.
- Antifungal agents demonstrate a greater impact on preventing Pseudomonas bacteremia compared to TAP.
- GSEM is crucial for detecting such complex microbial interactions that might otherwise be missed.
