Structural equation modelling the relationship between anti-fungal prophylaxis and Pseudomonas bacteremia in ICU patients

James C Hurley

doi:10.1186/s40635-022-00429-8

Abstract

PurposeAnimal 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.MethodsThree 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.ResultsIntroducing 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.ConclusionGSEM 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.

Highlights

Animal models implicate candida colonization facilitating invasive bacterial infections [1, 2]
Take home message Structural equation modelling of the Intensive care unit (ICU) infection prevention data from 279 studies supports the postulated influence of prophylaxis using anti-fungal agents in preventing Pseudomonas bacteremia
The model implicates that anti-fungal agents have greater impact in preventing bacteremia versus antibiotics, which have no impact

Summary

Introduction

Animal models implicate candida colonization facilitating invasive bacterial infections [1, 2]. Clinical investigation of this postulated interaction would manipulate candida colonization among patients and measure the resulting Pseudomonas bacteremia incidence [6,7,8]. Such an investigation would be logistically complex. Additional challenges to such an approach are that the blood stream infection (BSI) endpoints are generally uncommon or rare, the key body site location of any postulated interaction, whether the oropharynx or elsewhere, remains unclear and measuring colonization, whether bacterial or candida, is problematic. Whether changes in the metabolic activity, hyphal growth or the mere viable count of Candida colonisation drives any interaction towards a propensity for invasive infection remains moot

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