Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Hurley JC

PROVIDER: S-EPMC8776977 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Whether Candida interacts with Gram-positive bacteria, such as Staphylococcus aureus, coagulase negative Staphylococci (CNS) and Enterococci, to enhance their invasive potential from the microbiome of ICU patients remains unclear. Several effective anti-septic, antibiotic, anti-fungal, and non-decontamination based interventions studied for prevention of ventilator associated pneumonia (VAP) and other ICU acquired infections among patients receiving prolonged mechanical ventilation (MV) are known to variably impact Candida colonization. The collective observations within control and intervention groups from numerous ICU infection prevention studies enables tests of these postulated microbial interactions in the clinical context. Methods Four candidate generalized structural equation models (GSEM), each with Staphylococcus aureus, CNS and Enterococci colonization, defined as latent variables, were confronted with blood culture and respiratory tract isolate data derived from 460 groups of ICU patients receiving prolonged MV from 283 infection prevention studies. Results Introducing interaction terms between Candida colonization and each of S aureus (coefficient + 0.40; 95% confidence interval + 0.24 to + 0.55), CNS (+ 0.68; + 0.34 to + 1.0) and Enterococcal (+ 0.56; + 0.33 to + 0.79) colonization (all as latent variables) improved the fit for each model. The magnitude and significance level of the interaction terms were similar to the positive associations between exposure to topical antibiotic prophylaxis (TAP) on Enterococcal (+ 0.51; + 0.12 to + 0.89) and Candida colonization (+ 0.98; + 0.35 to + 1.61) versus the negative association of TAP with S aureus (− 0.45; − 0.70 to − 0.20) colonization and the negative association of anti-fungal exposure and Candida colonization (− 1.41; − 1.6 to − 0.72). Conclusions GSEM modelling of published ICU infection prevention data enables the postulated interactions between Candida and Gram-positive bacteria to be tested using clinically derived data. The optimal model implies interactions occurring in the human microbiome facilitating bacterial invasion and infection. This interaction might also account for the paradoxically high bacteremia incidences among studies of TAP in ICU patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12982-022-00116-9. Keypoints GSEM modelling of published ICU infection prevention data from > 250 studies enables a test of and provides support to the interaction between Candida and Gram-positive bacteria. The various ICU infection prevention interventions may each broadly impact the patient microbiome. Supplementary Information The online version contains supplementary material available at 10.1186/s12982-022-00116-9.

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