Candida and the Gram-positive trio: testing the vibe in the ICU patient microbiome using structural equation modelling of literature derived data

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. 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.

Automated summary

It remains unclear whether Candida enhances the invasive potential of Gram-positive bacteria in ICU patients. This study used GSEM modeling to test the interactions between Candida and Staphylococcus aureus, coagulase negative Staphylococci (CNS), and Enterococci. The findings suggest that these interactions may occur in the human microbiome, facilitating bacterial invasion and infection.