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

Abstract

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.

Staphylococcus aureus hitchhiking from colonization to bacteremia via Candida within ICU infection prevention studies: a proof of concept modelling

“…2 & 3) and indicate strong contextual effects arising from concurrency which, in any one study, would be inapparent. In the optimal model (model A), these contextual effects are similar in size, but contrary in direction, to the modest direct effect of TAP on Staphylococcus aureus colonization [31][32][33][34][35][36].…”

“…The direct anti-bacterial effect of TAP is more evident within models containing either Pseudomonas or Acinetobacter colonization and infection data than is the case here with the model containing Staphylococcus aureus colonization and infection data. These four modelling studies are based on 328 studies, of which < 200 are common to all three [ 14 , 33 , 35 ].…”

Epidemiological patterns of candidaemia: A comprehensive analysis over a decade

“…Also, prolonged use of antibiotics is another cause of candidaemia which may be the main reason why gram-positive bacteria were detected more than gram-negative bacteria in polymicrobial candidaemia episodes. 26 In mixed fungaemia patients, C. albicans and N. glabrata were found to be the most frequent combination in previous studies. [18][19][20][21][22][23] Previous studies have also found that N. glabrata is more frequently isolated in mixed fungaemia infections than in all other candidiasis.…”

“…Another reason could be that prolonged hospitalisation is a significant risk factor of candidaemia which also results in the growth of known colonisers. Also, prolonged use of antibiotics is another cause of candidaemia which may be the main reason why gram‐positive bacteria were detected more than gram‐negative bacteria in polymicrobial candidaemia episodes 26 …”

Rebound Inverts the Staphylococcus aureus Bacteremia Prevention Effect of Antibiotic Based Decontamination Interventions in ICU Cohorts with Prolonged Length of Stay

“…In these models the antibiotic-BDI are factorized into TAP and PPAP components. The GSEM methodology used here is described in detail in previous publications [19,48].…”