How to apply structural equation modelling to infectious diseases concepts

Eur J Clin Microbiol Infect Dis

2023

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Whether Candida within the patient microbiome drives the pathogenesis of Staphylococcus aureus bacteremia, described as microbial hitchhiking, cannot be directly studied. Group-level observations from studies of various decontamination and non-decontamination-based ICU infection prevention interventions and studies without study interventions (observational groups) collectively enable tests of this interaction within causal models. Candidate models of the propensity for Staphylococcus aureus bacteremia to arise with versus without various antibiotic, anti-septic, and antifungal exposures, each identified as singleton exposures, were tested using generalized structural equation modelling (GSEM) techniques with Candida and Staphylococcus aureus colonization appearing as latent variables within the models. Each model was tested by confrontation against blood and respiratory isolate data, obtained from 467 groups within 284 infection prevention studies. Introducing an interaction term between Candida colonization and Staphylococcus aureus colonization substantially improved GSEM model fit. Model-derived coefficients for singular exposure to anti-septic agents (− 1.28; 95% confidence interval; − 2.05 to − 0.5), amphotericin (− 1.49; − 2.3 to − 0.67), and topical antibiotic prophylaxis (TAP; + 0.93; + 0.15 to + 1.71) as direct effects versus Candida colonization were similar in magnitude but contrary in direction. By contrast, the coefficients for singleton exposure to TAP, as with anti-septic agents, versus Staphylococcus colonization were weaker or non-significant. Topical amphotericin would be predicted to halve both candidemia and Staphylococcus aureus bacteremia incidences versus literature derived benchmarks for absolute differences of < 1 percentage point. Using ICU infection prevention data, GSEM modelling validates the postulated interaction between Candida and Staphylococcus colonization facilitating bacteremia.

Section: Introductionmentioning

confidence: 99%

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

Eur J Clin Microbiol Infect Dis

2023

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Structural equation modelling the impact of antimicrobials on the human microbiome. Colonization resistance versus colonization susceptibility as case studies

Journal of Antimicrobial Chemotherapy

2022

The impact of antimicrobials on the human microbiome and its relationship to human health are of great interest. How antimicrobial exposure might drive change within specific constituents of the microbiome to effect clinically relevant endpoints is difficult to study. Clinical investigation of each step within a network of causation would be challenging if done ‘step-by-step’. An analytic tool of great potential to clinical microbiome research is structural equation modelling (SEM), which has a long history of applications to research questions arising within subject areas as diverse as psychology and econometrics. SEM enables postulated models based on a network of causation to be tested en bloc by confrontation with data derived from the literature. Case studies for the potential application of SEM techniques are colonization resistance (CR) and its counterpart, colonization susceptibility (CS), wherein specific microbes within the microbiome are postulated to either impede (CR) or facilitate (CS) invasive infection with pathogenic bacteria. These postulated networks have three causation steps: exposure to specific antimicrobials are key drivers, clinically relevant infection endpoints are the measurable observables and the activity of key microbiome constituents mediating CR or CS, which may be unobservable, appear as latent variables in the model. SEM methods have potential application towards evaluating the activity of specific antimicrobial agents within postulated networks of causation using clinically derived data.

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

2022

Emerg Themes Epidemiol

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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.