Identifying patient-level risk factors associated with non-β-lactam resistance outcomes in invasive MRSA infections in the United States using chain graphs

BACKGROUND: MRSA is one of the most common causes of hospital- and community-acquired infections. MRSA is resistant to many antibiotics, including β-lactam antibiotics, fluoroquinolones, lincosamides, macrolides, aminoglycosides, tetracyclines and chloramphenicol. OBJECTIVES: To identify patient-level characteristics that may be associated with phenotype variations and that may help improve prescribing practice and antimicrobial stewardship. METHODS: Chain graphs for resistance phenotypes were learned from invasive MRSA surveillance data collected by the CDC as part of the Emerging Infections Program to identify patient level risk factors for individual resistance outcomes reported as MIC while accounting for the correlations among the resistance traits. These chain graphs are multilevel probabilistic graphical models (PGMs) that can be used to quantify and visualize the complex associations among multiple resistance outcomes and their explanatory variables. RESULTS: Some phenotypic resistances had low connectivity to other outcomes or predictors (e.g. tetracycline, vancomycin, doxycycline and rifampicin). Only levofloxacin susceptibility was associated with healthcare-associated infections. Blood culture was the most common predictor of MIC. Patients with positive blood culture had significantly increased MIC of chloramphenicol, erythromycin, gentamicin, lincomycin and mupirocin, and decreased daptomycin and rifampicin MICs. Some regional variations were also observed. CONCLUSIONS: The differences in resistance phenotypes between patients with previous healthcare use or positive blood cultures, or from different states, may be useful to inform first-choice antibiotics to treat clinical MRSA cases. Additionally, we demonstrated multilevel PGMs are useful to quantify and visualize interactions among multiple resistance outcomes and their explanatory variables.