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Updated: May 29, 2026

Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Colonization with antibiotic-susceptible strains protects against methicillin-resistant Staphylococcus aureus but not
Susan S Huang1, Rupak Datta, Sheryl Rifas-Shiman
1Division of Infectious Diseases and Health Policy Research Institute, University of California Irvine School of Medicine, 100 Theory, Ste 110, Irvine, CA 92697, USA. sshuang@uci.edu
Introduction:
Harboring sensitive strains may prevent acquisition of resistant pathogens by competing for colonization of ecological niches. Competition may be relevant to decolonization strategies that eliminate sensitive strains and may predispose to acquiring resistant strains in high-endemic settings. We evaluated the impact of colonization with methicillin-sensitive Staphylococcus aureus (MSSA) and vancomycin-sensitive enterococci (VSE) on acquisition of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), respectively, when controlling for other risk factors.
Methods:
We conducted a nested case-control study of patients admitted to eight ICUs performing admission and weekly bilateral nares and rectal screening for MRSA and VRE, respectively. Analyses were identical for both pathogens. For MRSA, patients were identified who had a negative nares screen and no prior history of MRSA. We evaluated predictors of MRSA acquisition, defined as a subsequent MRSA-positive clinical or screening culture, compared to those with a subsequent MRSA-negative nares screen within the same hospitalization. Medical records were reviewed for the presence of MSSA on the initial MRSA-negative nares screen, demographic and comorbidity information, medical devices, procedures, antibiotic utilization, and daily exposure to MRSA-positive patients in the same ward. Generalized linear mixed models were used to assess predictors of acquisition.
Results:
In multivariate models, MSSA carriage protected against subsequent MRSA acquisition (OR = 0.52, CI: 0.29, 0.95), even when controlling for other risk factors. MRSA predictors included intubation (OR = 4.65, CI: 1.77, 12.26), fluoroquinolone exposure (OR = 1.91, CI: 1.20, 3.04), and increased time from ICU admission to initial negative swab (OR = 15.59, CI: 8.40, 28.94). In contrast, VSE carriage did not protect against VRE acquisition (OR = 1.37, CI: 0.54, 3.48), whereas hemodialysis (OR = 2.60, CI: 1.19, 5.70), low albumin (OR = 2.07, CI: 1.12, 3.83), fluoroquinolones (OR = 1.90, CI: 1.14, 3.17), third-generation cephalosporins (OR = 1.89, CI: 1.15, 3.10), and increased time from ICU admission to initial negative swab (OR = 15.13, CI: 7.86, 29.14) were predictive.
Conclusions:
MSSA carriage reduced the odds of MRSA acquisition by 50% in ICUs. In contrast, VSE colonization was not protective against VRE acquisition. Studies are needed to evaluate whether decolonization of MSSA ICU carriers increases the risk of acquiring MRSA when discharging patients to high-endemic MRSA healthcare settings. This may be particularly important for populations in whom MRSA infection may be more frequent and severe than MSSA infections, such as ICU patients.
Insights
Colonization with methicillin-sensitive Staphylococcus aureus (MSSA) halves the risk of acquiring methicillin-resistant Staphylococcus aureus (MRSA) in ICUs. However, vancomycin-sensitive enterococci (VSE) did not protect against vancomycin-resistant enterococci (VRE) acquisition.
Area of Science:
- Infectious Diseases
- Microbiology
- Critical Care Medicine
Background:
- Colonization with sensitive bacterial strains can prevent the acquisition of resistant pathogens through niche competition.
- Decolonization strategies that eliminate sensitive strains may inadvertently increase the risk of acquiring resistant strains in high-prevalence settings.
Purpose of the Study:
- To evaluate the impact of methicillin-sensitive Staphylococcus aureus (MSSA) colonization on the acquisition of methicillin-resistant Staphylococcus aureus (MRSA).
- To assess the effect of vancomycin-sensitive enterococci (VSE) colonization on the acquisition of vancomycin-resistant enterococci (VRE).
Main Methods:
- A nested case-control study was conducted in eight ICUs.
- Patients underwent admission and weekly screening for MRSA and VRE.
- Predictors of acquisition were analyzed using generalized linear mixed models, controlling for various risk factors.
Main Results:
- MSSA carriage was associated with a 50% reduced odds of MRSA acquisition (OR = 0.52).
- Predictors of MRSA acquisition included intubation, fluoroquinolone exposure, and delayed initial negative swab.
- VSE carriage did not protect against VRE acquisition (OR = 1.37); hemodialysis, low albumin, and specific antibiotic exposures were predictive.
Conclusions:
- MSSA colonization significantly reduces MRSA acquisition in ICUs.
- VSE colonization offers no protection against VRE acquisition.
- Further research is needed to determine if MSSA decolonization increases MRSA acquisition risk in high-endemic settings.
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