Vancomycin-resistant enterococci in intensive-care hospital settings: transmission dynamics, persistence, and the impact of infection control programs

Abstract

Vancomycin-resistant enterococci (VRE) recently have emerged as a nosocomial pathogen especially in intensive-care units (ICUs) worldwide. Transmission via the hands of health-care workers is an important determinant of spread and persistence in a VRE-endemic ICU. We describe the transmission of nosocomial pathogens by using a micro-epidemiological framework based on the transmission dynamics of vector-borne diseases. By using the concept of a basic reproductive number, R0, defined as the average number of secondary cases generated by one primary case, we show quantitatively how infection control measures such as hand washing, cohorting, and antibiotic restriction affect nosocomial cross-transmission. By using detailed molecular epidemiological surveillance and compliance monitoring, we found that the estimated basic reproductive number for VRE during a study at the Cook County Hospital, Chicago, was approximately 3-4 without infection control and 0.7 when infection control measures were included. The impact of infection control was to reduce the prevalence from a predicted 79% to an observed 36%. Hand washing and staff cohorting are the most powerful control measures although their efficacy depends on the magnitude of R0. Under the circumstances tested, endemicity of VRE was stabilized despite infection control measures, by the constant introduction of colonized patients. Multiple stochastic simulations of the model revealed excellent agreement with observed pattern. In conjunction with detailed microbiological surveillance, a mathematical framework provides a precise template to describe the colonization dynamics of VRE in ICUs and impact of infection control measures. Our analyses suggest that compliance for hand washing significantly in excess of reported levels, or the cohorting of nursing staff, are needed to prevent nosocomial transmission of VRE in endemic settings.

Figure 1

Ross-Macdonald model of indirect patient-HCW-patient VRE transmission in an ICU showing the possible effect of infection control measures. Once patients become colonized they are assumed to remain colonized for the duration of their stay in the ICU.

Figure 2

(a) Endemic prevalence of VRE colonization as a function of admission prevalence (parameters used: δ = 55%, R_h = 0.1R₀). Transmission of VRE always increases the endemic prevalence above the admission prevalence. Arrow indicates the effect of infection control measures on the endemic prevalence of VRE colonization at Cook County Hospital (CCH) ICU. (b) Combined infection control and nurse cohorting measures necessary to eradicate endemic VRE colonization assuming no further VRE-colonized patient admissions. Contours show R(p, q) = 1. Gray lines indicate the effect of a 50% reduction in third-generation cephalosporin usage (parameters used: α = 50% of LOS, α′ = 25%, relative risk ξ = 3). Increased cohorting of nursing staff frequently can be more effective than other precautions, although when R₀ is large cohorting only nursing contacts will not be sufficient. Antibiotic restriction facilitates VRE control when transmission is low, but has little effect when VRE is highly endemic.

Figure 3

(a) Time series data showing prevalence of VRE colonization in a 16-bed ICU in Cook County General Hospital, Chicago, showing observed prevalence, with mean and 95% confidence intervals generated by 10⁵ stochastic realizations of the model using parameters shown in Table 1 (dashed lines). LOSs are highly variable, and a mean value is calculated by using the relationship 1/μ = occupancy × beds × study duration/number of patients in study. (b) Two simulated VRE outbreaks in an ICU showing both eradication and endemic stability using the same infection control measures (all parameters are as before). A single VRE-positive patient is admitted on the first day of the outbreak. After 30 days strict infection control measures are implemented (P = 50%). After 45 days a program of cohorting nursing staff with individual patients begins (qn = 64%). After 60 days antibiotic restriction is used to reduce consumption by 50% (α′ = 25%, ξ = 3). However, this intervention proves ineffectual because nosocomial transmission already has been contained. Finally, after 90 days all further VRE-positive admissions are isolated. Other curves indicate the mean cumulative effects of each successive policy for 10⁵ stochastic simulations.