Persistent colonization and the spread of antibiotic resistance in nosocomial pathogens: resistance is a regional problem

Abstract

Infections with antibiotic-resistant bacteria (ARB) in hospitalized patients are becoming increasingly frequent despite extensive infection-control efforts. Infections with ARB are most common in the intensive care units of tertiary-care hospitals, but the underlying cause of the increases may be a steady increase in the number of asymptomatic carriers entering hospitals. Carriers may shed ARB for years but remain undetected, transmitting ARB to others as they move among hospitals, long-term care facilities, and the community. We apply structured population models to explore the dynamics of ARB, addressing the following questions: (i) What is the relationship between the proportion of carriers admitted to a hospital, transmission, and the risk of infection with ARB? (ii) How do frequently hospitalized patients contribute to epidemics of ARB? (iii) How do transmission in the community, long-term care facilities, and hospitals interact to determine the proportion of the population that is carrying ARB? We offer an explanation for why ARB epidemics have fast and slow phases and why resistance may continue to increase despite infection-control efforts. To successfully manage ARB at tertiary-care hospitals, regional coordination of infection control may be necessary, including tracking asymptomatic carriers through health-care systems.

Figures

Fig. 1.

A diagram of the general model. Individuals move among subpopulations, such as hospitals, LTCFs, and the community. The subpopulation is assumed to be well mixed with respect to the transmission of ARB. The population is also classified by group, based on some epidemiologically important difference. The size of the population at each location, Nj, and the proportion of each group, qg,j, are constant by assumption. The admission rate is equal to the discharge rate, σg,jqg, jNj. The portion of discharged individuals from subpopulation j that move to k is ωg,j,k. The portion of admitted individuals to subpopulation j that are from k is αg, j,k.

Fig. 2.

Colonization on admission interacts with local transmission dynamics to determine the equilibrium prevalence. We plotted the equilibrium prevalence of ARB (from Eq. 3) as a function of the single-stay reproductive number S when the proportion colonized without local transmission is κm = 0,0.04 (solid trace). We used three approximations to subdivide institutions into those that sustain internal epidemics (S » 1; dashed trace), for which prevalence is determined by patient-to-patient transmission; nonepidemics (S « 1; dotted trace), for which prevalence is determined by immigration of carriers; and quasiepidemics (S ≈ 1; dashed-dotted trace), for which prevalence is strongly influenced by both immigration and transmission. For example, for S = 1, prevalence is , either 0% or 20%.

Fig. 3.

Structured population models may have fast and slow phases, depending on whether the hospital, the community, or neither is a self-sustaining source. (a) Carriers may accumulate slowly in the hospital population (solid trace) and community (dashed trace), even if neither one can sustain an internal epidemic. (b) When the hospital has a self-sustaining epidemic, the epidemic of ARB in the catchment population has fast and slow phases. Rapid early increases in prevalence are due to the epidemic in the hospital. Without colonization on admission, prevalence would rapidly reach a lower equilibrium (dashed trace and dashed-dotted trace). Slow increases after the initial epidemic reflect admission of carriers from the community. (c) The community may be a self-sustaining source, but prevalence increases slowly because resistance is initially rare and turnover is very slow. Prevalence remains higher in the hospital because daily transmission rates are higher. The role of community transmission may be underappreciated.

Fig. 4.

The elderly are frequently hospitalized, so they are more likely to be exposed and expose others. As a result of frequent hospitalization, ARB invade a catchment population more easily and prevalence is higher. One essential difference is that the period between hospital visits is shorter, so the likelihood of colonization on readmission is higher. The elderly population accounts for 12.6% of the population but about half of all days of care in the hospital. A greater portion of the elderly in each subpopulation are carriers (solid gray trace). Here, the daily transmission rates in the hospital and community are similar to those in Fig. 3a. The average prevalence in the hospital (solid black trace) and the community (dashed black trace) increases more rapidly and reaches a higher equilibrium than it would if the population were homogeneous.

Fig. 5.

LTCFs (dashed-dotted trace) may be the most important type of institution in health-care networks because LTCF patients are frequently hospitalized and receive a similar level and type of care as hospitalized patients. Single-stay reproductive numbers for the hospital and community are identical to those in Figs. 3a and 4. In this simulation, the single-stay reproductive numbers in the LTCF and hospital are identical, but the closed-population reproductive rate for the LTCF is much lower than the hospital because of the longer LOS. Compared with earlier simulations, prevalence increases faster and reaches a higher equilibrium in hospitals (solid trace) and the community (dashed trace).