Mathematical Model of the Impact of a Nonantibiotic Treatment for Clostridium difficile on the Endemic Prevalence of Vancomycin-Resistant Enterococci in a Hospital Setting

Introduction. Clostridium difficile-associated disease (CDAD) is treated using antibiotics, which often leads to the emergence of antibiotic-resistant bacteria such as vancomycin-resistant enterococci (VRE). This study estimated the impact of a non antibiotic treatment for CDAD on VRE prevalence. Methods. A previously published model describing the impact of in-hospital antibiotic use on VRE prevalence was adapted to include CDAD treatment. Simulations compared the prevalence of VRE when nonantibiotic versus antibiotic therapy was used. Results. Nonantibiotic treatment in 50% of CDAD patients resulted in an 18% relative reduction in the prevalence of VRE colonization compared with antibiotic use only. Sensitivity analysis found the model to be most sensitive to rates of antibiotic initiation and discontinuation, prevalence of VRE in admitted patients, length of stay of colonized patients, probability of CDAD acquisition, and hand-washing compliance. Conclusion. Nonantibiotic treatment of patients hospitalized with CDAD may significantly reduce the incidence of VRE colonization

Efficacy of Infection Control Interventions in Reducing the Spread of Multidrug-Resistant Organisms in the Hospital Setting

Multidrug-resistant organisms (MDRO) continue to spread in hospitals globally, but the population-level impact of recommended preventive strategies and the relative benefit of individual strategies targeting all MDRO in the hospital setting are unclear. To explore the dynamics of MDRO transmission in the hospital, we develop a model extending data from clinical individual-level studies to quantify the impact of hand hygiene, contact precautions, reducing antimicrobial exposure and screening surveillance cultures in decreasing the prevalence of MDRO colonization and infection. The effect of an ongoing increase in the influx of patients colonized with MDRO into the hospital setting is also quantified. We find that most recommended strategies have substantial effect in decreasing the prevalence of MDRO over time. However, screening for asymptomatic MDRO colonization among patients who are not receiving antimicrobials is of minimal value in reducing the spread of MDRO

The Impact of Different Antibiotic Regimens on the Emergence of Antimicrobial-Resistant Bacteria

Backgroud: The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address. Methods/Principal Findings: A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains. Conclusions/Significance: The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance

ASYMPTOTIC BEHAVIOR IN NOSOCOMIAL EPIDEMIC MODELS WITH ANTIBIOTIC RESISTANCE

We study a model of an antibiotic resistance in a hospital setting. The model connects two population levels - bacteria and patients. The bacteria population is divided into non-resistant and resistant strains. The bacterial strains satisfy ordinary differential equations describing the recombination and reversion processes producing the two strains within each infected individual. The patient population is divided into susceptibles, infectives infected with the non-resistant bacterial strain, and infectives infected with the resistant bacterial stain. The infective classes satisfy partial differential equations for the infection age densities of the two classes. We establish conditions for the existence of three possible equilibria for this model: (1) extinction of both infective classes, (2) extinction of the resistant infectives and endemicity of the non-resistant infectives, and (3) endemicity of both infective classes. We investigate the asymptotic behavior of the solutions of the model with respect to these equilibria

Competition of hospital-acquired and community-acquired methicillin-resistant Staphylococcus aureus strains in hospitals

Recently, we [E.M.C. D'Agata, G.F. Webb, M.A. Horn, R.C. Moellering Jr., and S. Ruan, Modelling the invasion of community-acquired methicillin-resistant Staphylococcus aureus into the hospital setting, Clin. Infect. Dis. 48 (2009), pp. 274-284] proposed a deterministic mathematical model to characterize the factors contributing to the replacement of hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) with the community-acquired MRSA (CA-MRSA) and to quantify the effectiveness of interventions aimed at limiting the spread of CA-MRSA in the hospital setting. Numerical simulations of the model strongly suggest that CA-MRSA will become the dominant MRSA strain in the hospital setting. In this companion paper, we provide steady-state analysis and more numerical simulations of the model. It is shown that when no colonized or infected patients enter the hospital, competitive exclusion of HA-MRSA by CA-MRSA will occur with increased severity of CA-MRSA infections resulting in longer hospitalizations and a larger in-hospital reservoir of CA-MRSA. Improving compliance with hand hygiene and decolonization of CA-MRSA carriers are effective control strategies

Efficacy of Infection Control Interventions in Reducing the Spread of Multidrug-Resistant Organisms in the Hospital Setting

Multidrug-resistant organisms (MDRO) continue to spread in hospitals globally, but the population-level impact of recommended preventive strategies and the relative benefit of individual strategies targeting all MDRO in the hospital setting are unclear. To explore the dynamics of MDRO transmission in the hospital, we develop a model extending data from clinical individual-level studies to quantify the impact of hand hygiene, contact precautions, reducing antimicrobial exposure and screening surveillance cultures in decreasing the prevalence of MDRO colonization and infection. The effect of an ongoing increase in the influx of patients colonized with MDRO into the hospital setting is also quantified. We find that most recommended strategies have substantial effect in decreasing the prevalence of MDRO over time. However, screening for asymptomatic MDRO colonization among patients who are not receiving antimicrobials is of minimal value in reducing the spread of MDRO