We implement an agent-based model for Clostridium difficile transmission in hospitals that accounts for several processes and individual factors including environmental and antibiotic heterogeneity in order to evaluate the efficacy of various control measures aimed at reducing environmental contamination and mitigating the effects of antibiotic use on transmission. In particular, we account for local contamination levels that contribute to the probability of colonization and we account for both the number and type of antibiotic treatments given to patients. Simulations illustrate the relative efficacy of several strategies for the reduction of nosocomial colonizations and nosocomial diseases.
Keywords
Clostridium difficileControl Agent-based model
This is a preview of subscription content, log in to check access.
Notes
Acknowledgments
The work of all the authors was partially supported by the National Institute of Mathematical and Biological Synthesis (NIMBioS), an Institute sponsored by National Science Foundation, the US Department of Homeland Security, and the US Department Agriculture through NSF Awards #EF-0832858 and #DBI-1300426, with additional support from University of Tennessee, Knoxville. This work was also supported by the joint NSF/NIGMS Mathematical Biology Program through NIH award R01GM113239. Lenhart’s work is also partially supported by the University of Tennessee Center for Business and Economic Research.
References
Bartlett JG (2002) Antibiotic-associated diarrhea. N Engl J Med 346(5):334–339CrossRefGoogle Scholar
Bignardi G (1998) Risk factors for Clostridium difficile infection. J Hosp Infect 40(1):1–15CrossRefGoogle Scholar
Codella J, Safdar N, Heffernan R, Alagoz O (2015) An agent-based simulation model for Clostridium difficile infection control. Med Decis Mak 35(2):211–229CrossRefGoogle Scholar
Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH (2010) Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 31(5):431–455CrossRefGoogle Scholar
Curry SR, Muto CA, Schlackman JL, Pasculle AW, Shutt KA, Marsh JW, Harrison LH (2013) Use of multilocus variable number of tandem repeats analysis genotyping to determine the role of asymptomatic carriers in Clostridium difficile transmission. Clin Infect Dis 57(8):1094–1102CrossRefGoogle Scholar
D’Agata EM, Magal P, Olivier D, Ruan S, Webb GF (2007) Modeling antibiotic resistance in hospitals: the impact of minimizing treatment duration. J Theor Biol 249(3):487–499MathSciNetCrossRefGoogle Scholar
Dancer S, Kirkpatrick P, Corcoran D, Christison F, Farmer D, Robertson C (2013) Approaching zero: temporal effects of a restrictive antibiotic policy on hospital-acquired Clostridium difficile, extended-spectrum \(\beta \)-lactamase-producing coliforms and meticillin-resistant Staphylococcus aureus. Int J Antimicrob Agents 41(2):137–142CrossRefGoogle Scholar
Donskey CJ (2010) Preventing transmission of Clostridium difficile: Is the answer blowing in the wind? Clin Infect Dis 50(11):1458–1461CrossRefGoogle Scholar
Dubberke ER, Gerding DN, Classen D, Arias KM, Kelly CP, Deverick MC, Anderson J, Burstin H, Calfee DP, Coffin SE, Fraser V, Griffin FA, Gross P, Kaye KS, Klompas M, Lo E, Marschall J, Mermel LA, Nicolle L, Pegues DA, Perl TM, Saint S, Salgado CD, Weinstein RA, Wise R, Yokoe DS (2008) Strategies to prevent Clostridium difficile infections in acute care hospitals. Infect Control Hosp Epidemiol 29(S1):S81–S92CrossRefGoogle Scholar
Dubberke ER, Carling PM, Carrico R, Donskey CJ, Loo VG, McDonald LC, Maragakis LL, Sandora TJ, Weber DJ, Yokoe DS, Gerding DN (2014) Strategies to prevent Clostridium difficile infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 35(6):628–645CrossRefGoogle Scholar
Dubberke ER, Olsen MA (2012) Burden of Clostridium difficile on the healthcare system. Clin Infect Dis 55(suppl 2):S88–S92CrossRefGoogle Scholar
Feazel LM, Malhotra A, Perencevich EN, Kaboli P, Diekema DJ, Schweizer ML (2014) Effect of antibiotic stewardship programmes on Clostridium difficile incidence: a systematic review and meta-analysis. J Antimicrob Chemother 69(7):1748–1754CrossRefGoogle Scholar
Gerding DN, Muto CA, Owens RC (2008) Measures to control and prevent Clostridium difficile infection. Clin Infect Dis 46(Supplement 1):S43–S49CrossRefGoogle Scholar
Grimm V, Berger U, DeAngelis DL, Polhill JG, Giske J, Railsback SF (2010) The ODD protocol: a review and first update. Ecol Model 221(23):2760–2768CrossRefGoogle Scholar
Hsieh Y-H, Liu J, Tzeng Y-H, Wu J (2014) Impact of visitors and hospital staff on nosocomial transmission and spread to community. J Theor Biol 356:20–29MathSciNetCrossRefGoogle Scholar
Hsu J, Abad C, Dinh M, Safdar N (2010) Prevention of endemic healthcare-associated Clostridium difficile infection: reviewing the evidence. Am J Gastroenterol 105(11):2327–2339CrossRefGoogle Scholar
Lanzas C, Dubberke ER, Lu Z, Reske KA, Grohn Y (2011) Epidemiological model for Clostridium difficile transmission in healthcare settings. Infect Control Hosp Epidemiol 32(06):553–561CrossRefGoogle Scholar
Lanzas CP, Dubberke ER (2014) Effectiveness of screening hospital admissions to detect asymptomatic carriers of Clostridium difficile: a modeling evaluation. Infect Control Hosp Epidemiol 35(8):1043–1050CrossRefGoogle Scholar
Leffler DA, Lamont JT (2015) Clostridium difficile infection. N Engl J Med 372(16):1539–1548CrossRefGoogle Scholar
Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, Wilson LE, Winston LG, Cohen JA, Limbago BM, Fridkin SK, Gerding DN, McDonald LC (2015) Burden of Clostridium difficile infection in the United States. N Engl J Med 372(9):825–834CrossRefGoogle Scholar
McFarland LV (2008) Update on the changing epidemiology of Clostridium difficile-associated disease. Nat Clin Pract Gastroenterol Hepatol 5(1):40–48MathSciNetCrossRefGoogle Scholar
McMaster-Baxter N L, Musher D M (2007) Clostridium difficile: recent epidemiologic findings and advances in therapy. Pharmacother J Hum Pharmacol Drug Therapy 27(7):1029–1039CrossRefGoogle Scholar
Otten AM, Reid-Smith RJ, Fazil A, Weese JS (2010) Disease transmission model for community-associated Clostridium difficile infection. Epidemiol Infect 138:907–914CrossRefGoogle Scholar
Owens RC, Donskey CJ, Gaynes RP, Loo VG, Muto CA (2008) Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis 46:S19–31CrossRefGoogle Scholar
Planche T, Aghaizu A, Holliman R, Riley P, Poloniecki J, Breathnach A, Krishna S (2008) Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect Dis 8(12):777–784CrossRefGoogle Scholar
Rubin MA, Jones M, Leecaster M, Khader K, Ray W, Huttner A, Huttner B, Toth D, Sablay T, Borotkanics RJ, Gerding DN, Samore MH (2013) A simulation-based assessment of strategies to control Clostridium difficile transmission and infection. PLoS One 8(11):e80671CrossRefGoogle Scholar
Rupnik M, Wilcox MH, Gerding DN (2009) Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 7(7):526–536CrossRefGoogle Scholar
Slimings C, Riley TV (2014) Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother 69(4):881–891CrossRefGoogle Scholar
Steiner C, Barrett M, Terrel L (2012) HCUP projections:Clostridium difficile hospitalizations 2011 to 2012. HCUP Projections Report # 2012-01Google Scholar
Sullivan A, Edlund C, Nord CE (2001) Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis 1(2):101–114CrossRefGoogle Scholar
Talpaert MJ, Gopal Rao G, Cooper BS, Wade P (2011) Impact of guidelines and enhanced antibiotic stewardship on reducing broad-spectrum antibiotic usage and its effect on incidence of Clostridium difficile infection. J Antimicrob Chemother 66(9):2168–2174CrossRefGoogle Scholar
U.S. Department of Health and Human Services (2013) National action plan to prevent health care-associated infections: road map to elimination. Technical reportGoogle Scholar
Webb G, Blaser MJ, Zhu H, Ardal S, Wu J (2004) Critical role of nosocomial transmission in the toronto sars outbreak. Math Biosci Eng 1(1):1–13MathSciNetCrossRefzbMATHGoogle Scholar
Yahdi M, Abdelmageed S, Lowden J, Tannenbaum L (2012) Vancomycin-resistent enterococci colonization-infection model: parameter impacts and outbreak risks. J Biol Dyn 6(2):645CrossRefGoogle Scholar