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Association between Vancomycin-Resistant Enterococci Bacteremia and Ceftriaxone Usage

  • James A. McKinnell (a1) (a2), Danielle F. Kunz (a3), Eric Chamot (a4), Mukesh Patel (a5) (a6), Rhett M. Shirley (a5), Stephen A. Moser (a7), John W. Baddley (a5) (a6), Peter G. Pappas (a5) and Loren G. Miller (a1)...



Vancomycin-resistant enterococci (VRE) have become a public health concern with implications for patient mortality and costs. Hospital antibiotic usage may impact VRE incidence, but the relationship is poorly understood. Animal investigations suggest that ceftriaxone may be associated with VRE proliferation. We measured antimicrobial usage and VRE bloodstream infection (VRE-BSI) incidence to test our hypothesis that increased ceftriaxone usage would be associated with a higher incidence of VRE-BSI.


Retrospective cohort study.


University of Alabama at Birmingham Medical Center, a 900-bed urban tertiary care hospital.


All patients admitted during the study period contributed data.


We conducted a retrospective analysis of antimicrobial usage and VRE-BSI from 2005 to 2008 (43 months). Antimicrobial usage was quantified as days of therapy (DOTs) per 1,000 patient-days. VRE-BSI incidence was calculated as cases per 1,000 patient-days. Negative binomial regression with adjustment for correlation between consecutive observations was used to measure the association between antimicrobial usage and VRE-BSI incidence at the hospital- and care-unit levels.


VRE-BSI incidence increased from 0.06 to 0.17 infections per 1,000 patient-days. Hospital VRE-BSI incidence was associated with prior-month ceftriaxone DOTs (incidence rate ratio, 1.38 per 10 DOTs; P = .005). After controlling for ceftriaxone, prior-month cephalosporin usage (class) was not predictive of VRE-BSI (P = .70). Similarly, prior-month usage of piperacillin-tazobactam, ceftazidime, cefepime, cefazolin, or vancomycin was not predictive of VRE-BSI when considered individually (P ≥ .4 for all comparisons). The final model suggests that type of intensive care unit was related to VRE-BSI incidence.


Ceftriaxone usage in the prior month, but not cephalosporin (class) or vancomycin usage, was related to VRE-BSI incidence. These findings suggest that an antimicrobial stewardship program that limits ceftriaxone may reduce nosocomial VRE-BSI incidence.


Corresponding author

Infectious Disease Clinical Outcomes Research Unit, 1124 West Carson Street, Box 466, Torrance, CA 90502 (


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1. Hidron, AI, Edwards, JR, Patel, J, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007. Infect Control Hosp Epidemiol 2008;29(11):9961011.
2. Wisplinghoff, H, Bischoff, T, Tallent, SM, Seifert, H, Wenzel, RP, Edmond, MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004;39(3):309317.
3. Deshpande, LM, Fritsche, TR, Moet, GJ, Biedenbach, DJ, Jones, RN. Antimicrobial resistance and molecular epidemiology of vancomycin-resistant enterococci from North America and Europe: a report from the SENTRY antimicrobial surveillance program. Diagn Microbiol Infect Dis 2007;58(2): 163170.
4. National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004;32(8):470485.
5. Scott, RD. The Direct Medical Costs of Healthcare-Associated Infections in U.S. Hospitals and the Benefits of Prevention. Division of Healthcare Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention. Published March 2009. Accessed November 5, 2011.
6. Klevens, RM, Edwards, JR, Richards, CL Jr, et al. Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007;122(2):160166.
7. Carmeli, Y, Eliopoulos, G, Mozaffari, E, Samore, M. Health and economic outcomes of vancomycin-resistant enterococci. Arch Intern Med 2002;162(19):22232228.
8. Song, X, Srinivasan, A, Plaut, D, Perl, TM. Effect of nosocomial vancomycin-resistant enterococcal bacteremia on mortality, length of stay, and costs. Infect Control Hosp Epidemiol 2003; 24(4):251256.
9. Reik, R, Tenover, FC, Klein, E, McDonald, LC. The burden of vancomycin-resistant enterococcal infections in US hospitals, 2003 to 2004. Diagn Microbiol Infect Dis 2008;62(1):8185.
10. Song, JH, Ko, KS, Suh, JY, et al. Clinical implications of vancomycin-resistant Enterococcus faecium (VRE) with VanD phe-notype and vanA genotype. J Antimicrob Chemother 2008;61(4): 838844.
11. DiazGranados, CA, Zimmer, SM, Klein, M, Jernigan, JA. Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis 2005;41(3):327333.
12. Garbutt, JM, Ventrapragada, M, Littenberg, B, Mundy, LM. Association between resistance to vancomycin and death in cases of Enterococcus faecium bacteremia. Clin Infect Dis 2000;30(3): 466472.
13. Lucas, GM, Lechtzin, N, Puryear, DW, Yau, LL, Flexner, CW, Moore, RD. Vancomycin-resistant and vancomycin-susceptible enterococcal bacteremia: comparison of clinical features and outcomes. Clin Infect Dis 1998;26(5):11271133.
14. Vergis, EN, Hayden, MK, Chow, JW, et al. Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia: a prospective multicenter study. Ann Intern Med 2001; 135(7):484492.
15. Bhavnani, SM, Drake, JA, Forrest, A, et al. A nationwide, multicenter, case-control study comparing risk factors, treatment, and outcome for vancomycin-resistant and -susceptible enterococcal bacteremia. Diagn Microbiol Infect Dis 2000;36(3): 145158.
16. Siegel, JD, Rhinehart, E, Jackson, M, Chiarello, L. Management of multidrug-resistant organisms in health care settings, 2006. Am J Infect Control 2007;35(10 suppl 2):S165S193.
17. Boucher, HW, Talbot, GH, Bradley, JS, et al. Bad bugs, no drugs: no ESKAPE! an update from the Infectious Diseases Society of America. Clin Infect Dis 2009;48(1):112.
18. Quale, J, Landman, D, Saurina, G, Atwood, E, DiTore, V, Patel, K. Manipulation of a hospital antimicrobial formulary to control an outbreak of vancomycin-resistant enterococci. Clin Infect Dis 1996;23(5):10201025.
19. Bradley, SJ, Wilson, AL, Allen, MC, Sher, HA, Goldstone, AH, Scott, GM. The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing antibiotic usage. J Antimicrob Chemother 1999;43(2):261266.
20. Montecalvo, MA, Jarvis, WR, Uman, J, et al. Infection-control measures reduce transmission of vancomycin-resistant enterococci in an endemic setting. Ann Intern Med 1999;131(4): 269272.
21. Smith, DW. Decreased antimicrobial resistance after changes in antibiotic use. Pharmacotherapy 1999;19(8 pt 2):129S132S; discussion 133S-137S.
22. Manzella, J, Benenson, R, Pellerin, G, et al. Choice of antibiotic and risk of colonization with vancomycin-resistant Enterococcus among patients admitted for treatment of community-acquired pneumonia. Infect Control Hosp Epidemiol 2000;21(12):789791.
23. May, AK, Melton, SM, McGwin, G, Cross, JM, Moser, SA, Rue, LW. Reduction of vancomycin-resistant enterococcal infections by limitation of broad-spectrum cephalosporin use in a trauma and burn intensive care unit. Shock 2000;14(3):259264.
24. Nourse, C, Byrne, C, Murphy, H, Kaufmann, ME, Clarke, A, Butler, K. Eradication of vancomycin resistant Enterococcus faecium from a paediatric oncology unit and prevalence of colonization in hospitalized and community-based children. Epidemiol Infect 2000;124(1):5359.
25. Puzniak, LA, Mayfield, J, Leet, T, Kollef, M, Mundy, LM. Acquisition of vancomycin-resistant enterococci during scheduled antimicrobial rotation in an intensive care unit. Clin Infect Dis 2001;33(2):151157.
26. Lautenbach, E, LaRosa, LA, Marr, AM, Nachamkin, I, Bilker, WB, Fishman, NO. Changes in the prevalence of vancomycin-resistant enterococci in response to antimicrobial formulary interventions: impact of progressive restrictions on use of vancomycin and third-generation cephalosporins. Clin Infect Dis 2003;36(4): 440446.
27. Loeffler, JM, Garbino, J, Lew, D, Harbarth, S, Rohner, P. Antibiotic consumption, bacterial resistance and their correlation in a Swiss university hospital and its adult intensive care units. Scand J Infect Dis 2003;35(11-12):843850.
28. Paterson, DL. “Collateral damage” from cephalosporin or quin-olone antibiotic therapy. Clin Infect Dis 2004;38(suppl 4): S341S345.
29. Empey, KM, Rapp, RP, Evans, ME. The effect of an antimicrobial formulary change on hospital resistance patterns. Pharmacotherapy 2002;22(1) :8187.
30. Donskey, CJ, Chowdhry, TK, Hecker, MT, et al. Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients. N Engl J Med 2000;343(26): 19251932.
31. Donskey, CJ, Hoyen, CK, Das, SM, Helfand, MS, Hecker, MT. Recurrence of vancomycin-resistant Enterococcus stool colonization during antibiotic therapy. Infect Control Hosp Epidemiol 2002;23(8):436440.
32. Paterson, DL, Muto, CA, Ndirangu, M, et al. Acquisition of rectal colonization by vancomycin-resistant Enterococcus among intensive care unit patients treated with piperacillin-tazobactam versus those receiving cefepime-containing antibiotic regimens. Antimicrob Agents Chemother 2008;52(2):465469.
33. Donskey, CJ, Hanrahan, JA, Hutton, RA, Rice, LB. Effect of parenteral antibiotic administration on persistence of vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract. J Infect Dis 1999;180(2):384390.
34. Lakticova, V, Hutton-Thomas, R, Meyer, M, Gurkan, E, Rice, LB. Antibiotic-induced enterococcal expansion in the mouse intestine occurs throughout the small bowel and correlates poorly with suppression of competing flora. Antimicrob Agents Chemother 2006;50(9):31173123.
35. Rice, LB, Lakticova, V, Helfand, MS, Hutton-Thomas, R. In vitro antienterococcal activity explains associations between exposures to antimicrobial agents and risk of colonization by multi-resistant enterococci. J Infect Dis 2004;190(12):21622166.
36. Rice, LB, Hutton-Thomas, R, Lakticova, V, Helfand, MS, Donskey, CJ. β-Lactam antibiotics and gastrointestinal colonization with vancomycin-resistant enterococci. J Infect Dis 2004;189(6): 11131118.
37. Horan, TC, Andrus, M, Dudeck, MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008;36(5):309332.
38. Fridkin, SK, Edwards, JR, Courval, JM, et al. The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 U.S. adult intensive care units. Ann Intern Med 2001;135(3):175183.
39. Kritsotakis, EI, Christidou, A, Roumbelaki, M, Tselentis, Y, Gikas, A. The dynamic relationship between antibiotic use and the incidence of vancomycin-resistant Enterococcus: time-series modelling of 7-year surveillance data in a tertiary-care hospital. Clin Microbiol Infect 2008;14(8):747754.
40. Harbarth, S, Cosgrove, S, Carmeli, Y. Effects of antibiotics on nosocomial epidemiology of vancomycin-resistant enterococci. Antimicrob Agents Chemother 2002;46(6):16191628.
41. Harris, AD, Karchmer, TB, Carmeli, Y, Samore, MH. Methodological principles of case-control studies that analyzed risk factors for antibiotic resistance: a systematic review. Clin Infect Dis 2001;32(7):10551061.
42. Carmeli, Y, Eliopoulos, GM, Samore, MH. Antecedent treatment with different antibiotic agents as a risk factor for vancomycin-resistant Enterococcus . Emerg Infect Dis 2002;8(8):802807.
43. Ostrowsky, BE, Venkataraman, L, D'Agata, EM, Gold, HS, DeGirolami, PC, Samore, MH. Vancomycin-resistant enterococci in intensive care units: high frequency of stool carriage during a non-outbreak period. Arch Intern Med 1999;159(13): 14671472.
44. Carmeli, Y, Samore, MH, Huskins, C. The association between antecedent vancomycin treatment and hospital-acquired vancomycin-resistant enterococci: a meta-analysis. Arch Intern Med 1999;159(20):24612468.
45. de Bruin, MA, Riley, LW. Does vancomycin prescribing intervention affect vancomycin-resistant enterococcus infection and colonization in hospitals? a systematic review. BMC Infect Dis 2007;7:24.
46. Guggenbichler, JP, Kofler, J, Allerberger, F. The influence of third-generation cephalosporins on the aerobic intestinal flora. Infection 1985;13(suppl 1):S137S139.
47. Donskey, CJ, Hume, ME, Callaway, TR, Das, SM, Hoyen, CK, Rice, LB. Inhibition of vancomycin-resistant enterococci by an in vitro continuous-flow competitive exclusion culture containing human stool flora. J Infect Dis 2001;184(12):16241627.
48. Winston, LG, Charlebois, ED, Pang, S, Bangsberg, DR, Perdreau-Remington, F, Chambers, HE Impact of a formulary switch from ticarcillin-clavulanate to piperacillin-tazobactam on colonization with vancomycin-resistant enterococci. Am J Infect Control 2004;32(8):462469.
49. Bonten, MJ, Slaughter, S, Ambergen, AW, et al. The role of “colonization pressure” in the spread of vancomycin-resistant enterococci: an important infection control variable. Arch Intern Med 1998;158(10):11271132.
50. Aldeyab, MA, Harbarth, S, Vernaz, N, et al. Quasiexperimental study of the effects of antibiotic use, gastric acid-suppressive agents, and infection control practices on the incidence of Clostridium dijficile-associated diarrhea in hospitalized patients. Antimicrob Agents Chemother 2009;53(5):20822088.
51. Kaier, K, Frank, U. Relationship between antibiotic consumption and Clostridium dijficile-associated diarrhea: an epidemiological note. Antimicrob Agents Chemother 2009;53(10):45744575.
52. McKinnell, JA, Powderly, AL, Kunz, DF, Patel, M. Individual antimicrobials and risk of VRE colonization. Presented at: 48th Annual Meeting of the Infectious Diseases Society of America; Vancouver; October 21-24, 2010. Abstract 3365.
53. Ramsey, AM, Zilberberg, MD. Secular trends of hospitalization with vancomycin-resistant Enterococcus infection in the United States, 2000-2006. Infect Control Hosp Epidemiol 2009;30(2): 184186.
54. Huskins, WC, Huckabee, CM, O'Grady, NP, et al. Intervention to reduce transmission of resistant bacteria in intensive care. N Engl J Med 2011;364(15):14071418.


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