Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-28T16:26:39.389Z Has data issue: false hasContentIssue false
  • English
  • Français

Increased Susceptibility to Vancomycin-Resistant Enterococcus Intestinal Colonization Persists After Completion of Anti-Anaerobic Antibiotic Treatment in Mice

Published online by Cambridge University Press:  02 January 2015

Usha Stiefel ,
Nicole J. Pultz ,
Marion S. Helfand  and
Curtis J. Donskey
Usha Stiefel
Affiliation:
Division of Infectious Diseases, University Hospitals of Cleveland, Cleveland, Ohio
Nicole J. Pultz
Affiliation:
Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio
Marion S. Helfand
Affiliation:
Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio Infectious Diseases Section, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio
Curtis J. Donskey*
Affiliation:
Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio Infectious Diseases Section, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio
*
Infectious Diseases Section (111 W), Louis Stokes Cleveland VA Medical Center, 10701 East Blvd., Cleveland, OH 44106
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

Antibiotic-associated disruption of the indigenous intestinal microflora may persist beyond the treatment period. Although piperacillin/tazobactam inhibits the establishment of vancomycin-resistant Enterococcus (VRE) stool colonization in mice during treatment, we hypothesized that this agent and other anti-anaerobic antibiotics would increase susceptibility to colonization during the period of recovery of the intestinal microflora.

Design:

Mice received 104 colony-forming units of vancomycin-resistant E. faecium by orogastric inoculation 2, 5, or 10 days after completing 5 days of subcutaneous antibiotic treatment, or both during and 2 days after the completion of treatment. Denaturing gradient gel electrophoresis (DGGE) was performed to assess changes in the intestinal microflora.

Results:

Anti-anaerobic antibiotics (ie, piperacillin/tazobactam, cefoxitin, and clindamycin) caused significant disruption of the indigenous microflora (mean DGGE similarity indices ≤ 27% in comparison with saline controls) and promoted the establishment of high-density colonization when VRE was inoculated 2 or 5, but not 10, days following treatment (P < .001). Piperacillin/tazobactam exhibited a biphasic effect on the establishment of colonization (ie, inhibition when exposed to VRE during treatment and promotion when exposed to VRE after discontinuation of treatment), resulting in greater overall promotion of colonization than did agents with minimal anti-anaerobic activity (ie, levofloxacin, cefepime, and aztreonam) when VRE was inoculated both during and 2 days after treatment (P< .001).

Conclusion:

Patients receiving anti-anaerobic antibiotics, including piperacillin/tazobactam, may be susceptible to the establishment of high-density VRE colonization during the period of recovery of the anaerobic microflora.

Type
Original Articles
Information
Infection Control & Hospital Epidemiology , Volume 25 , Issue 5 , May 2004 , pp. 373 - 379
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.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;180:384–390.Google Scholar
2.Donskey, CJ, Hanrahan, JA, Hutton, RA, Rice, LB. Effect of parenteral antibiotic administration on the establishment of colonization with vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract. J Infect Dis 2000;181:1830–1833.Google Scholar
3.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;343:1925–1932.Google Scholar
4.Donskey, CF, Hoyen, CK, Das, SM, Farmer, S, Dery, M, Bonomo, RA. Effect of oral Bacillus coagulans administration on density and persistence of colonization with vancomycin-resistant enterococci in the mouse gastrointestinal tract. Lett Appl Microbiol 2001;33:84–88.CrossRefGoogle Scholar
5.Donskey, CJ, Hoyen, CK, Das, SM, Helfand, MS, Hecker, MT. Recurrence of vancomycin-resistant Enterococcus stool colonization during antibiotic therapy. Infect Control Hasp Epidemiol 2002;23:436–440.CrossRefGoogle ScholarPubMed
6.Baden, LR, Critchley, IA, Sahm, DF, et al.Molecular characterization of vancomycin-resistant enterococci repopulating the gastrointestinal tract following treatment with a novel glycolipodepsipeptide, ramo-planin. J Clin Microbiol 2002;40:1160–1163.Google Scholar
7.Finegold, SM, Mathisen, GE, George, WL. Changes in human intestinal flora related to the administration of antimicrobial agents. In: Hentges, D, ed. Human Intestinal Microflora in Health and Disease. New York: Academic Press; 1983:355–446.CrossRefGoogle Scholar
8.Vollaard, EJ, Clasener, HAL. Colonization resistance. Antimicrob Agents Chemother 1994;38:409–414.Google Scholar
9.Nord, CE, Heimdahl, A, Kager, L, Malmborg, AS. The impact of different antimicrobial agents on the normal gastrointestinal microflora of humans. Rev Infect Dis 1984;6(suppl 1):S270–S275.Google Scholar
10.Mulligan, ME, Citron, D, Gabay, E, Kirby, BD, Georgi, WL, Finegold, SM. Alterations in human fecal flora, including ingrowth of Clostridium difficile, related to cefoxitin therapy. Antimicrob Agents Chemother 1984;26:343–346.CrossRefGoogle ScholarPubMed
11.Kager, L, Liljeqvist, L, Malmborg, AS, Nord, CE. Effect of clindamycin prophylaxis on the colonic microflora in patients undergoing colorectal surgery. Antimicrob Agents Chemother 1981;20:736–740.Google Scholar
12.Nord, CE, Brismar, B, Hasholm-Tengve, B, Tunevall, G. Effect of piperacillin/tazobactam therapy on intestinal microflora. Scand J Infect Dis 1992;24:209–213.Google Scholar
13.Bacher, K, Schaeffer, M, Lode, H, Nord, CE, Borner, K, Koeppe, P. Multiple dose pharmacokinetics, safety, and effects on faecal microflora, of cefepime in healthy volunteers. J Antimicrob Chemother 1992;30:365–375.CrossRefGoogle ScholarPubMed
14.Freireich, EJ, Gehan, EA, Rail, DP, Schmidt, LH, Skipper, HE. Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey and man. Cancer Chemotherapy Reports 1966;50:219–244.Google ScholarPubMed
15.Donskey, CJ, Hujer, A, Das, SM, Pultz, NJ, Bonomo, RA, Rice, LB. Use of denaturing gradient gel electrophoresis for analysis of the stool microbiota of hospitalized patients. J Microbiol Methods 2003;54:249–256.Google Scholar
16.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;23:1020–1025.Google Scholar
17.Bradley, SJ, Wilson, ALT, Allen, MC, Sher, HA, Goldstone, AH, Scott, GM. The control of hyperendemic glycopeptide-resistant Enterococcus species on a haematology unit by changing antibiotic usage. J Antimicrob Chemother 1999;43:261–266.Google Scholar
18.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;14:259–264.Google Scholar
19.Donskey, CJ, Schreiber, JR, Jacobs, MR, et al.A polyclonal outbreak of predominantly VanB vancomycin-resistant enterococci in Northeast Ohio. Clin Infect Bis 1999;29:573–579.Google ScholarPubMed
20.Maraki, S, Barbounakis, E, Chatzinikolaou, I, et al.Effects of cefepime, cefixime, and ceftibuten on murine gut colonization by Candida albicans. Chemotherapy 1998;44:405–408.Google Scholar
21.Hoyen, CK, Pultz, NJ, Paterson, DL, Aran, DC, Donskey, CJ. Effect of parenteral antibiotic administration on the establishment of intestinal colonization with extended-spectrum β-lactamase-producing Klebsiella pneumoniae in mice. Antimicrob Agents Chemother 2003;47:3610–3612.CrossRefGoogle ScholarPubMed
22.Patterson, JE, Hardin, TC, Kelly, CA, Garcia, RC, Jorgenson, JH. Association of antibiotic utilization measures and control of multiple-drug resistance in Klebsiella pneumoniae. Infect Control Hosp Epidemiol 2000;21:455–458.Google Scholar
23.Bhalla, A, Pultz, NJ, Ray, AJ, Hoyen, CK, Eckstein, EC, Donskey, CJ. Antianaerobic antibiotic therapy promotes overgrowth of antibiotic-resistant, gram-negative bacilli and vancomycin-resistant enterococci in the stool of colonized patients. Infect Control Hosp Epidemiol 2003;24:644–649.CrossRefGoogle ScholarPubMed
24.Paterson, DL, Ndirangu, M, Clarke, L, Bandlamuri, S, Donskey, CJ. Relative “collateral damage” caused by piperacillin/tazobactam and cefepime in patients treated in the intensive care unit. Presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Washington, DC. Abstract K-1418.Google Scholar
25.Thomas, C, Golledge, CL, Riley, TV. Ciprofloxacin and Clostridium difficile-associated diarrhea. Infect Control Hosp Epidemiol 2002;23:637–638.Google Scholar
26.Wistrom, J, Norrby, SR, Myhre, EB, et al.Frequency of antibiotic-associated diarrhoea in 2,462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother 2001;47:43–50.Google Scholar
27.Edlund, C, Nord, CE. Effect of quinolones on intestinal ecology. Drugs 1999;58(suppl 2):65–70.Google Scholar
28.Harbarth, S, Cosgrove, S, Carmeli, Y. Effects of antibiotics on nosocomial epidemiology of vancomycin-resistant enterococci. Antimicrob Agents Chemother 2002;46:1619–1628.Google Scholar
29.Donskey, CJ, Helfand, MS, Pultz, NJ, Rice, LB. Effect of parenteral fluoroquinolone administration on persistence of vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract. Antimicrob Agents Chemother 2004;48:326–328.CrossRefGoogle ScholarPubMed
30.Hecker, MT, Aron, DC, Patel, NP, Lehman, MK, Donskey, CJ. Unnecessary use of antimicrobials in hospitalized patients: current patterns of misuse with an emphasis on the antianaerobic spectrum of activity. Arch Intern Med 2003;163:972–978.Google Scholar
31.Stiefel, U, Pultz, NJ, Harmoinen, J, Koski, P, Lindevall, K, Donskey, CJ. Oral administration of recombinant β-lactamase prevents piperacillin-induced overgrowth of nosocomial pathogens in the intestinal tract of mice. J Infect Dis 2003;188:1605–1609.Google Scholar