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Metronizadole has a similar effect on enteric biota, suppressing anaerobic microorganisms so that VRE faces less competition.⁴ A previous study also concluded that antimicrobials with high activity against strict anaerobic bacteria, such as metronizadole, led to higher density populations of VRE in the gastrointestinal tract than antimicrobials with minimal activity against anti-anaerobic bacteria.⁵

This study also stated that the inhibition of competitive intestinal microorganisms allows the VRE to overpopulate the gastrointestinal tract.

In 2005, during the investigation of an outbreak of VRE infections in a hematology ward in a Greek hospital, epidemiologic genetic analysis indicated that the bacteria were being spread patient to patient, healthcare worker to patient, or by inanimate objects.⁶

A total of 465 rectal swabs from 370 patients and 106 environmental specimens throughout the hospital were screened for VRE. One environmental specimen was positive as was 73 rectal specimens from 53 (14.3 percent) patients. All VRE isolates were identified as E. faecium containing the vanA gene. Six of the isolates were identified as linezolid and vancomycin resistant E. faecium (VLRE).

The researchers found that patients who had received either an aminoglycoside or a carbepenem were at increased risk for VLRE compared to VRE-negative controls.

Increased Risk of Infection
VRE are a significant cause of hospital acquired infections. The establishment of VRE in healthcare facilities and patients is dependent on several factors, including exposure to VRE reservoirs, host factors and use of antimicrobial agents.

Studies have shown that the use of antimicrobial agents to treat other bacterial infections can increase the risk of colonization by VRE and lead to a higher population density of the bacteria in the gastrointestinal tract, although, the exact mechanism of this process is open to speculation. The gastrointestinal tract of animals normally contains thousands of species of commensal bacteria, the majority being strict anaerobes. Antimicrobial therapy leads to the suppression of the natural intestinal biota, allowing malevolent microorganisms to colonize and invade the intestinal tract.

It has been theorized that the commensal bacteria compete with the more pathogenic bacteria for space and nutrients. In addition, it is possible that the commensal bacteria release compounds that inhibit the pathogenic species.

An alternative hypothesis is that normal biota indirectly contributes to inhibiting VRE colonization by activating mucosal innate immune defenses.⁷ It was demonstrated that antimicrobial treatment of mice down-regulated the expression of RegIIIc, a lectin that is capable of killing gram-positive bacteria including VRE. The down-regulation of RegIIIc resulted in markedly decreased killing of VRE in the intestines of antimicrobial treated mice.

Colonization by pathogenic bacteria after suppression of normal biota can result in the invasion of tissue or the blood stream, especially in patients with other underlying health problems. This invasion can cause a septicemia and lead to serious illness or death.

Studies have indicated that carbapenam, cephalosporins and metronizadole therapy, in particular, increase the likelihood of colonization by VRE.  This is not to say, however, that these drugs should not be used to treat infections. It is possible that replacing these agents with others could select for different antimicrobial resistant bacteria more dangerous than VRE.  In contrast, beta-lactam-beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, have been rarely associated with VRE colonization and infection.^{8, 9, 10}

Angela Welsh is a senior student and Donald Lehman is an associate professor in the Department of Medical Technology at the University of Delaware, Newark, DE.

References

1. Farley, J.  Vancomycin Resistant Enterococcus. Available at: www.hopkinsmedicine.org/heic/ID/vre. Last accessed Apr. 30, 2012.
2. Ubeda C, Taur Y, Jenq R, et al. 2010. Vancomycin resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J  Clinical Invest, 120:4332-4341.
3. Tacconelli E, De Angelis G, Cataldo M, et al. 2009. Antibiotic usage and risk of colonization and infection with antibiotic-resistant bacteria: a hospital based population study. Antimicrobial Agents Chemother, 53:4264-4269.
4. Carmeli Y, Eliopoulos G, Samore M. 2002. Antecedent treatment with different antibiotic agents as a risk factor for vancomycin resistant Enterococcus. Emerg Infect Dis, 8:802-807.
5. Donskey CJ, Chowdhry TK, Hecker MT, et al. 2000. Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients. New England Journal Med. 343:1925-1932.
6. Soulia M, Sakkaa V, Galania I, et al. 2009. Colonisation with vancomycin- and linezolid-resistant Enterococcus faecium in a university hospital: molecular epidemiology and risk factor analysis. Intl J Antimicrobial Agents, 33:137-142.
7. Brandi K, Plitas G, Mihu CN, et al. 2008. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature, 455:804-807.
8. DiNubilea MJ, Friedlanda IR, Chan CY, et al. 2007. Bowel colonization with vancomycin-resistant enterococci after antimicrobial therapy for intra-abdominal infections: observations from 2 randomized comparative clinical trials of ertapenem therapy. Diag Microbiol Infect Dis, 58:491-494.
9. Kritsotakis EI, Christidou A, Roumbelaki M, et al. 2008. The dynamic relationship between antibiotic use and the incidence of vancomycin-resistant Enterococcus: time-series modeling of 7-year surveillance data in a tertiary-care hospital. Clin Microbiol Infect, 14:747-754.
10. Paterson DL, Muto CA, Ndirangu M, et al. 2008. Acquisition of rectal colonization by vancomycin-resistant Enterococcus among intensive care unit patients treated with piperacillin-tazobactam versus those receiving cefepime-containing antibiotic regimens. Antimicrobial Agents Chemother, 52:465-469.