Antibiotics and VRE transmission

Antibiotics may increase the likelihood of transmission of VRE by their effect on patients colonized with VRE. Most importantly, fecal incontinence or diarrhea in VRE carriers may cause environmental contamination with VRE. Unfortunately, few studies have examined the question of which classes of antibiotics are more likely to increase VRE transmission in the hospital setting. VRE can be isolated from the stool of healthy adults and hospitalized patients during vancomycin therapy. Parenteral vancomycin treatment does not eliminate all gram-positive cocci in the oral and fecal microbiota and may increase the intestinal VRE load in VRE carriers. This may also facilitate VRE transmission, since the number of VRE in a given clinical sample is proportional to the ease with which VRE is transmitted to other body sites or to another patient .

First, most of the commonly used antibiotics in hospitals (cephalosporins fluoroquinolones, extended spectrum penicillins, aminoglycosides) have little or no activity against enterococcal strains, and even less so resistant strains. Moreover, E. faecium generally expresses higher MICs to β-lactam antibiotics than E. faecalis and therefore has advantages in an environment where these agents are widely used. Second, colonization can be promoted by antibiotic inhibition of other bacteria (such as intestinal anaerobes) that compete with enterococci for colonization niches. An association between antibiotic use and colonization and infection with resistant enterococci has been supported by a large number of studies over the years. Long duration of antibiotic therapy, use of multiple antibiotics and single use of vancomycin, third-generation cephalosporins, imipenem and antianaerobic antibiotics have all been found to be risk factors. Oral vancomycin and particularly teicoplanin administration strongly selected for VRE in the fecal microbiota of healthy volunteers.

Vancomycin use has frequently been pointed out as the most important risk factor for the emergence of VRE in hospitals. However, to blame the use of one single antibiotic class for the emergence of antimicrobial resistance is probably a simplification In 2001, use of both vancomycin and third generation cephalosporins were reported to be independently associated with increased prevalence of VRE in 126 U.S. intensive care units. Recently, a meta-analysis of U.S. studies, performed before 1996, and reporting an association between vancomycin use and VRE infection and colonization was carried out. When adjusted for publication bias, confounding by length of stay and the selection of wrong control groups, vancomycin was no longer significantly associated with VRE.

The duration of vancomycin-resistant enterococcal carriage varies among studies, which have often differed in terms of the selective mediums used, sensitivity, and definition of clearance. Nonetheless, some patients have persistent colonization, occasionally for years, whereas others have persistently negative cultures. Other patients intermittently have stools positive for the same strain; some who have had positive and then multiple negative cultures have later had positive cultures of their original strain, a finding that suggests that the organism had been present all along in very low numbers. Among patients with cancer who had gastrointestinal colonization and were discharged from the hospital , percent were still positive for vancomycin-resistant enterococci on readmission an average of 2.5 weeks later.

In a long-term care facility, spontaneous clearance (defined as two consecutive negative cultures at least 2 weeks apart) of vancomycin-resistant enterococci from the gastrointestinal tract was less rapid (median, more than 100 days) in patients who received antibiotics after the identification of colonization than in those who had not (median, 67 days).

These results are consistent with studies showing that colonization of animals by human vancomycin-resistant enterococcal strains was more easily established after the administration of vancomycin or other antibiotics and that the continuation of antibiotics caused persistence of VRE.

Reports of the use of oral bacitracin with or without gentamicin or a tetracycline suggest that these drugs are not particularly successful for decolonization .

Although some have reported high rates of suppression of vancomycin-resistant enterococci, particularly with high doses of bacitracin (50,000 to 75,000 units four times daily), with subsequent recrudescence after therapy has ended, suppression has not been a consistent finding.

Although it may not be unreasonable to consider a drug like bacitracin for a high-risk patient who has fecal colonization with vancomycin-resistant enterococci, current data do not support widespread therapy to prevent infection by or the spread of these organisms. Another drug undergoing phase 3 trials for the elimination of colonization with vancomycin resistant enterococci is ramoplanin .