Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients

Abstract

Background: Colonization and infection with vancomycin-resistant enterococci have been associated with exposure to antibiotics that are active against anaerobes. In mice that have intestinal colonization with vancomycin-resistant enterococci, these agents promote high-density colonization, whereas antibiotics with minimal antianaerobic activity do not.

Methods: We conducted a seven-month prospective study of 51 patients who were colonized with vancomycin-resistant enterococci, as evidenced by the presence of the bacteria in stool. We examined the density of vancomycin-resistant enterococci in stool during and after therapy with antibiotic regimens and compared the effect on this density of antianaerobic agents and agents with minimal antianaerobic activity. In a subgroup of 10 patients, cultures of environmental specimens (e.g., from bedding and clothing) were obtained.

Results: During treatment with 40 of 42 antianaerobic-antibiotic regimens (95 percent), high-density colonization with vancomycin-resistant enterococci was maintained (mean [+/-SD] number of organisms, 7.8+/-1.5 log per gram of stool). The density of colonization decreased after these regimens were discontinued. Among patients who had not received antianaerobic antibiotics for at least one week, 10 of 13 patients who began such regimens had an increase in the number of organisms of more than 1.0 log per gram (mean increase, 2.2 log per gram), whereas among 10 patients who began regimens of antibiotics with minimal antianaerobic activity, there was a mean decrease in the number of enterococci of 0.6 log per gram (P=0.006 for the difference between groups). When the density of vancomycin-resistant enterococci in stool was at least 4 log per gram, 10 of 12 sets of cultures of environmental specimens had at least one positive sample, as compared with 1 of 9 sets from patients with a mean number of organisms in stool of less than 4 log per gram (P=0.002).

Conclusions: For patients with vancomycin-resistant enterococci in stool, treatment with antianaerobic antibiotics promotes high-density colonization. Limiting the use of such agents in these patients may help decrease the spread of vancomycin-resistant enterococci.

Figure 1

The Effect of Antibiotic Therapy on the Numbers of Vancomycin-Resistant Enterococci and the Total Number of Aerobic and Facultative Gram-Negative Bacilli in Stool Samples from a 57-Year-Old Man with Cirrhosis Resulting from Hepatitis C. Six weeks before entering the study, the patient received a course of oral clindamycin; two weeks before entering the study, he received a course of oral ciprofloxacin. Five weeks after the study began, he received two days of oral clindamycin prophylactically before having teeth extracted at a time when he was doing well in the nursing home unit.

Figure 2

Effect on the Density of Vancomycin-Resistant Enterococci in Stool of Therapy with Antianaerobic-Antibiotic Regimens in 13 Patients and Regimens of Antibiotics with Minimal Antianaerobic Activity in 10 Patients. A selected isolate from each study patient demonstrated a high level of resistance to vancomycin (minimal inhibitory concentration, >60 μg per milliliter) and ampicillin (minimal inhibitory concentration, >256 μg per milliliter). Isolates from patients who received ciprofloxacin or levofloxacin as part of a regimen of antibiotics with minimal antianaerobic activity had a high level of resistance to ciprofloxacin in vitro (minimal inhibitory concentration, >100 μg per milliliter) but not to levofloxacin (minimal inhibitory concentration, >10 μg but <100 μg per milliliter). Isolates from the two patients who received trimethoprim–sulfamethoxazole were resistant to this agent in vitro. All antibiotics were given intravenously unless the route is designated as oral.

Figure 3

Effect of Therapy with Antianaerobic-Antibiotic Regimens and Regimens of Antibiotics with Minimal Anti-anaerobic Activity on the Density of Vancomycin-Resistant Enterococci in Stool Samples from a 69-Year-Old Male Nursing Home Resident with a History of Cerebrovascular Accidents. The patient initially received an antianaerobic-antibiotic regimen consisting of intravenous meropenem and vancomycin for 17 days, beginning in week 1. He then received a regimen of antibiotics with minimal antianaerobic activity: oral trimethoprim–sulfamethoxazole (TMP-SMX) for five days, beginning in week 10, followed by oral levofloxacin (Levo) for three days. The third regimen consisted of a combination of the two types of antibiotics: intravenous piperacillin–tazobactam (P-T) and cefepime (C) was given for 8 days, followed by oral ciprofloxacin (Cipro) for 10 days. The fourth regimen consisted of intravenous vancomycin — an antianaerobic antibiotic — for 14 days. Cultures of environmental specimens obtained from the patient’s bedside table and bed linen were positive during week 20, whereas cultures of specimens from the patient’s gown and bedrail were negative. Cultures of all four types of environmental specimens obtained during week 24 and week 27 were negative. The patterns on pulsed-field gel electrophoresis of three isolates obtained from stool cultures and an isolate obtained from the culture of an environmental specimen were identical. Vancomycin-resistant enterococci were detectable in all samples.