Influence of Low Dose Ciprofloxacin on Microbial Colonization of the Digestive Tract in Healthy Volunteers During Normal and During Impaired Colonization Resistance

Abstract

Ciprofloxacin in low doses is, in volunteers, effective for decontaminating the digestive tract [elimination of aerobic Gram-negative bacilli (GNB)] without disturbing colonization resistance. Before using this concept in neutropenic patients, we investigated if a low dose quinolone is still effective when the colonization resistance is disturbed by another antimicrobial agent. Ciprofloxacin 20 mg daily was effective in eliminating Gram-negative bacilli from the digestive tract in 4/5 volunteers, in 1 volunteer the GNB persisted in low concentration. No colonization with exogenous resistant GNB occurred. Following impairment of colonization resistance by addition of clindamycin 300 mg daily, 3/5 volunteers became colonized by spontaneously acquired exogenous GNB resistant to ciprofloxacin. We conclude that selective decontamination with a quinolone in low dosage cannot be recommended in neutropenic patients because there is, in the case of disturbed colonization resistance, a real risk of acquisition of quinolone-resistant strains.

Ciprofloxacin at low levels disrupts colonization resistance of human fecal microflora growing in chemostats

“…An increased incidence of resistance to CI in E. coli has been seen by some (Borzio et al, 1997;Carman and Woodburn, 2001;Terg et al, 1998;Wistrom et al, 1992) but not in all studies (Bergan et al, 1986;Gismondo et al, 1995;Pecquet et al, 1990;van de Leur et al, 1997). Had there been already resistant E. coli strains in our fecal inoculum, we might have expected to see overgrowth of these strains in the presence of CI and a parallel retention of colonization resistance to less resistant S. kedougou.…”

“…This result has been confirmed since many times since for both oral and intravenous CI (Bergan et al, 1986;Enzensberger et al, 1985;Holt et al, 1986;Krueger et al, 1997Krueger et al, , 1999Ljungberg et al, 1990;Maijer-Severs et al, 1990;Pecquet et al, 1990;Tillonen et al, 1999;van de Leur et al, 1997;van Saene et al, 1988), in healthy infants (Ljungberg et al, 1990) and in patients (Borzio et al, 1997;Brismar et al, 1990;Esposito et al, 1987a,b;Rozenberg-Arska et al, 1985;Terg et al, 1998). The response has been reproduced in healthy rats (Beneni and Minelli, 1995;Nosova et al, 1999;Peltonen and Eerola, 1992), in human flora associated mice (Gismondo et al, 1995) and in chemostats (Bernhardt et al, 1998;Carman and Woodburn, 2001).…”

“…For each model (human, rodent, human flora associated rodent, and chemostat) we can consider the lowest reported test dose and the effects it elicited. van de Leur et al (1997) gave healthy volunteers 20 mg/d or for a 60 kg person, about 0.33 mg/kg/d. It led to the elimination of E. coli in 4 of 5 individuals.…”

Longitudinal Trends in Fluoroquinolone Resistance among Enterobacteriaceae Isolates from Inpatients and Outpatients, 1989–2000: Differences in the Emergence and Epidemiology of Resistance across Organisms

“…It is possible that the antianaerobic activity of clindamycin, by eliminating indigenous gastrointestinal (GI) tract bacterial colonization, might favor subsequent GI colonization with more-resistant bacteria. In fact, volunteer studies have noted that clindamycin use markedly increases the likelihood of GI colonization with FQ-resistant E. coli following FQ use [12].…”

Effects of Antibiotics on Gut Microbiota

“…The following effects on gut microbiota have been observed after treatment with frequently used antibiotics: treatment with fluoroquinolones, such as ciprofloxacin results in a strong reduction in aerobic Gram-negative bacilli without relevant compensatory colonization of Gram-positive bacteria or yeast [44,45]. The reduction of about one third of the taxa is highly variable across individuals and usually restored within 4 weeks after antibiotic treatment [12] but bares a relevant risk of developing quinolone-resistant strains in feces.…”