Antibiotic Selection of Escherichia coli Sequence Type 131 in a Mouse Intestinal Colonization Model

Abstract

The ability of different antibiotics to select for extended-spectrum ␤-lactamase (ESBL)-producing Escherichia coli remains a topic of discussion. In a mouse intestinal colonization model, we evaluated the selective abilities of nine common antimicrobials (cefotaxime, cefuroxime, dicloxacillin, clindamycin, penicillin, ampicillin, meropenem, ciprofloxacin, and amdinocillin) against a CTX-M-15-producing E. coli sequence type 131 (ST131) isolate with a fluoroquinolone resistance phenotype. Mice (8 per group) were orogastrically administered 0.25 ml saline with 10 8 CFU/ml E. coli ST131. On that same day, antibiotic treatment was initiated and given subcutaneously once a day for three consecutive days. CFU of E. coli ST131, Bacteroides, and Gram-positive aerobic bacteria in fecal samples were studied, with intervals, until day 8. Bacteroides was used as an indicator organism for impact on the Gram-negative anaerobic population. For three antibiotics, prolonged colonization was investigated with additional fecal CFU counts determined on days 10 and 14 (cefotaxime, dicloxacillin, and clindamycin). Three antibiotics (cefotaxime, dicloxacillin, and clindamycin) promoted overgrowth of E. coli ST131 (P < 0.05). Of these, only clindamycin suppressed Bacteroides, while the remaining two antibiotics had no negative impact on Bacteroides or Gram-positive organisms. Only clindamycin treatment resulted in prolonged colonization. The remaining six antibiotics, including ciprofloxacin, did not promote overgrowth of E. coli ST131 (P > 0.95), nor did they suppress Bacteroides or Gram-positive organisms. The results showed that antimicrobials both with and without an impact on Gram-negative anaerobes can select for ESBL-producing E. coli, indicating that not only Gram-negative anaerobes have a role in upholding colonization resistance. Other, so-far-unknown bacterial populations must be of importance for preventing colonization by incoming E. coli.

Isolation and Characterization of Escherichia coli Sequence Type 131 and Other Antimicrobial-Resistant Gram-Negative Bacilli from Clinical Stool Samples from Veterans

“…To the extent that traits regarded conventionally as associated with extraintestinal VGs also promote gut colonization (27), the abundance and distinctive combinations of VGs present in ST131 may confer enhanced fitness in the intestinal niche, thereby potentially contributing to ST131's epidemiological success (28,29).…”

Impact of Ceftiofur Injection on Gut Microbiota and Escherichia coli Resistance in Pigs

“…Few studies have reported the impact of cephalosporins on microflora. In a mouse intestinal colonization model, cefotaxime, given subcutaneously once a day for 3 days, has no impact on Bacteroides or aerobic Gram-positive flora evaluated using culture methods (29).…”

Systematic analysis of the relationship between antibiotic use and extended-spectrum beta-lactamase resistance in Enterobacteriaceae in a French hospital: a time series analysis

“…The association between tetracycline use and ESBL resistance, as previously described for other antibiotics, may be mediated by transferable multidrug resistance plasmids [27]. The association between lincosamide use and ESBL resistance is supported by case-control and experimental studies [14,15,28]. Incidentally, clindamycin has also been reported to promote carbapenemase-producing K. pneumoniae carriage in a murine model, and its use has been associated with vancomycin resistance in Enterococcus spp.…”

“…However, these results have to be confirmed. Considering the number of antibacterial agents that may promote ESBL resistance, a systematic analysis of the link between ESBL resistance and consumption of most antibiotics used in the hospital is necessary [15]. Our objective was to explore the association between ESBL incidence and hospital use of various classes of antibacterial agents.…”