Relation between the therapeutic efficacy of imipenem in an experimental infection in granulocytopenic mice and its effect on murine intestinal microbial ecology.
A study was performed to assess the effect of parenteral administration of imipenem on the intestinal microbial ecology of mice in relation to the therapeutic efficacy of the drug. The therapeutic effect of imipenem was assessed in a short-term experimental thigh muscle infection with Escherichia coli in irradiated mice. The maximum antibacterial effect of imipenem was approached at a single dose of 80 mg/kg. At this dose of imipenem the number of viable E. coli in the thigh muscle decreased from 9 x 10(6) to 4 x 10(5), whereas in untreated controls this number increased from 9 x 10(6) to 2 x 10(8). Daily administration of a dose of 80 mg/kg imipenem caused significant changes in the intestinal flora of conventional mice, despite the low concentrations of the drug (about 1 mg/kg) found in the caecum 30 min after infection of this dose. These changes consisted of an increase in the number of E. coli and enterococci and a decrease in the number of Staphylococcus aureus in the faeces. Furthermore, at this dose of imipenem, the number of Candida albicans recovered from the faeces after oral contamination with this organism was increased. We conclude from these animal experiments that the use of imipenem in high doses causes ecological changes in the intestinal bacterial flora with the potential to promote colonization by candida.
van Ogtrop
M L
ML
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Mattie
H
H
Guiot
H F
HF
van Furth
R
R
D000818:Animals; D015377:Cilastatin / Q000494:pharmacology* / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D015169:Colony Count, Microbial; D004338:Drug Combinations; D004927:Escherichia coli Infections / Q000188:drug therapy*; D015378:Imipenem / Q000494:pharmacology* / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007422:Intestines / Q000382:microbiology*; D008297:Male; D051379:Mice; D009135:Muscular Diseases / Q000188:drug therapy / Q000382:microbiology; D013047:Specific Pathogen-Free Organisms; D013848:Thigh
D004338:Drug Combinations; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination