Effects of six antimicrobial drugs on rat intestinal flora: is the rat model of predictive value in clinical practice?

The effects of six antimicrobial agents on rat intestinal microflora after oral and/or parenteral administration were studied in parallel. Antimicrobial drugs were administered by the oral (norfloxacin, pefloxacin, ciprofloxacin) and parenteral routes (pefloxacin, imipenem, aztreonam, teicoplanin) at the doses used in clinical practice. Faecal specimens were collected before and after two, four, seven or 11 treatments. Qualitative and quantitative determination of flora composition was performed using a modified version of standard methods. Fluoroquinolones reduced the levels of enterobacteria, while gram-positive bacteria (enterococci, staphylococci, lactobacilli) were little affected. Comparable effects were observed after intraperitoneal and oral administration of pefloxacin. The changes induced by fluoroquinolones on intestinal flora showed a uniform trend: certain differences may be ascribed to different pharmacokinetic properties such as bioavailability and metabolism. Imipenem caused a significant decrease in mean concentrations of E. coli, clostridia and fungi. Aztreonam induced a prompt and marked inhibition of E. coli and Proteus spp., while prolonged treatment induced an overgrowth of fungi and bacteroides. Teicoplanin caused a significant decrease in the levels of clostridia and anaerobic lactobacilli. Irregular concentrations of all drugs, with great intersubject variability, were detected at different times. These results are comparable to those observed in humans. The potential of an antimicrobial agent to change the intestinal microflora is related to its antibacterial activity, route of administration and pharmacokinetic properties. The parenteral route induced changes in the intestinal ecosystem, as did oral administration. The rat appears to be a useful experimental model for studying the effects of antimicrobial drugs on intestinal flora.