Biological inactivation by faeces of antimicrobial drugs applicable in selective decontamination of the digestive tract

Abstract

The in-vitro inactivation of seven antimicrobial drugs by human faecal substance has been investigated. Nalidixic acid, colistin, neomycin, tobramycin, temocillin, trimethoprim, and aztreonam were separately mixed in graded concentrations with faecal suspensions prepared from faeces of eight healthy volunteers. Each was mixed separately with a sample of each of the eight suspensions. All seven antimicrobial drugs appeared to be rapidly biologically inactivated by intestinal contents in a dose-dependent fashion, although not all to the same extent. The results may explain why with some unabsorbed or minimally absorbed drugs higher oral doses are required to achieve eradication of Gram-negative bacilli from the digestive tract than others, when selective decontamination (SD) is attempted in clinical practice.

Effect of broad-spectrum parenteral antibiotics on composition of intestinal microflora of humans

“…The high concentrations of cefoperazone were not related to unusual stability of this drug in the stool; indeed, cefoxitin was the most.stable and aztreonam was the next most stable drug in the feces, whereas piperacillin and cefoperazone were degraded by more than 99% in 24 h. Others have reported aztreonam to be fairly stable in feces (29).…”

Effects of Exposure of Clostridium difficile PCR Ribotypes 027 and 001 to Fluoroquinolones in a Human Gut Model

“…Following fluoroquinolone instillation, the antibiotic concentrations achieved in vessels 2 and 3 were often markedly lower than those achieved in vessel 1. This may be due to antibiotic inactivation by components of the normal flora or binding of the antimicrobial to fecal material, which has previously been demonstrated for other fluoroquinolones (17,49). Previous investigations into the inactivation of antimicrobial agents, including nalidixic acid, neomycin, and trimethoprim, found evidence of rapid biological inactivation by intestinal contents (49).…”

Colonization resistance

“…For example, pefloxacin reaches high concentrations in feces, although it is almost completely absorbed (22,58,59). Conversely, extensive inactivation may cause in feces unexpectedly low levels of activity of drugs that are poorly absorbed (25,55,56). It is therefore of major interest that more data on the active concentration of antimicrobial agents in the bowel be obtained.…”

“…Antibiotics are inactivated to a variable extent in the intestines by decomposition (15,29,52) or binding (25,55,56). The remaining activities of many antimicrobial agents are sufficiently high to disrupt the ecological balance of the microbial flora in the bowel.…”