Thein vitro inactivation of thirteen β-lactam antibiotics by other mechanisms than adsorption to faecal substance

Abstract

We have investigated the antibiotic inactivating capacity of intestinal contents in vitro in faeces. In the presently reported study the influence of beta-lactamase catalyzed hydrolysis on the antimicrobial activity of 13 commonly used beta-lactam antibiotics was investigated, while the influence of non-specific adsorption of antibiotics to faecal compounds was also taken into account. The following antibiotics were tested: benzylpenicillin, amoxicillin, amoxicillin/clavulanate, cloxacillin, piperacillin, temocillin, cefuroxime, cefamandole, cephradine, cefotaxime, ceftazidime, aztreonam and imipenem. Faecal samples were obtained from 30 healthy volunteers. Six different concentrations of each antibiotic were added to 1 g of faeces. After 24 h of incubation at 37 degrees C the remaining amount of active antibiotic was determined by means of a "growth inhibition assay". The contribution to the test results of non-specific adsorption to macromolecules was calculated by means of a model and the inactivation data were subsequently corrected. The amount of antibiotic non-specifically bound to faecal macromolecules varied from 0% to 80% of the amount of antibiotic initially added to the faeces. A considerable difference was found in the degree of inactivation of several antibiotics. However, in contrast to earlier investigations, the results of this study show that in a normal population the influence of beta-lactamase catalyzed hydrolysis on the activity of beta-lactam antibiotics is apparently very small when compared to the influence of non-specific adsorption of beta-lactam antibiotics to faecal compounds.

Removal of ciprofloxacin in simulated digestive media by activated charcoal entrapped within zinc-pectinate beads

“…Incomplete absorption of orally administered drugs, secretion of an antimicrobial agent by intestinal mucosa, salivary glands and bile can actually disturb the colonisation resistance of commensal colonic flora which give rise to the emergence of resistance to antibiotics by the indirect two-steps process described above (de Vries-Hospers et al, 1993). In this context, it is hypothesised that colonic inactivation of residual antibiotics can be a solution to maintain the stability of the intestinal microflora.…”

“…Nevertheless, as new antibiotics were being made available on a regular basis, it was not considered a major public health problem until the last decade (Okeke et al, 2005a,b). Indeed, as experience has shown, new antibiotics may be effective for a restricted period only and resistance appears sooner or later to each new drug mainly in relation with both their misuse and overuse in humans and animals (de Vries-Hospers et al, 1993). Emergence of resistance in bacteria can result from two different sequences of events, including either a direct one-step selection of resistant clones at the site of infection, or an indirect two-steps process in which commensal resistant bacteria are first selected in the natural ecosystems of humans.…”

“…In this context, it is hypothesised that colonic inactivation of residual antibiotics can be a solution to maintain the stability of the intestinal microflora. Antibiotics inactivation can be achieved enzymatically as well as non-enzymatically (Welling et al, 1992;de Vries-Hospers et al, 1993). To deliver inactivating agent to the colon, it is possible to use bacteria responsive systems that allow site-specific targeting (Bourgeois et al, 2005a,b For this purpose, we have designed beads made of pectin, a natural polysaccharide that can be enzymatically degraded by enzymes produced by colonic microflora (Sinha and Kumria, 2001;Vandamme et al, 2002).…”

Bovine Intestinal Bacteria Inactivate and Degrade Ceftiofur and Ceftriaxone with Multiple β-Lactamases

“…The chromosomal ampC gene has traditionally been considered the predominant ␤-lactamase in bacteria from animals that have not been treated with antibiotics (37), but it is not clear whether natural selection resulting from antibiotic use is really responsible for dissemination of mobile resistance genes (46). Additional mechanisms that inactivate ceftiofur without degradation of the drug molecule may exist in bovine intestinal tracts, such as adsorption to bacteria and fecal molecules (11). In fact, adsorption of drug, instead of ␤-lactamase activity, was the major inactivation mechanism in human feces in the 1993 study (11).…”

“…Additional mechanisms that inactivate ceftiofur without degradation of the drug molecule may exist in bovine intestinal tracts, such as adsorption to bacteria and fecal molecules (11). In fact, adsorption of drug, instead of ␤-lactamase activity, was the major inactivation mechanism in human feces in the 1993 study (11).…”