The non-enzymatic inactivation of thirteen ß-lactam antibiotics in human faeces

In order to obtain a method that could predict the in vitro inactivation of an antibiotic in the digestive tract, the non-enzymatic inactivation of 13 beta-lactam antibiotics by human faeces was investigated. Benzylpenicillin, amoxicillin, amoxicillin/clavulanate, cloxacillin, piperacillin, temocillin, cefuroxime, cefamandole, cephradine, cefotaxime, ceftazidime, aztreonam and imipenem were mixed in six graded concentrations with faecal suspensions of 30 healthy volunteers. After incubation the remaining antimicrobial activity was measured by means of a serial dilution method. A relationship between the initial antibiotic concentration (Aia) and the remaining antimicrobial activity after incubation (Asd) was derived, namely: Asd = 1/2[(Aia-K-F)+square root ((Aia-K-F)2 + 4 K Aia)]. The parameters K and F represent the intrinsic dissociation constant and the amount of available bindingsites in the faeces, respectively. Asd values were predicted with a reasonable degree of accuracy for all thirteen antibiotics. Dissociation constants differed significantly between the penicillins and the cephalosporins but F- values did not differ between cephalosporins and penicillins.