The non-enzymatic inactivation of thirteen beta-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.
Jansen
G
G
Laboratory of Medical Microbiology, University of Groningen, The Netherlands.
Weissing
F
F
de Vries-Hospers
H
H
Tonk
R
R
van der Waaij
D
D
D000327:Adsorption; D000328:Adult; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D005243:Feces; D005260:Female; D006801:Humans; D008297:Male; D008433:Mathematics; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams