Effect of antibiotics eliminated by first order kinetics

We wanted to simulate the conditions within the body where bacteria are exposed to antibiotics at concentrations which diminish exponentially and thus do not remain constant as in the usual test systems for determination of the minimum inhibitory or bactericidal concentrations (MIC, MBC). For this purpose we employed a model with a glass chamber containing a constant volume of culture which was supplied continuously with medium at a constant rate. We studied the pattern of bacterial response using a series of bactericidal and bacteriostatic agents added to the system at various multiples of the MIC of several bacterial strains, and using different rates of elimination of the antibacterial agent. Strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes were exposed to amoxicillin, ampicillin, benzylpenicillin, carbenicillin, cefazolin, chloramphenicol, flucloxacillin, gentamicin, or oxytetracyclin. The bacteria were killed or maintained at their initial density depending on the antibiotic and its concentration. The main findings were: for most drugs drop in bacterial number persisted while the concentration of the chamber remained above MIC, a period of time elapsed before recovery and bacterial multiplication resumed at the same rate as in control cultures, the period of antibacterial postantibiotic effect lasted longer with Gram-positive than with Gram-negative species, the point in time when the bacteria resumed multiplication corresponded to the IC50. We observed only minor differences in the pattern of bacteria during exposure to potentially bactericidal agents compared to antibiotics with mainly bacteriostatic effects.