Study of the influence of protein binding on serum bactericidal titres and killing rates in volunteers receiving ceftazidime, cefotaxime and ceftriaxone.

The influence of protein binding on anti-staphylococcal activity of cefotaxime, ceftazidime and ceftriaxone was evaluated using an ex vivo cross-over study in human volunteers. Serum inhibitory and bactericidal titres were measured using samples collected 1 h and 6 h after infusion of 2 g of cefotaxime and ceftazidime and 1 g of ceftriaxone. Time-kill curves were done using the same samples. Twelve strains of Staphylococcus aureus were studied including six capsulated strains of known capsule types. Two media were compared: Mueller-Hinton and 'capsule' medium. The MICs and MBCs of oxacillin-susceptible strains measured in capsule medium were higher than in Mueller-Hinton, hence the higher serum inhibitory and bactericidal titres in the latter medium. The effect of protein binding was evaluated, using the difference between expected serum titres, from serum concentration and MICs or MBCs measured in serum-free medium, and the area under the time-kill curve corrected for the serum concentration and the sensitivity of the strains. The anti-staphylococcal activity of ceftriaxone was markedly affected by its strong protein binding.