Temocillin, in-vitro activity and the pharmacokinetics and tissue penetration in healthy volunteers

Abstract

The in-vitro activity of temocillin was studied using recent clinical isolates and its activity was compared with that of other agents. Temocillin was active against the Enterobacteriaceae (the MIC⁹⁰, being 2–8 mg/l) and the ranges of MICs for these strains were narrow. Temocillin was also active against Haemophilus influenzae and Neisseria gonorrhoeae. It was not active against Bacteroides fragilis, Staphylococcus aureus or Pseudomonas aeruginosa. The pharmacokinetics of temocillin were studied in six healthy male volunteers each receiving a 1 g dose as an intravenous bolus. Tissue penetration of the antibiotic was estimated using a cantharides blister method. The mean elimination half-life was about 4-5 h which is considerably longer than those of other penicillins. Temocillin penetrated the blister fluid rapidly and reached levels about 50% of those in serum by 2–3 h. Over a 12 h period the serum and blister fluid levels exceeded the MIC⁹⁰ of susceptible bacteria by about two-fold or greater suggesting that twice or even once daily dosing of temocillin may be sufficient.