The pharmacokinetics of temocillin was studied in 16 subjects with varying degrees of renal functional impairment. The subjects were divided into three groups, depending on their creatinine clearance: Group A greater than 70 ml/min/1.73 m2; Group B 20-70ml/min/1.73 m2 and Group C less than 20 ml/min/1.72 m2. Following intravenous administration the total serum clearance of temocillin was reduced in patients with renal insufficiency. The distribution of temocillin into the tissues was not affected by renal dysfunction, apparent distribution volumes being 15.11, 16.01 and 13.81 in Groups A, B and C respectively. The change in clearance was reflected in an increased area under the serum concentration versus time curve from 418 mg h/l in Group A to 1301 mg h/l and 1553 mg h/l in Groups B and C respectively. The beta elimination half-life was also prolonged from 3.5 h in Group A 12.7 h in Group B and 17.5 h in Group C. The urinary excretion of temocillin was both delayed and reduced according to the extent of kidney damage. The reduction in temocillin clearance was proportional to the extent of reduction from normal of the clearance of creatinine. This relationship has been used to suggest dosage schedules for temocillin in patients with renal insufficiency.

The minimal inhibitory concentration of temocillin (BRL 17421) against 476 clinical isolates was determined by an agar dilution method. Temocillin was active against most of the Enterobacteriaceae, Haemophilus, and Neisseria strains tested. The compound showed low activity or was inactive against Bacteroides, Campylobacter, Acinetobacter, Pseudomonas, and Staphylococcus aureus strains. Within each species, individual strains showed a high degree of uniformity in their susceptibility to temocillin; the drug concentrations that inhibited the growth of 90% of organisms were the same or close to those which inhibited the growth of 50% of organisms. In contrast, the same strains showed a very wide range of susceptibility to the other antibiotics tested, including third-generation cephalosporins. Against strains of Enterobacteriaceae highly susceptible to thirdgeneration cephalosporins, temocillin was considerably less active than cefotaxime, ceftazidime, and moxalactam, although it was more active than cefazolin and piperacillin. Against certain strains of Enterobacter and Citrobacter resistant to third-generation cephalosporins, temocillin was more active than cefotaxime and ceftazidime. An increase in the inoculum size did not alter the activity of temocillin, indicating that the compound has high stability to ,-lactamases. The minimal lethal concentration was also very similar to the minimal inhibitory concentration when an inoculum of 105 colony-forming units was used.Temocillin (BRL 17421) is a new semisynthetic ,3-lactam antibiotic that is highly stable to the bacterial P-lactamases and is active against most Enterobacteriaceae, Haemophilus, and Neisseria strains (3, 4). We investigated the in vitro activity of temocillin and compared it with the activities of cephalothin, cefotaxime, ceftazidime, moxalactam, and piperacillin against a wide range of recent clinical isolates.

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