Temocillin

Summary

Temocillin, a 6-α-methoxy penicillin derivative, was tested in vitro against 516 recent clinical isolates of Enterobacteriaceae. The compound exhibited good antibacterial activity, with 95% of isolates inhibited by a range 2 to 16 mg/L. Further studies, against selected isolates resistant to ticarcillin, piperacillin and cefuroxime (Klebsiella oxytoca, 25; Enterobacter species, 34; and Citrobacter species, 5), showed about half of the isolates of K. oxytoca (11/25) to be resistant to aztreonam (MIC range 16-⩾128 mg/L), but susceptible to temocillin, cefotaxime and latamoxef In general, the resistant strains of Enterobacter species tested were not susceptible to cefotaxime (MIC range 16–128 mg/L), or aztreonam (MIC range 1.0–64 mg/L), and many exhibited reduced susceptibility to latamoxef (MIC range 2–128 mg/L). In contrast, all the strains were susceptible to temocillin (MIC range 4–16 mg/L).

The bactericidal activity of temocillin was confirmed against selected aztreonam-resistant strains of K. oxytoca and Enterobacter cloacae by conventional time-kill studies, and against a strain of E. cloacae in an in vitro model system designed to simulate the temocillin concentration profiles attained in extravascular fluid such as peripheral lymph. In the time-kill studies, temocillin concentrations of 16 and 32 mg/L were shown to effectively reduce the numbers of viable bacteria by 99 and 99.9%, respectively, within 12 hours. In the in vitro model system the numbers of bacteria were reduced 99.9% over the initial 4-hour period.

In combination with aminoglycoside antibiotics, temocillin exerted a synergistic or partially synergistic effect (∑FIC ⩽ 0.75) against the majority of strains of Pseudomonas aeruginosa tested. When combined with piperacillin, cefotaxime or latamoxef, temocillin, unlike cefoxitin, exhibited no antagonism against strains of Enterobacteriaceae producing inducible cephalosporinases.