Temocillin. In vitro antibacterial activity

Temocillin, a 6-alpha-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-greater than or equal to 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 (sigma FIC less than or equal to 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.