Labia R, Baron P, Masson JM, Hill G, Cole M. Diagnostic et antibiothérapie des infections urinaires bactériennes communautaires de l’adulte. Development and validation of a high performance liquid chromatography assay for the determination of temocillin in serum of haemodialysis patients. Miranda Bastos AC, Vandecasteele SJ, Tulkens PM, Spinewine A, Van Bambeke F. Data regarding actual wild-type MIC distribution, clinical efficacy, PK profiling in volunteers or patients, and PD targets are scarce, and further studies are required to support appropriate dosing recommendations and determination of clinical breakpoints. In less severely ill patients or in specific foci of infection, such as urinary tract infection, a 4 g daily regimen should be adequate for strains with temocillin MIC up to 16 mg/L. Monte Carlo simulations performed in critically ill patients showed that the 2 g every 12 h and 2 g every 8 h regimens provide a 95% probability of target attainment of 40% fT > MIC up to an MIC of 8 mg/L. An fT > MIC of 40–50% is associated with antibacterial effect and survival in vivo.
#Ticarcillin binding pbp3 free
The cumulative percentage of a 24-h period during which the free drug concentration exceeds the minimum inhibitory concentration (fT > MIC) at steady-state pharmacokinetic conditions seems to be the best pharmacokinetic/pharmacodynamic (PK/PD) index correlating with temocillin efficacy. Furthermore, the penetration of temocillin into bile and peritoneal fluid is high, but poor into cerebrospinal fluid.
Temocillin clearance is mainly renal, and urinary recovery is high, ranging from 72 to 82% after 24 h. The percentage of protein binding of temocillin is high (approximately 80%), and is concentration-dependent. After intravenous infusion, temocillin showed a prolonged elimination half-life of approximately 5 h. The proportion of spontaneous resistant mutants in vitro to temocillin is low, as found in vivo. Temocillin is bactericidal, and the effect of inoculum size on its activity is relatively mild. The addition of the α-methoxy moiety on ticarcillin confers resistance to hydrolysis by Ambler classes A and C β-lactamases (extended spectrum β-lactamases, Klebsiella pneumoniae carbapenemase and AmpC hyperproduced enzymes). Temocillin spectrum is almost restricted to Enterobacteriaceae.
Temocillin, a 6-α-methoxy derivative of ticarcillin, is a forgotten antibiotic that has recently been rediscovered, and issues about clinical breakpoints and optimal therapeutic regimens are still ongoing.