IN-VIVO PHARMACOKINETIC OF AMIKACIN AND I TS PHARMACODYNAMIC IN COMBINATION WITH CEFEPIME, CEFPIROME AND MEROPENEM IN AN IN-VITRO EX-VIVO MICROPIG MODEL

Three female Yucatan micropigs were included and received a single dos e of amikacin (15 mg/kg) by short infusion (30 min) combined either wi th a single dose of cefepime or cefpirome (30 mg/kg/12 h) or meropenem (7 mg/kg/8 h). The beta-lactams were administered either by intraveno us intermittent injection or by continuous infusion. The mean eliminat ion half-life and clearance value of amikacin were 1.88 h and 2.15 ml/ min.kg(-1) respectively. These pharmacokinetic parameters were similar to those obtained in man (t1/2 = 2,42 h et Cl = 1,61 ml/min kg(-1)). Furthermore, they were not affected by coadministration of cefepime, c efpirome and to meropenem. While resistant to cefepime, cefpirome and amikacin, Klebsiella pneumoniae producing ESBL was susceptible to comb ination of these cephalosporins with amikacin in an in vitro/ex vivo m icropig model. For the six dosage regimens used in this study, the kil ling activities were similar and resulted in at least 4 log decrease a t 6h after drug exposure. For antimicrobial combination consisting of bolus dosing of amikacin plus continuous infusion of cefepime or cefpi rome, the 12 h serum bactericidal titers (SBTs) were 1:8 for cefepime and 1:2 for cefpirome dosage regimen. When each drug administered inte rmittently, the 12 h SBTs were 1.4 for cefepime and 1:2 for cefpirome. The 8 h SBTs for dosing schedule containing meropenem combined with a mikacin were 1:4 and 1:16 after 30 min short infusion and continuous i nfusion respectively. In conclusion, our study showed that the micropi g model is a reliable model for pharmacokinetic investigation of amika cin. It was concluded that beta-lactam antibiotics tested with amikaci n may be coadministered by using the standard recommended dosing regim en of amikacin. Continuous infusion of beta-lactams combined with once dosing of amikacin seems to be as or more effective than intermittent injection of each drug.