Efficacy of teicoplanin-gentamicin given once a day on the basis of pharmacokinetics in humans for treatment of enterococcal experimental endocarditis

With the aim of investigating home therapy for enterococcal endocarditis, w e compared the efficacy of teicoplanin combined with gentamicin given once a day or in three daily doses (t.i.d.) with the standard treatment, ampicil lin plus gentamicin administered t,i.d., for treating experimental enteroco ccal endocarditis. The antibiotics were administered by using "human-like p harmacokinetics" (H-L), i,e, pharmacokinetics like those in humans, that si mulated the profiles of these drugs in human serum. Animals with catheter-i nduced endocarditis were infected intravenously with 10(8) CFU of Enterococ cus faecalis EF91 (MICs and MBCs of ampicillin, gentamicin, and teicoplanin , 0.5 and 32, 16 and 32, and 0.5 and 1 mug/ml, respectively) and were treat ed for 3 days with ampicillin H-L at 2 g every 4 h plus gentamicin H-L at I mg/kg every 8 h, or teicoplanin H-L at 10 mg/kg every 24 h, alone or combi ned with gentamicin, administered at dose of H-L at 1 mg/kg every 8 h or H- L at 4.5 mg/kg every 24 h, The results of therapy for experimental endocard itis due to EF91 showed that teicoplanin alone was as effective as ampicill in alone in reducing the bacterial load (P > 0.05), The combination of ampi cillin or teicoplanin with gentamicin was more effective than the administr ation of both drugs alone in reducing the log(10)CFU/gram of aortic vegetat ion (P < 0.01 and P < 0.05, respectively). Teicoplanin plus gentamicin H-L at 4.5 mg/kg, both administered every 24 h, showed an efficacy equal to the "gold standard," ampicillin plus gentamicin H-L at 1 mg/kg t,i,d, (P > 0.0 5), Increasing the interval of administration of gentamicin to a single dai ly dose combined with teicoplanin resulted in a reduction of bacteria in th e vegetations equivalent to that achieved with the recommended regimen of a mpicillin plus thrice-daily gentamicin in the treatment of experimental end ocarditis due to E. faecalis, Teicoplanin plus gentamicin, both administere d once a day, may be useful home therapy for selected cases of enterococcal endocarditis,