Fantin B, Leclercq R, Ottaviani M, Vallois J M, Maziere B, Duval J, Pocidalo J J, Carbon C
Institut National de la Santé et de la Recherche Médicale, Hôpital Bichat, Université Paris, VII, France.
Antimicrob Agents Chemother. 1994 Mar;38(3):432-7. doi: 10.1128/AAC.38.3.432.
We evaluated the in vivo activity and the diffusion of radiolabelled RP 57669 (RPI) and RP 54476 (RPII), the two components of the injectable streptogramin RP 59500, alone or in combination, in aortic vegetations from experimental endocarditis in rabbits. RPI and RPII demonstrated in vitro bacteriostatic and bactericidal synergy against a clinical strain of Staphylococcus aureus resistant to methicillin and susceptible to erythromycin. In experimental staphylococcal endocarditis, RP 59500 was as effective as vancomycin and significantly more effective than RPI (P < 0.01) and RPII (P < 0.05). Autoradiography studies showed different patterns of distribution into cardiac vegetations infected with Streptococcus sanguis for [14C]RPI and [14C]RPII. [14C]RPI was homogeneously distributed throughout the vegetations whereas [14C]RPII showed a decreasing gradient of concentration between the periphery and the core of the vegetation, with an approximately 2:1 ratio. [14C]RPI diffused approximately 2 to 4 times more than [14C]RPII into the core of the vegetations. Since the injected ratio of RPI and RPII is 30:70 in RP 59500, the actual RPI:RPII ratio in the core of the vegetation may range from 0.8 to 1.7, a ratio which remains compatible with the in vivo synergism demonstrated between the two components.
我们评估了放射性标记的RP 57669（RPI）和RP 54476（RPII）这两种注射用链阳性菌素RP 59500的成分单独或联合使用时在兔实验性心内膜炎主动脉赘生物中的体内活性和扩散情况。RPI和RPII在体外对一株耐甲氧西林但对红霉素敏感的金黄色葡萄球菌临床菌株表现出抑菌和杀菌协同作用。在实验性葡萄球菌性心内膜炎中，RP 59500与万古霉素一样有效，且显著比RPI（P < 0.01）和RPII（P < 0.05）更有效。放射自显影研究显示，[14C]RPI和[14C]RPII在感染血链球菌的心脏赘生物中的分布模式不同。[14C]RPI在整个赘生物中均匀分布，而[14C]RPII在赘生物的周边和核心之间显示出浓度递减梯度，比例约为2:1。[14C]RPI向赘生物核心的扩散比[14C]RPII多大约2至4倍。由于在RP 59500中RPI和RPII的注射比例为30:70，赘生物核心中实际的RPI:RPII比例可能在0.8至1.7之间，该比例与这两种成分之间显示的体内协同作用相符。
