Gavaldà J, Pahissa A, Almirante B, Laguarda M, Crespo E, Pou L, Fernández F
Infectious Diseases Research Laboratory, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
Antimicrob Agents Chemother. 1995 Sep;39(9):2098-103. doi: 10.1128/AAC.39.9.2098.
This study compares the effects of a total daily dose of gentamicin given once a day (q.d.) or three times a day (t.i.d.) in the therapy of experimental endocarditis in rabbits caused by penicillin-susceptible, penicillin-tolerant, or penicillin-resistant viridans streptococci. Four isolates were used in vivo: one penicillin susceptible (MIC < or = 0.03 microgram/ml), one penicillin tolerant (MBC/MIC, < or = 0.03/ > 32 micrograms/ml), and two penicillin resistant (MICs = 0.5 and 2 micrograms/ml). Animals were infected with one of the four isolates and assigned to one of the following treatment regimens: no treatment, procaine penicillin at 1.2 million IU intramuscularly (i.m.) t.i.d., procaine penicillin plus gentamicin at 1 mg/kg of body weight i.m. t.i.d., procaine penicillin plus gentamicin at 3 mg/kg i.m. q.d., or procaine penicillin plus gentamicin at 1 mg/kg i.m. q.d. (only animals infected with the penicillin-susceptible isolate). Serum drug concentrations measured 30 min after administration of 1.2 million IU of penicillin and 1 or 3 mg of gentamicin per kg were 22.6, 3.8, and 8.5 micrograms/ml, respectively. The reduced total daily dose of gentamicin was ineffective among animals infected with penicillin-susceptible viridans streptococci; treatment with 1 mg of gentamicin per kg per day plus penicillin was less effective (P < 0.05) than was treatment with 3 mg of gentamicin per kg per day plus penicillin. The 1-mg/kg/day gentamicin treatment regimen was not further studied. The gentamicin dosing interval did not significantly affect (q.d. versus t.i.d., P > 0.05) the relative efficacy of penicillin plus gentamicin for treatment of experimental endocarditis among animals infected with each of the four isolates tested.
本研究比较了每日一次（qd）或每日三次（tid）给予庆大霉素总日剂量，对由青霉素敏感、耐青霉素或耐青霉素的草绿色链球菌引起的兔实验性心内膜炎的治疗效果。体内使用了4种分离株：1种青霉素敏感株（MIC≤0.03微克/毫升），1种耐青霉素株（MBC/MIC，≤0.03/>32微克/毫升），以及2种耐青霉素株（MIC分别为0.5和2微克/毫升）。动物感染4种分离株之一后，被分配至以下治疗方案之一：不治疗、普鲁卡因青霉素120万国际单位肌肉注射（im）每日三次、普鲁卡因青霉素加庆大霉素1毫克/千克体重im每日三次、普鲁卡因青霉素加庆大霉素3毫克/千克im每日一次，或普鲁卡因青霉素加庆大霉素1毫克/千克im每日一次（仅感染青霉素敏感分离株的动物）。每千克给予120万国际单位青霉素和1或3毫克庆大霉素后30分钟测得的血清药物浓度分别为22.6、3.8和8.5微克/毫升。在感染青霉素敏感草绿色链球菌的动物中，减少庆大霉素总日剂量无效；每日每千克1毫克庆大霉素加青霉素治疗的效果（P<0.05）不如每日每千克3毫克庆大霉素加青霉素治疗。未进一步研究每日每千克1毫克庆大霉素的治疗方案。在感染所测试的4种分离株之一的动物中，庆大霉素给药间隔对青霉素加庆大霉素治疗实验性心内膜炎的相对疗效无显著影响（每日一次与每日三次，P>0.05）。
