Tone J, Niki K, Maeda H, Ihara I, Kawakami M
Jpn J Antibiot. 1976 May;29(5):559-70.
Growth inhibitory effect of combined treatment of tetracycline (TC) and oleandomycin (OM), at a ratio of 2:1, on certain species of pathogenic bacteria including drug-resistant ones was examined. By the crossed paper strip method, synergistic effects were demonstrated against 9 of the 16 strains of Staphylococcus aureus, and all of the 5 strains of Escherichia coli studied. Antagonism was observed with none of the strains and with 2 strains of Streptococcus pyogenes and 2 strains of Streptococcus pneumoniae tested in the present experiments. The MICs determined by the agar dilution method, also gave similar results, although synergism was not conclusively demonstrated by this method. With representative strains of S. aureus, synergism was evidenced by quantitative measurement of growth inhibition. In some strains, 1.0 mug of one drug per ml of medium inhibited the induction of resistance to the second drug. Such a small dose of one drug also inhibited the development of a mutant resistant to the second drug. These inhibitory actions were thought to be one of the important factors causing the synergistic effect of TC and OM on drug resistant bacteria.
研究了四环素（TC）与竹桃霉素（OM）以2:1比例联合处理对包括耐药菌在内的某些病原菌的生长抑制作用。通过交叉纸条法，对16株金黄色葡萄球菌中的9株以及所研究的5株大肠杆菌均显示出协同作用。在本实验中，对所测试的化脓性链球菌的2株菌株和肺炎链球菌的2株菌株均未观察到拮抗作用。通过琼脂稀释法测定的最低抑菌浓度（MIC）也得出了类似结果，尽管该方法未最终证实协同作用。对于金黄色葡萄球菌的代表性菌株，通过生长抑制的定量测量证明了协同作用。在某些菌株中，每毫升培养基中1.0微克的一种药物可抑制对第二种药物耐药性的诱导。如此小剂量的一种药物也抑制了对第二种药物耐药的突变体的产生。这些抑制作用被认为是导致TC和OM对耐药菌产生协同作用的重要因素之一。
