Miles A A, Maskell J P
J Med Microbiol. 1985 Aug;20(1):17-26. doi: 10.1099/00222615-20-1-17.
To test the hypothesis that the in-vivo antibiotic action of tetracycline might be affected by ferric iron and the enhancement of infection by ferric iron by tetracycline, the actions of intraperitoneal antibiotic and local ferric ammonium citrate, given separately and together, were measured in the dorsal skin of guinea-pigs bearing lesions due to staphylococci, streptococci, a Proteus sp., an Erysipelothrix sp., Clostridium perfringens, Pseudomonas aeruginosa, Aeromonas hydrophila and Klebsiella pneumoniae. Tetracycline, given in two intraperitoneal doses of 25 mg/kg at 0 and 2 h after intracutaneous challenge, maintained plasma concentrations of 4-6 micrograms/ml for more than the first 4 h of infection, after which the local lesions had become largely insusceptible to the antibiotic. The intracutaneous injection of Fe 10 micrograms in a volume of 0.1 ml containing the bacteria was sufficient to enhance infection by those strains susceptible to this effect. The in-vivo efficacy of tetracycline was not always related to low MIC; a low MIC was sometimes associated with little action and a high MIC with moderate action. Sixteen organisms were tested. The iron diminished the tetracycline effect only feebly with one staphylococcal strain and the strain of E. rhusiopathiae. In only one case, with a strain of Proteus sp., was the tetracycline action grossly diminished. On the other hand, tetracycline diminished the enhancement effect of iron moderately with three strains of staphylococci and one strain each of K. pneumoniae, P. aeruginosa and C. perfringens, and strongly with two strains of staphylococci, a group-C streptococcus and one strain each of K. pneumoniae, E. rhusiopathiae and A. hydrophila. It is evident that the diminution of tetracycline action by moderate excess of readily available Fe , whether endogenous or administered, is an unlikely event (three instances among the 16 tested) whereas the diminution of the infection-enhancing effect of iron by tetracycline is much more likely (12 instances among the 16). Insofar as a decrease in iron available for enhancement of infection is valid evidence of a diminution of the iron available for necessary physiological processes of the subject treated, our results suggest that these processes might be affected by tetracycline.
为了验证四环素的体内抗生素作用可能受到三价铁影响以及四环素会增强三价铁的感染增强作用这一假说，分别单独及联合给予腹腔内抗生素和局部枸橼酸铁铵后，在患有由葡萄球菌、链球菌、变形杆菌属、红斑丹毒丝菌属、产气荚膜梭菌、铜绿假单胞菌、嗜水气单胞菌和肺炎克雷伯菌引起的损伤的豚鼠背部皮肤中测量其作用。在皮内接种细菌后0小时和2小时，以25mg/kg的剂量腹腔内注射两次四环素，在感染的最初4小时内，血浆浓度维持在4 - 6微克/毫升以上，此后局部损伤对该抗生素基本不再敏感。在含有细菌的0.1毫升体积中皮内注射10微克铁就足以增强那些对这种作用敏感的菌株的感染。四环素的体内疗效并不总是与低最低抑菌浓度（MIC）相关；低MIC有时与作用微弱相关，而高MIC与中等作用相关。测试了16种微生物。铁仅对一种葡萄球菌菌株和红斑丹毒丝菌菌株微弱地降低了四环素的作用。仅在一种变形杆菌属菌株的情况下，四环素的作用大幅降低。另一方面，四环素对三种葡萄球菌菌株以及肺炎克雷伯菌、铜绿假单胞菌和产气荚膜梭菌各一种菌株适度降低了铁的增强作用，对两种葡萄球菌菌株、一种C组链球菌以及肺炎克雷伯菌、红斑丹毒丝菌和嗜水气单胞菌各一种菌株强烈降低了铁的增强作用。很明显，适度过量的易获得的铁（无论是内源性的还是给予的）降低四环素作用是不太可能发生的事件（在16种测试情况中有3例），而四环素降低铁的感染增强作用则更有可能（在16种中有12例）。就可用于增强感染的铁的减少是所治疗对象必要生理过程可用铁减少的有效证据而言，我们的结果表明这些生理过程可能受到四环素的影响。
