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妥布霉素:抗菌及药代动力学特性与治疗用途综述

Tobramycin: a review of its antibacterial and pharmacokinetic properties and therapeutic use.

作者信息

Brogden R N, Pinder R M, Sawyer P R, Speight T M, Avery G S

出版信息

Drugs. 1976;12(3):166-200. doi: 10.2165/00003495-197612030-00002.

Abstract

Tobramycin is a new aminoglycoside antibiotic with a broad antibacterial spectrum in vitro, and pharmacokinetic properties similar to those for gentamicin. Tobramycin is more active than gentamicin against Pseudomonas aeruginosa and active against many gentamicin resistant strains, but is not active against enterobacteriaceae resistant to gentamicin. Theoretically, tobramycin has an advantage over gentamicin against infections caused by P. aeruginosa, but any advantage in clinical practice has yet to be adequately demonstrated. Clinical experience with tobramycin is considerably less than with gentamicin. Whilst tobramycin appears to offer no clear advantages over gentamicin against sensitive organisms it is indicated in infection caused by strains of P. aeruginosa which are resistant to gentamicin, but sensitive to tobramycin. Like gentamicin, tobramycin acts synergistically with corbenicillin and the cephalosporins. The efficacy of the tobramycin-carbenicillin combination has been shown in endocarditis caused by P. aeruginosa which was unresponsive to gentamicin plus carbenicillin. Ototoxicity and nephrotoxicity similar to that seen with other animoglycosides have been encountered in therapeutic trials with tobramycin and wider clinical experience is necessary to determine the relative incidence of these side-effects with gentamicin and tobramycin used under similar conditions. Antimicrobial activity: In comparative studies, in vitro, tobramycin is more active than gentamicin against clinical isolates of Pseudomonas aeruginosa. Similarly, the inhibitory index, which is the ratio between the serum concentration attained at usual therapuetic doses and the minimum inhibitory concentration, for Pseudomonas aeruginosa is higher for tobramycin than for gentamicin. Against Gram-negative bacteria other than Pseudomonas spp. the spectrum of activity of tobramycin is similar to that of gentamicin. For most species the activity of tobramycin is slightly less than that of gentamicin. Gentamicin is consistently more active than tobramycin against Serratia marcescens. Like other aminoglycoside antibiotics, tobramycin is active in vitro in low concentrations against Staphylococcus aureus. Tobramycin is essentially inactive against Streptococcus pyogenes, Streptococcus faecalis and Streptococcus pneumoniae (pneumococci). Maner aminoglycosides and of other antibiotics against various bacteria in vitro, but comparisons between studies cannot always be interpreted literally because the activity of many antibiotics in vitro, including tobramycin, is influenced by the nature of the culture media and the presence of certain salts. The sensitivity of P. aeruginosa to tobramycin is influenced by the magnesium, and calcium content of the culture media whilst that of all species is reduced by sodium ions. Wide variations in the concentration of these ions may result in divergent MIC values and an inappropriate choice of antibacterial agent to treat pseudomonas infection...

摘要

妥布霉素是一种新型氨基糖苷类抗生素,体外抗菌谱广,药代动力学特性与庆大霉素相似。妥布霉素对铜绿假单胞菌的活性比庆大霉素强,对许多耐庆大霉素菌株也有活性,但对耐庆大霉素的肠杆菌科细菌无活性。理论上,妥布霉素在治疗铜绿假单胞菌引起的感染方面优于庆大霉素,但在临床实践中的任何优势尚未得到充分证实。妥布霉素的临床经验远少于庆大霉素。虽然妥布霉素在针对敏感菌方面似乎没有比庆大霉素更明显的优势,但它适用于由耐庆大霉素但对妥布霉素敏感的铜绿假单胞菌菌株引起的感染。与庆大霉素一样,妥布霉素与羧苄西林和头孢菌素协同作用。妥布霉素 - 羧苄西林联合用药在治疗对庆大霉素加羧苄西林无反应的铜绿假单胞菌引起的心内膜炎方面已显示出疗效。在妥布霉素治疗试验中也出现了与其他氨基糖苷类药物类似的耳毒性和肾毒性,需要更广泛的临床经验来确定在相似条件下使用庆大霉素和妥布霉素时这些副作用的相对发生率。抗菌活性:在体外比较研究中,妥布霉素对铜绿假单胞菌临床分离株的活性比庆大霉素强。同样,对于铜绿假单胞菌,抑制指数(即常用治疗剂量下达到的血清浓度与最低抑菌浓度之比)妥布霉素高于庆大霉素。对于除假单胞菌属以外的革兰氏阴性菌,妥布霉素的活性谱与庆大霉素相似。对于大多数菌种,妥布霉素的活性略低于庆大霉素。庆大霉素对粘质沙雷氏菌的活性始终比妥布霉素强。与其他氨基糖苷类抗生素一样,妥布霉素在体外低浓度时对金黄色葡萄球菌有活性。妥布霉素对化脓性链球菌、粪肠球菌和肺炎链球菌(肺炎球菌)基本无活性。许多氨基糖苷类抗生素和其他抗生素在体外对各种细菌的活性,但不同研究之间的比较不能总是从字面上解释,因为包括妥布霉素在内的许多抗生素在体外的活性受培养基性质和某些盐类存在的影响。铜绿假单胞菌对妥布霉素的敏感性受培养基中镁和钙含量的影响,而所有菌种对钠离子的存在都敏感。这些离子浓度的广泛变化可能导致不同的最低抑菌浓度值,并导致治疗假单胞菌感染时抗菌药物选择不当……

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