Debbia E A, Pesce A, Chiesa M, Ricotta N, Schito G C
Institute of Microbiology, University of Genoa, Italy.
Drugs Exp Clin Res. 1992;18(4):129-39.
The bactericidal activity of ceftibuten, alone and in combination with other drugs, has been assessed in vitro. The ability to induce a post-antibiotic effect (PAE), the rate of emergence of spontaneous resistant mutants, and the presence of Eagle's phenomenon were also investigated. Ceftibuten rapidly killed most Enterobacteriaceae, Haemophilus, Moraxella and Streptococcus species tested, including beta-lactamase-producing strains with over 90% cfu reduction after only 2 h. Using chequerboard and time-kill tests, ceftibuten was found to react synergistically with aminoglycosides, and to give an indifferent response with ofloxacin against a large number of Gram-negative aerobes and streptococci. Antagonism was never observed. Ceftibuten induced a PAE of approximately 1 h on S. pneumoniae. As expected, no PAE was observed with Gram-negative species. Spontaneous emergence of ceftibuten-resistant strains exposed to supra-MICs of the drug was rare (< or = 10(-8)) in all pathogens tested. No marked Eagle effect was detected when bacteria were treated with ceftibuten at concentrations exceeding 100-fold their MICs. This rules out the possibility that in vivo the high concentrations of ceftibuten reached in the urinary tract may hinder its excellent bactericidal activity.
已在体外评估了头孢布烯单独及与其他药物联合使用时的杀菌活性。还研究了其诱导抗生素后效应（PAE）的能力、自发耐药突变体的出现率以及Eagle现象的存在情况。头孢布烯能迅速杀死大多数受试的肠杆菌科细菌、嗜血杆菌属、莫拉克斯氏菌属和链球菌属细菌，包括产β-内酰胺酶的菌株，仅2小时后cfu减少就超过90%。通过棋盘法和时间杀菌试验发现，头孢布烯与氨基糖苷类药物有协同反应，而与氧氟沙星对大量革兰氏阴性需氧菌和链球菌的反应呈无关作用。从未观察到拮抗作用。头孢布烯对肺炎链球菌诱导的PAE约为1小时。正如预期的那样，革兰氏阴性菌未观察到PAE。在所有受试病原体中，暴露于高于最低抑菌浓度（MIC）的头孢布烯时，头孢布烯耐药菌株的自发出现很少见（≤10^(-8)）。当用超过其MIC 100倍的浓度的头孢布烯处理细菌时，未检测到明显的Eagle效应。这排除了在体内尿路中达到的高浓度头孢布烯可能阻碍其优异杀菌活性的可能性。
