Kaczmarska Ludmiła, Jakoniuk Piotr
Zakład Mikrobiologii Akademii Medycznej w Białymstoku.
Med Dosw Mikrobiol. 2003;55(1):1-10.
The aim of the study was to demonstrate of whether the therapeutic effects of antibiotics depend on their in vitro activity in sub-inhibitory concentrations against staphylococci. Cloxacillin, gentamicin and lincomycin were used in the study. Groups of S. aureus strains, containing 6 strains with similar MIC values each but different sensitivity to sub-inhibitory antibiotic concentrations (sub-MIC) were selected (a total of 36 trains): i. strains increasing their sensitivity to phagocytosis and bactericidal activity of rabbit leukocytes after incubation with an antibiotic in 0.1 MIC concentration, ii. strains with sensitivity to the above factors unaffected by incubation with an antibiotic in 0.5 MIC concentration. The doses of staphylococci causing death of 90-100% of Swiss albino mice 10 days after i.p. infection were determined. The injected doses (LD 90-100) and various doses of antibiotics were used to determine ED50 values as well as the survival rate of the mice with experimental staphylococcal infections after treatment with these antibiotics. It was demonstrated that effective doses (ED 50) of the antiboitics were significantly lower when the antibiotics were administered once to mice infected with strains S. aureus sensitive to sub-MIC concentrations of the investigated antibiotics than for mice infected with strains resistant to their sub-MIC concentrations. Similar correlations were observed in mice which were given the antibiotics several times (for 7 days): the percentage of the surviving mice was higher in the group infected with sub-MIC sensitive strains. The therapeutic effect of cloxacillin, gentamicin and lincomycin demonstrated a significant correlation with the S. aureus strains used to induce the infections and their sensitivity, or lack of sensitivity in vitro, to phagocytosis and bactericdal activity of leukocytes in the presence of antibiotics in sub-MIC concentrations.
本研究的目的是证明抗生素的治疗效果是否取决于其在亚抑制浓度下对葡萄球菌的体外活性。本研究使用了氯唑西林、庆大霉素和林可霉素。选择了金黄色葡萄球菌菌株组,每组包含6株MIC值相似但对亚抑制抗生素浓度(亚MIC)敏感性不同的菌株(共36株):i. 与0.1 MIC浓度的抗生素孵育后,对兔白细胞吞噬作用和杀菌活性敏感性增加的菌株;ii. 与0.5 MIC浓度的抗生素孵育后,对上述因素的敏感性未受影响的菌株。确定了腹腔注射感染后10天导致90 - 100%瑞士白化小鼠死亡的葡萄球菌剂量。使用注射剂量(LD 90 - 100)和各种抗生素剂量来确定ED50值以及用这些抗生素治疗后实验性葡萄球菌感染小鼠的存活率。结果表明,当对感染了对所研究抗生素亚MIC浓度敏感的金黄色葡萄球菌菌株的小鼠单次给药时,抗生素的有效剂量(ED 50)显著低于感染了对其亚MIC浓度耐药菌株的小鼠。在多次(7天)给予抗生素的小鼠中也观察到了类似的相关性:感染亚MIC敏感菌株的组中存活小鼠的百分比更高。氯唑西林、庆大霉素和林可霉素的治疗效果与用于诱导感染的金黄色葡萄球菌菌株及其在亚MIC浓度抗生素存在下对白细胞吞噬作用和杀菌活性的敏感性或缺乏敏感性之间存在显著相关性。