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氟氯西林和庆大霉素联合使用可抑制金黄色葡萄球菌在对数生长期和稳定期产生中毒性休克综合征毒素1。

Combination of flucloxacillin and gentamicin inhibits toxic shock syndrome toxin 1 production by Staphylococcus aureus in both logarithmic and stationary phases of growth.

作者信息

van Langevelde P, van Dissel J T, Meurs C J, Renz J, Groeneveld P H

机构信息

Department of Infectious Diseases, Leiden University Hospital, The Netherlands.

出版信息

Antimicrob Agents Chemother. 1997 Aug;41(8):1682-5. doi: 10.1128/AAC.41.8.1682.

Abstract

Production of exotoxins by staphylococci and streptococci may lead to the development of toxic shock syndrome (TSS). Because clindamycin inhibits exotoxin production, its use has been advocated for the treatment of TSS. However, the bacteriostatic action of clindamycin might be a disadvantage for the treatment of overwhelming infections. We investigated the effects of flucloxacillin and gentamicin on exotoxin production, because incubation with these antibiotics combines bactericidal action with protein synthesis inhibition. Staphylococcus aureus during the logarithmic and stationary phases of growth was incubated with either clindamycin, flucloxacillin, or a combination of flucloxacillin and gentamicin at concentrations of 2 or 10 times the MIC. In logarithmic-phase cultures clindamycin had a static effect on bacterial growth. After incubation with flucloxacillin, either alone or in combination with gentamicin, a rapid and large reduction in the number of viable bacteria was demonstrated. In stationary-phase cultures none of the antibiotics significantly changed the number of viable bacteria. TSS toxin 1 (TSST-1) production during logarithmic-phase growth was inhibited by > or =95% by all antibiotics. In stationary-phase cultures, clindamycin, flucloxacillin, and the combination of flucloxacillin and gentamicin inhibited TSST-1 production by 95, 30, and 75%, respectively, compared with the level of exotoxin production in the controls. The present results indicate that clindamycin inhibits TSST-1 production and exerts bacteriostatic activity in both bacterial growth phases. Because the combination of flucloxacillin and gentamicin combines the inhibition of exotoxin production with high bactericidal activity at least in logarithmic-phase cultures, it should be considered an alternative to clindamycin for the treatment of exotoxin-mediated diseases, especially in patients with overwhelming infections.

摘要

葡萄球菌和链球菌产生的外毒素可能导致中毒性休克综合征(TSS)的发生。由于克林霉素可抑制外毒素的产生,因此有人主张使用克林霉素治疗TSS。然而,克林霉素的抑菌作用对于治疗严重感染可能是一个不利因素。我们研究了氟氯西林和庆大霉素对外毒素产生的影响,因为用这些抗生素孵育可将杀菌作用与蛋白质合成抑制作用结合起来。将处于对数生长期和稳定期的金黄色葡萄球菌与浓度为最低抑菌浓度(MIC)2倍或10倍的克林霉素、氟氯西林或氟氯西林与庆大霉素的组合进行孵育。在对数生长期培养物中,克林霉素对细菌生长有抑制作用。用氟氯西林单独或与庆大霉素联合孵育后,可观察到活菌数量迅速大幅减少。在稳定期培养物中,没有一种抗生素能显著改变活菌数量。在对数生长期,所有抗生素对TSS毒素1(TSST-1)产生的抑制率均≥95%。在稳定期培养物中,与对照中外毒素产生水平相比,克林霉素、氟氯西林以及氟氯西林与庆大霉素的组合分别抑制TSST-1产生95%﹑30%和75%。目前的结果表明,克林霉素在两个细菌生长阶段均能抑制TSST-1的产生并发挥抑菌活性。由于氟氯西林与庆大霉素的组合至少在对数生长期培养物中能将外毒素产生的抑制作用与高杀菌活性结合起来,因此对于外毒素介导的疾病,尤其是严重感染患者,它应被视为克林霉素的替代药物。

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