Stout J E, Arnold B, Yu V L
Special Pathogens Laboratory, Veterans Affairs Medical Center, Pittsburgh, Pennsylvania, USA.
Diagn Microbiol Infect Dis. 1998 Jan;30(1):37-43. doi: 10.1016/s0732-8893(97)00174-0.
Animal lung macrophages or human peripheral blood mononuclear cells have been used for testing intracellular activity of anti-Legionella antibiotics; such studies are labor intensive such that comparative antibiotic studies for the many Legionella species are few. We evaluated a human monocyte cell line (HL-60) as an alternative model. HL-60 (1.5 x 10(6) cells/well) was differentiated into adherent cell and infected with 1.5 x 10(7) CFU of Legionella pneumophilia (L. pneumophilia). Erythromycin and quinolones, ciprofloxacin, ofloxacin, and levofloxacin were added to cells at 1 and 8 x MIC. Percent (%) inhibition ratios equal to total L. pneumophila with agent divided by L. pneumophila without agent x 100 were determined at 48 h; lower ratios implied greater potency. By broth dilution in buffered yeast extract broth, the most potent agents against L. pneumophila were (MIC): ciprofloxacin (0.015-0.03), ofloxacin (0.015-0.03), levofloxacin (0.015-0.03), erythromycin (0.125-1.0 microgram/mL). In the intracellular model, the most potent inhibitors of L. pneumophila multiplication at 8 x MIC were (in order of potency) levofloxacin (24.2%), ciprofloxacin (30.6%), ofloxacin (37.1%), and erythromycin (55.0%). All the quinolones were highly active and significantly more potent against L. micdadei and L. bozemanii when compared to L. pneumophila.
动物肺巨噬细胞或人类外周血单核细胞已被用于测试抗军团菌抗生素的细胞内活性;此类研究劳动强度大,以至于针对众多军团菌物种的抗生素比较研究较少。我们评估了人类单核细胞系(HL - 60)作为替代模型。将HL - 60(1.5×10⁶个细胞/孔)分化为贴壁细胞,并感染1.5×10⁷CFU的嗜肺军团菌(L. pneumophilia)。在1倍和8倍最低抑菌浓度(MIC)下,将红霉素和喹诺酮类药物环丙沙星、氧氟沙星和左氧氟沙星添加到细胞中。在48小时时测定抑制率百分比(%),其等于有药物时嗜肺军团菌总数除以无药物时嗜肺军团菌总数×100;较低的比率意味着更强的效力。通过在缓冲酵母提取物肉汤中进行肉汤稀释,对嗜肺军团菌最有效的药物(MIC)为:环丙沙星(0.015 - 0.03)、氧氟沙星(0.015 - 0.03)、左氧氟沙星(0.015 - 0.03)、红霉素(0.125 - 1.0微克/毫升)。在细胞内模型中,在8倍MIC时,对嗜肺军团菌增殖最有效的抑制剂(按效力顺序)为左氧氟沙星(24.2%)、环丙沙星(30.6%)、氧氟沙星(37.1%)和红霉素(55.0%)。与嗜肺军团菌相比,所有喹诺酮类药物都具有高活性,且对米克戴德军团菌(L. micdadei)和博兹曼军团菌(L. bozemanii)的效力明显更强。