Hunter R L, Jagannath C, Tinkley A, Behling C A, Nolte F
Department of Pathology, Emory University, Atlanta, Georgia 30322, USA.
Antimicrob Agents Chemother. 1995 Feb;39(2):435-9. doi: 10.1128/AAC.39.2.435.
The resistance of Mycobacterium avium complex (MAC) to antibiotics is thought to be enhanced by its outer glycolipid layer, which protects the organisms from antibiotics and host defense mechanisms. We hypothesized that surfactants which disrupt the lipid barrier might be of therapeutic value. We evaluated the ability of 10 poloxamer surfactants to inhibit the growth of MAC organisms and to potentiate antimycobacterial drug activity in broth culture using a radiometric assay. Very large, small, or hydrophilic poloxamers had little or no effect. However, certain hydrophobic poloxamers, especially P331, retarded the growth of most isolates of MAC and produced a synergistic effect with rifampin. The MIC of rifampin required to inhibit the growth of MAC was reduced from a mean of 14.6 micrograms/ml (range, 4 to > 32 micrograms/ml) to 1.4 micrograms/ml (range, < 1.125 to 4 micrograms/ml) by 1.0 mg of P331 per ml (P < 0.01). Enhancement of antibiotic susceptibility was observed with concentrations of poloxamer as low as 10 micrograms/ml. These studies suggest that P331 might be useful in increasing the effectiveness of antibiotic therapy of MAC infections.
鸟分枝杆菌复合体（MAC）对抗生素的耐药性被认为是由其外层糖脂层增强的，该糖脂层保护生物体免受抗生素和宿主防御机制的影响。我们假设破坏脂质屏障的表面活性剂可能具有治疗价值。我们使用放射性测定法评估了10种泊洛沙姆表面活性剂在肉汤培养中抑制MAC生物体生长和增强抗分枝杆菌药物活性的能力。非常大、小或亲水性的泊洛沙姆几乎没有或没有效果。然而，某些疏水性泊洛沙姆，尤其是P331，抑制了大多数MAC分离株的生长，并与利福平产生协同作用。每毫升1.0毫克的P331将抑制MAC生长所需的利福平MIC从平均14.6微克/毫升（范围为4至>32微克/毫升）降至1.4微克/毫升（范围为<1.125至4微克/毫升）（P<0.01）。在低至10微克/毫升的泊洛沙姆浓度下观察到抗生素敏感性增强。这些研究表明，P331可能有助于提高MAC感染抗生素治疗的有效性。
