INTRACELLULAR MULTIPLICATION OF LEGIONNAIRES-DISEASE BACTERIA (LEGIONELLA-PNEUMOPHILA) IN HUMAN-MONOCYTES IS REVERSIBLY INHIBITED BY ERYTHROMYCIN AND RIFAMPIN
INTRACELLULAR MULTIPLICATION OF LEGIONNAIRES-DISEASE BACTERIA (LEGIONELLA-PNEUMOPHILA) IN HUMAN-MONOCYTES IS REVERSIBLY INHIBITED BY ERYTHROMYCIN AND RIFAMPIN
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DOI：
10.1172/jci110744
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
SILVERSTEIN, SC
中科院分区：
文献类型：
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作者：
HORWITZ, MA;SILVERSTEIN, SC
研究了红霉素和利福平对体外嗜肺军团菌-单核细胞相互作用的影响。根据菌落形成单位的测量，无论是在嗜肺军团菌感染单核细胞之前或之后添加抗生素，还是在感染后2天（当嗜肺军团菌处于单核细胞的对数生长期时）添加抗生素，嗜肺军团菌的细胞内增殖均受到红霉素和利福平的抑制。 1.25μg/ml可抑制嗜肺军团菌的细胞内增殖，但≤1.25μg/ml则不抑制。 0.125 .mu.g/ml 红霉素和 0.01 .mu.g/ml 但不是 .ltoreq。 0.001.mu.g/ml利福平。这些抗生素浓度与在人工培养基中无细胞条件下抑制嗜肺军团菌胞外增殖的浓度相当；红霉素的最低抑制浓度为0.37μg/ml，利福平的最低抑制浓度为0.002μg/ml。添加抗生素后 1 小时内，单核细胞中对数生长期的嗜肺军团菌增殖受到抑制。被抗生素抑制繁殖的细胞内细菌不会被杀死。通过电镜观察，细菌在布满核糖体样结构的膜结合液泡中显得完整。在人工培养基上在细胞外繁殖的嗜肺军团菌很容易被相对低浓度的红霉素和利福平杀死；红霉素的最低细菌浓度为1.mu.g/ml，利福平的最低细菌浓度为0.009.mu.g/ml。在细胞内繁殖的嗜肺军团菌对这些浓度的红霉素和利福平或等于或大于人类血清峰值水平的浓度具有抗杀灭作用。处于稳定期的胞外嗜肺军团菌也能抵抗红霉素和利福平的杀伤作用。因此，在体内，嗜肺军团菌对杀灭红霉素和利福平具有抗性。抗生素对单核细胞中嗜肺军团菌增殖的抑制是可逆的；当两天后从受感染的单核细胞培养物中除去抗生素时，嗜肺军团菌恢复繁殖。这项研究表明，接受红霉素和利福平治疗的退伍军人病患者需要宿主防御来消除嗜肺军团菌；宿主防御不足可能导致治疗停止后复发。
The effect of erythromycin and rifampin on L. pneumophila-monocyte interaction in vitro was studied. The intracellular multiplication of L. pneumophila is inhibited by erythromycin and rifampin, as measured by colony-forming units, whether the antibiotics are added just before or just after infection of monocytes with L. pneumophila, or 2 days after infection when L. pneumophila is in the log growth phase in monocytes. Intracellular multiplication of L. pneumophila is inhibited by 1.25 .mu.g/ml but not .ltoreq. 0.125 .mu.g/ml erythromycin and 0.01 .mu.g/ml but not .ltoreq. 0.001 .mu.g/ml rifampin. These concentrations of antibiotics are comparable to those that inhibit extracellular multiplication of L. pneumophila under cell-free conditions in artificial medium; the minimal inhibitory concentration is 0.37 .mu.g/ml for erythromycin and 0.002 .mu.g/ml for rifampin. Multiplication of L. pneumophila in the log growth phase in monocytes is inhibited within 1 h of the addition of antibiotics. Intracellular bacteria inhibited from multiplying by antibiotics are not killed. By EM, the bacteria appear intact within membrane-bound vacuoles studded with ribosomelike structures. L. pneumophila multiplying extracellularly on artificial medium is killed readily by relatively low concentrations of erythromycin and rifampin; the minimal bacterical concentration is 1 .mu.g/ml for erythromycin and 0.009 .mu.g/ml for rifampin. L. pneumophila multiplying intracellularly is resistant to killing by these concentrations of erythromycin and rifampin or by concentrations equal to or greater than peak serum levels in humans. Extracellular L. pneumophila in stationary phase is also resistant to killing by erythromycin and rifampin. Thus, in vivo, L. pneumophila is resistant to killing erythromycin and rifampin. Inhibition of L. pneumophila multiplication in monocytes by antibiotics is reversible; when the antibiotics are removed from infected monocyte cultures after 2 days, L. pneumophila resumes multiplication. This study indicates that patients with Legionnaires'' disease under treatment with erythromycin and rifampin require host defenses to eliminate L. pneumophila; inadequate host defenses may result in relapse after cessation of therapy.