van den Broek P J
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Rev Infect Dis. 1989 Mar-Apr;11(2):213-45. doi: 10.1093/clinids/11.2.213.
The literature on the interaction between antimicrobial drugs, microorganisms, and phagocytes is reviewed. Critical assessment of the methods used in various studies is indispensable in the interpretation of results. The available data seldom permit firm conclusions, but a number of interactions can be postulated. Chemotaxis is influenced by beta-lactam antibiotics, which induce an increased release of chemoattractants from bacteria; inhibitors of protein synthesis (erythromycin, tetracyclines) reduce the release of chemoattractants. Rifampin and tetracyclines inhibit chemotactic activity of granulocytes. Phagocytosis is diminished by tetracyclines and bacitracin. Intracellular killing is impaired by trimethoprim and sulfamethoxazole. Antimicrobial drugs that inhibit protein synthesis alter the surface of bacteria, changing the opsonic requirements for phagocytosis. Antimicrobial agents that act on the cell wall or disrupt the organization of the outer membrane of gram-negative bacteria increase bacterial vulnerability to the lethal action of granulocytes. Cellular enzymes of granulocytes act synergistically with a variety of drugs. Synergism between monocytes and penicillins has also been shown. The degree of penetration of an antimicrobial drug into phagocytic cells is not correlated with the intracellular activity of the drug. Polymyxin B, colistin, rifampin, vancomycin, clindamycin, and quinolones kill bacteria phagocytosed by granulocytes. Penicillins, rifampin, and chloramphenicol show microbicidal activity against bacteria ingested by monocytes or macrophages.
本文综述了关于抗菌药物、微生物和吞噬细胞之间相互作用的文献。在解释研究结果时，对各项研究中使用的方法进行批判性评估是必不可少的。现有数据很少能得出确凿的结论，但可以推测出一些相互作用。趋化性受β-内酰胺类抗生素影响，这类抗生素会促使细菌释放更多趋化因子；蛋白质合成抑制剂（红霉素、四环素）会减少趋化因子的释放。利福平和四环素会抑制粒细胞的趋化活性。四环素和杆菌肽会削弱吞噬作用。甲氧苄啶和磺胺甲恶唑会损害细胞内杀菌作用。抑制蛋白质合成的抗菌药物会改变细菌表面，从而改变吞噬作用的调理素需求。作用于细胞壁或破坏革兰氏阴性菌外膜结构的抗菌药物会增加细菌对粒细胞致死作用的易感性。粒细胞的细胞内酶与多种药物协同作用。单核细胞与青霉素之间的协同作用也已得到证实。抗菌药物进入吞噬细胞的程度与该药物的细胞内活性无关。多粘菌素B、黏菌素、利福平、万古霉素、克林霉素和喹诺酮类药物可杀死被粒细胞吞噬的细菌。青霉素、利福平和氯霉素对被单核细胞或巨噬细胞吞噬的细菌具有杀菌活性。
