Pocidalo J J
INSERM Hôpital Claude Bernard, Paris, France.
Rev Infect Dis. 1989 Jul-Aug;11 Suppl 5:S979-84. doi: 10.1093/clinids/11.supplement_5.s979.
Current microbiologic techniques (determinations of minimal inhibitory and/or microbicidal concentrations) are unable to delineate the true role of anti-infectious drugs in the treatment of human infections due to intracellular pathogens. The prediction and evaluation of the efficacy of quinolones against intracellular pathogens requires information on four different steps. (1) Quinolones should be able to penetrate phagocytes; intramacrophagic concentration is highly dependent on serum pharmacokinetics; finally, the best quinolone should have the longest serum half-life and reach highest maximum serum concentrations. (2) The evaluation of antibacterial activity requires an adequate cellular model (e.g., multiplication of Legionella pneumophila within human monocyte-derived macrophages). (3) The prediction of drug efficacy requires an experimental animal model. (4) Clinical trials in human disease are necessary. This stage is difficult when the evaluation concerns severe infectious diseases because the rarity of these diseases makes random clinical trials difficult. In this paper we describe methodologies for assessing the efficacy of quinolones against intracellular bacterial pathogens with a particular focus on Legionella pneumophila.
当前的微生物学技术（最低抑菌浓度和/或杀菌浓度的测定）无法阐明抗感染药物在治疗由细胞内病原体引起的人类感染中的真正作用。预测和评估喹诺酮类药物对细胞内病原体的疗效需要有关四个不同步骤的信息。（1）喹诺酮类药物应能够穿透吞噬细胞；巨噬细胞内浓度高度依赖于血清药代动力学；最后，最佳的喹诺酮类药物应具有最长的血清半衰期并达到最高的血清最大浓度。（2）抗菌活性的评估需要一个合适的细胞模型（例如，嗜肺军团菌在人单核细胞衍生的巨噬细胞内繁殖）。（3）药物疗效的预测需要一个实验动物模型。（4）人类疾病的临床试验是必要的。当评估涉及严重传染病时，这一阶段很困难，因为这些疾病的罕见性使得随机临床试验变得困难。在本文中，我们描述了评估喹诺酮类药物对细胞内细菌病原体疗效的方法，特别关注嗜肺军团菌。
