Bermudez L E, Young L S
Kuzell Institute for Arthritis and Infectious Diseases, Medical Research Institute of San Francisco, Pacific Presbyterian Medical Center, California 94115.
Antimicrob Agents Chemother. 1988 Aug;32(8):1149-53. doi: 10.1128/AAC.32.8.1149.
The effect of amikacin and two new macrolides (roxithromycin and azithromycin) used either alone or in combination with recombinant tumor necrosis factor (TNF) to inhibit or kill Mycobacterium avium complex in human macrophages was examined in vitro. Macrophage monolayers infected with M. avium complex (strain 101, serotype 1) were treated with antibiotics or TNF by using three different protocols: (i) antibiotics or TNF was added to the monolayers immediately after infection and washed out after 24 h, (ii) antibiotics or TNF was replenished daily for 4 dys, or (iii) infected macrophage monolayers were treated with antibiotics plus TNF for 4 consecutive days. The number of viable intracellular bacteria was determined after 2 and 4 days of treatment by lysing cultured macrophages. Treatment for 24 h resulted in an inhibition of growth, as determined by macrophage lysis at day 4, for all three antimicrobial drugs and killing of 22% of intracellular bacteria after treatment with TNF. After treating the monolayers with amikacin, roxithromycin, or azithromycin for 4 consecutive days and replenishing the drug concentration daily, we observed 18 +/- 6, 20 +/- 4, and 22 +/- 1% killing, respectively. TNF (100 U/ml) was added daily to the monolayers, which resulted in 54 +/- 5% killing after 4 days. Combinations of antibiotics with TNF were associated with 62 +/- 3% killing with TNF-azithromycin, 73 +/- 6% killing with TNF-roxithromycin, and 56 +/- 4% killing of intracellular M. avium complex with TNF-amikacin after 4 days. The mycobactericidal effect was enhanced (91 +/- 4% killing by roxithromycinamikacin). Combinations of antimicrobial agents with immunomodulators like TNF may be useful for treatment of M. avium complex infection.
在体外研究了阿米卡星和两种新型大环内酯类药物（罗红霉素和阿奇霉素）单独使用或与重组肿瘤坏死因子（TNF）联合使用对人巨噬细胞中鸟分枝杆菌复合群的抑制或杀伤作用。用三种不同方案，将感染鸟分枝杆菌复合群（菌株101，血清型1）的巨噬细胞单层用抗生素或TNF处理：（i）感染后立即向单层中加入抗生素或TNF，并在24小时后洗去；（ii）抗生素或TNF每日补充4天；或（iii）感染的巨噬细胞单层连续4天用抗生素加TNF处理。处理2天和4天后，通过裂解培养的巨噬细胞来确定存活的细胞内细菌数量。处理24小时导致所有三种抗菌药物的生长受到抑制（通过第4天巨噬细胞裂解确定），用TNF处理后可杀死22%的细胞内细菌。用阿米卡星、罗红霉素或阿奇霉素连续4天处理单层并每日补充药物浓度后，我们分别观察到18±6%、20±4%和22±1%的杀伤率。每天向单层中加入TNF（100 U/ml），4天后导致54±5%的杀伤率。抗生素与TNF联合使用在4天后，TNF-阿奇霉素联合导致62±3%的杀伤率，TNF-罗红霉素联合导致73±6%的杀伤率，TNF-阿米卡星联合导致56±4%的细胞内鸟分枝杆菌复合群杀伤率。杀菌效果增强（罗红霉素-阿米卡星联合导致91±4%的杀伤率）。抗菌剂与TNF等免疫调节剂联合使用可能对鸟分枝杆菌复合群感染的治疗有用。
