Antimicrobial therapy for Chlamydia pneumoniae: its potential role in atherosclerosis and asthma.
Antimicrobial therapy for Chlamydia pneumoniae: its potential role in atherosclerosis and asthma.
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DOI：
10.1093/jac/44.2.145
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发表时间：
1999-08
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影响因子：
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通讯作者：
P. Cook
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文献类型：
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作者：
P. Cook
主要文章被接受，但仅仅是因为其他技术的证实证据，如PCR。这些证据表明，动脉疾病与肺炎梭菌存在的相关性比与其他感染因子的相关性更可靠。如果这些关联是重要的，我们是否可以确定有哮喘或动脉粥样硬化性血管疾病风险的个体应该针对谁进行抗衣原体治疗？答案是：有可能，在未来。为了在巨噬细胞内存活，衣原体不能引起th1型CD4淋巴细胞反应，如干扰素-会促进th1型CD4淋巴细胞反应。在人肺炎球菌感染中，干扰素mrna的表达主要与HLA DR4分子背景下的抗原识别相关。先前报道的肺炎梭菌感染与促动脉粥样硬化血清胆固醇谱的关联29似乎也特别适用于某些HLA DR分子的存在。因此，具有特定HLA II类基因型的人患慢性肺炎梭菌相关疾病的风险可能更高。抗生素对哮喘有效的证据很少，但正在积累。大环内酯类药物长期以来被报道可改善慢性哮喘36并降低支气管组胺反应性。37 Hahn等人38给3名控制不良的成年哮喘患者服用克拉霉素或阿奇霉素6-16周，血清学证据显示他们最近感染了肺炎原体。治疗后，所有三名患者都能够停止口服类固醇，并且仅在吸入抗哮喘治疗中保持良好3-24个月。38同样的研究人员还用强力霉素、阿奇霉素或红霉素治疗46名稳定的慢性哮喘患者3-9周。在6个月（平均）以上，4例肺炎原体感染后发生哮喘的患者哮喘完全消退。在其余42例患者中，3例完全缓解，18例主要临床改善。39关于冠心病，在3315例单次急性心肌梗死患者和13139例无明显心血管疾病危险因素的年龄和性别匹配的对照中，先前使用四环素或喹诺酮类抗生素（但不使用大环内酯类药物）分别与心肌梗死风险降低30%和55%相关。在一项前瞻性、双盲、随机、安慰剂对照试验中，202例不稳定型心绞痛或非q波型心肌梗死患者接受了30天的罗红霉素治疗，6个月内严重复发性心肌缺血的发生率显著降低。41在60例持续存在肺炎c抗体滴度为1:64的心肌梗死存活男性中，随机分配到3-6天的阿奇霉素或安慰剂组，阿奇霉素治疗（40例患者）导致肺炎c IgG滴度显著下降和不良心血管事件。42相比之下，在34名既往冠状动脉搭桥并患有轻度高血压或中度高胆固醇血症的男性中，4个月的多西环素治疗对肺炎c抗体或冠心病危险因素没有影响。这样的试验继续引起人们的怀疑。首先，通过抗生素完全根除衣原体感染仍然是困难的或不可能的，即使在体外活性良好的抗生素长期大剂量服用时也是如此。在体内治疗期间，阿奇霉素的mic值已显示增加。46在细胞培养中，暴露于高浓度阿奇霉素和强力霉素后，在没有抗生素的情况下进一步传代后，可反复恢复活的肺炎梭菌。其次，哮喘的病理基础似乎很清楚……
Leading articles accepted, but only because of confirmatory evidence from other techniques, such as PCR. Such evidence suggests that arterial disease is more reliably correlated with the presence of C. pneumoniae than with other infectious agents. 17 If these associations are important, can we identify individuals at risk of asthma or atheromatous vascular disease who should be targeted for anti-chlamydial therapy? The answer is: possibly, in the future. To survive within macrophages, chlamydiae must not elicit a TH1-type CD4 lymphocyte response, such as would be promoted by interferon-. 34 In human C. pneumoniae infection, the expression of interferon-mRNA is predominantly associated with antigen recognition in the context of the HLA DR4 molecule. 35 The reported association of previous C. pneumoniae infection with a pro-atherogenic serum cholesterol profile29 also appears to apply particularly in the presence of certain HLA DR molecules. 11 People with particular HLA class II genotypes might therefore be at a higher risk of chronic C. pneumoniae-associated disease. Evidence for the efficacy of antibiotics in asthma is sparse, but is accumulating. Macrolides have long been reported to ameliorate chronic asthma36 and to reduce bronchial histamine responsiveness. 37 Hahn et al. 38 gave clarithromycin or azithromycin for 6–16 weeks to three poorly controlled adult asthmatics with serological evidence of recent C. pneumoniae infection. Following treatment, all three patients were able to discontinue oral steroids, and remained well on inhaled anti-asthma therapy only for 3–24 months. 38 The same investigators also treated 46 stable chronic asthmatics for 3–9 weeks with doxycycline, azithromycin or erythromycin. Over 6 months (on average), there was complete resolution of asthma in four patients who had developed it after C. pneumoniae infection. Of the remaining 42 patients, three had complete remission and 18 major clinical improvement. 39 With respect to CAD, in a comparison of 3315 patients with a single episode of acute myocardial infarction and 13,139 age-and sex-matched controls with no apparent risk factors for cardiovascular disease, previous use of a tetracycline or quinolone antibiotic (but not a macrolide) was associated with 30% and 55% reductions, respectively, in the risk of myocardial infarction. 40 In a prospective, double-blind, randomized, placebo-controlled trial in 202 patients with unstable angina or non-Q-wave myocardial infarction, 30 days’ roxithromycin treatment led to a significant reduction in severe recurrent myocardial ischaemia over 6 months. 41 In 60 men surviving MI with persisting C. pneumoniaeantibody titres of 1: 64, randomly assigned to 3–6 days’ azithromycin or placebo, treatment with azithromycin (in 40 patients) led to significant falls in C. pneumoniae IgG titres and adverse cardiovascular events. 42 In contrast, 4 months’ doxycycline treatment in 34 men with previous coronary bypass and mild hypertension or moderate hypercholesterolaemia had no effect on C. pneumoniae antibodies or coronary heart disease risk factors. 43 Such trials continue to provoke scepticism. Firstly, the complete eradication of chlamydial infection by antibiotics remains difficult or impossible, even when antibiotics with good in-vitro activity are given in high doses for long periods. 44, 45 MICs of azithromycin have been shown to increase during treatment in vivo. 46 In cell cultures, following exposure to high concentrations of azithromycin and doxycycline, viable C. pneumoniae can repeatedly be recovered after further passages without antibiotics. 47 Secondly, it seems clear that the pathological foundations of asthma …