红霉素可减少支气管扩张加重和耐药

旧金山——澳大利一项随机安慰剂对照研究显示，非囊性纤维化(CF)支气管扩张患者长期使用小剂量红霉素，可减少肺病加重、痰液分泌和呼吸困难。而且小剂量红霉素比阿奇霉素更不容易引起耐药。

David Serisier博士

由于这些原因，主要研究者、澳大利亚昆士兰大学的David Serisier博士在美国胸科学会(ATS)国际大会上指出，红霉素“应被列为非CF支气管扩张患者的治疗药物”。

在这项研究中，共有117例不吸烟的成年患者被随机分组，其中59例接受琥乙红霉素400 mg每日2次治疗，58例使用安慰剂，治疗48周。所有患者在入组前1年内至少发生了2次感染加重。

结果显示，红霉素组患者的加重次数减少了近40%[比值比(OR)，0.64；95%置信区间(CI)，0.48~0.86；P=0.02]，每例患者每年加重次数平均减少了0.7次。在试验期间发生≥2次加重的患者，在红霉素组约占1/3（19例），在安慰剂组则超过一半（30例）（P=0.039）。红霉素组仅有1例患者因QT间期延长而在6个月时停药。

两组患者的1秒用力呼气量（FEV1）均略有下降，但在安慰剂组更多见，治疗效应为2.02%（95%CI，0.04~4.2；P=0.046）且有利于红霉素。红霉素组患者每天分泌的痰液也比安慰剂组减少了约6 g。

至研究结束时，从红霉素组分离出的口咽链球菌约36%具有耐药性，而这一比例在安慰剂组为5%（P＜0.0001）。研究者指出：“红霉素治疗确实会使大环内酯类耐药链球菌所占比例明显增加。但阿奇霉素似乎更易诱发耐药，根据比利时一项随机试验，仅仅治疗3天后大环内脂类耐药口咽链球菌所占比例就增加了53.4%（P＜0.0001）(Lancet 2007;369:482-90)。”

“虽然这并非头对头比较，但即便用红霉素治疗1年，诱发耐药的作用仍然弱于阿奇霉素。”不过，Serisier博士同时强调，红霉素可能只适用于气道感染较严重的患者，而并不适用于所有的非CF支气管扩张患者，对于仅有轻度咳嗽的患者肯定不适用。

Serisier博士报告称无相关利益冲突。

爱思唯尔  版权所有

By: M. ALEXANDER OTTO, Internal Medicine News Digital Network

SAN FRANCISCO – Long-term, low-dose erythromycin reduces pulmonary exacerbations, sputum production, and breathing problems in patients with non–cystic fibrosis bronchiectasis, according to a randomized, placebo-controlled Australian study.

Low-dose erythromycin also may be less likely than azithromycin to induce antibiotic resistance, the usual choice for antibiotic prophylaxis. For these reasons, erythromycin "should be considered for the management of subjects with" non-CF bronchiectasis, said lead investigator Dr. David Serisier at an international conference of the American Thoracic Society.

A total of 59 nonsmoking adults with the disease were randomized to erythromycin ethylsuccinate 400 mg twice daily and 58 to placebo, for 48 weeks. (The dosage of the better-tolerated salt is the equivalent of 250 mg of erythromycin b.i.d.) All patients had at least two infective exacerbations in the preceding year, said Dr. Serisier, a chest physician and associate professor of medicine at the University of Queensland in Brisbane.

The erythromycin group had almost 40% fewer exacerbations (odds ratio, 0.64; 95% confidence interval [CI], 0.48-0.86; P = .02), corresponding to a mean reduction of 0.7 exacerbations per patient per year. About a third of the erythromycin patients (19) and more than half (30) of the placebo patients had two or more exacerbations during the trial (P = .039). Only one erythromycin patient was withdrawn for possible QTc prolongation at 6 months.

Forced expiratory volume in 1 second (FEV1) declined slightly in both groups, but more so in the placebo arm, with a treatment effect of 2.02% (95% CI, 0.04-4.2; P = .046) in favor of erythromycin. Erythromycin patients also produced about 6 g less of sputum per day.

By study’s end, about 36% of oropharyngeal streptococci isolates in the erythromycin group were resistant, versus about 5% in the placebo group (P less than .0001). "Erythromycin resulted in a very substantial increase in the proportion of macrolide-resistant streptococci," Dr. Serisier said.

Azithromycin, however, appears to be a more potent inducer of resistance, according to a randomized Belgian trial that found a 53.4% increase (P less than .0001) in macrolide-resistant oral streptococci after just 3 days of treatment (Lancet 2007;369:482-90).

"We are not exactly comparing apples with apples, but there’s a suggestion that this effect is less with erythromycin," even after an entire year of therapy, he said.

Even so, "I think [erythromycin] should be reserved for subjects who have evidence of more severe airway infection. I don’t think it’s something we should be throwing at all non-CF bronchiectasis patients, and [certainly] not those who just have a mild, troublesome cough. I want this drug to be used in patients who really need it," Dr. Serisier said.

Dr. Serisier said he had no relevant disclosures.