Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial.
Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial.
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DOI：
10.1136/thoraxjnl-2015-207194
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发表时间：
2015-10
期刊：
影响因子：
10
通讯作者：
Wedzicha JA
中科院分区：
文献类型：
--
作者：
Brill SE;Law M;El-Emir E;Allinson JP;James P;Maddox V;Donaldson GC;McHugh TD;Cookson WO;Moffatt MF;Nazareth I;Hurst JR;Calverley PM;Sweeting MJ;Wedzicha JA
长期抗生素治疗用于预防COPD恶化，但是否能减少气道细菌尚不确定。最佳抗生素选择仍然未知。我们在稳定的COPD患者中进行了一项探索性试验，比较三种抗生素方案与安慰剂。这是一项单中心、单盲、随机安慰剂对照试验。年龄≥45岁的COPD、FEV 1 <80%预测值和慢性排痰性咳嗽患者被随机分配接受利福沙星400 mg/d，每4周5天，多西环素100 mg/d，阿奇霉素250 mg/周3次或安慰剂片剂每日1片，共13周。 主要结局是痰液中总培养细菌载量较基线的变化;次要结局包括16 S定量PCR（qPCR）测定的细菌载量、痰液炎症和抗生素耐药性。99例患者接受随机化; 86例完成随访，能够咳出痰液并进行分析。调整后，与安慰剂相比，阿普沙星、多西环素和阿奇霉素的细菌载量分别降低0.42 log 10 cfu/mL（95%CI-0.08 - 0.91，p=0.10）、0.11（-0.33 - 0.55，p=0.62）和0.08（-0.38 - 0.54，p=0.73），但无显著性差异。 通过16 S qPCR测量的细菌负荷或气道炎症也没有显著变化。与治疗相关的不良事件更多的发生与阿托沙星。值得注意的是，在所有治疗组中，培养分离株的平均抑制浓度比安慰剂至少增加3倍。抗生素治疗3个月后，总气道细菌负荷没有显著下降。在所有治疗组中均观察到抗生素耐药性的大幅增加，这对未来的研究具有重要意义。clinicaltrials.gov（NCT01398072）。
Long-term antibiotic therapy is used to prevent exacerbations of COPD but there is uncertainty over whether this reduces airway bacteria. The optimum antibiotic choice remains unknown. We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo. This was a single-centre, single-blind, randomised placebo-controlled trial. Patients aged ≥45 years with COPD, FEV1<80% predicted and chronic productive cough were randomised to receive either moxifloxacin 400 mg daily for 5 days every 4 weeks, doxycycline 100 mg/day, azithromycin 250 mg 3 times a week or one placebo tablet daily for 13 weeks. The primary outcome was the change in total cultured bacterial load in sputum from baseline; secondary outcomes included bacterial load by 16S quantitative PCR (qPCR), sputum inflammation and antibiotic resistance. 99 patients were randomised; 86 completed follow-up, were able to expectorate sputum and were analysed. After adjustment, there was a non-significant reduction in bacterial load of 0.42 log10 cfu/mL (95% CI −0.08 to 0.91, p=0.10) with moxifloxacin, 0.11 (−0.33 to 0.55, p=0.62) with doxycycline and 0.08 (−0.38 to 0.54, p=0.73) with azithromycin from placebo, respectively. There were also no significant changes in bacterial load measured by 16S qPCR or in airway inflammation. More treatment-related adverse events occurred with moxifloxacin. Of note, mean inhibitory concentrations of cultured isolates increased by at least three times over placebo in all treatment arms. Total airway bacterial load did not decrease significantly after 3 months of antibiotic therapy. Large increases in antibiotic resistance were seen in all treatment groups and this has important implications for future studies. clinicaltrials.gov (NCT01398072).