Griffith David E, Brown-Elliott Barbara A, Langsjoen Brett, Zhang Yansheng, Pan Xi, Girard William, Nelson Kenwyn, Caccitolo James, Alvarez Julio, Shepherd Sara, Wilson Rebecca, Graviss Edward A, Wallace Richard J
The University of Texas Health Center, Department of Medicine, 11937 U.S. Hwy 271, Tyler, TX 75708, USA.
Am J Respir Crit Care Med. 2006 Oct 15;174(8):928-34. doi: 10.1164/rccm.200603-450OC. Epub 2006 Jul 20.
The clinical features and outcome of macrolide-resistant Mycobacterium avium complex (MAC) lung disease are not known.
Characterize patients, treatment, and isolates in macrolide-resistant MAC lung disease.
Retrospective chart review, susceptibility testing, molecular fingerprinting, and DNA sequence analyses of resistant MAC isolates.
We identified 51 patients over a 15-yr period with clarithromycin-resistant MAC (minimum inhibitory concentration (MIC)>or=32 microg/ml) lung disease at a single referral center. Twenty-four (47%) patients had nodular disease with bronchiectasis and 27 (53%) had upper lobe cavitary disease. Most patients (77%) had M. intracellulare. Sequencing of the 23S r-RNA gene showed 49 of 51 isolates (96%) with the expected mutation in adenine 2058 or 2059. Risk factors for resistance included macrolide monotherapy or combination with a quinolone only (39/51 or 76%). Macrolide resistance developed in 12 of 303 (4.0%) patients started on the American Thoracic Society-recommended two companion drugs, with no risk difference in clarithromycin versus azithromycin and daily versus intermittent therapy. Sputum conversion with macrolide-resistant MAC occurred in 11 of 14 (79%) patients who received more than 6 mo of injectable aminoglycoside therapy and lung resection, compared with 2 of 37 (5%) who did not. The 1-yr mortality in patients who remained culture positive was 34% (13/38) compared with 0% (0/13) of patients who became culture negative (converted).
Macrolide resistance rarely occurs in patients also receiving ethambutol and a rifamycin. Macrolide-resistant MAC lung disease requires aggressive drug and surgical therapy for cure.
大环内酯类耐药鸟分枝杆菌复合群（MAC）肺病的临床特征和转归尚不清楚。
对大环内酯类耐药MAC肺病患者、治疗情况及分离菌株进行特征描述。
对耐药MAC分离菌株进行回顾性病历审查、药敏试验、分子指纹分析及DNA序列分析。
在一家转诊中心，我们在15年期间确定了51例患有克拉霉素耐药MAC（最低抑菌浓度（MIC）≥32μg/ml）肺病的患者。24例（47%）患者患有结节性疾病伴支气管扩张，27例（53%）患有上叶空洞性疾病。大多数患者（77%）感染胞内分枝杆菌。对23S r-RNA基因进行测序显示，51株分离菌株中有49株（96%）在腺嘌呤2058或2059处有预期突变。耐药的危险因素包括大环内酯类单药治疗或仅与喹诺酮类联合使用（39/51或76%）。在开始使用美国胸科学会推荐的两种联合药物治疗的303例患者中，有12例（4.0%）出现大环内酯类耐药，克拉霉素与阿奇霉素以及每日给药与间歇给药之间的耐药风险无差异。在接受超过6个月注射用氨基糖苷类治疗和肺切除术的14例患者中，11例（79%）大环内酯类耐药MAC患者痰菌转阴，而未接受上述治疗的37例患者中只有2例（5%）痰菌转阴。仍培养阳性的患者1年死亡率为34%（13/38），而培养转阴的患者死亡率为0%（0/13）。
同时接受乙胺丁醇和利福霉素治疗的患者很少出现大环内酯类耐药。大环内酯类耐药MAC肺病需要积极的药物和手术治疗才能治愈。
