Hansen C R, Pressler T, Hoiby N, Johansen H K
Copenhagen CF centre, Department of Pediatrics, Denmark.
J Cyst Fibros. 2009 Jan;8(1):58-62. doi: 10.1016/j.jcf.2008.09.001. Epub 2008 Oct 11.
Since 2001, long-term, low-dose azithromycin treatment has been used for CF patients chronically infected with Pseudomonas aeruginosa in the Copenhagen CF centre. Our study investigates changes in incidence of colonization with Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and changes in macrolide sensitivity in these microorganisms during azithromycin treatment.
CF patients treated continuously with azithromycin for at least 3 months were included. Results of microbiological examination, including phage typing results of S. aureus, obtained during treatment were compared to results obtained 2 years before treatment.
70 patients (median age 29.1 years) treated for a median of 4 years (range 0.7-5.1) were included. Before treatment, 44 patients had at least one culture positive for S. aureus compared to 25 patients during treatment (p<0.01). Mean percentage of sputum samples with growth of S. aureus decreased from 12.1% (range 0-82.6%) before treatment to 6.1% (range 0-93.2) during treatment (p<0.0006). Prevalence's of H. influenzae and S. pneumoniae also decreased significantly. Fifteen of 214 isolates (7%) of S. aureus were macrolide resistant before treatment, increasing to 95 of 181 isolates (52.5%) during treatment (p<0.001). Macrolide resistant strains were found in 3 of 44 S. aureus colonized patients before treatment and in 11 of 25 patients at some time during treatment (p<0.03), all belonging to different phage types. First resistant S. aureus isolate was isolated after a median treatment duration of 1.5 years (range 0.3-2.9). No MRSA were isolated. Only 1 macrolide resistant isolate of M. catarrhalis was found during treatment. No macrolide resistance was found in H. influenzae or S. pneumoniae.
Long-term, low-dose treatment with azithromycin in CF patients leads to reduced prevalence of S. aureus, S. pneumoniae, and H. influenzae, but increased macrolide resistance in S. aureus. Reduction in the prevalence of S. aureus will make increasing macrolide resistance clinically insignificant in these patients.
自2001年以来，哥本哈根囊性纤维化（CF）中心一直对长期慢性感染铜绿假单胞菌的CF患者采用低剂量阿奇霉素进行治疗。我们的研究调查了金黄色葡萄球菌、肺炎链球菌、流感嗜血杆菌和卡他莫拉菌的定植发生率变化，以及这些微生物在阿奇霉素治疗期间对大环内酯类药物敏感性的变化。
纳入连续接受阿奇霉素治疗至少3个月的CF患者。将治疗期间获得的微生物学检查结果，包括金黄色葡萄球菌的噬菌体分型结果，与治疗前2年获得的结果进行比较。
纳入70例患者（中位年龄29.1岁），中位治疗时间为4年（范围0.7 - 5.1年）。治疗前，44例患者至少有一次金黄色葡萄球菌培养阳性，治疗期间为25例（p<0.01）。金黄色葡萄球菌生长的痰液样本平均百分比从治疗前的12.1%（范围0 - 82.6%）降至治疗期间的6.1%（范围0 - 93.2%）（p<0.0006）。流感嗜血杆菌和肺炎链球菌的患病率也显著下降。治疗前214株金黄色葡萄球菌分离株中有15株（7%）对大环内酯类耐药，治疗期间增至181株中的95株（52.5%）（p<0.001）。治疗前44例金黄色葡萄球菌定植患者中有3例发现大环内酯类耐药菌株，治疗期间25例患者中有11例在某个时间点发现（p<0.03），均属于不同的噬菌体类型。第一株耐药金黄色葡萄球菌分离株在中位治疗持续时间1.5年（范围0.3 - 2.9年）后分离得到。未分离到耐甲氧西林金黄色葡萄球菌（MRSA）。治疗期间仅发现1株卡他莫拉菌大环内酯类耐药分离株。在流感嗜血杆菌或肺炎链球菌中未发现大环内酯类耐药。
CF患者长期低剂量阿奇霉素治疗可降低金黄色葡萄球菌、肺炎链球菌和流感嗜血杆菌的患病率，但会增加金黄色葡萄球菌对大环内酯类的耐药性。金黄色葡萄球菌患病率的降低将使这些患者中不断增加的大环内酯类耐药性在临床上变得不那么重要。
