Biannual Treatment of Preschool Children with Single Dose Azithromycin to Reduce Mortality: Impact on Azithromycin Resistance in the MORDOR Trial in Tanzania
Biannual Treatment of Preschool Children with Single Dose Azithromycin to Reduce Mortality: Impact on Azithromycin Resistance in the MORDOR Trial in Tanzania
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DOI：
10.4269/ajtmh.19-0086
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发表时间：
2020-09-01
影响因子：
3.3
通讯作者：
West, Sheila K.
中科院分区：
文献类型：
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作者：
Bloch, Evan M.;Coles, Christian L.;West, Sheila K.
大环内酯类药物耐药研究表明，对学龄前儿童每年两次单剂量阿奇霉素可降低死亡率。我们应该评估其对阿奇霉素耐药的影响。在坦桑尼亚Kilosa区随机选择30个社区，对1-59个月的儿童随机接受6个月单剂量阿奇霉素（类似于20mg /kg）和安慰剂治疗。在基线、12个月和24个月时，从每个社区随机选择40名儿童（1-59个月）。分别用鼻咽拭子和直肠拭子对肺炎链球菌和大肠杆菌进行分离和耐药检测。采用纸片扩散法测定阿奇霉素耐药菌株的携带率和比例。在基线时，随机选择的儿童的特征与治疗组相似。在基线和年度横断面调查中，治疗组之间肺炎链球菌和大肠杆菌的分离率相似。在基线、12个月和24个月时，阿奇霉素治疗与安慰剂治疗社区儿童中阿奇霉素耐药肺炎链球菌的比例分别为26.5% （18.1%,P = 0.26）、26.8% （16.5%,P = 0.29）和13.4% （17.0%,P = 0.57）。在基线、12个月和24个月时，阿奇霉素组（与安慰剂组相比）耐阿奇霉素大肠杆菌分离株的比例分别为14.9% （18.9%,P = 0.16）、21.5% （16.6%,P = 0.10）和14.9% （14.7%,P = 0.95）。在24个月内，阿奇霉素和安慰剂的平均治疗覆盖率分别为76.9%和74.8% （P = 0.49）。在24个月的随访中，儿童一年两次给予单剂量阿奇霉素似乎并未导致肺炎链球菌和大肠杆菌分离株阿奇霉素过度耐药。
The Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance study showed that administration of biannual, single-dose azithromycin to preschool children reduces mortality. Wesought to evaluate its impact on azithromycin resistance. Thirty randomly selected communities in Kilosa district, Tanzania, were randomized to receive 6-monthly single-dose azithromycin (similar to 20 mg/kg) versus placebo treatment of children aged 1-59 months. From each community, 40 children (aged 1-59 months) were randomly selected at baseline, 12 and 24 months. Isolation and resistance testing of Streptococcus pneumoniae and Escherichia coli were evaluated using nasopharyngeal and rectal swabs, respectively. The carriage prevalence and the proportion of azithromycin-resistant isolates were determined using disk diffusion. At baseline, the characteristics of the randomly selected children were similar by treatment arms. Both at baseline and in annual cross-sectional surveys, rates of S. pneumoniae and E. coli isolation between treatment arms were similar. The proportions of azithromycin-resistant S. pneumoniae isolates in the children in communities treated with azithromycin versus placebo at baseline, 12 months, and 24 months were 26.5% (18.1%; P = 0.26), 26.8% (16.5%; P = 0.29), and 13.4% (17.0%; P = 0.57), respectively. The proportions of azithromycin-resistant E. coli isolates at baseline, 12 months, and 24 months in the azithromycin (versus placebo) arms were 14.9% (18.9%; P = 0.16), 21.5% (16.6%; P = 0.10), and 14.9% (14.7%; P = 0.95), respectively. Over the 24 months, the mean treatment coverage for the azithromycin and placebo was 76.9% and 74.8%, respectively (P = 0.49). Biannual administration of single-dose azithromycin to children did not appear to result in excess azithromycin resistance in S. pneumoniae and E. coli isolates over 24 months of follow-up.