非洲地區阿奇黴素大量分發增加抗生素耐藥性
作者：
小柯機器人發布時間：2020/11/16 13:38:17
美國加州大學Thuy Doan團隊研究了阿奇黴素大量分發與大環內酯類和非大環內酯類耐藥的相關性。2020年11月11日，該研究發表在《新英格蘭醫學雜誌》上。
此前研究表明，兩年內每年兩次向學齡前兒童大量分發阿奇黴素可降低撒哈拉以南非洲地區的兒童死亡率，但增加了大環內酯類藥物的耐藥性。尚不清楚長期每年兩次使用阿奇黴素對腸道耐藥性的影響。
研究組對接受了每年兩次、連續4年阿奇黴素治療的兒童的腸道耐藥性進行了調查。研究組在尼日進行了一項並行試驗，招募了30個村莊，這些村莊被隨機分配，接受阿奇黴素或安慰劑的大規模分發，每6個月向所有1至59個月大的兒童提供4年。在基線、36個月和48個月時收集這些兒童的直腸拭子，來分析腸道耐藥性。
在48個月期間，接受安慰劑村莊的平均覆蓋率為86.6％，接受阿奇黴素村莊為83.2％。在整個試驗期間，研究組共收集了3232個樣本；在48個月的監測隨訪中，對15個接受安慰劑村莊的546個樣本和14個接受阿奇黴素村莊的504個樣本進行了分析。
與安慰劑組相比，阿奇黴素組大環內酯類藥物耐藥的決定因素更高：36個月時高7.4倍，48個月時高7.5倍。持續的大規模阿奇黴素分發也被確定為非大環內酯類耐藥的決定因素，包括對β-內醯胺類抗生素的耐藥，這是非洲該區域經常開的一種抗生素。
研究結果表明，抗生素耐藥性在接受阿奇黴素的村莊比接受安慰劑的村莊更為普遍，即阿奇黴素的大量分發可能會增加抗生素耐藥性。
附：英文原文
Title: Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution
Author: Thuy Doan, M.D., Ph.D.,, Lee Worden, Ph.D.,, Armin Hinterwirth, Ph.D.,, Ahmed M. Arzika, M.S.,, Ramatou Maliki, M.S.,, Amza Abdou, M.D.,, Lina Zhong, B.S.,, Cindi Chen, M.S.,, Catherine Cook, M.P.H.,, Elodie Lebas, R.N.,, Kieran S. O』Brien, Ph.D., M.P.H.,, Catherine E. Oldenburg, Sc.D., M.P.H.,, Eric D. Chow, Ph.D.,, Travis C. Porco, Ph.D., M.P.H.,, Marc Lipsitch, Ph.D.,, Jeremy D. Keenan, M.D., M.P.H.,, and Thomas M. Lietman, M.D.
Issue&Volume: 2020-11-11
Abstract:
BACKGROUND
Mass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear.
METHODS
We investigated the gut resistome of children after they received twice-yearly distributions of azithromycin for 4 years. In the Niger site of the MORDOR trial, we enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years. Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants』 gut resistome. The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months.
RESULTS
Over the entire 48-month period, the mean (±SD) coverage was 86.6±12% in the villages that received placebo and 83.2±16.4% in the villages that received azithromycin. A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were analyzed. Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95% CI, 3.8 to 23.1) at 48 months. Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa.
CONCLUSIONS
Among villages assigned to receive mass distributions of azithromycin or placebo twice yearly for 4 years, antibiotic resistance was more common in the villages that received azithromycin than in those that received placebo. This trial showed that mass azithromycin distributions may propagate antibiotic resistance.
DOI: NJ202011123832009
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2002606