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多西环素作为抗疟药:对旅行者腹泻和各种粪便细菌中多西环素耐药性的影响 - 前瞻性研究和文献综述。

Doxycycline as an antimalarial: Impact on travellers' diarrhoea and doxycycline resistance among various stool bacteria - Prospective study and literature review.

机构信息

Meilahti Vaccine Research Center MeVac, Department of Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Multidiciplinary Center of Excellence in Antimicrobial Resistance Research, University of Helsinki, Helsinki, Finland; Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Meilahti Vaccine Research Center MeVac, Department of Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Multidiciplinary Center of Excellence in Antimicrobial Resistance Research, University of Helsinki, Helsinki, Finland; Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

出版信息

Travel Med Infect Dis. 2022 Sep-Oct;49:102403. doi: 10.1016/j.tmaid.2022.102403. Epub 2022 Jul 21.

Abstract

BACKGROUND

Antibiotics predispose travellers to acquire multidrug-resistant bacteria, such as extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). Although widely used in antimalarial prophylaxis, doxycycline has scarcely been studied in this respect.

METHODS

We explored the impact of doxycycline on rates of traveller's diarrhoea (TD), ESBL-PE acquisition and, particularly, doxycycline co-resistance among travel-acquired ESBL-PE in a sample of 412 visitors to low- and middle-income countries. We reviewed the literature on traveller studies of doxycycline/tetracycline resistance among stool pathogens and the impact of doxycycline on TD rates, ESBL-PE acquisition, and doxycycline/tetracycline resistance.

RESULTS

The TD rates were similar for doxycycline users (32/46; 69.6%) and non-users (256/366; 69.9%). Of the 90 travel-acquired ESBL-PE isolates, 84.4% were co-resistant to doxycycline: 100% (11/11) among users and 82.3% (65/79) among non-users. The literature on doxycycline's effect on TD was not conclusive nor did it support a recent decline in doxycycline resistance. Although doxycycline did not increase ESBL-PE acquisition, doxycycline-resistance among stool pathogens proved more frequent for users than non-users.

CONCLUSIONS

Our prospective data and the literature review together suggest the following: 1) doxycycline does not prevent TD; 2) doxycycline use favours acquisition of doxy/tetracycline-co-resistant intestinal bacteria; 3) although doxycycline does not predispose to travel-related ESBL-PE acquisition per se, it selects ESBL-PE strains co-resistant to doxycycline; 4) doxycycline resistance rates are high among stool bacteria in general with no evidence of any tendency to decrease.

摘要

背景

抗生素使旅行者更容易感染多药耐药菌,如产超广谱β-内酰胺酶的肠杆菌科(ESBL-PE)。虽然在抗疟预防中广泛使用,但多西环素在这方面的研究甚少。

方法

我们在 412 名前往中低收入国家的旅行者样本中,探讨了多西环素对旅行者腹泻(TD)、ESBL-PE 感染率的影响,特别是旅行获得的 ESBL-PE 中多西环素/四环素耐药的协同性。我们回顾了关于旅行者中多西环素/四环素对粪便病原体耐药性的研究文献,以及多西环素对 TD 发生率、ESBL-PE 感染率和多西环素/四环素耐药性的影响。

结果

多西环素使用者(32/46;69.6%)和非使用者(256/366;69.9%)的 TD 发生率相似。90 株旅行获得的 ESBL-PE 分离株中,84.4%对多西环素协同耐药:使用者中为 100%(11/11),非使用者中为 82.3%(65/79)。关于多西环素对 TD 影响的文献没有定论,也没有支持多西环素耐药性最近下降的证据。虽然多西环素没有增加 ESBL-PE 的获得,但粪便病原体对多西环素的耐药性在使用者中比非使用者更为常见。

结论

我们的前瞻性数据和文献综述表明:1)多西环素不能预防 TD;2)多西环素的使用有利于获得多西环素/四环素协同耐药的肠道细菌;3)虽然多西环素本身不会导致与旅行相关的 ESBL-PE 获得,但它选择对多西环素协同耐药的 ESBL-PE 菌株;4)粪便细菌中的多西环素耐药率普遍较高,没有任何减少的趋势。

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