PLoS ONE：抗疟药“对抗生素耐药性有贡献”
一项新的研究表明，过度使用一种预防和治疗疟疾的药物可能对一种相关抗生素不断增长的耐药性有贡献。
科学家在《公共科学图书馆 综合》杂志上报告说，他们在圭亚那偏远的雨林社区的村民的消化道内探测到了埃希氏大肠杆菌对抗生素环丙沙星（一种氟喹诺酮类药物）耐药，尽管这些村民从未服用过该药。
大多数村民服用过氯喹——一种与环丙沙星关系非常近的药物——用于防治疟疾。
在为期3年的研究中，共采集了535名村民的样本用于检测耐药细菌，其中4.8%携带耐环丙沙星的大肠杆菌。
圭亚那卫生部部长Leslie Ramsammy博士告诉本网站说，该国去年记录了超过1.1万名疟疾病例。他说这些发现“很吸引人”，而卫生部将进行自己的研究从而验证这个研究结果的准确性。
抗生素环丙沙星在全世界被用于治疗细菌感染，包括肺炎、尿道感染和性传播疾病。该研究首次展示了耐药性可以在从未接触过该药的人的体内出现。
该研究的作者之一、加拿大渥太华Lakeridge卫生网络的传染病专家Michael Silverman说，已知耐药细菌起源于抗生素的过度使用，这就是科学家对发现这种耐药细菌也可以在不能获得环丙沙星的地区出现感到惊讶的原因。
他说，事实上耐环丙沙星大肠杆菌在圭亚那偏远村落的分布比在美国重症监护病房——其中有一半的患者正在使用抗生素——的分布更广。
多伦多大学Sunnybrook卫生科学中心的高级科学家Andrew Simor 说：“大肠杆菌是人类最常见的导致感染的病原体。10年前它还几乎普遍对环丙沙星敏感。”
他说，如今对医院患者进行检验，其中至多有30%患者的大肠杆菌对环丙沙星不敏感。
这组作者写道，对环丙沙星的耐药性可能对疟疾流行地区——因此那里使用氯喹也很常见——造成重大的公共卫生问题，因为环丙沙星和其他氟喹诺酮类药物可能效果更低。
Silverman强调该研究凸显了继续使用经杀虫剂处理的蚊帐以及开发有效的疫苗从而设法预防疟疾的必要性。
推荐原始出处：
PLoS ONE 3(7): e2727. doi:10.1371/journal.pone.0002727
Antimalarial Therapy Selection for Quinolone Resistance among Escherichia coli in the Absence of Quinolone Exposure, in Tropical South America
Ross J. Davidson1,2, Ian Davis3,4, Barbara M. Willey5, Keyro Rizg2, Shelly Bolotin4, Vanessa Porter5, Jane Polsky6, Nick Daneman4, Allison McGeer4,5, Paul Yang7, Dennis Scolnik4, Roy Rowsell3, Olga Imas5, Michael S. Silverman3,4*
1 Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Canada
2 Dalhousie University, Halifax, Canada
3 Lakeridge Health Center, Oshawa, Canada
4 University of Toronto, Toronto, Canada
5 Toronto Medical Laboratories/Mount Sinai Hospital Department of Microbiology, Mount Sinai Hospital, Toronto, Canada
6 St. Michael's Hospital Department of Family & Community Medicine, Toronto, Canada
7 Ontario Ministry of the Environment, Etobicoke, Canada
Background
Bacterial resistance to antibiotics is thought to develop only in the presence of antibiotic pressure. Here we show evidence to suggest that fluoroquinolone resistance in Escherichia coli has developed in the absence of fluoroquinolone use.
Methods
Over 4 years, outreach clinic attendees in one moderately remote and five very remote villages in rural Guyana were surveyed for the presence of rectal carriage of ciprofloxacin-resistant Gram-negative bacilli (GNB). Drinking water was tested for the presence of resistant GNB by culture, and the presence of antibacterial agents and chloroquine by HPLC. The development of ciprofloxacin resistance in E. coli was examined after serial exposure to chloroquine. Patient and laboratory isolates of E. coli resistant to ciprofloxacin were assessed by PCR-sequencing for quinolone-resistance-determining-region (QRDR) mutations.
Results
In the very remote villages, 4.8% of patients carried ciprofloxacin-resistant E. coli with QRDR mutations despite no local availability of quinolones. However, there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic (p<0.01). Antibacterial agents were not found in the drinking water, but chloroquine was demonstrated to be present. Chloroquine was found to inhibit the growth of E. coli in vitro. Replica plating demonstrated that 2-step QRDR mutations could be induced in E. coli in response to chloroquine.
Conclusions
In these remote communities, the heavy use of chloroquine to treat malaria likely selected for ciprofloxacin resistance in E. coli. This may be an important public health problem in malarious areas.
