The Problem

A 42-year-old woman presents to you with a 5-day history of nonproductive cough, postnasal drainage, and sore throat. She denies fevers, shortness of breath, or headache. She had received amoxicillin 2 weeks ago for similar symptoms, and although she improved, she feels that she has not completely recovered. On examination she is afebrile and her head and neck, lymph node, and lung exams are normal. You deliver your speech about antibiotic resistance and how important it is to use antibiotics only when absolutely necessary. She becomes quite irritated. You acquiesce by offering her a delayed antibiotic prescription for azithromycin. You inform her not to take it unless she develops fever, shortness of breath, or increased cough. You also ask her to inform the nurse if she starts the antibiotic. You once again berate yourself for “caving.” You also wonder what the evidence is for her personally being resistant to amoxicillin because of the first course of antibiotics she received, and you wonder how long this antibiotic resistance lasts.

The Question

In patients receiving antibiotics in primary care, what is the evidence for personal antibiotic resistance, and how long does it last?

The Search

You open PubMed and enter “antibiotic resistance” AND “primary care.” You find a relevant study.

Our Critique

This systematic review was well conceived and answered an important clinical question with broad application to and relevance for primary care. The search was thorough, and methods of abstraction and quality assessment were standard. What is most striking and profound about this study is that it provides overwhelming evidence for antibiotic resistance in our individual patients after antibiotic treatment, rather than within the abstract concept of “the community.” It is important to remember that antibiotic resistance can be transferred from commensal and pathogenic organisms so that even if the pathogen is eradicated, new pathogens can pick up resistance from the remaining nonpathogenic bacteria. This information should be incorporated into the counseling that we provide patients who, when ill, may not be concerned about antibiotic resistance at the population level but who may be more influenced by hearing about possible increased difficulty with their own treatment if they “really get sick.”

Clinical Decision

The patient calls the next day to tell the nurse that she started the antibiotic because she was not getting any better. You work on your antibiotic speech to make it more convincing for the next patient.

The Evidence

Costelloe C., et al. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: Systematic review and meta-analysis. BMJ 2010;340:c2096.

–Criteria for study inclusion: Studies were eligible for inclusion if they investigated the relationship between antibiotics prescribed in primary care and antimicrobial resistance in bacteria sampled from any body site, were observational and experimental, and were analyzed at the level of the individual.

–Study identification: Investigators searched MEDLINE (1955 to May 2009), EMBASE (1980 to May 2009), Cochrane databases, and the ISI Web of Knowledge.

–Data extraction and quality assessment: Full articles were reviewed independently by two reviewers who extracted study data and assessed study quality.

–Outcomes: Outcomes included bacteria type, sampling location, antibiotics to which resistance was measured, and the method of measuring resistance. The outcome measure was the odds ratio (OR) of resistance among participants exposed to antibiotics, compared with those who were not exposed. ORs were tabulated by bacterium type and sampling location and by time since antibiotic exposure.

–Results: Twenty-four papers were included in the review, including 5 randomized controlled trials and 19 observational studies (2 prospective, 17 controlled observational or case-control). Twenty-two studies sampled bacteria from patients with urinary tract infection, upper respiratory infection, otitis media, chronic obstructive pulmonary disease, methicillin-resistant Staphylococcus aureus (MRSA), or trachoma; two studies were conducted in healthy adult volunteers. A wide variety of antibiotics were given 2-104 weeks before measurement of antibiotic resistance. For the five studies of urinary tract bacteria including more than 14,000 subjects, the ORs for resistance were 2.5 (95% CI: 1-2.9) within 2 months of antibiotic treatment and 1.33 (95% CI: 1.2-1.5) within 12 months. For the seven studies of respiratory tract infections including more than 2,600 patients, the ORs were 2.4 (95% CI: 1.4-3.9) within 2 months and 2.4 (95% CI: 1.3-4.5) within 12 months. Antibiotic resistance changed over time from 12.2 (95% CI: 6.8-22.1) at 1 week to 6.1 (95% CI: 2.8-13.4) at 1 month, 3.6 (95% CI: 2.2-6.0) at 2 months, and 2.2 (95% CI: 1.3-3.6) at 6 months. Longer durations and multiple courses were associated with higher rates of antibiotic resistance. One study found an association between MRSA and the prescription of an antibiotic in the previous 0-6 months (OR 3.1; 95% CI: 1.1-8.6).

Dr. Ebbert and Dr. Tangalos write the “Mindful Practice” column, which regularly appears in Internal Medicine News, an Elsevier publication. They are with the Mayo Clinic in Rochester, Minnesota. They report no conflicts of interest.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

问题

 

患者女性，42岁，因干咳、鼻后滴漏及咽喉痛持续5天而来就诊。患者否认有发烧、气短或头痛的症状。2周前曾服用阿莫西林，尽管有所改善，但自觉仍未痊愈。体格检查：无发热体征，头、颈、淋巴结及肺部检查均未见异常。当向患者介绍有关抗生素耐药性的知识及仅在绝对需要使用抗生素时方使用的重要性时，其情绪转为异常激动。给她提供了一个延迟的阿奇霉素处方，默许其服用抗生素。告知她仅在出现发烧、气短或咳嗽次数增加时服用，同时要求她通知护士开始服用抗生素的日期。你再次为“妥协”而感到自责。你也想知道她个人因接受第一个疗程的抗生素而产生阿莫西林耐药性的证据，并想知道这次抗生素耐药性会持续多久。

 

问题

 

对于在初级医疗保健中接受抗生素治疗的患者，有哪些证据表明他们产生了个体抗生素耐药性，这会持续多久？

 

研究

 

打开PubMed 网页，输入“antibiotic resistance”和 “primary care”，你会查到一项相关研究。

 

评论

 

这项系统性综述构思很好，并对初级医疗保健中广泛应用抗生素或与之相关的问题做出了解答。该研究很全面，摘录的方法和质量评估均很标准。这项研究最惊人且最有意义之处是它可以为个体患者在抗生素治疗后产生耐药性方面提供极具说服力的证据，而非限于“社区”的抽象范畴内。“应谨记，抗生素耐药性可源自共生或致病的微生物，因此即便是致病菌被消除，新的致病菌还能从其余的非致病菌中获得耐药性”。患者在患病时整体上可能都不会关注抗生素耐药性，但在听说若其“确实患病”则采用他们自己的疗法难度有可能会加大时情绪便会受到影响，我们在为他们提供咨询服务时应该对上述耐药性问题加以介绍。

 

临床决策

 

患者次日打电话告诉护士她没有任何好转，故开始服用抗生素。所以，你可对抗生素的描述进行修改，使之对下一例患者更具说服力。

 

证据

 

—研究纳入标准：探讨初级医疗保健中的抗生素处方与人体任何部位获取的细菌样本的抗菌药耐受性之间的关联；属观察性和实验性研究；从患者个人角度进行分析。

 

—研究检索：研究者搜索了MEDLINE(1955年至2009年5月)、EMBASE(1980年至2009年5月)、Cochrane数据库及ISI网页的知识

 

—数据摘录和质量评估：由2位摘录研究数据并评估研究质量的评审员独立地对全文进行审查。

 

—结局：结局包括细菌类型、取样部位、测量耐药性的抗生素以及测量耐药性的方法。结局指标为与未应用抗生素者相比，应用抗生素的受试者中耐药性的比值比(OR)。根据细菌类型、取样部位及距应用抗生素的时间将OR制成表。

 

—结果：综述中共纳入24篇论文，包括5项随机对照试验和19项观察性研究(2项前瞻性研究、17项对照观察或病例对照研究)。22项研究的细菌样本取自泌尿道感染、上呼吸道感染、中耳炎、慢性阻塞性肺病和沙眼患者及耐甲氧西林金黄色葡萄球菌(MRSA)感染者；两项研究在健康的成人志愿者中开展。各种抗生素于抗生素耐药性测定前2~104周用药。对于5项有关泌尿道细菌的研究(包括逾14,000位受试者)， 2个月内接受抗生素治疗的耐药性OR为2.5 (95% CI：1~2.9)，12个月内为1.33 (95% CI：1.2~1.5)。对于7项有关呼吸道感染的研究(受试者逾2,600位)，2个月内的OR为2.4(95% CI：1.4~3.9)，12个月内为2.4 (95% CI：1.3~4.5) 。抗生素耐药性随时间的变化：1周时为12.2(95% CI：6.8~22.1)，1个月时为6.1 (95% CI：2.8~13.4)，2个月时为3.6(95% CI：2.2~6.0)，6个月时为2.2 (95% CI：1.3~3.6)。疗程较长和多个疗程与抗生素耐药的高发率有关。一项研究发现，MRSA与前0~6个月内开的抗生素处方有关(OR 3.1；95% CI：1.1-8.6)。

 

Ebbert博士和Tangalos博士编写“正念实践”栏目，后者为爱思唯尔出版物《内科新闻》的常规内容。他们工作于明尼苏达州罗彻斯特梅奥诊所，无利益冲突的报告。

 

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