Spurling G K P, Del Mar C B, Dooley L, Foxlee R
Discipline of General Practice, University of Queensland, Level 2, Edith Cavell Building, Royal Brisbane Hospital, Brisbane, 4029, Queensland, Australia.
Cochrane Database Syst Rev. 2004 Oct 18(4):CD004417. doi: 10.1002/14651858.CD004417.pub2.
The use of antibiotics for upper respiratory tract infections is controversial. Any benefits have to be weighed against common adverse reactions (including rash, abdominal pain, diarrhoea and vomiting), cost and antibacterial resistance. There has been interest in ways to reduce antibiotic prescribing for acute respiratory infections. One is delaying the use of prescribed antibiotics by more than 48 hours for acute upper respiratory tract infections. Such methods have been shown to reduce prescribing. This review asks what effect this practice has on the clinical course of the illness.
To evaluate the clinical effect of delayed antibiotic use in acute upper respiratory tract infections compared to immediate use of antibiotics
The following electronic databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004) which includes the Acute Respiratory Infection Groups' specialised register; MEDLINE (January 1966 to January Week 1 2004), EMBASE (1990 to September 2003) and Current Contents (1998 to 2003). The search was carried out by an expert librarian. Abstracts of identified articles were used to determine which studies were trials.
Randomised controlled trials involving patients of all ages defined as having acute otitis media, acute pharyngitis, sore throat, common cold, a viral upper respiratory tract infection, acute sinusitis, and acute bronchitis were included in which delayed antibiotics are compared to antibiotics used immediately. Delayed antibiotic use was defined as the use of or advice to use antibiotics more than 48 hours after the initial consultation. 'Immediate antibiotic use' was defined as the immediate use of oral antibiotics given at the initial consultation. Clinical outcomes measured included: the presence or absence of fever, cough, pain, duration and severity of illness, complications of the disease, adverse effects from the antibiotics. Trial quality was assessed independently by two reviewers who were blinded to the author, journal and results of each study.
Data was collected by two reviewers who were blinded to the author and journal. Data were analysed and reported using RevMan.
Seven trials were eligible on the basis of design and all reported patient-centred outcomes. Methodological quality of included trials was generally high. There was no difference between immediate and delayed antibiotic groups for symptoms on day one and day seven. For most symptom measures there was no significant difference between the immediate and delayed antibiotic groups. Missing data and marked heterogeneity between study outcomes prevented pooling of results as a meta-analysis. Three studies out of six reporting fever, all involving patients with sore throat, indicated that there was more fever in the delayed antibiotic group. The remaining three studies showed no difference. There was no significant symptom difference for patients with cough or the common cold between the two intervention groups. Pain and malaise severity scores at day three significantly favoured the immediate antibiotic group in children with acute otitis media (Little 2001). In this study by Little 2001 of children with otitis media proxies for other malaise related outcomes were reported, including 'last day of crying' which favoured the immediate antibiotic group by approximately 16 hours (0.69 days; 95% CI 0.31 to 1.07). In the same study, just over half a spoon of paracetamol a day less was used in the immediate antibiotic group (0.59; 95% CI 0.25 to 0.93). There was no significant difference between the intervention groups for the adverse outcome of rash. Two studies reported the outcome of vomiting which was reduced in the immediate antibiotic group in children with suspected streptococcal pharyngitis in El-Daher 1991 but there was no difference in children with sore throat in Little 1997. Diarrhoea was reported by three studies of which two showed no difference Little 1997; Arroll 2002a while Little 2001 reported less diarrhoea in the delayed antibiotic group in children with otitis media.
REVIEWERS' CONCLUSIONS: When considering treatment options for upper respiratory tract infections, the option of delayed antibiotics has been used in an attempt to reduce the use of antibiotic prescriptions. This review shows that for all symptom scores the evidence varies between trials. Most symptom outcomes show no difference between immediate and delayed antibiotic groups. Three of the six studies, all involving patients with sore throat, indicated that patients in the delayed antibiotic group had significantly more fever that their counterparts in the immediate antibiotic group. The other three showed no difference for the outcome of fever. There is evidence indicating that for children with otitis media, pain and malaise scores are worse in the delayed antibiotic group compared to the immediate antibiotic group. This price must be weighed up against the benefits of reduced antibiotic prescribing. Future randomised controlled trials of delaying antibiotics as an intervention should fully report symptoms as well as changes of prescription rates.
抗生素在上呼吸道感染中的使用存在争议。任何益处都必须与常见不良反应(包括皮疹、腹痛、腹泻和呕吐)、成本以及抗菌耐药性相权衡。人们一直对减少急性呼吸道感染抗生素处方的方法感兴趣。其中一种方法是将急性上呼吸道感染处方抗生素的使用推迟超过48小时。此类方法已被证明可减少处方量。本综述探讨这种做法对疾病临床病程有何影响。
评估与立即使用抗生素相比,延迟使用抗生素在急性上呼吸道感染中的临床效果。
检索了以下电子数据库:Cochrane对照试验中心注册库(CENTRAL)(《Cochrane图书馆》2004年第1期),其中包括急性呼吸道感染组的专业注册库;MEDLINE(1966年1月至2004年1月第1周)、EMBASE(1990年至2003年9月)和《现刊目次》(1998年至2003年)。检索由一位专业图书馆员进行。已识别文章的摘要用于确定哪些研究为试验。
纳入涉及所有年龄段患者的随机对照试验,这些患者被定义为患有急性中耳炎、急性咽炎、咽喉痛、普通感冒、病毒性上呼吸道感染、急性鼻窦炎和急性支气管炎,比较延迟使用抗生素与立即使用抗生素的情况。延迟使用抗生素定义为在初次就诊后超过48小时使用或建议使用抗生素。“立即使用抗生素”定义为在初次就诊时立即使用口服抗生素。测量的临床结局包括:发热、咳嗽、疼痛的有无,疾病的持续时间和严重程度,疾病并发症,抗生素的不良反应。两名对作者、期刊和每项研究结果不知情的评审员独立评估试验质量。
数据由两名对作者和期刊不知情的评审员收集。使用RevMan对数据进行分析和报告。
基于设计,七项试验符合要求,所有试验均报告了以患者为中心的结局。纳入试验的方法学质量总体较高。在第1天和第7天,立即使用抗生素组和延迟使用抗生素组的症状无差异。对于大多数症状测量指标,立即使用抗生素组和延迟使用抗生素组之间无显著差异。缺失数据以及研究结果之间明显的异质性使得无法将结果合并进行荟萃分析。六项报告发热的研究中有三项,均涉及咽喉痛患者,表明延迟使用抗生素组发热更多。其余三项研究显示无差异。两个干预组中咳嗽或普通感冒患者的症状无显著差异。在急性中耳炎儿童中,第3天疼痛和不适严重程度评分明显有利于立即使用抗生素组(Little,2001年)。在Little 2001年这项关于中耳炎儿童的研究中,报告了与其他不适相关结局的替代指标,包括“停止哭闹的最后一天”,立即使用抗生素组在此指标上比延迟使用抗生素组快约16小时(0.69天;95%置信区间0.31至1.07)。在同一研究中,立即使用抗生素组每天使用的对乙酰氨基酚量少半匙多(0.59;95%置信区间0.25至0.93)。干预组在皮疹不良结局方面无显著差异。两项研究报告了呕吐结局,在El-Daher 1991年疑似链球菌性咽炎儿童中,立即使用抗生素组呕吐减少,但在Little 1997年咽喉痛儿童中无差异。三项研究报告了腹泻情况,其中两项显示无差异(Little 1997;Arroll 2002a),而Little 2001年报告中耳炎儿童中延迟使用抗生素组腹泻较少。
在考虑上呼吸道感染的治疗方案时,延迟使用抗生素这一选择已被用于试图减少抗生素处方量。本综述表明,对于所有症状评分,各试验的证据有所不同。大多数症状结局在立即使用抗生素组和延迟使用抗生素组之间无差异。六项研究中有三项,均涉及咽喉痛患者,表明延迟使用抗生素组患者的发热明显多于立即使用抗生素组的患者。其他三项研究在发热结局方面显示无差异。有证据表明,对于中耳炎儿童,延迟使用抗生素组的疼痛和不适评分比立即使用抗生素组更差。必须将此代价与减少抗生素处方的益处相权衡。未来将延迟使用抗生素作为一种干预措施的随机对照试验应充分报告症状以及处方率的变化。