Hedrick J A, Sher L D, Schwartz R H, Pierce P
Kentucky Pediatric/Adult Research, Bardstown 40004, USA.
Clin Ther. 2001 Feb;23(2):193-204. doi: 10.1016/s0149-2918(01)80002-3.
The recommendation of the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group that high-dose amoxicillin, with or without clavulanate, be used to treat acute otitis media (AOM) addressed concerns about the efficacy of existing therapies against drug-resistant S. pneumoniae. This recommendation relied on pharmacodynamic predictions of concentrations of amoxicillin in middle-ear fluid remaining higher than minimum inhibitory concentrations against intermediately resistant S. pneumoniae for >40% of the dosing interval.
This study compared the tolerability and efficacy of cefprozil and high-dose amoxicillin/clavulanate in patients with AOM.
Patients were randomized to receive 10 days of investigator-blinded oral treatment with either cefprozil suspension (30 mg/kg/d in 2 divided doses) or amoxicillin/clavulanate (45/6.4 mg/kg/d) plus amoxicillin (45 mg/kg/d) in 2 divided doses. The primary efficacy end point was the clinical cure rate 4 to 7 days after the end of treatment. Clinical response by age (6 months-<2 years vs > or =2-7 years), disease severity, and unilateral versus bilateral ear infection was also examined. The primary measures of tolerability were the frequency and severity of adverse events and their relation to study drug. Adverse events were either spontaneously reported or elicited during examination and questioning of the patient. Identified adverse events were coded and recorded using the COSTART (Coding Symbols for Thesaurus of Adverse Reaction Terms) system.
Three hundred four children between the ages of 6 months and 7 years with > or =1 sign or symptom of AOM were enrolled in the study, and 303 (150 cefprozil, 153 amoxicillin/clavulanate) were treated. Twenty-three patients in each treatment group were not evaluable; thus, 257 children were included in the analysis of evaluable patients. Clinical cure rates were 87% (110/127) with cefprozil and 89% (116/130) with amoxicillin/clavulanate (95% CI for the difference in cure rate, -10.7% to 4.1%). No between-group differences in efficacy were noted by age, disease severity, or unilateral or bilateral involvement. The overall incidence of drug-related adverse events was significantly lower with cefprozil than with amoxicillin/clavulanate (19% vs 32%, respectively; P = 0.008), as was the incidence of diarrhea (9% vs 19%, respectively; P = 0.021). Adverse events prompted discontinuation of therapy in 4 (3%) cefprozil patients and 8 (5%) amoxicillin/clavulanate patients.
Based on a search of MEDLINE, this study is the first direct comparison of cefprozil versus high-dose amoxicillin/clavulanate. Cefprozil was as effective as high-dose amoxicillin/clavulanate, with a lower incidence of adverse events.
耐青霉素肺炎链球菌治疗工作组建议使用高剂量阿莫西林（无论是否联用克拉维酸）治疗急性中耳炎（AOM），这一建议回应了人们对现有疗法治疗耐青霉素肺炎链球菌疗效的担忧。该建议基于药效学预测，即中耳液中阿莫西林浓度在给药间隔的40%以上时间内保持高于对中度耐药肺炎链球菌的最低抑菌浓度。
本研究比较头孢丙烯与高剂量阿莫西林/克拉维酸治疗AOM患者的耐受性和疗效。
患者被随机分为两组，接受为期10天的研究者设盲口服治疗，一组服用头孢丙烯混悬液（30mg/kg/d，分2次给药），另一组服用阿莫西林/克拉维酸（45/6.4mg/kg/d）加阿莫西林（45mg/kg/d，分2次给药）。主要疗效终点为治疗结束后4至7天的临床治愈率。还对不同年龄（6个月至<2岁与≥2至7岁）、疾病严重程度以及单侧与双侧耳部感染的临床反应进行了研究。耐受性的主要衡量指标是不良事件的发生频率和严重程度及其与研究药物的关系。不良事件通过患者自行报告或在检查及询问过程中引出。使用COSTART（不良反应术语词库编码符号）系统对识别出的不良事件进行编码和记录。
304名年龄在6个月至7岁、有≥1项AOM体征或症状的儿童纳入本研究，303名（150名服用头孢丙烯，153名服用阿莫西林/克拉维酸）接受了治疗。每个治疗组有23名患者不可评估；因此，257名儿童被纳入可评估患者的分析。头孢丙烯组的临床治愈率为87%（110/127），阿莫西林/克拉维酸组为89%（116/130）（治愈率差异的95%CI为-10.7%至4.1%）。在年龄、疾病严重程度或单侧或双侧受累方面，未观察到组间疗效差异。头孢丙烯组与药物相关的不良事件总发生率显著低于阿莫西林/克拉维酸组（分别为19%和32%；P = 0.008），腹泻发生率也是如此（分别为9%和19%；P = 0.021）。不良事件导致4名（3%）服用头孢丙烯的患者和8名（5%）服用阿莫西林/克拉维酸的患者停药。
基于对MEDLINE的检索，本研究是头孢丙烯与高剂量阿莫西林/克拉维酸的首次直接比较。头孢丙烯与高剂量阿莫西林/克拉维酸疗效相当，但不良事件发生率较低。
