Experimental acute otitis media due to nontypeable Haemophilus influenzae:: Comparison of high and low azithromycin doses with placebo
Experimental acute otitis media due to nontypeable Haemophilus influenzae:: Comparison of high and low azithromycin doses with placebo
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DOI：
10.1128/aac.46.7.2194-2199.2002
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发表时间：
2002-07-01
影响因子：
4.9
通讯作者：
Li, Z
中科院分区：
文献类型：
--
作者：
Babl, FE;Pelton, SI;Li, Z
阿奇霉素治疗急性中耳炎(AOM)取得了明显的临床成功，但对于从中耳初始培养中恢复的非分型流感嗜血杆菌(NTHI)儿童，在治疗开始后4-6天进行鼓室穿刺术，发现50%以上的病例持续感染。我们试图确定不同剂量的阿奇霉素对NTHI引起的中耳感染密度的影响，以提供对AOM临床和微生物学结果指标之间的二分法的进一步理解。在实验性中耳炎(EOM)的栗鼠模型中，接受安慰剂治疗的动物与每天每公斤体重单次注射30或120毫克阿奇霉素的动物进行比较，连续5天。在5天的疗程中和治疗后的1周内，通过从中耳获取定量培养来评估微生物学结果。测量阿奇霉素浓度以确定是否存在浓度依赖效应。每天30和120 mg/kg的阿奇霉素对NTHI所致中耳感染的定量评估显示出剂量依赖的效应。每天服用30 mg/kg阿奇霉素后，24小时的血药浓度和血药浓度-时间曲线下面积与已发表的儿童多次服用5-10 mg/kg阿奇霉素的数据相当。与安慰剂或每天30 mg/kg的方案相比，增加剂量的阿奇霉素(120 mg/kg)可以使血清中的水平增加2.5到4倍，细胞外中耳液的总水平和水平增加3到6倍，细菌密度更快地下降，完全灭菌的中耳比例更大。
Treatment of acute otitis media (AOM) with azithromycin results in apparent clinical success, but tympanocentesis performed 4 to 6 days after initiation of therapy in children with nontypeable Haemophilus influenzae (NTHI) recovered from initial middle ear cultures demonstrates persistence of infection in more than 50% of episodes. We sought to determine the effect of azithromycin at different doses on the density of middle ear infection due to NTHI to provide additional understanding of this dichotomy between clinical and microbiologic outcome measures in AOM. In a chinchilla model of experimental otitis media (EOM), animals treated with placebo were compared to animals receiving a single daily dose 30 or 120 mg of azithromycin per kg of body weight per day for 5 days. Microbiologic outcome was assessed by obtaining quantitative cultures from the middle ear during a 5-day course and for 1 week following therapy. Azithromycin concentrations were measured to ascertain whether a concentration-dependent effect was present. Azithromycin at 30 and 120 mg/kg/day demonstrated a dose-dependent effect on the quantitative assessment of middle ear infection due to NTHI. A 30-mg/kg dose of azithromycin daily resulted in levels in serum and areas under the serum concentration-time curve at 24 h comparable to published data obtained with children given azithromycin at 5 to 10 mg/kg in multiday regimens. Increased doses of azithromycin (120 mg/kg) achieved 2.5- to 4-fold-higher levels in serum and 3- to 6-fold-higher total levels and levels in extracellular middle ear fluid as well as more rapid reduction in bacterial density and a greater proportion of middle ears with complete sterilization than either placebo or the 30-mg/kg/day regimen.