Pediatric Infectious Diseases Unit, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Pediatr Infect Dis J. 2009 Dec;28(12):1105-10. doi: 10.1097/INF.0b013e3181b20e7a.
Culture-negative AOM is often milder and associated with lower local/systemic inflammatory responses than culture-positive AOM.
To compare the clinical outcome of culture-negative AOM with that of culture-positive AOM children.
Children aged 3 to 35 months with AOM were enrolled in 11 double-tympanocentesis antibiotic efficacy studies documenting both bacteriologic (days 4-6 of treatment) and clinical outcome (days 11-14, end of treatment). Univariate analysis (age, gender, ethnicity, previous AOM history, and antibiotic treatment) between culture-negative and culture-positive AOM patients was performed by Student t test, ANOVA, or chi2 test. Those found to be significant were further submitted to multivariable regression analysis.
A total of 1088 patients (mean age, 11.95 +/- 5.96 months, 209 culture-negative and 879 culture-positive AOM) were enrolled. No differences were recorded between culture-negative AOM and culture-positive AOM patients in age, gender, ethnicity and number of previous episodes. Seventy-four percent (650/879) culture-positive AOM patients achieved bacteriologic eradication within 3 to 5 days. Successful outcome (cured + improved) was recorded in 90% (189/209) culture-negative AOM patients versus 86% (758/879) in culture-positive AOM (P = 0.086). Successful clinical outcome was more frequent in culture-negative than in culture-positive AOM without bacteriologic eradication (90% vs. 67% [154/229], P < 0.001). No difference in successful clinical outcome was found between culture-negative versus culture-positive AOM patients with bacterial eradication (90% vs. 93% [604/650], P = 0.24). Overall, the inclusion of culture-negative AOM patients in the evaluation of clinical failures rates in study patients decreased the total clinical failure rate by 9%. We present a hypothetical antibiotic efficacy study enrolling 300 patients in whom 2 drugs with different bacteriologic efficacy rates (A-90% and B-60%) were used. When the culture-negative cases (5% clinical failure) enrolled increased from 50/300 (16.7%) to 150/300 (50%), the overall clinical failure rate decreased by 36% (from 17.4% to 11.2%, P = 0.08) for the less efficacious drug, while remaining unmodified for the more efficacious drug (9.6% and 8.8%, respectively).
(1) Clinical outcome in culture-negative AOM was similar to that of culture-positive AOM with bacteriologic eradication and both were superior to that of culture-positive AOM without eradication; (2) Inclusion of culture-negative AOM patients in series aiming at antibiotic efficacy may falsely improve the clinical outcome for antibiotics with reduced ability to eradicate AOM pathogens.
与培养阳性中耳炎相比，培养阴性中耳炎通常较轻，且与较低的局部/全身炎症反应相关。
比较培养阴性中耳炎与培养阳性中耳炎患儿的临床转归。
11 项双鼓膜切开术抗生素疗效研究共纳入 3 至 35 月龄患有中耳炎的儿童，这些研究记录了细菌学（治疗第 4-6 天）和临床结局（治疗第 11-14 天，治疗结束时）。采用学生 t 检验、方差分析或卡方检验对培养阴性和培养阳性中耳炎患者进行单变量分析（年龄、性别、种族、既往中耳炎病史和抗生素治疗）。将发现的有统计学意义的因素进一步进行多变量回归分析。
共纳入 1088 例患者（平均年龄 11.95±5.96 个月，209 例培养阴性中耳炎和 879 例培养阳性中耳炎）。培养阴性中耳炎和培养阳性中耳炎患者在年龄、性别、种族和既往发作次数方面无差异。74%（650/879）的培养阳性中耳炎患者在 3-5 天内达到细菌学清除。培养阴性中耳炎患者的治愈+好转率为 90%（189/209），培养阳性中耳炎患者为 86%（758/879）（P=0.086）。在未达到细菌学清除的情况下，培养阴性中耳炎的临床转归优于培养阳性中耳炎（90% vs. 67%[154/229]，P<0.001）。在达到细菌学清除的情况下，培养阴性中耳炎和培养阳性中耳炎患者的临床转归无差异（90% vs. 93%[604/650]，P=0.24）。总的来说，在评估研究患者的临床失败率时纳入培养阴性中耳炎患者可使总临床失败率降低 9%。我们提出了一个假设性的抗生素疗效研究，纳入了 300 例患者，这些患者使用了两种具有不同细菌学疗效的药物（A-90%和 B-60%）。当纳入的培养阴性病例（5%的临床失败）从 50/300（16.7%）增加到 150/300（50%）时，疗效较低的药物的总体临床失败率降低了 36%（从 17.4%降至 11.2%，P=0.08），而疗效较高的药物则无变化（分别为 9.6%和 8.8%）。
（1）培养阴性中耳炎的临床转归与培养阳性中耳炎且具有细菌学清除的患者相似，两者均优于未清除细菌的培养阳性中耳炎患者；（2）在旨在评估抗生素疗效的研究系列中纳入培养阴性中耳炎患者可能会错误地提高抗生素的临床转归，因为这些抗生素清除中耳炎病原体的能力降低。
