Heikkinen T, Ghaffar F, Okorodudu A O, Chonmaitree T
Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77555-0371, USA.
Pediatrics. 1998 Aug;102(2 Pt 1):296-9. doi: 10.1542/peds.102.2.296.
Increasing prevalence of antibiotic-resistant bacteria is a serious clinical problem that calls for reduction of unnecessary use of antibiotics. Acute otitis media (AOM) is the most common reason for antibiotic therapy in the United States. Approximately 30% of AOM cases do not have a bacterial etiology. Rapid identification of these cases could help withhold unnecessary antibiotic treatment.
To determine the usefulness of serum levels of interleukin-6 (IL-6), an acute phase cytokine shown to be a reliable marker of neonatal bacterial infection, in differentiation between bacterial and nonbacterial AOM in children.
IL-6 was measured in stored serum samples from 184 children (mean age, 22 months) with AOM who were enrolled in antibiotic efficacy trials at our department. The samples were obtained at enrollment and at 9 to 12 days after initiation of antibiotic therapy. Sera from 21 uninfected children (mean age, 23 months) were used as controls. The etiology of AOM was determined by bacterial and viral cultures as well as respiratory syncytial virus antigen detection in the middle ear fluids obtained by tympanocentesis.
Bacterial etiology of AOM was confirmed in 125 children (68%), whereas in 59 children (32%) no bacterial pathogen could be detected in the middle ear fluid. Children with bacterial AOM had significantly higher IL-6 levels than those with nonbacterial AOM (median, 11.5 vs 3.7 pg/mL). However, this difference was almost entirely attributable to pneumococcal AOM specifically. IL-6 levels in children with AOM caused by Streptococcus pneumoniae were significantly higher (median, 40.1 pg/mL) than in AOM caused by Haemophilus influenzae (7.3 pg/mL) or Moraxella catarrhalis (6.8 pg/mL). At the cutoff value of 30 pg/mL, the specificity of IL-6 for detection of pneumococcal AOM was 91% with a sensitivity of 61%, but its sensitivity for detection of bacterial AOM in general was only 27%.
Low levels of IL-6 do not rule out bacterial etiology of AOM in general; therefore, IL-6 is not sensitive enough as a marker of bacterial AOM. Surprisingly, serum IL-6 levels in pneumococcal AOM were significantly higher than the levels associated with other bacterial AOM, and serum IL-6 levels of >30 pg/mL were highly specific for pneumococcal AOM. These findings suggest a distinctive role for S pneumoniae in the pathogenesis of AOM.
抗生素耐药菌的日益流行是一个严重的临床问题，需要减少抗生素的不必要使用。急性中耳炎（AOM）是美国抗生素治疗最常见的原因。大约30%的AOM病例没有细菌病因。快速识别这些病例有助于避免不必要的抗生素治疗。
确定血清白细胞介素-6（IL-6）水平在儿童细菌性和非细菌性AOM鉴别诊断中的作用，IL-6是一种急性期细胞因子，已被证明是新生儿细菌感染的可靠标志物。
对184例（平均年龄22个月）患有AOM并参与我们科室抗生素疗效试验的儿童的储存血清样本进行IL-6检测。样本在入组时以及抗生素治疗开始后9至12天采集。将21例未感染儿童（平均年龄23个月）的血清用作对照。通过鼓膜穿刺获取的中耳液中的细菌和病毒培养以及呼吸道合胞病毒抗原检测来确定AOM的病因。
125例儿童（68%）确诊为AOM的细菌病因，而59例儿童（32%）的中耳液中未检测到细菌病原体。细菌性AOM儿童的IL-6水平显著高于非细菌性AOM儿童（中位数分别为11.5和3.7 pg/mL）。然而，这种差异几乎完全归因于肺炎球菌性AOM。由肺炎链球菌引起的AOM儿童的IL-6水平显著高于由流感嗜血杆菌（7.3 pg/mL）或卡他莫拉菌（6.8 pg/mL）引起的AOM儿童。在30 pg/mL的临界值时，IL-6检测肺炎球菌性AOM的特异性为91%，敏感性为61%，但它检测一般细菌性AOM的敏感性仅为27%。
一般来说，低水平的IL-6不能排除AOM的细菌病因；因此，IL-6作为细菌性AOM的标志物不够敏感。令人惊讶的是，肺炎球菌性AOM的血清IL-6水平显著高于其他细菌性AOM，血清IL-6水平>30 pg/mL对肺炎球菌性AOM具有高度特异性。这些发现表明肺炎链球菌在AOM发病机制中具有独特作用。
