Leibovitz Eugene, Greenberg David, Piglansky Lolita, Raiz Simon, Porat Nurith, Press Joseph, Leiberman Alberto, Dagan Ron
Pediatric Infectious Disease Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Pediatr Infect Dis J. 2003 Mar;22(3):209-16. doi: 10.1097/01.inf.0000066798.69778.07.
(1) To determine the relationship between acute otitis media (AOM) pathogens isolated in cases of early clinical recurrence of AOM (occurring within 1 month from completion of therapy) to the original pathogens causing the initial AOM episode; and (2) To determine whether shorter time intervals between completion of antibiotic therapy and clinical recurrences of AOM are associated with higher rates of true bacteriologic relapse.
From 1995 through 2000, 1077 infants and young children ages 3 to 36 months with AOM were enrolled in double tympanocentesis (performed on Day 1 in all patients and Days 4 to 6 in those initially culture-positive) studies. Of these, 834 (77%) completed successfully the antibiotic treatment [pathogen eradication on Days 4 to 6 of therapy or no pathogen on middle ear fluid (MEF) culture on Day 1 and clinical improvement at end of therapy]. Patients were followed for 3 to 4 weeks after completion of therapy, and additional MEF cultures were obtained if clinical recurrence occurred. True bacteriologic relapse was defined as the presence of a pathogen identical with that isolated before therapy by serotype and pulsed field gel electrophoresis for and by pulsed field gel electrophoresis for Streptococcus pneumoniae and beta-lactamase production for Haemophilus influenzae.
MEF cultures were performed in 108 consecutive patients with early recurrent AOM. One hundred pathogens were isolated at recurrence in 88 of 108 (81%) patients: 54 H. influenzae; 45 S. pneumoniae; and 1 Moraxella catarrhalis. Most recurrent AOM episodes developed during the first 2 weeks of follow-up; 39 (36%), 38 (35%), 21 (19%) and 10 (9%) recurrent AOM episodes occurred on Days 1 to 7, 8 to 14, 15 to 21 and 22 to 28 after completion of therapy, respectively. In most patients these episodes were caused by a new pathogen. True bacteriologic relapses were found in 30 (28%) of 108 patients whose MEF cultures were positive for 35 pathogens: 13 of 108 (12%) S. pneumoniae; 12 of 108 (11%) H. influenzae; and 5 of 108 (5%) both. When timing of recurrent AOM after completion of therapy was analyzed, true bacteriologic relapses were found in 16 of 39 (41%), 10 of 38 (26%), 3 of 21 (14%) and 1 of 10 (10%) of all episodes on Days 1 to 7, 8 to 14, 15 to 21 and 22 to 28 after completion of therapy, respectively (P = 0.01). The respective rates for were 11 of 17 (65%), 3 of 10 (30%), 3 of 13 (23%) and 1 of 5 (20%) (P = 0.02). For H. influenzae the respective rates were 8 of 19 (42%), 9 of 23 (39%), 0 of 8 (0%) and 0 of 4 (0%) (P = 0.02).
Most recurrent AOM episodes occurring within 1 month from completion of antibiotic therapy are in fact new infections. Most of the true bacteriologic AOM relapses occur within 14 days after completion of therapy, but even during this time interval most of the recurrences are caused by new pathogens. H. influenzae is very unlikely to cause true bacteriologic AOM relapses 14 days or later after completion of therapy.
（1）确定急性中耳炎（AOM）早期临床复发（治疗结束后1个月内发生）病例中分离出的病原体与引起初始AOM发作的原始病原体之间的关系；（2）确定抗生素治疗结束与AOM临床复发之间较短的时间间隔是否与较高的真正细菌学复发率相关。
1995年至2000年，1077名3至36个月大患有AOM的婴幼儿参加了双鼓膜穿刺术研究（所有患者在第1天进行，最初培养阳性的患者在第4至6天进行）。其中，834名（77%）成功完成了抗生素治疗[治疗第4至6天病原体清除或第1天中耳积液（MEF）培养无病原体且治疗结束时临床症状改善]。治疗结束后对患者随访3至4周，若发生临床复发则获取额外的MEF培养物。真正的细菌学复发定义为通过血清型和脉冲场凝胶电泳分离出与治疗前相同的病原体，肺炎链球菌采用脉冲场凝胶电泳，流感嗜血杆菌检测β-内酰胺酶产生情况。
对108例早期复发性AOM患者连续进行了MEF培养。108例患者中的88例（81%）复发时分离出100种病原体：54株流感嗜血杆菌；45株肺炎链球菌；1株卡他莫拉菌。大多数复发性AOM发作发生在随访的前2周；治疗结束后第1至7天、8至14天、15至21天和22至28天分别有39例（36%）、38例（35%）、21例（19%）和10例（9%）复发性AOM发作。在大多数患者中，这些发作由新的病原体引起。108例MEF培养阳性的患者中有30例（28%）出现真正的细菌学复发，共35种病原体：108例中的13例（12%）肺炎链球菌；108例中的12例（11%）流感嗜血杆菌；108例中的5例（5%）两者均有。分析治疗结束后复发性AOM的发生时间，治疗结束后第1至7天、8至14天、15至21天和22至28天所有发作中真正的细菌学复发分别为39例中的16例（41%）、38例中的10例（26%）、21例中的3例（14%）和10例中的1例（10%）（P = 0.01）。肺炎链球菌的相应复发率分别为17例中的11例（65%）、10例中的3例（30%）、13例中的3例（23%）和5例中的1例（20%）（P = 0.02）。流感嗜血杆菌的相应复发率分别为19例中的8例（42%）、23例中的9例（39%）、8例中的0例（0%）和4例中的0例（0%）（P = 0.02）。
抗生素治疗结束后1个月内发生的大多数复发性AOM发作实际上是新感染。大多数真正的细菌学AOM复发发生在治疗结束后14天内，但即使在此时间间隔内，大多数复发也是由新的病原体引起。流感嗜血杆菌在治疗结束后14天或更晚引起真正细菌学AOM复发的可能性非常小。
