Patel J A, Reisner B, Vizirinia N, Owen M, Chonmaitree T, Howie V
Department of Pediatrics, University of Texas Medical Branch, Galveston 77555-0371, USA.
J Pediatr. 1995 May;126(5 Pt 1):799-806. doi: 10.1016/s0022-3476(95)70415-9.
To evaluate the rate of bacteriologic failure of amoxicillin-clavulanate in the treatment of acute otitis media (AOM) and to identify the risk factors associated with failure.
Ninety-nine subjects (mean age, 21.4 months) with AOM were treated with amoxicillin-clavulanate in two prospective study trials that compared efficacy of two experimental antibiotics with amoxicillin-clavulanate. Tympanocentesis for microbiologic studies was performed in all subjects at enrollment; at 3 to 6 days, during amoxicillin-clavulanate therapy; and at other times when clinically indicated. The subjects were followed up for 1 month. Clinical, bacteriologic, and virologic characteristics of the subjects were analyzed.
Bacteriologic failure of treatment occurred in none of 39 subjects (0%) with Streptococcus pneumoniae, two of 25 (8%) with Moraxella catarrhalis, and 11 of 29 (38%) with nontypeable Haemophilus influenzae (NTHi) infection. The failure rate for NTHi was higher than that for other pathogens (p = 0.0007) and was increased when compared with the preceding study period (p = 0.017). Bacteriologic failure was also associated with clinical failure (p = 0.041). In subjects with AOM caused by NTHi the rates of adequate drug compliance were comparable in both success and failure groups. Antimicrobial susceptibility testing by minimum inhibitory concentration and minimum bactericidal concentration (MIC/MBC) assays showed that amoxicillin-clavulanate resistance was not significantly associated with bacteriologic failure of treatment. However, in two subjects, MIC/MBC of the NTHi isolates during therapy were higher than MIC/MBC of the isolates before therapy; these strains of isolates pretherapy and during therapy were discordant as determined by outer membrane protein analysis. The bacteriologic failure rate was higher in nonwhite boys (p = 0.026) and in subjects with a history of three or more previous episodes of AOM (p = 0.008). Other factors such as age, bilaterality of disease, polymicrobial infection, and biotype pattern of NTHi were not associated with treatment failure. When children with adequate drug compliance were analyzed separately, only those with concomitant viral infection of the nasopharynx or middle ear were found to be at an increased risk of bacteriologic failure of treatment (p = 0.04).
The bacteriologic failure rate of amoxicillin-clavulanate therapy for AOM caused by NTHi was higher in the current study period than in the preceding period. Factors contributing to treatment failure were race, gender, proneness to otitis, and concomitant viral infection.
评估阿莫西林-克拉维酸治疗急性中耳炎（AOM）的细菌学失败率，并确定与治疗失败相关的危险因素。
在两项前瞻性研究试验中，99名急性中耳炎患者（平均年龄21.4个月）接受了阿莫西林-克拉维酸治疗，这两项试验比较了两种实验性抗生素与阿莫西林-克拉维酸的疗效。所有受试者在入组时均进行鼓膜穿刺术以进行微生物学研究；在阿莫西林-克拉维酸治疗的3至6天期间，以及在其他临床指征明确时进行。对受试者进行1个月的随访。分析了受试者的临床、细菌学和病毒学特征。
39名肺炎链球菌感染患者中无一例治疗细菌学失败（0%），25名卡他莫拉菌感染患者中有2例（8%）治疗细菌学失败，29名非分型流感嗜血杆菌（NTHi）感染患者中有11例（38%）治疗细菌学失败。NTHi的治疗失败率高于其他病原体（p = 0.0007），与前一研究期相比有所增加（p = 0.017）。细菌学失败也与临床失败相关（p = 0.041）。在由NTHi引起的AOM患者中，成功组和失败组的药物依从性良好率相当。通过最低抑菌浓度和最低杀菌浓度（MIC/MBC）测定进行的药敏试验表明，阿莫西林-克拉维酸耐药与治疗细菌学失败无显著相关性。然而，在两名受试者中，治疗期间NTHi分离株的MIC/MBC高于治疗前分离株的MIC/MBC；通过外膜蛋白分析确定，这些治疗前和治疗期间的分离株菌株不一致。非白人男孩的细菌学失败率较高（p = 0.026），有三次或更多次AOM既往发作史的受试者细菌学失败率较高（p = 0.008）。其他因素，如年龄、疾病双侧性、混合微生物感染和NTHi的生物型模式与治疗失败无关。当单独分析药物依从性良好的儿童时，发现只有那些伴有鼻咽或中耳病毒感染的儿童治疗细菌学失败风险增加（p = 0.04）。
在本研究期间，阿莫西林-克拉维酸治疗由NTHi引起的AOM的细菌学失败率高于前一时期。导致治疗失败的因素包括种族、性别、中耳炎易感性和并发病毒感染。
