Averono Gianluca, Vidali Matteo, Olina Massimo, Basile Matteo, Bagnati Marco, Bellomo Giorgio, Aluffi Paolo
E.N.T. Department, Clinical Chemistry Unit, Maggiore della Carità Hospital, Novara, Italy.
Int J Pediatr Otorhinolaryngol. 2010 Sep;74(9):995-8. doi: 10.1016/j.ijporl.2010.05.023. Epub 2010 Jun 16.
Tonsillectomy is the most common surgery performed in the pediatric and young adult populations. Although recent guidelines based on meta-analysis suggest that perioperative chemoprophylaxis plays a role in reducing bacteraemia-related post-tonsillectomy complications, there is no evidence or agreement upon which specific antibiotic, dosage or administration route should be preferred. Since few previous studies have assessed the effectiveness of prophylaxis by direct measurement of antibiotic levels both in plasma and tissue, we designed an experimental study to quantitatively evaluate amoxicillin concentrations in children ready for tonsillectomy and compare these plasma and tissue levels with the Minimal Inhibitory Concentrations (MIC) of the bacteria more commonly involved in the upper airway infections.
Thirty-three pediatric patients under 14 years of age (median 5.0, IQR 4-7, range 3-11; M:F 18:15) with recurrent tonsillitis were treated with 3 doses (established on patient's weight) of amoxicillin-clavulanic acid given orally the day before plus a further dose 2h before tonsillectomy. Amoxicillin concentrations on both homogenated tonsillar cores and plasma were measured by HPLC-UV. Bacterial epidemiology and susceptibility were derived respectively from survey data collected by Microbiology Unit and MIC according to the National Committee for Clinical Laboratory Standards (NCCLS).
Median plasma and tissue amoxicillin concentrations were respectively 4.7 microg/ml (IQR 2.1-8.0; min-max 0.4-14.3) and 1.1 microg/g (IQR 0.4-2.1; min-max 0.4-12.9), considerably below the selected target MIC of pathogens involved in the upper respiratory tract infections (S. aureus, H. influenzae, M. catarrhalis). 20 Children showed undetectable amoxicillin levels in one or both tonsils. Interestingly, 7 out of these patients (35%) had plasma concentrations higher than the target MIC (8 microg/ml). No patient displayed plasma concentrations under the limit of sensitivity of the method. Poor core-plasma and left-right core correlation was observed among patients, suggesting that fibrosis developed after recurrent tonsillitis may hamper antibiotic penetration.
Based upon direct measurement of antibiotic levels in plasma and tissue, this study suggests that a revision of the oral prophylaxis in children is required in order to reduce microbial charge in the operative field and accordingly improve the recovery after tonsillectomy.
扁桃体切除术是儿科和青年人群中最常见的手术。尽管最近基于荟萃分析的指南表明围手术期化学预防在减少扁桃体切除术后与菌血症相关的并发症方面发挥作用，但对于应首选哪种特定抗生素、剂量或给药途径尚无证据或共识。由于以往很少有研究通过直接测量血浆和组织中的抗生素水平来评估预防效果，我们设计了一项实验研究，以定量评估准备进行扁桃体切除术的儿童体内阿莫西林的浓度，并将这些血浆和组织水平与上呼吸道感染中更常见细菌的最低抑菌浓度（MIC）进行比较。
33名14岁以下（中位数5.0，四分位间距4 - 7，范围3 - 11；男:女18:15）患有复发性扁桃体炎的儿科患者，在扁桃体切除术前一天口服3剂（根据患者体重确定）阿莫西林 - 克拉维酸，术前2小时再服一剂。通过高效液相色谱 - 紫外法测量匀浆扁桃体核心组织和血浆中的阿莫西林浓度。细菌流行病学和药敏性分别来自微生物科收集的调查数据以及根据美国国家临床实验室标准委员会（NCCLS）的MIC数据。
血浆和组织中阿莫西林浓度中位数分别为4.7微克/毫升（四分位间距2.1 - 8.0；最小值 - 最大值0.4 - 14.3）和1.1微克/克（四分位间距0.4 - 2.1；最小值 - 最大值0.4 - 12.9），大大低于上呼吸道感染相关病原体（金黄色葡萄球菌、流感嗜血杆菌、卡他莫拉菌）选定的目标MIC。20名儿童的一个或两个扁桃体中阿莫西林水平检测不到。有趣的是，这些患者中有7名（35%）血浆浓度高于目标MIC（8微克/毫升）。没有患者的血浆浓度低于该方法的灵敏度极限。患者之间扁桃体核心组织 - 血浆以及左右扁桃体核心组织之间的相关性较差，这表明复发性扁桃体炎后形成的纤维化可能会阻碍抗生素渗透。
基于对血浆和组织中抗生素水平的直接测量，本研究表明需要修订儿童口服预防方案，以减少手术部位的微生物负荷，从而改善扁桃体切除术后的恢复情况。
