Macrolide resistance: an increasing concern for treatment failure in children
Macrolide resistance: an increasing concern for treatment failure in children
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DOI：
10.1097/00006454-200308001-00004
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发表时间：
2003-08-01
影响因子：
3.6
通讯作者：
Johnson, CE
中科院分区：
文献类型：
--
作者：
Jacobs, MR;Johnson, CE
背景在过去的30年里，由于抗生素耐药性的存在，儿科呼吸道感染的抗菌治疗已经发生了变化。由于肺炎链球菌、流感嗜血杆菌和卡他莫拉菌等常见呼吸道病原体的抗菌药物耐药性急剧增加，这些疾病的抗菌治疗重点已从青霉素转向其他药物。对于临床医生来说，了解耐药性如何发展非常重要，以便他们可以帮助防止其他抗菌药物发生这种现象。方法。本文综述了儿科呼吸道常见病原菌对大环内酯类抗生素的耐药性，以及这些病原菌感染的临床和细菌学结果。常见儿科呼吸道病原体对大环内酯类抗生素的耐药主要通过两种机制发生，即靶位点的改变和主动外排。虽然耐药模式因地理区域而异，但大环内酯类药物的广泛使用导致了两种类型的大环内酯类耐药微生物的出现。有利于耐药菌株选择和增殖的条件包括经常接受抗菌治疗或预防的反复密切接触的儿童，例如参加日托的儿童。美国最近的监测数据显示，20%至30%的S。肺炎链球菌对大环内酯类具有抗性，其中约三分之二的大环内酯类抗性菌株与外排机制相关，其余的与核糖体甲基化酶相关。此外，虽然不太为人所知，但实际上所有的H.流感具有内在大环内酯外排泵。随着对大环内酯类抗生素耐药性的增加，导致了临床失败，这些药物不再被认为适合于急性中耳炎和鼻窦炎的经验性一线抗菌治疗，除非患者确实对青霉素过敏。因此，推荐使用其他抗菌药物，包括大剂量阿莫西林和阿莫西林/克拉维酸（阿莫西林90 mg/kg/d）、头孢呋辛酯和肌内注射头孢曲松。随着对大环内酯类抗生素耐药性的增加，以及此类抗生素在儿童中的临床失败越来越常见，因此需要谨慎使用抗生素。这包括限制病毒感染的抗菌药物使用，并在临床需要抗菌药物时使用最有效的药物，如更高剂量的阿莫西林和阿莫西林/克拉维酸。应用这些原则可以防止扩散和进一步发展的阻力。
Background. Antimicrobial treatment of pediatric respiratory tract infections has evolved during the past 30 years as a result of antimicrobial resistance. The focus of antimicrobial therapy in these conditions has shifted from penicillins to other agents because of the dramatic increase in antimicrobial resistance among common respiratory pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. It is important for clinicians to understand how resistance develops so that they can help prevent this phenomenon from occurring with other antimicrobials.Methods. This article reviews the published literature on resistance to macrolide antimicrobials among common pediatric respiratory tract pathogens and clinical and bacteriologic outcomes of infections with these pathogens.Results. Resistance among common pediatric respiratory tract pathogens to macrolides occurs through two main mechanisms, alteration of the target site and active efflux. Although resistance patterns vary by geographic region, the widespread use of macrolides has contributed to the emergence of both types of macrolide-resistant organisms. Conditions that favor the selection and proliferation of resistant strains include children with repeated, close contact who frequently receive antimicrobial treatment or prophylaxis, such as children who attend day care. Recent US surveillance data show that 20 to 30% of S. pneumoniae are resistant to macrolides, with approximately two-thirds of macrolide-resistant strains associated with an efflux mechanism and the remainder associated with a ribosomal methylase. Additionally, although less well-known, virtually all strains of H. influenzae have an intrinsic macrolide efflux pump. As resistance to macrolides has increased, clinical failures have resulted, and these agents are no longer considered appropriate for empiric first line antimicrobial therapy of acute otitis media and sinusitis unless patients are truly penicillin-allergic. Therefore, other antimicrobials are recommended for the empiric treatment of children with respiratory tract infections, including higher doses of amoxicillin and amoxicillin/clavulanate (90 mg/kg/day amoxicillin), cefuroxime axetil and intramuscular ceftriaxone.Conclusions. As resistance to macrolides increases and clinical failures in children become more common with this class of antimicrobials, judicious use of antimicrobials is needed. This includes limiting antimicrobial use for viral infections and using the most effective agents when antimicrobials are clinically indicated, such as higher doses of amoxicillin and amoxicillin/clavulanate. Application of these principles may prevent proliferation and further development of resistance.