Jacobs Michael R
Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA.
Pediatr Infect Dis J. 2003 Aug;22(8 Suppl):S109-19. doi: 10.1097/00006454-200308001-00002.
Respiratory tract infections among children are a common reason for health care provider visits and the primary reason for antimicrobial prescribing in this population. The increased prevalence of resistance among Streptococcus pneumoniae and Haemophilus influenzae pathogens poses a serious challenge in the successful treatment of respiratory tract infections caused by these pathogens.
This paper reviews worldwide trends in antimicrobial resistance among common respiratory tract pathogens, highlighting data obtained from the pediatric population where available.
S. pneumoniae resistance to beta-lactams is mediated through alterations in the penicillin-binding proteins and macrolide resistance to acquisition of efflux or methylation genes. The mechanisms of resistance to the fluoroquinolones include target enzyme alterations via genetic mutations and transport out of the bacterial cell via an efflux pump. Beta-lactamase production is the primary mechanism of resistance to penicillins among H. influenzae isolates. Although S. pneumoniae with reduced susceptibility to penicillin was first documented > 30 years ago, resistance has increased at an alarming rate worldwide in the past decade. According to recent surveillance data, the worldwide prevalence of S. pneumoniae with reduced susceptibility to penicillin is 18.2%. Beta-lactamase production among H. influenzae ranges from approximately 4% in Russia to 26% in the United States and to 31% in France. The prevalence of beta-lactamase-negative, ampicillin-resistant H. influenzae remains very low (< 1%) worldwide, except in Japan, where the incidence is higher. In general, the highest rates of resistance are observed in isolates obtained from children, and risk factors for infection with a resistant pathogen include young age, the site of infection, day-care center attendance and recent antimicrobial use.
Increased prevalence of antimicrobial resistance among respiratory tract pathogens isolated from children and adults is evident worldwide. Treatment of infections caused by S. pneumoniae and H. influenzae with older agents or ineffective dosing regimens may not eradicate infections and may contribute to the spread of resistance. These observations confirm the need for appropriate antimicrobial use to halt or at least limit the spread of resistance.
儿童呼吸道感染是就医的常见原因，也是该人群使用抗菌药物的主要原因。肺炎链球菌和流感嗜血杆菌病原体耐药性的增加，对成功治疗由这些病原体引起的呼吸道感染构成了严峻挑战。
本文综述了常见呼吸道病原体抗菌药物耐药性的全球趋势，重点介绍了从儿科人群中获取的数据（如有）。
肺炎链球菌对β-内酰胺类药物的耐药性是通过青霉素结合蛋白的改变介导的，而大环内酯类药物的耐药性是通过获得外排或甲基化基因介导的。对氟喹诺酮类药物的耐药机制包括通过基因突变改变靶酶以及通过外排泵将药物转运出细菌细胞。产生β-内酰胺酶是流感嗜血杆菌分离株对青霉素耐药的主要机制。尽管对青霉素敏感性降低的肺炎链球菌早在30多年前就有记录，但在过去十年中，全球耐药性以惊人的速度增加。根据最近的监测数据，全球对青霉素敏感性降低的肺炎链球菌患病率为18.2%。流感嗜血杆菌中β-内酰胺酶的产生率在俄罗斯约为4%，在美国为26%，在法国为31%。除日本发病率较高外，β-内酰胺酶阴性、氨苄西林耐药的流感嗜血杆菌在全球的患病率仍然很低（<1%）。一般来说，从儿童中分离出的菌株耐药率最高，感染耐药病原体的危险因素包括年龄小、感染部位、日托中心出勤情况和近期使用抗菌药物。
全球范围内，从儿童和成人中分离出的呼吸道病原体抗菌药物耐药性普遍增加。使用旧的药物或无效的给药方案治疗由肺炎链球菌和流感嗜血杆菌引起的感染，可能无法根除感染，还可能导致耐药性的传播。这些观察结果证实了需要合理使用抗菌药物来阻止或至少限制耐药性的传播。
