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[肺炎球菌中的抗生素耐药性]

[Antibiotic resistance in pneumococci].

作者信息

Moreillon P, Wenger A

机构信息

Département de médecine interne, CHUV, Lausanne.

出版信息

Schweiz Med Wochenschr. 1996 Feb 17;126(7):255-63.

PMID:8720323
Abstract

In 1875, 7 years prior to the description of the Koch bacillus, Klebs visualized the first Streptococcus pneumoniae in pleural fluid. Since then, this organism has played a decisive role in biomedical science. From a biological point of view, it was extensively involved in the development of passive and active immunization by serotherapy and vaccination respectively. Genetic transformation was also first observed in S. pneumoniae, leading to the discovery of DNA. From a clinical point of view, S. pneumoniae is today still a prime cause of otitis media in children and of pneumonia in all age groups, as well as a predominant cause of meningitis and bacteremia. In adults, bacteremia still has a mortality of over 25%. Although S. pneumoniae remained very sensitive to penicillin for many years, penicillin-resistant strains have emerged and increased dramatically over the last 15 years. During this period the frequency of penicillin-resistant isolates has increased from < or = 1% to frequencies varying from 20 to 60% in geographic areas as diverse as South Africa, Spain, France, Hungary, Iceland, Alaska, and numerous regions of the United States and South America. In Switzerland, the current frequency of penicillin-resistant pneumococci ranges between 5 and > or = 10%. The increase in penicillin-resistant pneumococci correlates with the intensive use of beta-lactam antibiotics. The mechanism of resistance is not due to bacterial production of penicillinase but to an alteration of the bacterial target of penicillin, the so-called penicillin-binding proteins. Resistance is subdivided into (1) intermediate level resistance (minimal inhibitory concentration [MIC] of penicillin of 0.1-1 mg/l) and (2) high level resistance (MCI > or = 2 mg/l). The clinical significance of intermediate resistance remains poorly defined. On the other hand, highly resistant strains have been responsible for numerous therapeutic failures, especially in cases of meningitis. Antibiotics recommended against penicillin-resistant pneumococci include cefotaxime, ceftriaxone, imipenem and in some instances vancomycin. However, penicillin-resistant pneumococci tend to present cross-resistances to all the antibiotics of the beta-lactam family and could even become resistant to the last resort drugs mentioned above. Thus, the explosion of resistance to penicillin in pneumococci is a ubiquitous phenomenon which must be fought against by (1) avoiding excessive use of antibiotics, (2) the practice of microbiological sampling of infected foci before treatment, (3) the systematic surveillance of resistance profiles of pneumococci against antibiotics and (4) adequate vaccination of populations at risk.

摘要

1875年,即在科赫氏杆菌被发现的7年前,克莱布斯在胸腔积液中首次发现了肺炎链球菌。从那时起,这种微生物在生物医学科学中发挥了决定性作用。从生物学角度来看,它分别通过血清疗法和疫苗接种广泛参与了被动免疫和主动免疫的发展。遗传转化也是在肺炎链球菌中首次被观察到,从而导致了DNA的发现。从临床角度来看,如今肺炎链球菌仍是儿童中耳炎、各年龄组肺炎的主要病因,也是脑膜炎和菌血症的主要病因。在成年人中,菌血症的死亡率仍超过25%。尽管多年来肺炎链球菌对青霉素一直非常敏感,但在过去15年中,耐青霉素菌株已经出现并急剧增加。在此期间,耐青霉素分离株的频率从≤1%增加到在南非、西班牙、法国、匈牙利、冰岛、阿拉斯加以及美国和南美洲的许多地区,频率在20%至60%之间变化。在瑞士,目前耐青霉素肺炎球菌的频率在5%至≥10%之间。耐青霉素肺炎球菌的增加与β-内酰胺类抗生素的大量使用有关。耐药机制不是由于细菌产生青霉素酶,而是由于青霉素的细菌靶点(即所谓的青霉素结合蛋白)发生改变。耐药性分为(1)中度耐药(青霉素的最低抑菌浓度[MIC]为0.1 - 1毫克/升)和(2)高度耐药(MCI≥2毫克/升)。中度耐药的临床意义仍不明确。另一方面,高度耐药菌株已导致许多治疗失败,尤其是在脑膜炎病例中。推荐用于治疗耐青霉素肺炎球菌的抗生素包括头孢噻肟、头孢曲松、亚胺培南,在某些情况下还包括万古霉素。然而,耐青霉素肺炎球菌往往对β-内酰胺类家族的所有抗生素都存在交叉耐药性,甚至可能对上述最后手段药物产生耐药性。因此,肺炎球菌对青霉素耐药性的激增是一种普遍现象,必须通过(1)避免过度使用抗生素,(2)在治疗前对感染灶进行微生物采样,(3)系统监测肺炎球菌对抗生素的耐药谱,以及(4)对高危人群进行充分疫苗接种来加以应对。

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