Moreillon P, Wenger A, Caldelari I
Département de médecine interne, CHUV, Lausanne.
Rev Med Suisse Romande. 2000 Aug;120(8):651-9.
In 1875, 7 years prior to the description of the Koch bacillus, Klebs visualized the first Streptococcus pneumoniae in a pleural fluid. Since then, this organism has played a determinant role in biomedical science. From a biological point of view, it was largely implicated 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 still today 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 is still entailed with a mortality of over 25%. Although S. pneumoniae remained very sensitive to penicillin for many years, penicillin-resistance has emerged and increased dramatically over the last 15 years. During this period of time, 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 (i) inter mediate level resistance (minimal inhibitory concentration [MIC] of penicillin of 0.1-1 mg/L) and (ii) high level resistance (MCI > or = 2 mg/L). The clinical significance of intermediate resistance remains poorly defined. On the other hand, highly resistant strains were responsible for numerous therapeutical 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 antibotics of the beta-lactam family and could even become resistant to the last resort drugs mentioned above. Thus, in conclusion, the explosion of resistance to penicillin in pneumococci is a ubiquitous phenomenon which must be fought against by (i) a strict utilization of antibiotics, (ii) the practice of microbiological sampling of infected foci before treatment, (iii) the systematic surveillance of resistance profiles of pneumococci against antibiotics and (iv) the adequate vaccination of populations at risk.
1875年，在科赫氏杆菌被发现的7年前，克莱布斯在一份胸水样本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，它在血清疗法和疫苗接种分别导致的被动免疫和主动免疫的发展过程中起到了重要作用。遗传转化也是在肺炎链球菌中首次被观察到，从而促成了DNA的发现。从临床角度来看，肺炎链球菌至今仍是儿童中耳炎以及各年龄段肺炎的主要病因，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，青霉素耐药性已经出现且急剧增加。在此期间，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，青霉素耐药菌株的比例已从≤1%增加到20%至60%不等。在瑞士，目前青霉素耐药肺炎球菌的比例在5%至≥10%之间。青霉素耐药肺炎球菌的增加与β-内酰胺类抗生素的大量使用有关。耐药机制并非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）发生了改变。耐药性可分为：（i）中度耐药（青霉素的最低抑菌浓度[MIC]为0.1 - 1毫克/升）和（ii）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，高度耐药菌株导致了众多治疗失败案例，尤其是在脑膜炎病例中。推荐用于治疗青霉素耐药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，青霉素耐药肺炎球菌往往对所有β-内酰胺类抗生素都呈现交叉耐药性，甚至可能对上述最后手段药物产生耐药性。因此，总之，肺炎球菌对青霉素耐药性的激增是一个普遍存在的现象，必须通过以下方式加以应对：（i）严格使用抗生素；（ii）在治疗前对感染病灶进行微生物采样；（iii）系统监测肺炎球菌对抗生素的耐药谱；（iv）对高危人群进行充分的疫苗接种。
