Jacobs M R
Department of Pathology, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Ohio 44106, USA.
Am J Med. 1999 May 3;106(5A):19S-25S; discussion 48S-52S. doi: 10.1016/s0002-9343(98)00351-9.
Increasingly, Streptococcus pneumoniae with reduced susceptibility to penicillin is becoming a healthcare concern, not only because of the high prevalence of infections caused by this pathogen but also because of the rate at which resistance has progressed. The incidence of penicillin resistance in strains of S. pneumoniae approaches 40% in some areas of the United States, and the incidence of high-level resistance has increased by 60-fold during the past 10 years. With the exception of meningitis and otitis media, there is no conclusive evidence that the acquisition of resistance by S. pneumoniae to beta-lactam antibiotics incurs greater morbidity and mortality in infections caused by this pathogen. However, if the current trends of resistance patterns continue, one can expect the morbidity and mortality to increase. The mechanism of beta-lactam resistance of S. pneumoniae involves genetic mutations which alter penicillin-binding protein structure, resulting in a decreased affinity for all beta-lactam antibiotics. In the treatment of infections caused by S. pneumoniae, it should not be assumed that nonsusceptibility to beta-lactam antibiotics correlates with clinical ineffectiveness of these agents. On the contrary, the recommended therapy for nonmeningeal pneumococcal infections (e.g., pneumonia, sepsis, acute otitis media) includes a beta-lactam antibiotic: penicillin G, amoxicillin, amoxicillin/clavulanate, cefuroxime, cefotaxime, or ceftriaxone. Recommended therapy for meningitis is cefotaxime or ceftriaxone, with the addition of vancomycin until susceptibility is known. These agents are recommended because of their ability to achieve serum/tissue concentrations greater than the minimum inhibitory concentrations (MICs) of these agents against penicillin-susceptible, penicillin-intermediate, and most penicillin-resistant strains (e.g., penicillin G, cefotaxime, ceftriaxone, amoxicillin, amoxicillin/clavulanate, and cefuroxime), or their ability to provide adequate concentrations in cerebrospinal fluid (e.g., cefotaxime, ceftriaxone).
对青霉素敏感性降低的肺炎链球菌日益成为医疗保健领域关注的问题，这不仅是因为该病原体引起的感染普遍存在，还因为耐药性发展的速度。在美国的一些地区，肺炎链球菌菌株中青霉素耐药的发生率接近40%，在过去10年中，高水平耐药的发生率增加了60倍。除脑膜炎和中耳炎外，没有确凿证据表明肺炎链球菌对β-内酰胺类抗生素产生耐药性会导致该病原体引起的感染中更高的发病率和死亡率。然而，如果目前的耐药模式趋势持续下去，可以预期发病率和死亡率将会增加。肺炎链球菌对β-内酰胺类抗生素耐药的机制涉及基因突变，这些突变会改变青霉素结合蛋白的结构，导致对所有β-内酰胺类抗生素的亲和力降低。在治疗肺炎链球菌引起的感染时，不应认为对β-内酰胺类抗生素不敏感就意味着这些药物临床无效。相反，非脑膜肺炎球菌感染（如肺炎、败血症、急性中耳炎）的推荐治疗包括一种β-内酰胺类抗生素：青霉素G、阿莫西林、阿莫西林/克拉维酸、头孢呋辛、头孢噻肟或头孢曲松。脑膜炎的推荐治疗是头孢噻肟或头孢曲松，并加用万古霉素直至药敏结果明确。推荐使用这些药物是因为它们能够达到高于这些药物对青霉素敏感、青霉素中介和大多数青霉素耐药菌株（如青霉素G、头孢噻肟、头孢曲松、阿莫西林、阿莫西林/克拉维酸和头孢呋辛）的最低抑菌浓度（MIC）的血清/组织浓度，或者它们能够在脑脊液中提供足够的浓度（如头孢噻肟、头孢曲松）。
