Affinity of Ceftaroline and Other β-Lactams for Penicillin-Binding Proteins from Staphylococcus aureus and Streptococcus pneumoniae
Affinity of Ceftaroline and Other β-Lactams for Penicillin-Binding Proteins from Staphylococcus aureus and Streptococcus pneumoniae
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DOI：
10.1128/aac.00019-10
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发表时间：
2010-05-01
影响因子：
4.9
通讯作者：
Appelbaum, P. C.
中科院分区：
文献类型：
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作者：
Kosowska-Shick, K.;McGhee, P. L.;Appelbaum, P. C.
我们在具有不同耐药表型的 6 株金黄色葡萄球菌和 7 株肺炎链球菌分离株中比较了头孢洛林对所有青霉素结合蛋白 (PBP) 的亲和力与头孢曲松和头孢噻肟的亲和力。头孢洛林 MIC 为 PBP2B，头孢洛林对 PBP2X、-2A、-2B 和 -3 的 50% 抑制浓度 (IC(50)s)（0.1 至 4 μg/ml）比其他测试的头孢菌素高 4 倍以上。在3个耐青霉素肺炎链球菌菌株中，头孢洛林对头孢菌素PBP结合活性的主要靶标PBP2X（IC50，0.1至1μg/ml）具有高亲和力，对PBP2B（IC50，0.5至4μg/ml）和PBP1A（IC50，0.125至0.25μg/ml）具有高亲和力。 g/ml），两者也被认为是头孢菌素 PBP 结合活性的主要靶点。对甲氧西林敏感的金黄色葡萄球菌菌株中的头孢洛林 PBP 亲和力大于或等于测试的其他 3 种 β-内酰胺。 Ceftaroline 与耐甲氧西林金黄色葡萄球菌中的 PBP2a 结合（IC50，0.01 至 1 μg/ml），其亲和力比其他药物高 256 倍。 Ceftaroline 对所有测试的金黄色葡萄球菌和肺炎链球菌菌株（包括耐药菌株）表现出非常好的 PBP 亲和力。
We compared the affinities of ceftaroline for all penicillin-binding proteins (PBPs) with those of ceftriaxone and cefotaxime in 6 Staphylococcus aureus and 7 Streptococcus pneumoniae isolates with various resistance phenotypes. Ceftaroline MICs were PBP2B, and ceftaroline had >= 4-fold higher 50% inhibitory concentrations (IC(50)s) (0.1 to 4 mu g/ml) for PBP2X, -2A, -2B, and -3 than those for the other cephalosporins tested. Among 3 penicillin-resistant S. pneumoniae strains, ceftaroline had a high affinity for PBP2X (IC50, 0.1 to 1 mu g/ml), a primary target for cephalosporin PBP binding activity, and high affinities for PBP2B (IC50, 0.5 to 4 mu g/ml) and PBP1A (IC50, 0.125 to 0.25 mu g/ml) as well, both of which are also known as major targets for PBP binding activity of cephalosporins. Ceftaroline PBP affinities in methicillin-susceptible S. aureus strains were greater than or equal to those of the 3 other beta-lactams tested. Ceftaroline bound to PBP2a in methicillin-resistant S. aureus (IC50, 0.01 to 1 mu g/ml) with up to 256-fold-higher affinity than those of other agents. Ceftaroline demonstrated very good PBP affinity against all S. aureus and S. pneumoniae strains tested, including resistant isolates.