Department of Pathology, Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
Antimicrob Agents Chemother. 2011 May;55(5):2344-51. doi: 10.1128/AAC.01602-10. Epub 2011 Feb 22.
Ceftaroline, the active component of the prodrug ceftaroline fosamil, is a novel broad-spectrum cephalosporin with bactericidal activity against Gram-positive and -negative isolates. This study evaluated the potential for ceftaroline and comparator antibiotics to select for clones of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis with elevated MICs. S. pneumoniae and S. pyogenes isolates in the present study were highly susceptible to ceftaroline (MIC range, 0.004 to 0.25 μg/ml). No streptococcal strains yielded ceftaroline clones with increased MICs (defined as an increase in MIC of >4-fold) after 50 daily passages. Ceftaroline MICs for H. influenzae and M. catarrhalis were 0.06 to 2 μg/ml for four strains and 8 μg/ml for a β-lactamase-positive, efflux-positive H. influenzae with a mutation in L22. One H. influenzae clone with an increased ceftaroline MIC (quinolone-resistant, β-lactamase-positive) was recovered after 20 days. The ceftaroline MIC for this isolate increased 16-fold, from 0.06 to 1 μg/ml. MICs for S. aureus ranged from 0.25 to 1 μg/ml. No S. aureus isolates tested with ceftaroline had clones with increased MIC (>4-fold) after 50 passages. Two E. faecalis isolates tested had ceftaroline MICs increased from 1 to 8 μg/ml after 38 days and from 4 to 32 μg/ml after 41 days, respectively. The parental ceftaroline MIC for the one K. pneumoniae extended-spectrum β-lactamase-negative isolate tested was 0.5 μg/ml and did not change after 50 daily passages.
头孢洛林是前体药物头孢洛林磷酸酯的活性成分，是一种新型的广谱头孢菌素，对革兰氏阳性和革兰氏阴性分离株具有杀菌活性。本研究评估了头孢洛林和对照抗生素选择肺炎链球菌、化脓性链球菌、流感嗜血杆菌、卡他莫拉菌、肺炎克雷伯菌、金黄色葡萄球菌和粪肠球菌的克隆的潜力，这些克隆对药物的 MIC 值升高。本研究中的肺炎链球菌和化脓性链球菌分离株对头孢洛林高度敏感（MIC 范围为 0.004 至 0.25 μg/ml）。经过 50 天的连续传代，没有链球菌菌株产生头孢洛林的耐药克隆（定义为 MIC 增加>4 倍）。四种流感嗜血杆菌和卡他莫拉菌的头孢洛林 MIC 为 0.06 至 2 μg/ml，而β-内酰胺酶阳性、外排阳性、L22 突变的流感嗜血杆菌的 MIC 为 8 μg/ml。经过 20 天，恢复了一个具有增加的头孢洛林 MIC 的流感嗜血杆菌克隆（耐喹诺酮、β-内酰胺酶阳性）。该分离株的头孢洛林 MIC 增加了 16 倍，从 0.06 增加至 1 μg/ml。金黄色葡萄球菌的 MIC 范围为 0.25 至 1 μg/ml。经过 50 天的传代，没有测试的金黄色葡萄球菌分离株具有增加的 MIC (>4 倍)的克隆。经过 38 天和 41 天，两种粪肠球菌的头孢洛林 MIC 分别从 1 增加到 8 μg/ml 和从 4 增加到 32 μg/ml。一个测试的产超广谱β-内酰胺酶阴性肺炎克雷伯菌的头孢洛林母本 MIC 为 0.5 μg/ml，经过 50 天的连续传代，MIC 值没有变化。
