Nishino T, Otsuki M, Hatano K, Nishihara Y
Department of Microbiology, Kyoto Pharmaceutical University, Japan.
Chemotherapy. 1994 May-Jun;40(3):167-82. doi: 10.1159/000239189.
In vitro and in vivo antibacterial activities of FK037, a new parenteral cephalosporin, were compared with those of cefpirome, ceftazidime and flomoxef. The advantages of in vitro activity of FK037 were as follows: (1) a broad-spectrum antibacterial activity, (2) the most potent activity (MIC90: 25 micrograms/ml) of the cephalosporins tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA), (3) a strong activity against Enterobacter spp. and Citrobacter freundii resistant to the third-generation cephalosporins tested. The MICs of FK037 for 90% of the clinical isolates tested (MIC90s) were 0.012 microgram/ml for Streptococcus pyogenes, 0.05 microgram/ml for Escherichia coli, 0.1 microgram/ml for Streptococcus pneumoniae, 0.2 microgram/ml for Haemophilus influenzae and Proteus mirabilis, 0.39 microgram/ml for Klebsiella pneumoniae, 1.56 micrograms/ml for methicillin-sensitive S. aureus, Proteus vulgaris and Enterobacter aerogenes, 3.13 micrograms/ml for Staphylococcus epidermidis and Moraxella catarrhalis, 6.25 micrograms/ml for C. freundii, 12.5 micrograms/ml for low-level methicillin-resistant S. aureus (L-MRSA), Enterobacter cloacae and Pseudomonas aeruginosa, and 25 micrograms/ml for H-MRSA and Serratia marcescens. FK037 was similar in potency to cefpirome against strains except MRSA, and was superior to ceftazidime and flomoxef against strains except P. vulgaris and/or M. catarrhalis. The increase in MICs of FK037 against 2 L-MRSA strains (2- or 4-fold) was smaller than that of cefpirome and flomoxef (16- to 64-fold) after the third serial culture in the presence of each drug. FK037 was highly bactericidal against S. aureus, E. coli, K. pneumoniae and P. aeruginosa at the MIC or higher. FK037 had a potent protective activity against murine experimental systemic infections due to a wide variety of bacteria. Its protective activity was the strongest among the cephalosporins tested against H-MRSA and Acinetobacter calcoaceticus. Against the other strains, FK037 was as effective as cefpirome and similar or superior to flomoxef and ceftazidime though it was inferior to ceftazidime against P. aeruginosa. Transmission electron microscopic studies revealed that FK037 inhibited septum formation and induced thick cross walls and bacteriolysis at the division sites in MRSA after 4 h incubation.
将新型胃肠外头孢菌素FK037的体外和体内抗菌活性与头孢匹罗、头孢他啶和氟氧头孢进行了比较。FK037的体外活性优势如下：（1）广谱抗菌活性；（2）在所测试的头孢菌素中，对耐甲氧西林金黄色葡萄球菌（H-MRSA）活性最强（MIC90：25微克/毫升）；（3）对耐第三代头孢菌素的阴沟肠杆菌属和弗氏柠檬酸杆菌有较强活性。FK037对90%受试临床分离株的MIC（MIC90）分别为：化脓性链球菌0.012微克/毫升、大肠埃希菌0.05微克/毫升、肺炎链球菌0.1微克/毫升、流感嗜血杆菌和奇异变形杆菌0.2微克/毫升、肺炎克雷伯菌0.39微克/毫升、甲氧西林敏感金黄色葡萄球菌、普通变形杆菌和产气肠杆菌1.56微克/毫升、表皮葡萄球菌和卡他莫拉菌3.13微克/毫升、弗氏柠檬酸杆菌6.25微克/毫升、低水平耐甲氧西林金黄色葡萄球菌（L-MRSA）、阴沟肠杆菌和铜绿假单胞菌12.5微克/毫升、H-MRSA和粘质沙雷菌25微克/毫升。除MRSA外，FK037对其他菌株的活性与头孢匹罗相似，除普通变形杆菌和/或卡他莫拉菌外，对其他菌株的活性优于头孢他啶和氟氧头孢。在每种药物存在下进行第三次连续培养后，FK037对2株L-MRSA菌株的MIC增加（2倍或4倍）小于头孢匹罗和氟氧头孢（16倍至64倍）。FK037在MIC或更高浓度时对金黄色葡萄球菌、大肠埃希菌、肺炎克雷伯菌和铜绿假单胞菌具有高度杀菌作用。FK037对多种细菌引起的小鼠实验性全身感染具有强大的保护活性。在针对H-MRSA和醋酸钙不动杆菌的受试头孢菌素中，其保护活性最强。针对其他菌株，FK037与头孢匹罗效果相当，与氟氧头孢相似或优于氟氧头孢和头孢他啶，不过在针对铜绿假单胞菌时不如头孢他啶。透射电子显微镜研究显示，孵育4小时后，FK037可抑制MRSA隔膜形成，并在分裂位点诱导形成厚的横壁并导致细菌溶解。
