Neu H C, Chin N X, Huang H B
Department of Medicine, College of Physicians & Surgeons, Columbia University, New York 10032, USA.
Antimicrob Agents Chemother. 1993 Mar;37(3):566-73. doi: 10.1128/AAC.37.3.566.
The in vitro activity of FK-037, 5-amino-2-[[(6R, 7R)-7-[[(Z)-2-(2-amino-4-thiazolyl)-2- methoxyimino) acetyl] amino]-2-carboxy-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-(2-hydroxyethyl)-1H-pyrazoli um hydroxide, inner salt, sulfate (1:1), a new parenteral cephem, was compared with those of cefepime, ceftazidime, imipenem, and ciprofloxacin. FK-037 inhibited methicillin-susceptible staphylocci at < or = 4 micrograms/ml. Of 98 isolates of homogenous methicillin-resistant Staphylococcus aureus, 55 (56.1%) were inhibited by 8 micrograms of FK-037 per ml, compared to 3.1% for cefepime. Imipenem was the most active beta-lactam tested against staphylococci. The MIC of FK-037 for 90% of the strains tested (MIC90) was 0.06 micrograms/ml for hemolytic streptococci, Streptococcus pneumoniae, viridans group streptococci, and Streptococcus bovis. The MIC90 for many of the members of the family Enterobacteriaceae was 1 microgram/ml, similar to that of cefepime and lower than those of ceftazidime and imipenem. The MIC90 for Klebsiella pneumoniae and Enterobacter cloacae was 8 micrograms/ml, similar to that for cefepime, but all isolates were inhibited by 2 micrograms of imipenem per ml. K. pneumoniae isolates with cefotaxime and ceftazidime MICs of > 32 micrograms/ml with Bush type 2b' beta-lactamases were inhibited by 4 micrograms of FK-037 per ml. E. cloacae, Citrobacter freundii, and S. aureus stably resistant to FK-037 could be selected by repeated transfer in the presence of FK-037. The FK-037 MIC90 for Pseudomonas aeruginosa was 4 microgram/ml, compared to 32 microgram/ml for cefepime and ceftazidime and 8 microgram/ml for imipenem. Xanthomonas maltophilia, Pseudomonas cepacia, Acinetobacter anitratus, and Bacteroides species were resistant to FK-037 (MIC, more than or equal 32 microgram/ml). MBCs were identical to or within twofold of the MICs except for a 32-fold greater MBC for P. aeruginosa. Inoculum size and acid environment did not lower the activity of FK-037. FK-037 was not appreciably hydrolyzed by Bush group 1, 2a, 2b, and 2e beta-lactamases but was hydrolyzed by 2b' and 2d enzymes at rates comparable to that of ceftazidime. Nonetheless, FK-037 inhibited bacteria possessing TEM-3, -5, and -7 and SHV -5 at less than or equal 8 microgram/ml. Overall, FK-037 has lower MICs against staphylococci and P. aeruginosa than the currently available iminomethoxy aminothiazolyl cephalosporins and has activity against members of the family Enterobacteriaceae comparable to that of cefepime.
新型肠外头孢菌素FK-037（5-氨基-2-[[(6R,7R)-7-[[(Z)-2-(2-氨基-4-噻唑基)-2-甲氧基亚氨基)乙酰]氨基]-2-羧基-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-3-基]甲基]-1-(2-羟乙基)-1H-吡唑鎓氢氧化内盐，硫酸盐(1:1)）的体外活性与头孢吡肟、头孢他啶、亚胺培南和环丙沙星进行了比较。FK-037对甲氧西林敏感葡萄球菌的抑制浓度≤4微克/毫升。在98株同源性耐甲氧西林金黄色葡萄球菌中，55株（56.1%）被每毫升8微克的FK-037抑制，而头孢吡肟的抑制率为3.1%。亚胺培南是所测试的对葡萄球菌活性最强的β-内酰胺类药物。FK-037对90%受试菌株（MIC90）的最低抑菌浓度，对溶血性链球菌、肺炎链球菌、草绿色链球菌和牛链球菌为0.06微克/毫升。对许多肠杆菌科菌属成员的MIC90为1微克/毫升，与头孢吡肟相似，低于头孢他啶和亚胺培南。肺炎克雷伯菌和阴沟肠杆菌的MIC90为8微克/毫升，与头孢吡肟相似，但所有菌株均被每毫升2微克的亚胺培南抑制。对头孢噻肟和头孢他啶MIC＞32微克/毫升且产Bush 2b'型β-内酰胺酶的肺炎克雷伯菌菌株，被每毫升4微克的FK-037抑制。通过在FK-037存在下反复传代，可筛选出对FK-037稳定耐药的阴沟肠杆菌、弗氏柠檬酸杆菌和金黄色葡萄球菌。FK-037对铜绿假单胞菌的MIC90为4微克/毫升，而头孢吡肟和头孢他啶为32微克/毫升，亚胺培南为8微克/毫升。嗜麦芽窄食单胞菌、洋葱假单胞菌、不动杆菌属和拟杆菌属对FK-037耐药（MIC≥32微克/毫升）。除铜绿假单胞菌的MBC比MIC高32倍外，MBC与MIC相同或相差不超过两倍。接种量和酸性环境不会降低FK-037的活性。FK-037不会被Bush 1、2a、2b和2e组β-内酰胺酶明显水解，但会被2b'和2d酶以与头孢他啶相当的速率水解。尽管如此，FK-037对携带TEM-3、-5和-7以及SHV -5的细菌的抑制浓度≤8微克/毫升。总体而言，FK-037对葡萄球菌和铜绿假单胞菌的MIC低于目前可用的亚胺甲氧基氨基噻唑基头孢菌素，对肠杆菌科菌属成员的活性与头孢吡肟相当。
