Bauernfeind A, Jungwirth R, Eberlein E, Klesel N, Adam F, Isert D, Limbert M, Markus A, Schrinner E, Seibert G
Max von Pettenkofer-Institut, München, Germany.
J Antibiot (Tokyo). 1992 Apr;45(4):505-20. doi: 10.7164/antibiotics.45.505.
The aminothiazolyl-cephalosporin RU 29 246 is the active metabolite of the prodrug-pivaloyl-oxyethyl-ester HR 916. RU 29 246 in vitro activity includes a wide range of clinically relevant bacterial pathogens. Against methicillin-sensitive Staphylococci RU 29 246 (MIC90 of 0.25 approximately 2 micrograms/ml) was clearly more active than cefaclor, cefuroxime, cefpodoxime, cefixime and ceftibuten, but slightly less active than cefdinir. RU 29 246 inhibited hemolytic Streptococci of the serogroups A, B, C and G as well as penicillin-sensitive Streptococcus pneumoniae at concentrations similar to cefdinir, cefpodoxime and cefuroxime (MIC90 less than or equal to 0.13 micrograms/ml), but less than the other oral cephalosporins investigated (cefixime, cefaclor and ceftibuten). MIC90s of RU 29 246 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella spp., Shigella spp., Proteus mirabilis and Haemophilus influenzae were less than or equal to 0.5 micrograms/ml. Only RU 29 246 and cefdinir demonstrated moderate activity against Acinetobacter baumannii (MIC90 greater than or equal to 4 micrograms/ml). Most strains of Pseudomonas spp., Serratia marcescens, Enterobacter spp., Hafnia alvei and Bacteroides spp. were resistant to RU 29 246. RU 29 246 killed Escherichia coli and Staphylococcus aureus at a rate of 99% to 99.9% at concentrations of two times MIC. The pH value of the medium (range 5.5 to 8.5) and the inoculum size (range 10(5) to 10(7) cfu/ml) had no or only low influence on the antibacterial activity of RU 29 246. RU 29 246 is a broad spectrum cephalosporin including in its activity both Gram-positive and Gram-negative pathogens and therefore--depending on the bioavailability of its prodrug--looks promising as to its therapeutic perspective.
氨基噻唑基头孢菌素RU 29 246是前药新戊酰氧乙酯HR 916的活性代谢产物。RU 29 246的体外活性涵盖多种临床相关的细菌病原体。对于耐甲氧西林葡萄球菌，RU 29 246（MIC90为0.25至约2微克/毫升）明显比头孢克洛、头孢呋辛、头孢泊肟、头孢克肟和头孢布烯更具活性，但比头孢地尼活性略低。RU 29 246在与头孢地尼、头孢泊肟和头孢呋辛相似的浓度下（MIC90小于或等于0.13微克/毫升）可抑制A、B、C和G血清群的溶血性链球菌以及青霉素敏感的肺炎链球菌，但低于所研究的其他口服头孢菌素（头孢克肟、头孢克洛和头孢布烯）。RU 29 246对大肠杆菌、肺炎克雷伯菌、产酸克雷伯菌、沙门氏菌属、志贺氏菌属、奇异变形杆菌和流感嗜血杆菌的MIC90小于或等于0.5微克/毫升。只有RU 29 246和头孢地尼对鲍曼不动杆菌表现出中度活性（MIC90大于或等于4微克/毫升）。大多数铜绿假单胞菌、粘质沙雷氏菌、肠杆菌属、蜂房哈夫尼亚菌和拟杆菌属菌株对RU 29 246耐药。RU 29 246在两倍MIC浓度下能以99%至99.9%的速率杀死大肠杆菌和金黄色葡萄球菌。培养基的pH值（范围为5.5至8.5）和接种量（范围为10⁵至10⁷ cfu/毫升）对RU 29 246的抗菌活性没有影响或影响很小。RU 29 246是一种广谱头孢菌素，其活性包括革兰氏阳性和革兰氏阴性病原体，因此——取决于其前药的生物利用度——从治疗前景来看很有希望。
