Edwards J R
Infection Research Department, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
J Antimicrob Chemother. 1995 Jul;36 Suppl A:1-17. doi: 10.1093/jac/36.suppl_a.1.
Meropenem is a parenteral carbapenem antibiotic which has excellent bactericidal activity in vitro against almost all clinically significant aerobes and anaerobes. Its high activity is explained by ease of entry into bacteria combined with good affinity for essential penicillin binding proteins, including those associated with cell lysis. Breadth of spectrum is due, in part, to stability to all serine-based beta-lactamases, including those which hydrolyse third-generation cephalosporins. Meropenem has an antibacterial spectrum which is broadly similar to that of imipenem but, whilst slightly less active against staphylococci and enterococci, it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae and Haemophilus influenzae. Amongst common human pathogens, only methicillin-resistant staphylococci and Enterococcus faecium are uniformly resistant to meropenem. The meropenem MICs for penicillin-resistant Streptococcus pneumoniae are higher than for penicillin-susceptible strains but the organisms remain susceptible. Clinical susceptibility in vitro to meropenem is defined by MICs of < or = 4 mg/L, intermediate susceptibility by MICs of 8 mg/L and MICs of > or = 16 mg/L define resistance; equivalent figures for zones of growth inhibition are > or = 14 (susceptible), 12-13 (intermediate) and < or = 11 (resistant) mm. Studies in guinea pig models of systemic infection and infections localised to the lungs, urinary tract and the central nervous system, some of which used immunocompromised animals, confirm the potential of meropenem demonstrated in vitro. These factors, combined with the human plasma, tissue or urinary concentrations of meropenem which exceed modal MICs for the pathogens isolated in clinical trials for most or all of the recommended 8 h dosing interval, predict that meropenem should be efficacious in the treatment of infections at many body sites.
美罗培南是一种肠胃外给药的碳青霉烯类抗生素,在体外对几乎所有临床上重要的需氧菌和厌氧菌都具有出色的杀菌活性。其高活性归因于它易于进入细菌体内,并与包括那些与细胞裂解相关的必需青霉素结合蛋白具有良好的亲和力。抗菌谱广部分是由于它对所有丝氨酸类β-内酰胺酶稳定,包括那些能水解第三代头孢菌素的酶。美罗培南的抗菌谱与亚胺培南大致相似,但虽然对葡萄球菌和肠球菌的活性略低,但对铜绿假单胞菌、所有肠杆菌科细菌和流感嗜血杆菌的活性更高。在常见的人类病原体中,只有耐甲氧西林葡萄球菌和粪肠球菌对美罗培南普遍耐药。耐青霉素肺炎链球菌对美罗培南的最低抑菌浓度(MIC)高于青霉素敏感菌株,但这些菌株仍保持敏感。美罗培南的体外临床敏感性定义为MIC≤4mg/L为敏感,MIC为8mg/L为中介,MIC≥16mg/L为耐药;生长抑制圈的等效数值为≥14mm(敏感)、12 - 13mm(中介)和≤11mm(耐药)。在豚鼠全身感染以及局限于肺部、泌尿道和中枢神经系统感染的模型研究中,其中一些使用了免疫受损动物,证实了美罗培南在体外所显示的潜力。这些因素,再加上美罗培南在人体血浆、组织或尿液中的浓度在大多数或全部推荐的8小时给药间隔内超过临床试验中分离出的病原体的常见MIC,预示美罗培南在治疗许多身体部位的感染时应该有效。