Livermore David M, Sefton Armine M, Scott Geoffrey M
Antibiotic Resistance Monitoring & Reference Laboratory, Central Public Health Laboratory, 61 Colindale Avenue, London NW9 5HT.
J Antimicrob Chemother. 2003 Sep;52(3):331-44. doi: 10.1093/jac/dkg375. Epub 2003 Aug 13.
Ertapenem is a carbapenem that shares the activity of imipenem and meropenem against most species, but is less active against non-fermenters. Activity is retained against most strains with AmpC and extended-spectrum beta-lactamases, although resistance can arise if these enzymes are combined with extreme impermeability. Resistance can also be caused by IMP, VIM, KPC and NMC carbapenemases, but again, co-requires impermeability. Although the spread of carbapenemases in the future is a concern, they are currently very rare. Given as a 1 g intravenous (iv) infusion once daily, ertapenem has a plasma half-life of approximately 4 h in healthy volunteers, and a Cmax of 155 mg/L and 13 mg/L for total and free drug, respectively. Excretion is largely renal, divided equally between native drug and an open-ring derivative. Trials show equivalence to piperacillin/tazobactam or ceftriaxone in (a) intra-abdominal infections, (b) community-acquired pneumonia, (c) acute pelvic infections, (d) skin and skin structure infections and (e) complicated urinary tract infections. The USA licence grants all these five indications; the EU licence grants the first three. Further potential uses include home iv therapy, directed therapy against Enterobacteriaceae with AmpC or extended-spectrum cephalosporinases, and tentatively, surgical prophylaxis. Widening the usage of carbapenems raises public health concerns, somewhat allayed by the continued rarity of carbapenemases after 17 years of imipenem use, and by the fact that carbapenemases occur mostly in non-fermenters outside the spectrum of ertapenem, and co-require impermeability to confer resistance in Enterobacteriaceae. Nevertheless, if ertapenem is to be used widely, its effects on the resistance ecology need to be monitored carefully.
厄他培南是一种碳青霉烯类药物,对大多数菌种的活性与亚胺培南和美罗培南相似,但对非发酵菌的活性较弱。对大多数产AmpC酶和超广谱β-内酰胺酶的菌株仍有活性,不过如果这些酶与极低的通透性共同存在,也可能出现耐药。IMP、VIM、KPC和NMC碳青霉烯酶也可导致耐药,但同样需要极低的通透性。尽管未来碳青霉烯酶的传播令人担忧,但目前其极为罕见。厄他培南每日一次静脉输注1g,在健康志愿者中的血浆半衰期约为4小时,总药物和游离药物的Cmax分别为155mg/L和13mg/L。排泄主要通过肾脏,原药和开环衍生物各占一半。试验表明,在(a)腹腔感染、(b)社区获得性肺炎、(c)急性盆腔感染、(d)皮肤及皮肤结构感染和(e)复杂性尿路感染方面,厄他培南与哌拉西林/他唑巴坦或头孢曲松等效。美国的药品许可涵盖了所有这五个适应证;欧盟的许可涵盖了前三个。进一步的潜在用途包括家庭静脉治疗、针对产AmpC酶或超广谱头孢菌素酶肠杆菌科细菌的靶向治疗,以及初步用于外科预防。碳青霉烯类药物使用范围扩大引发了公共卫生方面的担忧,不过亚胺培南使用17年后碳青霉烯酶仍然极为罕见,且碳青霉烯酶大多出现在厄他培南抗菌谱之外的非发酵菌中,并且在肠杆菌科细菌中需要极低的通透性才能产生耐药,这些情况在一定程度上缓解了担忧。然而,如果要广泛使用厄他培南,就需要仔细监测其对耐药生态的影响。