Pharmacology Review
Pharmacology Review
复制标题
药理学评论
作者：
H. Garges;K. Alexander
碳青霉烯类抗生素、亚胺培南/西司他丁和美罗培南为新生儿重症监护病房中遇到的罕见和高度耐药的微生物提供了治疗选择。这些药物具有非常广泛的抗生素活性，良好的安全性，以及良好的药物对所有身体部位的渗透性，使其成为患有难以治疗的感染的足月儿和早产儿的合理选择。尽管适量的药代动力学数据支持在新生儿中安全使用碳青霉烯类抗生素，但这些药物的广谱活性决定了它们的使用仅限于治疗高度耐药的医院获得性细菌以及需氧和厌氧混合感染。
碳青霉烯类抗生素是一种具有广谱需氧和厌氧活性的β-内酰胺类抗生素。与其他β-内酰胺类抗生素一样，它们通过结合青霉素结合蛋白发挥抗菌作用，从而扰乱细菌细胞壁的合成。由于亚胺培南可被肾近端小管二肽酶迅速降解，因此它与二肽酶抑制剂西司他丁联合上市。美罗培南对肾二肽酶稳定，不需要西司他丁。
在成人和年龄较大的儿童中，亚胺培南和美罗培南已被广泛用于治疗各种感染，最明显的是腹内、妇科、下呼吸道和尿路。这些临床应用，特别是在混合感染和高度耐药感染中，反映了碳青霉烯类抗生素对重要临床病原体的广谱活性。亚胺培南和美罗培南对链球菌(包括S化脓性链球菌、S无乳链球菌和绿链球菌)、肠球菌、肺炎球菌和对甲氧西林敏感(但不耐甲氧西林)的葡萄球菌具有良好的体外抗菌活性。这些药物对几乎所有肠道革兰氏阴性杆菌(GNR)(如大肠埃希菌、克雷伯氏菌、肠杆菌、沙雷氏菌、柠檬酸杆菌、变形杆菌)和大多数非肠道GNR(如假单胞菌、不动杆菌)也具有活性。一个明显的例外是嗜麦芽窄食单胞菌。厌氧菌，包括脆弱类杆菌和梭状芽孢杆菌，对碳青霉烯类抗生素非常敏感。尽管体外药敏数据显示亚胺培南具有优异的革兰氏阳性活性和…
The carbapenem antibiotics imipenem/cilastatin and meropenem offer therapeutic options for unusual and highly antibiotic-resistant organisms encountered in the neonatal intensive care unit. The agents have a very broad spectrum of antibiotic activity, favorable safety profiles, and good drug penetration into all body sites, making them a reasonable choice for term and preterm infants who have difficult-to-treat infections. Although a moderate amount of pharmacokinetic data support the safe use of carbapenem antibiotics in neonates, the broad-spectrum activity of the agents dictates that their use be limited to the treatment of highly resistant, nosocomially acquired bacteria and mixed aerobic and anaerobic infections.
Carbapenems are beta-lactam antibiotics that have broad-spectrum aerobic and anaerobic activity. Like other beta-lactam antibiotics, they exert an antibacterial effect by binding penicillin-binding proteins, thereby disrupting bacterial cell wall synthesis. Because imipenem is rapidly degraded by renal proximal tubule dipeptidases, it is marketed in combination with the dipeptidase inhibitor cilastatin. Meropenem is stable to renal dipeptidases and requires no cilastatin.
In adults and older children, imipenem and meropenem have been used extensively for treatment of a wide variety of infections, most notably intra-abdominal, gynecologic, lower respiratory tract, and urinary tract. These clinical uses, particularly in mixed and highly resistant infections, reflect the broad-spectrum activity of carbapenems against important clinical pathogens. Imipenem and meropenem have excellent in vitro activity against streptococci (including S pyogenes , S agalactiae , and viridans group streptococci), enterococci, pneumococci, and methicillin-susceptible (but not methicillin-resistant) staphylococci. These drugs also are active against almost all enteric gram-negative rods (GNRs) (eg, Escherichia coli, Klebsiella, Enterobacter, Serratia, Citrobacter, Proteus sp) and most nonenteric GNRs (eg, Pseudomonas, Acinetobacter sp). A notable exception is Stenotrophomonas maltophilia . Anaerobes, including Bacteroides fragilis and clostridia, are very susceptible to carbapenem antibiotics. Although in vitro susceptibility data suggest that imipenem offers superior gram-positive activity and …