Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
Department of Clinical Pharmacy, Deventer Hospital, Deventer, The Netherlands.
J Antimicrob Chemother. 2024 Nov 4;79(11):2750-2761. doi: 10.1093/jac/dkae310.
Patients with liver cirrhosis are prone to develop severe bacterial infections. Pharmacokinetics (PK) of antibiotics in cirrhosis are potentially affected by impaired biotransformation phases 0-3 and consequences of portal hypertension such as portovenous shunting, ascites formation and/or acute kidney injury (AKI). We aimed to elucidate to what extent PK of selected antibiotics and, therefore, dosage recommendations are affected in adults with cirrhosis.
We performed a systematic search in PubMed, Embase, Cochrane and CINAHL on effects of cirrhosis on PK profiles of ceftriaxone, fosfomycin, gentamicin, meropenem, nitrofurantoin, piperacillin/tazobactam and vancomycin in adults. Antibiotics were selected based on the lack of specific dosing recommendations for adults with cirrhosis. We included studies reporting on ≥1 of the following PK parameters: AUC, half-life (t½), CL, volume of distribution (Vd), peak (Cmax) or trough concentrations (Cmin).
We identified 15 studies (ceftriaxone, n = 5; gentamicin, n = 3; meropenem n = 5; vancomycin, n = 2), including 379 patients with cirrhosis, of which two were of high quality. No eligible studies were identified for fosfomycin, nitrofurantoin or piperacillin/tazobactam. Ceftriaxone unbound concentration increased in cirrhosis, but was mitigated by increased renal CL. Gentamicin levels in ascitic fluid were comparable to those in plasma. Meropenem PK parameters were not altered in cirrhosis without AKI, but in the presence of AKI a decrease in CL was observed. In contrast, vancomycin CL decreased in advanced cirrhosis.
Available data in studies of mostly moderate quality suggest that PK of ceftriaxone, meropenem and vancomycin are altered in cirrhosis. More advanced PK studies are needed to provide specific dosing recommendations.
肝硬化患者易发生严重细菌感染。肝硬化患者的抗生素药代动力学（PK）可能受到生物转化相 0-3 受损以及门脉高压的影响，如门体分流、腹水形成和/或急性肾损伤（AKI）。我们旨在阐明在肝硬化患者中，哪些抗生素的 PK 受到影响，以及因此对剂量建议的影响程度。
我们在 PubMed、Embase、Cochrane 和 CINAHL 上进行了系统检索，以了解肝硬化对成人头孢曲松、磷霉素、庆大霉素、美罗培南、呋喃妥因、哌拉西林/他唑巴坦和万古霉素 PK 谱的影响。选择这些抗生素是基于缺乏针对肝硬化成人的特定剂量建议。我们纳入了报告以下至少 1 个 PK 参数的研究：AUC、半衰期（t½）、CL、分布容积（Vd）、峰（Cmax）或谷浓度（Cmin）。
我们确定了 15 项研究（头孢曲松，n=5；庆大霉素，n=3；美罗培南，n=5；万古霉素，n=2），包括 379 例肝硬化患者，其中两项研究质量较高。未发现磷霉素、呋喃妥因或哌拉西林/他唑巴坦的合格研究。肝硬化时头孢曲松未结合浓度增加，但通过增加肾 CL 得到缓解。腹水和血浆中的庆大霉素水平相当。在没有 AKI 的情况下，肝硬化患者的美罗培南 PK 参数没有改变，但在存在 AKI 的情况下，CL 下降。相比之下，万古霉素 CL 在晚期肝硬化中下降。
大多数质量中等的研究提供的现有数据表明，头孢曲松、美罗培南和万古霉素的 PK 在肝硬化中发生改变。需要更先进的 PK 研究来提供特定的剂量建议。
