van Os Wisse, Wulkersdorfer Beatrix, Eberl Sabine, Oesterreicher Zoe, Schwabl Philipp, Reiberger Thomas, Paternostro Rafael, Weber Maria, Willinger Birgit, Zeitlinger Markus
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
Front Pharmacol. 2023 Mar 29;14:1124821. doi: 10.3389/fphar.2023.1124821. eCollection 2023.
The environment of the infection site affects bacterial growth and antibiotic activity. When bacterial growth and antibiotic activity are studied in body fluids, samples of multiple subjects are usually pooled, averaging out potentially relevant differences in composition. The ascitic fluid (AF) environment is frequently associated with spontaneous bacterial peritonitis (SBP) in cirrhotic patients. In this study, bacterial growth and ceftriaxone activity were evaluated in individual AF using an model of SBP, reflecting the environment and pharmacokinetics at the infection site. AF was obtained from nine cirrhotic patients with non-infected ascites. Growth of nine bacterial strains (three , four , one , and one ) in individual AF was assessed and correlated with biomarkers including potential risk factors for SBP. Ceftriaxone time-kill experiments, in which the pharmacokinetic profile observed in AF following a 1 g intravenous infusion was replicated, were performed with two and two isolates with minimum inhibitory concentrations around the ceftriaxone resistance breakpoint. Significant correlations were found between bacterial growth and AF levels of protein (Spearman's rank correlation coefficient ρ = -0.35), albumin (ρ = -0.31), and complement C3c (ρ = -0.28), and serum levels of bilirubin (ρ = 0.39) and aspartate aminotransferase (ρ = 0.25). Ceftriaxone was active in AF, even against resistant isolates, generally resulting in ≥2 log reductions in bacterial count within 24 h. Ascites patients may be predisposed to or protected against SBP based on the antimicrobial capacity of their AF. Ceftriaxone at clinical AF concentrations is active in the AF environment.
感染部位的环境会影响细菌生长和抗生素活性。在研究体液中的细菌生长和抗生素活性时，通常会汇集多个受试者的样本，从而平均掉成分中潜在的相关差异。腹水（AF）环境常与肝硬化患者的自发性细菌性腹膜炎（SBP）相关。在本研究中，使用SBP模型在个体腹水中评估细菌生长和头孢曲松活性，该模型反映了感染部位的环境和药代动力学。AF取自9例非感染性腹水的肝硬化患者。评估了9种细菌菌株（3种 、4种 、1种 和1种 ）在个体腹水中的生长情况，并将其与包括SBP潜在危险因素在内的生物标志物进行关联。进行了头孢曲松时间杀菌实验，该实验复制了1g静脉输注后在腹水中观察到的药代动力学特征，实验对象为两种 和两种 分离株，其最低抑菌浓度接近头孢曲松耐药断点。发现细菌生长与腹水蛋白水平（Spearman等级相关系数ρ = -0.35）、白蛋白（ρ = -0.31）、补体C3c（ρ = -0.28）以及血清胆红素水平（ρ = 0.39）和天冬氨酸转氨酶水平（ρ = 0.25）之间存在显著相关性。头孢曲松在腹水中具有活性，即使是对抗耐药菌株，通常也能在24小时内使细菌计数减少≥2个对数级。腹水患者可能因腹水的抗菌能力而易患或预防SBP。临床腹水中浓度的头孢曲松在腹水环境中具有活性。
