Rink Andreas D, Stass Heino, Delesen Heinz, Kubitza Dagmar, Vestweber Karl-Heinz
Department of General Surgery, Leverkusen General Hospital, Leverkusen, Germany.
Clin Drug Investig. 2008;28(2):71-9. doi: 10.2165/00044011-200828020-00001.
Intra-abdominal abscesses are usually polymicrobial and involve a variety of aerobic and anaerobic organisms. Thus, in addition to adequate drainage, empirical coverage with broad-spectrum antimicrobials is central to the management of such abscesses and an understanding of pharmacokinetic properties can be valuable when selecting antimicrobial agents. The present study examined the penetration of the fluoroquinolone antimicrobial moxifloxacin into abdominal abscess fluid in patients with an intra-abdominal abscess.
This was a non-randomized, open-label, single-centre trial. Eight patients with CT or ultrasound evidence of a localized intra-abdominal abscess requiring interventional drainage without signs of generalized peritonitis were considered suitable candidates for pharmacokinetic analysis. Each patient received a single dose of moxifloxacin 400 mg by intravenous infusion. Paired samples of blood and abscess fluid were collected over 24 hours for pharmacokinetic analysis.
Following intravenous infusion, moxifloxacin penetrated and accumulated in intra-abdominal abscess fluid. The abscess fluid/plasma concentration ratio increased continuously from 0.083 (95% CI 0.047, 0.147) at 2 hours after administration to 1.66 (95% CI 0.935, 2.946) at 24 hours; concentrations in abscess fluid tended to exceed those in plasma after 12-24 hours. Half-life and mean residence time were longer in abscess fluid than in plasma, suggesting that moxifloxacin accumulates in abscess fluid. The abscess fluid/plasma concentration ratio continued to increase throughout the 24-hour sampling period, indicating that equilibrium between plasma and abscess fluid was not reached during this time. High intersubject variability for total moxifloxacin concentrations in intra-abdominal abscess fluid was noted, suggesting that abscess wall permeability is likely to be the parameter most strongly influencing moxifloxacin pharmacokinetics in abscess fluid. Comparison of the study results with data obtained from other in vitro studies suggested that abscess fluid concentrations above the minimum inhibitory concentrations for pathogens commonly isolated in intra-abdominal infections were maintained for approximately 8 hours after administration in this study.
Moxifloxacin penetrates intra-abdominal abscesses after interventional drainage. Based on the pharmacokinetic data, moxifloxacin is a good candidate therapy for use in patients with intra-abdominal abscesses undergoing CT-guided percutaneous drainage and may also prove valuable in the general systemic management of intra-abdominal abscesses in the future.
腹腔内脓肿通常是多种微生物感染,涉及多种需氧菌和厌氧菌。因此,除了充分引流外,经验性使用广谱抗菌药物是此类脓肿治疗的关键,而了解药代动力学特性在选择抗菌药物时可能很有价值。本研究检测了氟喹诺酮类抗菌药物莫西沙星在腹腔内脓肿患者脓肿液中的渗透情况。
这是一项非随机、开放标签、单中心试验。8例经CT或超声证实有局限性腹腔内脓肿且需要介入引流且无弥漫性腹膜炎体征的患者被认为是药代动力学分析的合适人选。每位患者静脉输注单剂量400mg莫西沙星。在24小时内采集配对的血液和脓肿液样本进行药代动力学分析。
静脉输注后,莫西沙星渗透并积聚在腹腔内脓肿液中。脓肿液/血浆浓度比从给药后2小时的0.083(95%CI 0.047,0.147)持续增加至24小时时的1.66(95%CI 0.935,2.946);12 - 24小时后脓肿液中的浓度往往超过血浆中的浓度。脓肿液中的半衰期和平均驻留时间比血浆中的长,表明莫西沙星在脓肿液中积聚。在整个24小时采样期内,脓肿液/血浆浓度比持续增加,表明在此期间血浆与脓肿液之间未达到平衡。腹腔内脓肿液中莫西沙星总浓度存在较高的个体间变异性,提示脓肿壁通透性可能是最强烈影响莫西沙星在脓肿液中药代动力学的参数。将研究结果与其他体外研究数据进行比较表明,本研究中给药后腹腔内感染常见病原菌的最低抑菌浓度以上的脓肿液浓度维持约8小时。
介入引流后莫西沙星可渗透至腹腔内脓肿。基于药代动力学数据,莫西沙星是接受CT引导下经皮引流的腹腔内脓肿患者的良好候选治疗药物,未来在腹腔内脓肿的一般全身治疗中可能也具有重要价值。