Pharmacokinetics and Tissue Penetration of Moxifloxacin in??Intervention Therapy for Intra-Abdominal Abscess

Abstract

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.