Pefloxacin penetration into human necrotic pancreatic tissue

Antibiotic prophylaxis may be useful in acute necrotising pancreatis, a disease associated with a considerable incidence of infectious complications. The aim of this study was to assess pefloxacin penetration into necrotic pancreatic tissue during human necrotic pancreatitis. Ten patients (mean age 53.2 +/- 17.4 years) with severe acute pancreatitis (mean Ranson score 4.3) were studied. Pefloxacin was administered at a dose of 400 mg bd every 12 h by i.v. infusion (bolus, 15 min). Intraoperative samples of necrotic pancreatic tissue and blood were collected simultaneously 1, 2, 4.5, 6, 8.5 or 10 h after the last pefloxacin administration in patients treated for 1, 3, 4, 7, 8, 17 or 20 days. Drug concentrations were determined by the microbiological agar-well diffusion method (Escherichia coli Kp 05124 as test micro-organism in Isosensitest Agar). Levels in serum ranged from 2.0 to 9.0 mg/L (at 2 and 6 h, respectively), in necrotic pancreatic tissue from 2.0 to 29.0 micrograms/g depending on different sampling time. Maximum tissue peak concentrations appeared between 4 and 6 h. The necrotic pancreatic tissue/serum concentration ratio ranged from 0.9 to 5.1, values depending on tissue sample collection. Therapeutic concentrations (20.6 micrograms/g) above the MIC of potentially pathogenic enteric microorganisms were still present in necrotic pancreatic tissue 10 h after the last drug administration. Pefloxacin appeared to concentrate in necrotic pancreatic tissue, without appreciable accumulation after multiple-dose administration. The pefloxacin concentrations in necrotic pancreatic tissue showed high variability, depending on the degree of necrosis, inflammation and sample vascularization. Our results provided evidence of good, prompt penetration of pefloxacin into necrotic pancreatic tissue. Pefloxacin seems to exhibit favourable pharmacokinetic and pharmacodynamic properties for pancreatic infections.