Letter to the Editor Concentration of Ciprofloxacin in Non-Functional Gallbladder Mucosa after Single Dose Intravenous Administration Introduction The importance of antibiotic concentration in the bile and/or tissue for the treatment of biliary infection is still a matter of controversy. Although only such agents which achieve therapeutic concentration in the bile are capable of sterilizing the infected bile [t], no information is available on the situation where cystic duct obstruction is present. Cystic duct obstruction is of clinical importance because it is present in over 90% of the cases with acute cholecystitis. Ciprofloxacin, a fluoroquinolone, shows great potency and has a broad antibacterial spectrum, including gram-negative und grampositive bacteria [2]. Studies have demonstrated that ciprofloxacin reaches a therapeutic concentration both in the bile and gallbladder tissue after intravenous or oral administration [2-5]. The aim o f this study was to determine the concentration of ciprofloxacin in the gallbladder tissue in the presence of cystic duct obstruction. Patients a n d M e t h o d s Twelve adult patients (eight female, four male) scheduled for elective cholecystectomy, who were found to have a nonfunctioning gallbladder on two occasions with oral cholecystography or intravenous cholangiography, were included in the study. The age of the patients ranged from 28-66 years (average 51.4 years). The liver function tests, serum BUN and creatinine levels were within normal limits. None of the patients had received antimicrobial agents within 72 hours prior to surgery. All of the patients were informed about the study. The patients received a single dose of 300 mg ciprofloxacin given intravenously into a large anticubital vein as a 30 rain infusion. The gallbladder was removed 30, 60 or 120 min after the end of infusion. A sample from the gallbladder walt (whole layer and mucosa) was obtained separately in addition to a bile sample. The specimens were immediately frozen and stored at - 20 °C until the time of assay. The concentration of ciprofloxacin and its metabolites M1, M2 and M3 was determined by high pressure liquid chromatography (HPLC). Results The concentration of ciprofloxacin in the gallbladder wall (whole layer) ranged from 1.5 - 13 mg/kg tissue. The mean concentration was 6.23 ± 1.1, 5.43 ± 2.58 and 6.08 -+ 2.71 mg/kg tissue at 30, 60 and 120 mill, respectively. The gallbladder mucosal concentration of ciprofloxacin ranged from 2.4 - 25.8 mg/kg tissue. The mean

mucosal concentration was 9.52 ± 1.31, 14.8. + 4.51 and 10,27 + 4.08 mg/kg tissue at 30, 60and 120 rain, respectively (Table 1 ). The concentration of the metabolites of ciprofloxacin demonstrated that M2 had the highest value (peak 18.97 mg/kg tissue) compared to the other metabotites. The concentration of ciprofloxacin in the gallbladder bile was measured in nine patients. This concentration ranged from 0.1 17.2 mg/1 with a mean of 4.45 _+2.14 mg/l. In all of these patients except one the mucosal concentration was higher than the bile concentration, None of the patients developed wound infection after a single dose 300 mg of ciprofloxacin in this study. Discussion According to our study ciprofloxacin concentrations determined in the gallbladder tissue, especially in the mucosa, were well above the required MIC values reported for bacteria causing gallbladder infection [6]. The concentrations found in the bile were lower except in one patient which can be attributed to the presence of cystic duct obstruction. The high concentrations of ciprofloxacin achieved in gallbladder tissue after a single 300 mg infusion lasting 30 min in patients with non-functional gallbladder indicate a potential use for this antibiotic in the treatment of acute cholecystitis. A comparative clinical study might clarify the value of perioperativ'ely used ciprofloxacin in high risk biliary surgery. L Sayek, V. Kaynaroglu, H. Scholt References 1. Wacha, H., Helm, E.B.: J. Antimicrob. Chemother. 9 (Suppl. A) (1982) 131-137. 2. Jeht, F., Adloff, M., Monteil, H., Brogard, J.M.: Europ. J. Drug Metabol. Pharmacokin. 12 (1987) 115-122. 3. Dan, M., Verbin, N., Gorea, H., Berger, S. A.: Europ. J. C/in. Pharmacol. 32 (1987) 217-218. 4. Strachan, C. J. L., Them, B. T.: Excretion of intravenous and orally administered ciprofloxacin in biliary disease. In: Berkarda, B., Kuemmerle, 1t. P. (eds.). Proceedings of the 14th International Congress of Chemotherapy, Kyoto, Japan 1985, pp. 1591-1592. 5. Brogard, J. M., Arnaud, J. P., Jehi, F., Bliekle, J. F., Monteil, H.: Ciprofloxacin: evaluation of its biliary excretion in man. 1st International Ciprofloxacin Workshop, Leverkusen 1985, Excerpta Medica (1986) 130--135. 6. Brogard J.M., Jehl, F., Monteil, H., Adloff, M., Blicklem J. F., Levy, P.: Anfimicrob. Agents Chemother. 28 (1985) 311-314.

Table 1: Ciprofloxacin concentrations in gallbladder tissue (mean +_SEM mg/kg tissue).

Bile concentration (9 patients): 4.45 + 2.14 mg/l. 66 / 124

Received: 3I July 1989/Accepted: 9 February 1990 I. Sayek, M.D.F.A.C.S., V. Kaynaroglu, M.D., Hacettepe University Medical School, Department of Surgery, Ankara, Turkey. H. Scholl, Ph.D., Bayer AG, Posffach 10 17 09, D-5600 Wuppertat 1, FR Germany. Infection 18 (1990) No. 2 © MMV Medizin Verlag GmbH Miinchen, Mtinchen 1990