Gallbladder Wall Tissue Research Articles

Tissue penetration of moxifloxacin into human gallbladder wall in patients with biliary tract infections

Moxifloxacin, the newest fourth-generation fluoroquinolone, has a broad spectrum of antibacterial activity covering both Gram-positive and Gram-negative aerobic and anaerobic bacteria and is therefore very well suited for the treatment of biliary tract infections. The present study aimed to determine the penetration of moxifloxacin into gallbladder tissue to evaluate its antibiotic potential in this indication. Hospitalized patients with acute cholecystitis received a single, 1 h infusion of 400 mg of moxifloxacin before cholecystectomy. Serum and gallbladder wall tissue samples were collected during surgery, and the moxifloxacin concentrations were measured by HPLC. Sixteen patients (eight men and eight women) were included between January 2007 and April 2008. The time between start of infusion and gallbladder removal ranged from 50 min to 21 h 10 min. The serum concentration at the time of cholecystectomy was between 0.39 and 4.37 mg/L, and the tissue concentration between 1.73 and 17.08 mg/kg. The tissue-to-serum concentration ratio ranged from 1.72 to 6.33. The results show that moxifloxacin penetrates well into gallbladder tissue and is therefore a therapeutic option for biliary tract infection. The highest concentrations in serum and gallbladder tissue were measured shortly after the end of a 1 h infusion. As perioperative prophylaxis, moxifloxacin should therefore be administered 30-60 min before the first surgical incision.

Pharmacokinetics and Tissue Distribution of Intravenous Ofloxacin for Antibiotic Prophylaxis in Biliary Surgery

The plasma levels and tissue penetration of ofloxacin were studied after prophylactic administration in 17 patients undergoing elective biliary surgery. A single dose of ofloxacin 400mg given intravenously as an infusion was administered 1 hour before surgery. Adequate drug plasma levels [>/= minimum inhibitory concentration (MIC(90)) for Escherichia coli] were found throughout the procedure. Mean peak (1 hour) and last-determined (36 hours) ofloxacin serum levels were 7.97 +/- 3.79 mg/L and 0.19 +/- 0.13 mg/L, respectively. The elimination half-life (t((1/2)lambda)) was 8.86 +/- 3.07 hours, and the clearance and steady-state volume of distribution were 0.17 +/- 0.05 L/h.kg and 112.90 +/- 37.09L, respectively. The area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) was 41.60 +/- 12.51 mg/L.h. In bile, ofloxacin levels were higher than in plasma and showed great variability. Adequate ofloxacin levels in subcutaneous cell tissue and gallbladder wall tissue were observed during the surgical procedure. Patients were observed daily throughout their hospital stay. This included examination of the surgical wound and recording of body temperature. No cases of anaerobic infection were noted in the study patients. Other constants such as hospitalisation stay and time of recuperation were normal for this type of surgery.

Intraoperative concentrations of ofloxacin in serum, bile fluid, and gallbladder wall tissue

To evaluate concentrations of ofloxacin in serum, bile fluid, and gallbladder wall tissue after intravenous administration, patients greater than or equal to 16 years old diagnosed with acute cholecystitis were randomly assigned to receive ofloxacin (400 mg) intravenously every 12 h or ceftazidime (2 g) intravenously every 8 h. Doses of each regimen were given preoperatively. Serum, bile fluid, and gallbladder wall tissue samples of consecutive patients in the ofloxacin group were obtained intraoperatively. The samples were frozen at -70 degrees C until analyzed by high-pressure liquid chromatography. Twenty-three patients (6 males and 17 females) were evaluated. The mean (+/- the standard deviation) ofloxacin concentrations in serum, bile fluid, and gallbladder wall tissue were 2.9 +/- 2.4 and 6.0 +/- 7.9 micrograms/ml and 3.1 +/- 2.9 micrograms/g, respectively. The mean number of doses each patient received before surgery was 5.3 +/- 3.0, and the mean delta time (time elapsed between last antibiotic administration and when intraoperative samples were obtained) was 9.6 +/- 7.5 h. The mean tissue-to-serum ratio was 1.2 +/- 0.5, and the mean bile-to-serum ratio was 2.3 +/- 1.4. The mean serum ofloxacin concentrations were not statistically different from the concentrations in bile (P = 0.1) and tissue (P = 0.7) at the mean delta time. The study revealed that concentrations of ofloxacin in serum, bile fluid, and gallbladder tissue after intravenous dosing were adequate against susceptible organisms found in the biliary tract.

Biliary pharmacokinetics of sulbactam plus ampicillin in humans.

The biliary pharmacokinetics of sulbactam and ampicillin was investigated in 19 patients with normal liver function who were undergoing surgery of the biliary tract. The combination of sulbactam (0.5 g) plus ampicillin (1 g) was given intravenously to five patients with T-tube drainage of the common bile duct. Mean peak concentrations of sulbactam (19.4 micrograms/ml) and ampicillin (471 micrograms/ml) in the bile occurred 0.5-1 hr after administration. Biliary excretion was estimated to account for approximately 0.24% of the sulbactam dose and 2.8% of the ampicillin dose. Fourteen other patients received the same dose of sulbactam/ampicillin immediately before elective cholecystectomy. Respective mean concentrations of sulbactam and ampicillin at the time of gallbladder removal were 4.3 micrograms/ml and 15.9 micrograms/ml in gallbladder bile and 6.3 micrograms/g and 7.7 micrograms/g in gallbladder wall tissue. These results, together with the antibacterial spectrum and potency of the combination, suggest that sulbactam/ampicillin is suitable for prophylactic use in biliary tract surgery.