Biliary excretion of aztreonam in patients with biliary tract disease

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confidence: 99%

Decreased biliary excretion of cefamandole after percutaneous biliary decompression in patients with total common bile duct obstruction

Levi¹,

Martínez²,

Malinin³

et al. 1984

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“…The results demonstrate a high hepatobiliary concentration after drug administration. Although aztreonam excretion may be inhibited by biliary tract disease, previous studies have shown that therapeutic levels of the drug are rapidly attained in the bile following biliary decompression (7). The data suggest that aztreonam may be useful in the management of Enterobacteriaceae colonization following the anatomic and functional alterations arising in the biliary tract after a cholecystectomy.…”

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confidence: 77%

“…Filtered extracts, standards, and spiked tissue samples were analyzed by HPLC. Aztreonam in bile was assayed by a previously described method (7).…”

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confidence: 99%

Aztreonam concentration in abdominal tissues and bile

Condon¹,

Friedhoff²,

Edmiston³

et al. 1986

Abdominal tissue, serum, and bile samples were obtained from 37 patients given a single, 2-g intravenous infusion of aztreonam immediately prior to an elective abdominal operation. Samples were obtained at 0 to 6 h after dosing. Mean concentrations in tissues and fluids and specimen/serum ratios are reported. Levels in tissue and bile exceeded the reported MICs for 90% of most members of the family Enterobacteriaceae for up to 6 h.Aztreonam is a new synthetic, monocyclic beta-lactam antibiotic which has exhibited excellent activity against aerobic and facultative gram-negative microorganisms. MICs of <1.0 ,ug/ml have been reported for many members of the family Enterobacteriaceae (14,15). The compound has demonstrated effective bactericidal activity against clinical isolates of Pseudomonas aeruginosa and appears resistant to many of the plasma-mediated beta-lactamases (9). Aztreonam has also exhibited interesting synergistic properties when combined with aminoglycosides against multiplyresistant gram-negative bacteria (1, 2). The present study was undertaken to determine the concentrations of aztreonam in various abdominal tissues and fluids obtained from patients during elective operative procedures.A total of 37 patients (20 males and 17 females), ranging in age from 14 to 82 years (mean, 51 years), in weight from 43.9 to 104.5 kg (mean, 69.5 kg), and in height from 139 to 182 cm (mean, 166 cm) participated in the study. Prior to patient screening, we received approval to carry out the study from both the Milwaukee County Medical Complex and the Medical College of Wisconsin human subject review committees. Written informed consent was obtained from the patients or appropriate relatives. The elective operations were performed for a variety of indications; the most common operations were resection of a neoplasm, hernia repair, fundoplication for reflux esophagitis, cholecystectomy, and colostomy removal or closure.A total of 22 patients received concomitant antibiotics, 19 for prophylaxis and 3 for preexisting infections. The antibiotics were given intravenously for surgical prophylaxis (cefazolin, cefoxitin, gentamicin, tobramycin, clindamycin, and penicillin G potassium), orally for gut sterilization (erythromycin and neomycin), and topically for irrigation of tissues (kanamycin and bacitracin). The systemic antibiotics had been previously shown to be inactive in the aztreonam assay. Two patients received trimethoprim-sulfamethoxazole postoperatively for urinary tract infections. Specimens from these patients were not included in the study because of potential interference with the aztreonam assay.Aztreonam (sterile powder; arginine blend; 2,000 mg) was reconstituted, diluted with 5% glucose in water to a final volume of 50 ml, and infused intravenously over a period of 5 min following the induction of anesthesia. A heparinized * Corresponding author. venous blood sample was obtained preoperatively for the determination of hemoglobin. During surgery, 1 to 2 g of normal (i.e., not infected or malignant) specime...

“…In healthy male subjects given 14C-labeled aztreonam intravenously, 12.3% of the total radioactivity appeared in the feces, reflecting biliary secretion (19). In patients with biliary tract cannulation because of total obstruction of the common bile duct, biliary excretion accounted for a mean of 0.18% of the total administered dose (9). In patients with T-tube insertion postcholecystectomy, mean peak bilary concentrations of ca.…”

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confidence: 99%

“…In patients with T-tube insertion postcholecystectomy, mean peak bilary concentrations of ca. 40 ,ug/ml were reached 2.4 h after a single 1-g dose of aztreonam (9). Animal studies have also shown that aztreonam is excreted in the feces via the biliary route (16).…”

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confidence: 99%

Effects of cirrhosis on kinetics of aztreonam

MacLeod¹,

Bartley²,

Payne³

et al. 1984

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Aztreonam was administered as a single, 3-min, 1-g intravenous infusion to 18 subjects, including 6 with biopsy-proven, primary biliary cirrhosis, 6 with biopsy-proven, stable alcoholic cirrhosis, and 6 age-and sexmatched control subjects with normal hepatic functions. Aztreonam was well tolerated by all subjects. Multiple blood samples and timed, cumulative urine samples were taken for assay of aztreonam content and determination of pharmacokinetic profiles. Protein-free filtrates of serum were also assayed for drug levels. Analyses by microbiological and high-pressure liquid chromatographic procedures gave equivalent results. The kinetic data were described by an open, linear, two-compartment model. There were significant differences in elimination half-life (3.2 verus 1.9 h), serum clearance (0.8 versus 1.1 ml/min per kg), and nonrenal clearance (0.2 versus 0.4 ml/min per kg) between the alcoholic cirrhosis group and the normal control group and in elimination half-life (2.2 versus 1.9 h) between the primary biliary cirrhosis group and the normal control group. There was also a difference in nonrenal clearance between the alcoholic cirrhosis and primary biliary cirrhosis groups (0.2 versus 0.5 ml/min per kg). Although the handling of aztreonam differed in the three groups, the magnitude of the difference would warrant a change in aztreonam dosing only for the alcoholic cirrhosis group. In this group, dose adjustment might be required if long-term therapy with high doses of aztreonam is indicated.