Antibiotic Penetrance of Ascitic Fluid in Dogs

Simultaneous peritoneal fluid and serum gentamicin assays were performed at 1- or 4-h intervals after the intravenous administration of gentamicin (3 to 5 mg/kg per day) during nine episodes of spontaneous bacterial peritonitis in cirrhotic patients. Mean peritoneal fluid levels were 4.2 micrograms/ml, whereas simultaneous mean serum levels were 6.1 micrograms/ml (mean percent diffusion into ascites of 67.8%). Three additional patients with uninflamed ascites demonstrated lower levels of diffusion. Regression analysis revealed a positive correlation between simultaneous serum and peritoneal fluid levels. We conclude that diffusion of gentamicin from serum into peritoneal fluid during spontaneous peritonitis is therapeutically adequate if sufficient serum levels are maintained.

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Peritoneal fluid concentrations of gentamicin in patients with spontaneous bacterial peritonitis

Richey¹,

Schleupner²

1981

“…We have previously measured ascitic fluid concentrations of three cephalosporins in a dog model after a single parenteral dose (6). In this paper we extend these observations to include cefamandole in addition to cefazolin, cephaloridine, and cephalothin in a multiple-dose study of serum and ascitic fluid pharmacokinetics and protein binding of cephalosporins in dogs.…”

mentioning

confidence: 89%

“…Ascites was produced in mongrel dogs (initial weight, 14 to 18 kg) by partial ligation of the inferior vena cava as previously described (6). Dietary sodium chloride supplementation (15 g/day) was required in one dog to maintain ascites.…”

mentioning

confidence: 99%

Ascitic Fluid Cephalosporin Concentrations: Influence of Protein Binding and Serum Pharmacokinetics

Gerding

Peterson

Legler

et al. 1978

Self Cite

Mongrel dogs with ascites created by inferior vena cava ligation were given cephalothin, cephaloridine, cefazolin, and cefamandole to evaluate the effect of protein binding and serum pharrnacokinetics on the distribution of cephalosporins into ascitic fluid. Antibiotics were given intramuscularly (15 mg/kg) every 4 h for a total of eight doses. Antibiotic binding to dog serum and ascitic fluid was measured by ultracentrifugation. Binding of the cephalosporins to dog serum ranged from 31% for cephaloridine to 46% for cephalothin, considerably lower than human serum binding for cefazolin, cephalothin, and cefamandole. Antibiotic binding to ascitic fluid was only slightly lower than that to serum. Ascitic fluid antibiotic concentrations, which approached equilibrium at 16 to 28 h, were significantly higher for cefazolin and cephaloridine than for cephalothin and cefamandole. However, serum concentrations were also higher for cefazolin and cephaloridine, and percent penetration (ratio of serum peak to ascites peak x 100) was not statistically different among the four drugs. Binding of these cephalosporins to extravascular fluid protein was an important factor that determined the total ascitic fluid antibiotic level achieved. A formula utilizing the log mean serum level and binding to serum and extravascular fluid protein was used to accurately predict ascitic fluid drug levels at equilibrium.

“…These tics of pleural fluid in our patients suggest the presence of acute severe inflammation in pleural space, even though cell counts were not carried out. Third, Gerding et al (4) have reported that the levels of antibiotic in ascitic fluid of dogs are related inversely to the volume of ascitic fluid. The large volumes of extravascular fluid, i.e., 4 to 6 liters, could have disturbed circulation and drug kinetics, which might inhibit drug penetration into extravascular fluid.…”

Section: Resultsmentioning

confidence: 99%

Penetration and clearance of cefoperazone and moxalactam in pleural fluid

Yamada¹,

Iwanaga²,

Nakanishi³

et al. 1985

The penetration of cefoperazone and moxalactam into pleural fluid was studied in 11 patients after intravenous infusion of 2-g doses of these agents. Clearance of these agents from pleural fluid was studied in seven patients after instillation of 1-g doses into the pleural space. The concentrations in pleural fluid after intravenous infusion of 2-g doses reached a peak of 7 to 25 ,ug/ml for cefoperazone and 9 to 35 ,ug/ml for moxalactam at 4 to 6 h after administration. These levels exceeded reported MICs for most susceptible organisms. The elimination half-life of both agents was about two to five times longer in pleural fluid than in serum. These prolonged elimination rates of both agents might be of great advantage for killing bacteria in the pleural space.