Search

The pharmacokinetics of cefoxitin were studied in nine patients with pleural effusion of varied etiologies. All patients received a single intravenous bolus of 30 mg/kg. Cefoxitin levels were determined simultaneously in plasma and pleural fluid by means of a microbiologic plate diffusion method. The antibiotic follows a two-compartment open kinetic model. In the pleural fluid, maximum concentrations of cefoxitin of 19.72 +/- 9.72 microgram/ml were reached two hours after administration. The fraction of the antibiotic that reaches the pleural fluid represents 0.22% to 4.03% of the dose administered. The disappearance constant of the antibiotic from the pleural fluid is significantly smaller (Kd = 0.15 +/- 0.03 hours-1) than the elimination constant determined from the plasma levels (K13 = 2.27 +/- 0.90 hours-1). Cefoxitin was always found in antibacterial concentration in the pleural fluid for a considerable period of time.

Cefoxitin is a useful new chephamycin antibiotic available for IM of IV administration. It is a bactericidal beta-lactam antibiotic indicated for treatment of serious infections caused by a wide spectrum of gram-negative aerobic and anaerobic bacteria. Specific indications include: 1) polymicrobial infections (aerobic gram-negative rods and anaerobic bacteria); 2) nosocomial cephalothin-resistant gram-negative bacillary infections; 3) penicillin-resistant staphylococcal infections, and 4) anaerobic infections (pelvic, intraabdominal). Cefoxitin can be used as a single drug alternate to a two-drug antibiotic regimen (such as a cephalosporin-aminoglycoside combination) in polymicrobic infections of the pelvis, abdomen, skin, bones, or muscles. Cefoxitin is a significant drug in the armamentarium against anaerobic bacteria, particularly Bacteroides species. Since cefoxitin is highly resistant to staphylococcal beta-lactamase, it is effective against penicillin-resistant staphylococci. Cefoxitin has been effective in treating serious nosocomial infections caused by resistant aerobic gram-negative rods and anaerobic bacteria.

For elective alimentary tract operations in which contamination is moderate, single dose prophylaxis with piperacillin is equivalent to triple dose cefoxitin, a well established and effective regimen. Both methods failed to control infection arising in the perineal wound after abdominoperineal resection. Just as is the case with drain site infection, such infection often evolves from postoperative contamination and, indeed, is in theory and in fact unlikely to be controlled by perioperative prophylaxis. This study is among the first of several examining the issue of single dose prophylaxis and will be the harbinger of other studies from other groups examining whether or not the course of therapeutic antibiotics can be safely shortened in patients with peritoneal contamination.

The pharmacokinetics of cefoxitin were studied after the administration of a single intravenous dose of 40 mg/kg to rabbits with normal renal function and rabbits with varying degrees of renal impairment. The plasma and interstitial fluid concentrations of the antibiotic were determined by a microbiologic plate diffusion method. The antibiotic follows a two-compartment open kinetic model. The plasma half-life of slow disposition phase t1/2 beta, increases from 0.26 hour in rabbits with normal renal function to 5.41 hours in rabbits with severe renal impairment. In the interstitial fluid the elimination half-life increases from 1.18 hours in rabbits with normal renal function to 99.00 hours in rabbits with renal impairment. A linear relationship is established between the values that define the elimination of the antibiotic and the serum creatinine concentrations. The constant of the incorporation into the interstitial fluid decreases significantly in rabbits with renal impairment.

The secretion of cephalothin and cefoxitin in stimulated pure pancreatic juice was studied in 13 persons after intravenous administration of antibiotics. Of all these studied, three had acute relapsing pancreatitis, five chronic pancreatitis, and five were control subjects. Antibiotic levels were measured in paired pure pancreatic juice and serum samples at fixed time intervals after administration. Cephalothin was detected in very low levels (1 to 1.8 micrograms/ml) in the pure pancreatic juice of four of the six persons studied (3 micrograms/ml). Although therapeutic levels were not obtained in stimulated pure pancreatic juice with either antibiotic, additional studies evaluating antibiotic levels in unstimulated pure pancreatic juice and in pancreatic tissue would be helpful in assessing the role of antibiotic therapy in the treatment of pancreatitis.

Antibiotics were given intravenously to dogs with chronic pancreatic fistulas, and serum and pancreatic juice levels were measured. Despite adequate serum values, gentamicin, tetracycline, clindamycin, and moxalactam did not appear in the pancreatic juice, which suggested a barrier to their excretion. In contrast, chloramphenicol reached a peak concentration in the pancreatic juice that amounted to 36 percent of the peak serum value. In the pancreatic juice, ampicillin, cefoxitin, and cefamandole reached only 5 percent of the peak serum values but were still within the therapeutic range. We have concluded that there is a blood-pancreatic juice barrier to some antibiotics, which leads to selective excretion.