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An experimental model, where fibrin clots were inserted subcutaneously in rabbits, was adapted to study the in vivo efficacy of two cephalosporins against Bacteroides fragilis. The respective MIC's of cefamandole and cefoxitin against the microorganism were 16 microgram/ml and 1 microgram/ml. The clots were infected with 10(7) B. fragilis. Groups of seven animals received an intravenous bolus injection (100 mg/kg) of either drug. The serum levels of both drugs were similar to those seen in humans. The peak concentrations of cefamandole (40 microgram/mg) in the clots were found to be ten times higher than those of cefoxitin (4 microgram/mg). The log number of colony forming units in the clots averaged 7.5 at 0 h. At 6 hours, this number reached 8 in the untreated animals, 1.5 after cefoxitin, and 1.7 after cefamandole. The apparent in vitro superiority of cefoxitin against B. fragilis could not be demonstrated in vivo. This discrepancy between in vitro and in vivo data can be explained by the high degree of penetrance of cefamandole into the infected fibrin loci. In this animal system, both cefoxitin and cefamandole had similar in vivo activity against B. fragilis.

The objective of the study was to evaluate the concentrations obtained in serum and bronchial secretions after administration of five beta-lactam antibiotics: cephradin (1 g per os) and cefoxitin (2 g i.v. infusion), amoxycillin (1.0 g per os), bacampicillin (0.4 g and 0.8 g per os) and ampicillin (1.0 g per os). 123 adult patients were included in the study and received a single dose of the tested drug. Serum and mucus samples were collected simultaneously 30 minutes, 1, 2 or 4 hours after administration of the drugs. Mucus samples were taken by fibroscopy but in some patients the samples were collected through a tracheostomy cannula which allowed sampling at different time intervals. The results show that the concentrations of penicillins in bronchial secretions increase progressively between one and four hours after administration of the drugs. Bronchial levels obtained after oral administration of ampicillin are low, not more than 5 to 10% of serum levels. The other antibiotics tested show worthwhile concentrations in bronchial secretions, especially with cephalosporins and bacampicillin which exhibits higher serum and bronchial concentrations than ampicillin.

A review is given on the pharmacokinetic characteristics of some cephalosporin antibiotics. The use of the pharmacokinetic parameters serum concentration, serum protein binding, serum half life, and apparent volume of distribution as a basis for the selection of the clinically most effective cephalosporin derivative is discussed. It is concluded that these parameters must be used in conjunction with data on tissue distribution to specialized sites, and with information on antibacterial activity and toxicity.

The present study was undertaken to compare the ability of three cephalosporins--cephalothin, cephaloridine and cefuroxime--and a cephamycin--cefoxitin--to penetrate into extravasal compartments. The study was performed using female adult rabbits with subcutaneously implanted steel net cages. All antibiotics were given in a dose of 50 mg/kg b.w. parenterally as i.v. injections. The concentrations of the different antibiotics were determined simultaneously in serum and in fluid obtained from the cages. The concentrations were followed after single doses as well as after repeated doses using an agar well technique for the assays. To control the experimental conditions electrolyte and protein contents of the fluid in the different cages were followed and were found to be stable during the experimental period. All antibiotics were rapidly eliminated from serum. The concentrations in the cages reached its maximum 1.5-3 hours after administration. The highest concentrations in the extravasal compartments were obtained with cephaloridine and the lowest with cephalothin with the values of the other antibiotics ranging in between.

We have studied cefuroxime, a new beta-lactamase resistant cephalosporin, and cefoxitin, the first cephamycin antibiotic, which is also resistant to many beta-lactamases. Both of these antibiotics have been shown to be microbiologically superior to the "first generation" cephalosporins, cefuroxime having notable activity against Haemophilus influenzae, and cefoxitin against Bacteroides fragilis. Neither antibiotic is absorbed from the gut but, following parenteral administration, serum, urine and bile concentrations are high. Clinical trials have been conducted on both cefoxitin and cefuroxime. The results of these have been satisfactory and untoward side-effects minimal. We suggest that cefoxitin will be particularly valuable in the management of abdominal sepsis and cefuroxime in infections caused by H. influenzae.