The activity of cefoxitin in vitro against hospital pathogens, and in vivo in septicaemic patients

Cefoxitin is the first cephamycin antibiotic having a different structure to cephalosporin antibiotics. Cephamycins are remarkably resistant to all beta-lactamases, but some organisms including Pseudomonas species are resistant to cefoxitin either because the antibiotic fails to penetrate the cell or because the site of antibiotic activity is insensitive to cefoxitin. In Royal Perth Hospital Gram-negative bacteria are tested for their antibiotic sensitivity by inoculation onto agar containing an antibiotic. The concentration of antibiotic in the agar is related to the concentration achievable in clinical situations. Cefoxitin is administered intravenously as 1 g which results in a concentration over 20 mg/l for 60 min, or is administered as 2 g which gives concentrations twice as high. After probenecid and 1 g cefoxitin blood concentrations remain over 25 mg/l for 2 hours. For agar dilution tests the concentration of cefoxitin in the agar was 16 mg/l. Of 481 strains of E. coli tested 99% were sensitive to cefoxitin; all 179 strains of Proteus mirabilis were sensitive, and of 55 indole-positive Proteus strains 94% were sensitive. Of 200 strains of Klebsiella 94% were sensitive; of 35 strains of Citrobacter 56% were sensitive, all 6 strains of Providencia species were sensitive to cefoxitin, and of 21 strains of Serratia 73% were sensitive. Of 39 strains of Acinetobacter 18% were sensitive, and of 83 strains of Enterobacter 16% were sensitive. Cefoxitin, in addition to being active against Gram-positive and Gram-negative organisms, is active against anaerobic organisms. It is thus particularly useful in treating abdominal infections, and in patients with a raised serum creatinine it is likely to be more effective than gentamicin or tobramycin which have to be given at long intervals, and during the slow excretion period relatively inadequate concentrations of the aminoglycoside may not control the infection. At Royal Perth Hospital we have had several patients with abdominal infection and a raised serum creatinine, and cefoxitin has been used very successfully, with ticarcillin. Blood concentrations of 240 mg/l have been obtained without any toxic effects, and thus highly effective concentrations can be maintained without undue risk of toxicity.