Cefoxitin (Mefoxin®)
Classification:
Antiinfective Agents
» Cephalosporins
» Second-generation cephalosporins
Description: Cefoxitin is a parenteral cephamycin antibiotic that is classified as a second-generation cephalosporin. The drug has added stability against the beta-lactamases, providing better resistance to certain gram-negative species. When it was marketed, cefoxitin was the first cephalosporin-like antibiotic to exhibit activity against anaerobes. Many institutions have substituted cefotetan for cefoxitin since their spectra of activity is extremely similar, and cefotetan can be dosed less frequently. In addition, cefoxitin has been found to be a potent inducer of beta-lactamases. Therapeutic uses of cefoxitin include soft-tissue and skin infections, intra-abdominal infection, obstetric/gynecologic infection, and respiratory and urinary tract infections. Cefoxitin was approved by the FDA in 1978.
Mechanism of Action: Cefoxitin, a beta-lactam cephamycin similar to penicillins and cephalosporins, inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinisic activity of cefoxitin as well as the other cephalosporins and penicillins against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, cefoxitin’s ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor.
When it was released, cefoxitin possessed greater activity against gram-negative aerobes and anaerobes than currently available first-generation cephalosporins. Due to its added stability against beta-lactamase-producing organisms, it is active against E. coli, Klebsiella, H. influenzae, Proteus, and Providencia. In addition, it provides excellent coverage against N. gonorrhoeae and is the drug of choice for the treatment of pelvic inflammatory disease (PID) due to N. gonorrhoeae. Cefoxitin has good activity against most gram-positive bacteria including nonpenicillinase- and pencillinase-producing Staphylococcus aureus (methicillin-resistant strains are not susceptible), streptococci (except enterococci), and many anaerobic bacteria (including B. fragilis).
Pharmacokinetics: Cefoxitin is administered parenterally. It is not absorbed from the GI tract. Peak serum levels of cefoxitin occur within 20 - 30 minutes following an IM dose. Approximately 50 - 80% of the circulating drug is protein-bound. It is distributed into most body tissues and fluids including the gallbladder; liver; kidney; bone; uterus; cervix; ovary; sputum; bile; and peritoneal, pleural, and synovial fluids. It does not reach therapeutic levels within the CSF. It crosses the placenta. The drug is largely excreted unchanged into the urine via glomerular filtration and tubular secretion. A small percentage is excreted in breast milk. Approximately 2% of the drug is metabolized to an inactive metabolite. Elimination half-life is 40 - 60 minutes in patients with normal renal function. The elimination half-life increases to up to 6.5 to 21.5 hours in patients with end-stage renal disease. Dosages should be adjusted accordingly. Cefoxitin is significantly removed by hemodialysis.
[ Revised 4/18/2007 11:32:00 AM ]
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