Ceforanide

1. Christopher J. Harrison, MD* 2. Denise Bratcher, DO* 1. *Children's Mercy Hospitals and Clinics, Pediatric Infectious Diseases, University of Missouri at Kansas City, Kansas City, Mo After completing this article, readers should be able to: 1. Describe the mechanism of action of cephalosporins. 2. Delineate the two most common mechanisms of resistance to penicillins. 3. Discuss the most common adverse effects of common cephalosporins. 4. List which cephalosporins have activity against Pseudomonas. Cephalosporins are beta-lactam antimicrobials that share mechanisms of action and a similar structure with penicillins (Figure⇓). Penicillins and cephalosporins have the same four-member “core” beta-lactam ring, but cephalosporins have an additional atom in the side ring. Modified side chains on either ring alter antimicrobial activity, resistance to beta-lactamases, or pharmacokinetics. Penicillin-susceptible pathogens usually are cephalosporin-susceptible. Exceptions are Listeria and Pasteurella sp. Cephalosporins have activity against common gram-negative organisms such as Escherichia coli , nontypeable Haemophilus influenzae (ntHi), and methicillin-susceptible Staphylococcus aureus (MSSA), but all methicillin-resistant S aureus (MRSA) and enterococci are cephalosporin-resistant. Because of minimal use or current unavailability, we will not discuss cephalothin, moxalactam, cefamandole, cefonicid, ceforanide, ceftizoxime, cefoperazone, cefpirome, cefmetazole, or cefotetan. Figure. Cephalosporin versus penicillin ring structures. The solid arrows indicate the core four-member beta-lactam ring within both penicillins and cephalosporins. Open arrows indicate the five- and six-member side rings for penicillins and cephalosporins, respectively. R indicates additional side chain sites where substitutions of various chemical groups produce different antimicrobial spectra, pharmacokinetics, or stability to beta-lactamases. To help understand the mechanism of action of cephalosporins, rigid bacterial cell walls can be considered as a series of repeating interlocking units reminiscent of floor tiles. During replication, a bacterium removes “tiles” circumferentially to allow cell division via a pinching-like action, while quickly placing new “tiles” at the ends of what have become two bacteria. This process requires enzymes to interlock replacement tiles. Such enzymes are the targets of beta-lactam antibiotics and are called penicillin-binding proteins (PBPs). Antibiotic action requires binding to PBPs, preventing them from closing the …

The objective was to examine the biodistribution, the chemoprophylactic, and the bactericide efficacy of 80-mg gentamicin single or once-daily dosing.

Ninety-six patients who had had cesarean section or gynecological surgery received 80 mg gentamicin for chemoprophylaxis. A second group of 92 patients with Gram-negative infection received once-daily 80-mg gentamicin intramuscularly, combined with cefoxitin or ceforanide, for 5 days. Gentamicin serum and tissue concentration was determined 1 h after the first administration.

The chemoprophylactic efficacy of gentamicin was 93.7%. The treatment efficacy was high in patients with chorioamnionitis and endometritis (92.9%), moderate in those with wound infection (69.5%), and less effective in those with septicemia (55.6%). Twenty-six percent of patients continued with antibiotics for infection control. The mean serum level was 4.48+/-0.49 and 5.56+/-0.66 microg/ml in obstetrical and gynecological patients respectively (p>0.05). Serum levels >4 microg/ml were achieved in 91% of patients.

A single dose of 80 mg gentamicin offers chemoprophylaxis and achieves therapeutic serum-concentrations 1 h after administration. The 5-day combination of once-daily 80 mg gentamicin with a second-generation cephalosporin is effective in patients with chorioamnionitis and endometritis, but only moderately effective in those with wound infections and septicemia.