Review of cefonicid, a long-acting cephalosporin

The in vitro activity, pharmacokinetics, adverse effects, and clinical efficacy of cefonicid are reviewed. Also discussed are formulary considerations and bacterial resistance. Cefonicid, an investigational agent near approval, is less active than other currently available first- and second-generation cephalosporins against gram-positive cocci, particularly Staphylococcus. Cefonicid and cefamandole have similar activity that is superior to the first-generation cephalosporins against Escherichia coli, Klebsiella, Citrobacter spp., Enterobacter spp., indole-negative Proteus spp., and Providencia spp. Organisms such as Serratia marcescens, Acinetobacter, Pseudomonas, and Bacteroides fragilis are resistant to cefonicid. Despite a small volume of distribution and high protein binding, cefonicid achieves high tissue concentrations. Approximately 90% of an administered dose is excreted unchanged in the urine, and the elimination half-life is approximately four hours. Cefonicid is usually well tolerated. In treating skin infections, cefonicid was usually less effective than cefazolin against Staphylococcus aureus. In genitourinary infections, cefonicid 1 g daily (as the sodium salt) in a single dose has shown comparable efficacy to cefamandole or amoxicillin given in multiple daily doses. Based on available data, single daily dosing of cefonicid in the therapy of Staph. aureus endocarditis is not effective. In studies of patients undergoing hysterectomy, cesarean section, cholecystectomy, and colorectal surgery, cefonicid 1 g given as a single preoperative dose has produced results comparable with those of cefoxitin 1-2 g (as the sodium salt) given preoperatively and for several doses postoperatively. The major clinical uses of cefonicid will probably be as a possible cost-reducing alternative (based on a single daily dose) to currently available first- and second-generation cephalosporins for the treatment of community-acquired pneumonia and infections caused by enteric organisms. It may also be useful as a possible cost-reducing alternative to cefoxitin for prophylaxis in hysterectomy and biliary tract surgery.