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Cefepime is the only fourth-generation cephalosporin licensed for use in the United States. It is being used increasingly for treatment of infections caused by resistant gram-negative bacteria in older infants and children. Some hospitals have replaced antipseudomonal third-generation cephalosporin antibiotics (eg, ceftazidime) with cefepime because of high rates of infection caused by resistant gram-negative bacteria. Although cefepime generally is not used to treat infections in neonates, it is important for neonatologists to be familiar with the characteristics of the drug because there are a few circumstances in which cefepime may be appropriate therapy for an older infant hospitalized in a neonatal intensive care unit. It is important to understand the unique differences of the drug compared with older cephalosporins. The cephalosporin antibiotics are derivatives of cephalosporin C, a natural antibiotic derived from the fungus Emericellopsis minimum . Cephalosporins have a beta-lactam ring as their major structural component, and their spectrum of activity varies, depending on substitutions at the 3 and 7 positions of the cephalosporin nucleus. Traditionally, these antibiotics are grouped by their spectrum of activity against antimicrobial organisms (Table 1). First-generation cephalosporins are active against most gram-positive bacteria (except enterococci and Listeria ) and have limited activity against some gram-negative organisms. Second-generation cephalosporins have increased activity against gram-negative organisms. Cephamycins, which generally are classified with the second-generation cephalosporins, have enhanced activity against anaerobic bacteria. The third-generation cephalosporins have extended potency against gram-negative bacteria but are generally less active against susceptible staphylococci. Cefepime hydrochloride is a newer semisynthetic, broad-spectrum fourth-generation cephalosporin antibiotic. The other antibiotic in this class is cefpirome, which is not available for use in the United States. | | First Generation | Second Generation | Third Generation | Fourth Generation | |:----------:| ---------------- | ----------------- | ---------------- | ----------------- | | Oral | Cefadroxil | Cefaclor | Cefdinir | | | | Cephalexin | Cefprozil | Cefpodoxime | | | | Cephradine | Cefuroxime axetil | | | | | | Loracarbef | | | | Parenteral | Cefazolin | Cefamandole | Cefoperazone | Cefepime | | | Cephalothin | Cefuroxime | Cefotaxime | | | | Cephapirin | | Ceftizoxime | | | | | Cephamycins | Ceftriaxone | | | | | Cefotetan | Ceftazidime | | | | | Cefoxitin | | | Table 1. Generations of Cephalosporins Cefepime differs from the third-generation cephalosporins by having a quaternized N-methylpyrrolidine substitution at the C3 position of the cephem nucleus and an alkoxyimino group at the C7 position …