The cephalosporins are classified into generations (Table 45.2) according to their antibacterial spectrum and stability to p-lactamases. The first-generation cephalosporins have in vitro antimicrobial activity against streptococci, methicillin-sensitive S. aureus, and a few gram-negative bacilli. The second-generation cepha-losporins have greater stability against p-lactamase inac-tivation and possess a broader spectrum of activity to include gram-positive cocci, gram-negative organisms, and anaerobes. Among the second-generation cephalo-sporins, the cephamycins (cefoxitin [Mefoxin], cefotetan [Cefotan], and cefmetazole [Zefazone]) have the most activity against Bacteroides fragilis. The extended-spectrum, or third-generation, cephalosporins possess a high degree of in vitro potency and p-lactamase stability and a broader spectrum of action against many common gram-negative bacteria and anaerobes while retaining good activity against streptococci. Third-generation cephalosporins are less active against staphylococci than the earlier generations. The agents with the greatest activity against P. aeruginosa are cefepime, cefoperazone, and ceftazidime. Cefepime has been called a fourth-generation cephalosporin because of its great in vitro activity against several gram-positive and gram-negative organisms. The distinction between third and fourth
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