Cephalosporins are β-lactam antimicrobials used to manage various infections caused by both gram-positive and gram-negative bacteria. Cephalosporins are categorized into 5 generations based on their spectrum of coverage against gram-positive and gram-negative bacteria and their temporal discovery. The 5 generations of cephalosporins demonstrate efficacy in treating skin and soft tissue infections, pneumonia, meningitis, and other infections. First-generation cephalosporins have coverage against most gram-positive cocci and some gram-negative bacteria, including Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Second-generation cephalosporins have coverage against Haemophilus influenzae, Moraxella catarrhalis, and Bacteroides spp. Third-generation cephalosporins have less coverage against most gram-positive organisms but have increased coverage against Enterobacteriaceae, Neisseria spp, and H influenzae. Fourth-generation cephalosporins have similar coverage as third-generation cephalosporins but with additional coverage against gram-negative bacteria with antimicrobial resistance, such as β-lactamase. Fifth-generation cephalosporins have coverage against methicillin-resistant staphylococci and penicillin-resistant pneumococci.

First-generation cephalosporins include cefazolin, cephalothin, cephapirin, cephradine, cefadroxil, and cephalexin. First-generation cephalosporins have active coverage against most gram-positive cocci, such as staphylococci spp and streptococci spp, while having minimal coverage against gram-negative bacteria. Gram-negative bacteria that are more susceptible to first-generation cephalosporins include P mirabilis, E coli, and K pneumoniae. Oral first-generation cephalosporins are commonly prescribed against uncomplicated skin and soft tissue infections such as cellulitis and abscesses due to staphylococci spp or streptococci spp. Additionally, clinicians can use them for bone, respiratory tract, genitourinary tract, biliary tract, bloodstream infection, otitis media, and surgical prophylaxis. Cefazolin is the cephalosporin of choice for surgical prophylaxis. One off-label use is first-generation cephalosporins for endocarditis prophylaxis for those susceptible and undergoing a dental or respiratory procedure