Snapshot A 55-year-old man is in the medical step-down unit for management of his osteomyelitis. The patient has a past medical history of diabetes that is complicated by peripheral neuropathy and gastroparesis. After obtaining a bone culture he is started on empiric antibiotic treatment with vancomycin and ceftriaxone; however, the patient still has a fever. A bone culture grew Pseudomonas aeruginosa that is sensitive to cefepime; his antibiotics were narrowed. Introduction General principle rule of thumb lower generations favor gram-positive coverage higher generations favor gram-negative coverage except for 4th and 5th generation, which has extended gram-positive coverage Drugs 1st generation cefazolin cephalexin 2nd generation cefoxitin cefaclor cefuroxime 3rd generation ceftriaxone cefotaxime ceftazidime cefixime 4th generation cefepime 5th generation ceftaroline Mechanism of action binds to penicillin-binding proteins, inhibiting bacterial cell wall synthesis Mechanism of resistance altered penicillin-binding proteins production of cephalosporinases Clinical use 1st generation P. mirabilis E. coli K. pneumoniae preventative measure against S. aureus wound infection prior to surgery (cefazolin) 2nd generation H. influenzae Enterobacter aerogenes Neisseria spp. S. marcescens P. mirabilis E. coli K. pneumoniae 3rd generation gram-negative infections meningitis, gonorrhea, and disseminated Lyme disease (ceftriaxone) Pseudomonas (ceftazidime) 4th generation Pseudomonas 5th generation gram-negative and gram-positive organisms does not cover Pseudomonas Adverse events hypersensitivity reaction autoimmune hemolytic anemia disulfiram-like reaction vitamin K deficiency note that there is low cross-reactivity with penicillin (even in penicillin-allergic patients) increased nephrotoxicity with aminoglycosides