Infectious disease · USMLE Step 1 and Step 2

Cephalosporins song

Cephalosporins - Generations & Coverage, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

Cephalosporins

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Key points in this song10

First-generation cephalosporins (cefazolin, cephalexin) cover gram-positive cocci and basic gram-negatives (E. coli, Klebsiella, Proteus); cefazolin is the drug of choice for surgical prophylaxis.
Second-generation cephalosporins (cefoxitin, cefaclor, cefuroxime) add coverage against H. influenzae, Moraxella, and Neisseria, with cephamycins (cefoxitin, cefotetan) also covering anaerobes including Bacteroides fragilis.
Third-generation cephalosporins (ceftriaxone, cefotaxime, ceftazidime) have enhanced gram-negative coverage and cross the blood-brain barrier, making ceftriaxone first-line for bacterial meningitis and gonorrhea.
Ceftazidime is the only third-generation cephalosporin with significant anti-pseudomonal activity; it trades some gram-positive coverage for this expanded gram-negative spectrum.
Fourth-generation cefepime covers both Pseudomonas aeruginosa and gram-positive organisms (including Staphylococcus aureus), making it useful for febrile neutropenia and nosocomial infections.
All cephalosporins inhibit bacterial cell wall synthesis by binding penicillin-binding proteins (PBPs), blocking transpeptidation of peptidoglycan cross-links.
Approximately 1–2% cross-reactivity exists between cephalosporins and penicillins; cephalosporins are generally safe in penicillin-allergic patients unless there is a history of anaphylaxis.
Cephalosporins are beta-lactamase resistant relative to penicillins, but extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases can hydrolyze them; carbapenems are used instead for ESBL-producing organisms.
Cefotetan and cefoperazone contain an N-methylthiotetrazole (NMTT) side chain that inhibits vitamin K epoxide reductase, causing a disulfiram-like reaction with alcohol and increasing bleeding risk.
Ceftriaxone is avoided in neonates because it displaces bilirubin from albumin, increasing the risk of kernicterus; cefotaxime is the preferred alternative in this population.