Cephalosporins: Generations and Indications

Cephalosporins

• Cephalosporins are classified into five generations: 1st, 2nd, 3rd, 4th, and 5th.
• Each generation has its specific spectrum and indications.
• Examples of cephalosporins include Cefazolin, Cephalexin, Cefadroxil, Cefuroxime, Ceftriaxone, and Ceftobiprole.

Indications

• Cephalosporins are used for surgical prophylaxis, intraabdominal infections, urinary infections, respiratory infections, and meningitis.
• 1st generation cephalosporins are used for surgical prophylaxis and ENT infections.
• 2nd generation cephalosporins are used for intraabdominal infections and urinary infections.
• 3rd generation cephalosporins are used for meningitis, respiratory infections, and urinary infections.
• 4th generation cephalosporins are used for severe intraabdominal infections, CNS infections, and urinary infections.
• 5th generation cephalosporins are used for community-acquired pneumonia and severe MRSA infections.

Adverse Reactions

• Cephalosporins have similar adverse reactions to penicillins.
• High risk of C. difficile infection.
• Biliary sludge can occur with prolonged treatment with ceftriaxone.
• Only 10% of patients with a penicillin allergy are also allergic to cephalosporins.

Penicillins

• Adverse reactions include hypersensitivity, seizures, tubulointerstitial nephritis, cholestatic jaundice, and Herxheimer reaction.
• Herxheimer reaction occurs within the first 2 hours of antibiotic therapy and resolves after 24-36 hours.

Cephalosporins - Black Sheep

• Enterococci, Listeria, Clostridioides difficile, and atypical bacteria are not covered by cephalosporins.
• MRSA is not covered by cephalosporins except for the 5th generation.

Carbapenems

• Representatives include Imipenem, Meropenem, Ertapenem, and Doripenem.
• Ultralarge spectrum, but do not cover MRSA, Ampicillin-Resistant Enterococci, Cl. difficile, and Stenotrophomonas maltophilia.
• Indications include severe ESBL-producing GNB infections, hospital-acquired infections, and empirical treatment of febrile neutropenia and immunocompromised patients.
• Adverse reactions include seizures, nausea, vomiting, diarrhea, hepatic cytolysis, and C. difficile infection.

Beta-Lactam + Beta-Lactamase Inhibitor

• Representatives include Amoxicillin + Clavulanic acid, Ceftolozane + Tazobactam, and Ceftazidime + Avibactam.
• Indications include ABP, UTI, ENT and respiratory infections, and intraabdominal infections with KPC/OXA-48-producing bacteria.

Monobactams

• Representative: Aztreonam.
• Mechanism of action: binds to PBP3.
• Spectrum: MDR GNB (even MBL-producing bacteria).
• Indications: severe infections with MDR GNB sensitive to Aztreonam and inhalations in patients with bronchiectases colonized by Pseudomonas aeruginosa.

Glycopeptides

• Representatives: Vancomycin and Teicoplanin.
• Mechanism of action: binds to cell wall peptides D-ala termination preventing their cross-linking into the peptidoglycan form.
• FDA pregnancy category: B for Vancomycin PO and C for Vancomycin IV.