Ceftriaxone, Cefepime, Cefazoline: Key Cephalosporins in Medicine

Cephalosporins are beta-lactam antibiotics with a wide antibacterial range. This guide covers their generations, spectrum, uses, side effects, and interactions.

Introduction

Cephalosporins belong to the beta-lactam class and relate to penicillin. Researchers divide them into five generations, each with its own antibacterial properties. Cephalexin is the main drug of the first generation.

Medications in the class.

• 1st Generation: Cephalexin, Cefazolin

• 2nd Generation: Cefuroxime, Cefaclor

• 3rd Generation: Ceftriaxone, Ceftazidime, Cefotaxime

• 4th Generation: Cefepime

• 5th Generation: Ceftaroline (effective against MRSA)

Mechanism of Action

Cephalosporins block bacterial cell wall synthesis. They bind to penicillin-binding proteins (PBPs), preventing peptidoglycan cross-linking. This leads to bacterial lysis, making them bactericidal.

Spectrum of Activity

• 1st Generation: Effective against Gram-positive bacteria like Staphylococcus and Streptococcus. It has limited effects on Gram-negative bacteria such as E. coli and Klebsiella.

• 2nd Generation: Better Gram-negative coverage (H. influenzae, Enterobacter, Neisseria); less effective against Gram-positives.

• 3rd Generation: Broad Gram-negative coverage (Enterobacteriaceae, Neisseria, H. influenzae). Ceftriaxone and cefotaxime can enter the CNS, which is useful for meningitis. Ceftazidime targets Pseudomonas.

• 4th Generation: This antibiotic works well against many bacteria. It targets both Gram-positive and Gram-negative types, especially Pseudomonas aeruginosa (cefepime).

• 5th Generation: Targets Gram-positives, including MRSA, and some Gram-negatives (ceftaroline).

Generations Summary

• 1st Gen: Focus on Gram-positives

• 2nd Gen: Extended Gram-negative coverage

• 3rd Gen: Broad Gram-negative, CNS access

• 4th Gen: Very broad; includes Pseudomonas.

• 5th Gen: Covers MRSA.

Indications (When Used)

• Respiratory infections (pneumonia, bronchitis)

• Skin and soft tissue infections

• Urinary tract infections

• Meningitis (Ceftriaxone, Cefotaxime)

• Gonorrhea (Ceftriaxone is the first line)

• Intra-abdominal infections (with metronidazole)

• Sepsis (Cefepime or Ceftriaxone based on the pathogen)

Contraindications (When Not to Use)

• Severe allergic reactions to cephalosporins.

• Cross-reactivity with penicillin allergies.

• Neonates on ceftriaxone with calcium IV fluids (risk of precipitation).

Side Effects

• Allergic reactions (rash, hives, anaphylaxis)

• Gastrointestinal issues (diarrhea, nausea, C. difficile colitis)

• Rare: bone marrow suppression; seizures at high doses.

• Ceftriaxone: biliary sludging, pseudolithiasis

Drug Interactions

• Alcohol + Cefotetan/Cefoperazone: Disulfiram-like reaction

• Aminoglycosides: Increased risk of kidney damage.

• Warfarin: Enhanced blood-thinning effect

• Calcium IV products and ceftriaxone: dangerous precipitates in neonates.

Antidote

There is no specific antidote. Management is supportive: use epinephrine for anaphylaxis and benzodiazepines for seizures.

Monitoring of Potential Complications

• Check renal function during long- or high-dose therapy.

• Watch for allergic reactions with early doses.

• Screen for superinfections (e.g., C. difficile colitis)

• Long-term use: conduct routine checks of liver and kidney functions.

Cephalosporins are versatile antibiotics. Their generation-based spectrum guides clinical decisions. Their effectiveness and safety make them essential for treating infections.