Cephalosporins: Classification, Mechanism, Uses, and Side Effects

• First Generation: Cefazolin, Cephalexin - Effective against Gram-positive bacteria and some Gram-negative organisms.
• Second Generation: Cefuroxime, Cefoxitin - Broader Gram-negative coverage, including *Haemophilus influenzae* and *Moraxella catarrhalis*.
• Third Generation: Ceftriaxone, Cefotaxime - Increased Gram-negative coverage, including *Pseudomonas aeruginosa* (except ceftriaxone).
• Fourth Generation: Cefepime - Broad-spectrum with enhanced activity against *Pseudomonas* and Gram-positive organisms.
• Fifth Generation: Ceftaroline, Ceftobiprole - Effective against MRSA and resistant Gram-negative organisms.

Cephalosporins inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) on the bacterial cell membrane. This prevents the cross-linking of peptidoglycan, leading to cell wall rupture and bacterial cell death due to osmotic instability.

• β-lactamase production: Bacteria produce enzymes that break the β-lactam ring of cephalosporins.
• Alteration of PBPs: Mutations in PBPs reduce their binding affinity to cephalosporins.
• Decreased drug permeability: Some bacteria decrease the permeability of their outer membrane to prevent drug entry.
• Efflux pumps: Some bacteria expel cephalosporins from the cell using efflux pumps.

• Infections caused by Gram-positive bacteria (e.g., *Staphylococcus* and *Streptococcus*)
• Respiratory tract infections (e.g., pneumonia, sinusitis, otitis media)
• Urinary tract infections (e.g., cystitis, pyelonephritis)
• Surgical prophylaxis
• Meningitis (third-generation cephalosporins like ceftriaxone)
• Bone and joint infections
• Sepsis and febrile neutropenia (for serious hospital-acquired infections)

• Hypersensitivity reactions: Rash, fever, and anaphylaxis in rare cases.
• Gastrointestinal: Diarrhea, nausea, vomiting.
• Hematologic: Thrombocytopenia, eosinophilia, neutropenia (rare).
• Renal: Renal toxicity, especially in high doses and renal impairment.
• Disulfiram-like reaction: With cefotetan, causing flushing, headache, nausea if alcohol is consumed.
• Superinfections: Fungal or bacterial overgrowth (e.g., Candida, *Clostridium difficile*).

• Hypersensitivity: Known allergy to cephalosporins or other β-lactam antibiotics (e.g., penicillins).
• Renal impairment: Caution or adjusted doses for renal failure patients.
• Pregnancy: Generally safe (category B), but caution is advised for prolonged use.
• Lactation: Generally safe for breastfeeding, but monitoring is recommended for prolonged use.