Cephalosporins

Cephalosporins: Introduction

Cephalosporins are a large group of β-lactam antibiotics structurally and functionally related to penicillins. They are widely used to treat bacterial infections because of their broad spectrum, efficacy, and safety profile. Like penicillins, cephalosporins work by inhibiting bacterial cell wall synthesis, leading to cell death.

History

• First discovered in 1945 by Italian scientist Giuseppe Brotzu from a fungus called Acremonium (formerly Cephalosporium).

• Cephalosporins were developed to overcome some limitations of penicillin, particularly resistance caused by β-lactamase-producing bacteria.

• Over time, multiple generations have been developed with increasing activity against Gram-negative bacteria.

Mechanism of Action

• Cephalosporins bind to penicillin-binding proteins (PBPs) in bacterial cell walls.

• This prevents cross-linking of peptidoglycan, weakening the wall and causing bacterial lysis.

• They are bactericidal, especially against actively dividing bacteria.

Classification (Generations)

Cephalosporins are classified into generations, primarily based on their spectrum of activity:

1. First-Generation

   • Strong against Gram-positive bacteria; limited Gram-negative activity.

   • Examples: Cefazolin, Cephalexin

   • Common uses: Skin infections, surgical prophylaxis

2. Second-Generation

   • Better Gram-negative coverage than first-generation; some retain Gram-positive activity.

   • Examples: Cefuroxime, Cefoxitin, Cefaclor

   • Common uses: Respiratory tract infections, abdominal infections

3. Third-Generation

   • Broad Gram-negative coverage; some cross blood-brain barrier (useful in meningitis).

   • Examples: Ceftriaxone, Ceftazidime, Cefotaxime

   • Common uses: Severe systemic infections, meningitis, gonorrhea

4. Fourth-Generation

   • Broad spectrum including Gram-positive and Gram-negative; resistant to many β-lactamases.

   • Example: Cefepime

   • Common uses: Severe hospital-acquired infections, febrile neutropenia

5. Fifth-Generation

   • Active against methicillin-resistant Staphylococcus aureus (MRSA) and other resistant bacteria.

   • Example: Ceftaroline

   • Common uses: Resistant infections, complicated skin infections, pneumonia

Common Uses

• Respiratory infections: Pneumonia, sinusitis, bronchitis

• Urinary tract infections

• Skin and soft tissue infections

• Sepsis and meningitis (certain third- and fourth-generation agents)

• Surgical prophylaxis

Advantages

• Broad spectrum of activity with multiple generations for targeted therapy

• Generally safe and well-tolerated

• Alternative for patients allergic to penicillin (though cross-reactivity exists)

Risks and Concerns

• Allergic reactions: Rash, urticaria, rarely anaphylaxis

• Gastrointestinal side effects: Diarrhea, nausea

• Superinfections: Overgrowth of resistant organisms (e.g., Clostridium difficile)

• Cross-reactivity with penicillin allergy: Higher with first-generation cephalosporins

Examples of Common Cephalosporins

• First-Generation: Cefazolin, Cephalexin

• Second-Generation: Cefuroxime, Cefoxitin

• Third-Generation: Ceftriaxone, Ceftazidime, Cefotaxime

• Fourth-Generation: Cefepime

• Fifth-Generation: Ceftaroline