Chemical Structure and Mechanism of Action
The molecular core of cephalosporins is 7-aminocephalosporanic acid, which consists of two key components: a beta-lactam ring and a dihydrothiazine ring.
Due to their structural similarity to penicillins, these drugs share a similar mechanism of action, cause bacterial cell death, and exhibit low toxicity. Their main advantages over penicillins are a broader antimicrobial spectrum and resistance to several enzymes.
Mechanism of Bactericidal Effect:
- Inhibition of the transpeptidase enzyme.
- Disruption of peptidoglycan synthesis—a critical component of the bacterial cell wall.
- Reduction of cell wall integrity, leading to lysis.
Classification and Spectrum Evolution
All agents in this group are divided into four generations, each including parenteral and oral formulations.
Transitioning from the first generation to the fourth reveals the following trends:
- The overall spectrum of antimicrobial activity expands.
- Activity against gram-negative (G–) bacteria increases significantly.
- Efficacy against gram-positive (G+) microorganisms decreases slightly.
- A common feature of all cephalosporins is absolute ineffectiveness against enterococci (Enterococcus).
Characteristics of Antibiotic Generations
- 1st Generation: Broad spectrum with activity against G+ flora (staphylococci, streptococci). Among parenteral agents, cefazolin is widely used for surgical prophylaxis. Oral representatives include cephalexin and cefadroxil.
- 2nd Generation: Feature enhanced activity against gram-negative microorganisms (Haemophilus influenzae, enteric bacteria) and greater resistance to beta-lactamases. This group includes cefuroxime, cefaclor, as well as agents with anti-anaerobic activity (cefoxitin).
- 3rd Generation: Possess a markedly expanded spectrum against G– flora and can cross the blood-brain barrier. Leading drugs are ceftriaxone and cefotaxime.
- 4th Generation: Parenteral agents (cefepime, cefpirome) with potent activity against resistant gram-negative strains.
Pharmacokinetic Features
Routes of administration and distribution of cephalosporins depend on the specific drug and generation:
- First-generation drugs (e.g., cefazolin) administered parenterally penetrate tissues well, but cross the blood-brain barrier poorly and are excreted unchanged by the kidneys.
- Oral formulations are well absorbed from the gastrointestinal tract, achieving necessary therapeutic concentrations.
- Third-generation agents (cefotaxime, ceftriaxone) penetrate various organs and tissues effectively, and most importantly, cross the blood-brain barrier, making them drugs of choice for meningitis.