Chemical structure and mechanism of action
The core of the cephalosporin molecule is 7-aminocephalosporanic acid, which consists of two key components: beta-lactam and dihydrothiazine rings.
Due to significant structural similarities with penicillins, these drugs share the same mechanism of action, cause microbial cell death, and exhibit low toxicity. Their main advantages over penicillins are a broader antimicrobial spectrum and resistance to a number of enzymes.
Mechanism of the bactericidal effect:
- Inhibition of the transpeptidase enzyme.
- Disruption of the synthesis of peptidoglycan, a vital component of the bacterial cell wall.
- Reduction of cell wall strength, leading to its lysis.
Classification and spectrum evolution
All members of the group are divided into four generations, each including parenteral and oral formulations.
When moving from the first generation to the fourth, the following trends are observed:
- 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 inefficacy against enterococci (Enterococcus).
Characteristics of antibiotic generations
- 1st generation: Have a broad spectrum with activity against Gram-positive flora (staphylococci, streptococci). Among parenteral agents, Cefazolin is actively used for surgical prophylaxis. Oral representatives include Cephalexin and Cefadroxil.
- 2nd generation: Characterized by increased activity against Gram-negative microorganisms (Haemophilus influenzae, enteric group) and greater resistance to beta-lactamases. This group includes Cefuroxime, Cefaclor, as well as agents with anti-anaerobic activity (Cefoxitin).
- 3rd generation: Have a markedly expanded spectrum against G– flora and are capable of crossing the blood-brain barrier. Leading drugs are Ceftriaxone and Cefotaxime.
- 4th generation: Parenteral drugs (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:
- 1st 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.
- 3rd generation agents (cefotaxime, ceftriaxone) penetrate various organs and tissues remarkably well, and most importantly, cross the blood-brain barrier, making them drugs of choice for meningitis.
Briefly: answers to topical questions
What are the main side effects and adverse reactions associated with cephalosporins?
The main side effects of cephalosporins include allergic, organotoxic, gastrointestinal, and specific reactions.
- Allergic reactions — urticaria, fever, anaphylactic shock; cross-allergy with penicillins exists.
- Organotoxicity — nephrotoxicity (specific to 1st-generation cephalosporins; also described for individual agents, e.g., cefamandole), hepatotoxicity (transient elevation of hepatic transaminases), leukopenia, agranulocytosis, and seizures.
- Dysbiosis and superinfections — including oral and intestinal candidiasis.
- Pseudomembranous colitis — bloody diarrhea resulting from the proliferation of Clostridium difficile against the background of suppressed competitive flora.
- Local reactions — phlebitis with intravenous administration.
- Specific reactions — disulfiram-like reaction and hemorrhagic syndrome associated with cefotetan and cefoperazone; antibody-mediated hemolysis is additionally described for cefotetan.
Cephalosporins: 1st gen — great for G+ (skin, soft tissues); 2nd gen — breathe easier (respiratory infections, Haemophilus influenzae); 3rd gen — across the barrier into the brain (meningitis, resistant flora); 4th gen — maximum defense.
Class and exam questions
What is the main advantage of cephalosporins over penicillins?
Cephalosporins have a broader spectrum of antimicrobial activity and increased resistance to beta-lactamases.
What chemical structure forms the basis of all cephalosporins?
The single chemical foundation of the group is 7-aminocephalosporanic acid, containing beta-lactam and dihydrothiazine rings.
Do 3rd-generation drugs cross the blood-brain barrier?
Yes, a key feature of 3rd-generation cephalosporins is good penetration across the blood-brain barrier, allowing them to be used in meningitis.
Do cephalosporins affect enterococci?
No, a characteristic feature of the entire cephalosporin group is the complete lack of antimicrobial activity against enterococci.
What else to study on this topic
- Criteria for antibiotic selection in surgical prophylaxis
- Comparative pharmacokinetics of ceftriaxone and cefotaxime
- Application of cephalosporins in Pseudomonas aeruginosa infection
- Side effects and complications of cephalosporin therapy
- Mechanisms of microbial resistance to cephalosporins
Master the entire topic in the «Pharmacology» course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Cephalosporins" and 5,304 other subject pages
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 116 video lessons on the subject
Other topics in the section "Antibacterial Chemotherapeutic Agents"
Free video lessons: pharmacologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.