Mechanism of bactericidal action
Cephalosporins, like other $\beta$-lactam antibiotics (including carbapenems), destroy bacteria by breaking down their cell wall. This process occurs in five consecutive stages:
- Due to structural similarity to the D-alanine-D-alanine molecule, the antibiotic integrates into the bacterial cell wall synthesis process.
- It binds to specific targets — penicillin-binding proteins (PBPs).
- The function of the key enzyme, transpeptidase, is inhibited.
- The formation of cross-links in the peptidoglycan molecule is disrupted.
- Autolytic enzymes of the cell wall itself are activated, leading to its irreversible damage and bacterial death.
Evolution of the spectrum of activity (from 1st to 4th generation)
The main pharmacological feature of cephalosporins is the clear dependence of their antimicrobial activity on the generation. When moving from early generations to more modern ones, strict patterns are observed:
- Broadening spectrum: The overall coverage of susceptible microorganisms steadily increases.
- Gram-negative flora: The efficacy against gram-negative bacteria increases significantly with each new generation.
- Gram-positive flora: Activity against gram-positive microorganisms slightly decreases, making way for activity against gram-negative pathogens.
- Intrinsic resistance: A crucial characteristic of the entire cephalosporin group is the absolute lack of activity against enterococci.
Characteristics of 1st and 2nd generations
- 1st generation: The drugs have a broad spectrum, but their action is directed predominantly toward gram-positive flora. Gram-negative activity is very limited: the antibiotics act only on certain species causing infections, such as Proteus mirabilis and Escherichia coli.
- 2nd generation: Demonstrate an expanded spectrum of activity compared to the first generation. They retain sufficient clinical activity against gram-positive cocci, while their spectrum also includes new gram-negative pathogens, notably Haemophilus influenzae and various species of the genus Neisseria.
Features of the 3rd generation
Drugs of this generation are characterized by high resistance to many $\beta$-lactamases produced by gram-negative microorganisms.
- Gram-negative flora: The spectrum of activity is maximized and includes strains resistant to other antibiotics. The drugs destroy the enteric group (Escherichia coli, indole-positive Proteus strains, Klebsiella, Enterobacter, Serratia, Citrobacter), as well as Neisseria spp., Neisseria meningitidis, Haemophilus influenzae, and pneumococci.
- Gram-positive flora: Activity is objectively lower compared to the 1st–2nd generations. However, there is an important exception: the drugs show high activity against penicillin-resistant Streptococcus pneumoniae (although resistance to them can also develop during treatment).
- Pseudomonas aeruginosa (Pseudomonas aeruginosa): Most 3rd-generation cephalosporins are powerless against it. Only specific drugs are active — ceftazidime and cefoperazone.
4th generation and alternative $\beta$-lactams
- 4th-generation cephalosporins: Possess the broadest spectrum of activity among all cephalosporins. They successfully combine high activity against gram-positive cocci and maximally expanded activity against gram-negative bacteria (including Pseudomonas aeruginosa). An important advantage is that they are more resistant to extended-spectrum $\beta$-lactamases.
- Carbapenems: If the pathogen is resistant even to 3rd- and 4th-generation cephalosporins, carbapenems are used. These are related synthetic $\beta$-lactams (in their thiazolidine ring, sulfur is replaced by a methyl group) with an ultra-broad spectrum of activity. They destroy both gram-positive and gram-negative aerobes and anaerobes due to their extremely high resistance to $\beta$-lactamases.
Hierarchy of 3rd-generation activity against Pseudomonas aeruginosa (strongest to weakest): Ceftazidime → Cefoperazone → Ceftriaxone → Cefotaxime (mnemonic: TAZ–PER–TRI–TAX).
Class and exam questions
Do cephalosporins affect enterococci?
No, the entire group of cephalosporins is characterized by a complete lack of activity against enterococci due to their intrinsic resistance.
How does drug activity change from the 1st to the 4th generation?
The overall spectrum expands: efficacy against gram-negative bacteria increases significantly, while activity against gram-positive flora slightly decreases.
Which 3rd-generation cephalosporins are active against Pseudomonas aeruginosa?
Only ceftazidime and cefoperazone exhibit pronounced antipseudomonal activity. Ceftriaxone and cefotaxime are significantly weaker in this regard.
What is the special feature of carbapenems compared to cephalosporins?
Carbapenems have an ultra-broad spectrum of activity (including anaerobes) and are active against strains that have already developed resistance to 3rd- and 4th-generation cephalosporins.
What else to study on this topic
- Pharmacokinetics of cephalosporins of various generations
- Indications for the use of specific drugs
- Side effects and toxicity of cephalosporins
- Classification and specific representatives of the 1st and 2nd generations
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 "Cephalosporin antibiotics" and another 5,304 pages of the subject
- 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 "Additional Topics" section
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.