Bactericidal antibiotics

Mechanisms of bactericidal action

The nature of an antibiotic's effect directly depends on its site of action (target) within the bacterial cell. The bactericidal effect, which leads to the death of the microorganism, is realized through several main mechanisms:

• Disruption of cell wall synthesis. This is one of the most common targets. This group includes β-lactam antibiotics, glycopeptides, cycloserine, and bacitracin. Destruction of the wall deprives the bacterium of protection.
• Disruption of cytoplasmic membrane permeability. Polymyxins and antifungal polyene antibiotics work on this principle. The membrane loses its barrier functions.
• Disruption of RNA synthesis. A prominent representative of this group is rifampicin, which blocks essential intracellular processes.
• Disruption of intracellular protein synthesis. As a rule, drugs with such a target (macrolides, tetracyclines, lincosamides, chloramphenicol) act predominantly in a bacteriostatic manner, meaning they only stop growth. However, there is an important exception — aminoglycosides, which exert a pronounced bactericidal effect when affecting protein synthesis.

Antibiotic interactions: combination rules

When prescribing combination therapy, a physician must consider the type of drug action (bactericidal or bacteriostatic) and the mechanism of their effect on the cell. Incorrect combination can negate all the benefits of treatment.

Synergism (mutual enhancement of effect) Occurs when two bactericidal drugs with different sites of action are combined.

• Example: Benzylpenicillin + Aminoglycosides.
• Mechanism: Benzylpenicillin purposefully disrupts the integrity of the bacterial cell wall. This physically facilitates the penetration of the second antibiotic (an aminoglycoside) deep into the bacterial cell.
• Result: A powerful mutual enhancement of the antimicrobial effect occurs, making it possible to cope with the infection faster.

Antagonism (weakening of the therapeutic effect) Observed when combining a bacteriostatic drug and a bactericidal agent that is a cell wall synthesis inhibitor.

• Example: Tetracycline + Benzylpenicillin.
• Mechanism: Tetracycline inhibits protein synthesis, causing bacterial growth and division to slow down or stop. Benzylpenicillin, on the other hand, is effective exclusively against actively growing and dividing cells (since it disrupts the process of building a new cell wall).
• Result: By halting division, tetracycline makes bacteria completely insensitive to the action of penicillin.

Carbapenems: ultra-broad spectrum

Carbapenems are a potent class of synthetic β-lactam antibiotics with a modified chemical structure. The main structural feature is that the sulfur atom in their thiazolidine ring is replaced by a methyl group. This fundamentally distinguishes them from classical penicillins.

Pharmacological properties:

• Possess an ultra-broad spectrum of activity: successfully destroy Gram-positive and Gram-negative aerobes, as well as anaerobes.
• Demonstrate high resistance to the destructive action of β-lactamase enzymes.
• Retain high activity against strains that have already developed resistance to 3rd and 4th generation cephalosporins.

Stages of bactericidal action: The mechanism of action of carbapenems represents a complex cascade of reactions:

1. The drug exhibits structural similarity to D-alanyl-D-alanine, an essential component of the bacterial wall.
2. Firm binding occurs with specific penicillin-binding proteins (PBPs).
3. The function of the key enzyme, transpeptidase, is inhibited.
4. The formation of necessary peptidoglycan cross-links is disrupted.
5. Finally, autolytic enzymes of the cell wall are activated, leading to its irreversible damage and guaranteed death of the microorganism.

Drugs with a dual mechanism

Certain broad-spectrum bactericidal antibiotics are distinguished by their predominant effect on Gram-negative flora and realize their destructive effect along two parallel directions simultaneously.

First, they interfere with ribosome function and disrupt the earliest stages of protein synthesis. Second, they directly damage the bacterial cytoplasmic membrane, critically increasing its permeability. Such a complex impact deprives the cell of the ability to adapt and leaves the microorganism no chance of survival.

Class and exam questions

What else to study on this topic

• Mechanism of action of glycopeptides and cycloserine
• Spectrum of activity of polymyxins and polyene antibiotics
• The role of penicillin-binding proteins (PBPs) in cell death
• Autolytic enzymes of the bacterial cell wall
• Pharmacology of rifampicin and inhibition of RNA synthesis

Other topics in the section "Antibacterial Chemotherapeutic Agents"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.