What is the Post-Antibiotic Effect?

Update Date: 2024-05-29 Source: Network

Post-antibiotic effect (PAE) refers to the effect whereby bacteria growth continues to be suppressed after a brief contact with antibiotics, even after the drug has been cleared. It is a specific effect of antibiotics on their target bacteria, revealing the interaction process between antibiotics and bacteria. The magnitude of PAE is measured in time, and is calculated using the colony count method as the time difference required for the number of colonies in the experimental and control groups to increase 10-fold during the resumption of logarithmic growth phase.

In the past decade, in-depth research has been conducted on this new theory of PAE abroad, and PAE has been used as an important parameter for evaluating the pharmacodynamics of new antibiotics.

Currently, the mechanism underlying how antibiotics cause PAE is not fully understood. One theory is that after brief contact with bacteria, antibiotics persistently bind to bacterial targets, causing non-fatal damage to bacteria, thereby extending the time required for their targets to resume normal function and for bacterial regrowth. Another theory is the post-antibiotic leukocyte effect (PALE), which refers to the deformation of bacteria after contact with antibiotics, making them easier to be recognized by phagocytic cells. This promotes the chemotaxis of phagocytic cells and the release of lytic enzymes and other bactericidal substances, resulting in a synergistic effect between antibiotics and leukocytes, which further exacerbates bacterial damage and prolongs the repair time.

The determining factors of PAE include the mechanism of drug action, the affinity between the drug and its target, the degree of bacterial damage, and the time required for target function recovery. Additionally, factors such as the type and concentration of the drug, the type of bacteria, and the duration of contact between the drug and bacteria also significantly influence PAE. Pharmacokinetic parameters such as peak drug concentration (Cmax) and the area under the drug concentration-time curve (AUC) have a particularly significant impact on the PAE of concentration-dependent drugs, especially aminoglycosides and fluoroquinolones.

Although the plasma half-life (t1/2) can affect the contact time between drugs and bacteria, and may have a certain impact on the in vivo PAE of some drugs, it is not a determining factor. Drugs that act on bacterial ribosomes and inhibit protein synthesis, such as aminoglycosides, macrolides, lincomycin, chloramphenicol, and tetracyclines, have a significant PAE against Gram-positive cocci and Gram-positive bacilli. Fluoroquinolones, which inhibit DNA gyrase, also have a prolonged PAE against Gram-positive cocci and Gram-negative bacilli.

Beta-lactam antibiotics, which act on the process of bacterial cell wall mucopeptide synthesis, have varying PAE values, which are related to the binding sites and affinity of the drugs with their target penicillin-binding proteins (PBPs). Most beta-lactam drugs have a certain PAE against Gram-positive cocci.