Related Experiment Video

Updated: Aug 22, 2025

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
11:15

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations

Published on: July 24, 2021

4.8K

The risk of drug resistance during long-acting antimicrobial therapy

Anjalika Nande1,2, Alison L Hill1,2

  • 1Program for Evolutionary Dynamics, Harvard University, Cambridge, MA 02138, USA.

Proceedings. Biological Sciences
|November 9, 2022
PubMed

Insights

Long-acting antimicrobial therapies may increase or decrease drug resistance risk depending on drug absorption and pathogen characteristics. Evaluating these complex kinetics is crucial for developing effective treatments against chronic infections.

Area of Science:

  • Pharmacokinetics and Pharmacodynamics
  • Infectious Diseases
  • Drug Resistance Evolution

Background:

  • Antimicrobial resistance is a significant global health threat, particularly for chronic infections like HIV, HBV, HCV, and TB.
  • Sub-optimal adherence to long-term antimicrobial treatments is a key driver of resistance.
  • Novel long-acting drug formulations aim to improve adherence through less frequent dosing but may prolong exposure to intermediate drug concentrations.

Purpose of the Study:

  • To analyze how dosing frequency influences the evolution of antimicrobial resistance under time-varying drug levels.
  • To investigate the complex interplay between drug pharmacokinetics and resistance development in chronic infections.

Main Methods:

  • Mathematical modeling was used to simulate the effect of dosing frequency on resistance evolution.
  • Analysis considered factors such as drug absorption and clearance rates, wild-type inhibition, and resistance source (pre-existing vs. de novo).

Main Results:

  • Long-acting therapies can either increase, decrease, or have a neutral effect on resistance risk.
  • Rapid absorption, slow clearance, and strong wild-type inhibition may reduce resistance from partially resistant strains early in treatment.
  • Conversely, if microbial subpopulations persist and reactivate, long-acting therapies might significantly elevate resistance risk.

Conclusions:

  • Drug kinetics profoundly impact antimicrobial resistance selection in a complex manner.
  • Pathogen-specific modeling is essential for accurately assessing the benefits and risks of new long-acting antimicrobial therapies.
Keywords:
HIVdrug resistancelong-acting therapymathematical modellingmicrobial evolutionviral dynamics

More Related Videos

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses11:17

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Published on: August 30, 2018

13.0K
Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes07:44

Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes

Published on: February 14, 2025

1.0K

Related Concept Videos

Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
108
Antibiotic Selection00:57

Antibiotic Selection

Overview
55.0K
Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
2.0K
Factors Affecting Drug Response: Overview01:21

Factors Affecting Drug Response: Overview

When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
2.1K
Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
4.5K
Pulmonary Tuberculosis V01:28

Pulmonary Tuberculosis V

Medical management of tuberculosis (TB) patients involves a comprehensive approach that includes diagnosis, treatment, and monitoring. The specific strategies can vary depending on the type of tuberculosis (latent or active), the patient's overall health status, and other considerations.
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
225