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Updated: Feb 17, 2026

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Simulating treatment effects for gonorrhoea using a within-host mathematical model.

Pavithra Jayasundara1, David G Regan2, Philip Kuchel3

  • 1School of Population Health, UNSW Sydney, NSW, Australia.

Infectious Disease Modelling
|February 16, 2026
PubMed
Summary
This summary is machine-generated.

Antibiotic resistance in Neisseria gonorrhoeae (NG) necessitates new treatments. A mathematical model shows intracellular bacteria clearance is key for treatment success, not just extracellular drug levels. Gepotidacin and combination therapies show promise.

Keywords:
AzithromycinGentamicinGepotidacinGonorrhoeaIntracellularPharmacodynamicPharmacokinetic

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Area of Science:

  • Microbiology
  • Pharmacology
  • Mathematical Modeling

Background:

  • Neisseria gonorrhoeae (NG) exhibits widespread antibiotic resistance.
  • Existing treatments for gonorrhoea are becoming less effective.
  • Mathematical modeling can predict treatment outcomes.

Purpose of the Study:

  • To extend a within-host mathematical model to include pharmacokinetic/pharmacodynamic (PK/PD) treatment dynamics.
  • To investigate gepotidacin monotherapy and gentamicin/azithromycin dual therapy for gonorrhoea.
  • To identify PK/PD indices predictive of treatment success.

Main Methods:

  • Developed an extended within-host mathematical model incorporating PK/PD features.
  • Simulated treatment regimens for gepotidacin and gentamicin/azithromycin.
  • Analyzed the relationship between PK indices (e.g., AUC/MIC) and treatment outcomes.
  • Evaluated the role of intracellular NG clearance in treatment success.

Main Results:

  • Simulated treatment success rates correlated with available clinical data.
  • Antibiotic failure linked to incomplete clearance of intracellular NG.
  • Extracellular PK indices alone could not predict treatment success/failure.
  • Intracellular gepotidacin AUC/MIC >150 predicted success.
  • Dual therapy AUC/MIC >140 also predicted success but was less informative.

Conclusions:

  • Intracellular bacterial load is a critical factor in gonorrhoea treatment outcomes.
  • PK/PD modeling, especially considering intracellular drug concentrations, is crucial for evaluating new antibiotics.
  • Further research on the killing of intracellular NG is needed to develop effective therapies against resistant strains.