ArticleAntimicrobial agents and chemotherapy2012
Pharmacokinetic-pharmacodynamic model for gentamicin and its adaptive resistance with predictions of dosing schedules in newborn infants.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 91 citations in OpenAlex.
- Evaluating renal function and age as predictors of amikacin clearance in neonates: model-based analysis and optimal dosing strategies.British journal of clinical pharmacology · 2016Trial
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- Impact of Postnatal Changes in Creatinine Levels on Plasma Gentamicin Concentrations in Neonates.Pharmaceutical research · 2026Observational
- Evolutionary digital twin framework for optimal aminoglycoside dosing in neonates with suspected sepsis.NPJ digital medicine · 2026Article
- Polydopamine-Antibiotic Composite Coating for Antibiofilm Applications.Macromolecular bioscience · 2026Article
- Model-based translation of the PKPD-relationship for linezolid and vancomycin on methicillin-resistant Staphylococcus aureus: from in vitro time-kill experiments to a mouse pneumonia model.The Journal of antimicrobial chemotherapy · 2025Article
- Factors associated with elevated gentamicin trough levels in neonates: a retrospective analysis of dosing and clinical parameters.Frontiers in pediatrics · 2025Article
- Model-based translation of results from in vitro to in vivo experiments for afabicin activity against Staphylococcus aureus.The Journal of antimicrobial chemotherapy · 2024Article
- Translational PK/PD for the Development of Novel Antibiotics-A Drug Developer's Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Use of Antibiotics in Preterm Newborns.Antibiotics (Basel, Switzerland) · 2022Review
- Pharmacokinetic/Pharmacodynamic Modeling and Application in Antibacterial and Antifungal Pharmacotherapy: A Narrative Review.Antibiotics (Basel, Switzerland) · 2022Review
- Formulation and Evaluation of Hybrid Niosomal In Situ Gel for Intravesical Co-Delivery of Curcumin and Gentamicin Sulfate.Pharmaceutics · 2022Article
- Application of Semi-Mechanistic Pharmacokinetic and Pharmacodynamic Model in Antimicrobial Resistance.Pharmaceutics · 2022Review
- Model-Informed Drug Development for Antimicrobials: Translational PK and PK/PD Modeling to Predict an Efficacious Human Dose for Apramycin.Clinical pharmacology and therapeutics · 2021Article
- Model-Informed Drug Development for Anti-Infectives: State of the Art and Future.Clinical pharmacology and therapeutics · 2021Review
- Optimizing aminoglycoside selection for KPC-producing Klebsiella pneumoniae with the aminoglycoside-modifying enzyme (AME) gene aac(6')-Ib.The Journal of antimicrobial chemotherapy · 2021Article
- Development of New Tuberculosis Drugs: Translation to Regimen Composition for Drug-Sensitive and Multidrug-Resistant Tuberculosis.Annual review of pharmacology and toxicology · 2021Review
- Simplified Dosing Regimens for Gentamicin in Neonatal Sepsis.Frontiers in pharmacology · 2021Article
- Sequential Time-Kill, a Simple Experimental Trick To Discriminate between Pharmacokinetics/Pharmacodynamics Models with Distinct Heterogeneous Subpopulations versus Homogenous Population with Adaptive Resistance.Antimicrobial agents and chemotherapy · 2020Article
- Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gentamicin is commonly used in the management of neonatal infections. Development of adaptive resistance is typical for aminoglycosides and reduces the antibacterial effect. There is, however, a lack of understanding of how this phenomenon influences the effect of different dosing schedules. The aim was to develop a pharmacokinetic-pharmacodynamic (PKPD) model that describes the time course of the bactericidal activity of gentamicin and its adaptive resistance and to investigate different dosing schedules in preterm and term newborn infants based on the developed model. In vitro time-kill curve experiments were conducted on a strain of Escherichia coli (MIC of 2 mg/liter). The gentamicin exposure was either constant (0.125 to 16 mg/liter) or dynamic (simulated concentration-time profiles in a kinetic system with peak concentrations of 2.0, 3.9, 7.8, and 16 mg/liter given as single doses or as repeated doses every 6, 12, or 24 h). Semimechanistic PKPD models were fitted to the bacterial counts in the NONMEM (nonlinear mixed effects modeling) program. A model with compartments for growing and resting bacteria, with a function allowing the maximal bacterial killing of gentamicin to reduce with exposure, characterized both the fast bactericidal effect and the adaptive resistance. Despite a lower peak concentration, preterm neonates were predicted to have a higher bacterial killing effect than term neonates for the same per-kg dose because of gentamicin's longer half-life. The model supported an extended dosing interval of gentamicin in preterm neonates, and for all neonates, dosing intervals of 36 to 48 h were as effective as a 24-h dosing interval for the same total dose.
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