The use of in vitro pharmacodynamic models of infection to optimize fluoroquinolone dosing regimens
Abstract
In vitro pharmacodynamic models of infection are widely used to assess the likely efficacy of various antibacterial dosing regimens against relevant common pathogens. A significant body of data has been accumulated on the pharmacodynamics of fluoroquinolones using such systems, but there are conflicts with data from other in vitro models and with animal and human findings. To ensure clarity in the development of dosing with fluoroquinolones, and to ensure that regimens are optimized in terms of antibacterial effect and/or preventing emergence of resistance, it is important to seek explanations for these divergent findings. In this review we will discuss the methodological and analytical factors involved in pharmacodynamic analyses using in vitro models of infection and how these may affect the conclusions drawn. The simplest type of experiment using in vitro pharmacodynamic models tests the simulated serum pharmacokinetic profile of a drug at a defined dose against a range of pathogens likely to be encountered in clinical trials and subsequent clinical use. Efficacy is judged by bacterial killing over the time of study.1–3 For example, many studies have recently been published on the effects of ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, sparfloxacin and trovafloxacin against Streptococcus pneumoniae.4–9 Variations on this basic design include the simulation of increasing doses at the same frequency (dose escalation studies); studying the emergence of antibacterial…
How strong is the evidence?
Evidence Hub reads this as a review, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Pharmacokinetic aspects of retinal drug delivery
- A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis
- From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics
- Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus
- In Vitro Pharmacodynamic Evaluation of the Mutant Selection Window Hypothesis Using Four Fluoroquinolones against Staphylococcus aureus
- Discovery of Potent, Selective Multidrug and Toxin Extrusion Transporter 1 (MATE1, SLC47A1) Inhibitors Through Prescription Drug Profiling and Computational Modeling
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.