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Modeling the influence of non-adherence on antibiotic efficacy: application to ciprofloxacin
1Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. lansky@biomed.cas.cz
Objective:
To evaluate the consequences for antibiotic efficacy of different types of poor adherence to a short-term dosing regimen. Ciprofloxacin was taken as an example.
Method:
A simulation study on a 2-compartment pharmacokinetic model and parameter estimates taken from the literature was performed. Two empirical efficacy measures as well as a specific pharmacodynamic model of the bacterial kill curve were used. Four patterns of non-adherence were investigated: dosage omission, irregular dosing intervals, delayed dosing and treatment discontinuation.
Results:
Errors in timing of doses with a standard deviation less than 2 h had a minor effect on antibiotic efficacy. Dosage omission, in contrast, has a significant influence on the antibacterial effect of ciprofloxacin.
Conclusions:
non-adherence patterns are difficult to measure experimentally, thus, recommended dosing regimens should be sufficiently robust against most of the nonintentional disturbances.
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