Klin Farmakol Farm. 2007;21(3):98-102

The importance of dosage intervals for the therapy using time-dependent antibiotics: Examples of therapeutic drug monitoring

Josef Šedivý¹, Anna Jedličková¹, Olga Černá²

¹ Ústav klinické biochemie a laboratorní diagnostiky 1. LF UK a VFN, Praha

² Klinika dětského a dorostového lékařství 1. LF UK a VFN, Praha

Based on growth/killing microbial parameters in vitro and individual drug concentration/time fluctuations, the rate of bactericidal effect of two time-dependent antibiotics, vancomycin and amoxicillin/clavulanate, was calculated to optimize the next therapy. Predicted time to decrease the number of viable bacteria to 10–6 (as compared with the start of therapy) was adopted as surrogate criterion of the bactericidal effect. Even of highly susceptible strains, microbial killing activity of time-dependent antibiotic agent ceases when its concentration declines under about 4 times the MIC-level. It takes place mainly at the end of too long intermittent dosage interval. For example, the dosage interval for standard oral forms of amoxicillin/clavulanate should not be longer than 8 hours. Shortening the dosage interval (being much more effective than higher dose administered intermittently) or continuous IV-infusion of standard daily dose of these antibiotics accelerates bactericidal effect in some pacients. On the other hand, the available therapeutic monitoring of vancomycine and the recommendation to hold its Cmin over 5 mg/L seems to be rational and satisfactory in the treatment of susceptible infections.

Keywords: vancomycin, amoxicillin/clavulanate, dosage interval, microbial growth/killing rates, therapeutic drug monitoring

Published: January 1, 2008  Show citation