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Nephrotoxicity of vancomycine after implementation of higher therapeutic range. Validation of Windows vision of MW-Pharm for pharmacokinetic modelling for therapeutic monitoring of vancomycin
Project IdSGS08/LF/2019-2020
Main solverPharmDr. Blanka Kořístková, Ph.D.
Period1/2019 - 12/2020
ProviderSpecifický VŠ výzkum
Statefinished
AnotationVancomycin is a glycopeptide antibiotic that has been in clinical use as a penicilllin alternative to treat severe infections (endokarditis, sepsis, spondylodiscitis) caused by sensitive pathogens (esp. penicillinase-producing strains of Staphylococus aureus). Vancomycin has a narrow therapeutic range ? higher trough and peak concentrations can contribute to nephrotoxicity and ototoxicity. Increase of vancomycin levels without any difference in dose or serum creatinine level were observed during long-term treatment. The therapeutic drug monitoring (TDM) is thus necessary for appropriate treatment with vancomycin. According to consensus of American Society of Health-System Pharmacist, the Infectious Disease Society of Amerika a Society of Infectious Diseases Pharmacists (Am J Health-Syst Pharm 2009;66:82-98) the therapeutic range was changed. Opposite to 10-15mg/L for trough level with no regard to diagnosis, 15-20 mg/L is recommended for severe infections esp. on the early period of the treatment. MW-Pharm 3:30 (DOS) has been long-term used for PK/PD monitoring in therapeutic drug monitoring. The Windows version was introduced recently. The validation of vancomycin_adult_C2 model was provided in our pilot study. The model produced comparable outcomes with vancomycin adult model in DOS. The Spearman correlation R was low in both models (0.51 ? 0.53, P<0.0001). Percentual prediction error oscillated from -34% do +20%. Despite the same demographic parameters, the outcomes of both models were not the same. The validation of further models is thus necessary.