Vpliv farmakokinetičnih parametrov vankomicina na varnostne izide zdravljenja

Marovič, Astrid (author), Vovk, Tomaž (mentor), Petre, Maja (comentor)

Vankomicin je glikopeptidni antibiotik, ki se uporablja za zdravljenje okužb z grampozitivnimi bakterijami. Eden resnejših neželenih učinkov vankomicina je akutna ledvična okvara (ang. acute kidney injury – AKI). Za zmanjšanje tveganja za AKI in zagotavljanje učinkovitosti terapije se zanj priporoča terapevtsko spremljanje koncentracij (ang. therapeutic drug monitoring – TDM). Prve smernice za TDM iz leta 2009 so priporočale spremljanje minimalnih plazemskih koncentracij vankomicina (Cmin), ki naj bi bile v območju 10–20 mg/L. Zaradi vse več dokazov o nefrotoksičnosti pri Cmin vankomicina ⡥ 15 mg/L so bile smernice leta 2020 posodobljene. Trenutno se priporoča spremljanje razmerja AUC/MIK (razmerje med površino pod plazemsko krivuljo (ang. area under the curve – AUC) in minimalno inhibitorno koncentracijo – MIK), saj razmerje AUC/MIK 400–600 velja za optimalni kazalnik učinkovitosti in varnosti terapije z vankomicinom. Z magistrsko nalogo smo želeli ugotoviti, ali so se varnostni izidi zdravljenja po uvedbi novih priporočil za TDM vankomicina izboljšali. Dodatno smo želeli identificirati dejavnike tveganja za AKI pri bolnikih na terapiji z vankomicinom. V retrospektivno opazovalno raziskavo smo vključili bolnike, ki so v letih 2018 in 2021 (pred uvedbo novih priporočil za TDM in po njej) v Univerzitetnem kliničnem centru Maribor prejemali vankomicin. Iz pregleda medicinske dokumentacije smo ugotavljali, ali se je pri bolnikih razvila AKI. Primerjali smo demografske, klinične, mikrobiološke in farmakokinetične lastnosti bolnikov z AKI in brez nje ter bolnikov iz let 2018 in 2021. V raziskavo smo vključili 224 bolnikov, od tega 85 iz leta 2018 in 169 iz leta 2021 oz. 42 z AKI in 182 brez nje. Incidenca AKI in smrtnost sta se po uvedbi novih smernic zmanjšali, vendar ne značilno. Z novim načinom vodenja bolnikov se je zmanjšala izpostavljenost vankomicinu v stacionarnem stanju, kar dokazujejo nižje vrednosti parametrov AUC in Cmin. Dejavniki tveganja za AKI so bili višja starost, daljši čas terapije, zdravljenje na enotah intenzivne terapije, usmerjeno zdravljenje, prisotnost odpornih bakterij ter višji AUC in Cmin. Pokazali smo, da lahko s prehodom na TDM vankomicina s pomočjo razmerja AUC/MIK zmanjšamo nepotrebno visoko izpostavljenost vankomicinu, kar pa se ni izrazilo v bistveno izboljšanih varnostnih izidih zdravljenja.

• Language: Slovenian
• Keywords: vankomicin, terapevtsko spremljanje koncentracij, akutna ledvična okvara, minimalna plazemska koncentracija, površina pod plazemsko krivuljo
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-152820
• Publication date in RUL: 08.12.2023

Secondary language

• Language: English
• Title: Influence of vancomycin pharmacokinetic parameters on treatment safety outcomes

Abstract

Vancomycin is a glycopeptide antibiotic used to treat infections with gram-positive bacteria. One of the more serious adverse effects of vancomycin is acute kidney injury (AKI). In order to reduce the risk of AKI while ensuring therapeutic efficacy, therapeutic drug monitoring (TDM) is recommended for vancomycin. The first TDM guidelines from 2009 recommended monitoring vancomycin trough concentrations (Cmin) while targeting a Cmin range of 10–20 mg/L. Due to increasing evidence of nephrotoxicity at vancomycin Cmin ⡥ 15 mg/L, the guidelines were updated in 2020. Monitoring of the AUC/MIC ratio (area under the curve – AUC to minimum inhibitory concentration – MIC) is currently recommended, as an AUC/MIC ratio of 400–600 is considered the optimal indicator of vancomycin treatment efficacy and safety. The aim of this master's thesis was to determine whether patients' safety outcomes have improved after the introduction of the new vancomycin TDM recommendations. In addition, we aimed to identify risk factors for AKI in patients receiving vancomycin. This retrospective observational study included patients who received vancomycin in 2018 and 2021 (before and after the introduction of the new TDM recommendations, respectively) at the University Medical Centre Maribor. We reviewed patients' medical documentation and determined whether they had developed AKI. We compared demographic, clinical, microbiological, and pharmacokinetic characteristics of patients with and without AKI and of patients from 2018 and 2021. We included 224 patients in the study, 85 of which were from 2018 and 169 from 2021. 42 patients developed AKI while 182 did not. The incidence of AKI and mortality decreased after introducing new guidelines, although not significantly. The new way of monitoring reduced steady-state vancomycin exposure, as evidenced by lower AUC and Cmin values. Risk factors for AKI were older age, longer duration of therapy, intensive care unit admission, targeted therapy, presence of resistant bacteria, and higher AUC and Cmin values. Switching to AUC/MIC-guided TDM can reduce unnecessarily high vancomycin exposure, but this has not resulted in significantly improved treatment safety outcomes.

• Keywords: vancomycin, therapeutic drug monitoring, acute kidney injury, trough concentration, area under the curve