Covariate determinants of effective dosing regimens for time-dependent beta-lactam antibiotics for critically ill patients
Jazyk angličtina Země Česko Médium print-electronic
Typ dokumentu časopisecké články, pozorovací studie
PubMed
29582860
DOI
10.5507/bp.2018.011
Knihovny.cz E-zdroje
- Klíčová slova
- beta-lactam antibiotics, critically ill patient, meropenem, pharmacokinetics/pharmacodynamics target, piperacillin,
- MeSH
- antibakteriální látky aplikace a dávkování farmakokinetika farmakologie MeSH
- beta-laktamy aplikace a dávkování farmakokinetika farmakologie MeSH
- dospělí MeSH
- kritický stav terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- meropenem aplikace a dávkování farmakokinetika farmakologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- peritonitida komplikace farmakoterapie MeSH
- piperacilin aplikace a dávkování farmakokinetika farmakologie MeSH
- polytrauma komplikace farmakoterapie MeSH
- prospektivní studie MeSH
- rozvrh dávkování léků MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sepse farmakoterapie MeSH
- septický šok farmakoterapie MeSH
- syndrom systémové zánětlivé reakce farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- antibakteriální látky MeSH
- beta-laktamy MeSH
- meropenem MeSH
- piperacilin MeSH
AIMS: Critically ill patients undergoing aggressive fluid resuscitation and treated empirically with hydrosoluble time-dependent beta-lactam antibiotics are at risk for sub-therapeutic plasma concentrations. The aim of this study was to assess the impact of two covariates - creatinine clearance (Clcr) and cumulative fluid balance (CFB) on pharmacokinetics/pharmacodynamics (PK/PD) target attainment within a week of treatment with meropenem (ME) or piperacillin/tazobactam (PIP/TZB). METHODS: In this prospective observational pharmacokinetic (PK) study, 18 critically ill patients admitted to a surgical Intensive Care Unit (ICU) were enrolled. The primary PK/PD target was free antibiotic concentrations above MIC at 100% of the dosing interval (100%fT>MIC) to obtain maximum bactericidal activity. Drug concentration was measured using liquid chromatography-tandem mass spectrometry. RESULTS: The treatment of both 8 septic patients with IV extended ME dosing 2 g/3 h q8 h and 10 polytraumatized patients with IV intermittent PIP/TZB dosing 4.0/0.5 g q8 h was monitored. 8/18 patients (44%) manifested augmented renal clearence (ARC) where Clcr ≥130 mL/min/1.73 m2. Maximum changes were reported on days 2-3: the median positive CFB followed by the large median volume of distribution: Vdme=70.3 L (41.9-101.5), Vdpip = 46.8 L (39.7-60.0). 100%fTme>MIC was achieved in all patients on ME (aged ≥60 years), and only in two patients (non-ARC, aged ≥65 years) out of 10 on PIP/TZB. A mixed model analysis revealed positive relationship of CFBpip with Vdpip (P=0.021). CONCLUSION: Assuming that the positive correlation between CFB and Vd exists for piperacillin in the setting of the pathological state, then CFB should predict Vdpip across subjects at each and every time point.
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