Covariate determinants of effective dosing regimens for time-dependent beta-lactam antibiotics for critically ill patients
Language English Country Czech Republic Media print-electronic
Document type Journal Article, Observational Study
PubMed
29582860
DOI
10.5507/bp.2018.011
Knihovny.cz E-resources
- Keywords
- beta-lactam antibiotics, critically ill patient, meropenem, pharmacokinetics/pharmacodynamics target, piperacillin,
- MeSH
- Anti-Bacterial Agents administration & dosage pharmacokinetics pharmacology MeSH
- beta-Lactams administration & dosage pharmacokinetics pharmacology MeSH
- Adult MeSH
- Critical Illness therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Meropenem administration & dosage pharmacokinetics pharmacology MeSH
- Adolescent MeSH
- Young Adult MeSH
- Peritonitis complications drug therapy MeSH
- Piperacillin administration & dosage pharmacokinetics pharmacology MeSH
- Multiple Trauma complications drug therapy MeSH
- Prospective Studies MeSH
- Drug Administration Schedule MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sepsis drug therapy MeSH
- Shock, Septic drug therapy MeSH
- Systemic Inflammatory Response Syndrome drug therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
- beta-Lactams MeSH
- Meropenem MeSH
- Piperacillin 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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