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Individualized antibiotic dosage regimens for patients with augmented renal clearance.

ABSTRACT: Objectives: Augmented renal clearance (ARC) is a state of enhanced renal function commonly observed in 30%-65% of critically ill patients despite normal serum creatinine levels. Using unadjusted standard dosing regimens of renally eliminated drugs in ARC patients often leads to subtherapeutic concentrations, poor clinical outcomes, and the emergence of multidrug-resistant bacteria. We summarized pharmaceutical, pharmacokinetic, and pharmacodynamic research on the definition, underlying mechanisms, and risk factors of ARC to guide individualized dosing of antibiotics and various strategies for optimizing outcomes. Methods: We searched for articles between 2010 and 2022 in the MEDLINE database about ARC patients and antibiotics and further provided individualized antibiotic dosage regimens for patients with ARC. Results: 25 antibiotic dosage regimens for patients with ARC and various strategies for optimization of outcomes, such as extended infusion time, continuous infusion, increased dosage, and combination regimens, were summarized according to previous research. Conclusion: ARC patients, especially critically ill patients, need to make individualized adjustments to antibiotics, including dose, frequency, and method of administration. Further comprehensive research is required to determine ARC staging, expand the range of recommended antibiotics, and establish individualized dosing guidelines for ARC patients.

SUBMITTER: Shi AX

PROVIDER: S-EPMC10410082 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Individualized antibiotic dosage regimens for patients with augmented renal clearance.

Shi A-Xi AX Qu Qiang Q Zhuang Hai-Hui HH Teng Xin-Qi XQ Xu Wei-Xin WX Liu Yi-Ping YP Xiao Yi-Wen YW Qu Jian J

Frontiers in pharmacology 20230726

<b>Objectives:</b> Augmented renal clearance (ARC) is a state of enhanced renal function commonly observed in 30%-65% of critically ill patients despite normal serum creatinine levels. Using unadjusted standard dosing regimens of renally eliminated drugs in ARC patients often leads to subtherapeutic concentrations, poor clinical outcomes, and the emergence of multidrug-resistant bacteria. We summarized pharmaceutical, pharmacokinetic, and pharmacodynamic research on the definition, underlying me ...[more]

PMID: 37564179

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Project description:BackgroundThe purpose of this study was to examine the impact of ARC on levetiracetam concentrations during the first week following acute TBI. The hypothesis was levetiracetam concentrations are significantly lower in TBI patients with augmented renal clearance (ARC) compared to those with normal renal clearance.MethodsThis is a prospective cohort pharmacokinetic study of adults with moderate to severe TBI treated with levetiracetam during the first week after injury. Serial blood collections were performed daily for analysis of levetiracetam, cystatin C, and 12-hr creatinine clearance (CrCl) determinations. Patients were divided into two cohorts: with (CrCl ≥130 ml/min/1.73 m2) and without ARC.ResultsTwenty-two patients with moderate to severe TBI were included. The population consisted primarily of young male patients with severe TBI (mean age 40 years old, 68% male, median admission GCS 4). Each received levetiracetam 1000 mg IV every 12 h for the study period. ARC was present in 77.3% of patients, with significantly lower levetiracetam concentrations in ARC patients and below the conservative therapeutic range (< 6mcg/mL) for all study days. In patients without ARC, the serum concentrations were also below the expected range on all but two study days (Days 4 and 5). Four of the 22 (18.2%) patients exhibited seizure activity during the study period (two of these patients exhibited ARC). Cystatin C concentrations were significantly lower in patients with ARC, though the mean for all patients was within the typical normal range.ConclusionsARC has a high prevalence in patients with moderate to severe TBI. Levetiracetam concentrations after standard dosing were low in all TBI patients, but significantly lower in patients with ARC. This study highlights the need to consider personalized drug dosing in TBI patients irrespective of the presence of ARC.Clinical trial registrationThis study was registered at cliicaltrials.gov (NCT02437838) Registered on 08/05/2015, https://clinicaltrials.gov/ct2/show/NCT02437838 .

Project description:BackgroundUsing standard vancomycin dosage in critically ill patients might lead to therapy failure and worse patient outcomes, augmented renal clearance (ARC) may be the leading risk factor. In this study, we comprehensively investigated the pharmacokinetics-pharmacodynamics (PK-PD) of vancomycin in critically ill patients with ARC, hoping to explore the precise and accurate dose adjustment method for vancomycin.MethodsAll critically ill patients tested for steady-state trough vancomycin serum concentrations during the recent 6 years in a tertiary level hospital were collected retrospectively and divided into ARC and non-ARC groups, respectively, according to creatinine clearance (CLcr). Serum vancomycin concentrations were measured by the fluorescence polarization immunoassay method. PK-PD parameters of vancomycin were recorded or calculated. The desired daily dose successful in achieving the lower target trough levels (10 mg/L) of vancomycin were investigated correspondingly.ResultsA total of 280 vancomycin concentrations were eligible for analysis. The ARC group (n=139) contained more male patients (64.7%) with average age and CLcr of 40 years old (P<0.05) and 180.8 mL/min (P<0.001), respectively. Those patients exhibited higher clearance (CL) and lower trough serum concentrations than the non-ARC patients under comparable daily doses of vancomycin. All the ICU patients demonstrated lower AUC24h values than the target level of 400 µg·h/mL, and this value showed a lower trend in the ARC group than the non-ARC group (232.9 vs. 316.2 µg·h/mL). Subtherapeutic trough concentrations of vancomycin (<10.0 mg/L) were observed in 77.7% and 68.8% of the ARC and non-ARC patients (P<0.05). The proportion of patients with a trough concentration of 10-15 and 15-20 mg/L was 17.9% and 4.3%, respectively, in the ARC group and 24.8% and 2.8%, respectively, in the non-ARC group., a daily dose of 46.0 and 35.5 mg/kg of vancomycin is needed, respectively, in the ARC and non-ARC group to achieve a target trough concentration of 10 mg/L.ConclusionsA higher dose of vancomycin is needed in critically ill patients, especially those with ARC, and appropriate TDM-guided dose adjustment should be considered to achieve the targeted therapeutic range and to provide dosing guidance for this: patient population.

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Individualized antibiotic dosage regimens for patients with augmented renal clearance.

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Individualized antibiotic dosage regimens for patients with augmented renal clearance.

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