Relationship between PK/PD of Cefepime and Clinical Outcome in Febrile Neutropenic Patients with Normal Renal Function

Yamashita, Yugo; Kamiyama, Hidekazu; Yamamoto, Akira; Kanoh, Hiroki; Yuhki, Yoshimitsu; Ueda, Akira; Kawamoto, Yukari; Gotoh, Y; Yamamoto, Satoshi

doi:10.1248/yakushi.16-00168

Cited by 6 publications

(3 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For febrile neutropenic patients with normal renal function or ARC, cefepime 2 g t.i.d. with 3 h of infusion was effective in several cases (Yamashita et al, 2016). A study on pediatric patients recommended a regimen of 100 mgkg-1d-1 administered as a continuous infusion to attain higher target values (de Cacqueray et al, 2022).…”

Section: Cefepimementioning

confidence: 99%

Individualized antibiotic dosage regimens for patients with augmented renal clearance

Shi

Zhuang

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

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.

show abstract

Section: Cefepimementioning

confidence: 99%

Individualized antibiotic dosage regimens for patients with augmented renal clearance

Shi

Zhuang

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…17 Clinical studies using cefepime doses of 4-6 g/d have been reported [18][19][20] ; higher doses may improve clinical response based on the pharmacokinetic/ pharmacodynamic principles. [21][22][23][24][25][26][27][28][29] However, high doses, such as 6 g, increase the risk of encephalopathy in a dosedependent manner, with the upper limit for trough concentrations ranging from 22 to 35 mcg/mL. 30,31 Cefepime requires a lower limit of at least 8 mcg/mL, which is equivalent to an unbound concentration time above the minimum inhibitory concentration (%fT .…”

Section: Introductionmentioning

confidence: 99%

Dose Individualization of Cefepime for Febrile Neutropenia in Patients With Lymphoma or Multiple Myeloma: Implications for Therapeutic Drug Monitoring

Oda,

Yamaguchi,

Matsumoto

et al. 2023

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

Background: Optimal cefepime dosing is a challenge because of its dose-dependent neurotoxicity. This study aimed to determine individualized cefepime dosing for febrile neutropenia in patients with lymphoma or multiple myeloma. Methods: This prospective study enrolled 16 patients receiving cefepime at a dose of 2 g every 12 hours. Unbound concentrations were determined at 0.5 hours, 7.2 hours [at the 60% time point of the 12 hours administration interval (C7.2h)], and 11 hours (trough concentration) after the first infusion (rate: 2 g/h). The primary and secondary end points were the predictive performance of the area under the unbound concentration–time curve (AUCunbound) and the effect of unbound cefepime pharmacokinetic parameters on clinical response, respectively. Results: The mean (SD) AUCunbound was 689.7 (226.6) mcg h/mL, which correlated with C7.2h (R2 = 0.90), and the Bayesian posterior AUCunbound using only the trough concentration (R2 = 0.66). Although higher exposure was more likely to show a better clinical response, each parameter did not indicate a statistical significance between positive and negative clinical responses (P = 0.0907 for creatinine clearance (Ccr), 0.2523 for C7.2h, 0.4079 for trough concentration, and 0.1142 for AUCunbound). Cutoff values were calculated as 80.2 mL/min for Ccr (sensitivity: 0.889, specificity: 0.714), 18.6 mcg/mL for C7.2h (sensitivity: 0.571, specificity: 1.000), and 9.2 mcg/mL for trough concentration (sensitivity: 0.571, specificity: 1.000). When aiming for a time above 100% the minimum inhibitory concentration, both continuous infusion of 4 g/d and intermittent infusion of 2 g every 8 hours achieved a probability of approximately 100% at a minimum inhibitory concentration of 8 mcg/mL. Conclusions: Therapeutic drug monitoring by sampling at C7.2h or trough can facilitate rapid dose optimization. Continuous infusion of 4 g/d was recommended. Intermittent dosing of 2 g every 8 hours was alternatively suggested for patients with a Ccr of 60–90 mL/min.

show abstract

“…Cefepime, like other β-lactams, has pharmacodynamic activity governed by 'time-dependent' activity. The fraction of time that the unbound drug concentration exceeds the MIC (fT >MIC ) for the dosing interval is the pharmacokinetic/pharmacodynamic (PK/PD) efficacy target for cefepime [4], and a target of 60-74% has been previously proposed [5][6][7][8]. For the currently approved cefepime product and combination agents in the pipeline [9,10], understanding cefepime disposition and variability is crucial to for optimal treatment of patients.…”

Section: Introductionmentioning

confidence: 99%

Development of Population and Bayesian Models for Applied Use in Patients Receiving Cefepime

et al. 2020

View full text Add to dashboard Cite

Background and Objective Understanding pharmacokinetic disposition of cefepime, a β-lactam antibiotic, is crucial for developing regimens to achieve optimal exposure and improved clinical outcomes. This study sought to develop and evaluate a unified population pharmacokinetic model in both pediatric and adult patients receiving cefepime treatment. Methods Multiple physiologically relevant models were fit to pediatric and adult subject data. To evaluate the final model performance, a withheld group of 12 pediatric patients and two separate adult populations were assessed. Results Seventy subjects with a total of 604 cefepime concentrations were included in this study. All adults (n = 34) on average weighed 82.7 kg and displayed a mean creatinine clearance of 106.7 mL/min. All pediatric subjects (n = 36) had mean weight and creatinine clearance of 16.0 kg and 195.6 mL/min, respectively. A covariate-adjusted two-compartment model described the observed concentrations well (population model R 2 , 87.0%; Bayesian model R 2 , 96.5%). In the evaluation subsets, the model performed similarly well (population R 2 , 84.0%; Bayesian R 2 , 90.2%). ConclusionThe identified model serves well for population dosing and as a Bayesian prior for precision dosing.

show abstract

Relationship between PK/PD of Cefepime and Clinical Outcome in Febrile Neutropenic Patients with Normal Renal Function

Cited by 6 publications

References 15 publications

Individualized antibiotic dosage regimens for patients with augmented renal clearance

Individualized antibiotic dosage regimens for patients with augmented renal clearance

Dose Individualization of Cefepime for Febrile Neutropenia in Patients With Lymphoma or Multiple Myeloma: Implications for Therapeutic Drug Monitoring

Development of Population and Bayesian Models for Applied Use in Patients Receiving Cefepime

Contact Info

Product

Resources

About