Augmented Renal Clearance and Hypoalbuminemia-Induced Low Vancomycin Trough Concentrations in Febrile Neutropenic Patients With Hematological Malignancies

Alzahrani, Abdullah M.; Hakami, Alqassem Y.; AlAzmi, Aeshah; Karim, Shahid; Ali, Ahmed; Burzangi, Abdulhadi S.; Alkreathy, Huda Mohammed; Khan, Mansoor A.; Alzhrani, Rami M.; Basudan, Samah S.; Alzahrani, Yahya A.

doi:10.7759/cureus.29568

Cited by 4 publications

(3 citation statements)

References 29 publications

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“…Among the most important subjects of recent research is the ability to predict the factors substantially responsible for the failure to achieve the desired vancomycin therapeutic goal in patients with FN. Here, we illustrate in Figure 5 the possible hypothetical mechanism behind such failure based on the findings of the current work and our previous work [ 33 ]. The first and foremost mechanism assumes that FN exerts its effect by causing variation in the PK parameters of vancomycin, which includes (1) a significant increase in vancomycin clearance, which will lead to a marked short in the half-life of the drug.…”

Section: Discussionmentioning

confidence: 89%

Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation

Alzahrani,

Naeem,

AlAzmi

et al. 2023

Antibiotics

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The pharmacokinetics of vancomycin vary significantly between specific groups of patients, such as critically ill patients and patients with hematological malignancy (HM) with febrile neutropenia (FN). Recent evidence suggests that the use of the usual standard dose of antibiotics in patients with FN may not offer adequate exposure due to pharmacokinetic variability (PK). Therefore, the purpose of this study is to assess the effect of FN on AUC0–24 as a key parameter for vancomycin monitoring, as well as to determine which vancomycin PK parameters are affected by the presence of FN using Bayesian software PrecisePK in HM with FN. This study was carried out in King Abdulaziz Medical City. All adult patients who were admitted to the Princess Norah Oncology Center PNOC between 1 January and 2017 and 31 December 2020, hospitalized and received vancomycin with a steady-state trough concentration measured before the fourth dose, were included. During the trial period, 297 patients received vancomycin during their stay at the oncology center, 217 of them meeting the inclusion criteria. Pharmacokinetic parameters were estimated for the neutropenic and non-FN patients using the precise PK Bayesian platform. The result showed that there was a significant difference (p < 0.05) in vancomycin clearance Clvan, the volume of distribution at a steady-state Vdss, the volume of distribution for peripheral compartment Vdp, half-life for the elimination phase t½β, and the first-order rate constant for the elimination process β in FN compared to non-FN patients. Furthermore, AUC0–24 was lower for FN patients compared to non-FN patients, p < 0.05. FN has a significant effect on the PK parameters of vancomycin and AUC0–24, which may require specific consideration during the treatment initiation.

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Section: Discussionmentioning

confidence: 89%

Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation

Alzahrani,

Naeem,

AlAzmi

et al. 2023

Antibiotics

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“…Based on the demographic information presented by Álvarez et al, this approximately corresponds to a CrCl of 200 mL/min. Altough a CrCl of 200 mL/min is generally considered high, this may be explained by augmented renal clearance, which has been associated with febrile neutropenia [ 32 , 33 , 34 ].…”

Section: Resultsmentioning

confidence: 99%

Beta-Lactam Probability of Target Attainment Success: Cefepime as a Case Study

et al. 2023

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Introduction: Probability of target attainment (PTA) analysis using Monte Carlo simulations has become a mainstay of dose optimization. We highlight the technical and clinical factors that may affect PTA for beta-lactams. Methods: We performed a mini review in adults to explore factors relating to cefepime PTA success and how researchers incorporate PTA into dosing decisions. In addition, we investigated, via simulations with a population pharmacokinetic (PK) model, factors that may affect cefepime PTA success. Results: The mini review included 14 articles. PTA results were generally consistent, given the differences in patient populations. However, dosing recommendations were more varied and appeared to depend on the definition of pharmacodynamic (PD) target, definition of PTA success and specific clinical considerations. Only 3 of 14 articles performed formal toxicological analysis. Simulations demonstrated that the largest determinants of cefepime PTA were the choice of PD target, continuous vs. intermittent infusion and creatinine clearance. Assumptions for protein binding, steady state vs. first dose, and simulating different sampling schemes may impact PTA success under certain conditions. The choice of one or two compartments had a minimal effect on PTA. Conclusions: PTA results may be similar with different assumptions and techniques. However, dose recommendation may differ significantly based on the selection of PD target, definition of PTA success and considerations specific to a patient population. Demographics and the PK parameters used to simulate time-concentration profiles should be derived from patient data applicable to the purpose of the PTA. There should be strong clinical rationale for dose selection. When possible, safety and toxicity should be considered in addition to PTA success.

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“…Published data on ARC appear to be limited to adult patients, whereas in recent years, studies have indicated that accelerated clearance of vancomycin exists in children with febrile neutropenia [ 25 ] or sepsis [ 26 ], which may be related to ARC. Studies in adults with a haematologic malignancy showed that febrile neutropenia is associated with low vancomycin concentrations, possibly driven by ARC [ 27 ]. Our study in paediatric patients with haematologic diseases demonstrated a high prevalence of ARC and that neutropenia was a possible influencing factor in the univariate analysis, but serum creatinine level mediated by age was the dominant factor for ARC in the multivariate regression.…”

Section: Discussionmentioning

confidence: 99%

Age-associated augmented renal clearance and low BMI trigger suboptimal vancomycin trough concentrations in children with haematologic diseases: data of 1453 paediatric patients from 2017 to 2022

Wang,

Zhou,

Wang

et al. 2023

BMC Pediatr

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Background It is usually difficult for the trough concentration of vancomycin to reach the recommended lower limit of 10 mg/L per the label dose in the paediatric population. Moreover, children with haematologic diseases who suffer from neutropenia are more likely to have lower exposure of vancomycin, and the risk factors have been poorly explored. Method We reviewed and analysed the initial trough concentration of vancomycin and synchronous cytometry and biochemical parameters in the blood of 1453 paediatric patients with haematologic diseases over a 6 year period, from 2017 to 2022. Results Forty-five percent of the enrolled children had vancomycin trough concentrations below 5 mg/L after receiving a dose of 40 mg/kg/day, and the multiple regression showed that age (OR = 0.881, 95% CI 0.855 to 0.909, P < 0.001), BMI (OR = 0.941, 95% CI 0.904 to 0.980, P = 0.003) and the glomerular filtration rate (OR = 1.006, 95% CI 1.004 to 1.008, P < 0.001) were independent risk factors. A total of 79.7% of the children experienced augmented renal clearance, which was closely correlated to age-associated levels of serum creatinine. The vancomycin trough concentration was higher in children with aplastic anaemia than in those with other haematologic diseases due to a higher BMI and a lower glomerular filtration rate. Conclusion Age-associated augmented renal clearance and low BMI values contributed to suboptimal trough concentrations of vancomycin in children with haematologic diseases, and the effects of long-term use of cyclosporine and glucocorticoids need to be taken into account.

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Augmented Renal Clearance and Hypoalbuminemia-Induced Low Vancomycin Trough Concentrations in Febrile Neutropenic Patients With Hematological Malignancies

Cited by 4 publications

References 29 publications

Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation

Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation

Beta-Lactam Probability of Target Attainment Success: Cefepime as a Case Study

Age-associated augmented renal clearance and low BMI trigger suboptimal vancomycin trough concentrations in children with haematologic diseases: data of 1453 paediatric patients from 2017 to 2022

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