<p>A Systematic Review of Vancomycin Dosing in Patients with Hematologic Malignancies or Neutropenia</p>

Abstract

Objective: To provide a comprehensive review of vancomycin dosing in patients with hematologic malignancies or neutropenia. Methods: PubMed, Embase and the Cochrane Library were searched through April 2, 2020. Original studies relevant to vancomycin dosing regimen in adults with hematologic malignancies or neutropenia were included. No restriction was applied in study design and language. A descriptive analysis was performed. Results: Twenty-three studies were included eventually, of which eighteen were case series studies, four were cohort studies and another one was a randomized controlled trial. Five case series studies made a clinical audit of conventional vancomycin dosing in patients with malignancies or neutropenia, showing that the proportion of patients with sub-therapeutic trough levels remained high, ranging from 32% to 88%. Seven case series studies and four cohort studies demonstrated that vancomycin clearance (CLva) tended to be higher in patients with hematologic malignancies or neutropenia, whereas volume of distribution (V) seemed to be comparable to the control group. Five studies proposed individualized initial dosing regimen per the pharmacokinetic changes; however, no prospective validation has been conducted in clinical setting. Additionally, four case series studies suggested that the correlation between vancomycin clearance and estimated creatinine clearance was relatively poor, bringing a great challenge to proper dosing strategy. A randomized controlled trial stated that therapeutic drug monitoring (TDM) of vancomycin could decrease the incidence of nephrotoxicity in immunocompromised febrile patients with hematologic malignancies. Conclusion:The available evidence indicates that conventional vancomycin dosing leads to suboptimal concentration in patients with hematologic malignancy or neutropenia. TDM accompanied by pharmacokinetic interpretation can decrease the risk of nephrotoxicity. The individualization of the initial dosing regimen and mechanisms of augmented clearance require further research.

Clinical Practice Guidelines for Therapeutic Drug Monitoring of Vancomycin in the Framework of Model-Informed Precision Dosing: A Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

“…Patients with altered V d and renal function and those with unstable haemodynamics might be candidates for AUC-guided dosing to increase the prediction accuracy [ 42 , 52 , 96 , 117 , 118 , 119 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ] (III-A).…”

“…Augmented renal clearance [ 127 ] is experienced by patients with sepsis [ 128 , 129 , 130 ]. Enhanced clearance is also observed in patients with hematopoietic tumours or febrile neutropaenia [ 131 ]. Furthermore, patients with heart failure [ 132 , 133 ], oedema [ 132 , 134 ], dehydration [ 117 , 119 ], burns [ 135 , 136 ], obesity [ 137 , 138 , 139 , 140 ], or emaciation [ 140 ] have different V d and clearance from individuals in the normal population.…”

Association of Vancomycin Trough Concentration and Clearance With Febrile Neutropenia in Pediatric Patients

“…Febrile neutropenia is reported to promote renal blood flow due to enhanced cardiac output, which leads to enhanced renal clearance of drugs, such as vancomycin relative to bodyweight and decreased serum drug concentrations. 13 In this study, the effect of febrile neutropenia on vancomycin concentration/dose ratio and vancomycin clearance in pediatric patients stratified by age was evaluated. Compared with those in the nonfebrile neutropenia cohort, eGFR and vancomycin clearance were significantly higher, and the vancomycin concentration/dose ratio was significantly lower in the febrile neutropenia cohort.…”

“…A recent systematic review indicated that a conventional dose of vancomycin leads to suboptimal blood concentrations in patients with hematological malignancies or neutropenia. 13 Similarly, another study suggested that vancomycin clearance in pediatric patients with febrile neutropenia increases due to ARC. 14 However, the authors analyzed all pediatric subjects aged 1-14.7 years without age stratification.…”

Causes of vancomycin dosing error; problem detection and practical solutions; a retrospective, single-center, cross-sectional study

“…A systemic review conducted in 2020 by He et al confirmed that the current conventional vancomycin protocol is accompanied by a low sub-therapeutics trough in patients with hematological malignancy or neutropenia. The mechanism by which neutropenia induces the sub-therapeutic level is not well understood ( He et al, 2020 ); However, other studies explained this sub-therapeutic level due to the high volume of distribution and clearance in a neutropenic patient ( Hochart et al, 2011 , Guilhaumou et al, 2016 ). Neutropenia can cause the augmentation of vancomycin clearance, and many hypotheses exist to explain that, including; i) kidney function and urine output can be altered by cancer and excessive hydration, ii) induction of non-renal metabolism of vancomycin such as hepatic elimination by conjugation, and iii) vascular permeability is enhanced by infection and neutropenia, which leads to extravasations of vancomycin and caused decreased serum concentration ( Al-Kofide et al, 2010 , Choi et al, 2017 ).…”