Vancomycin (VCM) is a glycopeptide antibiotic frequently used in treating severe bacterial infections caused by gram-positive cocci, including methicillin-resistant Staphylococcus aureus. It is commonly initiated as an empirical therapy for febrile neutropenia (FN) occurred in cancer patients [1]. Owing to its narrow therapeutic index, well-established therapeutic drug monitoring (TDM) has been widely used for decades. Conventionally, a trough value of 10–20 mg/L has been accepted for optimal dosing safety [2,3]. Instead of measured concentration, new consensus guidelines recommend a target area under the 24-h time-concentration curve (AUC24) of 400–600 mg h/L to maximize efficacy and minimize the risk of nephrotoxicity assuming a minimum inhibitory concentration (MIC) of 1 mg/L [4].

Patients with underlying hematologic malignancies, especially those undergoing intensified chemotherapy and hematopoietic cell transplantation are susceptible to various types of microorganisms due to their profound immunocompromised status including severe neutropenia [1,[5], [6], [7], [8], [9]]. It has been reported that FN incidence can be as high as 80% in this population compared to 10%–50% in patients with solid tumors [1]. Thus, pathophysiological changes may occur in patients with hematologic malignancies leading to altered pharmacokinetic (PK) parameters [[10], [11], [12]]. In particular, these physiological fluctuations include augmented renal clearance (ARC), which is a phenomenon characterized by enhanced glomerular filtration [13]. Several studies in patients admitted to the intensive care unit (ICU) have identified sepsis, multitrauma, and young age with lower illness severity as potential risk factors for developing ARC [[14], [15], [16], [17], [18]]. ARC has been the topic of numerous studies in the ICU population [13,[19], [20], [21]] and has been strongly associated with a risk of underexposure to antimicrobial drugs [15,22,23]. However, limited information is available about VCM PK in patients with ARC [[24], [25], [26]]. Additionally, although previous studies have reported that patients with neutropenia or hematologic malignancies exhibit increased VCM clearance (CLVCM) [25,[27], [28], [29]], the effect of neutropenia on CLVCM in patients with hematologic malignancies is still not well understood.

The increased risk of treatment failure due to either suboptimal or elevated concentrations calls for optimization of VCM therapy in patients with hematologic malignancies. According to our preliminary narrative review, no population pharmacokinetic (popPK) model for a large sample size of hematologic malignancies with concomitant neutropenia and ARC has been described. Moreover, no AUC-based dosing regimen has been proposed to date. Therefore, we aimed to develop a popPK model for VCM in adult patients with hematologic malignancies, evaluate the effect of neutropenia and ARC on the PK of VCM, and propose an optimal dosing regimen.