Optimization of dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus in neutropenic patients with cancer by Monte Carlo simulations

Abstract

The objective of this study was to evaluate the efficacy of various dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus (MRSA) in neutropenic patients with cancer. Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to determine cumulative fraction of response (CFRs) in terms of area under the concentration-time curve/minimum inhibition concentration target. Currently clinical standard dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin were insufficient to provide expected CFRs against MRSA for neutropenic patients with cancer. The high dosing regimens of vancomycin (3500 mg/d), teicoplanin (800 mg/d) and daptomycin (8 mg/kg/d) could provide CFRs of ≥ 80%, showing a higher treatment success. However, the majority of CFRs with linezolid simulated dosing regimens reached < 80% against MRSA. Therefore, a strategy of high dosages of vancomycin, teicoplanin and daptomycin may be needed to attain optimal therapeutic efficacy against MRSA in neutropenic patients with cancer.

Keywords:

• Vancomycin
• teicoplanin
• linezolid
• daptomycin
• methicillin-resistant Staphylococcus aureus
• neutropenia
• cancer
• pharmacokinetic/pharmacodynamic

Disclosure of interest

The authors report no conflict of interest.

Additional information

Funding

All authors declare: No external funding has been received.

Notes on contributors

Xiaochen Wei

Xiaochen Wei, MS, Department of Pharmacy, Tianjin First Central Hospital, Tianjin, PR China. Research interests include clinical pharmacy, pharmacology, pharmacokinetics/pharmacodynamics, and evidence-based medicine.

Mingfeng Zhao

Mingfeng Zhao, MD, PhD, Department of Hematology, Tianjin First Central Hospital, Tianjin, PR China. Research interests include hematologic malignancies and hematopoietic stem cell transplantation.

Xia Xiao

Xia Xiao, MD, Department of Hematology, Tianjin First Central Hospital, Tianjin, PR China. Research interests include hematologic malignancies and hematopoietic stem cell transplantation.