Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Staphylococcus aureus Infection: A Comparative Study between Elderly and Adult Patients

Author:

Xi Lin123ORCID,Li Shanshan4,Chen Mengting123,Huang Xiaolan123,Li Nanyang5,Chen Nanye5,Wu Hailan123,Bian Qiyu6,Bian Xingchen5,Li Xin123,Yang Minjie123,Liang Xiaoyu123,Wu Jufang1235,Guo Beining123,Fan Yaxin123ORCID,Zhang Jing123

Affiliation:

1. Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China

2. Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China

3. National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China

4. Huashan Worldwide Medical Center, Huashan Hospital, Fudan University, Shanghai 200040, China

5. Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai 200040, China

6. Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK

Abstract

Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18–64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019. A total of 164 patients with MRSA infections were enrolled, including 83 elderly and 81 adult patients. Vancomycin therapeutic drug monitoring (TDM) was performed in all patients, indicating significantly higher vancomycin trough concentrations (Ctrough), 24-h area under the curve (AUC24) values, and AUC24/minimum inhibitory concentration (AUC24/MIC) values in elderly patients compared to adult patients. The incidence of vancomycin-associated nephrotoxicity was nearly three times higher in elderly patients (18.1% vs. 6.2%, p = 0.020), despite similar clinical and microbiological efficacy. Of particular importance, a Ctrough > 20 mg/L was found as an independent factor of nephrotoxicity in elderly patients. Further analysis of patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 also revealed that elderly patients had significantly higher vancomycin-related PK/PD indices and more nephrotoxicity than adult patients. In conclusion, elderly patients receiving vancomycin therapy face a higher risk of nephrotoxicity, which requires close vancomycin TDM, especially when the Ctrough exceeds 20 mg/L.

Funder

National Natural Science Foundation of China

Research Startup Fund of Huashan Hospital, Fudan University

Municipal Hospital Emerging Frontier Technology Joint Research Project of Shanghai Shenkang Development Center

Community infectious disease research capacity building project

Publisher

MDPI AG

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