Limited association between serum vancomycin pharmacokinetic/ pharmacodynamic indices and clinical outcomes in gram-positive complicated urinary tract infections.

Authors

Yaxin Fan, Jinjin Zhao, Yuancheng Chen, Lin Xi, Hailan Wu, Beining Guo, Nanyang Li, Ping Yang, Qiyu Bian, Jufang Wu, Jing Zhang

Published in

Frontiers in pharmacology. Volume 17. Pages 1772367. Epub Jul 16, 2026.

Abstract

Vancomycin, primarily excreted through the urine, is used for complicated urinary tract infections (cUTIs) caused by Gram-positive bacteria. Although serum therapeutic drug monitoring (TDM) is usually performed in vancomycin therapy, its benefits and risk factors in patients with cUTIs remain unclear.
Adults with Gram-positive bacterial cUTIs receiving serum vancomycin TDM were enrolled from three prospective, multicenter trials. Minimal inhibitory concentration (MIC) was measured by agar dilution for pathogens collected from all patients. Clinical characteristics and pharmacokinetic/pharmacodynamic (PK/PD) indices were analyzed between the vancomycin treatment success and failure groups.
A total of 74 adult patients with cUTIs were enrolled. Median initial daily dose of vancomycin was 1.0 g (interquartile range [IQR], 1.0-2.0 g), given in divided doses every 12 h or as a once-daily regimen. Most concomitant antibiotics targeted Gram-negative bacteria or fungi, with very limited anti-Gram-positive co-therapy. The median serum trough concentration (C_min) of vancomycin was 9.22 mg/L (IQR, 4.36-14.33 mg/L) and 24-h area under the concentration-time curve to MIC (AUC₂₄/MIC) was 455 (IQR, 268-627). Despite low attainment of the AUC₂₄/MIC 400-600 target (27/74, 36.5%), the treatment success rate was 86.5% (64/74) and the nephrotoxicity rate was 4.1% (3/74). Urinary pathogens isolated included Enterococcus spp (55/74), Streptococcus spp (10/74), and Staphylococcus aureus (9/74), including eight methicillin-resistant S. aureus [MRSA]). Both solid tumor and S. aureus infection showed exploratory associations with vancomycin treatment failure. Patients with solid tumor had a lower probability of attaining the target AUC₂₄/MIC, likely due to the elevated MIC of the predominant Enterococcus strains in this population. In contrast, patients with S. aureus-induced cUTIs achieved higher AUC₂₄/MIC levels. All isolates exhibited low MICs (≤1 mg/L), no heteroresistance was detected, and the predominant molecular type was clone complex 5 (CC5).
Vancomycin was effective in Enterococcus-dominant cUTIs and had a modest response in a few MRSA cases, despite low PK/PD target attainment. Serum C_min and AUC₂₄/MIC showed limited association with clinical outcomes, whereas solid tumor and S. aureus infection showed exploratory associations with treatment failure. However, TDM remains valuable for safety monitoring and individualized dosing. These findings should be validated in larger cohorts.

PMID:
42534591
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

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