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Antibiotic-associated vanishing bile duct syndrome: a real-world retrospective and pharmacovigilance database analysis

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Abstract

Purpose

Vanishing bile duct syndrome (VBDS) is a rare, but potentially fatal adverse reaction triggered by certain medications. Few real-world studies have shown association between antibiotics and VBDS. We sought to quantify the risk and evaluate the clinical features of VBDS associated with antibiotics.

Methods

Data from 2004 to 2022 on VBDS events induced by antibiotics were retrieved from the FDA Adverse Event Reporting System (FAERS) database and disproportionality analyses were conducted. Furthermore, case reports from 2000 to 31 December 2022 on antibiotics-induced VBDS were retrieved for retrospective analysis.

Results

We collected 132 VBDS reports from the FAERS database. Fluoroquinolones had the greatest proportion and highest positive signal values of VBDS. The RORs (95% CIs) for antibiotics were fluoroquinolones 23.68 (18.12–30.95), macrolides 19.37 (13.58–27.62), carbapenems 17.39 (7.77–38.96), beta-lactam 13.28 (9.69–18.20), trimethoprim/sulfamethoxazole 9.05 (5.57–14.7), and tetracycline 4.02 (1.50–10.77). Twenty-three cases from 22 studies showed evidence of VBDS, beta-lactam (52.2%) was the most frequently reported agent. The median age was 45 years, the typical initial symptoms included rash (30.4%), fatigue/asthenia (26.1%), dark urine (21.7%) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) (21.7%). The median time to onset of VBDS was 2 weeks. All cases had abnormal liver function test, and the median level of total bilirubin was 23.6 mg/dl (range 3.2–80 mg/dl). Cessation of culprit drugs and treatment with ursodeoxycholic acid (83.3%) were not associated with improved outcomes (57.1%).

Conclusion

This study identified thirteen antibacterial agents with significant reporting associations with VBDS. Fluoroquinolones may be a neglected agent of inducing VBDS.

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Authors and Affiliations

  1. Department of Pharmacy, The Third Xiangya Hospital, Central South University, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, China

    Jianglin Wang, Shengfeng Wang, Cuifang Wu & Zhenzhen Deng

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  1. Jianglin Wang
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  2. Shengfeng Wang
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  3. Cuifang Wu
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  4. Zhenzhen Deng
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Contributions

JlW and ZD conceived of the study; JlW and ZD drafted and revised the manuscript; and JlW and SfW made data elaboration and performed statistical analyses. All authors contributed to the final manuscript and approved the submitted version.

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Correspondence to Zhenzhen Deng.

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Wang, J., Wang, S., Wu, C. et al. Antibiotic-associated vanishing bile duct syndrome: a real-world retrospective and pharmacovigilance database analysis. Infection (2023). https://doi.org/10.1007/s15010-023-02132-6

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