Highlights
- •Warnings concerning fluoroquinolone-associated adverse events were recently issued.
- •Umbrella review was performed to assess credibility and quality of evidence.
- •Credible and highly suggestive associations with AAD and ATD were found.
- •Weak evidence of causality for the association with retinal detachment emerged.
- •Limitations of both umbrella review and observational evidence exist.
Abstract
Background
Regulatory agencies warned against fluoroquinolones for the management of minor infections
because of the risk of emerging adverse events (collagen-associated adverse events,
neuropsychiatric toxicity and long-term disability). We aimed to assess quality and
credibility of evidence as well as causality regarding these putative associations.
Methods
MEDLINE, Scopus, Web of Science and PROSPERO were searched, from inception to August
2019, for systematic reviews with meta-analyses investigating emerging adverse events.
Two investigators extracted data to grade quality (through validated AMSTAR-2 tool),
rank credibility of the evidence (convincing, highly suggestive, suggestive, weak)
through adapted criteria including E-value calculation, and assess causality (Hill's
criteria).
Results
Seven systematic reviews of observational studies providing 16 risk estimates [seven,
five and four, respectively, for aortic aneurysm/dissection (AAD), retinal detachment
(RD) and any tendon disorders (ATD)] met inclusion criteria. No systematic reviews
with meta-analysis investigating the risk of neuropsychiatric toxicity or long-term
disability were found. The associations between fluoroquinolones and AAD/ATD showed
highly suggestive credibility and were supported by strong evidence of causality (double
increased risk, especially within first 2 months of treatment). Conflicting data concerning
the emergence of RD were retrieved, resulting in weak evidence of causality. Quality
of the evidence ranged from high to low for AAD, from moderate to critically low for
RD, and it was moderate for ATD.
Conclusion
Our analysis supports credible, plausible and highly suggestive associations with
AAD (rare occurrence but strong causality) and ATD. Limitations of both umbrella reviews
and observational evidence should be considered.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: January 23, 2020
Accepted:
January 15,
2020
Received in revised form:
January 11,
2020
Received:
November 3,
2019
Identification
Copyright
© 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
