Fluoroquinolones are a type of antibiotic used to treat infections of the lungs and airways, urine tract, prostate and other parts of the body.
An increased risk of tendon problems with fluoroquinolone use has been recognised in the past. More recently, there have been further concerns that fluoroquinolone use may also be associated with eye disorders (retinal detachment and uveitis), with nerve damage (peripheral neuropathy), and with the widening of blood vessels (aortic aneurysm).
In this study we will investigate the association between fluoroquinolone use and not only tendon injury, but also retinal detachment, uveitis, peripheral neuropathy, glucose disorders, and aortic aneurysm. It is important that we understand the association of fluoroquinolones with these outcomes given they can have serious long-term consequences. Retinal detachment and uveitis can lead to loss of vision. Peripheral neuropathy can worsen quality of life. Aortic aneurysm can in some cases lead to death. Glucose disorders can lead to a number of health problems including mood disorders.
It is not clear whether fluoroquinolones cause all of these negative health outcomes. It may be that these associations occur because people who are prescribed fluoroquinolones have, on average, poorer health when they start treatment than people not prescribed fluoroquinolones, which is something we will investigate.
Fluoroquinolones have been associated with a number of adverse events including retinal detachment, uveitis, peripheral neuropathy, dysglycaemia, and aortic aneurysm or dissection. It is possible, however, that some of these associations are not causal but due to confounding. We will investigate these associations using both a cohort study design and two self-controlled study designs, namely the case-time-control study and the self-controlled case series.
We will use a cohort study of people prescribed fluoroquinolones or an alternative antibiotic class prescribed for similar indications, cephalosporin, to estimate the risk of uveitis, peripheral neuropathy, and hospitalisation with aortic aneurysm or dissection, associated with fluoroquinolone prescription. We will include a positive control outcome, tendon rupture, which has a well-established association with fluoroquinolones.
Propensity scores, calculated using logistic regression, will be used in this cohort study to adjust for measured covariates. Propensity score weighted Cox regression will be used to estimate the association of each outcome with fluoroquinolone exposure.
For retinal detachment and uveitis, self-controlled case series will be conducted to estimate the risk of these outcomes with fluoroquinolone prescription and with the control antibiotic exposures of cephalosporin, trimethoprim and co-amoxiclav. For hospitalisation with aortic aneurysm or dissection, a case-time-control study will be conducted to estimate the risk of hospitalisation with this outcome associated with fluoroquinolone prescription and associated with the control antibiotics cephalosporin, trimethoprim and co-amoxiclav. Both the self-controlled case series and the case-time-control study eliminate time-invariant confounding by design. However, time-varying confounding relating to the infection may be present, which we would detect from elevated risk observed with the control antibiotics.
We will also use quantitative bias analysis methods to assess the extent to which findings could be biased by residual confounding.
Retinal detachment; Uveitis; Peripheral neuropathy; Hospitalisation with aortic aneurysm or dissection; Tendon rupture (positive control outcome); dysglycaemia.
Ian Douglas - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Jeremy Brown - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
- Collaborator -
Clemence Leyrat - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
David Yorston - Collaborator - Tennent Institute of Ophthalmology
Kathryn Mansfield - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Kevin Wing - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Nicholas Galwey - Collaborator - GlaxoSmithKline Services Unlimited (UK)
Patrick Batty - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Stephen Evans - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Yun "Angel" Wong - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
HES Admitted Patient Care;Patient Level Carstairs Index for 2011 Census;Practice Level Carstairs Index for 2011 Census (Excluding Northern Ireland)