Providing wide coverage against gram-positive and gram-negative organisms, fluoroquinolones are a class of broad-spectrum antibiotics that are credited with having revolutionised healthcare when they were first introduced in the late 1980s.
After serving as first-line treatment for decades for various infections, such as those of the respiratory and urinary tracts, their use has been restricted in recent years, with the newest update in January 2024, owing to rare but very serious long-lasting, sometimes permanent, disabling side effects from their use.
However, despite this, fluoroquinolones are still heavily prescribed, with nearly 38 000 systemic fluoroquinolones still being prescribed by GPs across England (as of November 2023) (Lipanovic, 2024). This article will delve into the use, side effects, regularly restrictions and future of fluoroquinolone prescribing.
Fluoroquinolone use
In the UK, there are currently five fluoroquinolones licensed for use, which can be taken orally, given intravenously or via inhalation. These include the most common, ciprofloxacin, which is used to treat gram-negative infections, as well as delafloxacin, ofloxacin, and newer-generation agents, levofloxacin and moxifloxacin, which are effective against gram-positive bacteria (Lipanovic, 2024). They exhibit their antimicrobial activity via the inhibition of type II and type IV topoisomerase, which are needed in the replication, transcription, repair and recombination of DNA.
Fluoroquinolones are used in such a wide array of conditions that they are mentioned in 13 separate guidelines issue by the National Institute for Health and Care Excellence (NICE). They are used to treat respiratory infections such as hospital- or community-acquired pneumonia, bronchiectasis, chronic obstructive pulmonary disease (COPD) and tuberculosis. They are also used in urinary tract infections (UTIs), kidney infection (pyelonephritis) and prostatitis. In addition, they are prescribed for cirrhosis, gastro-oesophageal reflux disease, ear infections (otitis media) and neutropenic sepsis in people with cancer.
Fluoroquinolones are also commonly used for penicillin allergies. However, importantly, while 5.6% of the UK population are said to carry a label of penicillin allergy, it is estimated that fewer than 10% of these actually have a true allergy (Savic et al, 2022). This means that the allergy status of up to 4 million people in the UK may be incorrect (Royal Pharmaceutical Society (RPS), 2023) and many more people are likely being prescribed fluoroquinolones for this purpose unnecessarily. To help reduce the incorrect labelling of people with penicillin allergies (and associated inappropriate prescribing), the RPS (2023) has recently published a penicillin allergy checklist.
Adverse effects
Despite the broad range of indications for fluoroquinolones, they are not without their risks, which has become increasingly apparent with their long-term use since the 1980s. They have been shown to result in rare but serious and potentially irreversible musculoskeletal, nervous, psychiatric and sensory side effects such as musculoskeletal damage, psychiatric disorders, gastroenteritis, peripheral neuropathy and aortic aneurysm (Baggio et al, 2021; Medicines and Healthcare products Regulatory Agency (MHRA), 2024).
Potentially permanent musculoskeletal side effects of fluoroquinolones include tendonitis and tendon rupture. Reports of suspected musculoskeletal side effects associated with ciprofloxacin, the most commonly used fluoroquinolone, are currently at their highest, with 342 potential reactions across 197 reports in 2023 (Lipanovic, 2024).
Mental health effects associated with fluoroquinolones can include depression, suicidal thoughts or attempts of suicide (MHRA, 2023a). Adverse effects linked to fluoroquinolones have been reported irrespective of patients' age or risk factor profile and are said to occur in at least one in every 10 000 people who take a fluoroquinolone (MHRA, 2024). There are also concerns surrounding the bacterial resistance of fluoroquinolones and according to the World Health Organization (WHO) AWaRe (Access, Watch, Reserve) antibiotic book, they should only be used as second-line or essential first-line options and only for a limited number of infections.
Regulatory changes
As a result of the disabling long-term side effects that have been linked to the use of fluoroquinolones, noted via the increasing reports on the MHRA Yellow Card scheme, the MHRA restricted their use in 2019. After this restriction was put in place, their prescription steadily declines from close to 60 000 prescriptions per month down to less than 40 000 prescriptions but then hit a plateau in April 2021, with 37 969 fluoroquinolone prescriptions across GP surgeries in England prescribed in November 2023 (Lipanovic, 2024).
As a result, the MHRA has published three drug safety updates concerning fluoroquinolones in the last year, with the most recent being in January 2024. The 2023 restrictions noted not to prescribe fluoroquinolones for mild-to-moderate or self-limiting infections, or non-bacterial conditions (MHRA, 2023b). The most recent update highlights that fluoroquinolones should only be prescribed in cases where other recommended antibiotics are inappropriate (MHRA, 2024).
To further crack down on the high prescribing rate of fluoroquinolones, NHS England, the UK Health Security Agency (UKHSA) and NICE have come together in a multi-agency effort and are actively seeking out suitable alternatives to treat common infections.