Context
In January 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) released a Drug Safety Update for the prescribing of fluoroquinolone antibiotics (FQAs) including ciprofloxacin, levofloxacin, and ofloxacin. While evidence on which the update was based is yet to be published, concerns have been raised regarding serious adverse effects. This alert expanded upon 2019 guidance limiting their use, although by mid-2023 there had been no significant reduction in FQA prescribing in primary care.1
Most first-line indications for FQA prescribing apply to secondary care, although some, including genitourinary and respiratory infections, apply in primary care, albeit in the context of penicillin allergy or severe infection.
Box 1 describes a clinical case. The outcome is described at the end of the article.
| A 26-year-old female presents with symptomatic, dipstick-positive UTI, which has not responded to an empirical 3-day course of nitrofurantoin. She reports anaphylaxis to penicillin and is cephalosporin naïve. Urine MC&S demonstrated Escherichia coli, sensitive to ciprofloxacin, but resistant to trimethoprim. |
| How would you proceed? |
What are the adverse effects of concern?
Tendonitis and tendon rupture
FQAs are associated with an increased risk of acute tendinopathy and tendon rupture, with ofloxacin significantly more likely to increase the risk of tendon injury than other FQAs.2 Discontinuation is recommended at the first sign of tendonitis.
Aortic aneurysm and dissection
Evidence for risk of aortic aneurysm and dissection (AAD) with FQAs is conflicting, and rates are low (<0.1%).3,4 Nevertheless, if a diagnosis of AAD is suspected, FQAs should be discontinued immediately, particularly in patients with additional risk factors such as family history of aortic aneurysm, or connective tissue disease, such as Marfan syndrome.
Severe arrhythmia and sudden cardiac death
The absolute risk increase of severe arrhythmia or sudden cardiac death with FQAs is low, with one study5 reporting 160 additional cases per 1 000 000. Moxifloxacin was more likely to be associated with arrhythmia than other FQAs. However, the role of severe infection may be synergistic, and patients with other risk factors for QT interval prolongation may have arrhythmia risk increased by concomitant use of FQAs.
Delirium and psychosis
While many antibiotics are associated with adverse neuropsychiatric effects, these odds seem particularly increased in FQAs and similar to those of psychotic symptoms in macrolides.6 These can range from insomnia to psychosis.
Symptoms typically resolve spontaneously upon withdrawal, but informing patients of potential mood changes is advisable. Detailed evidence contributing to the MHRA alert, in particular regarding suicide risk, is yet to be published.
Peripheral neuropathy
Evidence of a relationship between peripheral neuropathy and FQAs is significant, with risk increasing by around 3% for each additional day of FQA therapy.7
Dysglycaemia
Association between FQAs and dysglycaemia is clinically significant and particular care should be taken in patients with diabetes who are concurrently receiving corticosteroid therapy. Moxifloxacin and levofloxacin appear most likely to cause dysglycaemia, while ciprofloxacin is least likely.8,9
What factors increase risk?
Older patients
In one UK study in primary care, 2–6% of all Achilles tendon injuries could be attributed to FQA use in those aged 60 or over.2
Corticosteroids
Risk of tendon rupture is significantly increased in patients who concurrently use oral corticosteroids.10
Cumulative exposure
Repeated exposure to FQAs is associated with increased risk, which appears to persist for approximately 8 weeks post-treatment.11
Renal failure
In men over 45, FQAs were 2 times more likely to cause acute kidney injury. When FQAs were co-prescribed with drugs affecting the renin–angiotensin–aldosterone system, such as ramipril and candesartan, FQAs were almost 4.5 times more likely to cause kidney injury.12
Are topical fluoroquinolones affected by the MHRA alert?
No. Adverse effects of topical FQAs are infrequent and typically mild. In ophthalmic and auricular use, most do not require discontinuation.
What else should the GP consider?
Where national guidance is still being reviewed, some local guidelines have been produced or adapted in response to the MHRA alert and, where guidance still recommends FQAs, they are generally reserved as second-line agents in severe infection and/or penicillin allergy. The advice of an antimicrobial specialist may be valuable in these cases, ideally with available culture results.
In the case of patients presenting with features of epididymoorchitis or prostatitis, FQAs remain first line. It would be reasonable to consider whether urology input can be sought, without delaying treatment. In the case of chronic or recurrent prostatitis symptoms, the GP might also consider differentials, such as chronic pelvic pain syndrome, which may be amenable to non-pharmacological interventions such as physiotherapy.
It may also be sensible to consider whether management of the infection in question is appropriate for primary care, or whether secondary or emergency care would be a more appropriate setting to commence patients on FQAs.
A detailed history taking of drug allergy including the name of the drug indicated, date of adverse reaction or decade of life, and severity (whether admission to hospital or treatment was required) can all improve the basis of clinical decision making in antibiotic choice.
Figure 1 shows the decision-making process for a GP considering prescribing FQAs.
Figure 1. Infographic aid for decision making when considering fluoroquinolone use in primary care. FQA = fluoroquinolone antibiotic. URTI = upper respiratory tract infection.
Some trusts may also facilitate confirmation testing for suspected penicillin allergy, which could be employed pre-emptively in higher-risk groups, such as those with cystic fibrosis or those who use long-term catheters, who face a higher likelihood of FQA-susceptible infections and therefore repeated exposure to FQAs. Unfortunately, waiting lists are often prohibitive.
Summary
FQAs may increase the risk of serious adverse effects but many of these are rare. Awareness of higher-risk patient groups, including those who are co-prescribed oral corticosteroids, and older patients, is important.
There are limited primary care indications for first-line systemic FQA use, but topical use remains permissible.
FQAs can still be prescribed in susceptible infections, and patients should be involved in discussions regarding risk and antimicrobial choice.
Increasing use of microscopy, culture, and sensitivities, with appropriate specialist advice, may facilitate the use of safe and effective alternative antimicrobial agents.
Establishing penicillin allergy status of patients who are more likely to require FQAs may facilitate the safe and effective use of penicillin antibiotics, where a true allergy can be excluded.
Clinical case — outcome
After confirming the patient’s allergy history, treatment options were discussed with the patient, including a longer course of nitrofurantoin, a supervised course of cefalexin with safety netting for allergic reaction, or a course of ciprofloxacin, with safety netting for risk of adverse effects.
Ultimately, the patient had a strong preference for nitrofurantoin, and her symptoms resolved following a 7-day course. Fosfomycin would have been a viable alternative and is increasingly considered second line alongside pivmecillinam, but neither appeared in local guidance at the time and were not considered by the clinician.
Involving microbiology colleagues can highlight recent updates to guidance and guide treatment decisions. Involving patients is also important in making treatment decisions.
Notes
Provenance
Freely submitted; externally peer reviewed.
Competing interests
The authors have declared no competing interests.
- © British Journal of General Practice 2025
