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Complications from ciprofloxacin

Gareth Gillespie and Sarah Baggot highlight the risk of tendon ruptures as a complication of ciprofloxacin

The antibiotic ciprofloxacin is widely used in Singapore and Hong Kong – but while its uses are well-known, a rare but well-established complication, tendon rupture, is less so.

MPS has recently handled a number of cases in Singapore where a patient has suffered tendon rupture after taking ciprofloxacin, yet the prescribing doctor was unaware of this complication. Our aim is not so much to influence clinical judgment about appropriate antibiotic use but to increase awareness, so that doctors and patients are better informed during the consent process.

The complication, although not very common, is more widely known in countries such as the United Kingdom and the United States; this article explores the available literature to highlight the complication’s symptoms and signs, patient risk factors, and the likelihood of it occurring.

How common is it?

Ciprofloxacin is part of a group of fluoroquinolone antibiotics and is used to treat respiratory, urinary tract, gastrointestinal and abdominal infections. Fluoroquinolone-associated tendinopathy was first reported in 1983, when a 56-year-old renal transplant patient who was taking norfloxacin for a urinary tract infection with septicemia, developed Achilles tendinopathy.1

Four years later, the first case of tendon rupture associated with ciprofloxacin was reported.2 Since then, there have been nearly 100 case reports and case-controlled studies published that are related to fluoroquinolone-associated tendon injuries.3 4 5Although norfloxacin, ofloxacin, pfloxacin and levofloxacin have been linked to tendon injuries, a study published in 2000 concluded that ciprofloxacin was the most common fluoroquinolone in such cases, appearing in 90% of them.6

Symptoms and signs

Abrupt onset of ciprofloxacin-associated tendon rupture is marked by pain, with other symptoms including swelling, tenderness, and warmth or erythema over tendinopathic sites – the Achilles tendon being the most commonly involved in such cases, occurring in nearly 90%.7 There can be some variation regarding the onset of the tendon rupture: although most occur after two weeks of drug therapy, they can occur a few hours after the initial dose, or up to six months later.3 Suggested factors in the time taken for this onset are an abnormal healing response8 and cystic degeneration.9

Abrupt onset of ciprofloxacin-associated tendon rupture is marked by pain, with other symptoms including swelling, tenderness, and warmth or erythema over tendinopathic sites

Risk factors

Although tendon ruptures are not a hugely common complication, there are a number of factors that make some patients more at risk of developing it. One study reported a mean age of 64 years and a male-to-female ratio of 2:1.10

Others reported risk factors of systemic corticosteroid therapy, renal failure, diabetes mellitus, sports activity and a history of musculoskeletal disorders.11 12 13Such factors must be taken into account in patients when considering prescribing any fluoroquinolone. Following diagnosis of tendon rupture associated with ciprofloxacin or another fluoroquinolone, the medication should be discontinued and the affected joint immobilised.

Informed consent: communicating the risk

The principle of informed consent applies as much to the prescribing of medication as it does to the performance of a surgical procedure

In a recent MPS case in Singapore, a patient experienced tendon pain while taking ciprofloxacin, and complained to their doctor that they weren’t warned of this potential sideeffect. Fortunately for the doctor, the patient accepted that the complication was a rare one and that awareness of it was low in Singapore.

When prescribing any medication, it is essential that you explain the risks to the patient so they can make an informed decision about their treatment. The principle of informed consent applies as much to the prescribing of medication as it does to the performance of a surgical procedure. No matter how rare the risk, patients need to be made aware.

Conclusion

Greater awareness of the complication of tendon ruptures will not only lead to earlier diagnosis and treatment, but it will ensure doctors are able to give the appropriate amount of information to patients when prescribing ciprofloxacin.

It is imperative that patients are equipped with the information they need to make informed choices about their treatment – which will ultimately reduce the likelihood of receiving a complaint or claim.

Case study one

Mr L, aged 82, visited his GP with breathlessness and a sore throat. He suffered from bronchiectasis and had developed regular chest infections over the years, usually treated with ciproxin. He saw GP Dr O, who prescribed 250mgs of ciprofloxacin. A year later, Mr L returned to the surgery and once again saw Dr O with a chest infection – this time he was prescribed 500mgs of ciprofloxacin, for two weeks, following a medication review.

Following completion of this second course of ciprofloxacin, Mr L developed pain around his ankle, radiating up his leg – he phoned the surgery for advice, and was told to take painkillers and call back a couple of days later if there was no improvement. Over the following month, Mr L’s pain did not subside and he repeatedly called his GP surgery for advice – twice he received home visits from Dr O, but at no time did he examine Mr L’s ankle or consider a referral to an orthopaedic surgeon.

Twice he received home visits from Dr O, but at no time did he examine Mr L’s ankle or consider a referral to an orthopaedic surgeon

After a further fortnight, Mr L attended the Emergency Department with worsening pain in both heels and an increasing inability to walk. He was referred to the fracture clinic with a diagnosis of bilateral Achilles tendon rupture. Following the incident, Mr L made a claim against Dr O for failing to diagnose his condition despite numerous opportunities to carry out an examination or make a referral.

Mr L’s legs would only support him for a few minutes at a time and he had to move to a nursing home because he was no longer able to take care of himself. Furthermore, a consultant orthopaedic surgeon, who acted as an expert on the case, said that Mr L’s deformities were inoperable due to his age, and that it was to be expected that Mr L was likely to end up in a wheelchair sooner than he would have had it not been for the bilateral ruptures.

The claim was settled for a substantial sum.

Case study two

Mrs U was a 62-year-old lady who had suffered from emphysema in recent years. She attended her GP, Dr N, with a cough and wheezing; Dr N diagnosed a chest infection and prescribed 500mgs of ciprofloxacin.

Eight days later, Mrs U was visited at home by Dr N after complaining of pain and swelling in her right ankle, and difficulty walking. Dr N did not carry out an examination but prescribed painkillers and gave Mrs U an elasticated support bandage stockinette.

A week later, Mrs U was visited at home by Dr Y. She reported pain in her tendons and said that painkillers were not working. There were no further records made of this visit. On a further three occasions over the next month, Mrs U contacted the surgery with pain in her feet – after her final home visit, again by Dr Y, she was prescribed painkillers.

Eventually, Mrs U self-referred to a consultant physiotherapist, who examined both Achilles tendons and carried out a Simmond’s test, which was positive for the left and negative for the right. Mrs U was referred to the Emergency Department, where she underwent surgery to repair a bilateral Achilles tendon rupture.

Both GPs were criticised for failing to perform the Simmond’s test or a palpation over the tendon, to look for a gap

Mrs U made a claim against both Dr Y and Dr N for the delay in diagnosing her tendon rupture, which led to unnecessary surgery and subsequent scarring on both calves. Both GPs were criticised for failing to perform the Simmond’s test or a palpation over the tendon, to look for a gap. Dr Y admitted to not being aware of the side-effects of ciprofloxacin, and was further criticised for his poor note-keeping during his first home visit to Mrs U.

These case studies are based on real MPS cases but facts have been altered to protect confidentiality.

References

  1. Bailey RR, Kirk JA, Peddie BA, Norfloxacin-induced rheumatoid disease, NZ Med J 96:590 (1983)
  2. McEwan SR, Davey PG, Ciprofloxacin and tenosynovitis, Lancet 2:900 (1988)
  3. Corrao G, Zambon A, Bertu L, Mauri A, Paleari V, Rossi C, Venegoni M, Evidence of tendinitis provoked by fluoroquinolone treatment: a case control study, Drug Saf29:889-96 (2006)
  4. Royer RJ, Pierfitte C, Netter P, Features of tendon disorders with fluoroquinolones, Therapie 49:75-6 (1994)
  5. Pierfitte C, Gillet P, Royer RJ, More on fluoroquinolone antibiotics and tendon rupture, N Engl J Med 332:193 (1995)
  6. Williams RJ 3rd, Attia E, Wickiewicz TL, Hannafin JA, The effect of ciprofloxacin on tendon, paratenon, and capsular fibroblast metabolism, Am J Sports Med 28: 364-9 (2000)
  7. Tsai W C, Fluoroquinolone-associated Tendinopathy, Chang Gung Med J 34:461-7 (2011)
  8. Movin T, Gad A, Guntner P et al, Pathology of the Achilles tendon in association with ciprofloxacin treatment, Foot Ankle Int 18:297-299 (1997)
  9. Petersen W, Laprell H, Insidious rupture of the Achilles tendon after ciprofloxacin-induced tendinopathy. A case report, Unfallchirurg 101:731-734 (1998)
  10. Akali AU, Niranjan NS, Management of bilateral Achilles tendon rupture associated with ciprofloxacin: a review and case presentation, J Plast Reconstr Aesthet Surg 61:830-4 (2008)
  11. van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HG, Stricker BH, Fluoroquinolones and risk of Achilles tendon disorders: case-control study, BMJ324:1306-7 (2002)
  12. Khaliq Y, Zhanel GG, Fluoroquinolone-associated tendinopathy: a critical review of the literature, Clin Infect Dis 36:1404-10 (2003)
  13. Van der Linden PD, van Puijenbroek EP, Feenstra J, Veld BA, Sturkenboom MC, Herings RM, Leufkens HG, Stricker BH, Tendon disorders attributed to fluoroquinolones: a study on 42 spontaneous reports in the period 1988 to 1998,Arthritis Rheum 45:235-9 (2001)
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