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Quinolone-associated tendonitis: a potentialproblem in COPD? MW Butler, JF Griffin, WR Quinlan, TJ McDonnell Departments of Respiratory Medicine, Radiology and Orthopaedics, St Vincent’s University Hospital, Dublin, Ireland.
Background Quinolones have traditionally had limited application in the area of community-acquired respiratory
tract infections due to poor cover against Streptococcus pneumoniae. This trend is changing with the broader spectrum of newer fluoroquinolones. A rare serious side effect of fluoroquinolones is tendinopathy.
Aims This study describes two cases of levofloxacin-associated tendinopathy in patients with severe chronic
obstructive pulmonary disease (COPD) and the implications and mechanisms involved are discussed.
Conclusions The finding of two cases of levofloxacin-induced tendinopathy in our patients suggests that the prob-
lem may be more frequent than previously considered. Patients with COPD treated with fluoroquinolones may have other risk factors for tendinopathy such as advanced age, corticosteroid use and renal impairment and merit Fluoroquinolone antibiotics have been in use for over 20 years.
A 55-year-old Caucasian male with a history of severe COPD In particular, they have been used for the treatment of Gram- (FEV1 18% predicted) presented in April 2000 with findings negative sepsis and are well tolerated with a good safety pro- characteristic of an acute infective exacerbation. He had normal file.1,2 However, their activity spectrum has tended to limit their renal function and severe steroid-induced osteopenia and was use to hospitals and as a second line agent in the community.3 undergoing assessment for possible lung transplantation. He A rare but debilitating side effect of fluoroquinolones is that of had no previous tendinopathy and there had been no change tendonitis, first reported in 1983 with norfloxacin but most to his medical therapy for the previous six months. In hospital frequently associated with ciprofloxacin, with a number of case he was treated conventionally with oxygen, nebulised bron- chodilators, rapidly reducing intravenous and oral corticos- Recently, newer fluoroquinolone agents have been devel- teroids to zero and commenced on a 10-day course of treat- oped such as levofloxacin and moxifloxacin, with increased ment with oral levofloxacin at a dose of 500mg once daily. He activity against Gram-positive organisms including Streptococcus pneumoniae.3 Such an activity spectrum has On the last day of treatment with levofloxacin he began to increased their usefulness and they are now recommended bysome authorities for both inpatient and outpatient manage-ment of community-acquired pneumonia and acute exacer-bations of chronic obstructive pulmonary disease (COPD).6This will presumably increase the use of the newerquinolones in the population with COPD, particularly inprimary care. Such patients may be older and frequentlyhave concomitant steroid use, risk factors in themselves fortendonitis.4 Two cases of levofloxacin-associated tendinopa-thy in patients with severe COPD are described and theimplications and mechanisms involved discussed.
Case report 1A 70-year-old Caucasian male with severe COPD (FEV1 35%predicted) presented in July 2000 with symptoms and signs ofa mild acute infective exacerbation. He had been treated forpulmonary tuberculosis at the age of 28. He had no previoustendinopathy, renal failure or quinolone therapy and had nochange in his medications for over a year. He had not been onregular steroid medication and had received occasional reduc-ing courses of oral corticosteroids in the past.
He was commenced on a 10 day course of oral levofloxacin at a dose of 500mg once daily as an outpatient. Five days aftercompleting the course of levofloxacin the patient began tocomplain of bilateral ankle pain. He was diagnosed with fluo- Figure 1. Longitudinal ultrasound scan of left-mid Achilles
roquinolone-induced tendonitis and underwent physiotherapy tendon demonstrates significant tendon thickening (measur-
and ultrasound examination of his Achilles tendons that ing 1.3cm; normal 0.4-0.7cm in thickness). There is altered
revealed bilateral rupture (see Figures 1 and 2). He was subse- echogenicity within the thickened tendon, (arrows) indicating
quently referred for surgical repair.
tendon injury. P, posterior; A, anterior; H, head; F, foot.
Irish Journal of Medical Science • Volume 170 • Number 3 Quinolone-associated tendonitis: a potential problem in COPD? notice pain in the Achilles tendon bilaterally. His symptoms got metabolism, a marker of tendon function, in canine tendinous progressively worse over a period of two weeks to the extent tissue.8 Physiologic concentrations of the drug were shown to that he had difficulty walking. His GP referred him for physio- cause increased matrix degrading activity, decreased matrix syn- therapy and an ultrasound examination of his Achilles tendons thesis and decreased fibroblast cell proliferation. These findings that out-ruled rupture. He steadily improved with rest, bilater- suggest a possible mechanism of fluoroquinolone-associated al ankle-foot supports and oral non-steroidal, anti-inflammato- tendonitis. Histologic examination of biopsies of ciprofloxacin- ry therapy. His symptoms resolved fully after a period of three associated tendinopathy reveal an inflammatory response simi- lar to that observed in overuse syndromes involving the sametendons.9 Recognised risk factors for quinolone-induced tendinopathy Quinolones have traditionally had limited application in the include advanced age, corticosteroid use, previous tendinopa- area of community-acquired respiratory tract infections where thy and renal failure as quinolones are excreted renally.4 The S. pneumoniae must be covered by any first-line antibiotic used development of newer fluoroquinolones with a broader spec- for empiric therapy. This trend is changing with the emergence trum will increase their use in patients with COPD.6,10 Increased of the newer fluoroquinolones with their extended activity age, steroid use and impaired renal function are found in this against such respiratory pathogens.3 The incidence of population and consequently such patients may have a higher quinolone-associated tendinopathy is unknown and difficult to incidence of tendonitis associated with quinolone therapy. The evaluate given its rarity and the lack of prospective studies. In finding of two cases of levofloxacin-induced tendinopathy in our review of the English language literature, there has been our patients suggest that the problem may be more frequent one previous report of levofloxacin-induced tendonitis7 and than previously considered. Our series suggests that patients reports have also been made to the manufacturer from post- with COPD treated with fluoroquinolones merit particular vig- ilance for signs of tendonitis, as prompt cessation of the offend- Pathologic mechanisms contributing to quinolone-induced ing drug may presumably avoid the need for surgery.
tendinopathy are poorly understood. In vitro studies havedemonstrated a direct effect of ciprofloxacin on fibroblast 1. Owens RC, Ambrose PG. Clinical use of the fluoro-quinolones. Med Clin North Am 2000; 84 (6): 1447-69.
2. Stahlman R, Lode H. Toxicity of quinolones. Drugs 1999;58 Suppl 2: 37-42.
3. Moss PJ, Finch RG. The next generation: fluoro-quinolones in the management of acute lower respiratoryinfection in adults. Thorax 2000; 55: 83-5.
4. Harrell RM. Fluoroquinolone-induced tendiopathy: whatdo we know? South Med J 1999; 92(6): 622-5.
5. Huston KA. Achilles tendonitis and tendon rupture due tofluoroquinolone antibiotics. New Eng J Med 1994; 331: 748.
6. Bartlett JG, Breiman RF, Mandell LA et al. Community-acquired pneumonia in adults: guidelines for management.
Clin Infect Dis 1998; 26: 811-38.
7. Lewis JR, Gums JG, Dickensheets DL. Levofloxacin-induced bilateral Achilles tendonitis. Ann Pharmacother1999; 33 (7-8): 792-5.
8. Williams RJ III, Attia E, Wickiewicz TL, Hannafin JA. Theeffect of ciprofloxacin on tendon, paratenon, and capsularfibroblast metabolism. Am J Sports Med 2000; 28 (3): 364-9.
9. Movin TGA, Gad A, Guntner P et al. Pathology of Achillestendon in association with ciprofloxacin treatment. FootAnkle Int 1997; 18: 297-9.
10. Huchon G, Woodhead M, Gialdroni-Grassi G et al.
Guidelines for management of adult community-acquired Figure 2. Longitudinal scan of right-mid Achilles tendon
lower respiratory infections. Eur Respir J 1998; 11: 986-91.
shows marked thinning of the tendon (between arrowheads)
indicating an almost complete tear. Areas of decreased
Correspondence to: Dr Timothy McDonnell, St Vincent's echogenicity (arrows) are due to haematoma. P, posterior;
University Hospital, Elm Park, Dublin 4, Ireland. Tel.: (01) A, anterior; H, head; F, foot.
Irish Journal of Medical Science • Volume 170 • Number 3

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