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Reoccurrence of Levofloxacin-Induced Tendinitis by Phenoxymethylpenicillin Therapy After 6 Months: a Rare Complication of Fluoroquinolone Therapy?

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Reoccurrence of Levofloxacin-Induced Tendinitis by Phenoxymethylpenicillin Therapy After 6 Months: a Rare Complication of Fluoroquinolone Therapy? Case Report Chemotherapy 2003;49:90–91 Received: October 7, 2002 Accepted: January 2, 2003 DOI: 10.1159/000069776 Reoccurrence of Levofloxacin-Induced Tendinitis by Phenoxymethylpenicillin Therapy after 6 Months: A Rare Complication of Fluoroquinolone Therapy? Christoph Schindler David Pittrow Wilhelm Kirch Institute of Clinical Pharmacology, Medical Faculty of the Dresden University of Technology, Dresden, Germany Levofloxacin has been characterized as safe and un- Symptoms usually resolve within a few weeks, but in likely to cause severe adverse events. Ball et al. [1] 10% of patients they may persist for several months. reported that adverse events associated with fluoroquino- Pharmacovigilance data revealed that tendinitis occurred lones range from 0.5% to almost 7%. New second-genera- in 1/500,000 levofloxacin prescriptions, with tendon rup- tion fluoroquinolones such as levofloxacin have an ex- tures only in 1/1,6 million prescriptions [3], but there are tended spectrum of antimicrobial activity compared with probably a considerable number of unidentified cases. older substances but a similar safety profile. Tendinopathy has been most frequently reported with The potential of fluoroquinolones to induce tendinitis perfloxacin, but also occurs with levofloxacin [4]. We and even tendon rupture, usually of the Achilles tendon, is describe for the first time a patient with levofloxacin-asso- low but well documented [2–7]. Although different patho- ciated tendinitis presenting with reoccurring symptoms physiological hypotheses are discussed, the mechanisms induced by phenoxymethylpenicillin therapy 6 months of this effect are poorly understood. Studies performed on after stopping levofloxacin treatment. rats suggest a toxic effect of fluoroquinolones on cellular A 65-year-old nonfebrile asymptomatic woman was components of connective tissue structures [2]. Lesions prescribed levofloxacin 500 mg/day for antibiotic treat- experimentally induced in rats by fluoroquinolone treat- ment of Yersinia-reactive arthritis in August 2001. After ment were characterized by edema and mononuclear cell day 10 of daily treatment with 500 mg levofloxacin, the infiltration in the inner sheath of the Achilles tendon, patient developed a painful inflammatory tendinopathy with infiltration into the adjacent synovial membrane and of the Achilles tendon of the right leg. Levofloxacin was joint space. Cellular pathological effects observed in the stopped immediately and the symptoms resolved within 3 cartilage and tendons show many identical features, indi- weeks after immobilization of the Achilles tendon. cating that quinolone-induced arthropathy and tendopa- The patient has a history of chronic bronchial asthma thy are probably different clinical manifestations of the and has been on oral low-dose steroids for 24 years, a same toxic effect on cellular components of connective known risk factor for developing fluoroquinolone-in- tissue structures [2]. However, the impact of additional duced tendinitis. In February 2002, phenoxymethylpeni- factors, if any, in determining susceptibility to such ad- cillin 600,000 IE (3 tablets) a day was prescribed after verse effects remains unclear. dental surgery. After taking the second dose of penicillin, © 2003 S. Karger AG, Basel Christoph Schindler, MD ABC 0009–3157/03/0492–0090$19.50/0 Institute of Clinical Pharmacology, Medical Faculty, Dresden University of Technology Fax + 41 61 306 12 34 Fiedlerstrasse 27, D–01307 Dresden (Germany) E-Mail [email protected] Accessible online at: Tel. +49 351 458 2027, Fax +49 351 458 4341 www.karger.com www.karger.com/che E-Mail [email protected] the patient developed again tendinopathy of the Achilles enced a tendinopathy after levofloxacin may be at risk of tendon of the right leg with painful induration, very simi- suffering a recurrence of their tendinitis following penicil- lar to the clinical manifestation induced by levofloxacin. lin, especially if they exhibit additional risk factors. Nev- Penicillin was discontinued and therapy was switched to ertheless, the mechanisms of tendinitis as a class-related clindamycin which was given for another 4 days. The side effect of fluoroquinolones remain unclear. patient’s subjective discomfort improved rapidly within This case report gives rise to the suspicion that a posi- 48 h after penicillin had been discontinued. After placing tive history of levofloxacin-associated tendinitis could the Achilles tendon at rest, the symptoms of tendinitis probably complicate any further antibiotic therapy in pre- completely resolved within 3 weeks. disposed patients. Phenoxymethylpenicillin could act as We informed the German Federal Institute for Drugs a trigger for the reoccurrence of tendinitis. As a potential and Medical Devices and the Drug Commission of the differential diagnosis for our patient’s symptoms after German Medical Profession. According to their database, phenoxymethylpenicillin therapy we cannot completely no other cases of levofloxacin-associated tendinitis reoc- exclude the development of enthesitis of the right heel as a curring after phenoxymethylpenicillin-therapy have ever reaction to Yersinia infection. However, this would not been reported. explain the rapid improvement of symptoms after stop- Age, renal dysfunction, magnesium deficiency and ping penicillin therapy and therefore seems unlikely. Dur- long-time steroid therapy have been identified as risk fac- ing therapy with clindamycin, no symptoms of tendinitis tors for quinolone-associated tendinitis [5]. Therefore, reoccurred. This very special case suggests a penicillin- some authors even recommend avoiding fluoroquino- induced side effect. Further research is necessary to clari- lones in elderly patients, especially those receiving higher fy the pathophysiologic mechanisms of phenoxymethyl- doses of corticosteroid therapy [6]. In very rare instances, penicillin. and for unknown reasons, patients who already experi- References 1 Ball P, Mandell L, Niki Y, Tillotson G: Com- 3 Carbon C: Comparison of side effects of levo- 6 Pierfitte C, Royer RJ: Tendon disorders with parative tolerability of the newer fluoroquino- floxacin versus other fluoroquinolones. Che- fluoroquinolones. Therapie 1996;51:419–420. lone antibacterials. Drug Saf 1999;21:407– motherapy 2001;47(suppl 3):9–14. 7Ribard P, Audisio F, Kahn MF, De Bandt M, 421. 4 Fleisch F, Hartmann K, Kuhn M: Fluoroqui- Jorgensen C, Hayem G, Meyer O, Palazzo E: 2 Shakibaei M, Pfister K, Schwabe R, Vormann nolone-induced tendinopathy: Also occurring Seven Achilles tendinitis including 3 compli- J, Stahlmann R: Ultrastructure of Achilles ten- with levofloxacin. Infection 2000;28:256–257. cated by rupture during fluoroquinolone thera- dons of rats treated with ofloxacin and fed a 5 De Sarro A, De Sarro G: Adverse reactions to py. J Rheumatol 1992;19:1479–1481. normal or magnesium-deficient diet. Antimi- fluoroquinolones. An overview on mechanistic crob Agents Chemother 2000;44:261–266. aspects. Curr Med Chem 2001;8:371–384. Reoccurrence of Levofloxacin-Induced Chemotherapy 2003;49:90–91 91 Tendinitis.
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