Laurence Baril,1 Thierry Maisonobe,2 Martine Jasson-Molinier,3 Julien Haroche,1 François Bricaire,1 and Eric Caumes1

1Services de Maladies Infectieuses et de Médecine Tropicale, 2Service de Neuropathologie, and 3Service de Pharmacovigilance, Hôpital de la Pitié-Salpêtrière, Paris, France

Reprints or correspondence: Dr. Eric Caumes, Service de Maladies Infectieuses, Hôpital de la Pitié-Salpêtrière, 47 boulevard de l'Hôpital, 75013 Paris, France.

Fluoroquinolones have an excellent safety record and good tolerability. The main adverse effects involve the gastrointestinal tract (5%), skin (1%2%, including phototoxicity), and CNS (<1%) [1]. We report a case of rhabdomyolysis that occurred shortly after the patient began taking ofloxacin.

In April 1998, 9 days after a 2-week stay in Cuba, a 54-year-old woman was admitted with a 1-week history of fever (40°C) and diarrhea (>10 stools daily, without blood or mucous). The day before admission, urine culture yielded Escherichia coli susceptible to amoxicillin, aminoglycosides, and fluoroquinolones. Intravenous ofloxacin therapy (400 mg/day) was started in the emergency room. She had been taking diltiazem for 9 years and also clonazepam for 2 years.

On admission to our department, she was afebrile, and abdominal palpation showed only mild pain of the left colon. The physical examination was otherwise normal. Measurements made 9 h after the first 200-mg intravenous dose of ofloxacin included the following values: WBC count, 14.0 × 109/L, with 80% segmented neutrophils and no hypereosinophilia; C-reactive protein, 430 mg/L; creatinine, 185 mmol/L; and creatine phosphokinase, 2000 IU (normal, <200 IU). Cultures of blood and urine were negative, as were fecal culture and direct examination for bacterial pathogens and parasites. On the second hospital day, she had marked tenderness, predominantly over her proximal muscles, and complained of muscle weakness; arthralgia and tendonitis were absent. Sensory and motor nerve conduction studies were normal. On the fourth hospital day, her C-reactive protein level fell to 4 mg/L; her WBC count was normal but her creatine phosphokinase level had increased to 24,000 IU. Her lactate dehydrogenase level was 18,000 IU, and her aspartate aminotransferase level was 15 times normal without renal failure.

Ofloxacin was considered as the possible cause of the acute nontraumatic rhabdomyolysis and was withdrawn 4 days after its introduction. We found no other explanation for the rhabdomyolysis, despite thorough infectious, metabolic, and immunologic testing. Axial fast-spin T2-weighted MRI of the legs showed an increased signal and fluid in both quadriceps, predominantly on the right. Needle electrode examination showed no spontaneous activity except low-amplitude and shortduration motor unit potentials in all muscles, pointing to a myopathic process. A deltoid muscle biopsy performed 1 week after onset showed no congenital or metabolic signs on histoenzymatic examination and no inflammatory infiltrate or infectious foci on serial paraffin sections. At this time, circulating muscle-enzyme activities had returned to normal, and the myalgia and muscle weakness had disappeared.

Ofloxacin probably played a causative role in the rhabdomyolysis, even though similar reports in the literature are very rare. Other antibiotics, such as trimethoprim-sulfamethoxazole [2], have been incriminated in the onset of rhabdomyolysis. Blain et al. [3] and Fujii et al. [4] reported cases of severe rhabdomyolysis in elderly patients receiving a combination of ciprofibrate and norfloxacin and receiving ciprofloxacin hydrochloride, respectively. The chronological criteria concerning the drug challenge and rechallenge and the clinical and extraclinical semiological criteria were suggestive of the drug-effect relationship. We did not perform a voluntary rechallenge of the drug. Thus, the intrinsic imputability [5] relating the possible drug-effect relationship between the drug and the occurrence of rhabdomyolysis points to the effect of the drug. Cases of rhabdomyolysis in patients undergoing treatment with fluoroquinolones should be reported to pharmacovigilance centers to ensure that the frequency of this adverse reaction is not underestimated.

References

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