Correspondence

Acute Eosinophilic Hepatitis from Trovafloxacin

N Engl J Med 2000; 342:359-360February 3, 2000

Article

To the Editor:

According to the Food and Drug Administration, trovafloxacin, a broad-spectrum quinolone antibiotic, has been associated with more than 100 cases of hepatic toxicity. Fourteen of these cases involved acute liver failure, with transplantation required in four patients; five patients died of liver disease. More than 300,000 prescriptions for trovafloxacin were written monthly in the United States before use of the drug was limited to certain serious infections in an inpatient setting.

There have been a few reports of hepatic toxicity associated with the use of quinolones1-3 but to our knowledge no published reports of toxicity associated with trovafloxacin. We describe a patient in whom severe acute hepatitis developed while he was receiving trovafloxacin for chronic sinusitis. This 66-year-old man presented with nausea, vomiting, malaise, and abdominal distention. He had taken 100 mg of trovafloxacin daily for four weeks for treatment of refractory chronic sinusitis. His medical history included hypertension, gout, osteoarthritis, and chronic idiopathic angioedema. He had been treated with losartan, metoprolol, hydrochlorothiazide, allopurinol, nabumetone, and doxepin for several years. He rarely drank alcohol.

On examination, the patient was febrile and had mild tachypnea. His abdomen was markedly distended but not tender; bowel sounds were decreased. There was no jaundice, ascites, or organomegaly. The initial white-cell count was 8000, with 16 percent eosinophils; the serum aspartate aminotransferase level, 537 IU per liter; the serum alanine aminotransferase level, 841 IU per liter; the direct bilirubin level, 1.0 mg per deciliter; the total bilirubin level, 1.6 mg per deciliter; the alkaline phosphatase level, 111 IU per liter; the blood urea nitrogen level, 30 mg per deciliter; and the creatinine level, 3.2 mg per deciliter. Tests for hepatitis A, B, and C infection were negative. A computed tomographic scan of the abdomen showed fluid adjacent to the liver and spleen, bilateral pleural effusions, and consolidation at the base of the right lung, but no hepatic parenchymal abnormality. Ultrasonography of the abdomen showed coarse echogenicity, a finding consistent with necrosis. Neither gallstones nor ascites was seen; the bile ducts were not distended. A biopsy specimen of the liver showed centrilobular and focal periportal necrosis and eosinophilic infiltration (Figure 1Figure 1Biopsy Specimen of the Liver (Hematoxylin and Eosin).). The sinusoids were dilated and contained lymphocytes and eosinophils; many hepatocytes were undergoing mitosis. A stool sample was positive for Clostridium difficile toxin, which may have accounted for the persistent abdominal distention.

Use of trovafloxacin was discontinued, while use of the other medications was continued. The patient was treated with prednisone for the hepatitis and metronidazole for the C. difficile infection. His hepatic and renal function returned to normal, and the eosinophilia gradually resolved. This is a biopsy-proved case of hepatic toxicity associated with the use of trovafloxacin. We are indebted to Dr. Peter B. Kelsey for permitting us to study this patient.

Henry J.L. Chen, M.D.
Kurt J. Bloch, M.D.
James A. Maclean, M.D.
Massachusetts General Hospital, Boston, MA 02114

3 References

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Citing Articles (17)

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   James H. Lewis, David E. Kleiner. 2012. Hepatic injury due to drugs, herbal compounds, chemicals and toxins. , 645-760.
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   Eric S. Orman, Hari S. Conjeevaram, Raj Vuppalanchi, James W. Freston, James Rochon, David E. Kleiner, Paul H. Hayashi. (2011) Clinical and Histopathologic Features of Fluoroquinolone-Induced Liver Injury. Clinical Gastroenterology and Hepatology 9:6, 517-523.e3
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   P. J. Shaw, P. E. Ganey, R. A. Roth. (2010) Idiosyncratic Drug-Induced Liver Injury and the Role of Inflammatory Stress with an Emphasis on an Animal Model of Trovafloxacin Hepatotoxicity. Toxicological Sciences 118:1, 7-18
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   Aaron J. Pugh, Ashutosh J. Barve, Keith Falkner, Mihir Patel, Craig J. McClain. (2009) Drug-Induced Hepatotoxicity or Drug-Induced Liver Injury. Clinics in Liver Disease 13:2, 277-294
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   Françoise Van Bambeke, Paul M. Tulkens. (2009) Safety Profile of the Respiratory Fluoroquinolone Moxifloxacin. Drug Safety 32:5, 359-378
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   Hiroki Yamaguchi, Hitomi Kawai, Takuyuki Matsumoto, Hiroo Yokoyama, Toshio Nakayasu, Masahiro Komiya, Jingoro Shimada. (2007) Post-Marketing Surveillance of the Safety of Levofloxacin in Japan. Chemotherapy 53:2, 85-103
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   2006. Alatrofloxacin and trovafloxacin. , 46-48.
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   Peter Ball, Ralf Stahlmann, Rolf Kubin, Shurjeel Choudhri, Robert Owens. (2004) Safety profile of oral and intravenous moxifloxacin: Cumulative data from clinical trials and postmarketing studies. Clinical Therapeutics 26:7, 940-950
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    Glenn S. Tillotson, Michael J. Rybak. (2001) New Milestones Achieved in Fluoroquinolone Safety. Pharmacotherapy 21:3, 358-360
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    Shivakumar Chitturi, Geoffrey C. Farrell. (2000) Drug-induced liver disease. Current Treatment Options in Gastroenterology 3:6, 457-462
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    &NA;. (2000) Trovafloxacin. Reactions Weekly &NA;:788, 12
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