Elevated Hepatic Transaminases Associated with Telithromycin Therapy
Elevated Hepatic Transaminases Associated with Telithromycin Therapy
Purpose: A case of mild hepatocellular injury associated with the administration of telithromycin in a patient with no risk factors for hepatotoxicity is presented.
Summary: A 44-year-old man with no significant past medical history arrived at the emergency room after six days of high fever, chills, headache, neck stiffness, and back pain. Five days earlier, he visited a family medicine clinic for his symptoms and oral telithromycin 800 mg daily was prescribed for a suspected upper-respiratory-tract infection. The patient stopped taking the drug after three days due to persistent symptoms. On admission, the patient's laboratory tests revealed an aspartate transaminase (AST) concentration of 68 units/L, an alanine transaminase (ALT) value of 155 units/L, and an erythrocyte sedimentation rate of 40 mm/hr. The patient was not taking any long-term medications, had taken only aspirin for his fever, and denied the use of alcohol and illegal drugs. The patient was admitted to the general medical unit with a diagnosis of possible viral hepatitis. His urine culture was negative, and serology tests later revealed no evidence of hepatitis A, B, or C. Ibuprofen, pantoprazole, and enoxaparin were prescribed. On hospital day 2, the patient's AST and ALT concentrations had decreased to 50 and 110 units/L, respectively. By day 3, the patient's symptoms had improved and he remained afebrile. His AST and ALT values had further decreased to 41 and 105 units/L, respectively. He was then diagnosed with acute viral upper-respiratory-tract infection with mild hepatotoxicity associated with telithromycin and was discharged home with orders for follow-up at the family medicine clinic.
Conclusion: A patient without risk factors for hepatotoxicity developed mild elevations in hepatic transaminases after receiving telithromycin for the treatment of a suspected upper-respiratory-tract infection.
Telithromycin is the first of a new class of antibiotics known as ketolides. It is a semisynthetic molecule similar to the macrolides, with side-chain modifications on the 14-membered ring structure, which allow it to be active against macrolide-resistant organisms. The mechanisms of action of macrolides and ketolides are similar. Both bind to the 70S bacterial ribosome, ultimately preventing protein synthesis. However, ketolides possess enhanced binding capability to domain II of the 23S ribosomal RNA, part of the 50S ribosomal subunit, allowing these antibiotics to maintain their position on the ribosome despite ribosomal alterations. In addition, the ketolides can prevent the formation of the 50S ribosomal subunit. These properties give ketolides activity against multidrug-resistant Streptococcus pneumoniae (MDRSP and erythromycin-resistant S. pneumoniae.
Telithromycin is approved for the treatment of mild-to-moderate community-acquired pneumonia (CAP), including CAP caused by MDRSP, in patients age 18 years or older. However, the use of telithromycin for the treatment of respiratory infections caused by Haemophilus influenzae remains controversial, as its activity against this organism is variable. Nonetheless, telithromycin has gained popularity as a frequently prescribed antibiotic for patients with common respiratory illnesses.
Phase III clinical trials revealed telithromycin to be generally well tolerated. Although some of the patients enrolled in these trials experienced elevations in alanine transaminase (ALT) levels, none were considered to be clinically significant. Other early clinical studies also found that patients treated with telithromycin had other laboratory abnormalities indicative of liver toxicity. More recently, telithromycin has been reported to cause severe hepatic dysfunction. Three published case reports have described severe hepatotoxicity and death related to telithromycin use. We present a case of mild hepatocellular injury associated with the administration of telithromycin in a patient with no risk factors for hepatotoxicity.
Purpose: A case of mild hepatocellular injury associated with the administration of telithromycin in a patient with no risk factors for hepatotoxicity is presented.
Summary: A 44-year-old man with no significant past medical history arrived at the emergency room after six days of high fever, chills, headache, neck stiffness, and back pain. Five days earlier, he visited a family medicine clinic for his symptoms and oral telithromycin 800 mg daily was prescribed for a suspected upper-respiratory-tract infection. The patient stopped taking the drug after three days due to persistent symptoms. On admission, the patient's laboratory tests revealed an aspartate transaminase (AST) concentration of 68 units/L, an alanine transaminase (ALT) value of 155 units/L, and an erythrocyte sedimentation rate of 40 mm/hr. The patient was not taking any long-term medications, had taken only aspirin for his fever, and denied the use of alcohol and illegal drugs. The patient was admitted to the general medical unit with a diagnosis of possible viral hepatitis. His urine culture was negative, and serology tests later revealed no evidence of hepatitis A, B, or C. Ibuprofen, pantoprazole, and enoxaparin were prescribed. On hospital day 2, the patient's AST and ALT concentrations had decreased to 50 and 110 units/L, respectively. By day 3, the patient's symptoms had improved and he remained afebrile. His AST and ALT values had further decreased to 41 and 105 units/L, respectively. He was then diagnosed with acute viral upper-respiratory-tract infection with mild hepatotoxicity associated with telithromycin and was discharged home with orders for follow-up at the family medicine clinic.
Conclusion: A patient without risk factors for hepatotoxicity developed mild elevations in hepatic transaminases after receiving telithromycin for the treatment of a suspected upper-respiratory-tract infection.
Telithromycin is the first of a new class of antibiotics known as ketolides. It is a semisynthetic molecule similar to the macrolides, with side-chain modifications on the 14-membered ring structure, which allow it to be active against macrolide-resistant organisms. The mechanisms of action of macrolides and ketolides are similar. Both bind to the 70S bacterial ribosome, ultimately preventing protein synthesis. However, ketolides possess enhanced binding capability to domain II of the 23S ribosomal RNA, part of the 50S ribosomal subunit, allowing these antibiotics to maintain their position on the ribosome despite ribosomal alterations. In addition, the ketolides can prevent the formation of the 50S ribosomal subunit. These properties give ketolides activity against multidrug-resistant Streptococcus pneumoniae (MDRSP and erythromycin-resistant S. pneumoniae.
Telithromycin is approved for the treatment of mild-to-moderate community-acquired pneumonia (CAP), including CAP caused by MDRSP, in patients age 18 years or older. However, the use of telithromycin for the treatment of respiratory infections caused by Haemophilus influenzae remains controversial, as its activity against this organism is variable. Nonetheless, telithromycin has gained popularity as a frequently prescribed antibiotic for patients with common respiratory illnesses.
Phase III clinical trials revealed telithromycin to be generally well tolerated. Although some of the patients enrolled in these trials experienced elevations in alanine transaminase (ALT) levels, none were considered to be clinically significant. Other early clinical studies also found that patients treated with telithromycin had other laboratory abnormalities indicative of liver toxicity. More recently, telithromycin has been reported to cause severe hepatic dysfunction. Three published case reports have described severe hepatotoxicity and death related to telithromycin use. We present a case of mild hepatocellular injury associated with the administration of telithromycin in a patient with no risk factors for hepatotoxicity.
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