amoxicillin-potassium-clavulanate-combination and Cholestasis--Intrahepatic

The association amoxicillin-clavulanic acid is a widely used medication. Only about 15 cases of cholestatic hepatitis were reported in Belgium between 1990 and 1993; about 100 cases have been reported to the pharmaceutical company. This effect is severe but reversible. The injury is probably idiosyncratic or immunologically based. Age, sex and treatment duration are as many agents of risk. The diagnosis is undertaken on basis of clinical examination, chronological study, biological evolution and histology.

Topics: Age Factors; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cholestasis, Intrahepatic; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Risk Factors; Sex Factors

Amoxicillin/clavulanate is a synthetic penicillin that is currently commonly used, especially for the treatment of respiratory and cutaneous infections. In general, it is a well-tolerated oral antibiotic. However, amoxicillin/clavulanate can cause adverse effects, mainly cutaneous, gastrointestinal, hepatic and hematologic, in some cases. Presented here is a case report of a 63-year-old male patient who developed cholestatic hepatitis after recent use of amoxicillin/clavulanate. After 6 wk of prolonged use of the drug, he began to show signs of cholestatic icterus and developed severe hyperbilirubinemia (total bilirubin > 300 mg/L). Diagnostic investigation was conducted by ultrasonography of the upper abdomen, serum tests for infection history, laboratory screening of autoimmune diseases, nuclear magnetic resonance (NMR) of the abdomen with bile duct-NMR and transcutaneous liver biopsy guided by ultrasound. The duration of disease was approximately 4 mo, with complete resolution of symptoms and laboratory changes at the end of that time period. Specific treatment was not instituted, only a combination of anti-emetic (metoclopramide) and cholestyramine for pruritus.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antiemetics; Antipruritics; Biopsy; Chemical and Drug Induced Liver Injury; Cholangiopancreatography, Magnetic Resonance; Cholestasis, Intrahepatic; Humans; Hyperbilirubinemia; Jaundice; Male; Middle Aged; Risk Factors; Time Factors; Treatment Outcome

Amoxicillin-clavulanate is the most common drug involved in drug-induced liver injury and the single most frequently prescribed product leading to hospitalization for drug-induced liver disease in Spain. The liver damage most frequently associated with amoxicillin-clavulanate is cholestasic type. The latency period between first intake and onset of symptoms is 3-4 weeks on average. A 76-year-old man developed fever, pruritus, and jaundice 3 weeks after having completed treatment with amoxicillin-clavulanate. Liver function tests showed cholestasic hepatitis (up to 50.75 mg/dL of total serum bilirubin level). The ultrasound-guided liver biopsy revealed severe canalicular cholestasis and portal and lobular eosinophilic infiltrates. Prednisone and ursodeoxycholic acid therapy were then prescribed. The patient became symptom-free with normal liver function tests. Amoxicillin-clavulanate can cause hepatocellular, cholestasic, or mixed liver injury. The presence of eosinophilic infiltrates in the liver biopsy and the clinical signs of hypersensitivity in some of the cholestasic cases suggest a pathophysiological immunoallergic mechanism. For this reason, corticosteroid treatment should be considered for patients with severe cholestasic liver injury.

Topics: Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Drug Therapy, Combination; Glucocorticoids; Humans; Liver Function Tests; Male; Prednisone; Treatment Outcome; Ursodeoxycholic Acid

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cholestasis, Intrahepatic; Humans; Male; Middle Aged

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bile Duct Diseases; Child; Cholestasis, Intrahepatic; Humans; Male; Treatment Outcome; Ursodeoxycholic Acid

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cholestasis, Intrahepatic; Humans; Male; Middle Aged

Topics: Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Diagnosis, Differential; Humans; Jaundice; Male; Middle Aged

This report describes two patients who developed jaundice within two weeks of receiving an amoxycillin-clavulanate potassium combination. Causes of jaundice, other than drug administration, were excluded. The patients' jaundice and clinical symptoms did not respond to stopping the drug. Ursodeoxycholic acid (750 mg/day) led to a prompt and sustained improvement in their hyperbilirubinaemia and symptoms such as pruritus and fatigue. These cases suggest that ursodeoxycholic acid may be an effective treatment for drug-associated cholestasis.

Topics: Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Biopsy; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Drug Therapy, Combination; Humans; Liver; Male; Prognosis; Ursodeoxycholic Acid

Topics: Aged; Amoxicillin-Potassium Clavulanate Combination; Bile Ducts, Intrahepatic; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Drug Therapy, Combination; Female; Humans; Time Factors

Amoxycillin/clavulanic acid (Augmentin) has been widely used as a broad spectrum antibiotic since its introduction in 1981, since which time a number of reports of adverse hepatic reaction to the drug combination have been published. This paper describes five patients presenting with cholestatic illness within 8 weeks of a course of amoxycillin/clavulanic acid. The clinical picture indicated a direct link between the illness and the drug combination. Hepatic histology revealed a distinctive focal destructive cholangiopathy in all five patients, which has not previously been reported. Two also showed a granulomatous reaction, which has only previously been reported in one patient. Parallels are drawn with other diseases displaying bile duct destruction, and it is suggested that immunologically mediated drug-induced biliary damage may be involved. One of the five patients developed chronic liver disease with persistence of cholestatic liver biochemical tests, which has not previously been reported. The severity of the reaction and its prolonged course merit wider recognition of the possible adverse hepatic reaction to amoxycillin/clavulanic acid.

Topics: Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Biopsy; Cholestasis, Intrahepatic; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Male; Middle Aged

Two cases (first cases from Poland and Eastern Europe) with liver injury due to amoxycillin-clavulanic acid (augmentin) are reported. Pruritus and jaundice were the main symptoms. Liver biopsy revealed mixed hepatocellular-cholestatic liver injury in both cases. In addition, in one case the microgranulomalike aggregate of inflammatory cells was found. Clinical and laboratory abnormalities returned to normal within 13 weeks.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Clavulanic Acid; Clavulanic Acids; Drug Combinations; Drug Therapy, Combination; Female; Granuloma; Humans; Male; Middle Aged; Respiratory Tract Infections; Tonsillitis

This 70-year-old man experienced an episode of cholestatic hepatitis most likely due to an immunologically mediated reaction to amoxicillin-clavulanate. The episode occurred after cessation of the drug combination. Duration of illness was 16 weeks, and the patient recovered completely.

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Clavulanic Acids; Drug Therapy, Combination; Humans; Liver Function Tests; Male; Sinusitis

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cholestasis, Intrahepatic; Clavulanic Acids; Drug Therapy, Combination; Humans

Two patients who developed a severe but reversible cholestatic jaundice during and after treatment with an amoxicillin/clavulanic acid preparation (Augmentin) are described. The diagnosis of drug-induced intrahepatic cholestasis was based on the clinical course, biochemical pattern and on histological findings. Since amoxicillin alone does not induce liver injury, the combination of amoxicillin and clavulanic acid or clavulanic acid alone could be responsible for this adverse reaction, probably through a metabolic idiosyncrasy or a hypersensitivity mechanism. Although more than 100 cases of hepatotoxic reactions have been reported to the pharmaceutical company (Beecham Laboratories) and several reports have been published, the incidence of hepatotoxicity of this antibiotic is relatively rare, since this antibiotic has been widely used. However, recognition of this benign and reversible cholestatic syndrome is important to avoid unnecessary, expensive and invasive diagnostic procedures.

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cholestasis, Intrahepatic; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Liver; Male

A 75-year-old man developed a biopsy-proven, drug-induced intrahepatic cholestasis after use of amoxycillin trihydrate combined with the beta-lactam inhibitor potassium clavulanate (Augmentin). Cholestatic liver injury is an uncommonly recognized, probably immunologically based adverse reaction to therapy with penicillin and its derivatives.

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cholestasis, Intrahepatic; Clavulanic Acids; Drug Therapy, Combination; Humans; Liver; Male

Five case histories are presented of patients developing cholestatic hepatitis associated with the intake of the antibiotic combination agent amoxicillin and clavulanic acid (Augmentin). In two of these cases, signs of hepatic injury recurred after readministration of this combination but not after the intake of amoxicillin alone. In none of the patients was another cause for cholestatic hepatitis found and extrahepatic causes were excluded by ultrasonography, CT scanning, or ERCP. Most viral causes of hepatic injury were excluded in these patients. With the exception of one patient, who developed a transient rash, no immunoallergic signs were present. Biopsy in two patients showed extensive cholestasis without significant necrosis. Clavulanic acid seems to be responsible for this adverse effect.

Topics: Aged; Alanine Transaminase; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bilirubin; Biopsy; Chemical and Drug Induced Liver Injury; Child, Preschool; Cholestasis, Intrahepatic; Clavulanic Acids; Drug Therapy, Combination; Humans; Male; Middle Aged; Time Factors

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Clavulanic Acids; Drug Therapy, Combination; Humans; Male