amoxicillin-potassium-clavulanate-combination and Jaundice

Leptospirosis is an anthropozoonose, an animal disease transmissible to humans, caused by a spirochete of the genus Leptospira that lives mainly among rodents but also in wetlands. It occurs worldwide, particularly in Asia, Latin America and Africa. In Europe, the incidence is small (except in France and Great Britain, where its frequency has increased in recent years) but the frequency may be underestimated. Some areas overseas are particularly affected. In France, the potential epidemic of leptospirosis is subject to climatic variations, justifying a constant monitoring of the disease provided by the National Reference Centre (CNR) of leptospires. Transmission to humans primarily occurs through contact with environments contaminated by the urine of infected animals. The disease can affect the liver and kidneys (hepatonephritis) as cytolysis, cholestasis and renal failure associated with fever. A coagulopathy usually accompanies the clinical table. Its diagnosis is difficult because of the clinical polymorphism. Early diagnosis of leptospirosis allows effective medical care, improving patient outcomes. This is currently based on gene amplification (PCR) or serology positive by the microscopic agglutination test (MAT), which is the reference method. Its evolution is usually favorable with appropriate antibiotic treatment (aminopenicillin). However 5-10% of symptomatic patients have a severe multisystem defaillance. Nearly a century after the discovery of the causative agent, this zoonosis remains a public health problem, zoonosis priority in terms of virulence, its reporting is mandatory in our country. We report the case of a severe form of hepatonephritis due to water contaminated with Leptospira observed in Northern France.

Topics: Acute Kidney Injury; Adult; Amoxicillin-Potassium Clavulanate Combination; Animal Husbandry; Animals; Anti-Bacterial Agents; Bacteremia; Disease Progression; Doxycycline; Fever; France; Humans; Immunologic Tests; Jaundice; Leptospira interrogans serovar icterohaemorrhagiae; Male; Occupational Diseases; Ofloxacin; Rats; Renal Dialysis; Sheep; Species Specificity; Water Microbiology; Water Pollution; Weil Disease; Zoonoses

To alert clinicians to the hepatotoxic potential of Augmentin (amoxycillin and clavulanic acid), a widely prescribed antibiotic, in susceptible patients, and to point out that the hepatic illness may be delayed but serious and protracted.. Case reports of patients with Augmentin-induced jaundice referred to the gastroenterology departments in three major teaching hospitals, and a review of cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC).. Eight patients with nine episodes of Augmentin-induced jaundice personally treated by the authors from March 1988 to February 1990 are described. A further 19 patients reported to ADRAC from May 1987 to November 1989 are discussed. All patient histories were carefully reviewed to ensure that there was a temporal relationship between the course of Augmentin and the onset of the hepatitic illness and that other causes of jaundice were reasonably excluded.. Jaundice developed in some of these patients several weeks after drug treatment was completed. The illness may be protracted over many weeks. As yet, there has been no case of progressive disease leading to the liver failure.. The data suggest that a hypersensitivity reaction to clavulanic acid is the likely cause of the jaundice. Therefore, Augmentin, although an important antibiotic, should be reserved for severe infections for which amoxycillin is unsuitable.

Topics: Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Clavulanic Acids; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Jaundice; Male; Middle Aged; Time Factors

Amoxicillin-clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs.. Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials.. One hundred and seventeen subjects with AC-DILI were identified from the cohort (n = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents (n = 479). Those with AC-DILI were older (60 vs. 48 years, P < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI.. AC-DILI causes a moderately severe, mixed hepatocellular-cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation.

Topics: Age Factors; Alanine Transaminase; Alkaline Phosphatase; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Bilirubin; Black or African American; Chemical and Drug Induced Liver Injury; Cholestasis; Cohort Studies; Ethnicity; Female; Hispanic or Latino; Humans; Jaundice; Jaundice, Obstructive; Liver; Male; Middle Aged; Prospective Studies; Registries; Sex Distribution; Time Factors; United States; White People

Leptospirosis is a disease caused by spp. Leptospira, also known as Weil's disease if it manifests with jaundice. It can be associated with respiratory, renal, hepatic and haematological complications and most importantly carries a high mortality when untreated. We describe a case of a 53 year old man presenting with myalgia and fever in whom the diagnosis of leptospirosis was not initially considered. Following a deterioration in his condition a careful history revealed an apparent brief exposure to animal urine and subsequent grossly positive Leptospira serology. Treatment of his condition led to complete resolution after a brief stay on the intensive care unit. This case highlights the atypical nature of a presentation of Leptospirosis, its respiratory complications, and importance of serological testing in its diagnosis.

Topics: Acute Kidney Injury; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Clarithromycin; Diagnosis, Differential; Fluid Therapy; Humans; Jaundice; Leptospira; Lung; Male; Middle Aged; Oxygen Inhalation Therapy; Pneumonia, Mycoplasma; Radiography; Serologic Tests; Treatment Outcome; Weil Disease

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

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Anticholesteremic Agents; Autoantibodies; Chemical and Drug Induced Liver Injury; Diagnostic Techniques, Digestive System; Female; Genes, MHC Class II; Hepatitis, Autoimmune; Humans; Immunoglobulins; Jaundice; Liver; Liver Failure, Acute; Male; Registries

To determine the incidence and causes of drug-induced jaundice in a rural community.. A retrospective analysis of 800 patients presenting to a single-centre jaundice referral system serving a community of 400 000 over a period of 66 months (1998-2004). Standard criteria for drug-induced liver injury were applied to patients with a putative diagnosis of drug-induced jaundice. The incidence rates per prescription of drug-induced jaundice caused by co-amoxiclav and flucloxacillin were derived from local and national annual prescription rates.. The incidence of drug-induced jaundice was 1.27 (confidence limits 0.85-1.8) per 100 000 per annum in a total of 28 patients (17 men, mean age 69 years). Antibiotics were the commonest cause of jaundice (n=21). Of these, co-amoxiclav (n=9) and flucloxacillin (n=7) caused the majority with an incidence rate per 100 000 prescriptions of 9.91 (4.6-18.0) and 3.60 (1.5-7.2), respectively. Co-amoxiclav-induced jaundice was observed more commonly in elderly males (age 65 years, M : F 7 : 2). In those patients with flucloxacillin or co-amoxiclav-induced jaundice, bilirubin ranged from 54 to 599 mumol/l (267 mumol/l) with a resolution of jaundice between 30 and 90 days. Counselling with regard to potential drug-induced liver injury and reporting of the adverse reaction had been performed in 1/28 patients.. 8.1% patients with no biliary obstruction and jaundice had a drug-induced and predominantly antibiotic-related aetiology particularly affecting an elderly population. We recommend that all patients receiving co-amoxiclav and flucloxacillin should be counselled before the therapy regarding the potential risk of jaundice and that an alternative antibiotic to co-amoxiclav is used if possible in men over the age of 60 years.

Topics: Age Factors; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; England; Female; Floxacillin; Humans; Incidence; Jaundice; Male; Middle Aged; Retrospective Studies; Rural Health

Topics: Amoxicillin-Potassium Clavulanate Combination; Cholelithiasis; Elbow; Female; Hand Dermatoses; Humans; Hypercholesterolemia; Jaundice; Middle Aged; Xanthomatosis

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

Toxic hepatitis secondary to amoxycillin-clavulanic acid is an infrequent clinical picture. Most of the cases are reported to have a benign course. We report two cases of severe hepatic failure following amoxycillin-clavulanic acid use. One of the cases had cholestatic features primarily, and the other had hepatocellular injury prominently. The first case had also findings of trombotic trombositic purpura and had a fatal course.

Topics: Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Jaundice; Male

We are describing a case of undesired side effect of the cure (toxic hepatocellular damage) by Augmentin. The main symptoms were jaundice and pruritus. This is the next documented case of the hepatocellular damage by Augmentin in Poland. In the conclusion, we draw the attention to the role of interview in the diagnosis of the illness described and therapeutic management.

Topics: Aged; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Humans; Jaundice; Liver Diseases; Male; Pruritus

Hepatotoxity associated with amoxicillin/clavulanic acid is usually a self-limited disease with complete recovery. We report a rapidly progressing liver disease with ductopenia and portal fibrosis in a 3-year-old boy treated with Augmentin.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bile Duct Diseases; Bile Ducts, Intrahepatic; Child, Preschool; Cholestasis; Drug Eruptions; Drug Therapy, Combination; Humans; Jaundice; Liver; Liver Cirrhosis; Male

Jaundice associated with co-amoxiclav has been increasingly recognised. We aimed to characterise its clinical and histological features and to investigate linkage with human leucocyte antigen class II haplotypes.. We identified cases in the west of Scotland in the period 1991-1997 and performed polymerase chain reaction amplification and oligonucleotide probing on whole blood.. Twenty two cases were identified (10 male, mean age 59.1 years). Jaundice occurred a median of 17 days after drug commencement, with a median peak bilirubin level of 225 micromol/l (range 84-598) and median duration of jaundice 69 days (range 29-150). Two patients had primary biliary cirrhosis and two other patients had persistently abnormal liver biochemistry on follow up. One death occurred in a frail elderly woman despite resolving jaundice. The frequency of jaundice was 1 in 78 209 co-amoxiclav prescriptions. Liver biopsy, available in 12 patients, showed perivenular bilirubinostasis, accompanying reactive ceroid laden macrophages, and portal inflammation with focal injury to interlobular bile ducts. Fourteen of 20 patients had DRB1*1501 compared with 27 of 134 controls (p<2.5 x 10(-6); odds ratio (OR) 9.25; relative risk (RR) 6.43). Of these, seven patients were homozygous for DRB1*1501(p< 10(-8); OR 35.54; RR=8.68) compared with two of 134 controls. All patients with DRB1*1501 had the extended haplotype DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602. There were no clinical or histological differences between genotypes.. Co-amoxiclav associated hepatotoxicity may have a genetic basis and be delayed, severe, and prolonged, although complete recovery is usual.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Bilirubin; Biopsy; Case-Control Studies; Drug Therapy, Combination; Female; Haplotypes; HLA-D Antigens; Humans; Jaundice; Liver Function Tests; Male; Middle Aged; Oligonucleotide Probes; Polymerase Chain Reaction

To identify risk factors for the development of amoxycillin-clavulanic acid associated jaundice.. Retrospective case-control study. Cases were selected from those reported to the Adverse Drug Reactions Advisory Committee from the time of introduction of amoxycillin-clavulanic acid to Australia in 1986 until December 1993.. Thirty-four cases, defined as individuals who developed jaundice within eight weeks of starting amoxycillin-clavulanic acid, with a biochemical picture of cholestasis, normal calibre bile ducts and no other recognised causes of jaundice or recent use of other hepatotoxic drugs, were selected. For each case, four controls who had been prescribed amoxycillin-clavulanic acid without developing jaundice were randomly selected from the patient register of the prescribing doctor.. Increasing age was a risk factor for amoxycillin-clavulanic acid associated jaundice; patients over 55 years had an odds ratio of 16.1 (95% confidence interval [CI], 2.9-88.9) compared with patients less than 30 years. Men had an odds ratio of 2.5 (95% CI, 1.1-5.4) compared with women, although the proportion of men in the study group was larger than in the reported cases overall. History of serious medical illness, drug dose, route and duration of therapy, other medications, smoking and previous drug allergies or use of amoxycillin-clavulanic acid were not significantly associated with jaundice.. Because of the higher risk of jaundice with increasing age, the risk-benefit ratio of amoxycillin-clavulanic acid should be carefully considered in older patients. Further assessment is necessary to clarify the association between jaundice and male sex.

Topics: Adult; Age Factors; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Clavulanic Acids; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Jaundice; Male; Middle Aged; Retrospective Studies; Risk Factors; Sex Factors

Fifteen cases of hepatitis related to a combination of amoxycillin and clavulanic acid are reported. Most patients were aged 60 years or more and there were more men than women (sex ratio 4:1). The amoxycillin-clavulanic acid had been given at doses ranging from 0.5 to 6 g/day (mean 2 g/day) for seven to 60 days (mean 18 days). In 11 cases, the first symptoms appeared one to four weeks after stopping treatment. Jaundice was observed in all patients and was frequently associated with pruritus. Serum aminotransferase activities were increased in all patients and were generally two to 10 times the upper limit of normal. Serum alkaline phosphatase activity was considerably increased, from two to seven times the upper limit of normal. Histological examination of the liver, performed in seven patients, showed centri- or panlobular cholestasis in all cases, associated with granulomatous hepatitis in one. The prognosis of amoxycillin-clavulanic acid induced hepatitis seemed to be good. None of the patients exhibited biological or clinical features of hepatic failure and the course of the disease was characterised by the resolution of jaundice within one to eight weeks and a complete recovery within four to 16 weeks. Taking into account the number of treated subjects and reported cases, we estimated the risk of developing hepatitis with this drug combination to be very low, probably below 1/100,000. Our data suggest that the risk of hepatotoxicity may be increased in elderly men given lengthy treatment. The association of hepatitis and signs of hypersensitivity may suggest an immunoallergic mechanism of hepatotoxicity in some patients.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Jaundice; Male; Middle Aged; Pruritus; Sex Factors; Time Factors