amoxicillin-potassium-clavulanate-combination and Liver-Diseases

The diagnosis of drug-induced liver injury is often one of exclusion with initial suspicion based on circumstantial evidence. The natural history, characteristics and limitations of this exclusion process are revised. Also, the numerous published attribution algorithms for evaluation of drug-related liver abnormalities are described and their characteristics and differences are illustrated with true patients from our clinical experience. Situations that complicate the diagnosis such as age, sex, concomitant use of other drugs, genetic polymorphism in metabolic pathways involved in activation or disposition of therapeutic drugs and drug-drug interactions are described. Finally, developing approach to diagnosis of drug-induced liver injury, different of attribution algorithms, are evaluated and explained using a new method based in a Bayesian approach developed and published by the authors. The authors' vision of all these potential advances and their clinical utility is provided.

Topics: Amoxicillin-Potassium Clavulanate Combination; Bayes Theorem; Chemical and Drug Induced Liver Injury; Female; Humans; Liver Diseases; Male; Polymorphism, Genetic

There is a growing body of evidence that amoxicillin-clavulanic acid may induce severe adverse effects in patients.. A medline search of case reports and reviews on amoxicillin-clavulanic acid induced adverse effects was performed. The criteria of a consensus conference on the reporting of drug-induced liver disease were applied.. Amoxicillin-clavulanic acid has been associated with drug-induced cholestatic hepatitis in 208 reported patients. In 153 evaluable patients there were 106 males and 47 females with a mean age of 60 years (1-90). Liver associated co-morbidity and co-medication does not play a major part in the development of disease. In most instances respiratory tract infection and sinusitis were treated by amoxicillin-clavulanic acid with a mean treatment duration of 13.9 days and a reaction time until first onset of jaundice of 25.2 days average. Infection and cholestasis from other reason were ruled out in most patients. Liver injury was classified according to laboratory parameters to be hepatocellular in 35 patients, cholestatic in 24 patients and mixed in 83 patients. Normalization of liver enzymes was observed 11.5 weeks after onset of drug administration (average); three of 153 patients did not survive the adverse event.. Amoxicillin-clavulanic acid which is marketed for treatment of respiratory infections and sinusitis/otitis may in some cases induce severe adverse effects and death in patients of different age, especially if they are on multidrug regimens. In consideration of this fact many authors recommend to reflect carefully, whether amoxicillin-clavulanic acid is necessary in treatment of patients with localized or uncomplicated infections. If amoxicillin-clavulanic acid is prescribed, transaminase, alkaline phosphatase and bilirubin tests should be obtained within the first two weeks and after four to five weeks after beginning of treatment to recognize early enough undesired hepatic side effects.

Topics: Adolescent; Adult; Age Distribution; Americas; Amoxicillin-Potassium Clavulanate Combination; Asia; Australia; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cholestasis; Comorbidity; Europe; Female; Humans; Infant; Liver Diseases; Liver Failure; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies; Sex Distribution

Drug-induced liver injury is a significant health issue, yet the exposure-based incidence remains to be characterized.. We aimed to assess the frequency, phenotypes, and outcomes of acute liver injury associated with amoxicillin/clavulanate using a large electronic health record system.. Using the Veterans Health Administration electronic health record system, we developed the framework to identify unexplained acute liver injury, defined by alanine aminotransferase and/or alkaline phosphatase elevation temporally linked to prescription records of amoxicillin/clavulanate, a major culprit of clinically significant drug-induced liver injury, excluding other competing causes. The population was subcategorized by pre-existing liver conditions and inpatient status at the time of exposure for the analysis.. Among 1,445,171 amoxicillin/clavulanate first exposures in unique individuals [92% men; mean age (standard deviation): 59 (15) years], 6476 (incidence: 0.448%) acute liver injuries were identified. Of these, 4427 (65%) had alternative causes, yielding 2249 (incidence: 0.156%) with unexplained acute liver injuries. The incidence of unexplained acute liver injury was lowest in outpatients without underlying liver disease (0.067%) and highest in inpatients with pre-existing liver conditions (0.719%). Older age, male sex, and American Indian or Alaska Native (vs White) were associated with a higher incidence of unexplained acute liver injury. Cholestatic injury affected 74%, exhibiting a higher frequency with advanced age, inpatient exposure, and pre-existing liver conditions. Hepatocellular injury with bilirubin elevation affected 0.003%, with a higher risk at age >45 years. During a 12-month follow-up, patients with unexplained acute liver injury had a higher adjusted overall mortality risk than those without evident acute liver injury.. This framework identifies unexplained acute liver injury following drug exposure in large electronic health record datasets. After validating in other systems, this framework can aid in deducing drug-induced liver injury in the general patient population and regulatory decision making to promote drug safety and public health.

Topics: Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Female; Humans; Liver Diseases; Male; Phenotype; Veterans Health

A 45-year-old man with dilated cardiomyopathy presented with acute leg pain and erythema suggestive of necrotising fasciitis. Initial surgical exploration revealed no necrosis and treatment for a soft tissue infection was started. Blood and tissue cultures unexpectedly grew a Gram-negative bacillus, subsequently identified by an automated broth microdilution phenotyping system as an extended-spectrum β-lactamase producing Escherichia coli. The patient was treated with a 3-week course of antibiotics (ertapenem followed by ciprofloxacin) and debridement for small areas of necrosis, followed by skin grafting. The presence of E. coli triggered investigation of both host and pathogen. The patient was found to have previously undiagnosed liver disease, a risk factor for E. coli soft tissue infection. Whole genome sequencing of isolates from all specimens confirmed they were clonal, of sequence type ST131 and associated with a likely plasmid-associated AmpC (CMY-2), several other resistance genes and a number of virulence factors.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactams; Ciprofloxacin; Diagnosis, Differential; Drug Resistance, Multiple, Bacterial; Ertapenem; Escherichia coli; Escherichia coli Infections; Floxacillin; Follow-Up Studies; Genome, Bacterial; Gentamicins; Humans; Liver Diseases; Male; Meropenem; Middle Aged; Sequence Analysis, DNA; Soft Tissue Infections; Thienamycins; Treatment Outcome; Vancomycin

Liver cancers in children are primitive (hepatoblastoma, fibrolamellar hepatocarcinoma, sarcomas), or arise on a genetic or viral disease. Their treatment is a combination of chemotherapy (hepatoblastoma) and surgery. Neonatal hemangioendotheliomas may induce heart failure. They are now successfully treated with propranolol. Focal nodular hyperplasia is the most frequent benign tumour in older children and adolescents. Drug hepatotoxicity is not very frequent. Antipyretic drugs may induce severe side effects. Liver failure due to valproic acid is diagnostic of a respiratory chain disorder. The liver side effects of antituberculous and antiretroviral drugs should be monitored. Intestinal failure-associated liver disease is common and can be prevented or treated. Early referral to a specialized centre is important for the prognosis.

Topics: Acetaminophen; Amoxicillin-Potassium Clavulanate Combination; Analgesics, Non-Narcotic; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anti-Retroviral Agents; Anticonvulsants; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Child; Humans; Intestinal Diseases; Liver Diseases; Liver Neoplasms; Mushroom Poisoning

The aim of our study was to compare three search strategies using a computerized administrative database to identify cases of idiosyncratic drug-induced liver injury (DILI) due to amoxicillin/clavulanic acid, phenytoin, valproic acid, and isoniazid.. In search 1, electronic medical records from patients seen between 1994 and 2004 with an ICD-9-CM code of acute liver injury were identified and cross-searched for the specific drug names in the dictation text. In search 2, all patients with an ICD-9-CM code of drug poisoning/overdose due to one of the four study drugs were identified. In search 3, patients with a poisoning code as well as an acute liver injury code were identified.. Review of the records from the 7,395 search 1 patients yielded 51 DILI cases (0.7%). In contrast, the 566 search 2 patients yielded only three DILI cases (0.5%). Finally, search 3 provided the greatest specificity but a low rate of detection with only two patients (3.9%) having DILI due to one of the four drugs.. Acute liver injury ICD-9-CM codes combined with a text search of the dictated medical record yielded the greatest number of DILI cases but was less specific than crossing acute liver injury and poisoning codes. Use of ICD-9-CM codes to identify rare adverse events like DILI remains problematic and highlights the need for prospective surveillance networks.

Topics: Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infant; International Classification of Diseases; Isoniazid; Liver Diseases; Male; Medical Records Systems, Computerized; Michigan; Middle Aged; Phenytoin; Population Surveillance; Sensitivity and Specificity; United States; Valproic Acid

Amoxicillin-clavulanate (AC) hepatotoxicity has been reported to exhibit a higher predominance of cholestatic types of damage, especially in males. However, the determinants of its clinical expression are unknown. This study prospectively evaluated the profile of AC hepatotoxicity. Data on all cases of hepatotoxicity reported to the Spanish Registry attributed to AC and assessed as definite or probable on the Council for International Organizations of Medical Sciences (CIOMS) scale were collated and compared to published case series. Hepatotoxicity related to amoxicillin-clavulanate was identified in 69 patients (36 males; mean age 56 years) representing 14% of all cases of hepatotoxicity submitted to the Registry. There was an overall sex distribution and the predominant pattern of lesion was hepatocellular (36%) which occurred at a shorter duration of treatment (P < .03). Mean time lapse between therapy initiation and jaundice onset was 16 days. Late onset of symptoms following end of treatment occurred in half the cases. Multiple logistic regression analysis identified advancing age as the factor associated with the development of cholestatic/mixed type of injury (odds ratio for an age interval for 1 year: 1.045 [95% CI = 1.013-1.078; P = .005). An unfavorable outcome was seen in 7% of patients. In conclusion, age is the most important determinant in the biochemical expression of AC hepatotoxicity; younger age is associated with cytolytic damage and shorter treatment duration, whereas cholestatic/mixed type of damage is related to older age and prolonged AC therapy.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Female; Humans; Liver; Liver Diseases; Logistic Models; Male; Middle Aged; Prospective Studies; Spain

A chronic adverse reaction may occur in some instances of drug-induced liver injury (DILI), even despite drug cessation. In our study, we obtained records from a Spanish registry and evaluated cases of DILI with biochemical evidence of long-term damage. Chronic outcome was defined as a persistent biochemical abnormality of hepatocellular pattern of damage more than 3 months after drug withdrawal or more than 6 months after cholestatic/mixed damage. Data on 28 patients with a chronic clinical evolution (mean follow-up 20 months) between November 1995 and October 2005 were retrieved (18 female; overall mean age 55 yr) and accounted for 5.7% of total idiosyncratic DILI cases (n = 493) submitted to the registry. The main drug classes were cardiovascular and central nervous system (28.5% and 25%, respectively), which, in contrast, represented only 9.8% and 13%, respectively, of all DILI cases. The most frequent causative drugs were amoxicillin-clavulanate (4 of 69 cases), bentazepam (3 of 7 cases), atorvastatin (2 of 7 cases), and captopril (2 of 5 cases). Patients with cholestatic/mixed injury (18 of 194 cases [9%]) were more prone to chronicity than patients with hepatocellular injury (10 of 240 cases; P < .031). In the case of chronic hepatocellular injury, 3 patients progressed to cirrhosis and 2 to chronic hepatitis. In the cholestatic/mixed group, liver biopsy indicated cirrhosis in 1 patient and ductal lesions in 3 patients. In conclusion, cholestatic/mixed type of damage is more prone to become chronic while, in the hepatocellular pattern, the severity is greater. Cardiovascular and central nervous system drugs are the main groups leading to chronic liver damage.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Atorvastatin; Azepines; Captopril; Cardiovascular Agents; Central Nervous System Agents; Chemical and Drug Induced Liver Injury; Chronic Disease; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Heptanoic Acids; Humans; Liver; Liver Diseases; Male; Middle Aged; Pyrroles; Registries; Spain

Progress in the understanding of susceptibility factors to drug-induced liver injury (DILI) and outcome predictability are hampered by the lack of systematic programs to detect bona fide cases.. A cooperative network was created in 1994 in Spain to identify all suspicions of DILI following a prospective structured report form. The liver damage was characterized according to hepatocellular, cholestatic, and mixed laboratory criteria and to histologic criteria when available. Further evaluation of causality assessment was centrally performed.. Since April 1994 to August 2004, 461 out of 570 submitted cases, involving 505 drugs, were deemed to be related to DILI. The antiinfective group of drugs was the more frequently incriminated, amoxicillin-clavulanate accounting for the 12.8% of the whole series. The hepatocellular pattern of damage was the most common (58%), was inversely correlated with age (P < .0001), and had the worst outcome (Cox regression, P < .034). Indeed, the incidence of liver transplantation and death in this group was 11.7% if patients had jaundice at presentation, whereas the corresponding figure was 3.8% in nonjaundiced patients (P < .04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% CI: 4.1-151; P < .0001), hepatocellular damage (OR = 7.9; 95% CI: 1.6-37; P < .009), and higher baseline plasma bilirubin value (OR = 1.15; 95% CI: 1.09-1.22; P < .0001).. Patients with drug-induced hepatocellular jaundice have 11.7% chance of progressing to death or transplantation. Amoxicillin-clavulanate stands out as the most common drug related to DILI.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Analysis of Variance; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Incidence; Liver; Liver Diseases; Liver Failure; Male; Middle Aged; Odds Ratio; Probability; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Sex Distribution; Spain; Survival Analysis

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