amoxicillin-potassium-clavulanate-combination and Stevens-Johnson-Syndrome

Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety.

Topics: Allopurinol; Amoxicillin-Potassium Clavulanate Combination; Carbamazepine; Dideoxynucleosides; Drug Hypersensitivity; Genotype; HLA-B Antigens; Humans; Nevirapine; Pharmacogenetics; Protein Conformation; Stevens-Johnson Syndrome

Rare but severe adverse drug reactions (ADRs) are an important issue in drug development and in the proper usage of drugs during the post-approval phase. The ability to predict patient susceptibility to severe ADRs would prevent drug administration to high-risk patients. This would save lives and ensure the quality of life for these patients, but occurrence of idiosyncratic severe ADRs had been very difficult to predict for a long time. However, in this decade, genetic markers have been found for several ADRs, especially for severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). In this review, we summarize recent progress in identifying genetic markers for SCARS and DILI, and discuss issues that remain unresolved. As for SCARs, associations of HLA-B*15:02 or HLA-A*31:01 and HLA-B*58:01 have been revealed for carbamazepine- and allopurinol-related Stevens-Johnson syndrome and toxic epidermal neclolysis, respectively. HLA-B*57:01 is strongly associated with abacavir-induced hypersensitivity syndrome. Several HLA alleles also demonstrate drug-specific associations with DILI, such as HLA-A*33:03 for ticlopidine, HLA-B*57:01 for flucloxacillin and HLA-DQA1*02:01 for lapatinib. Efforts should be continued to find other genetic markers to achieve high predictability for ADRs, with the goal being development of genetic tests for use in clinical settings.

Topics: Alleles; Allopurinol; Amoxicillin-Potassium Clavulanate Combination; Azetidines; Benzylamines; Carbamazepine; Chemical and Drug Induced Liver Injury; Diclofenac; Dideoxynucleosides; Drug Hypersensitivity; Floxacillin; Genetic Markers; HLA Antigens; HLA-A Antigens; HLA-B Antigens; HLA-DQ alpha-Chains; Humans; Lapatinib; Pharmacogenetics; Quinazolines; Skin; Stevens-Johnson Syndrome; Ticlopidine

Severe cutaneous adverse reactions (SCARs) are potentially lethal adverse drug reactions that involve the skin, mucous membranes, and internal organs, resulting in disability. SCARs include drug-induced epidermal necrolysis, which is Steven Johnson syndrome (SJS)/ Steven Johnson syndrome and toxic epidermal necrolysis overlap (SJS-TEN overlap)/ toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), generalised bullous fixed drug eruption (GBFDE), and acute erythroderma. Awareness of local epidemiology of SCARs plays an important role in prescribing practices by healthcare provider. Recognition of SCARs enables the offending drug to be withdrawn immediately, which is the definitive treatment of SCARs.. This is a retrospective study reviewing SCAR cases reported to the Malaysian Adverse Drug Reactions Advisory Committee (MADRAC) registry at the Department of Dermatology, Hospital Melaka, for 5 years and 3 months from December 2014 to February 2020.. A total of 41 SCARs cases were identified over the study duration. The incidence rate was 0.18%. All 41 cases require hospitalisations, with four cases (9.8%) managed in ICU and one mortality (2.4%) due to SJS-related complication. One patient had two episodes of SCARs. There were 22 male patients and 18 female patients. The majority were Malays (33, 80.5%), followed by Chinese (7, 17.1%) and Indonesian (1, 2.4%). There was no Indian patient with SCARs in this study. The mean age of patients was 47.2±17 years. Drug-induced epidermal necrolysis was the commonest type of SCARs (63.4%), and out of this, SJS accounted for the majority of cases (48.8%). Antibiotic was the main group of offending medication in this SCAR study (29.3%). The top five individual causative drugs of SCARs in sequence include allopurinol, phenytoin, carbamazepine, co-amoxiclav, and cephalexin. Allopurinol was the commonest culprit drug for drug-induced epidermal necrolysis and DRESS, phenytoin for acute erythroderma, and co-amoxiclav for AGEP.. SJS was the most common manifestation and Allopurinol was the commonest culprit drug for SCAR cases in our cohort.

Topics: Acute Generalized Exanthematous Pustulosis; Adult; Allopurinol; Amoxicillin-Potassium Clavulanate Combination; Cicatrix; Dermatitis, Exfoliative; Eosinophilia; Female; Hospitals; Humans; Malaysia; Male; Middle Aged; Phenytoin; Retrospective Studies; Stevens-Johnson Syndrome

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child, Preschool; Drug Hypersensitivity; Humans; Lymphocyte Activation; Male; Photography; Stevens-Johnson Syndrome

Stevens-Johnson syndrome is an uncommon life threatening disease generally induced by drugs. Antibiotics, mainly sulphonamides, are the most involved drugs in Stevens-Johnson syndrome in children. Co-amoxiclav is a well tolerated antibiotic. It has never been reported to cause, lonely this syndrome in children. Herein, we report a co-amoxiclav-induced Stevens-Johnson syndrome occurring in an 18-month-old child. The diagnosis of SJS is often challenging in children and other possible diseases should be ruled out. The etiology of this syndrome is not yet fully understood. It is thought to be mediated by an immunologic mechanism. Management involves early identification, withdrawal of the culprit drug and rapid initiation of supportive therapies.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Humans; Infant; Male; Stevens-Johnson Syndrome

Lyell's syndrome or toxic epidermal necrolysis (TEN) is an extremely rare and dangerous severe skin disorder characterized by a high proportion of cutaneous lesions leading to necrosis and subsequent shedding of the epidermis over large areas of skin after an idiosyncratic reaction triggered by a drug. The patients who suffer it pathophysiologically have similar complications to those seen in major burns. TEN traditionally has been treated with immunomodulators such as glucocorticoids, intravenous gammaglobulin, cyclophosphamide, thalidomide or plasmapheresis. A variable, and sometimes contradictory response, has been obtained in some series. Cyclosporin A has been tested as a single immunomodulator in patients with TEN since the end of the 90 s in a limited number series. The results have improved in regards to survival compared with studies with other drugs. We report three consecutive cases of toxic epidermal necrolysis treated with cyclosporin A in this article.

Topics: Adult; Allopurinol; Amoxicillin-Potassium Clavulanate Combination; Cyclosporine; Female; Humans; Immunologic Factors; Male; Middle Aged; Remission Induction; Stevens-Johnson Syndrome

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Humans; Lung Neoplasms; Male; Middle Aged; Ofloxacin; Skin; Stevens-Johnson Syndrome

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Etanercept; Exanthema; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Middle Aged; Receptors, Tumor Necrosis Factor; Stevens-Johnson Syndrome

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Humans; Male; Mycoplasma Infections; Mycoplasma pneumoniae; Stevens-Johnson Syndrome

The skin infections are common in pediatrics, ranging from furonculosis or impetigo to the severe forms of necrotizing dermohypodermitis. The general antibiotic treatments are not always indicated but when they are, they must take into account the resistance of two main species of bacteria (Staphylococcus aureus and Streptococcus pyogenes), the pharmacokinetics-pharmacodynamic parameters and the severity and type of infection. Two situations should be treated by topical treatements: limited impetigo and furonculosis. The two topical antibiotics used preferentially are mupirocine and fucidic acid. Soon, a third topical antibiotic, reptamuline will complete these. For uncomplicated superficial skin infections justifying an oral antibiotic, amoxicillin-clavulanate offers the best guarantee of efficiency. Poor pharmacodynamic-pharmacokinetic must lead to not prescribe oral M penicillins. In case of allergy, a first-generation cephalosporin, a macrolide (if the susceptibility of the strain was checked) or pristinamycine (after 6 years of age) are acceptable alternatives. For dermohypodermitis bacterial antibiotic of choice remains amoxicillin-clavulanate through IV route, to be active against S. pyogenes but also S. aureus and anaerobic bacteria. The IV route is maintained until regression general signs and a relay orally by the same drug is then possible. For toxinic syndromes and necrozing fascitis clindamycin should be added to a beta-lactam because of its action on protein synthesis in particular reducing the toxins production.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cellulitis; Cephalosporins; Child; Drug Resistance, Bacterial; Fasciitis, Necrotizing; Furunculosis; Fusidic Acid; Humans; Impetigo; Injections, Intravenous; Macrolides; Methicillin-Resistant Staphylococcus aureus; Mupirocin; Penicillins; Pristinamycin; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Scalded Skin Syndrome; Staphylococcal Skin Infections; Staphylococcus aureus; Stevens-Johnson Syndrome; Streptococcal Infections; Streptococcus pyogenes

To describe a patient who developed hepatic failure, Stevens-Johnson syndrome (SJS), and died after receiving amoxicillin/clavulanate therapy.. A 37-year-old white man without significant past medical history received a 10-day course of amoxicillin/clavulanate for treatment of pneumonia. Thirty-two days after starting amoxicillin/clavulanate, he developed jaundice, rash, pruritus, and increasing fatigue. On further evaluation, with the exclusion of toxicity from other drugs or diseases, the time course to development of cholestatic jaundice correlated with the use of amoxicillin/clavulanate. The patient consequently died with progressive hepatic failure, renal failure, and SJS.. Hepatic injury has been reported with amoxicillin/clavulanate. Signs and symptoms of jaundice and pruritus may appear up to to six weeks after stopping therapy. Most cases of liver injury have been benign and reversible on discontinuation of the amoxicillin/clavulanate. Reported hepatic reactions have been mainly cholestatic, with some mixed cholestatic/hepatocellular liver function test abnormalities.. Clinicians should be aware of amoxicillin/clavulanate as a drug capable of causing hepatitis with eventual systemic dysfunction. While recovery is usually complete following withdrawal of the drug, in patients with rash associated with hepatic dysfunction, renal insufficiency, or other unusual symptoms, earlier consideration of initiating systemic steroids or liver transplantation referral, in hopes of avoiding progressive systemic response, might be worthwhile.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Blood Chemical Analysis; Drug Therapy, Combination; Fatal Outcome; Humans; Liver Failure; Male; Pneumonia; Renal Insufficiency; Stevens-Johnson Syndrome

Six cases of drug-induced toxic epidermal necrolysis treated in a burns unit are presented. The mean skin loss was 67.3 per cent of the total body surface area. Two patients developed renal failure and two had ocular symptoms. The mortality rate was 50 per cent, with two patients dying from septicaemia and one from respiratory and renal failure. The diagnosis of toxic epidermal necrolysis can be confirmed by skin biopsy. We recommend that this disease is treated in a burns unit so that both adequate wound care and essential intensive supportive treatment can be given. Antibiotics are indicated only for specific infections such as septicaemia or pneumonia. Steroids have been shown to increase greatly the mortality from septic complications and are not recommended. The mortality ranges from 10 per cent to 70 per cent and bad prognostic factors include increasing age, greater than 50 per cent of body surface skin loss and neutropenia.

Topics: Adolescent; Adult; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Antimalarials; Chlorpromazine; Clavulanic Acids; Diagnosis, Differential; Drug Combinations; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Pyrimethamine; Retrospective Studies; Stevens-Johnson Syndrome; Sulfadoxine; Trimethoprim, Sulfamethoxazole Drug Combination; Zimeldine