ABSTRACT
Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.
ABSTRACT
OBJECTIVE: To characterize the incidence of adverse events (AEs) associated with antibiotics used to treat acute otitis media in children. STUDY DESIGN: We searched MEDLINE for studies conducted between January 1, 1966, and August 25, 2018. Two authors independently assessed potential studies and extracted the data. We included published randomized controlled trials, cross-sectional studies, and cohort studies that evaluated the incidence of diarrhea, generalized rash, diaper rash, and candidal diaper dermatitis associated with the use of amoxicillin, amoxicillin/clavulanate, azithromycin, cefdinir, and placebo in children with acute otitis media. RESULTS: We included 82 studies in the meta-analysis. The incidence of diarrhea, listed from lowest to highest, was azithromycin (2.2%), placebo (6.9%), low-dose amoxicillin (8.7%), cefdinir (13.0%), high-dose amoxicillin (13.8%), and high-dose amoxicillin/clavulanate (18.9%). The incidence of generalized rash, listed from lowest to highest, was azithromycin (1.4%), placebo (2.3%), low-dose amoxicillin (2.9%), high-dose amoxicillin/clavulanate (4.9%), and high-dose amoxicillin (6.5%). In studies of low-dose amoxicillin, we found a higher incidence of diarrhea in studies that used daily diaries to collect information about diarrhea and a lower incidence of generalized rash in studies that reported only rashes judged to be secondary to antibiotic use. CONCLUSIONS: The incidence of AEs varies widely depending on which antibiotic is used and how the information on AEs was collected or reported. The AEs rates reported here may be helpful to clinicians when choosing an antibiotic to treat acute otitis media.
Subject(s)
Anti-Bacterial Agents/adverse effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , Otitis Media/drug therapy , Acute Disease , Child , Global Health , Humans , IncidenceABSTRACT
OBJECTIVE: To evaluate the efficacy and tolerability of amoxicillin/clavulanic (AMX/CLV) acid as treatment for cutaneous actinomycosis. METHODS: We present a long-term follow-up study of cutaneous actinomycosis patients. Cervicofacial (CFA) and abdominal (AA) were recruited during 6 years. Diagnoses were based on clinical and microbiological characteristics; presence of granules, isolation and identification of etiological agents were carried out in each case. Patients received AMX-CLV 875/125 mg BID PO at a maximum period of 12 weeks. RESULTS: Twenty-two cases were enrolled; the mean age was 45.2 years old. Twenty patients (91%) presented CFA and two AA (9%). All patients with CFA had dental caries, seven (35%) with periodontal disease and 10 (50%) had type-2 diabetes mellitus (T2DM). One case of AA had history of intrauterine device and other appendicitis. Granules were observed in all the cases, the main etiological agent was Actinomyces israelii 16/22 (72.7%). Clinical and microbiological cure was achieved in 19/22 cases (86.4%), the remaining patients presented clinical improvement. The average duration of the treatment was 6.6 weeks. Side effects were recorded in 4/19 cases (18.2%), three of them presented nausea and one diarrhea. CONCLUSION: Treatment with AMX/CLV acid showed efficacy in the management of actinomycosis with cutaneous involvement.
Subject(s)
Actinomycosis/drug therapy , Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Skin Diseases, Bacterial/drug therapy , Adult , Aged , Dental Caries/complications , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
We report the in vitro drugs interaction by the resazurin drugs combination microtiter assay (REDCA) of amoxicillin (AMO)/clavulanate (CLAV) with isoniazid (INH), ethambutol (EMB), and rifampicin (RIF) against susceptible and resistant Mycobacterium tuberculosis isolates. The addition of AMO/CLAV to classical antituberculosis drugs should be explored as a promising alternative for the treatment of resistant tuberculosis (TB).
Subject(s)
Amoxicillin/pharmacology , Antitubercular Agents/pharmacology , Clavulanic Acid/pharmacology , Ethambutol/pharmacology , Isoniazid/pharmacology , Mycobacterium tuberculosis/drug effects , Rifampin/pharmacology , Drug Resistance, Multiple, Bacterial , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/isolation & purification , Oxazines/analysis , Xanthenes/analysisABSTRACT
Resistance to ß-lactam/ß-lactamase inhibitors in enterobacteria is a growing problem that has not been intensively studied in Argentina. In the present work, 54/843 enterobacteria collected in a teaching hospital of Buenos Aires city were ampicillin-sulbactam-resistant isolates remaining susceptible to second- and third-generation cephalosporins. The enzymatic mechanisms present in the isolates, which were also amoxicillin-clavulanic acid (AMC)-resistant (18/54) were herein analyzed. Sequencing revealed two different variants of blaTEM-1, being blaTEM-1b the most frequently detected allelle (10 Escherichia coli, 3 Klebsiella pneumoniae, 2 Proteus mirabilis and 1 Raoultella terrigena) followed by blaTEM-1a (1 K. pneumoniae). Amoxicillin-clavulanate resistance seems to be mainly associated with TEM-1 overproduction (mostly in E. coli) or co-expressed with OXA-2-like and/or SHV ß-lactamases (K. pneumoniae and P. mirabilis). A new blaTEM variant (TEM-163) was described in an E. coli strain having an AMC MIC value of 16/8µg/ml. TEM-163 contains Arg275Gln and His289Leu amino acid substitutions. On the basis of the high specific activity and low IC50 for clavulanic acid observed, the resistance pattern seems to be due to overproduction of the new variant of broad spectrum ß-lactamase rather than to an inhibitor-resistant TEM (IRT)-like behavior.
Subject(s)
Amoxicillin-Potassium Clavulanate Combination/pharmacology , Drug Resistance, Bacterial/genetics , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae/enzymology , beta-Lactamases/isolation & purification , Amino Acid Substitution , Argentina/epidemiology , Base Sequence , Cross Infection/epidemiology , Cross Infection/microbiology , DNA, Bacterial/genetics , Disk Diffusion Antimicrobial Tests , Enterobacteriaceae/drug effects , Enterobacteriaceae/genetics , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/epidemiology , Escherichia coli/drug effects , Escherichia coli/enzymology , Escherichia coli/genetics , Escherichia coli/isolation & purification , Escherichia coli Proteins/genetics , Escherichia coli Proteins/isolation & purification , Escherichia coli Proteins/metabolism , Genes, Bacterial , Hospitals, Teaching , Hospitals, Urban , Humans , Molecular Sequence Data , Sequence Homology, Nucleic Acid , Substrate Specificity , beta-Lactamases/genetics , beta-Lactamases/metabolismABSTRACT
La resistencia a la combinación de ß-lactámico/inhibidor de ß-lactamasa en enterobacterias es un problema creciente que no ha sido estudiado intensamente en Argentina. En el presente trabajo, 54/843 enterobacterias recolectadas en un hospital universitario de la ciudad de Buenos Aires fueron resistentes a ampicilina-sulbactama, pero se mantuvieron sensibles a las cefalosporinas de segunda y tercera generación. Se analizaron los mecanismos enzimáticos presentes en los aislamientos que también fueron resistentes a amoxicilina-ácido clavulánico (AMC) (18/54). La secuenciación reveló dos variantes diferentes de blaTEM-1, donde blaTEM-1b es el alelo más frecuentemente detectado (10 Escherichia coli, 3 Klebsiella pneumoniae, 2 Proteus mirabilis y 1 Raoultella terrigena), seguidos por blaTEM-1a(1 K. pneumoniae). La resistencia a AMC parece estar asociada principalmente con la hiperproducción de TEM-1 (sobre todo en E. coli) o con la coexpresión con ß-lactamasas tipo OXA-2 y/o SHV (K. pneumoniae y P. mirabilis). Se describió una nueva variante de blaTEM(TEM-163) en un aislamiento de E. coli que presentó una CIM frente a AMC de 16/8 Ag/ml. La enzima TEM-163 contiene dos sustituciones de aminoácidos respecto de TEM-1, Arg275Gln y His289Leu. Teniendo en cuenta la alta actividad específica observada y la baja IC50 para el ácido clavulánico, el patrón de resistencia de este aislamiento parece obedecer a la hiperproducción de la nueva variante de la ß-lactamasa de amplio espectro, en lugar de vincularse con un comportamiento similar al de una TEM resistente a inhibidores (IRT).(AU)
Resistance to ß-lactam/ß-lactamase inhibitors in enterobacteria is a growing problem that has not been intensively studied in Argentina. In the present work, 54/843 enterobacteria collected in a teaching hospital of Buenos Aires city were ampicillin-sulbactam-resistant isolates remaining susceptible to second-and third-generation cephalosporins. The enzymatic mechanisms present in the isolates, which were also amoxicillin-clavulanic acid (AMC)-resistant (18/54) were herein analyzed. Sequencing revealed two different variants of blaTEM-1, being blaTEM-1b the most frequently detected allelle (10 Escherichia coli, 3 Klebsiella pneumoniae, 2 Proteus mirabilis and 1 Raoultella terrigena) followed by blaTEM-1a(1 K. pneumoniae). Amoxicillin-clavulanate resistance seems to be mainly associated with TEM-1 overproduction (mostly in E. coli) or co-expressed with OXA-2-like and/or SHV ß-lactamases (K. pneumoniae and P. mirabilis). A new blaTEMvariant (TEM-163) was described in an E. coli strain having an AMC MIC value of 16/8 Ag/ml. TEM-163 contains Arg275Gln and His289Leu amino acid substitutions. On the basis of the high specific activity and low IC50 for clavulanic acid observed, the resistance pattern seems to be due to overproduction of the new variant of broad spectrumß-lactamase rather than to an inhibitor-resistant TEM (IRT)-like behavior.(AU)
ABSTRACT
La resistencia a la combinación de ß-lactámico/inhibidor de ß-lactamasa en enterobacterias es un problema creciente que no ha sido estudiado intensamente en Argentina. En el presente trabajo, 54/843 enterobacterias recolectadas en un hospital universitario de la ciudad de Buenos Aires fueron resistentes a ampicilina-sulbactama, pero se mantuvieron sensibles a las cefalosporinas de segunda y tercera generación. Se analizaron los mecanismos enzimáticos presentes en los aislamientos que también fueron resistentes a amoxicilina-ácido clavulánico (AMC) (18/54). La secuenciación reveló dos variantes diferentes de blaTEM-1, donde blaTEM-1b es el alelo más frecuentemente detectado (10 Escherichia coli, 3 Klebsiella pneumoniae, 2 Proteus mirabilis y 1 Raoultella terrigena), seguidos por blaTEM-1a(1 K. pneumoniae). La resistencia a AMC parece estar asociada principalmente con la hiperproducción de TEM-1 (sobre todo en E. coli) o con la coexpresión con ß-lactamasas tipo OXA-2 y/o SHV (K. pneumoniae y P. mirabilis). Se describió una nueva variante de blaTEM(TEM-163) en un aislamiento de E. coli que presentó una CIM frente a AMC de 16/8 µg/ml. La enzima TEM-163 contiene dos sustituciones de aminoácidos respecto de TEM-1, Arg275Gln y His289Leu. Teniendo en cuenta la alta actividad específica observada y la baja IC50 para el ácido clavulánico, el patrón de resistencia de este aislamiento parece obedecer a la hiperproducción de la nueva variante de la ß-lactamasa de amplio espectro, en lugar de vincularse con un comportamiento similar al de una TEM resistente a inhibidores (IRT).
Resistance to ß-lactam/ß-lactamase inhibitors in enterobacteria is a growing problem that has not been intensively studied in Argentina. In the present work, 54/843 enterobacteria collected in a teaching hospital of Buenos Aires city were ampicillin-sulbactam-resistant isolates remaining susceptible to second-and third-generation cephalosporins. The enzymatic mechanisms present in the isolates, which were also amoxicillin-clavulanic acid (AMC)-resistant (18/54) were herein analyzed. Sequencing revealed two different variants of blaTEM-1, being blaTEM-1b the most frequently detected allelle (10 Escherichia coli, 3 Klebsiella pneumoniae, 2 Proteus mirabilis and 1 Raoultella terrigena) followed by blaTEM-1a(1 K. pneumoniae). Amoxicillin-clavulanate resistance seems to be mainly associated with TEM-1 overproduction (mostly in E. coli) or co-expressed with OXA-2-like and/or SHV ß-lactamases (K. pneumoniae and P. mirabilis). A new blaTEMvariant (TEM-163) was described in an E. coli strain having an AMC MIC value of 16/8 µg/ml. TEM-163 contains Arg275Gln and His289Leu amino acid substitutions. On the basis of the high specific activity and low IC50 for clavulanic acid observed, the resistance pattern seems to be due to overproduction of the new variant of broad spectrumß-lactamase rather than to an inhibitor-resistant TEM (IRT)-like behavior.
Subject(s)
Humans , Amoxicillin-Potassium Clavulanate Combination/pharmacology , Drug Resistance, Bacterial/genetics , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae/enzymology , beta-Lactamases/isolation & purification , Amino Acid Substitution , Argentina/epidemiology , Base Sequence , Cross Infection/epidemiology , Cross Infection/microbiology , Disk Diffusion Antimicrobial Tests , DNA, Bacterial/genetics , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae/drug effects , Enterobacteriaceae/genetics , Enterobacteriaceae/isolation & purification , Escherichia coli Proteins/genetics , Escherichia coli Proteins/isolation & purification , Escherichia coli Proteins/metabolism , Escherichia coli/drug effects , Escherichia coli/enzymology , Escherichia coli/genetics , Escherichia coli/isolation & purification , Genes, Bacterial , Hospitals, Teaching , Hospitals, Urban , Molecular Sequence Data , Sequence Homology, Nucleic Acid , Substrate Specificity , beta-Lactamases/genetics , beta-Lactamases/metabolismABSTRACT
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.