RESUMO
Several hepatic disorders are influenced by gut microbiota, but its role in idiosyncratic drug-induced liver injury (iDILI), whose main causative agent is amoxicillin-clavulanate, remains unknown. This pioneering study aims to unravel particular patterns of gut microbiota composition and associated metabolites in iDILI and iDILI patients by amoxicillin-clavulanate (iDILI-AC). Thus, serum and fecal samples from 46 patients were divided into three study groups: healthy controls (n = 10), non-iDILI acute hepatitis (n = 12) and iDILI patients (n = 24). To evaluate the amoxicillin-clavulanate effect, iDILI patients were separated into two subgroups: iDILI non-caused by amoxicillin-clavulanate (iDILI-nonAC) (n = 18) and iDILI-AC patients (n = 6). Gut microbiota composition and fecal metabolome plus serum and fecal bile acid (BA) analyses were performed, along with correlation analyses. iDILI patients presented a particular microbiome profile associated with reduced fecal secondary BAs and fecal metabolites linked to lower inflammation, such as dodecanedioic acid and pyridoxamine. Moreover, certain taxa like Barnesiella, Clostridia UCG-014 and Eubacterium spp. correlated with significant metabolites and BAs. Additionally, comparisons between iDILI-nonAC and iDILI-AC groups unraveled unique features associated with iDILI when caused by amoxicillin-clavulanate. In conclusion, specific gut microbiota profiles in iDILI and iDILI-AC patients were associated with particular metabolic and BA status, which could affect disease onset and progression.
Assuntos
Combinação Amoxicilina e Clavulanato de Potássio , Ácidos e Sais Biliares , Doença Hepática Induzida por Substâncias e Drogas , Fezes , Microbioma Gastrointestinal , Metaboloma , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Fezes/microbiologia , Ácidos e Sais Biliares/metabolismo , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Masculino , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Metaboloma/efeitos dos fármacos , Pessoa de Meia-Idade , Adulto , IdosoRESUMO
Amoxicillin/clavulanate is a commonly used antibiotic. Though relatively rare, amoxicillin/clavulanate carries the highest incidence of idiosyncratic drug-induced liver disease. This case report presents an 80-year-old woman treated for simple respiratory tract infection with amoxicillin/clavulanate who was subsequently hospitalized with malaise and icterus and a biochemical cholestatic pattern with high alkaline phosphatase and bilirubin. Diagnostically challenging, ultimately, liver biopsy revealed drug-induced liver injury with a fatal course after attempt of supportive, symptomatic treatment.
Assuntos
Combinação Amoxicilina e Clavulanato de Potássio , Antibacterianos , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Feminino , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Idoso de 80 Anos ou mais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Evolução Fatal , Colestase Intra-Hepática/induzido quimicamenteAssuntos
Antibacterianos , Exantema , Linfoma Folicular , Pele , Síndrome de Stevens-Johnson , Idoso , Feminino , Humanos , Diagnóstico Diferencial , Exantema/etiologia , Pele/patologia , Dor/etiologia , Tomografia Computadorizada por Raios X , Exsudatos e Transudatos/diagnóstico por imagem , Canal Anal/diagnóstico por imagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Doxiciclina/efeitos adversos , Doxiciclina/uso terapêutico , Períneo , Abdome , Negro ou Afro-Americano , Biópsia , Linfoma Folicular/complicações , Linfoma Folicular/diagnóstico , Linfadenopatia ImunoblásticaRESUMO
INTRODUCTION: Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two DILI registries. METHODS: Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed. RESULTS: Of 1418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN. CONCLUSIONS: Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Sistema de Registros , Humanos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Prospectivos , Espanha/epidemiologia , Aspartato Aminotransferases/sangue , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversosRESUMO
BACKGROUND: Anorectal fistula, which is a relatively common pathology, is the chronic manifestation of the acute perirectal process that forms an anal abscess. The development of a fistula after incision and drainage of an anal abscess is seen in approximately 26-37%. Its treatment is a relevant topic, and the role of the use of antibiotic therapy in its prevention remains controversial, after the publication of several studies with contradictory results and several methodological limitations. Our hypothesis is that the combination of amoxicillin and clavulanic acid will reduce the incidence of anal fistula. METHOD: The aim of this study is to evaluate the efficacy of antibiotherapy after surgical drainage of perianal abscess in the development of perianal fistula. The PERIQxA study is a multicenter, randomized, double-blind controlled trial. The study has been designed to include 286 adult patients who will be randomly (1:1) assigned to either the experimental (amoxicillin/clavulanic acid 875/125 mg TDS for 7 days) or the control arm (placebo). The primary outcome measure is the percentage of patients that develop perianal fistula after surgery and during follow-up (6 months). DISCUSSION: This clinical trial is designed to evaluate the efficacy and safety of amoxicillin/clavulanic in the prevention of perianal fistula. The results of this study are expected to contribute to stablish the potential role of antibiotherapy in the therapeutics for anal abscess. TRIAL REGISTRATION: EudraCT Number: 2021-003376-14. Registered on November 26, 2021.
Assuntos
Doenças do Ânus , Fístula Retal , Dermatopatias , Adulto , Humanos , Abscesso/diagnóstico , Abscesso/etiologia , Abscesso/prevenção & controle , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Doenças do Ânus/complicações , Doenças do Ânus/prevenção & controle , Doenças do Ânus/cirurgia , Fístula Retal/diagnóstico , Fístula Retal/etiologia , Fístula Retal/prevenção & controle , Drenagem/efeitos adversos , Drenagem/métodos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
OBJECTIVES: Amoxycillin/clavulanic acid is the most common antimicrobial cause of drug-induced liver injury in adults. It is a less common cause of severe drug-related hepatotoxicity in children despite its frequent use. We studied the incidence, characteristics and predictive factors for amoxycillin/clavulanic acid hepatoxicity in children. DESIGN: Retrospective cohort study of children who received oral or intravenous amoxycillin/clavulanic acid at a quaternary children's hospital over a 5-year period. Children were included if they had liver function tests (LFTs) determined at baseline, during and within 3â months after the treatment course. Causality was assessed using the Naranjo criteria for adverse drug reactions and Roussel Uclaf Causality Assessment Method. RESULTS: Of 3271 children prescribed amoxycillin/clavulanic acid, 374 were included. Forty-nine (13%) had LFT abnormalities related to amoxycillin/clavulanic acid. Fourteen (3.6%) fulfilled Common Terminology Criteria for Adverse Events (CTCAE) grade 2 criteria with clinically significant hepatotoxicity. Age <2â years, sepsis, post-gastrointestinal surgical indications, prolonged treatment course of >7â days and higher cumulative amoxycillin (>10â g) and clavulanic acid dose (>1â g) were predictive of hepatotoxicity. The median time to resolution of LFT abnormalities was 4â weeks (range 3-7). CONCLUSIONS: The incidence of amoxycillin/clavulanic acid related LFT abnormalities (CTCAE Grade 2 or above) in children was 3.6%. A prolonged treatment course >7â days, high cumulative amoxycillin (10â g) and clavulanic acid (>1â g) doses, those aged <2â years, and patients with sepsis or post-gastrointestinal surgery were predictive of a higher likelihood of abnormal LFTs. LFT monitoring should be considered in children receiving ≥7â days of treatment, particularly in those with other predisposing factors.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Sepse , Adulto , Criança , Humanos , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Ácidos Clavulânicos/efeitos adversos , Incidência , Estudos Retrospectivos , Quimioterapia Combinada , Austrália/epidemiologia , Amoxicilina/farmacologia , Ácido Clavulânico/efeitos adversos , Sepse/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , HospitaisRESUMO
Context: Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the most common indications for probiotic treatment is the prevention of antibiotic-associated diarrhea (AAD). Unfortunately, many probiotic products used for AAD are not supported by rigorous independent research, and often results in non-evidence-based usage. Additionally, it is not clear when is the most appropriate time to take a probiotic when on an antibiotic course. Objectives: The primary aim is to determine the ability of BB-12 to impact antibiotic-induced reduction in short chain fatty acid concentration (SCFA), as reflected by the levels of acetate on day 14. Secondarily to determine the ability of BB-12 to impact antibiotic-induced disruption of the gut microbiota with 16S rDNA profiling, with the addition of the time variable of probiotic consumption. Study Design and Interventions: A five group randomized controlled trial, finished in December 2022, we are currently analyzing all the data, but will be finished much prior to NAPCRG. All participants were given a 7-day prescription for amoxicillin-clavulanic acid 875mg taken twice daily. One group received no other interventions. While the other participants were broken into 4 groups. Two groups consumed the yogurt intervention (either yogurt+probiotic or control yogurt) four hours after the antibiotic and two groups consumed the yogurt intervention (either yogurt+probiotic or control yogurt) concomitantly with antibiotics. This timing question is important, as it is unknown if the optimal time for patients to administer probiotics is concurrently with, or after four hours following antibiotic consumption. Setting: Capital Areal Primary Care Practice Based Research Network. Population Studied: 118 participants, ages 18-65 years, generally healthy. Outcome Measures: Change in SCFA among the five groups, microbiome reduced disruption and clinically diagnosed diarrhea. Results: Study is complete and analysis is underway. Should have full results by end of July 2023, much before NAPCRG. .
Assuntos
Probióticos , Humanos , Projetos Piloto , Probióticos/uso terapêutico , Diarreia/induzido quimicamente , Diarreia/prevenção & controle , Antibacterianos/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversosRESUMO
La falla hepática fulminante (FHF) debida a Virus Epstein Barr (VEB) es poco frecuente en inmunocompetentes. La utilidad de los esteroides en este cuadro no ha sido definida y permanece muy controversial. Objetivo: Reportar el caso de una paciente con mononucleosis infecciosa por VEB que presenta FHF y es tratada con corticoides. Caso clínico: Escolar con cuadro de 2 sem de síntomas respiratorios altos, fiebre, adenopatías, con ictericia y orina oscura. Bilirrubina total: 9; B. Directa: 6,3; Fosfatasas Alcalinas: 523; GOT: 7.527; GPT: 6.537; Protrombina (PT): 17 por ciento INR: 4,7; Amonio 510 y glicemia 33. Ecografía abdominal hígado normal y esplenomegalia. Monotest Positivo. Se transfirió a centro de trasplante hepático (TH). Laboratorio de ingreso PT 21 por ciento; bilirrubina en 9,8; GOT 2717; GPT 3716 y amonio 177. EEG con enlentecimiento difuso compatible con encefalopatía grado 1. IgM VEB positiva, descartándose otras etiologías. Se activó para TH por FHF y mientras se administró Metilprednisolona por 5 días. Evolucionó con normalización de las pruebas hepáticas y mejoría clínica. Conclusión: En este caso el uso de esteroides se asoció a una rápida y favorable respuesta tanto clínica como de laboratorio sin presentar efectos secundarios negativos. Al igual que en otras presentaciones de infección grave por VEB, debiera considerarse el uso de esteroides en FHF por VEB.
Acute liver failure (ALF) due to Epstein Barr Virus (EBV) is rare in immunocompetent patients. The role of steroids in this case is not well defined and remains controversial. Case report: 7 years old female presenting with unspecific respiratory symptoms for 2 weeks, fever, lymphadenopathy, jaundice and dark brown urine. Total bilirubin: 9 and direct: 6.3, alkaline phosphatases: 523; AST: 7.527, ALT: 6.537; Prothrombin (PT): 17 percent, INR: 4.7; ammonium 510 and glucose 33. Abdominal ultrasound: normal liver and splenomegaly. Monotest Positive. She was transferred to a liver transplant centre (LT). Lab results at admission: PT 21 percent, bilirubin 9.8, AST 2717, ALT 3.716 and ammonium 177. EEG with diffuse and slowing conductivity consistent with encephalopathy. Positive IgM EBV, other aetiologies were ruled out. She was activated for LT due to ALF and while in waiting list methylprednisolone was administered for 5 days. She evolved with normalization of liver tests and clinical improvement. Conclusion: In this case the use of steroids was associated with a rapid and favourable clinical and laboratory response without negative side effects. As in other presentations of serious infection by EBV, should consider the use of steroids in ALF due to EBV.
Assuntos
Humanos , Feminino , Criança , Falência Hepática/etiologia , Glucocorticoides/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Metilprednisolona/uso terapêutico , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Infecções por Vírus Epstein-Barr/diagnóstico , Mononucleose Infecciosa/complicações , Mononucleose Infecciosa/tratamento farmacológicoRESUMO
As IVAS em crianças e adultos são os motivos mais freqüentes de consulta médica e os que mais demandam o uso de antibióticos. A crescente resistência bacteriana causada pela produção das beta-lactamases constitui um dos mais sérios problemas atuais. A Sultamicilina é uma pró-droga dupla da ampicilina e do sulbactam, um potente inibidor de beta-lactamases que pode fazer frente a estas dificuldades. OBJETIVO: avaliar a eficácia, segurança e tolerabilidade da Ampicilina/Sulbactan comparada à Amoxacilina/Acido Clavulânico no tratamento de IVAS, em adultos. METODOLOGIA: 102 pacientes com diagnóstico de IVAS foram randomizados em dois grupos recebendo Ampicilina/Sulbactan ou Amoxacilina/Clavulanato por 10 dias. Foram avaliados 10 e 30 dias após para análise da resposta terapêutica. RESULTADOS: Não houve diferença entre os grupos com relação à proporção de pacientes curados ao final do tratamento (visita 2) ou do estudo (visita 3). No grupo que recebeu Amoxacilina/Clavulanato, as proporções de cura foram de 61.7 por cento e 93.2 por cento nas visitas 2 e 3, comparadas a 64.4 por cento e 97.4 por cento, respectivamente, no grupo que recebeu Ampicilina/Sulbactan. A proporção de pacientes que experimentou pelo menos um evento adverso foi semelhante nos dois grupos (p = 0.940). A diarréia foi significativamente mais freqüente no grupo Amoxacilina-Clavulanato (70.6 por cento) do que no grupo Ampicilina/Sulbactan (29.4 por cento), (p=0.0164). CONCLUSÕES: A Ampicilina/Sulbactan é tão segura e eficaz quanto a Amoxacilina/Clavulanato no tratamento empírico de IVAS em adultos. A ocorrência significativamente menor de quadros de diarréia no grupo recebendo Ampicilina/Sulbactan necessita confirmação em estudos posteriores.
Upper respiratory tract infections are the most common causes of medical visits in children and adults, demanding massive use of antibiotics. Bacterial resistance caused by beta-lactamase is one of the most serious problems in this matter. Sultamicillin, a double pro-drug of Ampicillin/Sulbactan, is a potent beta-lactamase inhibitor which can face this challenge. AIM: evaluate efficacy, safety and tolerability of Ampicillin/Sulbactan compared to Amoxicillin/Clavulanate in upper respiratory tract infections in adults. METHODS: 102 patients were enrolled and randomized to receive Ampicillin/Sulbactan or Amoxicillin/Clavulanate during 10 days. They were evaluated 10 and 30 days after treatment to learn about the therapeutic response. RESULTS: There were no differences between the two groups respecting cure at the end of treatment (visit 2) or at the end of the study (visit 3). Cure ratio was 61.7 percent and 93.2 percent (visits 2 and 3) in the Amoxicillin/Clavulanate group compared to 64.4 percent and 97.4 percent, respectively, in Ampicillin/Sulbactan group. The adverse events ratio for the two groups was the same (p=0.940). The number of patients with diarrhea was greater in the group of patients receiving Amoxicillin/Clavulanate (70.6 percent) than in the group receiving Ampicillin/Sulbactan (29.4 percent) (p=0.0164). CONCLUSIONS: Ampicillin/Sulbactan is as safe and efficient as Amoxicillin/Clavulanate in the empiric treatment of upper respiratory infections in adults. The low occurrence of diarrhea in the group receiving Ampicillin/Sulbactan needs confirmation in other studies.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Antibacterianos/efeitos adversos , Ampicilina/efeitos adversos , Ampicilina/uso terapêutico , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Sulbactam/efeitos adversos , Sulbactam/uso terapêutico , Resultado do TratamentoAssuntos
Humanos , Gravidez , Recém-Nascido , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Ruptura Prematura de Membranas Fetais , Centro Latino-Americano de Perinatologia, Saúde da Mulher e Reprodutiva , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Eritromicina , Mortalidade InfantilAssuntos
Humanos , Lactente , Pré-Escolar , Criança , Cefalosporinas/administração & dosagem , Cefalosporinas/efeitos adversos , Cefalosporinas/uso terapêutico , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Otite Média/tratamento farmacológico , Doença AgudaRESUMO
ORACLE es una investigación aleatorizada factorial pragmática multicéntrica, dirigida desde la Universidad de Leicester (Reino Unido), cuyo objetivo es verificar el rol de la antibióticoterapia (eritromicina y/o augmentina y/o placebo) en la amenaza de parto prematuro (APP), con o sin rotura prematura de membranas (RPM). Los puntos finales principales son mortalidad perinatal y morbilidad neonatal severa. El tamaño muestral propuesto es de 10.000 casos. Participan 164 maternidades de 16 países y se llevan incluidos 7.364 pacientes. Argentina, que inició su gestión en agosto de 1997, a marzo de 1999 lleva incluidos 762 pacientes, reclutados entre las 9 maternidades participantes, sitas en Buenos Aires, provincia de Buenos Aires y Salta. Dos de ellas, figuran 2º y 3º en la lista de hospitales con mayor índice de reclutamiento en el mundo. El 88 por ciento de las ingresadas presentó APP y el 12 por ciento, RPM. Ambas situaciones se combinaron en el 8 por ciento de ellas. La mediana de la edad gestacional al ingreso es 32 semanas (cuartilos: 29 y 34). El 82,6 por ciento ya finalizó su participación y sólo hay un 2 por ciento de pérdidas de seguimiento. El 58 por ciento de los nacimientos ocurrió al término. La mediana de peso al nacer es 2.870 g (cuartilos 2.250 y 3.250). El 27 por ciento requirió UTI y la mortalidad perinatal es 3,6 por ciento. No se han registrado efectos adversos fetoneonatales atribuibles a las medicaciones del estudio. Los efectos adversos maternos suman 14 casos y han sido los habituales ante el consumo de antibióticos.