RESUMEN
BACKGROUND: Epstein-Barr virus (EBV) infection frequently develops in children undergoing liver transplantation (LT) because of mandated immunosuppressive therapy. There is a risk of ampicillin rash when penicillin derivatives are used in patients with EBV-associated infectious mononucleosis. Hence, the administration of penicillin derivatives may raise concerns about ampicillin rash in patients with high EBV loads. However, no studies confirmed the risk of administering penicillin derivatives to EBV-infected children after LT. METHODS: This retrospective study was conducted at the largest pediatric transplantation center in Japan. We investigated all pediatric liver transplant recipients who received penicillin derivatives within 2 years of LT between 2014 and 2020. We separated the cohort into EBV-positive and EBV-negative groups to assess the frequency of ampicillin and antibiotic-associated rash. RESULTS: Two hundred eighty-six liver transplant recipients were enrolled. There were 111 recipients in the EBV-positive group and 175 recipients in the EBV-negative group. In the EBV-positive group, 49 patients had high EBV DNA loads (≥1000 copies/µg DNA). None of the patients in either group developed ampicillin rash, and the frequency of antibiotic-associated rash did not differ [8/111 (7.2%) vs. 10/175 (5.7%), P = 0.797]. Additional subgroup analysis revealed no difference in the frequency of antibiotic-associated rashes regardless of the presence or absence of high EBV loads. CONCLUSIONS: In this study, ampicillin rash was not observed, and antibiotic-associated rash was not associated with concurrent EBV infection. Penicillin derivatives can be used safely, even in liver transplant recipients with persistent asymptomatic EBV infection.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Exantema , Trasplante de Hígado , Trastornos Linfoproliferativos , Niño , Humanos , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4/genética , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Trastornos Linfoproliferativos/complicaciones , Ampicilina/efectos adversos , ADN Viral , Antibacterianos/efectos adversos , Penicilinas , Carga Viral , Receptores de TrasplantesRESUMEN
BACKGROUND: Drug-induced liver injury (DILI) is an adverse reaction caused by ampicillin/sulbactam (ABPC/SBT). The albumin-bilirubin (ALBI) score is an index of hepatic functional reserve. However, the relationship between ABPC/SBT-induced DILI and ALBI score remains unknown; therefore, we aimed to elucidate the risk of ABPC/SBT-induced DILI based on the ALBI score. METHODS: This was a single-center, retrospective, case-control study using electronic medical records. A total of 380 patients were enrolled in the present study, and the primary outcome was ABPC/SBT-induced DILI. The ALBI score was calculated using serum albumin and total bilirubin levels. In addition, we performed COX regression analysis using age ≥75 years, dose ≥9 g/day, alanine aminotransferase (ALT) ≥21 IU/L, and ALBI score ≥-2.00 as covariates. We also performed 1:1 propensity score matching between non-DILI and DILI groups. RESULTS: The incidence of DILI was 9.5% (36/380). According to COX regression analysis, the adjusted hazard ratio for ABPC/SBT-induced DILI with an ALBI score ≥-2.00 was 2.55 (95% confidence interval: 1.256-5.191, P = 0.010), suggesting that patients with baseline ALBI score ≥-2.00 may be at high risk for ABPC/SBT-induced DILI. However, significant differences were not observed in cumulative risk for DILI between non-DILI and DILI patients regarding an ALBI score ≥-2.00 after propensity score matching (P = 0.146). CONCLUSION: These findings suggest that ALBI score may be a simple and potentially useful index for predicting ABPC/SBT-induced DILI. In patients with an ALBI score ≥-2.00, frequent liver function monitoring should be considered to prevent ABPC/SBT-induced DILI.
Asunto(s)
Ampicilina , Infecciones Bacterianas , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Sulbactam , Anciano , Humanos , Factores de Edad , Ampicilina/efectos adversos , Infecciones Bacterianas/tratamiento farmacológico , Bilirrubina/uso terapéutico , Estudios de Casos y Controles , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Quimioterapia Combinada , Estudios Retrospectivos , Albúmina Sérica , Sulbactam/efectos adversosRESUMEN
BACKGROUND: Although most immunoglobulin E (IgE)-mediated penicillin allergy wanes with time, sensitisation may occasionally persist for many years. Previous reports on the loss of penicillin-specific IgE sensitisation were based on non-anaphylaxis cases and, although uncommon, persistent sensitisation may still be possible in the minority of cases. OBJECTIVE: This case highlights that irrespective of the elapsed duration since the index reaction, it is important to remain vigilant when approaching patients with a history of severe reactions. MATERIAL AND METHODS: We described a case of persistent IgE sensitisation almost two decades following ampicillin anaphylaxis. RESULTS: A 78-year-old male with a history of perioperative penicillin anaphylaxis in 2003 was referred for allergy workup in 2022 before his knee joint replacement surgery. The patient had strictly avoided all beta-lactams since the index reaction. However, his penicillin-specific sensitisation persisted, evidenced by positive skin tests (with generalised urticaria after intradermal testing) and basophil activation tests. CONCLUSION: To our knowledge, this was the first case of positive BAT tested around two decades following the index reaction. This case illustrates that a cautious approach may still be warranted in patients with a history of severe reaction to penicillin regardless of the duration since the reported index reaction.
Asunto(s)
Anafilaxia , Hipersensibilidad a las Drogas , Masculino , Humanos , Anciano , Inmunoglobulina E , Pruebas Cutáneas , Ampicilina/efectos adversos , Penicilinas/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Anafilaxia/diagnóstico , Anafilaxia/inducido químicamenteRESUMEN
BACKGROUND AND AIMS: Antibiotics (ATBx) and acetaminophen (APAP) are widely used worldwide. APAP is the most common cause of acute liver injury (ALI) and might be used in combination with ATBx in clinics. However, the impact of ATBx on APAP-induced ALI has rarely been studied. METHODS: First, we compared the effects of seven ATBx on APAP-induced ALI. Then, we analysed faecal, serum and liver samples to investigate the impact of the gut microbiota on this process. Finally, we assessed the role of short-chain fatty acids in this process. RESULTS: In this work, we found that the ALI was significantly aggravated in the mice treated with ampicillin (Amp) instead of other ATBx. Amp exposure reduced the diversity and altered the composition of gut microbiota. The altered gut microbiota aggravated APAP-induced ALF, which was proven by faecal microbiota transplantation from ATBx-treated mice. Metagenomic analysis showed a significantly decreased Lactobacillus abundance in Amp-treated mice. Gavage with Lactobacillus, especially Lactobacillus rhamnosus, significantly reversed the severer ALF induced by APAP and Amp. Moreover, Lactobacillus supplementation increased butyrate-producing clostridia and lowered butyrate levels in Amp-treated mice. In accordance, butyrate supplementation could also alleviate Amp-aggravated ALI. In addition, inhibition of nuclear factor erythroid 2-related factor 2 counteracted the protective effect of butyrate on aggravated ALI induced by Amp and APAP. CONCLUSION: Together, this study revealed a potential health impact of Amp that may exacerbate liver damage when co-exposed to excess APAP.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Microbioma Gastrointestinal , Animales , Ratones , Acetaminofén/toxicidad , Butiratos/farmacología , Hígado , Ampicilina/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Ratones Endogámicos C57BLRESUMEN
BACKGROUND AND AIMS: Many epidemiological studies suggest an association between antibiotic exposure and the development of inflammatory bowel disease [IBD]. However, the majority of these studies are observational and still the question remains, "Does the specific antibiotic administration regimen play a role in the development of colitis?" This study aimed to compare the possible effects of continuous and intermittent antibiotic exposure on the development of colitis using a colitis-susceptible IL-10 knockout [IL-10-/-] mouse model. METHODS: IL-10-/- mice [C57BL/6] were randomly assigned to a non-antibiotic group, continuous antibiotic group and intermittent antibiotic group, and observed for 30 weeks. The antibiotic cocktail was given via the drinking water. The differential response to antibiotics was assessed. RESULTS: Intermittent antibiotic treatment resulted in severe colitis with early disease onset in IL-10-/- mice. Higher unit colon weight and spleen weight were observed in intermittent antibiotic-treated mice but not in the continuous antibiotic group. Moreover, intermittent antibiotic treatment aggravated epithelial damage and colonic inflammation, mucosal barrier dysfunction and colonic allergic sensitization in IL-10-/- mice, whereas continuous antibiotic treatment ameliorated these symptoms. Male IL-10-/- mice with intermittent antibiotic exposure were more susceptible to colonic inflammation and allergic response than females. CONCLUSIONS: In summary, intermittent antibiotic exposure accelerated the development of severe colitis more than continuous antibiotic exposure in IL-10-/- male mice. In addition to the colonic damage and impaired barrier function, stimulation of allergic response may play a role in accelerating the development of colitis in genetically susceptible mice.
Asunto(s)
Ampicilina/efectos adversos , Antibacterianos/efectos adversos , Colitis/inducido químicamente , Interleucina-10/genética , Neomicina/efectos adversos , Animales , Colitis/metabolismo , Colitis/microbiología , Colitis/patología , Colon/efectos de los fármacos , Colon/microbiología , Colon/patología , Femenino , Hipersensibilidad a los Alimentos , Microbioma Gastrointestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Masculino , Ratones Noqueados , Mucina 2/metabolismo , PermeabilidadRESUMEN
BACKGROUND: Current guidelines recommend either ampicillin plus ceftriaxone (AC) or amoxicillin/ampicillin plus gentamicin (AG) with an equivalent class IB recommendation in Enterococcus faecalis endocarditis. However, previous observational studies suggest that AC might be favourable in terms of adverse events. OBJECTIVES: To investigate whether AC is non-inferior to AG, and if it is associated with less adverse events. METHODS: In June 2021, a systematic literature search using the databases PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS was conducted by two independent reviewers. Studies were considered eligible if (P) patients included were ≥ 18 years of age and had IE with E. faecalis, (I) treatment with AC was compared to (C) treatment with AG and (O) outcomes on in-hospital mortality, nephrotoxicity and adverse events requiring drug withdrawal were reported. Odds ratios and 95% confidence intervals were calculated using random-effects models with the Mantel-Haenszel method, the Sidik-Jonkman estimator for τ2 and the Hartung-Knapp adjustment. RESULTS: Treatment with AC was non-inferior to AG, as depicted by no significant differences in-hospital mortality, 3-month mortality, relapses or treatment failure. Furthermore, AC was associated with a lower prevalence of nephrotoxicity (OR 0.45 [0.26-0.77], p = 0.0182) and drug withdrawal due to adverse events (OR 0.11 [0.03-0.46], p = 0.0160) than AG. CONCLUSIONS: Treatment with AC was non-inferior to treatment with AG, and it was associated with a reduced prevalence of nephrotoxicity and drug withdrawal due to adverse events. Thus, combination therapy with AC appears favourable over AG in patients with E. faecalis IE.
Asunto(s)
Endocarditis Bacteriana , Endocarditis , Infecciones por Bacterias Grampositivas , Cardiopatías , Insuficiencia Renal , Amoxicilina/farmacología , Amoxicilina/uso terapéutico , Ampicilina/efectos adversos , Antibacterianos/efectos adversos , Ceftriaxona/efectos adversos , Quimioterapia Combinada , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/epidemiología , Enterococcus faecalis , Gentamicinas/efectos adversos , Infecciones por Bacterias Grampositivas/inducido químicamente , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Cardiopatías/tratamiento farmacológico , Humanos , Insuficiencia Renal/tratamiento farmacológicoRESUMEN
Inappropriate use of antibiotics in animal and human plays a role in the emergence and spread of bacteria resistant to antibiotics which threatens human health significantly. Although extensive use of these antibiotics could contribute to the development of drug resistance, information on the knowledge, attitude and practice of antimicrobial resistance and use among animal farm owners/workers in north western Ethiopia is rare. The objective of the present study was to assess knowledge, attitude and practice of animal farm owner/workers towards antibiotic resistance and use in Amhara regional state north western Ethiopia. A cross sectional study was conducted in selected cities of Amhara regional state from January to February, 2020. Data was collected from 91 participants using structured questionnaire and analyzed using SPSSS version 23. The results showed that 96.7% of respondents gave antibiotics to treat their livestock from different sources. Most of the respondents bought their antibiotics from private pharmacies without prescription and the most frequently mentioned antibiotics used to treat animal diseases was tetracycline (76.9%), followed by ampicillin (72.5%). Although, 90.1% of the animal farm owners heard about antibiotics and antibiotic resistance from different sources, they did not know the factors contributing to the transmission of resistant bacteria to humans and the impact of antibiotic resistance on human and animals' health. Using the mean score 4.44 ± 0.15 as the cut-off, half of the animal farm owners/workers had good knowledge about antimicrobial resistance and use. 52.5% of animal farm owners/workers had positive attitudes towards wise antibiotic use and resistance with a mean score of 28.4 ± 0.5. However, 52.75% participants had poor practice with the mean score of practice 4.95 ± 0.17. Better knowledge, positive attitudes and better practices on antibiotic use and resistance were associated with farm owners/workers who engaged in higher education. Although poor awareness on antimicrobial resistance was perceived by 76.9% of respondents as very important factors that contribute to increasing antibiotic resistance, increasing the use of complementary treatments was perceived by the majority of respondents as very important strategies that contribute to reduce antibiotic use and resistance. The current study disclosed that there is low level of awareness among animal farm owners about the correct use of antibiotics and resistance. It is necessary to raise awareness, develop and implement interventions to reduce antimicrobial use and antibiotic resistance in the study area.
Asunto(s)
Crianza de Animales Domésticos/métodos , Farmacorresistencia Bacteriana , Agricultores/psicología , Conocimientos, Actitudes y Práctica en Salud , Adulto , Anciano , Ampicilina/administración & dosificación , Ampicilina/efectos adversos , Crianza de Animales Domésticos/normas , Animales , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Etiopía , Femenino , Humanos , Ganado/crecimiento & desarrollo , Ganado/microbiología , Masculino , Persona de Mediana Edad , Tetraciclina/administración & dosificación , Tetraciclina/efectos adversosRESUMEN
BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis. OBJECTIVES: To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis. SEARCH METHODS: We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up. MAIN RESULTS: We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors. AUTHORS' CONCLUSIONS: Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.
ANTECEDENTES: La sepsis neonatal es una causa importante de morbilidad y mortalidad. Es la tercera causa de mortalidad neonatal a nivel mundial y constituye el 13% de la mortalidad neonatal total. A pesar de la elevada carga de la sepsis neonatal, la evidencia de alta calidad en el diagnóstico y el tratamiento es escasa. Debido a las dificultades de diagnóstico de la sepsis y a la relativa inmunosupresión del neonato, muchos reciben antibióticos por sospecha de sepsis. Los antibióticos se han convertido en el tratamiento más utilizado en las unidades de cuidados intensivos neonatales, y los estudios observacionales realizados en países de ingresos altos indican que entre el 83% y el 94% de los neonatos tratados con antibióticos por sospecha de sepsis tienen hemocultivos negativos. La última revisión Cochrane se actualizó en 2005. Se necesita una revisión sistemática actualizada que evalúe los efectos de los diferentes regímenes de antibióticos para la sepsis neonatal de inicio tardío. OBJETIVOS: Evaluar los efectos beneficiosos y perjudiciales de diferentes regímenes antibióticos para la sepsis neonatal de inicio tardío. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en las siguientes bases de datos electrónicas: CENTRAL (2021, número 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED y Conference Proceedings Citation Index Science el 12 de marzo de 2021. También se buscaron ensayos controlados aleatorizados (ECA) y cuasialeatorizados en las bases de datos de ensayos clínicos y en las listas de referencias de artículos identificados. CRITERIOS DE SELECCIÓN: Se incluyeron ECA que compararon diferentes regímenes de antibióticos para la sepsis neonatal de inicio tardío. Se incluyeron participantes mayores de 72 horas de vida en el momento de la asignación al azar, con sospecha o diagnóstico de sepsis neonatal, meningitis, osteomielitis, endocarditis o enterocolitis necrosante. Se excluyeron los ensayos que evaluaron el tratamiento de las infecciones micóticas. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron los estudios para inclusión, extrajeron los datos y evaluaron el riesgo de sesgo. Se utilizó el método GRADE para evaluar la certeza de la evidencia. El desenlace principal fue la mortalidad por todas las causas, y los desenlaces secundarios fueron: eventos adversos graves, asistencia respiratoria, apoyo circulatorio, nefrotoxicidad, deterioro del desarrollo neurológico, enterocolitis necrosante y ototoxicidad. El punto temporal principal de interés fue el seguimiento máximo. RESULTADOS PRINCIPALES: Se incluyeron cinco ECA (580 participantes). Todos los ensayos tuvieron alto riesgo de sesgo y evidencia de certeza muy baja. Los cinco ensayos incluidos evaluaron cinco comparaciones diferentes de antibióticos. No se realizó un metanálisis debido a la falta de datos relevantes. De los cinco ensayos incluidos, un ensayo comparó cefazolina más amikacina con vancomicina más amikacina; un ensayo comparó ticarcilina más ácido clavulánico con flucloxacilina más gentamicina; un ensayo comparó cloxacilina más amikacina con cefotaxima más gentamicina; un ensayo comparó meropenem con atención estándar (ampicilina más gentamicina o cefotaxima más gentamicina); y un ensayo comparó vancomicina más gentamicina con vancomicina más aztreonam. Ninguna de las cinco comparaciones encontró evidencia de una diferencia al evaluar la mortalidad por todas las causas, los eventos adversos graves, el apoyo circulatorio, la nefrotoxicidad, el deterioro del desarrollo neurológico o la enterocolitis necrosante; sin embargo, ninguno de los ensayos se acercó a un tamaño de información que pudiera contribuir significativamente a la evidencia de los beneficios y los riesgos comparativos de cualquier régimen antibiótico en particular. Ninguno de los ensayos evaluó la asistencia respiratoria o la ototoxicidad. Los efectos beneficiosos y perjudiciales de los diferentes regímenes de antibióticos aún no están claros debido a la falta de ensayos con un poder estadístico adecuado y al alto riesgo de errores sistemáticos. CONCLUSIONES DE LOS AUTORES: La evidencia actual no es suficiente para apoyar que un régimen de antibióticos sea superior a otro. Se justifica la realización de ECA con bajo riesgo de sesgo que evalúen diferentes regímenes antibióticos en la sepsis neonatal de inicio tardío.
Asunto(s)
Antibacterianos/uso terapéutico , Sepsis Neonatal/tratamiento farmacológico , Amicacina/efectos adversos , Amicacina/uso terapéutico , Ampicilina/efectos adversos , Ampicilina/uso terapéutico , Antibacterianos/efectos adversos , Aztreonam/efectos adversos , Aztreonam/uso terapéutico , Sesgo , Cefazolina/efectos adversos , Cefazolina/uso terapéutico , Ácido Clavulánico/efectos adversos , Ácido Clavulánico/uso terapéutico , Quimioterapia Combinada , Floxacilina/efectos adversos , Floxacilina/uso terapéutico , Gentamicinas/efectos adversos , Gentamicinas/uso terapéutico , Humanos , Recién Nacido , Ensayos Clínicos Controlados Aleatorios como Asunto , Ticarcilina/efectos adversos , Ticarcilina/uso terapéutico , Vancomicina/efectos adversos , Vancomicina/uso terapéuticoRESUMEN
BACKGROUND: Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2020. OBJECTIVES: To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis. SEARCH METHODS: We searched the following databases up to 3 September 2020: CENTRAL (2020, Issue 8), MEDLINE Ovid (from 1946), Embase Elsevier (from 1974), and Web of Science Thomson Reuters (from 2010). We also searched clinical trial registers on 3 September 2020. SELECTION CRITERIA: Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures as recommended by Cochrane. We assessed the risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We have reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results. MAIN RESULTS: We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both; heterogeneity; and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials; 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials; 1660 participants; very low-certainty evidence). We are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials; 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials; 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79, 95% CI 0.57 to 1.09; 6 trials; 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials; 802 participants; low-certainty evidence). Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial; 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29, 95% CI 0.11 to 0.73; 1 trial; 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial; 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial; 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials; 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better in preventing serious but rare complications. AUTHORS' CONCLUSIONS: We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. These results do not demonstrate that other antibiotics are more effective than penicillin in the treatment of GABHS pharyngitis. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities, where the risk of complications remains high.
Asunto(s)
Antibacterianos/uso terapéutico , Faringitis/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amoxicilina/efectos adversos , Amoxicilina/uso terapéutico , Ampicilina/efectos adversos , Ampicilina/uso terapéutico , Antibacterianos/efectos adversos , Azitromicina/efectos adversos , Azitromicina/uso terapéutico , Cefalosporinas/efectos adversos , Cefalosporinas/uso terapéutico , Niño , Preescolar , Clindamicina/efectos adversos , Clindamicina/uso terapéutico , Humanos , Lactante , Macrólidos/efectos adversos , Macrólidos/uso terapéutico , Persona de Mediana Edad , Penicilinas/efectos adversos , Penicilinas/uso terapéutico , Faringitis/microbiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones Estreptocócicas/microbiología , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Adulto JovenRESUMEN
This study sought to investigate whether dosing frequency (the number of doses per day) affects the antimicrobial efficacy and safety of ampicillin/sulbactam (ABPC/SBT) in Japanese elderly pneumonia patients treated with ABPC/SBT at 6 g/day. This was a retrospective observational study that included hospitalized elderly patients (aged ≥75 years, 10 ml/min ≤CLcr <50 ml/min) who received 3 g every 12 h (BID; n = 61) or 1.5 g every 6 h (QID; n = 45) for the treatment of pneumonia. The primary endpoint was clinical response, assessed by measuring body temperature, white blood cell count, and C-reactive protein levels. Pharmacokinetic and pharmacodynamic simulations were conducted in silico to rationalize the clinical findings. The clinical response rates (extremely effective and effective) in the BID and QID groups were 36.1% and 55.6%, respectively (p = .0459). QID tended to be more effective in patients with gram-negative rods detected (p = .0563). According to the simulated minimum plasma ABPC concentrations at steady state for BID and QID were 2.5 and 7.3 µg/ml, respectively (p < .0001). Based on the simulated time above minimum inhibitory concentration (MIC), pharmacological (not clinical) efficacy was predicted to be higher with QID. Both groups had similar safety profiles. The main adverse event in both groups was liver damage. The present retrospective survey demonstrated that ABPC/SBT treatment for elderly patients with pneumonia and renal dysfunction was more effective with QID than with BID. Therefore, the QID regimen is worthy of consideration to improve the clinical outcomes of ABPC/SBT therapy in the present patient population.
Asunto(s)
Antibacterianos/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Neumonía Bacteriana/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Ampicilina/administración & dosificación , Ampicilina/efectos adversos , Ampicilina/farmacocinética , Antibacterianos/efectos adversos , Antibacterianos/farmacocinética , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Simulación por Computador , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Tasa de Filtración Glomerular , Humanos , Inyecciones Intravenosas , Masculino , Eliminación Renal , Estudios Retrospectivos , Sulbactam/administración & dosificación , Sulbactam/efectos adversos , Sulbactam/farmacocinética , Resultado del TratamientoRESUMEN
Rates of perinatal maternal antibiotic use have increased in recent years linked to prophylactic antibiotic use following Caesarean section delivery. This antibiotic use is necessary and beneficial in the short-term; however, long-term consequences on brain and behaviour have not been studied in detail. Here, we endeavoured to determine whether maternal administration of antibiotics during a critical window of development in early life has lasting effects on brain and behaviour in offspring mice. To this end we studied two different antibiotic preparations (single administration of Phenoxymethylpenicillin at 31 mg/kg/day; and a cocktail consisting of, ampicillin 1 mg/mL; vancomycin 0.5 mg/mL; metronidazole 1 mg/mL; ciprofloxacin 0.2 mg/mL and imipenem 0.25 mg/mL). It was observed that early life exposure to maternal antibiotics led to persistent alterations in anxiety, sociability and cognitive behaviours. These effects in general were greater in animals treated with the broad-spectrum antibiotic cocktail compared to a single antibiotic with the exception of deficits in social recognition which were more robustly observed in Penicillin V exposed animals. Given the prevalence of maternal antibiotic use, our findings have potentially significant translational relevance, particularly considering the implications on infant health during this critical period and into later life.
Asunto(s)
Antibacterianos/efectos adversos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ampicilina/administración & dosificación , Ampicilina/efectos adversos , Animales , Antibacterianos/administración & dosificación , Ansiedad/inducido químicamente , Ciprofloxacina/administración & dosificación , Ciprofloxacina/efectos adversos , Cognición/efectos de los fármacos , Femenino , Fenómenos de Retorno al Lugar Habitual/efectos de los fármacos , Imipenem/administración & dosificación , Imipenem/efectos adversos , Masculino , Metronidazol/administración & dosificación , Metronidazol/efectos adversos , Ratones , Ratones Endogámicos C57BL , Penicilina V/administración & dosificación , Penicilina V/efectos adversos , Embarazo , Conducta Social , Vancomicina/administración & dosificación , Vancomicina/efectos adversos , Vocalización Animal/efectos de los fármacosAsunto(s)
Gentamicinas , Sepsis , Ampicilina/efectos adversos , Humanos , Sepsis/tratamiento farmacológicoRESUMEN
High consumption of irrational fixed-dose combination (FDC) antibiotics may pose a threat of antimicrobial resistance. In India, ampicillin-cloxacillin was the second highest sold FDC antibiotic behind amoxicillin and clavulanic acid. There remain, however, questions about its efficacy and safety and a lack of regulatory approval. We undertook a literature review for ampicillin-cloxacillin to identify available data on the safety and efficacy of its used as FDC. We identified 1071 studies for screening and 81 studies were considered for inclusion. Only 12 studies in English language were accessible full texts for final review. None of the studies identified provided strong evidence that ampicillin-cloxacillin differed in safety or efficacy to other treatments used, and in particular to the component antibiotics used alone. To fully assess the efficacy and safety of ampicillin-cloxacillin and other FDCs, a standardised search format would be required. This should include broad international collaboration, including contacting the relevant regulatory authorities to facilitate a more evidence-based approach to their use.
Asunto(s)
Antibacterianos , Cloxacilina , Amoxicilina , Ampicilina/efectos adversos , Antibacterianos/efectos adversos , Ácido Clavulánico , Cloxacilina/efectos adversos , HumanosRESUMEN
SCOPE: Soy protein is a high-quality protein and its consumption has been associated with a reduction of serum cholesterol and triglycerides and an improvement in insulin resistance. However, it is not known whether the effects of soy protein are mediated by the gut microbiota. Thus, the aim of this study is to assess whether using antibiotics to partially eradicate the gut microbiota can prevent the beneficial effects of soy protein in rats. METHODS AND RESULTS: Thus, rats are fed one of the following diets for 16 weeks: casein control, soy protein control, high-fat casein, and high-fat soy protein. The rats are then treated for 4 weeks with antibiotics. Body weight and composition, energy expenditure, glucose tolerance test, metabolic endotoxemia, and gut microbiota are measured before and after treatment with antibiotic. The results show that soy protein consumption decreases weight gain, body fat, metabolic endotoxemia, and increases energy expenditure and glucose tolerance. Antibiotic treatment suppresses all these metabolic effects. These changes are accompanied by modifying the diversity and taxonomy of the gut microbiota. CONCLUSION: In conclusion, the evidence suggests that the health benefits of soy protein are partly dependent of the gut microbiota.
Asunto(s)
Antibacterianos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Proteínas de Soja/farmacología , Tejido Adiposo/efectos de los fármacos , Ampicilina/efectos adversos , Ampicilina/farmacología , Animales , Antibacterianos/efectos adversos , Biomarcadores/metabolismo , Composición Corporal/efectos de los fármacos , Caseínas/farmacología , Dieta Alta en Grasa/efectos adversos , Endotoxemia/inducido químicamente , Metabolismo Energético/efectos de los fármacos , Ácidos Grasos Volátiles/metabolismo , Microbioma Gastrointestinal/fisiología , Inflamación/genética , Inflamación/metabolismo , Masculino , Neomicina/efectos adversos , Neomicina/farmacología , Ratas Wistar , Aumento de Peso/efectos de los fármacosRESUMEN
OBJECTIVES: Antibiotics play a great role in the treatment of infectious diseases, but meantime, they cause great disturbances to host microbiota. Studies on different antibiotic-induced changes in host microbiota are relatively scarce. This study aimed to investigate the changes in oral and gut microbiota and possible alterations of gut resistance to Salmonella induced by the administration of antibiotics. METHODS: The experiment was conducted by administering antibiotics to rats and detecting oral and gut microbiota by 16S rRNA gene sequencing. In second part, after treating with antibiotics or Lactobacillus rhamnosus the rats were infected by Salmonella Typhimurium and the pathogen burden in the gut was counted by colony forming unit assay. RESULTS: The gut microbiota underwent dramatic changes after both vancomycin and ampicillin treatment. The alpha diversity sharply decreased, and the microbiota composition showed a significant difference. However, the gut microbiota recovered within four weeks after stopping antibiotics administration, although this recovery was incomplete. Oral microbiota did not show significant alterations in both alpha and beta diversities. The number of pathogens in the gut in the control group was significantly lower than that in the antibiotic-treated group but only lasted for the first 4 days after infection. CONCLUSIONS: Antibiotics cause dramatic alterations in the number and diversity of gut microbiota but not oral microbiota. These changes in the gut microbiota could incompletely recover four weeks later. When infected with pathogens after antibiotic administration, the rats show a decrease in colonization resistance in the gut for the first four days after infection.
Asunto(s)
Antibacterianos/efectos adversos , Resistencia a la Enfermedad , Disbiosis/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Salmonelosis Animal , Ampicilina/efectos adversos , Animales , Boca/microbiología , ARN Ribosómico 16S , Ratas , Salmonella typhimurium , Vancomicina/efectos adversosRESUMEN
BACKGROUND & AIMS: The enteric nervous system (ENS) exists in close proximity to luminal bacteria. Intestinal microbes regulate ENS development, but little is known about their effects on adult enteric neurons. We investigated whether intestinal bacteria or their products affect the adult ENS via toll-like receptors (TLRs) in mice. METHODS: We performed studies with conventional C57/BL6, germ-free C57/BL6, Nestin-creERT2:tdTomato, Nestin-GFP, and ChAT-cre:tdTomato. Mice were given drinking water with ampicillin or without (controls). Germ-free mice were given drinking water with TLR2 agonist or without (controls). Some mice were given a blocking antibody against TLR2 or a TLR4 inhibitor. We performed whole gut transit, bead latency, and geometric center studies. Feces were collected and analyzed by 16S ribosomal RNA gene sequencing. Longitudinal muscle myenteric plexus (LMMP) tissues were collected, analyzed by immunohistochemistry, and levels of nitric oxide were measured. Cells were isolated from colonic LMMP of Nestin-creERT2:tdTomato mice and incubated with agonists of TLR2 (receptor for gram-positive bacteria), TLR4 (receptor for gram-negative bacteria), or distilled water (control) and analyzed by flow cytometry. RESULTS: Stool from mice given ampicillin had altered composition of gut microbiota with reduced abundance of gram-positive bacteria and increased abundance of gram-negative bacteria, compared with mice given only water. Mice given ampicillin had reduced colon motility compared with mice given only water, and their colonic LMMP had reduced numbers of nitrergic neurons, reduced neuronal nitric oxide synthase production, and reduced colonic neurogenesis. Numbers of colonic myenteric neurons increased after mice were switched from ampicillin to plain water, with increased markers of neurogenesis. Nestin-positive enteric neural precursor cells expressed TLR2 and TLR4. In cells isolated from the colonic LMMP, incubation with the TLR2 agonist increased the percentage of neurons originating from enteric neural precursor cells to approximately 10%, compared with approximately 0.01% in cells incubated with the TLR4 agonist or distilled water. Mice given an antibody against TLR2 had prolonged whole gut transit times; their colonic LMMP had reduced total neurons and a smaller proportion of nitrergic neurons per ganglion, and reduced markers of neurogenesis compared with mice given saline. Colonic LMMP of mice given the TLR4 inhibitor did not have reduced markers of neurogenesis. Colonic LMMP of germ-free mice given TLR2 agonist had increased neuronal numbers compared with control germ-free mice. CONCLUSIONS: In the adult mouse colon, TLR2 promotes colonic neurogenesis, regulated by intestinal bacteria. Our findings indicate that colonic microbiota help maintain the adult ENS via a specific signaling pathway. Pharmacologic and probiotic approaches directed towards specific TLR2 signaling processes might be developed for treatment of colonic motility disorders related to use of antibiotics or other factors.
Asunto(s)
Disbiosis/fisiopatología , Sistema Nervioso Entérico/fisiología , Microbioma Gastrointestinal/fisiología , Neurogénesis/fisiología , Receptor Toll-Like 2/metabolismo , Adulto , Ampicilina/administración & dosificación , Ampicilina/efectos adversos , Animales , Células Cultivadas , Colon/inervación , Colon/microbiología , Colon/fisiología , Modelos Animales de Enfermedad , Disbiosis/inducido químicamente , Disbiosis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Motilidad Gastrointestinal/efectos de los fármacos , Motilidad Gastrointestinal/fisiología , Vida Libre de Gérmenes , Humanos , Masculino , Ratones , Ratones Transgénicos , Plexo Mientérico/citología , Plexo Mientérico/fisiología , Nestina/genética , Neurogénesis/efectos de los fármacos , Neuronas Nitrérgicas/fisiología , Óxido Nítrico/metabolismo , Cultivo Primario de Células , Receptor Toll-Like 2/agonistas , Receptor Toll-Like 2/antagonistas & inhibidores , Receptor Toll-Like 4/agonistas , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/metabolismoRESUMEN
Vitiligo is impacted by environmental triggers. We studied the contribution of the microbiome in FH mice, in which depigmentation is mediated by tyrosinase-reactive T cells. The mice received oral antibiotics and were monitored for depigmentation. The microbiome was studied in fecal and skin samples using 16S rRNA analysis. The resulting T-cell distributions were evaluated. In untreated mice, pigment loss did not expand to the pelage, whereas mice in the ampicillin group were approximately 1/3 depigmented at 30 weeks. In contrast to models of autoimmunity that are less dependent on IFN-γ, ampicillin but not neomycin treatment correlated with accelerated disease and reduced bacteria in the fecal pellets. Modified cytokine patterns in the tissue and serum suggest a response that transcends the gut. Ampicillin-induced depigmentation was accompanied by gut but not skin dysbiosis, and reduced T cell numbers in both sites. Neomycin induced a redistribution of gut T cells and an accumulation of skin regulatory T cells. This treatment spurred a Bacteroides-dominated population of fecal bacteria. Reduced diversity is prominent particularly after ampicillin treatment, when the gut is dominated by Pseudomonas species. In line with current concepts relating the microbiome and the immune system, we predict that dietary measures might promote skin health and delay vitiligo onset.
Asunto(s)
Antibacterianos/efectos adversos , Disbiosis/inducido químicamente , Microbiota/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Vitíligo/inmunología , Administración Oral , Ampicilina/administración & dosificación , Ampicilina/efectos adversos , Animales , Antibacterianos/administración & dosificación , Bacteroides/genética , Bacteroides/aislamiento & purificación , Citocinas/análisis , Citocinas/inmunología , Citocinas/metabolismo , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Modelos Animales de Enfermedad , Disbiosis/inmunología , Disbiosis/microbiología , Heces/microbiología , Femenino , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Masculino , Ratones , Microbiota/inmunología , Neomicina/administración & dosificación , Neomicina/efectos adversos , Pseudomonas/genética , Pseudomonas/aislamiento & purificación , ARN Ribosómico 16S/genética , Piel/citología , Piel/inmunología , Piel/microbiología , Piel/patología , Vitíligo/sangre , Vitíligo/microbiología , Vitíligo/patologíaRESUMEN
BACKGROUND: Bacterial infection of the urinary tract is among the common reasons for seeking medical attention in the community. Rapidly increasing antibiotic resistance of uropathogens is resulting in limited treatment options. Therefore, knowledge of the current uropathogens and their antibiotic susceptibility is important for better treatment of urinary tract infection. METHODS: A cross-sectional study design was conducted from February to September thirty, 2017 among students who came to Mekelle University student's clinics with symptomatic urinary tract infection during the study period.. Mid-stream urine specimens were collected from 341individuals with suspected urinary tract infection for bacteriological identification and antimicrobial susceptibility testing. Data on socio-demographic, clinical and risk factors were also collected using a structured questionnaire. RESULTS: Among the 341 study participants, 72(21.1%) showed significant bacteriuria. Escherichia coli (48.6%), Coagulase-negative staphylococci (23%), Staphylococcus aureus (13.5%), and Klebsiella spp. (8.1%) were common bacterial isolates. Resistance to ampicillin (81-100%), amoxicillin/clavulanic acid (77-93.6%), co- trimoxazole (55 72.3%), nalidixic acid (57.4%) and tetracycline (46-55.5%) was seen by most isolates. Multidrug resistance was observed in 73% of the bacterial isolates, and 25.5% of the Gram-negative isolates were extended-spectrum beta-lactamase producers. Being female, a history of urinary tract infection, a history of catheterization and frequent sexual activity were found to be statistically associated with urinary tract infection. CONCLUSION: Urinary tract infection is a problem among university students with a prevalence of 21.1%. All isolates have developed resistance to most of the commonly used antibiotics. Therefore, health education on the transmission and causes of urinary tract infection are recommended for the students.