RESUMO
Objectives: To confirm the presence of allergy to penicillin and amoxicillin by in vivo exposure tests in patients with a history of immediate reaction to these drugs. Methods: Observational, cross-sectional, descriptive and prolective study. Patients between 12 and 60 years old with a history of immediate reaction after administration of penicillin and/or amoxicillin were included. Skin prick and intradermal tests were performed with benzylpenicilloyl polylysine and penicillin G, as well as oral challenge with amoxicillin. Results: Ten female and 3 male patients were included. The mean age was 39 years. In 84.6% of the cases the last adverse drug reaction occurred 10 years ago and in all cases it manifested with urticaria. Allergy to penicillin was corroborated in only 38.4% of cases. The most frequent adverse reaction after in vivo exposure tests was pruritus in 23%. Conclusions: Patients with suspected penicillin allergy should be evaluated by in vivo exposure testing with major and minor determinants to corroborate or rule out allergic reactions and improve treatment conditions.
Objetivos: Confirmar la presencia de alergia a penicilina y amoxicilina mediante pruebas de exposición in vivo, en pacientes que refieren antecedente de reacción inmediata con estos medicamentos. Métodos: Estudio observacional, transversal, descriptivo y prolectivo. Se incluyeron pacientes entre 12 y 60 años con antecedente de reacción inmediata tras administración de penicilina y/o amoxicilina. Se realizaron pruebas cutáneas por prick e intradérmicas con bencilpeniciloil polilisina y penicilina G, así como desafío oral con amoxicilina. Resultados: Se incluyeron 10 pacientes femeninos y 3 masculinos. La edad promedio fue 39 años. En 84,6% de los casos la última reacción adversa a medica- mentos ocurrió 10 años atrás y en todos los casos se manifestó con urticaria. Sólo en el 38,4% se corroboró alergia a penicilina. La reacción adversa más frecuen- te, tras las pruebas de exposición in vivo fue prurito en el 23%. Conclusiones: Los pacientes con sospecha de alergia a penicilina se deben evaluar mediante pruebas de exposición in vivo con los determinantes mayores y menores, para corroborar o descartar reacciones alérgicas y mejorar las condiciones de tratamiento.
Assuntos
Hipersensibilidade a Drogas , Urticária , Humanos , Masculino , Feminino , Adulto , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Estudos Transversais , Testes Cutâneos , Penicilinas/efeitos adversos , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversosRESUMO
Background: The most commonly reported antibiotic allergy is penicillin. The false label of "allergy" to penicillin negatively affects the patient's quality of life and medical care. Objective: To determine the frequency of allergy to penicillin and amoxicillin by in vivo exposure tests in patients with a history of immediate reaction to this class of medicinal products. Methods: Observational, cross-sectional, descriptive and prolective study in patients between 12 and 60 years of age with a history of immediate reaction to penicillin and/or amoxicillin. Prick and intradermal skin tests were performed with benzylpenicilloyl polylysine (Pre-Pen), penicillin G and oral challenge test with amoxicillin. The frequency of positivity and negativity in these tests was calculated with a 95% CI. Results were analyzed in Epi info 7.2.5.0. Results: In total 13 patients (10 women) were included, with a mean age of 39 years (SD 12.14). In 84.6% the last adverse drug reaction occurred 10 years ago and in all manifested with urticaria. The 38.4% confirmed penicillin allergy and the most frequent adverse reaction after in vivo tests was pruritus. Conclusions: The clinical history alone is not sufficient, all patients with suspected penicillin allergy should be evaluated by in vivo exposure tests with major and minor determinants to corroborate or rule out allergy to this pharmacological class.
Antecedentes: La alergia a antibióticos notificada con más frecuencia es la penicilina. La falsa etiqueta de "alergia" a la penicilina afecta negativamente la calidad de vida del paciente y la atención médica. Objetivo: Determinar la frecuencia de alergia a penicilina y amoxicilina mediante pruebas de exposición in vivo, en pacientes con antecedente de reacción inmediata a esta clase de medicamentos. Métodos: Estudio observacional, transversal, descriptivo y prolectivo en pacientes entre 12 y 60 años con antecedente de reacción inmediata a penicilina y/o amoxicilina. Se realizaron pruebas cutáneas por prick e intradérmicas con bencilpeniciloil polilisina y penicilina G, y prueba de reto oral con amoxicilina. La frecuencia de positividad y negatividad en estas pruebas fue calculado con un IC del 95%. Los resultados se analizaron en Epi info 7.2.5.0. Resultados: Se incluyeron 13 pacientes (10 mujeres), con una media de edad de 39 años (DE 12.14) y diagnóstico predominante de rinitis alérgica (61,5%). En 84,6% de casos la última reacción adversa a medicamentos ocurrió 10 años atrás y en todos se manifestó con urticaria. Sólo en cinco pacientes (38,4%) se corroboró alergia a penicilina y la reacción adversa más frecuente tras las pruebas in vivo fue prurito (23 %). Conclusiones: La historia clínica por sí sola no es suficiente, todos los pacientes con sospecha de alergia a penicilina deben ser evaluados mediante pruebas de exposición in vivo con los determinantes mayores y menores para corroborar o descartar alergia a esta clase farmacológica.
Assuntos
Hipersensibilidade a Drogas , Urticária , Adulto , Feminino , Humanos , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Estudos Transversais , Penicilinas/efeitos adversos , Qualidade de Vida , Testes Cutâneos/métodos , Masculino , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-IdadeAssuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina/efeitos adversos , Estudos Retrospectivos , Chile , Antibacterianos/efeitos adversos , Infecções por Helicobacter/tratamento farmacológico , Quimioterapia Combinada , Inibidores da Bomba de Prótons/efeitos adversos , Resultado do Tratamento , Claritromicina/efeitos adversosRESUMO
AIM: To evaluate the frequency of side effects associated with intake of metronidazole (MTZ) + amoxicillin (AMX) in periodontal treatment, and to explore associations between these events and patients' features. MATERIALS AND METHODS: Data of five randomized clinical trials testing MTZ + AMX adjunctive to mechanical therapy were evaluated. Volunteers answered an adverse event questionnaire. RESULTS: Information from 656 subjects was assessed. The frequency of side effects in the antibiotic- and placebo-treated groups ranged from 1.0% to 17.7% and 0.9% to 13.7%, respectively. The events more frequently observed in the antibiotic than in the placebo group were diarrhoea and metallic taste (p < .05). Diabetes significantly raised the odds of a patient reporting discomfort (odds ratio [OR] = 2.6), diarrhoea (OR = 4.0), weakness (OR = 6.0) and excessive sleepiness (OR = 2.9). In systemically healthy volunteers, using antibiotics 3 months post-mechanical treatment (healing phase) (OR = 3.0), being a woman (OR = 3.9) and aged ≤49 (OR = 4.5) significantly increased the chances of reporting adverse events. CONCLUSIONS: The occurrence of side effects during MTZ + AMX treatment ranged from uncommon (1%) to very common (17.7%). The main factors raising the chances of a patient reporting adverse events were diabetes and taking antibiotics in the healing phase, instead of in the active phase of treatment. Patients ≤ 49 years old and females also tend to report more side effects.
Assuntos
Amoxicilina , Periodontite Crônica , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Periodontite Crônica/terapia , Raspagem Dentária , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Metronidazol/efeitos adversos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos RetrospectivosRESUMO
BACKGROUND: The association of scaling and root planing (SRP) with systemic metronidazole (MTZ) plus amoxicillin (AMX) has shown to be an effective treatment protocol, particularly for periodontitis stages III and IV, generalized. More recently, probiotics have also been suggested as a promising adjunctive treatment for periodontal diseases due to their antimicrobial and anti-inflammatory properties. Therefore, the aim of this randomized clinical trial (RCT) is to evaluate the clinical, microbiological, and immunological effects of probiotics as adjuncts to SRP alone or with MTZ+AMX in the treatment of periodontitis. METHODS: Subjects with periodontitis are being randomly assigned to receive (i) SRP alone, or with (ii) two probiotic lozenges/day for 90 days (Prob), (iii) MTZ (400 mg) and AMX (500 mg) thrice a day (TID) for 14 days (MTZ+AMX), or (iv) Prob and MTZ+AMX. Subjects are being monitored for up to 12 months post-treatment. Nine subgingival plaque samples per patient are being collected at baseline and at 3, 6, and 12 months post-therapy and analyzed by checkerboard DNA-DNA hybridization for 40 bacterial species. Peripheral blood and gingival crevicular fluid (GCF) of four randomly selected periodontal sites will be analyzed by means of a multiplex fluorescent bead-based immunoassay for 17 cyto/chemokines. STATISTICAL ANALYSES: The significance of differences in each group (over the course of the study) will be sought using repeated measures ANOVA or Friedman tests and among groups (at each time point) using either ANOVA/ANCOVA or Kruskal-Wallis tests, depending on normality of the data. The chi-square test will be used to compare differences in the frequency of subjects achieving the clinical endpoint for treatment (≤ 4 sites with PD ≥ 5 mm) at 1 year and of self-perceived adverse effects. A stepwise forward logistic regression analysis will be performed in order to investigate the impact of different predictor variables on the percentage of patients achieving the clinical endpoint for treatment. The Number Needed to Treat (NNT) with different treatment protocols will be also calculated. Statistical significance will be set at 5%. TRIAL REGISTRATION: ClinicalTrials.gov NCT03733379. Registered on November 7, 2018.
Assuntos
Periodontite Crônica , Probióticos , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Raspagem Dentária , Método Duplo-Cego , Humanos , Metronidazol/efeitos adversos , Probióticos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Aplainamento RadicularRESUMO
PROBLEM: Gut dysbiosis is caused by several factors, including the use of antibiotics. Since intestinal dysbiosis is associated with a wide range of immunopathological and reproductive conditions, the main goal of this study was to evaluate amoxicillin-induced gut dysbiosis and its influence on the oestrous cycle in mice. METHOD OF STUDY: Mice were treated with amoxicillin or PBS, and faecal microbiota was evaluated by 16S rDNA metagenomic sequencing. The oestrous cycle was evaluated by vaginal cytology, vaginal opening and flow cytometry. After the induction of gut dysbiosis, the ovaries and the caecum were analysed to differential expression of IL-1ß and IL-10 genes and histological analysis. RESULTS: Amoxicillin-treated mice presented differing bacterial groups in the faecal microbiota when compared to the PBS-treated group indicating that amoxicillin treatment-induced gut dysbiosis and they gained weight. The vaginal cytology analysis showed that amoxicillin-induced gut dysbiosis decreased the number of cells but increased the relative number of leucocytes and altered the oestrous cycle. IL-1ß was shown to be upregulated in the caecum and in the ovary of the dysbiotic mice. On the other hand, IL-10 expression was shown to be diminished in both organs of the dysbiotic mice. The oocyte area from dysbiotic group presented lower than non-dysbiotic mice with increasing thickness of the pellucid zone. The follicular teak from dysbiotic mice showed lower thickness than non-dysbiotic mice. CONCLUSION: The results indicate that amoxicillin induces gut dysbiosis and influences the oestrous cycle and the inflammatory status of the ovary and the caecum.
Assuntos
Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Ceco/fisiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Disbiose/imunologia , Ciclo Estral/efeitos dos fármacos , Ovário/fisiologia , Animais , Citocinas/metabolismo , Disbiose/etiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Camundongos , Camundongos da Linhagem 129RESUMO
RESUMEN Introducción: la toxicidad de los fármacos es compleja y difícilmente valorable, por la cantidad de factores que intervienen en su producción, como modo de aparición, duración y gravedad de las reacciones adversas. La importancia de estas reacciones está dada por la frecuencia y gravedad con que un fármaco o familia de fármacos las producen. Objetivo: caracterizar las principales reacciones adversas que provocan los medicamentos, los grupos de edades con más riesgos, los sistemas de órganos que se afectan, la frecuencia, imputabilidad y la intensidad de las mismas. Materiales y métodos: estudio observacional, descriptivo, de serie de casos en farmacovigilancia. El universo fue las reacciones adversas de los 10 fármacos más notificados por la Unidad Coordinadora Provincial de Farmacovigilancia en Matanzas, en el periodo 2014-2017. Se estudiaron las variables: medicamentos, grupo farmacológico, datos demográficos, nivel de atención, tipo de efecto adverso, intensidad, imputabilidad y frecuencia. Resultados: se notificaron 10 fármacos con 2 216 reacciones. La vacuna pentavalente fue la más notificada, con un 17,6 %, seguido por la amoxicilina y las penicilinas. Predominó el sexo femenino con 1 279 reportes, (59,1 %) y los adultos, con 1 010 notificaciones, (46,6 %). La atención primaria de salud fue la de mayor número de notificaciones, 2 082 reportes, (96,1 %). Las principales reacciones fueron: la erupción cutánea, la fiebre y la urticaria. Predominaron reacciones moderadas; 1 972 reportes, (91,1 %), aquellas clasificadas como probables, 1 887 reportes, (87,1 %) y las frecuentes con 1 284 reportes, (59,2 %). Conclusiones: el sistema de farmacovigilancia en la provincia proporcionó sistemáticamente información sobre la seguridad de los medicamentos, lo que permitió el conocimiento de la relación beneficio-riesgo de los medicamentos presentes en el mercado, así como los más usados.
ABSTRACT Introduction: drugs toxicity is complex and of difficult assessment, due to the quantity of factors intervening in its production, like emergency way, duration, and seriousness of the adverse reactions. The importance of these reactions is given by the frequency and seriousness a drug or a drug family produces them. Objective: to characterize the main adverse reactions caused by medicines, the age groups having higher risk, the most affec6ted systems of organs, frequency, imputability and intensity. Material and methods: descriptive, observational study of a series of cases in pharmacovigilance. The universe was the adverse reactions of the ten drugs most reported by the Provincial Coordinating Unit of Pharmacovigilance in the period 2014-2017. The studied variables were: drugs, pharmacological group, demographic data, health care level, kind of adverse effect, intensity, imputability and frequency. Results: ten drugs were reported with 2 216 reactions. The pentavalent vaccine was the most reported one, with 17.6 %, followed by amoxicillin and penicillin. There was a predominance of the female sex with 1 279 reports (59.1 %), and adult people with 1 010 reports (46.6 %). The highest number of reports was made by the primary health care, 2 082 (96.1 %). The main reactions were skin rash, fever and urticaria. There was a predominance of mild reactions: 1 972 reports (91.1 %); reactions classified as probable: 1 887 reports (87.1 %): ands frequent ones: 1 284 reports (59.2 %). Conclusions: the pharmacovigilance system in the province systematically provided information on drugs´ safeness that allowed knowing the benefit-risk relation of the medicines that are in the market, and also which are the most used ones.
Assuntos
Humanos , Feminino , Adulto , Penicilinas/efeitos adversos , Medição de Risco , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Órgãos em Risco , Farmacovigilância , Amoxicilina/efeitos adversos , Urticária/diagnóstico , Epidemiologia Descritiva , Exantema Súbito/diagnóstico , Febre/diagnóstico , Estudo ObservacionalRESUMO
BACKGROUND: The combination of systemic metronidazole (MTZ) and amoxicillin (AMX) with scaling and root planing (SRP) has shown to be an effective periodontal treatment. However, some essential issues associated with the use of these antibiotics remain unanswered, such as the ideal time of administration during the course of periodontal treatment. Although these agents are often prescribed after the healing phase of the SRP procedure, there is biological plausibility to support its use in conjunction with the mechanical treatment. However, to date, no placebo controlled randomized clinical trial (RCT) has directly compared these two protocols. Therefore, the aim of this RCT is to compare the clinical, microbiological and immunological effects of the adjunctive systemic MTZ + AMX administered in different phases of the treatment of severe periodontitis. METHODS: Subjects with severe periodontitis (n = 180) are being randomly assigned into three groups (n = 60/group): (i) SRP-only (control group), SRP in combination with 400 mg MTZ + 500 mg AMX, starting (ii) at the first SRP session (active phase group), or (iii) after 3 months of its completion (healing phase group). All volunteers are receiving clinical and microbiological evaluation at baseline, 3, 6 and 12 months, and immunological assessment at baseline and 12 months post-therapy. Nine subgingival biofilm samples are being collected per subject and analyzed for counts and proportions of 40 bacterial species by checkerboard DNA-DNA hybridization, and six gingival crevicular fluid samples are being collected and analyzed for the levels of 20 chemokines by multiplex immunoassay. The primary outcome variable is the number of volunteers reaching the clinical endpoint for treatment (≤ 4 sites with probing depth ≥5 mm) at 1 year post-therapy. Differences in clinical, microbiological and immunological parameters among groups and over time will be evaluated using analysis of variance, analysis of covariance and the Chi-square and Tukey tests. Microbiological and immunological analyses will be performed using adjustments for multiple comparisons. Statistical significance will be set at 5%. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02954393 . Registered on 3 November 2016.
Assuntos
Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Metronidazol/administração & dosagem , Periodontite/tratamento farmacológico , Adulto , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Brasil , Raspagem Dentária , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metronidazol/efeitos adversos , Estudos Multicêntricos como Assunto , Periodontite/diagnóstico , Periodontite/microbiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Aplainamento Radicular , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Although antibiotic de-escalation is regarded as a measure that reduces selection pressure, adverse drug effects and costs, evidence supporting this practice in community-acquired pneumococcal pneumonia (CAPP) is lacking. METHODS: We carried out a retrospective analysis of prospectively collected data of a cohort of hospitalized adults with CAPP. Pneumococcal aetiology was established in patients with one or more positive cultures for Streptococcus pneumoniae obtained from blood, sterile fluids or sputum, and/or a positive urinary antigen test. De-escalation therapy was considered when the initial antibiotic therapy was narrowed to penicillin, amoxicillin or amoxicillin/clavulanate within the first 72 h after admission. The primary outcomes were 30 day mortality and length of hospital stay (LOS). Adjustment for confounders was performed with multivariate and propensity score analyses. RESULTS: Of 1410 episodes of CAPP, antibiotic de-escalation within the first 72 h after admission was performed in 166 cases. After adjustment, antibiotic de-escalation was not associated with a higher risk of mortality (ORâ=â0.83, 95% CIâ=â0.24-2.81), but it was found to be a protective factor for prolonged LOS (above the median) (ORâ=â0.46, 95% CIâ=â0.30-0.70). Similar results were found in patients classified into high-risk pneumonia severity index classes (IV-V), those with clinical instability and those with bacteraemia. No significant differences were documented in adverse drug reactions or readmission (<30 days). CONCLUSIONS: Antibiotic de-escalation seems to be safe and effective in reducing the duration of LOS, and did not adversely affect outcomes of patients with CAPP, even those with bacteraemia and severe disease, and those who were clinically unstable.
Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Amoxicilina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Bacteriemia/tratamento farmacológico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Penicilinas/uso terapêutico , Pneumonia Pneumocócica/tratamento farmacológico , Idoso , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Antibacterianos/uso terapêutico , Bacteriemia/mortalidade , Infecções Comunitárias Adquiridas/mortalidade , Feminino , Hospitalização , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Penicilinas/administração & dosagem , Penicilinas/efeitos adversos , Pneumonia Pneumocócica/mortalidade , Estudos Prospectivos , Estudos Retrospectivos , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Resultado do TratamentoRESUMO
BACKGROUND: Reactions to beta-lactams are frequent and it is difficult to establish the relationship between the drug and symptoms. OBJECTIVE: To describe the clinical characteristics and explore the immunological mechanisms of patients with suspected adverse reaction to beta-lactams. METHODS: Retrospective study of patients with a history of beta-lactam reaction and tests for reactions to drugs. RESULTS: Out of 125 patients, 71 were women (56.8%); 73 had a history of immediate reaction and 52 delayed reaction; 590 allergy tests were done: specific IgE measurement, skin prick, patch, and provocation tests. The drugs most often related were amoxycillin, in 62 patients (49.6%), crystalline penicillin in 17 (13.6%), benzathine penicillin in 15 (12%), and cefalexin in 13 (10.4%). The severity of the reaction was mild in the majority (82%). 7.7% had a history of anaphylaxis and 10.8% sought care for a positive penicillin skin test, without history of reaction. Only 6.7% resulted in a positive test. More than 62% began testing two years after the reaction for which they sought care. CONCLUSIONS: The clinical history is insufficient to determine allergy to beta-lactams. In our sample, few patients with a history of beta-lactam reaction had evidence of immune-mediated reactions.
Antecedentes: Las reacciones a betalactámicos son frecuentes y es difícil establecer la relación entre el medicamento y los síntomas. Objetivo: Describir las características clínicas y explorar los mecanismos inmunológicos de pacientes con sospecha de reacción adversa a betalactámicos. Métodos: Estudio retrospectivo de pacientes con antecedentes de reacción a betalactámicos y pruebas para reacción con medicamentos. Resultados: De 125 pacientes, 71 eran mujeres (56.8%); 73 tenían historia de reacción inmediata y 52 de reacción tardía; Se realizaron 590 pruebas de alergia: medición de IgE específica, pruebas intradérmicas, de parche y de provocación. Los medicamentos más relacionados fueron amoxicilina, en 62 pacientes (49.6%), penicilina cristalina en 17 (13.6%), penicilina benzatínica en 15 (12%) y cefalexina en 13 (10.4%). La severidad de la reacción fue leve en la mayoría (82%). 7.7% tuvo antecedente de anafilaxia y 10.8% consultaba por una prueba cutánea con penicilina positiva, sin antecedente de reacción. Solo 6.7% resultó con una prueba positiva. Más de 62% inició los estudios dos años después de la reacción por la que consultó. Conclusiones: La historia clínica es insuficiente para determinar la alergia a betalactámicos. En nuestra muestra, pocos pacientes con antecedente de reacción a betalactámicos tuvo evidencia de reacciones inmunológicamente mediadas.