Confianza y actitud tras un diagnóstico negativo de alergia a fármacos betalactámicos y/o AINE / Trust and attitude after a negative diagnosis for allergy to betalactam drugs and/or NSAIDs

Objetivo: determinar el grado de confianza en el diagnóstico de exclusión de alergia en pacientes con sospecha de hipersensibilidad a antibióticos betalactámicos y/o AINE. Adicionalmente se pretendía describir la actitud del paciente hacia la toma futura del fármaco que motivó el estudio.Método: se realizó un estudio descriptivo transversal. Se seleccionaron 103 pacientes mayores de 18 años, de ambos sexos y con un resultado negativo en las pruebas diagnósticas de alergia a betalactámicos y/o AINE. Los participantes fueron evaluados mediante un cuestionario heteroadministrado en la práctica clínica habitual de alergología.Resultados: el grado de confianza hacia la etiqueta previa de alergia fue moderado para antibióticos betalactámicos (6,4/10) y para AINE (6,1/10), elevado hacia el diagnóstico negativo de alergia (betalactámicos: 7,5/10; AINE: 7,9/10), y moderado con relación a la futura toma del fármaco estudiado, tras un diagnóstico negativo de alergia (betalactámicos: 6,7/10; AINE: 6,3/10). El grado de confianza hacia el diagnóstico de exclusión de alergia a betalactámicos o AINE aumenta con relación al conferido previamente por el de sospecha, en ambos fármacos (p= 0,01).Conclusiones: el grado de confianza de los pacientes en el diagnóstico de exclusión de alergia a fármacos betalactámicos y/o AINE es elevado. Sin embargo, la confianza para la toma futura del fármaco que motivó el estudio, tras un diagnóstico negativo de alergia, se reduce a moderada. Los profesionales de la salud deben proporcionar una educación sanitaria efectiva que resuelva las inseguridades hacia la realización de la prueba y refuerce la confianza del paciente para la toma futura del fármaco.(AU)

Objective: to determine the level of trust in the diagnosis excluding allergy in patients with suspected hypersensitivity to betalactam antibiotics and/or NSAIDs. Additionally, it was intended to describe the attitude of patients towards taking in the future the drug which motivated the study.Method: a descriptive cross-sectional study was conducted; 103 >18-year old patients were selected, of both genders and with a negative result in diagnostic tests for betalactam drugs and/or NSAIDs. Participants were evaluated through a heteroadministered questionnaire at their usual Allergology clinical practice.Results: the level of trust towards the previous allergy label was moderate for betalactam antibiotics (6.4/10) and for NSAIDs (6.1/10), high towards the negative diagnosis for allergy (betalactam drugs: 7.5/10; NSAIDs: 7.9/10), and moderate regarding taking in the future the drug under study, after a negative diagnosis for allergy (betalactam drugs: 6.7/10; NSAIDs: 6.3/10). The degree of trust towards the diagnosis excluding allergy to betalactam drugs or NSAIDs increased regarding the previous degree for suspected allergy, in both drugs (p= 0.01).Conclusions: there is a high degree of trust in patients regarding their diagnosis excluding allergy to betalactam drugs and/or NSAIDs. However, trust regarding taking in the future the drug which motivated the study, after a negative diagnosis of allergy, was reduced to moderate. Health professionals must provide effective health education that solves uncertainties in terms of conducting the test and reinforces trust by patients for taking the drug in the future.(AU)

Adverse events associated with antimicrobial compounds in a general hospital in Chile / Efectos adversos asociados al uso de antibióticos en un hospital general

ABSTRACT Background: Antimicrobial compounds are associated with a wide range of adverse events (AE) and some of them can be potentially preventable. Aim: To characterize AE associated with antimicrobial compounds. Patients and Methods: Retrospective analysis of AEs reported to the National Pharmacological Surveillance System from 2014 to 2017 in a regional hospital. Severity, causality and preventability were analyzed. Results: Sixty events were observed in 56 patients aged 2 months to 96 years. Cases were registered mostly in hospitalized patients. The most frequent AEs were skin disorders (56.7%), followed by hepatobiliary (13.3%), and CNS events (10%). Blood, kidney, respiratory gastrointestinal and immunological disorders were less frequently registered, including cases with anaphylactic shock and Stevens-Johnson syndrome (SJS). Causal analysis indicated a definitive association in 8.3%, probable in 70% and possible in 22%. Skin lesions were mostly associated with beta-lactams, hepatobiliary disorders with antituberculosis drugs and CNS manifestations with carbapenems. Cutaneous, neurological, and hepatobiliary events appeared at a median of 4, 2.5 and 10.5 days after starting the medication, respectively. AEs were managed with withdrawal of the suspected drug (83.3%) and other auxiliary therapies. AEs were categorized as severe in 22% and one case with SJS had a fatal outcome (1.7%). Preventability analysis revealed 25% of potentially avoidable events. Conclusions: Antimicrobial AE involved a wide diversity of compounds, occurred in different hospitalization units, affected patients of a wide age range and attacked different systems or organs. An important fraction was potentially avoidable.

Antecedentes: Los compuestos antimicrobianos están asociados a una amplia gama de eventos adversos (EA) y algunos de ellos pueden ser potencialmente prevenibles. Objetivos: Caracterizar los EA asociados a compuestos antimicrobianos. Pacientes y Métodos: Análisis retrospectivo de EA reportados al Sistema Nacional de Farmacovigilancia desde 2014 la 2017 en un hospital regional. Se incluyó un análisis de gravedad, causalidad y de posible prevención. Resultados: Se observaron 60 eventos en 56 pacientes de 2 meses a 96 años. Los casos se registraron principalmente en pacientes hospitalizados. Los EA más frecuentes fueron los trastornos de la piel (56,7%), seguidos de los hepatobiliares (13,3%) y del sistema nervioso central (10%). Los hematológicos, renales, respiratorios, gastrointestinales e inmunológicos se registraron con menos frecuencia, incluidos casos con shock anafiláctico y síndrome de Stevens-Johnson (SSJ). El análisis de causalidad indicó una asociación definitiva en 8.3%, probable en 70% y posible en 21.7%. Las lesiones cutáneas se asociaron principalmente a betalactámicos, los trastornos hepatobiliares a fármacos antituberculosos y las manifestaciones del SNC a carbapenémicos. Los eventos cutáneos, neurológicos y hepatobiliares se presentaron en una mediana de 4, 2,5 y 10,5 días después de iniciar el medicamento, respectivamente. Los EA se manejaron con el retiro del fármaco sospechoso (83,3%) y otras terapias auxiliares. Los EA se clasificaron como graves (21,7%) y un caso con SSJ tuvo un desenlace fatal (1,7%). Un 25% de los eventos fue potencialmente evitable. Conclusiones: Los resultados de este trabajo revelan que los AE por antimicrobianos involucran una amplia diversidad de compuestos, ocurren en diferentes unidades de hospitalización, afectan a pacientes de un amplio rango de edad y atacan diferentes sistemas u órganos.

Reacciones adversas a betalactámicos: una revisión de tema / Adverse reactions to beta-lactams: a topic review / Reações adversas a beta-lactâmicos: uma revisão de tópico

Las reacciones adversas a medicamentos son una de las principales causas de muerte en el mundo, producen muchos ingresos hospitalarios y aumentan los costos de atención. Dentro de los medicamentos que más se asocian con estas reacciones están los antibióticos y de estos los más comunes son los betalactámicos, ampliamente utilizados en las instituciones de salud. Las manifestaciones más frecuentes de las reacciones adversas a betalactámicos son alérgicas, dermatológicas, gastrointestinales, renales, hepáticas y neurológicas. Se realiza una revisión general de las reacciones adversas de estos medicamentos, se mencionan los distintos antibióticos betalactámicos con su clasificación y espectro de acción y más precisamente se explican las distintas reacciones adversas por uso de betalactámicos según el sistema comprometido.

Adverse drug reactions are one of the leading causes of death in the world. They are also responsible for an increase in hospital admissions and higher care costs. Among the most associated drugs with these reactions are antibiotics and of these the most common are beta-lactams, which are widely used in health institutions. The most fre-quent manifestations of adverse reactions to beta-lactams are allergic, dermatological, gastrointestinal, renal, hepatic and neurological reactions. A general review of the adverse reactions to these drugs is carried out. Also, the different beta-lactam antibiotics are described along with their classification and spectrum of action, and an accurate explanation of the different adverse reactions due to the use of beta-lactams according to the compromised system is made.

As reações adversas a medicamentos são uma das principais causas de morte no mundo, resultam em muitas admissões hospitalares e aumentam os custos do atendimento. Entre os medicamentos que mais se associam a essas reações estão os antibióticos e, destes, os mais comuns são os beta-lactâmicos, amplamente utilizados em instituições de saúde. As manifestações mais frequentes de reações adversas aos beta-lactâmicos são alérgicas, dermatológicas, gastrointestinais, renais, hepáticas e neurológicas. Faz-se uma revisão geral das reações adversas desses medicamentos, são mencionados os diferentes antibióticos beta-lactâmicos com sua classificação e espectro de ação, e mais precisamente explicam as diferentes reações adversas devidas ao uso de beta-lactâmicos de acordo com o sistema comprometido

Disparities in antimicrobial consumption and resistance within a country: the case of beta-lactams in Argentina / Disparidades en el consumo de antimicrobianos y la resistencia a estos dentro de un país: el caso de los betalactámicos en Argentina / Disparidades internas no consumo e na resistência aos antimicrobianos: o caso dos betalactâmicos na Argentina

ABSTRACT Objective. To describe bacterial resistance and antimicrobial consumption ratio at the subnational level in Argentina during 2018, considering beta-lactams group as a case-study. Methods. Antimicrobial consumption was expressed as defined daily doses (DDD)/1000 inhabitants. Resistance of Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus to beta-lactams was recorded. Resistance/consumption ratio was estimated calculating "R" for each region of Argentina, and this data was compared with other countries. Results. The most widely consumed beta-lactams in Argentina were amoxicillin (3.64) for the penicillin sub-group, cephalexin (0.786) for first generation cephalosporins, cefuroxime (0.022) for second generation; cefixime (0.043) for third generation and cefepime (0.0001) for the fourth generation group. Comparison between beta-lactams consumption and bacterial resistance demonstrated great disparities between the six regions of the country. Conclusions. The case-study of Argentina shows that antimicrobial consumption and resistance of the most common pathogens differed among regions, reflecting different realities within the same country. Because this situation might also be occurring in other countries, this data should be taken into account to target local efforts towards better antimicrobial use, to improve antimicrobial stewardship programs and to propose more suitable sales strategies in order to prevent and control antimicrobial resistance.

RESUMEN Objetivo. Determinar la razón entre la resistencia bacteriana y el consumo de antimicrobianos a nivel subnacional en Argentina en el 2018, considerando el grupo de los betalactámicos como estudio de caso. Métodos. El consumo de antimicrobianos se expresó como una dosis diaria determinada (DDD) por 1000 habitantes. Se registró la resistencia de Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae y Staphylococcus aureus a los betalactámicos. Se determinó la razón entre la resistencia y el consumo calculando "R" para cada región de Argentina, y estos datos se compararon con los de otros países. Resultados. Los betalactámicos más consumidos en Argentina fueron la amoxicilina (3,64) para el subgrupo de la penicilina; la cefalexina (0,786) para las cefalosporinas de primera generación; la cefuroxima (0.022) para las de segunda generación; la cefixima (0.043) para las de tercera generación, y la cefepima (0.0001) para el grupo de la cuarta generación. La comparación entre el consumo de betalactámicos y la resistencia bacteriana demostró que había grandes disparidades entre las seis regiones del país. Conclusiones. El estudio de caso en Argentina indica que el consumo de antimicrobianos y la resistencia a los patógenos más comunes difería entre las regiones; esto demuestra que hay distintas realidades dentro del mismo país. Como esta situación también se puede dar en otros países, estos datos se deben tener en cuenta para definir las actividades locales destinadas a fomentar un mejor uso de los antimicrobianos, para mejorar los programas de manejo de los antimicrobianos y para proponer estrategias de venta más adecuadas con el fin de prevenir y controlar la resistencia a los antimicrobianos.

RESUMO Objetivo. Descrever a relação entre o consumo de antimicrobianos e a resistência bacteriana no nível subnacional na Argentina em 2018, considerando o grupo dos betalactâmicos no estudo de caso. Métodos. O consumo de antimicrobianos foi representado por doses diárias definidas (DDD) por 1.000 habitantes. Foi registrada a resistência de Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae e Staphylococcus aureus aos betalactâmicos. A relação entre consumo e resistência foi calculada com base no "R" para cada região do país e os dados da Argentina foram comparados aos de outros países. Resultados. Os betalactâmicos de maior consumo na Argentina foram amoxicilina (3,64) no grupo das penicilinas, cefalexina (0,786) no grupo das cefalosporinas de primeira geração, cefuroxima (0.022) no grupo das cefalosporinas de segunda geração, cefixima (0.043) no grupo das cefalosporinas de terceira geração e cefepima (0.0001) no grupo das cefalosporinas de quarta geração. Ao se comparar o consumo de betalactâmicos e a resistência bacteriana, observou-se grande disparidade entre as seis regiões do país. Conclusões. O estudo de caso revela diferenças no consumo de antimicrobianos e na resistência dos patógenos mais comuns entre as regiões da Argentina, refletindo realidades distintas dentro do mesmo país. Como esta mesma situação pode estar ocorrendo em outros países, estes achados devem servir para direcionar os esforços locais a uma melhor utilização dos antimicrobianos, aperfeiçoar os programas de gestão do uso destes medicamentos e propor estratégias de venda mais apropriadas, visando a prevenir e controlar a resistência aos antimicrobianos.

Allergy to penicillin and betalactam antibiotics / Alergia a penicilina e antibióticos beta-lactâmicos

ABSTRACT Betalactams are the most frequent cause of hypersensitivity reactions to drugs mediated by a specific immune mechanism. Immediate reactions occur within 1 to 6 hours after betalactam administration, and are generally IgE-mediated. They clinically translate into urticaria, angioedema and anaphylaxis. Non-immediate or delayed reactions occur after 1 hour of administration. These are the most common reactions and are usually mediated by T cells. The most frequent type is the maculopapular or morbilliform exanthematous eruption. Most individuals who report allergies to penicillin and betalactams can tolerate this group of antibiotics. To make diagnosis, a detailed medical history is essential to verify whether it was an immediate or non-immediate reaction. Thereafter, in vivo and/or in vitro tests for investigation may be performed. The challenging test is considered the gold standard method for diagnosis of betalactam hypersensitivity. The first approach when suspecting a reaction to betalactam is to discontinue exposure to the drug, and the only specific treatment is desensitization, which has very precise indications. The misdiagnosis of penicillin allergy affects the health system, since the "penicillin allergy" label is associated with increased bacterial resistance, higher rate of therapeutic failure, prolonged hospitalizations, readmissions, and increased costs. Thus, it is essential to develop strategies to assist the prescription of antibiotics in patients identified with a label of "betalactam allergy" at hospitals, and to enhance education of patients and their caregivers, as well as of non-specialist physicians.

RESUMO Os beta-lactâmicos constituem a causa mais frequente de reações de hipersensibilidade a fármacos mediadas por mecanismo imunológico específico. As reações imediatas ocorrem em 1 até 6 horas após a administração do beta-lactâmico, sendo geralmente IgE-mediadas. Elas se traduzem clinicamente por urticária, angioedema e anafilaxia. As reações não imediatas ou tardias ocorrem após 1 hora da administração. São as reações mais comuns, sendo geralmente mediadas por células T. O tipo mais frequente é o exantema maculopapular ou morbiliforme. A maioria dos indivíduos que refere alergia aos beta-lactâmicos pode tolerar esse grupo de antibióticos. No diagnóstico, uma história clínica detalhada é fundamental para verificar se a reação foi do tipo imediato ou não imediato. A partir daí, podem ser realizados testes in vivo e/ou in vitro para investigação. O teste de provocação é considerado o método padrão-ouro no diagnóstico de hipersensibilidade aos beta-lactâmicos. A primeira conduta diante da suspeita de uma reação ao beta-lactâmico é suspender a exposição ao medicamento, e o único tratamento específico é a dessensibilização, que possui indicações bem precisas. O diagnóstico equivocado de alergia à penicilina afeta o sistema de saúde, pois o rótulo de "alergia à penicilina" está associado a aumento da resistência bacteriana, maior índice de falha terapêutica, hospitalizações prolongadas, readmissões e aumento dos custos. Assim, torna-se fundamental elaborar estratégias com o objetivo de auxiliar na prescrição de antibióticos em pacientes com rótulo de "alergia aos beta-lactâmicos" nos hospitais e melhorar a educação dos pacientes e seus responsáveis, além de médicos não especialistas.

Carbapenemasas y sensibilidad a los antibióticos no ß-lactámicos en Klebsiella pneumoniae resistente a los carbapenémicos en un hospital de tercer nivel de complejidad. Quito ­ Ecuador / Carbapenemases and sensitivity to non-ß-lactam antibiotics in Klebsiella pneumoniae resistant to carbapenems in a third level hospital. Quito - Ecuador

INTRODUCCIÓN. La resistencia de Klebsiella pneumoniae a carbapenémicos ha aumentado con los años, reduciendo opciones terapéuticas. Puede deberse a dos mecanismos principales, como: la producción de carbapenemasas y alteración de la permeabilidad de la membrana. OBJETIVO. Analizar la frecuencia de Klebsiella pneumoniae resistente a carbapenémicos, junto al mecanismo de resistencia informado por el Laboratorio Nacional de Referencia y la sensibilidad a antibióticos usados para uso terapéutico. MATERIA-LES Y MÉTODOS. Estudio retrospectivo, de población y muestra conocida. Se determinó la sensibilidad/resistencia de Klebsiella pneumoniae: todos los datos aislados de Klebsiella pneumoniae. Se reportaron 11 809 bacilos gram negativos pertenecientes a la familia Enterobacteriaceae. Se utilizó el sistema Whonet 5.6 2017 y BacLink2, así como la revisión de los resultados enviados al Centro Nacional de Referencia para la Resistencia a los Antimicrobianos del Instituto Nacional de Investigación de Salud Pública Izquieta Pérez para investigación de carbapenemasas en el Hospital de Especialidades Carlos Andrade Marín,en el período abril 2016 a mayo 2018. RESULTADOS. El 20,5% (2 421; 11 809) correspondieron a Klebsiella pneumoniae y de estos, 32,9% (797; 2 421) mostraron resistencia a Meropenem. Existió mayor frecuencia en muestra de orina, secreción, sangre y aspirado traqueal. Predominó en varones de más de 61 años. Se clasificó en 15 grupos fenotípicos según los perfiles de resistencia a los antibióticos utilizados como alternativa terapéutica. CONCLUSIÓN. La presencia de Klebsiella pneumoniae produjo una carbapenemasa resistente a los medi-camentos utilizados como tratamiento, llevó a pensar en el uso de otros medicamentos como: fosfomicina o ceftazidima/viabactam; sin embargo, se desarrolló medidas de control y prevención de infecciones, así como programas para el uso de antibióticos.

INTRODUCTION. The resistance of Klebsiella pneumoniae to carbapenems has increased over the years, reducing therapeutic options. It can be due to two main mechanisms, such as: the production of carbapene-mases and alteration of membrane permeability. OBJECTIVE. Analyse the frequency of carbapenem-resistant Klebsiella pneumoniae, along with the resistance mechanism reported by the National Reference Laboratory and sensitivity to antibiotics used for therapeutic use. MATERIALS AND METHODS. Retrospective study, po-pulation and known sample. The sensitivity / resistance of Klebsiella pneumoniae was determined: all isolated were Klebsiella pneumoniae. 11 809 gram negative bacillus belonging to the Enterobacteriaceae family were reported. The Whonet 5.6 2017 and BacLink2 system was used, as well as the review of the results sent to the National Reference Center for the Antimicrobial Resistance of the National Institute of Public Health Research Izquieta Pérez for carbapenemases research at the Carlos Andrade Marín Speciality Hospital, in the period april 2016 to may 2018. RESULTS. 20,5% (2 421; 11 809) were Klebsiella pneumoniae and of these, 32,9% (797; 2 421) showed resistance to Meropenem. There was a higher frequency in urine sample, secretion, blood and tracheal aspiration. Predominance in males over 61 years old. It was classified into 15 phenotypic groups according to antibiotic resistance profiles used as a therapeutic alternative. CONCLUSION. The pre-sence of Klebsiella pneumoniae produced a carbapenemase drug-resistance used as treatment, leading to thought on the use of other medicines such as phosphomycin or ceftazidima/avibactam; however, infection control and prevention measures were developed, as well as programs for the use of antibiotics.

Clonal relationships, antimicrobial susceptibilities, and molecular characterization of extended-spectrum beta-lactamase-producing Escherichia coli isolates from urinary tract infections and fecal samples in Southeast Iran

Abstract INTRODUCTION: Multidrug-resistant (MDR) Escherichia coli, a species that is a leading cause of urinary tract infections (UTIs) and is a major global public health concern. This study was designed to detect the differences in antibiotic resistance patterns, the production and type of extended spectrum β-lactamases (ESBLs), and the clonal relationships among E. coli isolates from UTIs and fecal samples. METHODS: Antibacterial resistance was determined by the disk diffusion method. ESBL, carbapenemase, and AmpC-producing isolates were detected phenotypically. Then, the ESBL genes were sequenced to detect the type. Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) was performed on the ESBL-positive isolates. RESULTS: The most common effective antibacterial agents were colistin, imipenem, and amikacin. Among the isolates, 204 (56.6%) were MDR. Of the 163 ESBL-positive isolates, 11 (6.7%) produced AmpC, and the frequencies of beta-lactamase-positive genes were as follows: bla CTX-Mgroup1, 76%; bla TEM1, 74.8%; bla SHV12, 1.2%; and bla OXA1, 12.88%. ERIC PCR showed a diverse pattern, suggesting that clonal spread of E. coli in this area is uncommon, and that most of the infecting strains are endogenous. CONCLUSIONS: The high rates of antibacterial-resistant and MDR isolates are quite important since these strains can act as source of resistant bacteria that can be spread in the community. Controlling antibiotic use, against inappropriate use and abuse, in the community and continuous surveillance of emerging resistance traits are critical to controlling the spread of resistance.

Prevalence of Quinolone Resistance Genes Among Extended-Spectrum B-Lactamase-Producing Escherichia coli in Mashhad, Iran.

BACKGROUND: Escherichia coli is an important bacterial species based on incidence and associated infection severity. Some E. coli strains produce extended-spectrum beta lactamase (ESBL) and are called ESBL-producing E. coli. These strains are resistant to most classes of cephalosporin and a number of other classes of antibiotics. Plasmids carrying qnr genes have been found to transmit quinolone resistance. OBJECTIVES: The aim of this study was to determine the frequency of qnr genes in ESBL-producing and non-ESBL-producing E. coli isolated from outpatient and hospitalized patient clinical specimens from Imam Reza hospital in Mashhad, Iran. MATERIALS AND METHODS: Two hundred E. coli strains, isolated from different clinical specimens were used. ESBL-producing E. coli were detected by determining susceptibility to ceftazidime, cefotaxime, and cefpodoxime with the phenotypic confirmatory test (PCT). PCR analysis was employed to detect the qnrA, qnrB, qnrS, bla TEM , and bla SHV genes. RESULTS: Eighty-six (43%) isolates were ciprofloxacin-resistant. The PCT identified 85 (42.5%) of 200 E. coli isolates as ESBL-producing. The bla TEM , bla SHV , qnrA, qnrB, and qnrS gene were found in 65 (76.47%), 23 (27%), 63 (31%), 34 (17%), and 14 (7%) isolates, respectively. CONCLUSIONS: The high prevalence of quinolone resistance genes, which indicates antibiotic resistance, in the Imam Reza Hospital of Mashhad is a major concern. Hence, the antibiotics prescription policy should be revised, and infection control measures should be improved.