Occurrence of high level methicillin resistance Staphylococcus aureusin patients from health facilities in Akwa Ibom State, Nigeria

Background:Methicillin resistant S. aureus(MRSA) has become a major public health predicament worldwide. This is owing to its involvement in the evolution of MDR strains and difficulty in therapeutic management of infected patients. This study was conducted to investigate the prevalence of methicillin resistance Staphylococcus aureusamong patients in two health facilities in Akwa Ibom State, Nigeria.Materials and Methods:Clinical isolates of patients from University of Uyo Teaching Hospital (UUTH), Uyo and General Hospital, Ikot Abasi (GHIA) were investigated based on the strategic location of the hospitals. The study design was a descriptive cross-sectional study. Three hundred clinical samples were collected from male and female in and out-patients of all ages and processed using standard bacteriological methods. Detection of Staphylococcus aureusand MRSAstrains were done according to standard protocols while antibiotic susceptibility testing of MRSAisolates was conducted using Kirby-Bauer disc diffusion method and interpreted following the CLSI 2021 guidelines. Results:The prevalence of MRSAstrains in this study was 42.9%. Majority of patients with MRSAwere from UUTH (44%) closely followed by patients from GHIA(40%). High antibiotics resistant rates of MRSAwere recorded for ampicillin (96.6%), ciprofloxacin (73.3%), erythromycin (63.3%) and cotrimoxazole (60%). Gentamicin and ceftriaxone sensitivity rates were 53.3% and 63.4%, respectively. Conclusion:Health facilities in the state should institute effective antimicrobial stewardship, intensify surveillance and screening of Staphylococcus aureusfor MRSAstrains to guard against dissemination of multidrug resistant strains in both hospital and community settings because of the clinical implications.

Patterns and outcomes of empirical antimicrobial use in elderly outpatients: A pilot observational study from North India

Introduction: Despite the rampant use of antimicrobials in health?care settings, the safety and clinical outcome data of antimicrobials are scarce in the elderly population. The main aim of this study is to assess the prescription pattern, therapeutic gains, and adverse reactions resulting out of antimicrobial use in elderly outpatients. Subjects and Methods: This was a prospective observational study conducted for 7 months from June 2019 to December 2019 in elderly patients visiting the geriatric outpatient department of a tertiary hospital of North India. Primary outcomes included clinical improvement as well as the incidence and type of adverse drug reactions (ADRs) observed with antimicrobial use. Results: Of 110 participants recruited, 107 were assessed for clinical outcomes. The common indications of antimicrobial use were lower respiratory tract infection (48.6%), urinary tract infection (18.7%), and worm infestations (14%). Macrolides (57%) and beta?lactams (43%) were the commonly prescribed individual antimicrobials. Outcome?wise, clinical improvement was seen in 91.3%, 88.5%, and 14.3% of patients receiving beta?lactams, macrolides, and antiprotozoals, respectively. ADRs occurred in 17.7% of participants and gastrointestinal disturbance was the commonly reported ADR. Beta?lactams and macrolides were responsible for the majority of ADRs, in 19.6% and 13.1% of participants, respectively. No association of antimicrobial?associated clinical responses or ADRs was observed with demographics and underlying comorbidities. Conclusions: Elderly patients with respiratory tract infections showed improvement with empirical extended-spectrum beta-lactams and azithromycin therapy. The response was suboptimal to empirically selected antiprotozoal therapy. Elderly patients are at increased risk of ADRs. Close to one out of every five elderly prescribed beta?lactams may develop ADR to the antimicrobial agent. Larger clinical studies are required to predict the risk factors of ADRs and poor responsiveness to antimicrobials.

Bacteriological Profile and Resistance of Escherichia coli to Beta-lactam for Patients Consulted at Douala Laquintinie Hospital

Enterobacteriaceae are the most common causes of community-acquired and nosocomial infections. They are usually treated with beta-lactam antibiotics, i.e., penicillins, broad-spectrum cephalosporins, and carbapenems (Imipenem, meropenem, ertapenem). In order to evaluate the resistance profile of Escherichia coli (E. coli) to beta-lactam antibiotics, a 3-year retrospective study was carried out in the medical biology laboratory of the Laquintinie Hospital in Douala. The aim was to compare the behavior of Escherichia coli bacteria to penicillins, carbapenems, and cephalosporins. In order to achieve this objective, we used the results obtained from E. coli strains isolated from urine, cervico-vaginal fluid, puncture fluid, pleural fluid and pus samples. Identification was confirmed using the API 20 E Enterobacteriaceae system of biochemical testing and the VITEK 2 system. The VITEK 2 system was used to perform the antibiogram. Statistical analyses obtained from GraphPad Prim V 5.0 software allowed us to perform tests such as ANOVA, Kruskal-Wallis test, and Spearman correlations. Preliminary results show that E. coli bacteria are highly resistant to penicillins and significantly susceptible to cephalosporins of all generations if they are not ESBL (extended-spectrum beta-lactamases). Data on carbapenem behavior show less resistance and moderate susceptibility.

Reatividade cruzada entre betalactâmicos: uma abordagem prática / Cross-reactivity among beta-lactams: a practical approach

Os betalactâmicos são a classe de drogas que mais causam reações de hipersensibilidade envolvendo um mecanismo imunológico específico, e são os principais desencadeantes entre os antimicrobianos. São representados pelas penicilinas, cefalosporinas, carbapenêmicos, monobactâmicos e inibidores da betalactamase. A estrutura química básica destes fármacos consiste na presença dos seguintes componentes: anel betalactâmico, anel adjacente e cadeias laterais, sendo todos potenciais epítopos. Os anticorpos da classe IgE e linfócitos T estão frequentemente envolvidos no reconhecimento desses epítopos. A reatividade cruzada depende da estabilidade dos produtos intermediários (determinantes antigênicos) derivados da degradação dos anéis betalactâmicos, anéis adicionais e da semelhança estrutural das cadeias laterais entre as drogas. Classicamente acreditava-se num grande potencial de reatividade cruzada dentro de cada classe e até entre as classes, mas estudos da última década mostraram que indivíduos alérgicos à penicilina (com testes cutâneos positivos) reagiam às cefalosporinas em aproximadamente 3% dos casos, aos carbapenêmicos em cerca de 1%, e praticamente não reagiam aos monobactâmicos. Essa reatividade ou tolerância parece estar vinculada ao grau de similaridade entre as cadeias laterais desses antibióticos. Nesta revisão, ressaltamos a importância da investigação sistematizada na confirmação ou exclusão de alergia aos betalactâmicos, descrevemos a prevalência da reatividade cruzada entre estes fármacos e sugerimos um algoritmo de abordagem desses pacientes baseados em sua estrutura química e nos dados publicados na literatura.

Beta-lactams are the drugs most commonly involved in hypersensitivity reactions mediated by a specific immune mechanism and are the main triggers among antibiotics. They include penicillins, cephalosporins, carbapenems, monobactams and beta-lactam inhibitors. The basic chemical structure of these drugs consist on the presence of the following components: betalactam ring, an adjacent ring and side chains, all of which are potential epitopes. IgE antibodies and T lymphocytes are often involved in recognizing those epitopes. Cross-reactivity depends on the stability of intermediate products (antigenic determinants) derived from the degradation of the beta-lactam ring, on the adjacent rings, and on the structural similarity of the side chains between drugs. Classically, it was believed that there was a great potential for cross-reactivity within each class and even between classes, but studies from the last decade showed that individuals allergic to penicillin (with positive skin tests) reacted to cephalosporins in approximately 3% of cases, to carbapenems in about 1%, and rarely reacted to monobactams. This reactivity or tolerance seems to be linked to the degree of similarity between the side chains of these antibiotics. In this review, we emphasize the importance of systematic investigation to confirm or exclude allergy to beta-lactams, we describe the prevalence of crossreactivity between these drugs and we suggest an algorithm for approaching these patients based on their chemical structure and on data published in the literature.

Síndrome de intolerancia a múltiples medicamentos / Syndrome of intolerance to multiple medicines

El síndrome de intolerancia a múltiples medicamentos (MDIS, por sus siglas en inglés) se caracteriza por la intolerancia a dos o más medicamentos no relacionados. Tiene una prevalencia baja y es común en pacientes con polifarmacia. A pesar de que las reacciones adversas a los medicamentos son muy frecuentes, es raro que los pacientes debuten con este síndrome, el cual tiene implicaciones clínicas de leves a graves que afectan su vida; de acuerdo con esto varían el abordaje y su manejo. La sintomatología presentada varía desde síntomas gastrointestinales como reflujo gastroesofágico, dolores musculares y cefalea, hasta síntomas cutáneos; estos son los más frecuentes, tales como urticaria y erupciones maculopapulares o presentaciones menos comunes como el síndrome de Stevens-Johnson. El MDIS es causado por una amplia variedad de fármacos; por ello el conocimiento del síndrome, así como un adecuado interrogatorio de los antecedentes del paciente, es necesario para realizar un diagnóstico oportuno e instaurar un manejo adecuado y preventivo, evitando reacciones adversas que pongan en riesgo su vida. Con los hallazgos del cuadro clínico en la paciente, y basados en los antecedentes alérgicos presentados anteriormente a diferentes medicamentos no relacionados entre ellos, más la presentación de un rash maculopapular generalizado posterior a la administración de trimetoprim/sulfametoxazol se realiza el diagnóstico de MDIS. Se decide cambiar de medicamento por fosfomicina, con una consecuente evolución favorable. (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.

Caracterización de bacilos gramnegativos multi-resistentes, aislados en pacientes hospitalizados en instituciones de salud de Barranquilla (Colombia) / Characterization of multiresistant gram-negative bacilli, isolated in patients hospitalized in health institutions in Barranquilla (Colombia)

Resumen Introducción: La resistencia a carbapenémicos en bacilos gramnegativos es un problema de salud pública mundial, debido a que se asocia con altas tasas de mortalidad, aumento en los niveles de resistencia a otros antimicrobianos, elevación en el potencial de diseminación e incremento en los costos de atención en salud. Objetivo: Caracterizar bacilos gramnegativos multirresistentes, aislados en pacientes hospitalizados en instituciones de salud de Barranquilla (Colombia). Material y Métodos: Estudio descriptivo acerca de la caracterización fenotípica y genotípica de la resistencia bacteriana en las infecciones asociadas a la atención en salud, mediada por carbapenemasas en aislados bacterianos enviados por los laboratorios pertenecientes a la red de laboratorios del Departamento del Atlántico. Resultados: La KPC fue la carbapenemasa más frecuente en las Enterobacterales (27,6%), predominando en Klebsiella pneumoniae (13,1%) sola y asociada a otras carbapenemasas. En Pseudomonas aeruginosa predominó la carbapenemasa VIM (32,8%) y la OXA en Acinetobacter baumannii (17,1%). Conclusión: Se encontró una amplia distribución de cepas multi-resistentes productoras de carbapenemasas en instituciones de salud de Barranquilla, las cuales expresaron los siguientes mecanismos de resistencia: KPC, VIM, NDM, OXA.

Abstract Background: The emergence of carbapenem resistant gramnegative bacilli has become a problem of public health worldwide, because it is associated with high mortality rates, increased levels of resistance to other antimicrobials, increased potential for dissemination transition and increase in health care costs. Aim: To characterize multiresistant gram-negative bacilli, isolated in patients hospitalized in health institutions of Barranquilla (Colombia). Methods: A descriptive study was conducted on the phenotypic and genotypic characterization of bacterial resistance in infections associated with health care, mediated by carbapenemases in bacterial isolates sent by laboratories belonging to the laboratory network of the Department of Atlántico. Results: KPC was the most frequent carbapenemase in Enterobacterales (27.6%), predominantly in Klebsiella pneumoniae (13.1%) alone and associated with other carbapenemases. In Pseudomonas aeruginosa, VIM carbapenemase (32.8%) predominated and OXA in Acinetobacter baumannii (17.1%). Conclusion: A wide distribution of multi-resistant strains producing carbapenemases in Atlantic health institutions was found, which expressed the following resistance mechanisms: KPC, VIM, NDM, OXA.

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

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.

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.

Resistencia a la colistina en cepas de Klebsiella pneumoniae multidrogorresistente del período 2015-2018 en un instituto materno perinatal de Lima, Perú / Colistin resistance in multidrug-resistant Klebsiella pneumoniae strains at a perinatal maternal institute in Lima, Peru, 2015-2018

RESUMEN El objetivo del estudio fue evaluar los niveles y mecanismos de resistencia a la colistina y a los carbapenémicos en cepas de Klebsiella pneumoniae multidrogorresistente aisladas durante el periodo 2015-2018 en el Instituto Materno Perinatal de Lima. Se analizó la sensibilidad mediante difusión en disco y microdilución. La presencia de genes de resistencia a los carbapenémicos y a la colistina se determinó por reacción en cadena de la polimerasa (PCR, por sus siglas en inglés) y se la relacionó con la clonalidad. Se analizaron 36 cepas de K. pneumoniae, cinco (13,8%) fueron resistentes a la colistina, pertenecían a diferentes grupos clonales. Se encontraron dos cepas con carbapenemasas (bla KPC y bla NDM) y no se detectaron genes plasmídicos para la colistina. Los niveles de resistencia al resto de antimicrobianos testados fueron elevados, a excepción de amikacina (13,9%). Los resultados destacan la presencia de cepas resistentes a la colistina (33,3% en 2018), situación preocupante por ser esta parte de las últimas alternativas de tratamiento para las infecciones causadas por patógenos multirresistentes.

ABSTRACT The objective of this study was to evaluate the presence of colistin- and carbapenemic-resistant genes in multidrug-resistant Klebsiella pneumoniae strains isolated at the Instituto Materno Perinatal de Lima (2015-2018). Susceptibility levels were analyzed by disk diffusion and microdilution. The presence of colistin- and carbapenemic-resistant genes was determined by polymerase chain reaction (PCR) and was related to clonality. A total of 36 K. pneumoniae strains were analyzed, 5 (13.8%) were resistant to colistin and belonged to different clonal groups. Only 2 strains were found with carbapenemases (bla KPC and bla NDM), and no colistin plasmid genes were detected. High resistance levels to the other tested antimicrobials were observed, except for amikacin (13.9%). The results highlight the presence of colistin-resistant strains (33.3% in 2018), a worrying situation as they are part of the latest treatment alternatives for infections caused by multiresistant pathogens.

Angina de Ludwig complicada con shock séptico / Ludwig´s angina complicated with septic shock

Introduction: Ludwig's angina is one of the soft tissue infections of the neck and tongue floor with the most admissions to intensive care units (ICU) due to its compromise of the airway and complications from septic shock. The incidence is higher in the adult population, and with the use of the latest generation antibiotics, its incidence has decreased. One of the most frequent causes is the presence of an odontogenic focus such as abscesses, mainly in the second and third molars. Objective: To describe a clinical case, admitted to the hospital ICU, highlighting the comprehensive management and adequate antibiotic therapy. Main data of the case: 24-year-old female patient, a native of Latacunga, went to the emergency service of the Hospital del Sur de Quito for a fever of 10 days of evolution and taking the general condition with signs of shock, and intense pain in the tongue, with edema, and impaired phonation. For initial management, intravenous tramal, IV hydrocortisone, and a broad spectrum antibiotic with piperacillin with tazobactam 4 grams IV every 6 hours, and IV metronidazole every 8 hours. Conclusions: Ludwig's angina is a pathology that usually involves young patients, whose evolution is rapid and its inadequate management leads to death, associated with obstructive respiratory failure and severe sepsis, which requires a timely diagnosis.

Introducción: La angina de Ludwig constituye una de las infecciones de los tejidos blandos del cuello y piso de la lengua con más ingresos en las unidades de cuidados intensivos (UCI) por su compromiso de la vía aérea y complicaciones por shock séptico. La incidencia es mayor en la población adulta, y con el uso de los antibióticos de última generación, su incidencia ha disminuido. Una de las causas más frecuentes es la presencia de un foco odontogénico como los abscesos, principalmente en el segundo y el tercer molar. Objetivo: Describir un caso clínico, internado en la UCI del hospital, destacando el manejo integral y la terapia antibiótica adecuada. Datos principales del caso: paciente femenina de 24 años, natural de Latacunga, acude al servicio de emergencias del Hospital del sur de Quito por fiebre de 10 días de evolución y toma del estado general con signos de shock, y dolor intenso en lengua, con edema, y deterioro de la fonación. Para el abordaje inicial se administra tramadol por vía intravenosa (IV), hidrocortisona IV y antibiótico de amplio espectro con piperacilina con tazobactam 4 gramos IV cada 6 horas, y metronidazol IV cada 8 horas. Conclusiones: la angina de Ludwig es una afección que habitualmente involucra pacientes jóvenes, cuya evolución es rápida y su inadecuado abordaje conlleva a la muerte, asociado con insuficiencia respiratoria obstructiva y sepsis grave, por lo que requiere un diagnóstico oportuno

Síndrome de Kounis. A propósito de um caso clínico / Kounis syndrome. Apropos of a clinical case

RESUMO A síndrome de Kounis, enquanto síndrome coronária aguda, ocorre em um contexto de reação de hipersensibilidade, alergia ou anafilaxia, e subdivide-se em três tipos: o espasmo coronário em artérias normais, a instabilidade de placas em artérias coronárias ateroscleróticas e a trombose de stent coronário. Apresenta-se o caso de uma doente de 73 anos que, após administração de amoxicilina/ácido clavulânico, entra em parada cardiorrespiratória, com evidência de supradesnivelamento do segmento ST-T em eletrocardiograma. Realiza coronariografia com ausência de lesões obstrutivas, verificando-se resolução espontânea das alterações eletrocardiográficas. Revisão da anamnese com a família documenta alergia prévia à penicilina. O doseamento de triptase foi fortemente positivo. Foi admitida provável síndrome de Kounis tipo 2, com boa evolução clínica posterior.

ABSTRACT Kounis syndrome, while an acute coronary syndrome, occurs in the context of a hypersensitivity reaction, allergies, or anaphylaxis and is subdivided into three types: coronary spasm in normal arteries, instability of plaques in atherosclerotic coronary arteries, and thrombosis of coronary stents. Herein, the case of a 73-year-old patient who, after administration of amoxicillin/clavulanic acid, went into cardiorespiratory arrest with evidence of ST-T segment elevation on electrocardiogram is reported. Coronarography revealed no obstructive lesions, and spontaneous resolution of electrocardiographic abnormalities was observed. A review of anamnesis with the family revealed a previous allergy to penicillin. The tryptase dosage was strongly positive. Kounis syndrome type 2 was diagnosed, and the clinical outcome was good.

Confirmación diagnóstica de alergia a la amoxicilina en niños tratados en una sección de alergia pediátrica / Diagnostic confirmation of amoxicillin allergy in children treated at a division of Pediatric Allergy

La amoxicilina es un antibiótico betalactámico comúnmente indicado en pediatría y es la causa más frecuente de alergia a medicamentos.Objetivos. Determinar la proporción de alergia confirmada a amoxicilina en niños con sospecha diagnóstica, atendidos en una sección de alergia pediátrica.Población y métodos. Estudio descriptivo retrospectivo entre enero de 2009 y enero de 2017, en menores de 18 años con sospecha diagnóstica de alergia a amoxicilina. Se realizó el diagnóstico según interrogatorio y pruebas específicas.Resultados. Fueron incluidos 234 pacientes; se diagnosticó alergia a la amoxicilina en el 10,7 % (intervalo de confianza del 95 %: 7-15). Estos pacientes tenían mayor prevalencia de síntomas inmediatos (el 40 % vs. el 22 %, p = 0,048) y de exposición previa a betalactámicos (el 84 % vs. el 56 %, p = 0,007).Conclusión. La confirmación de alergia a la amoxicilina en niños derivados a especialistas fue del 10,7 %.

Amoxicillin is a beta-lactam antibiotic commonly indicated in pediatrics and the most frequent cause of drug allergies.Objectives. To determine the proportion of confirmed amoxicillin allergy in children with diagnostic suspicion seen at the Division of Pediatric Allergy.Population and methods. This descriptive, retrospective study was done between January 2009 and January 2017 in children younger than 18 years with diagnostic suspicion of amoxicillin allergy. The diagnosis was based on questions and specific tests.Results. A total of 234 patients were included; amoxicillin allergy was diagnosed in 10.7 % (95 % confidence interval: 7-15). These patients had a higher prevalence of immediate symptoms (40 % vs. 22 %, p = 0.048) and prior exposure to beta-lactams (84 % vs. 56 %, p = 0.007).Conclusion. Amoxicillin allergy in children referred to specialists was confirmed in 10.7 %.

Uso de beta-lactámicos como alternativa del tratamiento empírico actual de sepsis neonatal tardía: revisión temática / Use of beta-lactams as an alternative to the current empirical treatment of late neonatal sepsis: review

OBJETIVO: Analizar el uso de beta-lactámicos en sepsis neonatal tardía, en comparación con el tratamiento empírico actual con vancomicina, mediante la revisión de artículos científicos. METODOLOGÍA: Revisión temática en Bases LILACS y PubMed. La selección de los artículos se realizó mediante la lectura de título, abstract y texto completo. Criterios de búsqueda: Estudios en humanos, artículos por abstract y texto completo, en inglés y español, y de no más de 10 años. RESULTADOS: No hay relación en la duración ni en la mortalidad de la sepsis al utilizar un betalactámico, o al utilizar vancomicina. Además, cepas resistentes a beta-lactámico, respondieron bien al usar un beta-lactámico como terapia empírica inicial, sin la necesidad de recurrir a vancomicina, excepto en casos de no mejoría clínica. CONCLUSIONES: Beta-lactámicos pueden ser utilizados como terapia empírica inicial en sepsis neonatal tardía como alternativa al tratamiento actual con vancomicina, restringiendo el uso de vancomicina a casos de resistencia, o cuando no haya mejoría clínica del recién nacido que está utilizando un beta-lactámico como tratamiento.

OBJECTIVE: To analyze the use of beta-lactams in late- onset neonatal sepsis, compared with empirical treatment with vancomycin used currently, through the revision of scientific articles. METHODOLOGY: Thematic review in LILACS and PubMed. The articles were selected by reading the title, abstract and full text. Searching criteria: Human studies, articles by abstract and full text, in English and Spanish, and no more than 10 years since published. RESULTS: There is no relationship in duration or mortality in Sepsis when using beta-lactam, or using vancomycin. In addition, resistant strains to beta-lactam responded well in using betalactam as initial empirical therapy, without the need to resort to vancomycin, except in cases of non-clinical improvement. CONCLUSIONS: Beta-lactams may be used as initial empirical therapy in late-onset neonatal sepsis as an alternative to current vancomycin therapy, restricting the use of vancomycin to resistance cases, or when there is no clinical improvement in the neonate, who is using a beta-lactam as a treatment.

Prevalencia de β -lactamasas de espectro extendido en enterobacterias causantes de sepsis neonatal y factores asociados / Prevalence of extended-spectrum beta-lactamases in enterobacteria of neonatal sepsis and associated factors

Resumen Introducción: Las infecciones causadas por enterobacterias productoras de β-talactamasas de espectro extendido (EP-BLEE) tienen implicaciones sobre la morbilidad y mortalidad neonatal. Objetivo: Describir la prevalencia de EP-BLEE en sepsis neonatal y los factores asociados. Métodos: Estudio de cohorte prospectivo, desde agosto del 2016 a agosto del 2017. Se incluyeron recién nacidos (RNs) ingresados en el Hospital Civil de Guadalajara "Dr. Juan I. Menchaca". Mediante prueba de difusión de doble disco se indagó la presencia de EP-BLEE y su asociación con características clínicas y demográficas de los RNs. Resultados: Se estudiaron 1.501 RNs hospitalizados, con edad gestacional promedio de 36,3 semanas. Se diagnosticaron 196 eventos de sepsis neonatal, la etiología más frecuente fueron enterobacterias (45,5%); 88,8% demostraron resistencia a ampicilina y más de 42% a cefalosporinas de amplio espectro. El 22,9% presentó fenotipo BLEE positivo. Tener Apgar ≤ 7 a los cinco minutos de vida (OR 4,6; IC 95% 1,47-14,6) y edad gestacional < 37 semanas (OR 5,4; IC 95%1,04-27,7) incrementaron el riesgo. Conclusión: En las enterobacterias causantes de sepsis neonatal, 22,9% son EP-BLEE; la infección es más probable en pacientes con Apgar ≤ 7 a los cinco minutos de vida y en prematuros.

Background: Infections caused by extended-spectrum beta-lactamases enterobacteria (ESBL-EP) have implications for neonatal morbidity and mortality. Aim: To describe the prevalence of ESBL-EP in neonatal sepsis and associated factors. Methods: A prospective cohort study was conducted from August 2016 to August 2017; newborn babies (NB) hospitalized in the Hospital Civil de Guadalajara "Dr. Juan I. Menchaca" were included. The ESBL-EP were investigated by double-disk synergy test and its association with clinical and demographic characteristics of the NB. Results. A total of 1,501 hospitalized NB were studied, with an average gestational age of 36.3 weeks. They were diagnosed 196 neonatal sepsis events, the most frequent etiologies were enterobacteria (45.5%). Resistance to ampicilin was found in 88.8% and to broad spectrum cephalosporins in more than 42% of the strains; 22.9% of them were ESBL phenotype. Apgar ≤ 7 at five minutes of life (OR 4.6; 95% CI 1.47-14.6) and gestational age < 37 weeks (OR 5.4; 95% CI 1.04-27.) increase the risk. Conclusion: In enterobacteria that cause neonatal sepsis, 22.9% were EP-ESBL; infection was more likely in patients with Apgar ≤ 7 at five minutes of age and in preterm infants.

Piperacillin/tazobactam in continuous infusion versus intermittent infusion in children with febrile neutropenia

Abstract Background Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/tazobactam (TZP) in febrile neutropenic pediatric patients. Methods This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.

Costos médicos directos de las infecciones del tracto urinario por bacilos Gram negativos resistentes a betalactámicos en un hospital de alta complejidad de Medellín, Colombia / Direct medical costs of urinary tract infections by Gram-negative bacilli resistant to beta-lactams in a tertiary care hospital in Medellín, Colombia

Resumen Introducción. Las infecciones del tracto urinario son muy frecuentes en el ámbito hospitalario. Debido a la aparición de la resistencia antimicrobiana, la complejidad de los procesos de atención ha aumentado y, con ello, la demanda de recursos. Objetivo. Describir y comparar el exceso de los costos médicos directos de las infecciones del tracto urinario por Klebsiella pneumoniae, Enterobacter cloacae y Pseudomonas aeruginosa resistentes a betalactámicos. Materiales y métodos. Se llevó a cabo un estudio de cohorte en una institución de tercer nivel de Medellín, Colombia, entre octubre del 2014 y septiembre del 2015. Se incluyeron los pacientes con infección urinaria, unos por bacterias sensibles a los antibióticos betalactámicos, y otros por bacterias resistentes a las cefalosporinas de tercera y cuarta generación y a los antibióticos carbapenémicos. Los costos se analizaron desde la perspectiva del sistema de salud. La información clínico-epidemiológica se obtuvo de las historias clínicas y los costos se calcularon utilizando los manuales tarifarios estándar. El exceso de costos se estimó mediante análisis multivariados. Resultados. Se incluyeron 141 pacientes con infección urinaria: 55 (39 %) por bacterias sensibles a los betalactámicos, 54 (38,3 %) por bacterias resistentes a las cefalosporinas y 32 (22,7 %) por bacterias resistentes a los carbapenémicos. El exceso de costos totales ajustado de los 86 pacientes con infecciones del tracto urinario por bacterias resistentes a las cefalosporinas y a los carbapenémicos, fue de USD$ 193 (IC95% -347 a 734) y USD$ 633 (IC95% -50 a 1.316), respectivamente comparados con el grupo de 55 pacientes por bacterias sensibles a los betalactámicos. Las diferencias se presentaron principalmente en el uso de antibióticos de amplio espectro, como el meropenem, la colistina y la fosfomicina. Conclusión. Los resultados evidenciaron un incremento sustancial de los costos médicos directos de los pacientes con infecciones del tracto urinario por bacterias resistentes a las cefalosporinas o a los carbapenémicos. Esta situación genera especial preocupación en los países endémicos como Colombia, donde la alta frecuencia de infecciones del tracto urinario y de resistencia a los betalactámicos puede causar un mayor impacto económico en el sector de la salud.

Abstract Introduction: Urinary tract infections are very frequent in the hospital environment and given the emergence of antimicrobial resistance, they have made care processes more complex and have placed additional pressure on available healthcare resources. Objective: To describe and compare excess direct medical costs of urinary tract infections due to Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa resistant to beta-lactams. Materials and methods: A cohort study was conducted in a third level hospital in Medellín, Colombia, from October, 2014, to September, 2015. It included patients with urinary tract infections caused by beta-lactam-susceptible bacteria, third and fourth generation cephalosporin-resistant, as well as carbapenem-resistant. Costs were analyzed from the perspective of the health system. Clinical-epidemiological information was obtained from medical records and the costs were calculated using standard tariff manuals. Excess costs were estimated with multivariate analyses. Results: We included 141 patients: 55 (39%) were sensitive to beta-lactams, 54 (38.3%) were resistant to cephalosporins and 32 (22.7%) to carbapenems. The excess total adjusted costs of patients with urinary tract infections due to cephalosporin- and carbapenem-resistant bacteria were US$ 193 (95% confidence interval (CI): US$ -347-734) and US$ 633 (95% CI: US$ -50-1316), respectively, compared to the group of patients with beta-lactam sensitive urinary tract infections. The differences were mainly found in the use of broad-spectrum antibiotics such as meropenem, colistin, and fosfomycin. Conclusion: Our results show a substantial increase in the direct medical costs of patients with urinary tract infections caused by beta-lactam-resistant Gram-negative bacilli (cephalosporins and carbapenems). This situation is of particular concern in endemic countries such as Colombia, where the high frequencies of urinary tract infections and the resistance to beta-lactam antibiotics can generate a greater economic impact on the health sector.

blaIMP-45 and armA co-carrying multidrug resistance Pseudomonas isolates and characterization of their genetic environment / 中华检验医学杂志

Objective The primary goal of this work is to discuss the molecular mechanism of multi-drug resistant Pseudomonas spp. resistance to carbapenam and aminoglycoside antibiotics. Methods From June 2012 to March 2013, six strains of P. aeruginosa and P. putida producing carbapenemasefrom 4 different district were collected. Species identification was performed using VITEK-2 compact system and by sequencing of 16S rDNA amplicons. Minimum inhibitory concentrations were determined by E-test method. Production of carbapenemase were detected by Carba NP method. Carbapenemase genes and aminoglycoside 16s rRNAmethylase genes were screened by PCR, and their subtypes combined with their immediate genetic context were worked out by assemble the sequence of overlapped PCR amplicons. SpeI-PFGE (Pulse field gel electrophoresis after SpeI enzyme digestion) were conducted to evaluate their clonal relatedness. S1-PFGE (Pulse field gel electrophoresis after S1 enzyme digestion) were conducted to conform the relatedness of plasmids they carried. Results Three multidrug resistant P. aeruginosa and three P. putida, were all positive for Carba NP test and conformed producing class B carbapenemase. PCR screening followed by sequencing confirmed carriage of blaIMP-45 and armA, which confer resistance to β-lactams (except aztreonam) and aminoglycosides. These two genes co-located in a Tn1548-associatedregion. SpeI-PFGE disclosed that these isolates were not clonal closely related to each other, except two P. aeruginosa isolates were clonal related. S1-PFGE results showed that these isolates all carried plasmids of large size (300-600 kb). Conclusions This study showed that Pseudomonas spp. isolates co-carried blaIMP-45 and armA were disseminated in clinical settings. Spread of these genes may attribute to horizontal gene transfer of related entities.

Interacciones farmacológicas relacionadas con la administración de antibióticos betalactámicos / Drug interactions related to the administration of beta-lactam antibiotics

Los antibióticos betalactámicos son los que más se usan en el tratamientoy profilaxis de las infecciones odontogénicas. Con frecuenciaes necesario prescribir un segundo antibiótico que incremente el efectodel primero. Debido a ello se hizo una revisión de los antibióticos y otros medicamentos que administrados simultáneamente o en forma secuencial con betalactámicos producen efectos deseados (sinergismo, potenciación) o indeseados (antagonismo) o provocan efectos adversos en el organismo.

Beta-lactams are the most commonly used antibiotics in the treatmentand prophylaxis of odontogenic infections. It is often necessary toprescribe a second antibiotic to increase the eff ect of the fi rst. For thisreason, we performed a review of antibiotics and other medicationswhich, when administered simultaneously or sequentially with betalactams,produce desirable (synergism, potentiation) or undesirable(antagonism) eff ects or provoke adverse eff ects in the organism.