Ceftriaxone-induced Kounis syndrome: A case report and review of the literature.

Kounis syndrome is defined as cardiovascular symptoms that occur secondary to allergic or hypersensitivity insults, and is also called allergic angina and allergic myocardial infarction. We report a case of pre-operative ceftriaxone-induced Kounis syndrome with no evident dermatological manifestation, and describe our diagnostic dilemma. The patient was symptomatically managed and discharged in stable condition with a warning against future use of ceftriaxone.

Intervención educativa para mejorar la prescripción de ceftriaxona en un servicio de urgencias / Educational intervention to improve ceftriaxone prescription in an emergency department

Objetivo: Evaluar prevalencia y adecuación de ceftriaxona tras una intervención educativa en un servicio de urgencias.Métodos: Estudio cuasi experimental que incluyó un mues-treo consecutivo de consultas no programadas de pacien-tes adultos, durante dos meses preintervención y posin-tervención. Dicha intervención consistió en capacitación a médicos para limitar su indicación sólo a situaciones clínicas específicas (meningitis, enfermedad pélvica infla-matoria y abdomen agudo). Se utilizaron datos retrospecti-vos, con adicional revisión manual de historias, para validar adecuación de inicio antibiótico y apropiabilidad de droga. Se utilizó estadística descriptiva y analítica.Resultados: De un total de 28.570 consultas, 512 recibie-ron ceftriaxona (1,79%; IC95% 1,64-1,95), y sólo 60,54% se hospitalizaron. En cuanto a la comparación antes-después, se observó una reducción en la tasa de uso (de 3,66% a 0,63%; p<0,001), la adecuación en el inicio de un antimicro-biano se mantuvo (de 84,52% a 86,21%; p=0,778), aunque la adecuación de ceftriaxona aumentó en forma significativa (de 41,78% a 84,00% respectivamente; p<0,001). Adicional-mente, se redujo el tiempo de estadía hospitalaria (media-na de 6 a 5 días; p=0,014), sin diferencias en la mortalidad intrahospitalaria (19,44% vs 17,24%; p=0,691), ni en la mor-talidad a los 30 días (23,41% vs 18,96%; p=0,464).Conclusiones: Esta intervención resultó eficaz. Los hallaz-gos representan un paso fundamental en los programas de optimización del uso de antimicrobianos hospitalarios, que apuntan a reducir su sobreutilización y la consecuente resistencia.

Objective: To evaluate the prevalence and appropriateness of ceftriaxone after an educational intervention in an emergency department.Methods: Quasi-experimental study, which included a consecutive sampling of unscheduled consultations of adult patients, during 2 months pre-intervention and post-intervention. The intervention consisted of training physicians to limit its indication only to specific clinical situations (meningitis, pelvic inflammatory disease, and acute abdomen). Retrospective data were used, with additional manual chart review, to validate appropriateness of antibiotic initiation and drug appropriateness. Descriptive and analytical statistics were used.Results: Among 28570 visits, 512 received ceftriaxone (1.79%; 95%CI 1.64-1.95), and only 60.54% were hospitalized. Regarding the before-after comparison, we observed a reduction in the rate of use (from 3.66% to 0.63%; p<0.001), the appropriateness in starting an antimicrobial was maintained (from 84.52% to 86.21%; p=0.778), and the appropriateness of ceftriaxone increased significantly (from 41.78% to 84.00% respectively; p<0.001). Additionally, hospital length of stay was reduced (median 6 to 5 days; p=0.014), with no difference in in-hospital mortality (19.44% vs 17.24%; p=0.691), nor in 30-day mortality (23.41% vs 18.96%; p=0.464)

Evaluation of the follow-up of children treated for congenital syphilis in a municipality in the state of Espírito Santo, when it lacked crystalline penicillin / valiação do acompanhamento de crianças tratadas para sífilis congênita em município do estado do espírito santo em época de falta de penicilina cristalina

Introduction: Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. In Brazil, its incidence has increased, along with the lack of penicillin, the antibiotic of choice for congenital syphilis, from 2014 to 2017. During this period, children were treated with alternative drugs, but to date, data from the scientific literature do not recommend another antibiotic. Objective: To compare the progression, according to the established treatment, and evaluate the follow-up in health care facilities in Vila Velha (Espírito Santo) of children with congenital syphilis aged up to two years, born in Hospital Infantil e Maternidade Alzir Bernardino Alves ­ a reference in neonatology and low-risk pregnancy in the state at the time ­ from 2015 to 2016, when the hospital experienced a greater lack of penicillin. Methods: This is a retrospective cross-sectional observational study based on data from medical records of the hospital and other healthcare facilities in the city. We performed statistical analyses, per health district, of epidemiological and sociodemographic data, as well as those related to visits, their frequency, and clinical profile, according to the follow-up parameters proposed by the Ministry of Health at the time. Results: Medical records of 121 children were evaluated, presenting as the main findings: only 35% of the children completed the follow-up; among those treated with ceftriaxone, 55.2% completed the follow-up, and 100% of the children whose venereal disease research laboratory was greater than that of their mother at birth completed the follow-up. Of the symptomatic children at birth who remained or became symptomatic at follow-up, 58.8% used ceftriaxone. Conclusion: Among symptomatic children at birth, most of those treated with ceftriaxone remained symptomatic at follow-up. The Counseling and Testing Center was the most successful facility in the follow-up of these children. District 5 had the lowest success rate in the follow-up of these patients, and districts 1 and 2 showed the lowest rates of appropriate approach to congenital syphilis during follow-up. (AU)

Introdução: A sífilis é uma infecção sexualmente transmissível causada pela bactéria Treponema pallidum. No Brasil, sua incidência vem aumentando, acompanhada da falta de penicilina, antibiótico de escolha para a sífilis congênita, no período de 2014­2017. Nesse período, as crianças foram tratadas com medicamentos alternativos, porém dados da literatura científica até o momento não recomendam outro antibiótico. Objetivo: Comparar a evolução, de acordo com o tratamento instituído, e avaliar o acompanhamento nas unidades de saúde em Vila Velha (ES), até os dois anos de idade, das crianças com sífilis congênita nascidas no Hospital Infantil e Maternidade Alzir Bernardino Alves ­ referência em neonatologia e gravidez de baixo risco no estado na época ­ de 2015 a 2016, período em que houve maior falta de penicilina no hospital. Métodos: Estudo observacional do tipo transversal, retrospectivo, baseado em dados dos prontuários do hospital e outras Unidades de Saúde do município. Foram analisados estatisticamente, por região de saúde, dados epidemiológicos, sociodemográficos, bem como relativos às consultas, sua periodicidade e ao perfil clínico, de acordo com os parâmetros de seguimento propostos pelo Ministério da Saúde na época. Resultados: Avaliaram-se os prontuários de 121 crianças, obtendo-se como principais achados: somente 35% das crianças tiveram seguimento completo; das crianças tratadas com ceftriaxona, 55,2% tiveram seguimento completo, e 100% das crianças que tiveram VDRL maior que o da mãe no parto completaram o seguimento. Das crianças sintomáticas ao nascimento e que permaneceram ou ficaram sintomáticas no seguimento, 58,8% fizeram uso de ceftriaxona. Conclusão: Das crianças sintomáticas ao nascimento, as tratadas com ceftriaxona, em sua maioria, mantiveram-se sintomáticas no seguimento. O Centro de Testagem e Aconselhamento teve maior êxito no acompanhamento dessas crianças. A região 5 teve a menor taxa de êxito no seguimento desses pacientes, e as regiões 1 e 2 menor taxa de abordagem correta para sífilis congênita durante o seguimento. (AU)

Dosificación de ceftriaxona en el paciente crítico hipoproteinémico: un factor más a tener en cuenta / Dosage of ceftriaxone in the critical hypoproteinemic patient: another factor to take into account

Introducción: El objetivo principal del estudio fue evaluar la necesidad de ajuste posológico de ceftriaxona en pacientes críticos hipoproteinémicos. Pacientes y métodos: Estudio observacional y retrospectivo, llevado a cabo en la unidad de cuidados intensivos (UCI) del Hospital General Universitario de Ciudad Real (médico-quirúrgica de 21 camas), en el que se incluyeron pacientes tratados con ceftriaxona en la UCI desde enero de 2014 a diciembre de 2019 y se clasificaron en dos grupos al inicio del tratamiento: pacientes normoproteinémicos (proteínas totales >5,5g/dl) e hipoproteinémicos (proteínas totales ≤5,5g/dl).Variables principales: Edad, sexo, APACHE II, diagnóstico-localización del foco infeccioso, estancia en UCI, dosis de ceftriaxona, pauta posológica, tratamiento antibiótico concomitante, empírico o dirigido, necesidad de cambio de tratamiento, días de antibioterapia y mortalidad. Resultados: Se incluyeron 98 pacientes (44 normoproteinémicos y 54 hipoproteinémicos). No se obtuvieron diferencias estadísticamente significativas entre las características basales de ambos grupos, exceptuando la localización del foco, siendo respiratorio con mayor frecuencia en el grupo de pacientes normoproteinémicos (p=0,044). Se obtuvieron diferencias estadísticamente significativas a favor del grupo de pacientes normoproteinémicos para: estancia en UCI (p=0,001), necesidad de cambio de tratamiento antibiótico (p=0,004), días de antibioterapia (p=0,007) y mortalidad (p=0,046). Conclusión: Los resultados terapéuticos obtenidos en el grupo de pacientes críticos hipoproteinémicos tratados con ceftriaxona ponen en evidencia la necesidad de considerar la hipoproteinemia como un factor que podría condicionar dicho resultado si se emplean las pautas posológicas de tratamiento habituales. (AU)

Introduction: The main objective of the study was to evaluate the need for posologic adjustment of ceftriaxone in critical hypoproteinemic patients. Patients and methods: Observational and retrospective study, carried out in the intensive care unit (ICU) of the General University Hospital of Ciudad Real (21-bed medical-surgical), which included patients treated with ceftriaxone in the ICU from January 2014 to December 2019 and classified into two groups at the beginning of treatment: normoproteinemic (total proteins >5.5 g/dl) and hypoproteinemic (total proteins ≤5.5g/dl) patients.Main variables: Age, sex, APACHE II, diagnosis-location of the infectious site, ICU stay, ceftriaxone dose, dosage regimen, concomitant antibiotic treatment, empirical or targeted antibiotic treatment, need to change treatment, days of antibiotic therapy and mortality. Results: 98 patients were included (44 normoproteinemics and 54 hypoproteinemics).No statistically significant differences were obtained between the basal characteristics of both groups, except for the location of the infectious site, being respiratory more frequently in the group of normoproteinemic patients (p=0.044).Statistically significant differences were obtained in favour of the group of normoproteinemic patients for: stay in ICU (p=0.001), need for change of antibiotic treatment (p=0.004), days of antibiotherapy (p=0.007) and mortality (p=0.046). Conclusion: The therapeutic results obtained in the group of critical hypoproteinemic patients treated with ceftriaxone show the need to consider hypoproteinemia as a factor that could condition such result if the usual treatment dosage guidelines are used.

Pustulosis exantematosa generalizada aguda

La pustulosis exantematosa generalizada aguda (PEGA) es una patología dermatológica poco frecuente, caracterizada por la aparición brusca y generalizada de múltiples pústulas puntiformes, estériles, no foliculares, sobre una base eritematosa y edematosa. Es desencadenada frecuentemente por fármacos, entre los cuales resaltan los antibióticos. Presentamos el caso de un paciente varón de 40 años, que ingresó a emergencia por síndrome doloroso abdominal a descartar patología tumoral intraabdominal, indicándole inicialmente ceftriaxona y metronidazol. Al día siguiente, reingresó a emergencia encontrando, tras la cirugía de emergencia, una apendicitis aguda complicada con perforación intestinal, por lo cual rotan la antibioticoterapia a imipenem-cilastatina + metronidazol. A las siguientes 48 horas, presentó eritema generalizado y algunas pústulas pequeñas y microvesículas en región torácica, extremidades superiores y cuello. Asimismo, se observó en los exámenes de laboratorio, leucocitosis neutrofílica e hipoalbuminemia. En la biopsia, se encontró pústulas neutrofílicas subcorneales e intraepidérmicas, con dermis papilar edematosa e infiltrado inflamatorio perivascular con presencia de neutrófilos y escasos eosinófilos. Con todo lo descrito anteriormente, llegamos a la conclusión de una PEGA, desencadenado por los antibióticos recibidos, ceftriaxona o imipenem-cilastatina. Tras 6 días de la suspensión de imipenem-cilastatina, paciente mostró mejoría de lesiones dérmicas, con leve eritema y escasa descamación fina.

Acute generalized exanthematic pustulosis (PEGA) is a rare dermatological pathology characterized by the sudden and generalized appearance of multiple, sterile, non-follicular, punctate pustules on an erythematous and edematous base. It is frequently triggered by drugs, among which antibiotics stand out. We present the case of a 40-year-old male patient who was admitted to the emergency room due to abdominal pain síndrome, to rule out intra-abdominal tumor pathology, initially indicating ceftriaxone and metronidazole. The next day, he was re-admitted to the emergency room, finding, after emergency surgery, acute appendicitis complicated with intestinal perforation, for which they rotated the antibiotic therapy to imipenem-cilastatin + metronidazole. At the next 48 hours, he presents generalized erythema and some small pustules and microvesicles in the thoracic region, upper extremities and neck. Likewise, it is shown in laboratory tests, neutrophilic leukocytosis and hypoalbuminemia. In the biopsy, subcorneal and intraepidermal neutrophilic pustules are found, with edematous papillary dermis and perivascular inflammatory infiltrate with the presence of neutrophils and few eosinophils. With everything described above, we reached the conclusion of a PEGA, triggered by received antibiotics, ceftriaxone or imipenemcilastatin. After 6 days of the suspension of imipenem-cilastatin, the patient shows improvement of dermal lesions, with mild erythema and scant fine scaling.

Gonorrhea in a Tertiary Care Portuguese Hospital: A 10-year Retrospective Study of the Evolution of Cases and Drug Resistance of the Isolates. / Estudio retrospectivo acerca de la evolución y el desarrollo de resistencias antimicrobianas en casos diagnosticados de gonorrea en un hospital de nivel terciario en Portugal durante 10 años.

BACKGROUND: Sexually Transmitted Infections remain a major public health concern worldwide. Although traditionally considered treatable, the emergence of Neisseria gonorrhoeae resistance to antimicrobials is currently a serious problem. The goal of this study was to evaluate the incidence and trends of antimicrobial resistance over the last 10 years in N. gonorrhoeae isolates from a Portuguese Centre. METHODS: Laboratorial confirmed N. gonorrhoeae infections diagnosed between 2009 and 2018 were evaluated. Susceptibilities to penicillin, tetracycline, ciprofloxacin, azithromycin and cefotaxime were studied, along with demographic and clinical characteristics. RESULTS: From 2009 to 2018, 440 cases of N. gonorrhoeae infection were diagnosed in our center, with a significant yearly increase (p<0.05). Most cases occurred in males (97.9%), with a median age of 25 years. In 88.7% of the cases, treatment with ceftriaxone plus azithromycin was used. Resistances to penicillin, tetracycline and ciprofloxacin remained high throughout the study period. CONCLUSIONS: Antimicrobial resistance of N. gonorrhoeae appeared shortly after the introduction of antimicrobials. To combat this problem, improved surveillance and more studies combining susceptibility and epidemiological data are needed. In our population, N. gonorrhoeae remains highly susceptible to the antibiotics currently recommended for its treatment, whereas ciprofloxacin, azithromycin (in monotherapy) and penicillin should be avoided as empirical treatment.

Arterite sifilítica / Retinal arteritis related to syphilis

Resumo Apresentamos um caso de neurosífilis em um homem jovem, com queixa de baixa acuidade visual (BAV) em olho esquerdo. Cursou com lesões eritemato-descamativas nas palmas das mãos, plantas dos pés e úlceras orais, sem lesões genitais. O exame oftalmológico revelou arterite em arcada nasal superior no olho afetado. Apresentou VDRL (1:4096) e FTA-Abs positivos. O exame do líquor cefalorraquidiano foi negativo. O tratamento foi realizado com ceftriaxona 2g/ dia por 14 dias, associado à prednisona 0,5mg/kg oral 48h após início do antibiótico. Após 15 dias de tratamento, houve melhora da AV, regressão da vasculite e redução da titulação do VDRL para 1:128.

Abstract We present a case of neurosyphilis in a young man with a complaint of low visual acuity in the left eye. He had erythematous-scaly lesions on the palms of the hands, soles of the feet and oral ulcers, without genital lesions. The ophthalmic examination revealed arteritis in the upper nasal arcade in the affected eye. He presented VDRL (1: 4096) and FTA-Abs positive. The cerebrospinal fluid cerebrospinal fluid test was negative. The treatment was performed with ceftriaxone 2g / day for 14 days, associated with prednisone 0.5mg / kg oral 48h after antibiotic onset. After 15 days of treatment, there was improvement of AV, regression of vasculitis and reduction of VDRL titration to 1: 128.

Impacto en el consumo de amikacina y ceftriaxone en una unidad de emergencias de adultos, luego de la implementación de una guía para el tratamiento de la infección urinaria alta / Impact on the consumption of ceftriaxone and amikacin in an adult emergency unit, after the implementation of a guide for the treatment of pyelonephritis

Introducción: los programas de optimización del uso de antimicrobianos son fundamentales para mejorar los resultados clínicos de los pacientes. Objetivos: determinar el impacto en el consumo de amikacina y ceftriaxona, además de cambios de sensibilidad de las principales bacterias en la unidad de emergencias del hospital Carlos van Buren de Valparaíso, Chile, luego de la implementación de una guía para el tratamiento de la ITU alta. Materiales y método: estudio cuasi-experimental antes/después. Se implementó una guía de tratamiento para la ITU alta, la cual fue enviada vía WhatsApp a los médicos de la unidad. Luego se midieron las dosis diarias definidas (DDD) de amikacina y ceftriaxona y se compararon con las DDD de los mismos meses del año anterior. Además se extrajo la sensibilidad de E.coli, K. pneumonia y P.mirabilis aisladas de urocultivos. Resultados: posterior a la intervención hubo un aumento de las DDD de amikacina y una disminución de las de ceftriaxona. K.pneumoniae mantuvo su sensibilidad a amikacina y la aumentó para cefotaxima, ertapenem y meropenem. Conclusiones: la implementación de una guía de tratamiento de la ITU alta aumentó el consumo de amikacina y disminuyó el de ceftriaxona. K.pneumoniae aumentó su sensibilidad a cefotaxima, ertapenem y meropenem.

Introduction: different antimicrobial stewardship programs are fundamental to improve clinical results in patients. Objectives: to determine the impact on amikacin and ceftriaxone consumption, in addition to knowing changes in sensitivity of the main agents in the emergency unit of the Carlos van Buren Hospital in Valparaíso, Chile, after the implementation of a treatment guide for pyelonephritis. Materials and methods: quasi-experimental before/after study. A treatment guide was implemented for pyelonephritis. The guide was sent by WhatsApp to all clinicians in the emergency unit. Following the intervention, amikacin and ceftriaxone defined daily dose (DDD) were measured and compared with the DDD for the same months of the previous year. In addition, the sensitivity of E.coli, K. pneumonia and P.mirabilis isolated from urine cultures was extracted. Results: after the intervention there was a sustained increase of the DDD of amikacin and a decrease in the DDD of ceftriaxone in the months studied period. K. pneumoniae maintained its sensitivity to amikacin and increased it to cefotaxime, ertapenem, and meropenem. Conclusions: The guide's implementation for treatment of high UTI in the emergency unit of the Carlos van Buren hospital increased the consumption of amikacin and decreased that of ceftriaxone. K. pneumoniae increased its sensitivity to cefotaxime, ertapenem and meropenem.

Cambios en las prescripciones y el consumo de antimicrobianos, luego de la implementación de recomendaciones de uso: experiencia en un hospital universitario / Changes in prescriptions and antibiotic consumption after the implementation of recommendations for use: experience in a university hospital

Resumen Introduccion: Actualmente cerca de la mitad de las prescripciones de antimicrobianos son inadecuadas, lo que aumenta la resistencia bacteriana. Tanto cefalosporinas como fluoroquinolonas se asocian con este fenomeno: aumento de bacterias productoras de β-lactamasas e infecciones por Clostridioides difficile, por lo que las agencias reguladoras buscan racionalizar su uso. Objetivo: Evaluar el efecto de recomendaciones para el uso adecuado de antimicrobianos en la proporcion de prescripciones inadecuadas de ceftriaxona y fluoroquinolonas. Metodologia: Se desarrollo un estudio de antes y despues, prospectivo e intervencional, que comparo la calidad y la cantidad de uso de ceftriaxona y fluoroquinolonas antes y despues de la implementacion de recomendaciones de uso para tratamientos de enfermedades infecciosas adquiridas en la comunidad. Los parametros medidos fueron: proporcion de prescripciones inadecuadas y DDD. Los datos se analizaron por medio del test de χ2, correccion de Fisher y test de Student. Resultados: Se evaluaron 206 pacientes, observandose una disminucion de 35% en las prescripciones inadecuadas, una reduccion del consumo de ceftriaxona y levofloxacina y un aumento significativo de la utilizacion de ampicilina/sulbactam. Conclusiones: La implementacion de recomendaciones de uso basadas en evidencia cientifica y susceptibilidad local, permitieron disminuir la proporcion de prescripciones inadecuadas y reducir el consumo de ceftriaxona y fluoroquinolonas.

Background: Nowadays about half of antibiotic prescriptions are inadequate, increasing bacterial resistance. Both cephalosporins and fluoroquinolones are associated with this phenomenon: increase of β-lactamase producing bacteria and Clostridioides difficile infections, which is why regulatory agencies seek to rationalize their use. Aim: To evaluate the effect of use recommendations on the proportion of inadequate prescriptions of ceftriaxone and fluoroquinolones. Methods: A prospective and interventional study was developed, comparing the quality and quantity of use of ceftriaxone and fluoroquinolones before and after the implementation of use recommendations for treatments of infectious diseases acquired at the community. The outcomes were: proportion of inadequate prescriptions and defined daily dose (DDD). Data were analyzed using the Chi-square test, Fisher's correction and Student's test. Results: A total of 206 patients were evaluated, a 35% decrease in inadequate prescriptions, a decline in the consumption of ceftriaxone and levofloxacin, and a significant increase in the use of ampicillin/ sulbactam was observed. Conclusions: The implementation of use recommendations based on scientific evidence and local susceptibility allowed to reduce the proportion of inadequate prescriptions and to reduce de consumption of ceftriaxone and fluoroquinolones.

Meningitis por Streptococcus pneumoniae resistente a ceftriaxona: reporte de un caso / Ceftriaxone-resistant Streptococcus pneumoniae meningitis: case report

RESUMEN La meningitis infecciosa es una emergencia médica. Dentro del espectro de agentes infecciosos, el más importante es el Streptococcus pneumoniae, agente etiológico más frecuente de la meningitis bacteriana. El inicio de tratamiento antimicrobiano empírico es de gran importancia y considera a las cefalosporinas de tercera generación como la primera alternativa. Sin embargo, casos de resistencia a ceftriaxona han sido reportados en diversas partes del mundo, siendo un problema emergente, por lo que necesita una reconsideración de los esquemas antibióticos empíricos actuales. Presentamos el caso de un varón de 56 años que presenta meningitis aguda infecciosa por Streptococcus pneumoniae resistente a ceftriaxona, que respondió favorablemente al tratamiento empírico combinado con ceftriaxona y vancomicina y que durante su estadía hospitalaria se detectó la presencia de hipotiroidismo y megacisterna magna.

ABSTRACT Infectious meningitis is a medical emergency. Within the spectrum of infectious agents, the most important is Streptococcus pneumoniae, the most frequent etiological agent of bacterial meningitis. The initiation of empirical antimicrobial treatment bears great importance and considers third-generation cephalosporins as the first alternative. However, cases of ceftriaxone resistance have been reported in several regions of the world. This has become an emerging problem in need of reconsideration of the current empirical antibiotic treatment schemes. We present the case of a 56-year old man with acute infectious meningitis caused by ceftriaxone-resistant Streptococcus pneumoniae, who responded favorably to combined empirical treatment with ceftriaxone and vancomycin and to whom, during his hospital stay, the presence of hypothyroidism and mega cisterna magna was diagnosed.

Clinical predictors of ceftriaxone resistance in microorganisms causing febrile urinary tract infections in men. / Factores clínicos predictivos de resistencia a ceftriaxona en microorganismos causantes de infección del tracto urinario febril en hombres.

OBJECTIVES: Because of high rates of resistance to fluoroquinolones, ceftriaxone has become one of the main options for treating febrile urinary tract infection (FUTI). This study aimed to identify predictors of ceftriaxone resistance in community-acquired FUTIs in men. MATERIAL AND METHODS: Cross-sectional ambispective study enrolling men with FUTIs treated in the emergency department of a local area hospital in Spain. RESULTS: A total of 552 FUTI episodes were studied; 103 (18.6%) were caused by a ceftriaxone-resistant microorganism. Variables associated with a ceftriaxone-resistant FUTI were older age, health care-associated FUTI, dementia, diabetes mellitus, neoplasms, a history of UTIs, urologic disease, and complicated FUTI. Patients with ceftriaxone-resistant FUTIs also had higher rates of recent antibiotic treatment. Independent variables associated with FUTI due to a ceftriaxoneresistant microorganism were cirrhosis of the liver (odds ratio [OR], 6,00 95% CI, 1.25-28; P = .025), health careassociated FUTI (OR, 2.3 95% CI, 1.23-4.27; P = .009), and prior treatment with antibiotics (OR, 2.15; 95% CI, 1.23-3.76 P = .007). Components of health care-associated FUTI were a history of admission to a long-term residence (OR, 2.90 95% CI, 1.21-7.16; P = .017) and use of penicillins with or without beta-lactamase inhibitors (OR, 2.16; 95% CI, 1.05-4.42; P = .035). CONCLUSION: Cirrhosis of the liver; history of health care-associated FUTI, especially in patients residing in a long-term care facility; and recent use of antibiotics, mainly penicillins with or without beta-lactamase inhibitors, are risk factors for ceftriaxone-resistant FUTI in men.

OBJETIVO: Las elevadas tasas de resistencia a fluoroquinolonas han hecho de la ceftriaxona una de las principales opciones terapéuticas en las infecciones del tracto urinario febriles (ITUF). El objetivo del estudio es identificar factores predictivos de infección por microorganismos resistentes a ceftriaxona (MRC) en ITUF comunitaria en hombres. METODO: Estudio transversal ambispectivo en el que se incluyeron hombres con ITUF atendidos en el servicio de urgencias de un hospital comarcal. RESULTADOS: Se incluyeron 552 episodios de ITUF, 103 (18,6%) causadas por MRC. Los pacientes con ITUF por MRC tenían mayor edad, más frecuencia de ITUF relacionada con la atención sanitaria (ITUF-AS), demencia, diabetes mellitus, neoplasia, ITU previa, patología urológica, ITUF complicada y antecedente de tratamiento antibiótico reciente. Las variables independientemente asociadas a ITUF por MRC fueron la cirrosis hepática (OR 6,00; IC 95%: 1,25-28; p = 0,025), tener una ITUF-AS (OR 2,3; IC 95%: 1,23-4,27; p = 0,009) y el consumo previo de antibióticos (OR 2,15; IC 95%: 1,23-3,76; p = 0,007). Entre los componentes de la ITUF-AS, el antecedentes de estancia en centro larga estancia (OR 2,90; IC 95%: 1,21-7,16; p = 0,017) y entre los antibióticos el consumo de penicilinas con/sin inhibidores de betalactamasa (OR 2,16; IC 95%: 1,05-4,42; p = 0,035) se asociaron a ITUF por MRC. CONCLUSIONES: La cirrosis, presentar una ITUF-AS, especialmente provenir de un centro de larga estancia, y el consumo reciente de antibióticos, principalmente de penicilinas con/sin inhibidores de betalactamasa, son factores de riesgo de ITUF por MRC en hombres.

Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos en pediatría: Caso clínico / DRESS syndrome in paediatrics: Clinical case

El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos es una enfermedad potencialmente mortal, caracterizada por exantema, fiebre, adenopatías, alteraciones hematológicas y compromiso de órganos internos. Objetivo: Presentar una afección poco frecuente en pediatría para facilitar la sospecha diagnóstica y el rápido reconocimiento por parte de los médicos. Caso clínico: Lactante de 9 meses hospitalizada por un cuadro de neumonía viral grave con ventilación mecánica no invasiva, tratada con ceftriaxona entre otros medicamentos. Al quinto día de suspendido el antibiótico presentó un exantema maculopapular violáceo, confluente de predominio en el tronco, la cara y las extremidades superiores, asociado a fiebre, eosinofilia y elevación de transaminasas. Se manejó con prednisona oral más corticoides tópicos por 6 semanas, con buena evolución a los 3 meses de seguimiento. Conclusiones: El diagnóstico de síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos se realiza por clínica y exámenes de laboratorio, además de biopsia cutánea en caso de duda diagnóstica. Si bien su causa más frecuente son los anticonvulsivantes se han descrito casos con un sinnúmero de fármacos. El manejo consiste en la suspensión del fármaco sospechoso asociado a medidas de soporte y tratamiento corticosteroide por tiempos prolongados.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially life-threatening, drug-induced hypersensitivity reaction that includes skin eruption, haematological abnormalities, lymphadenopathy, and internal organ involvement. Objective: Presenting a rare condition in children, to facilitate a rapid diagnostic suspicion and recognition by doctors. Case report: An 9 months old infant admitted due to a severe viral pneumonia, managed with non-invasive ventilation and ceftriaxone. Five days after stopping antibiotics, a confluent maculopapular rash appeared, which was predominantly in the trunk, face and upper extremities, combined with a fever, eosinophilia, and elevated serum levels of transaminase. She received treatment with oral prednisone and topical corticosteroids for 6 weeks, with a good outcome after 3 months. Conclusions: The diagnosis of DRESS syndrome is made using clinical criteria, laboratory values, and histopathology, if there is any query. Although it is classically caused by anticonvulsants and sulphonamides, many other drugs have been implicated. The offending drug should be immediately discontinued and the patient given supportive treatment, and systemic corticosteroids for long periods of treatment.

Actividad in vitro de ampicilina-ceftriaxona frente a aislamientos de Enterococcus faecalis recuperados de infecciones invasivas / In vitro activity of ampicillin-ceftriaxone against Enterococcus faecalis isolates recovered from invasive infections

Se evaluó la actividad in vitro de la asociación entre ampicilina y ceftriaxona frente a 30 aislamientos de Enterococcus faecalis obtenidos de infecciones invasivas de pacientes atendidos en el Hospital de Clínicas José de San Martín, Ciudad Autónoma de Buenos Aires. Las sinergias entre ampicilina y ceftriaxona se determinaron mediante la técnica de dilución en caldo Müeller-Hinton con el agregado de diferentes concentraciones subinhibitorias de ceftriaxona o sin este. La asociación fue sinérgica en 22/30 aislamientos. En 14/30 aislamientos la asociación disminuyó los valores de concentración inhibitoria mínima (CIM) y de concentración bactericida mínima (CBM); en 6/30 se observó solamente una disminución de la CIM, mientras que en 2 solo se determinó una reducción de la CBM. La actividad bactericida de la asociación fue mayor a bajas concentraciones de ampicilina (menor de 1µg/ml). Se demostró la sinergia in vitro entre ampicilina-ceftriaxona; se confirmó así la utilidad de esta asociación en el tratamiento de infecciones severas causadas por E. faecalis

In vitro activity of the combination of ampicillin- ceftriaxone against 30 Enterococcus faecalis isolates recovered from invasive infections in patients admitted to Hospital de Clínicas José de San Martin in the city of Buenos Aires was assessed. Ampicillin- ceftriaxone synergies were determined by microdilution in Müeller-Hinton (MH) broth with and without subinhibitory concentrations of ceftriaxone. Synergy was detected in 22/30 isolates. A decrease in both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was observed in 14/30 isolates, whereas in 6/30 isolates the decrease was observed in the MIC value and only in the MBC value in the 2 remaining isolates. The bactericidal activity of the combination showed to be higher at low concentrations of ampicillin (< 1µg/ml). We detected in vitro synergy using the ampicillin-ceftriaxone combination and thus, its efficacy was confirmed in the treatment of severe infections by E. faecalis

[In vitro activity of ampicillin-ceftriaxone against Enterococcus faecalis isolates recovered from invasive infections]. / Actividad in vitro de ampicilina-ceftriaxona frente a aislamientos de Enterococcus faecalis recuperados de infecciones invasivas.

In vitro activity of the combination of ampicillin- ceftriaxone against 30 Enterococcus faecalis isolates recovered from invasive infections in patients admitted to Hospital de Clínicas José de San Martin in the city of Buenos Aires was assessed. Ampicillin- ceftriaxone synergies were determined by microdilution in Müeller-Hinton (MH) broth with and without subinhibitory concentrations of ceftriaxone. Synergy was detected in 22/30 isolates. A decrease in both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was observed in 14/30 isolates, whereas in 6/30 isolates the decrease was observed in the MIC value and only in the MBC value in the 2 remaining isolates. The bactericidal activity of the combination showed to be higher at low concentrations of ampicillin (< 1 µg/ml). We detected in vitro synergy using the ampicillin-ceftriaxone combination and thus, its efficacy was confirmed in the treatment of severe infections by E. faecalis.

[Gallstones in association with the use of ceftriaxone in children]. / Cálculos biliares asociados al uso de ceftriaxona en niños.

INTRODUCTION: Ceftriaxone associated pseudolithiasis is fairly frequent in children, but rarely taken into account. It occurs in 15% to 57% of children, and in most cases is asymptomatic and resolves spontaneously. PATIENTS AND METHODS: A prospective, observational, and descriptive study was conducted that included patients aged 1 month to 18 years-old who received ceftriaxone. Liver and gallbladder ultrasound was performed at the start of treatment, and every 5 days until it was completed. Patients with abnormal ultrasound findings were followed up clinically every week until they were resolved. The findings were compared with risk factors described in the literature. RESULTS: A total of 73 patients aged between 4 months and 17 years (mean=4.2 years) were included, of whom 57.5% were female. Pseudolithiasis was present in 31 patients (42.5%) and was documented in 96.8% (n=30) of this group on day 5. The stone size was between 4 and 14mm (mean=8.1mm). The duration of pseudolithiasis was between 9 and 55 days (mean=24.1 days). Symptoms were present in 22.6% (n=7) and 1 had a serious complication. In the multivariate analysis, Ringer's Lactate as fluid dilution was 1.86 times higher risk (P=.019). No relationship was found with age, duration and dose of antibiotic, fasting, use of calcium supplements, parenteral nutrition, or use of other antibiotics. CONCLUSION: Pseudocolelitiasis associated with ceftriaxone take place in 4 of 10 children who receive, unrelated to traditional risk factors. The trend is towards self resolution although about 20% have symptoms.

A fully validated microbiological assay to evaluate the potency of ceftriaxone sodium

Ceftriaxone (CFTX) sodium is a third-generation, broad-spectrum cephalosporin that is resistant to beta-lactamases. An alternative bioassay for the assessment of the potency of this drug in pharmaceutical formulations has not been previously reported. Thus, this paper reports the development and full validation of a 3 x 3 agar diffusion bioassay using a cylinder-plate method to quantify CFTX sodium in pharmaceutical samples. The strain Staphylococcus aureus ATCC 6538P was used as the test microorganism, and the results of the proposed bioassay displayed high linearity, precision, accuracy, specificity and robustness. All potency results were statistically analyzed using an analysis of variance (ANOVA) and were found to be linear (r=0.99999) in the range of 16-64 µg/mL, accurate (100.5%), and precise [repeatability: relative standard deviation (RSD)=1.4%; intermediate precision: between-day RSD=2.1% and between-analyst RSD=2.5%]. The specificity of the bioassay was determined by evaluating a degraded sample (50 ºC) at 0, 24 and 48 hours as compared against the results from the pharmacopeial liquid chromatography method for CFTX. The results validated the proposed microbiological assay, which allows reliable quantitation of CFTX in pharmaceutical samples. Moreover, it is a useful, simple and low-cost alternative method for monitoring the quality of this medicine.

A ceftriaxona sódica é uma cefalosporina de terceira geração de uso parenteral, com amplo espectro de atividade e resistente a b-lactamases. Este estudo apresenta o desenvolvimento e validação de um bioensaio por difusão em ágar usando o método de cilindros em placas para determinação da potência deste antibiótico. A validação desenvolvida apresentou bons resultados em termos de linearidade, precisão, exatidão, especificidade e robustez. Empregou-se o Staphylococcus aureus ATCC 6538P como micro-organismo teste. Os resultados dos ensaios foram tratados estatisticamente utilizando-se análise de variância (ANOVA). O método apresentou linearidade (r=0,99999) na faixa de doses selecionada (16-64 µg/mL), precisão (repetibilidade: DPR=1,4%; precisão intermediária: inter-dias DPR=2,1% e inter-analistas: DPR=2,5%) e exatidão de 100,5%. A especificidade do bioensaio foi avaliada através da análise comparativa, por cromatografia líquida de alta eficiência, de amostras degradadas a 50 ºC nos tempos zero, 24 e 48 h. Os resultados encontrados demonstraram a validade do bioensaio proposto, o qual permite a quantificação confiável de ceftriaxona sódica em produtos farmacêuticos comerciais. Por ser metodologia simples e de baixo custo constitui-se em alternativa para a análise de rotina do controle de qualidade de medicamentos.

Coledocolitiasis y colangitis como complicación del uso de ceftriaxona en niños: reporte de caso / Choledocholithiasis and cholangitis as a complication of ceftriaxone in children: a case report

La ceftriaxona es ampliamente usada en pediatría debido a su espectro de acción, larga vida media y buena penetración en los sitios donde se asientan las infecciones más frecuentes. Es bien tolerada, aunque, con frecuencia, en niños que la reciben, se presenta barro biliar y pseudocolelitiasis. Esto se ve favorecido porque cerca del 40% del fármaco es eliminado por la bilis sin modificaciones, donde se comporta como un anión con alta afinidad por las sales de calcio. Resumen La mayoría de los casos cursan asintomáticos o mínimamente sintomáticos, y de resolución espontánea solo al suspender el uso del fármaco. Se presenta el caso de una niña de 4 años que recibe ceftriaxona durante 14 días por sinusitis, desarrollando al quinto día cálculos en la vesícula biliar que crecen hasta 11 mm y tardan 55 días en desaparecer; el día 34, presenta colecistitis, colangitis y coledocolitiasis que requieren manejo hospitalario.

Ceftriaxone is widely used in children because it has a great spectrum, long half-life and good penetration. Is generally well tolerated, although in children who receive the drug, it often presented pseudocolelitiasis and biliary sludge. This is favored because about 40% of the drug is eliminated unchanged in bile where it behaves as an anion with high affinity for calcium salts. Most cases present as asymptomatic or minimally symptomatic and spontaneous resolution, only when the drug is no longer taken. A case of a 4 year old girl who received ceftriaxone for 14 days for sinusitis and on day 5 develops gall bladder stones that grow to 11 mm and last 55 days to go away, the day 34 presents cholecystitis, cholangitis and choledocholithiasis requiring medical management to resolution.

Anemia hemolítica autoimune induzida por ceftriaxona: relato de caso e breve revisão da literatura / Ceftriaxone-induced immune hemolysis: case report and a concise review of the literature

JUSTIFICATIVA E OBJETIVOS: As cefalosporinas de segunda e terceira geração têm sido descritas como a causa mais comum de anemia hemolítica (HA) induzida por fármacos. A AH causada por ceftriaxona apesar de ser um evento raro, vem sendo descrita tanto em crianças quanto em adultos sendo estes a maioria idosa, acima de 60 anos. A apresentação clínica da AH induzida pelo ceftriaxona é usualmente abrupta com palidez, taquipneia,parada cardiorrespiratória e choque. O objetivo deste estudo foi relatar um caso de AH autoimune associada ao ceftriaxona com evolução fatal e breve revisão da literatura. RELATO DO CASO: Paciente do sexo feminino, 55 anos, com diagnóstico de infecção urinária apresentou AH autoimune intravascular com hemoglobina de 4,5 g/dL, após infusão de ceftriaxona não sobrevivendo ao evento apesar de todo o suporte intensivo. CONCLUSÃO: O ceftriaxona é um fármaco comumente usado e pode causar AH fatal; o reconhecimento precoce da AH e a instituição de suporte intensivo são fundamentais para a tentativa de um prognóstico mais favorável.

BACKGROUND AND OBJECTIVES: The second and third generation cephalosporins have been reported as the most common cause of drug-induced hemolytic anemia (HA). The ceftriaxone-induced HA despite being a rare event, has been described both in children and adults and these mostly elderly above 60 years. The clinical presentation of ceftriaxone-induced HA isusually abrupt with pallor, tachypnea, cardio-respiratory arrestand shock. We report here a ceftriaxone-induced HA case withfatal outcome and a concise review of the literature. CASE REPORT: Female patient, 55 years, with urinary infection had HA autoimmune intravascular resulting in hemoglobinof 4.5 g/dL, after ceftriaxone infusion, not surviving the event despite all the intensive care. CONCLUSION: Ceftriaxone is a drug commonly used and can cause fatal HA; early recognition of HA and the institution of intensive support are essential for attempting a more favorable prognosis.

Antibiotic treatment schemes for very severe community-acquired pneumonia in children: a randomized clinical study / Esquemas de tratamiento antibiótico para la neumonía extrahospitalaria muy grave en niños: estudio clínico aleatorizado

OBJECTIVE: To compare clinical response to initial empiric treatment with oxacillin plus ceftriaxone and amoxicillin plus clavulanic acid in hospitalized children diagnosed with very severe community-acquired pneumonia (CAP). METHODS: A prospective randomized clinical study was conducted among children 2 months to 5 years old with a diagnosis of very severe CAP in the pediatric ward of São Paulo State University Hospital in Botucatu, São Paulo, Brazil, from April 2007 to May 2008. Patients were randomly divided into two groups by type of treatment: an oxacillin/ceftriaxone group (OCG, n = 48) and an amoxicillin/clavulanic acid group (ACG, n = 56). Analyzed outcomes were: time to clinical improvement (fever and tachypnea), time on oxygen therapy, length of stay in hospital, need to widen antimicrobial spectrum, and complications (including pleural effusion). RESULTS: The two groups did not differ statistically for age, sex, symptom duration before admission, or previous antibiotic treatment. Time to improve tachypnea was less among ACG patients than OCG patients (4.8 ± 2.2 versus 5.8 ± 2.4 days respectively; P = 0.028), as was length of hospital stay (11.0 ± 6.2 versus 14.4 ± 4.5 days respectively; P = 0.002). There were no statistically significant differences between the two groups for fever improvement time, time on oxygen therapy, need to widen antimicrobial spectrum, or frequency of pleural effusion. CONCLUSIONS: Both treatment plans are effective in treating very severe CAP in 2-month-to 5-year-old hospitalized children. The only analyzed outcome that favored amoxicillin/clavulanic acid treatment was time required to improve tachypnea.

OBJETIVO: Comparar la respuesta clínica al tratamiento empírico inicial con oxacilina más ceftriaxona frente a amoxicilina más ácido clavulánico en niños hospitalizados con diagnóstico de neumonía extrahospitalaria muy grave. MÉTODOS: Se llevó a cabo un estudio clínico prospectivo aleatorizado en niños de 2 meses a 5 años de edad con diagnóstico de neumonía extrahospitalaria muy grave en la sala de pediatría del Hospital Universitario del Estado de São Paulo en Botucatu, São Paulo, Brasil, entre abril del 2007 y mayo del 2008. Los pacientes se dividieron aleatoriamente en dos grupos según el tratamiento administrado: un grupo recibió oxacilina/ceftriaxona (n = 48) y otro amoxicilina/ácido clavulánico (n = 56). Los criterios de valoración analizados fueron el tiempo hasta la mejoría clínica (de la fiebre y la taquipnea), el tiempo de administración de oxigenoterapia, la duración de la internación, la necesidad de ampliar el espectro antibiótico y las complicaciones (como el derrame pleural). RESULTADOS: Los dos grupos no presentaban diferencias estadísticas con respecto a la edad, el sexo, la duración de los síntomas antes de la internación o el tratamiento previo con antibióticos. El tiempo hasta la mejoría de la taquipnea fue menor en los pacientes tratados con amoxicilina/ácido clavulánico que en los que recibieron oxacilina/ceftriaxona (4,8 ± 2,2 días frente a 5,8 ±2,4 días, respectivamente; P = 0,028), y también fue menor la duración de la internación (11,0 ± 6,2 días frente a 14,4 ± 4,5 días, respectivamente; P = 0,002). No hubo diferencias estadísticamente significativas entre los dos grupos en relación con el tiempo hasta la mejoría de la fiebre, el tiempo de administración de oxigenoterapia, la necesidad de ampliar el espectro antibiótico ni la frecuencia de derrame pleural. CONCLUSIONES: Ambos esquemas de tratamiento son eficaces para tratar la neumonía extrahospitalaria muy grave en niños de 2 meses a 5 años de edad hospitalizados. El único criterio de valoración analizado que favoreció el tratamiento con amoxicilina/ ácido clavulánico fue el tiempo hasta la mejoría de la taquipnea.

Uso de ceftriaxona en monodosis para el tratamiento de la otitis media aguda supurada en pacientes de edad pediátrica / Ceftriaxone´s use in monodoses for the treatment of otitis media acute suppurativa in pediatric age patients

La otitis media aguda supurada es muy frecuente en pediatría. El 80 por ciento de los niños en edad preescolar y el 50 por ciento de los lactantes hacen un cuadro de supuración de oídos dos veces al año. Objetivo: evaluar la efectividad de la ceftriaxona en dosis única en pacientes pediátricos con otitis media aguda supurada. Método: se realizó un ensayo clínico, fase IV, durante el segundo semestre del año 2008, a 51 niños ingresados con el diagnóstico de Otitis Media Aguda Supurada, en el Hospital Pediátrico Provincial de Camagüey Eduardo Agramante Piña. Resultados: se encontró un ligero aumento del sexo masculino; con predominio significativo de la raza blanca. Existió una alta incidencia en los pacientes menores de un año. El 58,8 por ciento de los pacientes recibieron tratamiento previamente con antimicrobianos. El tratamiento antimicrobiano utilizado con mayor frecuencia fue la amoxicillina, la penicilina y el Claforan. Más del 66 por ciento presentó una evolución favorable dentro de las 72h siguientes al tratamiento con la monodosis de ceftriaxona. En 48 de los pacientes estudiados se obtuvo una evolución otoscópica favorable, lo que correspondió a un 94,12 por ciento de los casos estudiados. Al estudiar el comportamiento de los pacientes según edad y otras enfermedades asociadas, se pudo observar que sólo dos pacientes no presentaron otras enfermedades asociadas. Conclusiones: se logró una evolución favorable dentro de las 72h siguientes al tratamiento con la monodosis de ceftriaxona en casi la totalidad de los casos.

Otitis media acute suppurativa is very frequent disease in pediatrics. The 80 percent of children in preschool age and 50 percent of infants make ear suppuration twice a year. Objective: to evaluate the efficacy of an only dose of ceftriaxone in pediatric patients with otitis media acute suppurativa. Method: a phase IV clinical trial was performed, during the second semester of 2008 to 51 children admitted with otitis media acute suppurativa as diagnosis, at the provincial pediatric hospital of Camagüey Eduardo Agramonte Piña. Results: a slight increase of the masculine sex was found; with significant prevalence of the white race (44,86 percent). There was a high incidence in patients under one year (29) for 56,9 percent. The 58,8 percent (30) of patients previously received antimicrobial treatment. The most frequent antimicrobial treatment used was amoxicillin (44,1 percent), penicillin (20,5 percent) and claforan (11,7 percent). More than the 66 percent presented a favorable evolution within 72 hours next to the treatment with ceftriaxone monodoses. In 48 of studied patients a favorable otoscopic evolution was obtained, what corresponded to 94,12 percent of studied cases. Conclusions: a favorable evolution was achieved within 72 hours following to the treatment with ceftriaxone monodoses in more than the half of cases.