GenoType MTBDRsl for detection of second-line drugs and ethambutol resistance in multidrug-resistant Mycobacterium tuberculosis isolates at a high-throughput laboratory

We assessed the performance of MTBDRsl for detection of resistance to fluoroquinolones, aminoglycosides/cyclic peptides, and ethambutol compared to BACTEC MGIT 960 by subjecting simultaneously to both tests 385 phenotypically multidrug-resistant-Mycobacterium tuberculosis isolates from Sao Paulo, Brazil. Discordances were resolved by Sanger sequencing. MTBDRsl correctly detected 99.7% of the multidrug-resistant isolates, 87.8% of the pre-XDR, and 73.9% of the XDR. The assay showed sensitivity of 86.4%, 100%, 85.2% and 76.4% for fluoroquinolones, amikacin/kanamycin, capreomycin and ethambutol, respectively. Specificity was 100% for fluoroquinolones and aminoglycosides/cyclic peptides, and 93.6% for ethambutol. Most fluoroquinolone-discordances were due to mutations in genome regions not targeted by the MTBDRsl v. 1.0: gyrA_H70R and gyrB_R446C, D461N, D449V, and N488D. Capreomycin-resistant isolates with wild-type rrs results on MTBDRsl presented tlyA mutations. MTBDRsl presented good performance for detecting resistance to second-line drugs and ethambutol in clinical isolates. In our setting, multidrug-resistant. isolates presented mutations not targeted by the molecular assay.

Características microbiológicas de los pacientes con úlcera del pie diabético / Microbiologic characteristics of patients with diabetic foot ulceration

RESUMEN Introducción: Las infecciones de las úlceras del pie diabético son comunes, complejas, de alto costo y constituyen la principal causa de amputación no traumática de las extremidades inferiores. Objetivo: Identificar los microorganismos aislados para estimar tanto la sensibilidad a los antibióticos como la coincidencia entre el tratamiento empírico y los resultados microbiológicos en pacientes con úlceras del pie diabético. Métodos: Se realizó una investigación descriptiva-retrospectiva. La población de estudio estuvo constituida por 210 pacientes ingresados en el Hospital Universitario Clínico Quirúrgico "Comandante Faustino Pérez Hernández" de Matanzas entre junio de 2017 y junio de 2020. Las variables de salida fueron la frecuencia y el tipo de germen, la cantidad de gérmenes por úlcera, la sensibilidad para cada tipo de antibiótico, y el porcentaje de coincidencia entre el tratamiento empírico y el resultado microbiológico. Resultados: Se identificaron 259 gérmenes y se observaron 1,23 gérmenes por úlcera. El 62,5 por ciento de los gérmenes encontrados fueron Gram negativos, pero el germen más representado fue el Staphylococcus aureus. El 58,8 por ciento de los Staphylococcus aureus se mostraron resistentes a la meticillin. La vancomicina y el linezolid resultaron efectivos en el 100 por ciento de los Gram positivos. La amikacina fue el antibiótico más efectivo para los Gram negativos. Se observó coincidencia entre el tratamiento empírico y el resultado del antibiograma en el 27,6 por ciento de los pacientes. Conclusiones: Resulta necesario un apropiado diagnóstico microbiológico de las úlceras del pie diabético para identificar los gérmenes presentes en las lesiones y diseñar algoritmos de terapia antimicrobiana adecuados(AU)

ABSTRACT Introduction: Diabetic foot ulcer infections are common, complex, high cost and are the leading cause of non-traumatic lower extremity amputation. Objective: To identify the microorganisms isolated to estimate both the sensitivity to antibiotics and the coincidence between empirical treatment and microbiological results in patients with diabetic foot ulcers. Methods: A descriptive-retrospective investigation was performed. The study population consisted of 210 patients admitted to the University Hospital "Comandante Faustino Pérez Hernández" of Matanzas between June 2017 and June 2020. The output variables were the frequency and type of germ, the number of germs per ulcer, the sensitivity for each type of antibiotic, and the percentage of coincidence between the empirical treatment and the microbiological result. Results: A total of 259 germs were identified and 1.23 germs per ulcer were observed. The 62.5 percent of the germs found were Gram negative, but the most represented germ was Staphylococcus aureus. Of the Staphylococcus aureus, 58.8 percentwere resistant to methicillin. Vancomycin and linezolid were effective in 100 percent of Gram positives. Amikacin was the most effective antibiotic for Gram-negatives. Agreement between empirical treatment and antibiogram result was observed in 27.6 percent of patients. Conclusions: An appropriate microbiological diagnosis of diabetic foot ulcers is necessary to identify the germs present in the lesions and to design adequate antimicrobial therapy algorithms(AU)

Impacto del monitoreo terapéutico de vancomicina y amikacina en la optimización de dosis de antimicrobianos en pacientes pediátricos / Impact of the vancomycin and amikacin therapeutic monitoring in the optimization of antimicrobial dose in pediatric patients

INTRODUCCIÓN: La monitorización de antimicrobianos mediante sus concentraciones plasmáticas permite determinar la posología óptima de éstos, conducta esencial en pediatría. OBJETIVOS: Describir la monitorización de concentraciones plasmáticas de antimicrobianos y el ajuste de dosis en población pediátrica para determinar si las dosis utilizadas alcanzan rangos terapéuticos. PACIENTES Y MÉTODOS: Estudio descriptivo, retrospectivo, utilizando una base de datos con medición de concentraciones plasmáticas de amikacina y vancomicina en pacientes pediátricos del Hospital San Borja Arriarán, entre 2015-2018. Se determinó el número de pacientes que alcanzó rango terapéutico con dosis inicial, cuántos requirieron ajuste y sus características. RESULTADOS: Se monitorizó 104 concentraciones totales. Para vancomicina 65 concentraciones plasmáticas eran basales encontrándose fuera de rango terapéutico 56,5%; de los que requirieron ajuste, 25% fueron neonatos con mayor probabilidad de estar fuera de rango versus otros (p = 0,022). Para amikacina la Cpeak estuvo en rango en 60% de mediciones; 15,4% requirió ajuste incluyendo pacientes con fibrosis quística y oncológicos. No fue necesario efectuar ajustes en pacientes sin co-morbilidad. CONCLUSIÓN: La medición de concentraciones plasmáticas es necesaria para ajustar de forma individualizada la dosis, especialmente en pacientes pediátricos con fibrosis quística, oncológicos y en neonatología, donde es más probable no alcanzar rango terapéutico con las dosis iniciales.

BACKGROUND: The monitoring of antimicrobial therapy through plasma levels makes it possible to determine the optimal dosage of antimicrobials, an essential approach in pediatrics. AIM: To describe the monitoring of plasma antimicrobial levels and dose adjustment in the pediatric population to determine if the doses used reach therapeutic ranges. METHODS: Retrospective, descriptive study using a database with measurement of plasma levels of amikacin and vancomycin in pediatric patients at San Borja Arriarán Hospital between 2015-2018. The number of patients who reached the therapeutic range with the initial dose, how many required adjustment and their characteristics were determined. RESULTS: 104 total levels were monitored. For vancomycin 65 plasmatic levels were baseline, being outside the therapeutic range 56.5%; 25% of those requiring adjustment were neonates with a higher probability of being out of range versus others (p = 0.022). For amikacin, Cpeak was in range in 60% of measurements; 15.4% required adjustment, including patients with cystic fibrosis and cancer, without adjustments in patients without comorbidity. CONCLUSION: Measurement of plasma levels is necessary to individually adjust the dose, especially in pediatric patients with cystic fibrosis, oncology and in neonatology where it is more likely not to reach a therapeutic range with initial doses.

Gérmenes bacterianos aislados con frecuencia en úlceras flebostáticas de pacientes ingresados / Bacterial germs frequently isolated in phlebostatic ulcers of admitted patients

Introducción: Las úlceras flebostáticas constituyen una patología importante en la práctica médica diaria en todos los niveles de asistenciales; después del dolor y del edema, las úlceras de los miembros inferiores representan el tercer problema más común en las consulta de angiología. Objetivo: Caracterizar los gérmenes bacterianos aislados con frecuencia en las úlceras flebostáticas de los pacientes ingresados. Métodos: Se realizó un estudio descriptivo retrospectivo de corte transversal en 60 pacientes ingresados por diagnóstico de úlceras flebostáticas entre julio de 2016 y junio de 2017. A todos se les hizo cultivo microbiológico de la lesión con el respectivo antibiograma. Se tuvieron en cuenta las variables: tipo de úlcera flebostática, gérmenes bacterianos aislados, antibióticos analizados in vitro y patrón de sensibilidad antibiótica. Se calcularon las frecuencias absolutas y relativas. Resultados: Se encontró un predominio de úlceras varicosas (67 por ciento). El germen bacteriano que más se aisló fue Pseudomas spp. (41,7 por ciento), con más frecuencia en las úlceras varicosas que en las postrombóticas (47,5 por ciento vs. 30 por ciento). Los mejores porcentajes de sensibilidad in vitro se mostraron ante los siguientes antibióticos: Clindamicina (100 por ciento), Tobramicina (79,2 por ciento), Ciprofloxacino (78,4 por ciento), Amikacina (68,4 por ciento), Cotrimoxazol (68,2 por ciento), Cefepime (67,6 por ciento), Doxiciclina (66,7 por ciento), Cloranfenicol (60 por ciento), Meropenem (62,1 por ciento), Penicilina G (57 por ciento) y Aztreonam (55,9 por ciento). Conclusiones: Pseudomas spp. fue el germen bacteriano que más se aisló en los pacientes con úlceras varicosas y postrombóticas; además, se manifestó sensibilidad a 11 de los 23 antibióticos que se probaron in vitro en más del 50 por ciento de los aislados a los que se enfrentaron(AU)

Introduction: Phlebostatic ulcers are an important pathology in daily medical practice at all levels of care; after pain and edema, lower limb ulcers are the third most common problem in angiology consultations. Objective: Characterize frequently isolated bacterial germs in the phlebostatic ulcers of admitted patients. Methods: A descriptive, cross-sectional, retrospective study was conducted in 60 patients admitted due to a diagnosis of phlebostatic ulcers from July 2016 to June 2017. It was made a microbiological cultivation of the lesion with the respective antibiogram to all the patients. Variables were taken into account, like: type of phlebostatic ulcer, isolated bacterial germs, antibiotics tested in vitro and antibiotic sensitivity pattern. The absolute and relative frequencies were calculated. Results: A predominance of varicose ulcers (67 percent) was found. The most isolated bacterial germ was Pseudomasspp. (41.7 percent), and it was more often in varicose ulcers than in post-thrombotic ulcers (47.5 percent vs. 30 percent). The best percentages of in vitro sensitivity were shown against the following antibiotics: Clindamycin (100 percent), Tobramycin (79.2 percent), Ciprofloxacin (78.4 percent), Amikacin (68.4 percent), Cotrimoxazol (68.2 percent), Cefepime (67.6 percent), Doxycycline (66.7 percent), Chloramphenicol (60 percent), Meropenem (62.1 percent), Penicillin G (57 percent), Aztreonam (55.9 percent). Conclusions: Pseudomasspp. was the most isolated bacterial germ in patients with varicose and post-thrombotic ulcers; in addition, sensitivity was present in 11 of the 23 antibiotics that were tested in vitro in more than 50 percent of the isolates they faced(AU)

Resistência aos antimicrobianos e diversidade genética de variantes fenotípicas de Pseudomonas aeruginosa não sensíveis aos carbapenêmicos recuperadas de pacientes com fibrose cística com infecção pulmonar crônica: uma análise temporal / Antimicrobial resistance and genetic diversity of phenotypic variants of carbapenem non susceptible Pseudomonas aeruginosa recovered from patients with cystic fibrosis with chronic lung infection: a temporal analysis

Pseudomonas aeruginosa, bactéria ubíqua e versátil, pode se comportar como um patógeno oportunista, com ampla capacidade adaptativa, por múltiplos fatores de virulência e resistência. Como agente patogênico nas infecções pulmonares em pacientes com fibrose cística (FC), é motivo de prognóstico ruim, aumento de hospitalizações e altas taxas de morbimortalidade, sendo quase impossível a sua erradicação, ao evoluírem para a cronicidade. Globalmente, é notável o aumento nos índices de amostras não sensíveis aos carbapenêmicos e a múltiplos antimicrobianos, essenciais à terapêutica. Assim, avaliamos temporalmente a susceptibilidade aos antimicrobianos e a presença de amostras hipermutáveis (HPM) em P. aeruginosa de diferentes morfotipos, não sensíveis aos carbapenêmicos (PANSC), obtidas de pacientes FC com infecção pulmonar crônica, acompanhados em dois centros de referência no Rio de Janeiro. De 2007 a 2016, a análise retrospectiva, através dos resultados obtidos no teste de disco-difusão (TDD), permitiu selecionar amostras de PANSC incluídas neste trabalho. Usando os resultados obtidos no TDD, foi definida a susceptibilidade a outros antimicrobianos, bem como os fenótipos de resistência, multi-(MDR), extensivo-(XDR) e pandroga resistentes (PDR). Adicionalmente, determinou-se a concentração inibitória mínima (CIM) para imipenem (IPM), meropenem (MEM), doripenem (DOR) e polimixina (POL). Através de teste fenotípico, foi calculada a frequência de mutação espontânea e as amostras hipermutáveis foram caracterizadas. O sequenciamento de genoma total (SGT) foi realizado em seis amostras de diferentes morfotipos, incluindo uma variante fenotípica rara, a small colony variant (SCV). Essas amostras foram recuperadas em dois episódios de exacerbação do paciente. Foram investigadas a clonalidade, resistência a antimicrobianos e virulência. Das 143 amostras, de 18 pacientes (9 pediátricos e 9 adultos), os resultados do TDD apontaram taxas de não susceptibilidade superiores a 44% para gentamicina, amicacina, tobramicina e ciprofloxacina, e maiores de 30 % para POL. Pela determinação da CIM, quase a totalidade (96%) das amostras foram não sensíveis a IMP, seguidos de 56% para MEM e 44% para DOR. Analisando-se a distribuição dos valores da CIM50 e CIM90 nos dois grupos de pacientes, os valores para IMP foram maiores entre as amostras dos pacientes pediátricos, equivalendo a 32 µg/mL e 64 µg/mL, respectivamente. Cerca de 25%, 37% e 6% eram MDR, XDR e PDR, respectivamente. Aproximadamente 12% eram HPM, e mais da metade destas foram XDR. Após o SGT, as seis amostras, recuperadas do caso clínico foram classificadas em um novo sequence type (ST2744), com a presença de genes de resistência adquiridos blaPAO, blaOXA-50, aph(3')-Iib, fosA, catB7 e crpP, apresentando mutações em genes codificadores de porinas e bombas de efluxo. Entretanto, não foram observados marcadores genéticos clássicos exclusivos para os fenótipos SCV e HPM. Este é o primeiro relato de P. aeruginosa SCV na FC, no Brasil. A vigilância epidemiológica de P. aeruginosa é crucial para a conduta terapêutica, bem como para o sucesso da resposta do paciente e erradicação da infecção pulmonar, justificando o uso de técnicas fenotípicas e moleculares na detecção dos mecanismos de resistência e virulência desse microrganismo na FC.

Pseudomonas aeruginosa, a ubiquitous and versatile bacterium, can behave as an opportunistic pathogen, with strong adaptive capacity, due to multiple virulence and resistance factors. As a pulmonary infection pathogen in patients with cystic fibrosis (CF), it is related with poor prognosis, increased hospitalizations and high rates of morbidity and mortality, and the eradication is almost impossible, especially after chronicity. The increase rates of isolates non-susceptible to carbapenem and multiple antimicrobials, essentials to therapy, have been observed worldwide. Therefore, we assessed the antimicrobial susceptibility and the presence of hypermutability (HPM) in non-susceptible to carbapenem P. aeruginosa (PANSC) isolates from different morphotypes, obtained from CF patients with chronic pulmonary infection, followed at two reference centers in Rio de Janeiro. Using the results obtained by disk-diffusion test (DDT) between 2007 to 2016, we select 143 PANSC and susceptibility to other antimicrobials was defined, as well as the resistance phenotypes, multi- (MDR), extensive- (XDR) and pandrug resistant (PDR). Additionally, the minimum inhibitory concentration (MIC) for imipenem (IPM), meropenem (MEM), doripenem (DOR) and polymyxin (POL) was determined. Hypermutable isolates were characterized by determination of mutation frequency. Whole genome sequencing (WGS) was performed in six morphotypes isolates, including the small colony variant (SCV), a rare variant phenotype. These isolates were recovered in two exacerbation episodes. Clonality, antimicrobial resistance and virulence were investigated. Of the total (143 isolates) isolated from 18 patients (9 pediatric and 9 adults), non-susceptibility rates above than 44% for gentamicin, amikacin, tobramycin and ciprofloxacin, and more than 30% for POL were observed. Almost all (96%) of the isolates were non-susceptible to IPM by MIC determination, followed by 56% for MEM and 44% for DOR. MIC50 (32 µg/mL) and MIC90 (64 µg/mL) rates for IPM were higher among pediatric patient isolates and 25%, 37% and 6% were MDR, XDR and PDR, respectively. 12% of all isolates were classified as HPM and more than half were categorized as XDR. Using WGS, the six isolates recovered from the clinical case, were identified as a new sequence type (ST2744). Acquired resistance genes blaPAO, blaOXA-50, aph (3')-Iib, fosA, catB7 and crpP and mutations in encoding genes for porins and efflux pumps, was annotated. None exclusive classic genetic markers related to SCV and HPM phenotypes were not observed. This is the first Brazilian report of P. aeruginosa SCV in CF. Our results highlight the importance of epidemiological surveillance in P. aeruginosa. The application of phenotypic and molecular techniques to investigate resistance and virulence mechanisms, can contribute to therapeutic success in CF.

Infecciones del tracto urinario en neonatos sin explicación. Hiperbilirrubinemia: Prevalencia y predictivo factores de riesgo / Urinary tract infections in unexplained neonatal hyperbilirubinemia: Prevalence and predictive risk factors

Introduction: Urinary tract infections (UTIs) are widespread clinical disorder among early neonates. Neonates with UTIs were susceptible to higher rates of morbidity and mortality, particularly when presented with hyperbilirubinemia. Early diagnosis may help in complete recoveryrather than being threatened in terms of complications. The study aimed at determining the prevalence and predictive risk factors of UTIs in neonates with an unexplained hyperbilirubinemia. Method: A cross-sectional study was carried out in the NICU of Aswan University Hospital, Egypt from August 2018 to February 2019. The study was conducted on 140 newborns who were diagnosed with indirect hyperbilirubinemia in the first 4 weeks of life after exclusion of unrelated criteria. Demographic and clinical data were collected by an interview questionnaire. Biochemical markers including bilirubin level, CBC, urine analysis and urine cultures and sensitivity were determined. Results: The prevalence rate of UTIs in the studied newborns was 25%. Escherichia -coli was the dominant organism isolated. Amikacin was the most common antibiotic sensitive to the isolates. There was a significant difference between the UTI positive and negative neonates in the univariate analysis regarding some studied variables. While, an increase in the number of WBCs in the blood (OR = 6.90, P = 0.001), small for gestational age (OR = 4.07, P = 0.021), prolonged phototherapy (OR = 3.50, P = 0.034), and presence of maternal complications (OR = 2.92, P = 0.001) were statistically associated with a positive urine culture in multivariate analysis. Conclusions and recommendations: The prevalence rate of UTIs was 25%. The study indicated the importance of routine screening of UTI (urine culture) as part of the clinical assessment of unexplained hyperbilirubinemia in neonates with an increase in the number of WBCs in their blood, small for gestational age, prolonged duration of phototherapy, and neonates born from mothers who had a history of obstetric complications

Mycobacterium abscessus urinary tract infection: case report / Infecção urinária por Mycobacterium abscessus: relato de caso

Abstract Urinary tract infection is a serious public health issue that predominantly affects women. In men, it is more often associated with prostatic hyperplasia and bladder catheterization. Urogenital tuberculosis presents with nonspecific with nonspecific symptoms and the diagnosis can be made in the presence of sterile leukocyturia and recurrent infection with acid urine. Non-tuberculous mycobacteria or other non-tuberculosis mycobacteria are opportunistic pathogens that inhabit the soil, water or environment surfaces, and usually cause diseases in immunocompromised individuals. Mycobacterium abscessus is an agent that causes lung, skin and soft tissue hospital infections. Urinary tract infections by this pathogen are rare.

Resumo Infecção do trato urinário é um sério problema de saúde pública que acomete predominantemente as mulheres. Em homens, está mais relacionada com hiperplasia prostática e cateterismo vesical. A tuberculose urogenital cursa com sintomas inespecíficos e o diagnóstico pode ser aventado na presença de leucocitúria estéril, e infecção recorrente com urina ácida. Micobactérias não tuberculosas ou mycobacteria other than tuberculosis são patógenos oportunistas que habitam o solo, a água ou superfícies do meio ambiente, e geralmente causam doenças em imunodeprimidos. Mycobacterium abscessus é um agente que causa infecções nosocomiais, pulmonares, de pele e de tecidos moles. Infecção urinária decorrente desse patógeno é considerada rara.

Antibiotic-Resistant Salmonella, isolated from cloacal swab samples from turtles in Guatemala / Salmonella resistente a antibióticos, aislada de muestras de hisopados cloacales en tortugas de Guatemala

Salmonellosis is a relevant public health threat worldwide. Reptiles are commonly involved in human cases. A microbiological survey was conducted from August to October 2018 to isolate Salmonella bacteria and de-termine if they were resistant to regularly used antibiotics in eight species of pet turtles (Kinosternon acutum sp., K. leucostomum, K. scorpioides, Rhinoclemmys areolata sp., R. pulcherrima, Staurotypus salvinii sp., Trachemys scripta and T. venusta) in Guatemala city, San Lucas Sacatepéquez and Antigua Guatemala. Cloacal swabs were taken from 63 turtles and cultivated in the Microbiology Laboratory at the Veterinary Medicine and Animal Hus-bandry Faculty, University of San Carlos of Guatemala, in Guatemala City. Three samples were positive to the presence of Salmonella sp. One of these isolates (from Trachemys scripta) was resistant to gentamicin, penicillin and amikacin, other isolate (from T. scripta) was partially resistant to amoxicilin + clavulanic acid and penicillin, and other (from T. venusta) to penicillin. These findings highlight the need for better biosecurity practices and show the capacity of bacteria to develop survival strategies that involve resistance to harmful substances like antibiotics.

La salmonelosis es una importante enfermedad zoonótica considerada una amenaza a la salud pública a nivel mundial. Los reptiles están comúnmente involucrados en la transmisión animal-humano. Con el objetivo de determinar la presencia de Salmonella y determinar su resistencia a antibióticos de uso común, se realizó un estudio exploratorio en ocho especies de tortugas (Kinosternon acutum sp., K. leucostomum, K. scorpioides, Rhinoclem-mys areolata sp., R. pulcherrima, Staurotypus salvinii sp., Trachemys scripta y T. venusta) en Guatemala y en San Lucas Sacatepéquez. Se tomaron hisopados cloacales de 63 especímenes y se cultivaron en el Laboratorio de Microbiología de la Facultad de Medicina Veterinaria y Zootecnia de la Universidad de San Carlos de Guatemala. Tres muestras fueron positivas a la presencia de Salmonella sp. Uno de los aislados (de Trachemys scripta) fue resistente a gentamicina, penicilina y amikacina, otro aislado (de T. scripta) fue parcialmente resistente a amoxicilina + ácido clavulánico y a penicilina y un tercer aislado (de T. venusta) a penicilina. Estos hallazgos resaltan la necesidad de mejores prácticas de bioseguridad y muestran la capacidad de las bacterias para desarrollar estrategias de sobrevivencia que involucran la resistencia a sustancias que les son nocivas, como los antibióticos.

Culture-Positive Spontaneous Ascitic Infection in Patients with Acute Decompensated Cirrhosis: Multidrug-Resistant Pathogens and Antibiotic Strategies

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.

Multirresistencia de Escherichia coli y Klebsiella pneumoniae provenientes de pacientes con infección del tracto urinario adquirida en la comunidad / Escherichia coli and Klebsiellap neumoniae multiresistance from patients with urinary tract infection acquired in the community

Introducción: El incremento de la multirresistencia bacteriana constituye un problema de salud pública a nivel internacional. Objetivos: Determinar la susceptibilidad antimicrobiana y los patrones de multirresistencia en cepas de Escherichia coli y Klebsiella pneumoniae aisladas de urocultivos. Métodos: Se realizó un estudio descriptivo retrospectivo en el Centro Municipal de Higiene, Epidemiología y Microbiología, municipio Güines, provincia Mayabeque, Cuba, en el periodo comprendido de enero a diciembre de 2017. El estudio incluyó 250 cepas de Escherichia coli y 62 de Klebsiella pneumoniae aisladas e identificadas de muestras de orina de pacientes con infección del tracto urinario adquirida en la comunidad. La susceptibilidad antimicrobiana fue evaluada con el método de difusión en agar empleado la técnica de Kirby Bauer. Resultados: En Escherichia coli se observó niveles de resistencia superiores al 60 por ciento a los antimicrobianos ácido nalidíxico, cefotaxima, trimetoprim - sulfametoxazol y ceftazidima. La nitrofurantoína y la amikacina presentaron 88,8 por ciento y 83,8 por ciento de efectividad, respectivamente. Se apreció en Klebsiella pneumoniae altos valores de resistencia a ceftazidima, trimetoprim - sulfametoxazol y ácido nalidíxico. Amikacina, presentó niveles de sensibilidad de un 71 por ciento. La resistencia a las cefalosporinas de tercera generación se detectó en 78 (31,2 por ciento) de Escherichia coli y 26 (41,9 por ciento) de Klebsiella pneumoniae. De los aislados de Escherichia coli 143 (57,2 por ciento) y Klebsiella pneumoniae 35 (56,4 por ciento) presentaron multidrogoresistencia. Conclusiones: Existe la circulación de cepas resistentes a cefalosporinas de tercera generación y multidrogorresistentes causantes de infecciones de las vías urinarias adquiridas en la comunidad y se informa sobre los antibióticos (nitrofurantoína y amikacina) que podrían ser utilizados para combatirlas de forma empírica en esta área geográfica(AU)

Introduction: The increase of bacterial multiresistance constitutes a public health problem at the international level. Objectives: To determine antimicrobial sensitivity and multiresistance patterns in strains of Escherichia coli and Klebsiellapneumoniae isolated from urine cultures. Methods: A retrospective, descriptive study was conducted at the Municipal Center for Hygiene, Epidemiology and Microbiology, Güines municipality, Mayabeque Province, Cuba, in the period from January to December, 2017. The study included 250 Escherichia coli and 62 Klebsiellapneumoniae strains isolated and identified from urine samples from patients with urinary tract infection acquired in the community. Antimicrobial sensitivity was evaluated with the method of diffusion in agar using Kirby Bauer´s technique. Results: In Escherichia coli, resistance levels higher than the 60% were observed in antimicrobial nalidixic acid, cefotaxime, trimethoprim-sulfamethoxazole and ceftazidime. Nitrofurantoin and amikacin presented 88.8 percent and 83.8 percent of effectiveness, respectively. High values of resistance to ceftazidime, trimethoprim-sulfamethoxazole and nalidixic acid were present in Klebsiellapneumoniae. Amikacin presented sensitivity levels of 71 percent. Resistance to third-generation cephalosporins was detected in 78 (31.2 percent) of Escherichia coli and 26 (41.9 percent) Klebsiellapneumoniae. From the Escherichia coli and Klebsiellapneumoniae isolates, 143 (57.2 percent) and 35 (56.4 percent),respectively, presented multidrug resistance. Conclusions: There is circulation of strains which are resistant to third generation cephalosporins and multidrug resistants that cause urinary tract infections acquired in the community and there are reports on antibiotics (nitrofurantoin and amikacin) that might be used to combat them empirically in this geographical area(AU)

Treatment of Mycobacterium avium Complex Pulmonary Disease / 결핵및호흡기질환

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

Evaluation of a Carbapenem-Saving Strategy Using Empirical Combination Regimen of Piperacillin-Tazobactam and Amikacin in Hemato-Oncology Patients

We implemented a carbapenem-saving strategy in hemato-oncology patients from 2013, using an empirical combination of piperacillin-tazobactam and amikacin for high-risk hemato-oncology patients with febrile neutropenia, who remain hemodynamically unstable > 72 hours despite initial cefepime treatment. All-cause mortality was not different between the two periods (6.54 and 6.57 deaths per 1,000 person-day, P = 0.926). Group 2 carbapenem use significantly decreased after strategy implementation (78.43 vs. 67.43 monthly days of therapy, P = 0.018), while carbapenem-resistant gram-negative bacilli did not show meaningful changes during the study period. Our carbapenem-saving strategy could effectively suppress carbapenem use without an increase of overall mortality.

Prevalence and molecular characteristics of 16s rRNA methylase gene rmtB in amikacin resistant Escherichia coli isolated from South Korea / 대한수의학회지

The production of rmtB-encoded 16S rRNA methylases has emerged as a novel mechanism promoting high-level resistance toward aminoglycosides in Gram-negative bacteria. Between 2015 and 2017, 636 distinct commensal Escherichia (E.) coli isolates were collected from different farms in South Korea to determine the prevalence and molecular characteristics of rmtB. The positive rates of rmtB between all the isolates and amikacin-resistant isolates were 1.1 and 100%, respectively. High-level aminoglycoside resistance could be transferred by conjugation from rmtB-positive donors to higher amikacin-resistance efficacies. This is the first report of 16S rRNA methylase-encoding genes in E. coli isolated from food-producing animals in Korea.

Antimicrobial Susceptibility of Microorganisms Isolated from Patients with Intraabdominal Infection in Korea: a Multicenter Study

Change in the Annual Antibiotic Susceptibility of Escherichia coli in Community-Onset Urinary Tract Infection between 2008 and 2017 in a Tertiary Care Hospital in Korea

The susceptibility of Escherichia coli from community onset urinary tract infection (UTI) was evaluated by dividing community onset UTI into the simple community acquired-UTI (CA-UTI) and healthcare associated UTI (HCA-UTI) groups for a period of 10 years. The susceptibility of E. coli to most antibiotics, except amikacin and imipenem, continued to decrease. In the CA-UTI group, the susceptibility to cefotaxime was 88% in 2015, but rapidly decreased to 79.3% in 2017. The susceptibility to cefepime and piperacillin-tazobactam were 88.8% and 90.5% in 2017, respectively. In the HCA-UTI group, the susceptibility to most antibiotics markedly decreased to less than 60% by 2017. The incidence of ESBL-producing E. coli increased to 23.3% in the CA-UTI group in 2017.

Antibiotic Sensitivity Patterns in Children with Urinary Tract Infection: Retrospective Study Over 8 Years in a Single Center

PURPOSE: We studied the pathogens and trends in antibiotic sensitivity pattern in children with urinary tract infection (UTI) over 8 years in order to evaluate adequate treatment. METHODS: We performed a retrospective review of medical records of children with UTI from January 2009 to December 2016 in Daegu Fatima Hospital. Uropathogens and antibiotic sensitivity patterns were selected. Only 1 bacterial species with a colony count of ≥105 CFU/mL was considered a positive result. We compared 2 periods group (A: 2009~2012, B: 2013~2016) to investigate trends of antibiotic sensitivity pattern. RESULTS: During the 8 year period, 589 cases are identified (E. coli was cultured in 509 cases, 86.4%). Among all patients, this study investigated the antibiotic sensitivity of E. coli . Antimicrobial susceptibility to ampicillin was steadily low for both periods (A: 32.6%, B: 40.1%, P=0.125), and to amikacin was consistently high for both periods (A: 99.4%, B: 99.3%, P=1.000). Antibiotic sensitivity to third-generation cephalosporin decreased from period A to B (A: 91.7%, B: 75.5%, P=0.000). Antibiotic sensitivity to quinolone significantly decreased from A to B (A: 88.4%, B: 78.2%, P=0.003). The prevalence of extended-spectrum β-lactamase-producing E. coli increased from period A to B (A: 6.1%, B: 17.1%, P=0.000). CONCLUSION: This study showed that conventional antibiotic therapy for the treatment of pediatric UTI needs to be reevaluated. A careful choice of antibiotic is required due to the change in antibiotic sensitivity and the emergence of antibiotic-resistant bacteria.

Treatment of Mycobacterium Abscessus Pulmonary Disease / 대한내과학회지

Mycobacterium abscessus is the second most important pathogen in pulmonary disease caused by nontuberculous mycobacteria (NTM), following Mycobacterium avium. Mycobacterium abscessus is classified into three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. Mycobacterium abscessus is the most difficult to treat NTM due to its resistance to many antibiotics. Treatment should include an initial regimen of 2–3 injectable and oral antibiotics for several weeks or months, followed by inhaled amikacin and 1–3 oral antibiotics, depending on the subspecies and drug susceptibility patterns, including macrolide susceptibility. The continuation phase should be continued for a minimum of 12 months after culture conversion. Suitable injectable antibiotics include amikacin, imipenem, cefoxitin, and tigecycline, while oral antibiotics include macrolides (azithromycin or clarithromycin), clofazimine, linezolid, and moxifloxacin. Surgery can be a useful adjunctive therapy for some patients with refractory disease. However, the overall treatment prognosis is still unsatisfactory. Therefore, novel and more effective interventions are required for the treatment of M. abscessus pulmonary disease.

Uso de la amikacina como profilaxis en pacientes sometidos a prostatectomía / Use of amikacin as prophylaxis in patients undergoing prostatectomy / Uso de amicacina como profilaxia em pacientes submetidos à prostatectomia

Resumen 17. El objetivo de este artículo es presentar la mejor evidencia científica disponible sobre el uso de la amikacina como profilaxis en pacientes sometidos a prostatectomía. La indicación de amikacina en cirugías tipo prostatectomías se remite al uso profiláctico, razón por la cual surge la inquietud sobre el beneficio de la administración del medicamento en estos pacientes tomando en cuenta que, entre los efectos adversos, se evidencia nefrotoxicidad y ototoxicidad principalmente en personas adultas mayores o con problemas renales previos. Se utilizó la metodología de práctica clínica basada en la evidencia (PCBE), partiendo de una pregunta clínica para posteriormente hacer las búsquedas electrónicas en bases de datos como: MEDLINE, Google académico y Cochrane Library Plus. Después de establecer los criterios de inclusión y exclusión y análisis crítico, se seleccionó cuatro documentos que se relacionan con la respuesta a la pregunta planteada. Los resultados para el análisis crítico fueron revisados minuciosamente a través de la plataforma informática FCL 2.0 con las plantillas correspondientes. La evidencia señala que ningún estudio respondió directamente a la pregunta clínica planteada, las investigaciones analizadas no demuestran evidencia que confirme que el uso profiláctico de la amikacina sea beneficioso en pacientes intervenidos quirúrgicamente. Se concluye que no se encuentró evidencia significativa que respalde el uso profiláctico de la amikacina para disminuir las infecciones. La profilaxis se enfoca en administrar en pacientes sometidos a procedimientos quirúrgicos urológicos como primera elección un antibiótico de menor espectro, ya que para administrar amikacina hay que cumplir con los lineamientos institucionales establecidos según la condición de cada usuario, tomando en cuenta los resultados de las pruebas de función renal pre y post administración.

Abstract 21. The aim of this article is to present the best available scientific evidence on the use of amikacin as prophylaxis in patients undergoing prostatectomy. The indication of amikacin in prostatectomy-type surgeries refers to prophylactic use, which is why the concern about the benefit of administering the drug in these patients arises, taking into account that, among the adverse effects, nephrotoxicity and ototoxicity are evidenced mainly in people older adults or with previous kidney problems. We used the evidence-based clinical practice methodology (PCBE), based on a clinical question to later perform the electronic searches in databases such as: MEDLINE, Google academic and Cochrane Library Plus. After establishing the inclusion and exclusion criteria and critical analysis, four documents were selected that relate to the answer to the question posed. The results for the critical analysis were thoroughly reviewed through the FCL 2.0 computer platform with the corresponding templates. The evidence indicates that no study directly responded to the clinical question posed, the investigations analyzed do not demonstrate evidence confirming that the prophylactic use of amikacin is beneficial in patients undergoing surgery. It was concluded that no significant evidence was found to support the prophylactic use of amikacin to reduce infections. Prophylaxis focuses on administering patients with urological surgical procedures as first choice a lower spectrum antibiotic, since to administer amikacin it is necessary to comply with established institutional guidelines according to the condition of each user, taking into account the results of the tests of renal function pre and post administration.

Resumo 25. O objetivo deste artigo é apresentar as melhores provas disponíveis sobre o uso da doença como profilaxia em pacientes com uma prostatectomia. A indicação de amicacina em cirugias tipo prostatectomia é remediada com o uso de profiláctico, a razão pela investigação surge sobre o benefício da administração do medicamento em estágios, a tomada de controle, entre os efetivos adversos, a evidência nefrotoxicidad e ototoxicidad principalmente em personas adultas mayores o com problemas renales previos. Use a metodologia de prática clínica baseada na evidência (PCBE), partindo de uma clínica pré-existente para o futuro sobre as bússulas electrónicas em bases de dados como: MEDLINE, Google académico e Biblioteca Cochrane Plus. Depois de estabelecer os critérios de inclusão e exclusão e análise crítica, selecione o documento que se relaciona com a resposta à pregunta plantada. Os resultados para a análise crítica foram revisados ​​minuciosamente através da plataforma informática FCL 2.0 com os plantillas correspondentes. A evidência é que o exame é respondido diretamente à consulta clínica plantada, as investigações não demonstram evidências que confirmam o uso profiláctico da amidação do mar em pacientes intervencionados quirúrgicamente. Se concluye que não há provas de que são importantes o uso do termo profiláctico da amicina para disminuir as infecciones. A profilaxia do enfarte na administração de doentes é um procedimento quirúrgico urológico como a primeira eleição do antibiótico de menor espectro, o que ajuda a administrar o feno que cumplir com os lineamentos institucionais estabelecidos segundo a condição de cada um, tomando os resultados dos exames de función renal pré y pós administración.

Sequential analysis as a tool for detection of amikacin ototoxicity in the treatment of multidrug-resistant tuberculosis / Análise sequencial como ferramenta na detecção da ototoxicidade da amicacina no tratamento da tuberculose multirresistente

ABSTRACT Objective: To investigate early detection of amikacin-induced ototoxicity in a population treated for multidrug-resistant tuberculosis (MDR-TB), by means of three different tests: pure-tone audiometry (PTA); high-frequency audiometry (HFA); and distortion-product otoacoustic emission (DPOAE) testing. Methods: This was a longitudinal prospective cohort study involving patients aged 18-69 years with a diagnosis of MDR-TB who had to receive amikacin for six months as part of their antituberculosis drug regimen for the first time. Hearing was assessed before treatment initiation and at two and six months after treatment initiation. Sequential statistics were used to analyze the results. Results: We included 61 patients, but the final population consisted of 10 patients (7 men and 3 women) because of sequential analysis. Comparison of the test results obtained at two and six months after treatment initiation with those obtained at baseline revealed that HFA at two months and PTA at six months detected hearing threshold shifts consistent with ototoxicity. However, DPOAE testing did not detect such shifts. Conclusions: The statistical method used in this study makes it possible to conclude that, over the six-month period, amikacin-associated hearing threshold shifts were detected by HFA and PTA, and that DPOAE testing was not efficient in detecting such shifts.

RESUMO Objetivo: Verificar a detecção precoce de ototoxicidade causada pelo uso de amicacina numa população tratada para tuberculose multirresistente (TBMR) por meio da realização de três testes distintos: audiometria tonal liminar (ATL), audiometria de altas frequências (AAF) e pesquisa de emissões otoacústicas por produto de distorção (EOAPD). Métodos: Estudo longitudinal de coorte prospectiva incluindo pacientes de ambos os sexos, com idade entre 18 e 69 anos, com diagnóstico de TBMR pulmonar e que necessitaram utilizar amicacina por seis meses em seu esquema medicamentoso antituberculose pela primeira vez. A avaliação auditiva foi realizada antes do início do tratamento e depois de dois e seis meses do início do tratamento. A análise dos resultados foi realizada por meio de análise estatística sequencial. Resultados: Foram incluídos 61 pacientes, mas a população final foi constituída de 10 pacientes (7 homens e 3 mulheres), em razão da análise sequencial. Ao se comparar os valores das respostas dos testes com aqueles encontrados na avaliação basal, foram verificadas mudanças nos limiares auditivos compatíveis com ototoxicidade após dois meses de tratamento através da AAF e após seis meses de tratamento através da ATL. Entretanto, essas mudanças não foram verificadas através da pesquisa de EOAPD. Conclusões: Ao se considerar o método estatístico utilizado nessa população, é possível concluir que mudanças nos limiares auditivos foram associadas ao uso da amicacina no período de seis meses por meio de AAF e ATL e que a pesquisa de EOAPD não se mostrou eficiente na identificação dessas mudanças.