Antibiotic consumption in secondary and tertiary hospitals in Colombia: national surveillance from 2018-2020.

Objective: To assess the compliance in secondary and tertiary level hospitals with monthly reporting of antibiotic consumption to the Colombian National Public Health Surveillance System (SIVIGILA-INS), and to describe reported antibiotic consumption during 2018-2020. Methods: This study involved a secondary analysis of antibiotic consumption data reported to SIVIGILA-INS. Frequency of hospital reporting was assessed and compared against expected reports, disaggregated by intensive care units (ICU)/non-ICU wards and geographical regions. Consumption was expressed as defined daily dose (DDD) per 100 occupied beds for seven antibiotics. Results: More than 70% of hospitals reported antibiotic consumption at least once in each of the three years (79% in ICU and 71% in non-ICU wards). Of these, ICU monthly reporting was complete (12 monthly reports per year) for 59% in the period 2018-2019 but only 4% in 2020. Non-ICU reporting was complete for 52% in 2019 and for 2% in 2020. Most regions had an overall decrease in reporting in 2020. Analysis of antibiotic consumption showed an increase for piperacillin/tazobactam, ertapenem, and cefepime from 2019 to 2020. Conclusions: There were gaps in the consistency and frequency of reporting. Efforts are needed to improve compliance with monthly reporting, which declined in 2020, possibly due to the COVID-19 pandemic. Non-compliance on reporting and data quality issues should be addressed with the hospitals to enable valid interpretation of antibiotic consumption trends.

Antibiotic consumption in secondary and tertiary hospitals in Colombia: national surveillance from 2018–2020

[ABSTRACT]. Objective. To assess the compliance in secondary and tertiary level hospitals with monthly reporting of antibi- otic consumption to the Colombian National Public Health Surveillance System (SIVIGILA-INS), and to describe reported antibiotic consumption during 2018–2020. Methods. This study involved a secondary analysis of antibiotic consumption data reported to SIVIGILA-INS. Frequency of hospital reporting was assessed and compared against expected reports, disaggregated by intensive care units (ICU)/non-ICU wards and geographical regions. Consumption was expressed as defined daily dose (DDD) per 100 occupied beds for seven antibiotics. Results. More than 70% of hospitals reported antibiotic consumption at least once in each of the three years (79% in ICU and 71% in non-ICU wards). Of these, ICU monthly reporting was complete (12 monthly reports per year) for 59% in the period 2018–2019 but only 4% in 2020. Non-ICU reporting was complete for 52% in 2019 and for 2% in 2020. Most regions had an overall decrease in reporting in 2020. Analysis of antibiotic consumption showed an increase for piperacillin/tazobactam, ertapenem, and cefepime from 2019 to 2020. Conclusions. There were gaps in the consistency and frequency of reporting. Efforts are needed to improve compliance with monthly reporting, which declined in 2020, possibly due to the COVID-19 pandemic. Non-compliance on reporting and data quality issues should be addressed with the hospitals to enable valid interpretation of antibiotic consumption trends.

[RESUMEN]. Objetivo. Evaluar el cumplimiento de los hospitales de segundo y tercer nivel en la presentación mensual de información sobre el consumo de antibióticos en el Sistema Nacional de Vigilancia en Salud Pública de Colombia (SIVIGILA-INS) y describir el consumo de antibióticos reportado en el período 2018-2020. Métodos. Este estudio incluyó un análisis secundario de los datos del consumo de antibióticos reportado en SIVIGILA-INS. Se evaluó la frecuencia de los informes hospitalarios y se comparó con los informes esperados, desglosados por unidad de cuidados intensivos (UCI) y otros servicios distintos a la UCI, y por región geográ- fica. El consumo se expresó en dosis diaria definida (DDD) por 100 camas ocupadas para siete antibióticos. Resultados. Más del 70% de los hospitales notificaron el consumo de antibióticos al menos una vez en cada uno de los tres años (79% en la UCI y 71% en los servicios distintos a la UCI). De estos, el 59% de las UCI completaron los informes mensuales (12 informes en un año) entre el 2018 y el 2019, pero solo el 4% en el 2020. El 52% de los servicios distintos a la UCI completó los informes en el 2019 y el 2% en el 2020. En la mayoría de las regiones hubo una disminución general de la notificación en el 2020. El análisis del consumo de antibióticos mostró un aumento de piperacilina/tazobactam, ertapenem y cefepima del 2019 al 2020. Conclusiones. Se encontraron disparidades en la coherencia y en la frecuencia de la presentación de informes. Es necesario destinar esfuerzos para mejorar el cumplimiento de la notificación mensual, que disminuyó en el 2020 posiblemente debido a la pandemia de COVID-19. La falta de cumplimiento en la pre- sentación de los reportes y los problemas de calidad de los datos deben abordarse con los hospitales para facilitar la interpretación válida de las tendencias de consumo de antibióticos.

[RESUMO]. Objetivo. Avaliar o cumprimento da exigência de notificar mensalmente o consumo de antibióticos em hospi- tais secundários e terciários ao Sistema Nacional de Vigilância em Saúde Pública da Colômbia (SIVIGILA-INS) e descrever o consumo informado de antibióticos de 2018 a 2020. Métodos. Este estudo envolveu uma análise secundária dos dados de consumo de antibióticos enviados para o SIVIGILA-INS. A frequência de notificação pelos hospitais foi avaliada e comparada com a frequência esperada. Os dados foram desagregados entre unidades de terapia intensiva (UTIs) e enfermarias gerais e por regiões geográficas. O consumo foi expresso como dose diária definida (DDD) por 100 leitos ocupados para sete antibióticos. Resultados. Mais de 70% dos hospitais notificaram consumo de antibióticos pelo menos uma vez em cada um dos três anos (79% na UTI e 71% nas enfermarias gerais). Entre eles, 59% dos hospitais enviaram todas as notificações relativas a UTIs (12 notificações mensais) no período de 2018 a 2019, mas apenas 4% o fiz- eram em 2020. No caso das enfermarias gerais, 52% dos hospitais enviaram todas as notificações em 2019 e 2% o fizeram em 2020. A maioria das regiões teve uma diminuição geral no número de notificações envia- das em 2020. A análise do consumo de antibióticos revelou um aumento no uso de piperacilina/tazobactam, ertapeném e cefepima de 2019 para 2020. Conclusões. Houve lacunas na uniformidade e frequência das notificações. São necessários esforços para melhorar o cumprimento da exigência de notificações mensais, que, possivelmente devido à pandemia de COVID-19, diminuiu em 2020. Problemas relacionados ao não cumprimento da exigência de notificação e à qualidade dos dados devem ser resolvidos junto aos hospitais para permitir uma interpretação válida das tendências de consumo de antibióticos.

Antibiotic consumption in secondary and tertiary hospitals in Colombia: national surveillance from 2018-2020 / Consumo de antibióticos en hospitales de segundo y tercer nivel en Colombia: vigilancia nacional entre 2018 y 2020 / Consumo de antibióticos em hospitais secundários e terciários da Colômbia: vigilância nacional de 2018 a 2020

ABSTRACT Objective. To assess the compliance in secondary and tertiary level hospitals with monthly reporting of antibiotic consumption to the Colombian National Public Health Surveillance System (SIVIGILA-INS), and to describe reported antibiotic consumption during 2018-2020. Methods. This study involved a secondary analysis of antibiotic consumption data reported to SIVIGILA-INS. Frequency of hospital reporting was assessed and compared against expected reports, disaggregated by intensive care units (ICU)/non-ICU wards and geographical regions. Consumption was expressed as defined daily dose (DDD) per 100 occupied beds for seven antibiotics. Results. More than 70% of hospitals reported antibiotic consumption at least once in each of the three years (79% in ICU and 71% in non-ICU wards). Of these, ICU monthly reporting was complete (12 monthly reports per year) for 59% in the period 2018-2019 but only 4% in 2020. Non-ICU reporting was complete for 52% in 2019 and for 2% in 2020. Most regions had an overall decrease in reporting in 2020. Analysis of antibiotic consumption showed an increase for piperacillin/tazobactam, ertapenem, and cefepime from 2019 to 2020. Conclusions. There were gaps in the consistency and frequency of reporting. Efforts are needed to improve compliance with monthly reporting, which declined in 2020, possibly due to the COVID-19 pandemic. Non-compliance on reporting and data quality issues should be addressed with the hospitals to enable valid interpretation of antibiotic consumption trends.

RESUMEN Objetivo. Evaluar el cumplimiento de los hospitales de segundo y tercer nivel en la presentación mensual de información sobre el consumo de antibióticos en el Sistema Nacional de Vigilancia en Salud Pública de Colombia (SIVIGILA-INS) y describir el consumo de antibióticos reportado en el período 2018-2020. Métodos. Este estudio incluyó un análisis secundario de los datos del consumo de antibióticos reportado en SIVIGILA-INS. Se evaluó la frecuencia de los informes hospitalarios y se comparó con los informes esperados, desglosados por unidad de cuidados intensivos (UCI) y otros servicios distintos a la UCI, y por región geográfica. El consumo se expresó en dosis diaria definida (DDD) por 100 camas ocupadas para siete antibióticos. Resultados. Más del 70% de los hospitales notificaron el consumo de antibióticos al menos una vez en cada uno de los tres años (79% en la UCI y 71% en los servicios distintos a la UCI). De estos, el 59% de las UCI completaron los informes mensuales (12 informes en un año) entre el 2018 y el 2019, pero solo el 4% en el 2020. El 52% de los servicios distintos a la UCI completó los informes en el 2019 y el 2% en el 2020. En la mayoría de las regiones hubo una disminución general de la notificación en el 2020. El análisis del consumo de antibióticos mostró un aumento de piperacilina/tazobactam, ertapenem y cefepima del 2019 al 2020. Conclusiones. Se encontraron disparidades en la coherencia y en la frecuencia de la presentación de informes. Es necesario destinar esfuerzos para mejorar el cumplimiento de la notificación mensual, que disminuyó en el 2020 posiblemente debido a la pandemia de COVID-19. La falta de cumplimiento en la presentación de los reportes y los problemas de calidad de los datos deben abordarse con los hospitales para facilitar la interpretación válida de las tendencias de consumo de antibióticos.

RESUMO Objetivo. Avaliar o cumprimento da exigência de notificar mensalmente o consumo de antibióticos em hospitais secundários e terciários ao Sistema Nacional de Vigilância em Saúde Pública da Colômbia (SIVIGILA-INS) e descrever o consumo informado de antibióticos de 2018 a 2020. Métodos. Este estudo envolveu uma análise secundária dos dados de consumo de antibióticos enviados para o SIVIGILA-INS. A frequência de notificação pelos hospitais foi avaliada e comparada com a frequência esperada. Os dados foram desagregados entre unidades de terapia intensiva (UTIs) e enfermarias gerais e por regiões geográficas. O consumo foi expresso como dose diária definida (DDD) por 100 leitos ocupados para sete antibióticos. Resultados. Mais de 70% dos hospitais notificaram consumo de antibióticos pelo menos uma vez em cada um dos três anos (79% na UTI e 71% nas enfermarias gerais). Entre eles, 59% dos hospitais enviaram todas as notificações relativas a UTIs (12 notificações mensais) no período de 2018 a 2019, mas apenas 4% o fizeram em 2020. No caso das enfermarias gerais, 52% dos hospitais enviaram todas as notificações em 2019 e 2% o fizeram em 2020. A maioria das regiões teve uma diminuição geral no número de notificações enviadas em 2020. A análise do consumo de antibióticos revelou um aumento no uso de piperacilina/tazobactam, ertapeném e cefepima de 2019 para 2020. Conclusões. Houve lacunas na uniformidade e frequência das notificações. São necessários esforços para melhorar o cumprimento da exigência de notificações mensais, que, possivelmente devido à pandemia de COVID‑19, diminuiu em 2020. Problemas relacionados ao não cumprimento da exigência de notificação e à qualidade dos dados devem ser resolvidos junto aos hospitais para permitir uma interpretação válida das tendências de consumo de antibióticos.

Perspectiva histórica del origen evolutivo de la resistencia a antibióticos / Evolutionary origin of antibiotic resistance, a historical perspective

Resumen La resistencia a antimicrobianos representa un aspecto natural de evolución bacteriana, que puede resultar de mutaciones o por adquisición de genes foráneos. Hay diferentes posturas sobre el origen de ésta resistencia que explican la habilidad de estos microorganismos de adquirir nuevas características. Las teorías de la evolución de Lamarck y Darwin, han dado pie a experimentos diseñados para explorar el origen de la variación bacteriana y surgimiento de nuevas características. Estos estudios muestran que la resistencia está relacionada con mutaciones en genes cromosomales y/o la transferencia de elementos genéticos extracromosomales, que se expresan según la presión antibiótica ejercida. Está revisión recopila los principales experimentos y las conclusiones derivadas para explicar el fenómeno de resistencia a antibióticos.

Abstract Antimicrobial resistance is a natural aspect of bacterial evolution that can result from mutations or acquisition of foreign genes. Various views on the origin of this resistance explain the ability of these organisms to acquire new features. Lamarck and Darwin's theories of evolution have led to experiments designed to explore the origin of bacterial variation and the emergence of new features. These experiments show that antimicrobial resistance is related to mutations in chromosomal genes and/or transfer of extrachromosomal genetic elements that can be expressed based on the antibiotic pressure exerted. The main experiments and findings that seek to explain the phenomenon of antibiotic resistance are reviewed here in.

Identificación de Mycobacterium spp a través de métodos moleculares en el Laboratorio de Salud Pública de Bogotá, Colombia / Identification of mycobacteria to the species level by molecular methods in the Public Health Laboratory of Bogotá, Colombia

INTRODUCCIÓN: Globalamente la situación epidemiológica de la enfermedad por micobacterias no tuberculosas (MNT) es desconocida debido a que no es una enfermedad de notificación en la mayoría de los países, sin embargo los diversos reportes de infecciones y brotes por MNT publicados sugieren su creciente incremento en los últimos años. Tradicionalmente la identificación se realiza a través de metodologías bioquímicas, las cuales permiten la diferenciación inicial entre M. tuberculosis y MNT, y en algunos casos la identificación de la especie micobacteriana. Sin embargo, esta metodología tiene importantes limitaciones técnicas y la obtención de resultados requiere tiempos prolongados. Por otra parte, la introducción de metodologías basadas en biología molecular ha facilitado significativamente el diagnóstico de las MNT desde el laboratorio. OBJETIVO: Establecer la frecuencia de MNT en los cultivos positivos para bacilos ácido alcohol resistentes remitidos al Laboratorio de Salud pública de Bogotá en un período de 12 meses. MATERIALES Y MÉTODOS: Un total de 100 cultivos provenientes de hospitales públicos y privados de Bogotá fueron identificados a través de pruebas bioquímicas y de las metodologías moleculares; PRA (PCR-análisis de restricción) y PCR múltiplex. Así mismo, la presencia de especies de baja prevalencia, así como el estudio de los casos no concluyentes se realizó través de análisis de secuenciación del blanco molecular 16SrDNA. RESULTADOS: El estudio identificó MNT en el 11% de los cultivos a través de la metodología PRA. Adicionalmente, esta metodología molecular permitió detectar la ocurrencia de más de una especie micobacteriana en el 4% de los cultivos evaluados. Interesantemente un nuevo patrón de restricción-PRA para la especie M. kubicae es reportado en nuestro estudio. CONCLUSIÓN: El uso de un algoritmo de identificación micobacteriana que incluya la metodología molecular PRA incrementa el poder diagnóstico de los métodos convencionales, y contribuye al mejor conocimiento de la epidemiología de las MNT y control de las micobacteriosis

INTRODUCTION: Global epidemiology of non-tuberculous mycobacteria (NTM) is unknown due to the fact that notification is not required in many countries, however the number of infection reports and outbreaks caused by NTM suggest a significant increase in the last years. Traditionally, mycobacteria identification is made through biochemical profiles which allow to differentiate M. tuberculosis from NTM, and in some cases the mycobacteria species. Nevertheless, these methods are technically cumbersome and time consuming. On the other hand, the introduction of methods based on molecular biology has improved the laboratory diagnosis of NTM. OBJECTIVE: To establish the NTM frequency in positive cultures for acid-fast bacilli (AAFB) which were sent to Laboratorio de Salud Pública de Bogotá over a 12 month period. MATERIALS AND METHODS: A total of 100 positive cultures for acid-fast bacilli from public and private hospitals from Bogotá were identified by both biochemical methods and the molecular methods PRA (PCR-restriction enzyme analysis) and multiplex-PCR. Furthermore, low prevalence mycobacteria species and non-interpretable results were confirmed by 16SrDNA sequentiation analysis. RESULTS: Identification using the PRA method showed NMT occurrence in 11% of cultures. In addition, this molecular methodology allowed to detect the occurrence of more than one mycobacteria in 4% of the cultures. Interestingly, a new M. kubicae pattern of PCR-restriction analysis is reported in our study. CONCLUSION: Using a mycobacteria identification algorithm, which includes the molecular method PRA, improves the diagnostic power of conventional methods and could help to advance both NTM epidemiology knowledge and mycobacteriosis control

[Identification of mycobacteria to the species level by molecular methods in the Public Health Laboratory of Bogotá, Colombia]. / Identificación de Mycobacterium spp a través de métodos moleculares en el Laboratorio de Salud Pública de Bogotá, Colombia.

INTRODUCTION: Global epidemiology of non-tuberculous mycobacteria (NTM) is unknown due to the fact that notification is not required in many countries, however the number of infection reports and outbreaks caused by NTM suggest a significant increase in the last years. Traditionally, mycobacteria identification is made through biochemical profiles which allow to differentiate M. tuberculosis from NTM, and in some cases the mycobacteria species. Nevertheless, these methods are technically cumbersome and time consuming. On the other hand, the introduction of methods based on molecular biology has improved the laboratory diagnosis of NTM. OBJECTIVE: To establish the NTM frequency in positive cultures for acid-fast bacilli (AAFB) which were sent to Laboratorio de Salud Pública de Bogotá over a 12 month period. MATERIALS AND METHODS: A total of 100 positive cultures for acid-fast bacilli from public and private hospitals from Bogotá were identified by both biochemical methods and the molecular methods PRA (PCR-restriction enzyme analysis) and multiplex-PCR. Furthermore, low prevalence mycobacteria species and non-interpretable results were confirmed by 16SrDNA sequentiation analysis. RESULTS: Identification using the PRA method showed NMT occurrence in 11% of cultures. In addition, this molecular methodology allowed to detect the occurrence of more than one mycobacteria in 4% of the cultures. Interestingly, a new M. kubicae pattern of PCR-restriction analysis is reported in our study. CONCLUSION: Using a mycobacteria identification algorithm, which includes the molecular method PRA, improves the diagnostic power of conventional methods and could help to advance both NTM epidemiology knowledge and mycobacteriosis control.

Ambiente genético del gen blaCTX-M-12 en aislamientos hospitalarios de klebsiella pneumoniae / The blaCTX-M-12 gene's genetic environmnt in klebsiella pneumoniae hospital isolates

En Colombia se han detectado genes del grupo CTX-M-1 con alta frecuencia en aislamientos de Klebsiella pneumoniae causantes de infección intrahospitalaria. El conocimiento de los factores genéticos que pueden favorecer la diseminación de estos genes entre especies bacterianas es un aspecto importante para el control de la resistencia. En este estudio se identificaron los plásmidos portadores del gen blaCTX-M-12 en 21 aislamientos clínicos de K. pneumoniae. Se evaluó por conjugación la transferencia de resistencia a antibióticos. Integrones, secuencias de inserción y otros elementos genéticos fueron detectados por amplificación del ADN plasmídico con la reacción en cadena de la polimerasa (PCR). Mediante análisis por PCR se determinó la relación entre el gen blaCTX-M-12 y los elementos genéticos detectados. En todos los aislamientos, el gen blaCTX-M-12 se encontró en plásmidos conjugativos de tamaños entre 65 y 106 kpb. La transferencia por conjugación de estos elementos móviles puede explicar la amplia diseminación de este gen entre enterobacterias causantes de infección nosocomial en hospitales de Bogotá, Colombia. El gen blaCTX-M-12 se encontró corriente abajo de ISEcp1, secuencia de inserción que se ha asociado con la movilización de determinantes genéticos de resistencia. Los promotores de ISEcp1, detectados por análisis de secuencia, pueden facilitar la expresión de la cefotaximasa codificada por este gen.

Genes from CTX-M-1 group have been detected with great frequency in Colombia in intrahospital infection-causing Klebsiella pneumoniae isolates. Knowledge regarding the genetic factors favouring such genes’ dissemination amongst bacterial species is an important issue for resistance control blaCTX-M-12 gene-carrying plasmids were identified in this study in 21 clinical K. pneumoniae isolates. Antibiotic resistance transfer was evaluated by mating. Integrons, insertion sequences and other genetic elements were detected by plasmid DNA amplification using polymerase chain reaction (PCR). The relationship between the blaCTX-M-12 gene and other genetic elements was determined by PCR analysis. The blaCTX-M-12 gene was disemifound on 52 to 106 Kpb conjugative plasmids in all isolates. These mobile elements’ transfer by mating may explain their wide dissemination amongst nosocomial infection-causing enterobacteria in hospitals in Bogota, Colombia. The blaCTX-M-12 gene was found downstream from ISEcp1, this being an insertion sequence which has been associated with resistance genetic determinants’ mobilisation. ISEcp1 promoters (detected by sequence analysis) may increase the expression of cefotaximase encoded by this gene.