Impacto clínico y ecológico de un Programa de Optimización del Tratamiento Antimicrobiano (PROA) específico para atención primaria

Introducción El desarrollo y propagación de las resistencias bacterianas es uno de los principales problemas de salud pública a nivel mundial, siendo el uso excesivo e inadecuado de los antibióticos una de sus principales causas. Los programas para la optimización de los antimicrobianos (PROAs) son uno de los elementos clave para hacer frente a esta situación. Estos programas han demostrado su beneficio en los hospitales; sin embargo, existe escasa evidencia sobre su efecto en Atención Primaria, que es donde se prescriben la mayoría de los antibióticos en humanos. El objetivo de esta Tesis Doctoral es determinar si un PROA multimodal de base educativa, específico para Atención Primaria, puede reducir cuantitativamente y mejorar cualitativamente el uso de antimicrobianos, así como disminuir la incidencia de las infecciones causadas por Escherichia coli multirresistente en la comunidad mediante la optimización del uso de los antibióticos, y ser sostenible en el tiempo. Material y métodos Estudio de intervención cuasi-experimental para evaluar el impacto de un PROA dirigido a 1.387 médicos (1.116 médicos de familia y 271 pediatras) de 214 centros de salud, pertenecientes a cuatro distritos de Atención Primaria de Andalucía, que atienden a una población de 1.937.512 habitantes. El estudio comprende un periodo pre-intervención de 8 trimestres, de 2012 a 2013, y otro de intervención de 16 trimestres, entre 2014 y 2017. Se diseñó un PROA no impositivo, basado en cinco medidas educativas llevadas a cabo por equipos multidisciplinares pertenecientes a los distritos, centros de salud y sus hospitales de referencia, y con apoyo institucional. La medida nuclear del programa fue la asesoría clínica, una actividad formativa entre pares, realizada por el médico de referencia y uno de los médicos prescriptores de su propio centro de salud sobre una prescripción de antibióticos real. Juntos evalúan la calidad de la misma siguiendo un cuestionario estructurado y la guía de terapéutica antimicrobiana de referencia. Las variables del estudio, que se evaluaron con una frecuencia ii trimestral, fueron: la tasa de tratamientos antimicrobianos inadecuados; el uso de los antimicrobianos, medido como dosis diarias definidas por 1000 tarjetas sanitarias/día (DTD); el coste directo en antimicrobianos; el grado de aceptación del programa; la densidad de incidencia, medida como el número de aislamientos de E. coli resistente a quinolonas; E. coli resistente a cefalosporinas de tercera generación; y E. coli BLEE por paciente en cultivos de orina/1000 habitantes y trimestre; el porcentaje de resistencia, medido como el número de aislamientos de E. coli resistente por paciente en cultivos de orina x 100/número total de aislados de E. coli. Para evaluar el efecto de la intervención se realizó un análisis de series temporales interrumpidas del uso trimestral de los antibióticos, del porcentaje de resistencia y de la densidad de incidencia de E. coli resistente. Resultados Se realizaron 24.150 asesorías clínicas a lo largo de los 4 años de la intervención. La prescripción inadecuada de antibióticos se redujo de un 36,5% en 2014, a un 26,9% en 2017. La principal causa de prescripción inadecuada fue la elección incorrecta del antibiótico, seguida de la duración inadecuada del tratamiento. El porcentaje de prescripciones inadecuadas tuvo una tendencia descendente significativa en el tratamiento de las infecciones del tracto urinario, del tracto respiratorio superior e inferior, y de piel y partes blandas, permaneciendo estable en las infecciones bucodentales y en el resto de infecciones. El consumo acumulado anual del total de antibióticos sistémicos en la comunidad descendió de 20,1 DTD en el año previo al inicio del programa hasta 16,7 DTD en el último año, una reducción neta de 3,4 DTD (-16,9%), aunque los cambios de nivel y de tendencia tras el inicio de la intervención no alcanzaron significación estadística respecto a la tendencia pre-intervención. La intervención sí se asoció con una reducción sostenida significativa del uso de ciprofloxacino (-15,9% a los cuatro años) y cefalosporinas (-22,6%), y un aumento sostenido del uso de amoxicilina (22,2%) y fosfomicina trometamol (6,1%). La densidad de incidencia de infecciones del tracto urinario en la comunidad causadas por E. coli resistente mostró una disminución de nivel y un cambio de tendencia significativos tras el inicio de intervención, alcanzando reducciones a los cuatro años para E. coli productor de beta-lactamasas de espectro extendido (-65,6%), para E. coli resistente a iii cefalosporinas de tercera generación (-51,0%), y para E. coli resistente a ciprofloxacino (-46,9%). El grado de aceptación de la intervención por los prescriptores fue del 94%. Conclusiones Los resultados de esta Tesis Doctoral muestran que la implementación de este PROA multimodal de base educativa en Atención Primaria mejora el uso de los antibióticos de manera sostenida en el tiempo y conduce a una reducción significativa de las infecciones urinarias producidas por E. coli resistente a los antimicrobianos en la comunidad

Impact of an Antimicrobial Stewardship Program on the Incidence of Carbapenem Resistant Gram-Negative Bacilli: An Interrupted Time-Series Analysis

This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship.Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a critical public health threat, and carbapenem use contributes to their spread. Antimicrobial stewardship programs (ASPs) have proven successful in reducing antimicrobial use. However, evidence on the impact of carbapenem resistance remains unclear. We evaluated the impact of a multifaceted ASP on carbapenem use and incidence of CR-GNB in a high-endemic hospital. An interrupted time-series analysis was conducted one year before and two years after starting the ASP to assess carbapenem consumption, CR-GNB incidence, death rates of sentinel events, and other variables potentially related to CR-GNB incidence. An intense reduction in carbapenem consumption occurred after starting the intervention and was sustained two years later (relative effect −83.51%; 95% CI −87.23 to −79.79). The incidence density of CR-GNB decreased by −0.915 cases per 1000 occupied bed days (95% CI −1.743 to −0.087). This effect was especially marked in CR-Klebsiella pneumoniae and CR-Escherichia coli, reversing the pre-intervention upward trend and leading to a relative reduction of −91.15% (95% CI −105.53 to −76.76) and −89.93% (95% CI −107.03 to −72.83), respectively, two years after starting the program. Death rates did not change. This ASP contributed to decreasing CR-GNB incidence through a sustained reduction in antibiotic use without increasing mortality rates.This research was funded by the Plan Nacional de I + D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0008; RD16/0016/0009) co-financed by European Development Regional Fund ‘A way to achieve Europe’ and Operative program intelligent Growth 2014–2020, which did not participate in the development of the program or the analysis of its results

Application of new indicators to assess the quality of antimicrobial use in intensive care units

This study explored the feasibility of a bundle of indicators aimed at assessing the quality of antimicrobial use in intensive care units (ICUs) through an observational prospective study spanning 12 quarters (January 2019-December 2021) in a 1290-bed teaching hospital in Spain. Members of the antimicrobial stewardship programme team selected the indicators to analyse the quality of antimicrobial use based on consumption data from a list proposed in a previous study. Antimicrobial use in the ICU was measured as defined daily dose (DDD) per 100 occupied bed-days. Trends and points of change were analysed with segmented regression. The intravenous macrolides/intravenous respiratory fluoroquinolones ratio in the ICU increased progressively, although not significantly, by 11.14% per quarter, likely related to prioritization of the use of macrolides in serious community-acquired pneumonia and the coronavirus disease 2019 pandemic. A remarkable upward trend of 2.5% per quarter was detected in the anti-methicillin-susceptible Staphylococcus aureus/anti-methicillin-resistant S. aureus agents ratio in the ICU, which could be explained by the low prevalence of methicillin-resistant S. aureus at the study centre. Patterns of amoxicillin-clavulanic acid/piperacillin-tazobactam ratio and diversification of anti-pseudomonal beta-lactams showed an increment in use over the study. The use of these novel indicators provides additional information for the current analysis of DDD. Implementation is feasible, and led to the detection of patterns that agree with local guidelines and cumulative antibiogram reports, and foster targeted improvement actions within antimicrobial stewardship programmes.A.B.G. receives financial support from Subprograma Juan Rodés, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain (JR21/00017). G.P. receives a grant from the Plan Andaluz de Investigación, Desarrollo e Innovación, Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, Spain (Grant PAIDI2020/POSTDOC_21_00831). L.H. and M.M. receive financial support from Subprograma Río Hortega, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain (CM19/00152 and CM21/00115).Peer reviewe

Clinical and Ecological Impact of an Educational Program to Optimize Antibiotic Treatments in Nursing Homes (PROA-SENIOR): A Cluster, Randomized, Controlled Trial and Interrupted Time-Series Analysis

[Background] Antimicrobial stewardship programs (ASPs) are recommended in nursing homes (NHs), although data are limited. We aimed to determine the clinical and ecological impact of an ASP for NHs.[Methods] We performed a cluster, randomized, controlled trial and a before–after study with interrupted time-series analyses in 14 NHs for 30 consecutive months from July 2018 to December 2020 in Andalusia, Spain. Seven facilities implemented an ASP with a bundle of 5 educational measures (general ASP) and 7 added 1-to-1 educational interviews (experimental ASP). The primary outcome was the overall use of antimicrobials, calculated monthly as defined daily doses (DDD) per 1000 resident days (DRD).[Results] The total mean antimicrobial consumption decreased by 31.2% (−16.72 DRD; P = .045) with respect to the preintervention period; the overall use of quinolones and amoxicillin–clavulanic acid dropped by 52.2% (P = .001) and 42.5% (P = .006), respectively; and the overall prevalence of multidrug-resistant organisms (MDROs) decreased from 24.7% to 17.4% (P = .012). During the intervention period, 12.5 educational interviews per doctor were performed in the experimental ASP group; no differences were found in the total mean antimicrobial use between groups (−14.62 DRD; P = .25). Two unexpected coronavirus disease 2019 waves affected the centers increasing the overall mean use of antimicrobials by 40% (51.56 DRD; P < .0001).[Conclusions] This study suggests that an ASP for NHs appears to be associated with a decrease in total consumption of antimicrobials and prevalence of MDROs. This trial did not find benefits associated with educational interviews, probably due to the coronavirus disease 2019 pandemic.[Clinical Trials Registration] NCT03543605.Peer reviewe

La crisis de los antibióticos: profesionales sanitarios, ciudadanos y políticos, todos somos responsables

Peer reviewe

Evaluation of the impact of a nationwide massive online open course on the appropriate use of antimicrobials

[Objectives] To evaluate the impact of a massive online open course (MOOC) design on the appropriate use of antimicrobial agents, to determine specific study areas with better learning outcomes and to identify weak points.[Methods] A pre- and post-intervention study in the context of a training course on infectious diseases aimed at health professionals. We designed a questionnaire with 30 questions related to the management of infectious diseases in different clinical situations. Participants had to answer the questions based on their competencies and training for these situations. We analysed the scores obtained before and after the course and the resulting progress. In addition, an open response section was provided to enable a qualitative evaluation.[Results] Two thousand one hundred and forty-eight health professionals were enrolled in the course. The questionnaire was completed before and after the course by 606 participants, mainly physicians (81.2%) and pharmacists (15.4%). The mean overall scores for the pre- and post-course questionnaires were 6.2 (SD 1.38) and 7.9 (SD 0.88), respectively (overall score increase = 1.8, SD 1.21, P < 0.001). A significant increase in self-assessment was detected (P < 0.001) for all the questions. Qualitative assessments were provided by 218 participants with 225 comments, most of which were very positive.[Conclusions] The course with a MOOC design showed a great teaching capacity in the infectious diseases area for all the clinical situations analysed, notably in the management of severe infections with higher mortality. For future editions of this training activity, the need to include other infectious diseases, especially infections in primary care, was highlighted.The e-learning course was supported by Merck Sharp & Dohme Corp. through an unrestricted grant.Peer reviewe

Effect of the COVID-19 pandemic on antibiotic use in primary care

During the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disruption of antimicrobial stewardship interventions has become a matter of concern. Antimicrobial resistance and the many unintended negative clinical consequences resulting from antibiotic misuse and overuse will persist and may potentially be aggravated by the pandemic, making it necessary to measure its impact on antibiotic use in all healthcare settings.1Peer reviewe

Has the COVID-19 pandemic wiped out the seasonality of outpatient antibiotic use and influenza activity? A time-series analysis from 2014 to 2021

Objective To assess the influence of the emergence of severe acute respiratory syndrome coronavirus 2 and the implementation of public health measures on the seasonality of outpatient antibiotic use and their possible association with the incidence of influenza. Methods We performed a time-series ecological study in 1516 primary care centres of Andalusia, Spain, comparing the coronavirus disease 2019 period (April 2020 to March 2021) with the 6 previous years. We assessed the number of packs and defined daily doses per 1000 inhabitants of antibacterials and key antibiotics commonly used for acute respiratory tract infections and the number of influenza-positive cases per 100 000 inhabitants. We calculated the correlation between variables and analyzed the seasonal patterns and differences in quarterly antibiotic use. Results For all quarters, a significant correlation was observed between influenza activity and antibiotic use (Spearman's r = 0.94; p < 0.001). Before the pandemic period, both variables presented similar seasonal patterns. After the start of the pandemic, influenza activity was suppressed and the pattern of antibiotic use flattened into a straight line (R2 = 0.96; p = 0.022) with a quarterly change of 3.9% (p = 0.007). Total antibiotic use and antibiotics used for treating acute respiratory tract infections showed significant reductions in all quarters compared to the previous year (p < 0.01). Discussion The coronavirus disease 2019 pandemic has strongly influenced the seasonality of antibiotic use in primary care. The decline in respiratory viruses, among which the influenza virus is a major player that may act as a proxy for general prevalence, is proposed as a reason for the flattening of the seasonal fluctuations of outpatient antibiotic use in our region.Peer reviewe

A multimodal intervention program to control a long-term Acinetobacter baumannii endemic in a tertiary care hospital

In representation of A. baumannii eradication program.[Background] Acinetobacter baumannii causes frequently nosocomial infections worldwide. Its ability to survive on dry surfaces facilitates its spread and the persistence of endemic situations, especially in the intensive care units (ICUs). The objective of this paper is to describe a multicomponent intervention program designed to control a hyperendemic persistence of multidrug-resistant A. baumannii (MDR-Ab) and to characterize its impact. [Methods] Design: Quasi-experimental intervention study based on open cohorts. Setting: Public tertiary referral centre. Period: January 2009–August 2017. Intervention: multifaceted program based on environmental decontamination, hand hygiene, antimicrobial stewardship, contact precautions, active surveillance, weekly reports and regular meetings. Analysis: joinpoint regression and interrupted time-series analysis. [Results] The intervention was successfully implemented. Through the study period, the compliance with contact precautions changed from 0 to 100% and with hand hygiene, from 41.8 to 82.3%. Between 2012 and 2016, the antibiotic consumption decreased from 165.35 in to 150.44 daily-defined doses/1000 patients-days in the ICU. The incidence density of MDR-Ab in the ICU was 10.9 cases/1000 patients-days at the beginning of the intervention. After this moment, the evolution of the incidence density of MDR-Ab was: between months 0 and 6°, it remained stable; between months 7° and 10°: there was an intense decrease, with an average monthly percentage change (AMPC) = − 30.05%; from 11° month until the end, the decrease was lighter but continuous (AMPC:-2.77%), achieving an incidence density of 0 cases/1000 patients-days on the 18° month, without any new case for 12 months. From the 30° month until the end of the study period, several little outbreaks of MDR-Ab were detected, all of them rapidly controlled. The strains of MDR-Ab isolated during these outbreaks were not clonally related with the previously endemic one, which supports its eradication from the environmental reservoirs. [Conclusion] The multicomponent intervention performed by a multidisciplinary team was effective to eradicate the endemic MDR-Ab