PAUSATE Study: Prevalence and appropriateness of the use of antimicrobials in Spanish hospitals

Prevalencia; AntimicrobianosPrevalence; AntimicrobialPrevalença; AntimicrobiansObjetivo: Conocer la prevalencia y el grado de adecuación del uso de antimicrobianos en los hospitales españoles mediante una revisión sistemática transversal realizada por farmacéuticos. Método: Estudio multicéntrico, nacional, transversal sobre el 10% de los pacientes ingresados en los hospitales participantes un día del mes de abril de 2021. La participación de los hospitales fue voluntaria y la selección de la población aleatoria. De la población se disgregó la muestra de estudio, constituida por los pacientes que recibían el día del corte al menos un antimicrobiano perteneciente a los grupos J01, J02, J04, J05AB, J05AD y J05AH del Sistema de Clasificación Anatómica, Terapéutica y Química. Sobre la muestra de estudio, el farmacéutico realizó un registro y evaluación de la adecuación del tratamiento antimicrobiano siguiendo una metódica propuesta y validada por el Grupo de trabajo de Atención Farmacéutica al Paciente con Enfermedad Infecciosa de la Sociedad Española de Farmacia Hospitalaria. La metódica de evaluación consideró cada una de las dimensiones que conforman la prescripción del antimicrobiano e incluyó un algoritmo para calificar la prescripción global como adecuada, mejorable, inadecuada y no valorable. Resultados: Participaron 103 hospitales y se revisó el tratamiento de 3.568 pacientes, de los que 1.498 (42,0%) recibieron terapia antimicrobiana, 424 (28,3%) en combinación. La prevalencia de los antimicrobianos más frecuentes fue: amoxicilina-clavulánico 7,2%, ceftriaxona 6,4%, piperacilina-tazobactam 5,8% y meropenem 4,0%. Respecto a la adecuación del tratamiento la prescripción, fue considerada adecuada en el 34% de los casos, mejorable en el 45%, inadecuada en el 19% y no valorable en el 2%. Las dimensiones que más influyeron en la calificación de la prescripción como mejorable fueron el registro en la historia clínica, la elección del agente, la duración del tratamiento y la monitorización de la eficacia y seguridad, y como inadecuada la indicación de antimicrobiano. Conclusiones: La metódica utilizada permite conocer la prevalencia y adecuación del uso de antimicrobianos, paso previo para diseñar y emprender acciones de mejora y medir el impacto de su implantación en el marco de los programas de optimización del uso de antimicrobianos.Objective: To determine the prevalence and appropriateness of antimicrobial use in Spanish hospitals through a pharmacist-led systematic cross-sectional review. Method: A nationwide multicenter cross-sectional study was conducted on 10% of the patients admitted to the participating hospitals on one day in April 2021. Hospital participation was voluntary, and the population was randomly selected. The study sample was made up of patients who, on the day of the study, received at least one antimicrobial belonging to groups J01, J02, J04, J05AB, J05AD or J05AH in the Anatomical Therapeutic Chemical Classification System. The pharmacist in charge made a record and carried out an evaluation of the appropriateness of antimicrobial use following a method proposed and validated by the Pharmaceutical Care of Patients with Infectious Diseases Working Group of the Spanish Society of Hospital Pharmacy. The evaluation method considered each of the items comprising antimicrobial prescriptions. An algorithm was used to assess prescriptions as appropriate, suboptimal, inappropriate and unevaluable. Results: One-hundred three hospitals participated in the study and the treatment of 3,568 patients was reviewed. A total of 1,498 (42.0%) patients received antimicrobial therapy, 424 (28.3%) of them in combination therapy. The most commonly prescribed antimicrobials were amoxicillin-clavulanic acid (7.2%), ceftriaxone (6.4%), piperacillin-tazobactam (5.8%), and meropenem 4.0%. As regards appropriateness, prescriptions were considered appropriate in 34% of cases, suboptimal in 45%, inappropriate in 19% and unevaluable in 2%. The items that most influenced the assessment of a prescription as suboptimal were completeness of medical record entries, choice of agent, duration of treatment and monitoring of efficacy and safety. The item that most influences the assessment of a prescription as inappropriate was the indication of antimicrobial agent. Conclusions: The method used provided information on the prevalence and appropriateness of the use of antimicrobials, a preliminary step in the design and implementation of actions aimed at measuring the impact of the use of antimicrobials within the antimicrobial stewardship programs

A critical view on the current use of daptomycin in Spain: The daptomise study

Background: The Study on the Clinical Use of DAPTOMycin in Spain (DAPTOMISE Study) is a national surveillance program of daptomycin use. The objectives of this study are to evaluate the current variability in daptomycin consumption across the different hospitals and the adequacy of therapy, specially focused on underdosing. Methods: All adult and pediatric patients who received, at least, one dose of daptomycin in a single week in 98 institutions in Spain were included. The adequacy of daptomycin use was evaluated with respect to the indication, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. Results: A total of 615 patients received daptomycin during the study week. The prevalence use was 2.3 patients / 100,000 inhabitants per week, 12.4 patients / 1000 admissions and 9.2 Days of Therapy (DOT) / 1000 hospital stays. These rates varied between hospitals: from 0 to 13.9 patients / 100,000 inhabitants, from 0 to 76.1 patients / 1000 admissions and from 0 to 49.4 DOT / 1000 hospital stays. The most frequent infections were bacteremia (31.6 %) and skin and soft tissue infections (17.9 %). Microbiological results were available in only 65.4 % of infections. The most frequent microorganisms were Staphylococcus aureus (192 isolates, of which 87 were resistant to methicillin) and coagulase-negative staphylococci (124 isolates). A total of 136 prescriptions (22.1 %) were underdosed. Dosages < 8 mg/kg were used for 35.6 % of endovascular infections and for 26.2 % of osteoarticular infections. Overall, 57.2 % of prescriptions were not optimal in, at least, one item. Clinical cure rate was 76.1% and mortality attributable to the infection 8.1%. Conclusion: This is the first registry that identifies the prevalence of use of daptomycin in Spain and shows a high variability in the consumption between the different hospitals. Daptomycin underdosing was present in more than 20 % of cases. (c) 2023 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Stability of temocillin in outpatient parenteral antimicrobial therapy: is it a real option?

[Background] Temocillin is an interesting alternative to carbapenems for susceptible Enterobacteriaceae. Although its use in outpatient parenteral antimicrobial therapy (OPAT) programmes has generated interest, this has been hampered by the lack of stability data.[Objectives] The purpose of the present study was to evaluate the physical and chemical stability of temocillin at the recommended dose for its use in OPAT programmes, contained in polypropylene infusion bags or polyisoprene elastomeric devices at different temperatures, and to describe a novel LC-MS/MS developed for the quantification of temocillin.[Methods] Temocillin daily dose (6 g) was diluted in 500 mL of 0.9% sodium chloride to obtain a final concentration of 12 g/L. This solution was stored at 4°C, 25°C, 32°C and 37°C for 72 h, both in polypropylene infusion bags and in polyisoprene elastomeric pumps. Physical and chemical stability were evaluated during 72 h after manufacturing. Solutions were considered stable if colour, clearness and pH remained unchanged and if the percentage of intact drug was ≥90%.[Results] Temocillin attained the chemical stability criterion of ≥90% of the original concentration for the whole experiment in both devices at 4°C, 25°C and 32°C. At 37°C, temocillin was stable for 24 h but its concentration dropped below 90% from that timepoint. No precipitation occurred and minor colour changes were observed.[Conclusions] Temocillin is stable under OPAT conditions and it would be an appropriate candidate for the treatment of patients who can be discharged to complete therapy in an OPAT programme. For this study, an LC-MS/MS method was developed.This work was supported by the Sociedad Española de Farmacia Hospitalaria and the AFinf Working Group for the project ‘Stability study of antimicrobials under conditions analogous to the outpatient parenteral antibiotic therapy program (OPAT)’. A.G.-V. and L.H.-H. were supported by the Instituto de Salud Carlos III, co-financed by the European Development Regional Fund (‘A way to 251 achieve Europe’). A.G.-V. received financial support from the Subprograma Miguel Servet (CP19/00159). L.H.-H. received financial support from the Subprograma Juan Rodés (JR22/00049).Peer reviewe

Adaptación nacional de la herramientaStart Smart-Then Focus para la optimización del uso de antimicrobianos

[EN] Objective: The Start Smart-Then Focus tool of the United Kingdom’s National Health System is a tool to be implemented in antimicrobial stewardship programs. The objective of this work is the adaptation of Start Smart-Then Focus tool to the Spanish health system. Method: Delphi methodology was used. Two rounds were conducted by email. In the first, a questionnaire was sent out that included the criteria of the tool. These criteria were independently assessed by 16 experts. They rated the suitability and applicability of each criterion on a scale from 1 to 9 and made free comments on each one. The tool was modified and sent out again to all the experts. They re-scored the questionnaire individually, while aware of the anonymized results of the first round. Results: The first questionnaire was made up of 19 indicators. Of these, 16 indicators had a median of more than 7 in suitability and applicability. However, regarding applicability, 3 indicators had a median of less than 7 and 10 had a minimum of less than 5. From the initial 19 indicators, we obtained 8 final indicators and 8 options were added to the sixth indicator. Conclusions: It would be very useful to implement the Spanish adaptation of the Start Smart-Then Focus tool in antimicrobial stewardship programs at a national level. It would also contribute to improving the use of antimicrobials.[ES] Objetivo: La herramienta Start Smart-Then Focus del Sistema Nacional de Salud de Reino Unido es una herramienta de ayuda de los programas de optimización de antibióticos. El objetivo de este trabajo es la adaptación de la herramienta Start Smart-Then Focus al sistema de salud español. Método: Se utilizó la metodología Delphi, mediante dos rondas de evaluación por correo electrónico. En la primera se envió un cuestionario con los criterios de la herramienta, estos fueron evaluados de forma independiente por 16 expertos. Puntuaron de 1-9 la idoneidad y aplicabilidad de cada criterio, y realizaron comentarios libres. La herramienta fue modificada y enviada de nuevo a todos los expertos, volvieron a puntuar individualmente, pero conociendo los resultados de la primera ronda. Resultados: El primer cuestionario estaba constituido por 19 indicadores; 16 indicadores obtuvieron una mediana mayor de 7 en idoneidad y aplicabilidad, 3 indicadores obtuvieron mediana menor de 7 y 10 indicadores con mínimos menores de 5 en aplicabilidad. De 19 indicadores iniciales pasamos a 8; con 8 opciones dentro del sexto indicador. Conclusiones: La adaptación de la herramienta Start Smart-Then Focus a nivel nacional puede ser de utilidad para implantarla en los programas de optimización de antibióticos y contribuir a la mejora del uso de los antimicrobianos.The training stay of María Victoria Gil-Navarro was funded by the Spanish Ministry of Health, General Directorate of Research and Knowledge Management, Modality Training stays for research and innovation. Project number: EF-0468-2018. Call for proposals 2018-19

Analysis of the appropriateness of antibiotic prophylaxis in surgical procedures in Spain. Protocol for the "ProA-Q" study

Article disponible en castellà: http://hdl.handle.net/10230/59321Abstract: Surgical antibiotic prophylaxis is one of the most useful measures to prevent surgical wound infection. Objective: The aim of this project is to evaluate the appropriateness of the use of antibiotic prophylaxis in surgical procedures performed in Spanish hospitals, both globally and according to the type of surgery performed. Method: For this purpose, an observational, retrospective, cross-sectional, and multicentre study has been designed to collect all the variables that allow the evaluation of the appropriateness of surgical antibiotic prophylaxis by comparing the prescribed treatment, the recommendations included in the local guidelines, and the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology and the Spanish Association of Surgeons. Indication, choice of antimicrobial, dose, route and duration of administration, timing, re-dosing, and duration of the prophylaxis will be taken into account. The sample will consist of patients who underwent scheduled or emergency surgery, either as inpatients or outpatients, in hospitals in Spain. A sample size of 2335 patients has been established to estimate, with 95% confidence and 80% power, a percentage of appropriateness that is expected to be around 70%. Differences between variables will be analysed using Student's t-test, Mann–Whitney U test, Chi-square test, or Fisher's test, as appropriate. The degree of agreement between the antibiotic prophylaxis recommended by the guidelines of the different hospitals and that recommended in the literature will be analysed by calculating the Cohen's kappa indicator. Binary logistic regression analysis using generalised linear mixed models will be performed to identify possible factors associated with differences in the appropriateness of antibiotic prophylaxis. Discussion: The results of this clinical study will allow us to focus on specific surgical areas with higher rates of inappropriateness, identify key points of action and guide future strategies for antimicrobial stewardship programs in the area of antibiotic prophylaxis

Stability of ampicillin plus ceftriaxone combined in elastomeric infusion devices for outpatient parenteral antimicrobial therapy

Currently, ampicillin plus ceftriaxone (AC) is one of the preferred treatments for Enterococcus faecalis infective endocarditis. However, there is a lack of stability data for the combination of both drugs in elastomeric devices, so the inclusion of AC in Outpatient Parenteral Antimicrobial Therapy (OPAT) programs is challenging. The objective of the study was to determine the stability of AC in elastomeric pumps when stored at 8 ± 2 °C, 25 ± 2 °C, 30 ± 2 °C and 37 ± 2 °C using LC-MS/MS. The combination was diluted in 0.9% sodium chloride and the final concentrations were ampicillin 24 g/L plus ceftriaxone 8 g/L. Physical and chemical stability were evaluated at 12, 20, 24, 36 and 48 h after preparation. Stability was met at each time point if the percentage of intact drug was ≥90% of its respective baseline concentration and color and clearness remained unchanged. The drug combination was stable for 48 h when it was kept at 8 ± 2 °C. At 25 ± 2 °C and 30 ± 2 °C, they were stable for 24 h of storage. At 37 ± 2 °C, the stability criterion was not met at any time point. These results prove that AC could be included in OPAT programs using elastomeric infusion devices for the treatment of E. faecalis infections

Stability Studies of Antipseudomonal Beta Lactam Agents for Outpatient Therapy

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Outpatient parenteral antimicrobial therapy (OPAT) is a useful treatment strategy against Pseudomonas aeruginosa and other multidrug-resistant bacteria. However, it is hindered by the lack of stability data for the administration of antibiotics under OPAT conditions. Our objective was to investigate the stability of nine antipseudomonal and broad-spectrum beta lactam antibiotics (aztreonam, cefepime, cefiderocol, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, meropenem/vaborbactam, and piperacillin/tazobactam) to allow the spread of OPAT programs. All the antibiotics were diluted in 500 mL 0.9% sodium chloride and stored at 4, 25, 32, and 37 °C for 72 h in two different devices (infusion bags and elastomeric pumps). The solutions were considered stable if the color, clearness, and pH remained unchanged and if the percentage of intact drug was ≥90%. All the antimicrobials remained stable 72 h under refrigerated conditions and at least 30 h at 25 °C. At 32 °C, all the antibiotics except for meropenem and meropenem/vaborbactam remained stable for 24 h or more. At 37 °C, only aztreonam, piperacillin/tazobactam, cefepime, cefiderocol, and ceftolozane/tazobactam were stable for at least 24 h. The stability results were the same in the two devices tested. All the antibiotics studied are actual alternatives for the treatment of antipseudomonal or multidrug-resistant infections in OPAT programs, although the temperature of the devices is crucial to ensure antibiotic stability.This work was supported by the Sociedad Española de Farmacia Hospitalaria and the AFinf Working Group for the project “Stability study of antimicrobials under conditions analogous to the outpatient parenteral antibiotic therapy program (OPAT)”. A.G.-V. and L.H.-H. were supported by the Instituto de Salud Carlos III, co-financed by the European Development Regional Fund (“A way to 251 achieve Europe”). A.G.-V. received financial support from the Subprograma Miguel Servet (CP19/00159). L.H.-H. received financial support from the Subprograma Juan Rodés (JR22/00049).Peer reviewe

Development of Antimicrobial Defined Daily Dose (DDD) for the Pediatric Population

Antimicrobial stewardship programs (ASPs) optimize antimicrobial use, improve patient outcomes, and reduce resistance. To assess the effectiveness of ASPs, it is necessary to have indicators that can be widely used. Defined daily dose (DDD) was designed by WHO for the adult population as a consumption indicator. However, there are no DDDs adapted to the pediatric population. The main objective of this study is to establish the most appropriate DDD values in this population. An observational, retrospective, multicenter study was conducted. Antimicrobial prescriptions were collected from pediatric wards of seven Spanish tertiary hospitals for 2 years. The DDDs obtained from the prescriptions were compared with the theoretical DDDs agreed upon in the first stage. To select the optimal DDD, the following were analyzed: power value, magnitude obtained from the differences in the DDD, statistical significance, and degree of agreement in the stipulated doses. A total of 4788 prescriptions were collected. Pediatric DDD was defined for 30 different antimicrobials. A potency &gt;80% was obtained in 24 antibiotics. 51.2% of the selected DDD correspond to Phase I and 39.5% from Phase II. Pediatric DDD of different antimicrobials was obtained, providing an indicator that can be used globally in different hospitals to analyze the consumption and efficacy of ASPs

Development of Antimicrobial Defined Daily Dose (DDD) for the Pediatric Population

Antimicrobial stewardship programs (ASPs) optimize antimicrobial use, improve patient outcomes, and reduce resistance. To assess the effectiveness of ASPs, it is necessary to have indicators that can be widely used. Defined daily dose (DDD) was designed by WHO for the adult population as a consumption indicator. However, there are no DDDs adapted to the pediatric population. The main objective of this study is to establish the most appropriate DDD values in this population. An observational, retrospective, multicenter study was conducted. Antimicrobial prescriptions were collected from pediatric wards of seven Spanish tertiary hospitals for 2 years. The DDDs obtained from the prescriptions were compared with the theoretical DDDs agreed upon in the first stage. To select the optimal DDD, the following were analyzed: power value, magnitude obtained from the differences in the DDD, statistical significance, and degree of agreement in the stipulated doses. A total of 4788 prescriptions were collected. Pediatric DDD was defined for 30 different antimicrobials. A potency >80% was obtained in 24 antibiotics. 51.2% of the selected DDD correspond to Phase I and 39.5% from Phase II. Pediatric DDD of different antimicrobials was obtained, providing an indicator that can be used globally in different hospitals to analyze the consumption and efficacy of ASPs

Análisis de la adecuación de la profilaxis antibiótica en procedimientos quirúrgicos en España. Protocolo del estudio ProA-Q

Article disponible en anglès: http://hdl.handle.net/10230/59318Resumen: La profilaxis antibiótica quirúrgica es una de las medidas más útiles para la prevención de la infección de la herida quirúrgica. Objetivo: el objetivo de este proyecto es evaluar la adecuación del uso de profilaxis antibiótica en procedimientos quirúrgicos realizados en centros hospitalarios españoles, tanto de forma global como en función del tipo de cirugía realizada. Metodología: para ello, se ha diseñado un estudio observacional, retrospectivo, transversal y multicéntrico, donde se recopilarán todas aquellas variables que permitan evaluar la adecuación de la profilaxis antibiótica quirúrgica mediante la comparación del tratamiento prescrito, las recomendaciones recogidas en las guías locales y el documento de consenso de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica y la Asociación Española de Cirujanos. Se tendrán en cuenta la indicación, elección del antimicrobiano, dosis, vía de administración y tiempo de infusión, momento de la administración de la primera dosis, redosificación y la duración de la profilaxis. La muestra estará constituida por pacientes que hayan sido intervenidos de forma programada o urgente, en régimen de hospitalización o ambulatorio, en centros hospitalarios de España. Se ha establecido un tamaño muestral de 2.335 pacientes para estimar con una confianza del 95% y una potencia del 80%, un porcentaje de adecuación que se espera esté en torno al 70%. Las diferencias entre las variables se analizarán mediante la prueba t-Student, U de Mann-Whitney, el test Chi2 o test de Fisher, según proceda. El grado de concordancia entre la profilaxis antibiótica recomendada por las guías de los distintos hospitales y la recomendada en la literatura se analizará mediante el cálculo del indicador Kappa de Cohen. Con el fin de identificar posibles factores que puedan asociarse con diferencias en la adecuación de uso de profilaxis antibiótica, se llevará a cabo un análisis de regresión logística binario y mediante modelos lineales mixtos generalizados. Discusión: los resultados de este proyecto nos permitirán poner el foco en determinadas áreas quirúrgicas con mayor porcentaje de inadecuación de tratamientos, detectar puntos clave de actuación y dirigir las futuras estrategias de los programas de optimización del uso de antimicrobianos en el ámbito de la profilaxis antibiótica