Stability Studies of Antipseudomonal Beta Lactam Agents for Outpatient Therapy.

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.

Agreement between pharmacists and physicians on the assessment of appropriateness of antimicrobial prescribing.

INTRODUCTION: Audits for monitoring the quality of antimicrobial prescribing are a main tool in antimicrobial stewardship programs; however, interobserver reliability has not been conclusively assessed. Our objective was to measure the level of agreement between pharmacists and physicians on the appropriateness of antimicrobials prescribing in hospitals. METHODS: A national multicenter, cross-sectional study was conducted of patients who were receiving antimicrobials one day of April 2021. Hospital participation was voluntary, and the study population was randomly selected. Pharmacists and physicians performed a simultaneous, independent assessment of the quality of antimicrobial prescriptions. The observers used an assessment method by which all indicators of the quality of antimicrobial use were considered. Finally, an algorithm was used to rate overall antimicrobial prescribing as appropriate, suboptimal, inappropriate, or not assessable. Gwet's AC1 coefficient was used to assess interobserver agreement. RESULTS: In total, 101 hospitals participated, and 411 hospital antimicrobial prescriptions were reviewed. The strength of agreement was moderate regarding the overall quality of prescribing (AC1=0.51; 95%CI=[0.44-0.58]). A very good level of agreement (AC1>0.80) was observed between pharmacists and physicians in all indicators of the quality, except for duration of treatment, rated as good (AC1=0.79; 95%CI=[0.75-0.83]), and registration on the medical record, rated as fair (AC1=0.34; 95%CI=[0.26-0.43]). The agreement was greater in critical care, onco-hematology, and pediatric units than in medical and surgery units. CONCLUSIONS: In this point prevalence study, a moderate level of agreement was observed between pharmacists and physicians in the evaluation of the appropriateness of antimicrobials prescribing in hospitals.

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

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.

Análisis de la adecuación de la profilaxis antibiótica en procedimientos quirúrgicos en España. Protocolo del estudio ProA-Q / Analysis of the appropriateness of antibiotic prophylaxis in surgical procedures in Spain. Protocol for the "ProA-Q" study

La profilaxis antibiótica quirúrgica es una de las medidas más útiles para la prevención de la infección de la herida quirúrgica.Objetivoel 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... (AU)

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 multicenter 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 2,335 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 analyzed 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 analyzed by calculating the Cohen's kappa indicator. Binary logistic regression analysis using generalized linear mixed models will be performed to identify possible factors associated with differences in the appropriateness of antibiotic prophylaxis... (AU)

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.

Analysis of the appropriateness of antibiotic prophylaxis in surgical procedures in Spain. Protocol for the "ProA-Q" study. / Análisis de la adecuación de la profilaxis antibiótica en procedimientos quirúrgicos en España. Protocolo del estudio ProA-Q.

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 multicenter 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 2,335 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 analyzed 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 analyzed by calculating the Cohen's kappa indicator. Binary logistic regression analysis using generalized 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.

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.

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

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 unevaluableResults: 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  moxicillin-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  f 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  ntimicrobial 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  ntimicrobials within the antimicrobial stewardship programs.

OBJETIVO: 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  nfermedad 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.

Estudio PAUSATE: Prevalencia y adecuación del uso hospitalario de antimicrobianos en España / PAUSATE Study: Prevalence and appropriateness of the use of antimicrobials in Spanish hospitals

Objetivo: Conocer la prevalencia y el grado de adecuación del usode antimicrobianos en los hospitales españoles mediante una revisiónsistemática transversal realizada por farmacéuticos.Método: Estudio multicéntrico, nacional, transversal sobre el 10% de lospacientes ingresados en los hospitales participantes un día del mes deabril de 2021. La participación de los hospitales fue voluntaria y la selección de la población aleatoria. De la población se disgregó la muestrade estudio, constituida por los pacientes que recibían el día del corte almenos un antimicrobiano perteneciente a los grupos J01, J02, J04, J05AB,J05AD y J05AH del Sistema de Clasificación Anatómica, Terapéutica yQuímica. Sobre la muestra de estudio, el farmacéutico realizó un registroy evaluación de la adecuación del tratamiento antimicrobiano siguiendouna metódica propuesta y validada por el Grupo de trabajo de AtenciónFarmacéutica al Paciente con Enfermedad Infecciosa de la Sociedad Española de Farmacia Hospitalaria. La metódica de evaluación consideró cadauna de las dimensiones que conforman la prescripción del antimicrobiano eincluyó un algoritmo para calificar la prescripción global como adecuada,mejorable, inadecuada y no valorable. (AU)

Objective: To determine the prevalence and appropriateness of antimicrobial use in Spanish hospitals through a pharmacist-led systematiccross-sectional review.Method: A nationwide multicenter cross-sectional study was conductedon 10% of the patients admitted to the participating hospitals on one dayin April 2021. Hospital participation was voluntary, and the populationwas randomly selected. The study sample was made up of patients who,on the day of the study, received at least one antimicrobial belonging togroups J01, J02, J04, J05AB, J05AD or J05AH in the Anatomical Therapeutic Chemical Classification System. The pharmacist in charge madea 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 theSpanish Society of Hospital Pharmacy. The evaluation method consideredeach of the items comprising antimicrobial prescriptions. An algorithm wasused to assess prescriptions as appropriate, suboptimal, inappropriateand unevaluable. (AU)

Selection of AmpC ß-Lactamase Variants and Metallo-ß-Lactamases Leading to Ceftolozane/Tazobactam and Ceftazidime/Avibactam Resistance during Treatment of MDR/XDR Pseudomonas aeruginosa Infections.

Infections caused by ceftolozane-tazobactam and ceftazidime-avibactam-resistant P. aeruginosa infections are an emerging concern. We aimed to analyze the underlying ceftolozane-tazobactam and ceftazidime-avibactam resistance mechanisms in all multidrug-resistant or extensively drug-resistant (MDR/XDR) P. aeruginosa isolates recovered during 1 year (2020) from patients with a documented P. aeruginosa infection. Fifteen isolates showing ceftolozane-tazobactam and ceftazidime-avibactam resistance were evaluated. Clinical conditions, previous positive cultures, and ß-lactams received in the previous month were reviewed for each patient. MICs were determined by broth microdilution. Multilocus sequence types (MLSTs) and resistance mechanisms were determined using short- and long-read whole-genome sequencing (WGS). The impact of Pseudomonas-derived cephalosporinases (PDCs) on ß-lactam resistance was demonstrated by cloning into an ampC-deficient PAO1 derivative (PAOΔC) and construction of 3D models. Genetic support of acquired ß-lactamases was determined in silico from high-quality hybrid assemblies. In most cases, the isolates were recovered after treatment with ceftolozane-tazobactam or ceftazidime-avibactam. Seven isolates from different sequence types (STs) owed their ß-lactam resistance to chromosomal mutations and all displayed specific substitutions in PDC: Phe121Leu and Gly222Ser, Pro154Leu, Ala201Thr, Gly214Arg, ΔGly203-Glu219, and Glu219Lys. In the other eight isolates, the ST175 clone was overrepresented (6 isolates) and associated with IMP-28 and IMP-13, whereas two ST1284 isolates produced VIM-2. The cloned PDCs conferred enhanced cephalosporin resistance. The 3D PDC models revealed rearrangements affecting residues involved in cephalosporin hydrolysis. Carbapenemases were chromosomal (VIM-2) or plasmid-borne (IMP-28, IMP-13) and associated with class-1 integrons located in Tn402-like transposition modules. Our findings highlighted that cephalosporin/ß-lactamase inhibitors are potential selectors of MDR/XDR P. aeruginosa strains producing PDC variants or metallo-ß-lactamases. Judicious use of these agents is encouraged.

Adaptación nacional de la herramienta Start Smart-Then Focus para la optimización del uso de antimicrobianos / Spanish adaptation of the Start Smart-Then Focus tool for optimizing the use of antimicrobials

Objetivo: La herramienta Start Smart-Then Focus del Sistema Nacional deSalud de Reino Unido es una herramienta de ayuda de los programasde 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 deevaluación por correo electrónico. En la primera se envió un cuestionariocon 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 fuemodificada y enviada de nuevo a todos los expertos, volvieron a puntuarindividualmente, 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 yaplicabilidad, 3 indicadores obtuvieron mediana menor de 7 y 10 indicadores con mínimos menores de 5 en aplicabilidad. De 19 indicadoresiniciales pasamos a 8; con 8 opciones dentro del sexto indicador.Conclusiones: La adaptación de la herramienta Start Smart-Then Focus anivel nacional puede ser de utilidad para implantarla en los programas de optimización de antibióticos y contribuir a la mejora del uso de los antimicrobianos. (AU)

Objective: The Start Smart-Then Focus tool of the United Kingdom’sNational Health System is a tool to be implemented in antimicrobialstewardship programs. The objective of this work is the adaptation of StartSmart-Then Focus tool to the Spanish health system.Method: Delphi methodology was used. Two rounds were conductedby email. In the first, a questionnaire was sent out that included the criteriaof the tool. These criteria were independently assessed by 16 experts.They rated the suitability and applicability of each criterion on a scalefrom 1 to 9 and made free comments on each one. The tool was modifiedand 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 than7 and 10 had a minimum of less than 5. From the initial 19 indicators, weobtained 8 final indicators and 8 options were added to the sixth indicator.Conclusions: It would be very useful to implement the Spanish adaptationof the Start Smart-Then Focus tool in antimicrobial stewardship programs at anational level. It would also contribute to improving the use of antimicrobials. (AU)

Spanish adaptation of the Start Smart-Then Focus tool for optimizing the use of antimicrobials.

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.

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.

Stability of Antimicrobials in Elastomeric Pumps: A Systematic Review.

Outpatient parenteral antimicrobial therapy (OPAThttp) programs have become an important healthcare tool around the world. Portable elastomeric infusion pumps are functional devices for ambulatory delivery of antimicrobial drugs, and their stability is an essential point to guarantee an appropriate infusion administration. We conducted a systematic review to provide a synthesis and a critical evaluation of the current evidence regarding antimicrobial stability in elastomeric pumps. Data sources were PubMed, EMBASE, and Web of Sciences. The review protocol was registered on the Center for Open Science, and it was carried out following the PRISMA guidelines. Studies were eligible if the aim was the evaluation of the physicochemical stability of an antimicrobial agent stored in an elastomeric device. Of the 613 papers identified, 33 met the inclusion criteria. The most studied group of antimicrobials was penicillins, followed by cephalosporins and carbapenems. In general, the stability results of the antimicrobials that have been studied in more than one article agree with each other, with the exception of ampicillin, flucloxacillin, and ceftazidime. The antibiotics that displayed a longer stability were glycopeptides and clindamycin. Regarding the stability of antifungals and antivirals, only caspofungin, voriconazole, and ganciclovir have been investigated. The information provided in this article should be considered in patient treatments within the OPAT setting. Further stability studies are needed to confirm the appropriate use of the antimicrobials included in this program to ensure optimal patient outcomes.

[Increasing compliance with a surgical antibiotic prophylaxis protocol in the Urology Service.] / Incremento del cumplimiento de un protocolo de profilaxis antibiótica quirúrgica en el Servicio de Urología.

INTRODUCTION: Surgical site infectionis the most common nosocomial infection in Spain. Theuse of surgical antibiotic prophylaxis (SAP) in clinical practice is frequently inadequate, confirming the need to adopt prevention strategies for this kind of infections. In this sense, promoting actions to improve the SAP in order to reduce surgical site infections is an unavoidable commitment of every surgical department. OBJECTIVE: To evaluate the adequacy of the PAQ after PAQ system implementation based on the use of prophylaxis protocols in compliance with the quality indicator sestablished in the Urology Department. MATERIALS AND METHODS: Retrospective observational study of the SAP of the surgical procedures performed in the Urology Service of a Spanish tertiary-level hospital. An intervention based on the introduction of the prophylaxis protocols was performed. Each prophylaxis kit contains sufficient antibiotic doses to perform an adequate PAQ with a registration form where the administration of doses is recorded. A period of pre-intervention (2005-2010) and post-intervention (2012-2017) were established  and the differences in the values were determined in the following six quality indicators: indication of SAP (indicated and administered prophylaxis), antibiotic selection (according to established protocol), dose and route of administration (therapeutic dose and intravenous route), time of administration of the first dose (between15 min and 1 hour before the surgical incision), intraoperative dose (necessary if the surgery is prolonged more than twice the half-life of the antibiotic or there is significant bleeding) and duration (not to exceed 24 hours). RESULTS: Compliance with the selection of the antibiotic,the time of administration of the first dose, the duration of prophylaxis and the overall adequacy of the SAP increased after the introduction of prophylaxis protocols (p <0.001). CONCLUSIONS: The use of prophylaxis protocols promotes an adequate SAP as it facilitates the appropriate antibiotic selection (active substance, dose and route) and helps to prevent SAP from being unnecessarily prolonged.

INTRODUCCIÓN: La infección de localización quirúrgica es la infección nosocomial más frecuente en España. El uso de la profilaxis antibiótica quirúrgica (PAQ) en la práctica clínica se realiza frecuentemente de manera inadecuada, lo cual pone de manifiesto la necesidad de desarrollar estrategias de prevención de este tipo de infecciones. En este sentido,la promoción de acciones de mejora de la PAQ con el fin de disminuir las infecciones de localización quirúrgica es un compromiso ineludible de todo servicio quirúrgico. OBJETIVO: Nuestro objetivo es evaluar el incremento de la adecuación de la PAQ tras la implantación de un sistema basado en la utilización de los kits de profilaxis conforme al cumplimiento de los indicadores de calidad establecidos en el Servicio de Urología.MATERIALES Y MÉTODOS: Estudio retrospectivo observacional de la PAQ de los procedimientos quirúrgicos realizados en un Servicio de Urología de un hospital español de nivel terciario. Se llevó a cabo una intervención basada en la introducción de los kits de profilaxis, cada kit de profilaxis contiene las dosis de antibiótico necesarias y suficientes para la realización de una adecuada PAQ junto con un impreso donde se registra la administración de dichas dosis. Se estableció un período pre-intervención (2005-2010) y post-intervención (2012-2017) y se determinaron las diferencias encontradas en los valores los siguientes seis indicadores de calidad: indicación de la PAQ (profilaxis indicada y administrada), selección del antibiótico (según protocolo establecido), dosis y vía de administración (dosis terapéutica y vía intravenosa), momento de la administración de la primera dosis (entre 15 min. y 1 hora antes de la incisión quirúrgica), dosis intraoperatoria (necesaria sI la cirugía se prolonga más de dos veces la vida media del antibiótico o hay hemorragia importante) y duración (no exceder 24 horas). RESULTADOS: El cumplimiento de la selección del antibiótico,el momento de administración de la primera dosis, la duración de la profilaxis y la adecuación global de la PAQ se incrementaron de manera estadísticamente significativa tras la introducción de los kits de profilaxis (p<0,001).CONCLUSIONES: La utilización kits de profilaxis constituye una estrategia de mejora que promueve la realización de una adecuada PAQ porque facilita que el antibiótico seleccionado sea el correcto (principio activo,dosis y vía) y ayuda a evitar que la PAQ se prolongue innecesariamente.

Incremento del cumplimiento de un protocolo de profilaxis antibiótica quirúrgica en el Servicio de Urología / Increasing compliance with a surgical antibiotic prophylaxis protocol in the Urology Service

INTRODUCCIÓN: La infección de localización quirúrgica es la infección nosocomial más frecuente en España. El uso de la profilaxis antibiótica quirúrgica (PAQ) en la práctica clínica se realiza frecuentemente de manera inadecuada, lo cual pone de manifiesto la necesidad de desarrollar estrategias de prevención de este tipo de infecciones. En este sentido, la promoción de acciones de mejora de la PAQ con el fin de disminuir las infecciones de localización quirúrgica es un compromiso ineludible de todo servicio quirúrgico. OBJETIVO: Nuestro objetivo es evaluar el incremento de la adecuación de la PAQ tras la implantación de un sistema basado en la utilización de los kits de profilaxis conforme al cumplimiento de los indicadores de calidad establecidos en el Servicio de Urología. MATERIALES Y MÉTODOS: Estudio retrospectivo observacional de la PAQ de los procedimientos quirúrgicos realizados en un Servicio de Urología de un hospital español de nivel terciario. Se llevó a cabo una intervención basada en la introducción de los kits de profilaxis, cada kit de profilaxis contiene las dosis de antibiótico necesarias y suficientes para la realización de una adecuada PAQ junto con un impreso donde se registra la administración de dichas dosis. Se estableció un período pre-intervención (2005-2010) y post-intervención (2012-2017) y se determinaron las diferencias encontradas en los valores los siguientes seis indicadores de calidad: indicación de la PAQ (profilaxis indicada y administrada), selección del antibiótico (según protocolo establecido), dosis y vía de administración (dosis terapéutica y vía intravenosa), momento de la administración de la primera dosis (entre 15 min. y 1 hora antes de la incisión quirúrgica), dosis intraoperatoria (necesaria sI la cirugía se prolonga más de dos veces la vida media del antibiótico o hay hemorragia importante) y duración (no exceder 24 horas). RESULTADOS: El cumplimiento de la selección del antibiótico, el momento de administración de la primera dosis, la duración de la profilaxis y la adecuación global de la PAQ se incrementaron de manera estadísticamente significativa tras la introducción de los kits de profilaxis (p < 0,001). CONCLUSIONES: La utilización kits de profilaxis constituye una estrategia de mejora que promueve la realización de una adecuada PAQ porque facilita que el antibiótico seleccionado sea el correcto (principio activo, dosis y vía) y ayuda a evitar que la PAQ se prolongue innecesariamente

INTRODUCTION: Surgical site infection is the most common nosocomial infection in Spain. The use of surgical antibiotic prophylaxis (SAP) in clinical practice is frequently inadequate, confirming the need to adopt prevention strategies for this kind of infections. In this sense, promoting actions to improve the SAP in order to reduce surgical site infections is an unavoidable commitment of every surgical department. OBJECTIVE: To evaluate the adequacy of the PAQ after PAQ system implementation based on the use of prophylaxis protocols in compliance with the quality indicators established in the Urology Department. MATERIALS AND METHODS: Retrospective observational study of the SAP of the surgical procedures performed in the Urology Service of a Spanish tertiary-level hospital. An intervention based on the introduction of the prophylaxis protocols was performed. Each prophylaxis kit contains sufficient antibiotic doses to perform an adequate PAQ with a registration form where the administration of doses is recorded. A period of pre-intervention (2005- 2010) and post-intervention (2012-2017) were established and the differences in the values were determined in the following six quality indicators: indication of SAP (indicated and administered prophylaxis), antibiotic selection (according to established protocol), dose and route of administration (therapeutic dose and intravenous route), time of administration of the first dose (between 15 min and 1 hour before the surgical incision), intraoperative dose (necessary if the surgery is prolonged more than twice the half-life of the antibiotic or there is significant bleeding) and duration (not to exceed 24 hours). RESULTS: Compliance with the selection of the antibiotic, the time of administration of the first dose, the duration of prophylaxis and the overall adequacy of the SAP increased after the introduction of prophylaxis protocols (p <0.001). CONCLUSIONS: The use of prophylaxis protocols promotes an adequate SAP as it facilitates the appropriate antibiotic selection (active substance, dose and route) and helps to prevent SAP from being unnecessarily prolonged