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.

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.

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.

Treatment of Enterococcus faecalis Infective Endocarditis: A Continuing Challenge.

Today, Enterococcus faecalis is one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. Enterococci are partially resistant to many commonly used antimicrobial agents such as penicillin and ampicillin, as well as high-level resistance to most cephalosporins and sometimes carbapenems, because of low-affinity penicillin-binding proteins, that lead to an unacceptable number of therapeutic failures with monotherapy. For many years, the synergistic combination of penicillins and aminoglycosides has been the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, like dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have necessitated the search of new guidelines with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6-8 weeks) to avoid relapses has forced to the consideration of other viable options as outpatient parenteral strategies, long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed.

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.

Traducción y adaptación transcultural al español de la escala MULTIPleS en pacientes de edad avanzada con multimorbilidad / Cross-cultural adaptation into Spanish of the MULTIPleS scale in elderly patients with multimorbidity

Antecedentes y objetivo: La escala Multimorbidity Illness Perceptions Scale (MULTIPleS) analiza si padecer dos o más enfermedades crónicas repercute en la calidad de vida, coste y resultados clínicos de los pacientes. El objetivo fue traducir y adaptar transculturalmente al español la escala MULTIPleS.MétodosTraducción directa y retrotraducción seguidas de síntesis y adaptación por un tercer traductor y un panel de expertos para garantizar la equivalencia conceptual, semántica y de contenido entre ambas versiones. Posteriormente, se realizó un análisis de comprensibilidad en una muestra de pacientes.ResultadosSe obtuvo la versión española de la escala MULTIPleS. El grado de dificultad medio en la traducción directa y la retrotraducción del título y de las preguntas demostró una dificultad baja. En la fase de síntesis y adaptación, se resolvieron 6 discrepancias. El análisis de comprensibilidad se realizó en 10 pacientes, lográndose el requisito establecido (> 80%) para todos los ítems.ConclusionesSe trata de la primera adaptación transcultural al español de la escala MULTIPleS. Disponer de esta escala retrotraducida permitirá analizar la percepción de los pacientes ante la enfermedad y aplicar así mejoras en su asistencia sanitaria. (AU)

Background and objective: The Multimorbidity Illness Perceptions Scale (MULTIPleS) analyzes whether suffering from two or more chronic diseases affects the quality of life, cost and clinical results of patients. The objective was to translate and cross-culturally adapt the MULTIPleS scale into Spanish.MethodsDirect translation and back translation followed by synthesis and adaptation by a third translator and a panel of experts to guarantee the conceptual, semantic and content equivalence between both versions. Subsequently, a comprehensibility analysis was performed on a sample of patients.ResultsThe Spanish version of the MULTIPleS scale was obtained. The medium degree of difficulty in the direct translation and the back translation of the title and the questions showed a low difficulty. In the synthesis and adaptation phase, 6 discrepancies were resolved. The comprehensibility analysis was performed in 10 patients, achieving the established requirement (> 80%) for all items.ConclusionsThis is the first cross-cultural adaptation to Spanish of the MULTIPleS scale. Having this back-translated scale will make it possible to analyze patients’ perception of the disease and thus apply improvements in their healthcare. (AU)

Cross-cultural adaptation into Spanish of the MULTIPleS scale in elderly patients with multimorbidity. / Traducción y adaptación transcultural al español de la escala MULTIPleS en pacientes de edad avanzada con multimorbilidad.

BACKGROUND AND OBJECTIVE: The Multimorbidity Illness Perceptions Scale (MULTIPleS) analyzes whether suffering from two or more chronic diseases affects the quality of life, cost and clinical results of patients. The objective was to translate and cross-culturally adapt the MULTIPleS scale into Spanish. METHODS: Direct translation and back translation followed by synthesis and adaptation by a third translator and a panel of experts to guarantee the conceptual, semantic and content equivalence between both versions. Subsequently, a comprehensibility analysis was performed on a sample of patients. RESULTS: The Spanish version of the MULTIPleS scale was obtained. The medium degree of difficulty in the direct translation and the back translation of the title and the questions showed a low difficulty. In the synthesis and adaptation phase, 6 discrepancies were resolved. The comprehensibility analysis was performed in 10 patients, achieving the established requirement (> 80%) for all items. CONCLUSIONS: This is the first cross-cultural adaptation to Spanish of the MULTIPleS scale. Having this back-translated scale will make it possible to analyze patients' perception of the disease and thus apply improvements in their healthcare.

Identification and characterisation of deprescribing tools for older patients: A scoping review.

BACKGROUND: Deprescription is the revision of the therapeutic plan with the aim of simplifying it, taking into account patient preferences, prognosis and environment. This strategy is particularly relevant in older patients, mostly polymedicated individuals, since they are exposed to numerous adverse effects and interactions and tend to have less adherence to treatments. OBJECTIVE: To identify the deprescribing tools for older patients available in the scientific literature, classify them according to their design and describe their main features and potential applicability in clinical practice. METHODS: A search was conducted in PubMed and EMBASE for relevant literature published before July 2021. The PRISMA-ScR method was applied, extracting variables related to study and tool characteristics as well as potential clinical applicability. The main inclusion criteria were studies focused on designing or developing deprescribing tools for older patients and those that indicated the features of the deprescribing tool used in detail. RESULTS: Fourteen of 723 papers met the inclusion criteria, and 12 tools were identified: 6 "algorithm-based tools" and 6 "criterion-based tools". Though all tools are aimed at older patients, there are certain peculiarities regarding their design, population, application setting and variables included. Of the 6 criterion-based tools found, 4 used the Delphi method for their design and development. Furthermore, most of them agree on the pharmacological groups that are likely to be deprescribed. CONCLUSIONS: Taking into account the importance of the clinical situation and priorities in the care plan in the deprescribing process, the authors believe that tools which help to evaluate these aspects are the most suitable for application in clinical practice. However, it is necessary to continue studying applicability in real-life clinical scenarios and to obtain health results.

Probable ertapenem-induced encephalopathy; case report and suggested alternatives for chronic prostatitis.

Ertapenem is a carbapenem antibiotic usually reserved for complicated infections. Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem, and may be directly related to its chemical structure. We report a case of a 64-year-old male with a hematological history and chronic prostatitis that was admitted to hospital for gait instability, clumsiness, dysarthria and tremors. He started ertapenem intravenous 1 g once daily a week prior to admission. Creatinine clearance calculation by the Cockcroft-Gault method was 52 mL/min and total protein levels were low. Ertapenem's administration was discontinued and the patient's neurological symptoms improved dramatically just one day after. The result of the Naranjo Scale was six, suggesting a probable adverse drug reaction. We discussed if he could receive meropenem in case of severe infection such as septic shock. Considering the patient's medical history, the chemical structure of meropenem and the fact that there are almost no reported cases of neurotoxicity from this drug, we assume that meropenem could be used in case of severe infection in patients with history of neurotoxicity caused by ertapenem if no added risk factors are present, such as renal failure.

[Transcultural translation and adaptation into spanish of the questionnaire "Healthcare task difficulty (hctd) among older-adults with multimorbidity".] / Traducción y adaptación transcultural al español del cuestionario "Healthcare task difficulty (HCTD) among older-adults with multimorbidity".

OBJECTIVE: The increase in chronic diseases as a consequence of the rising life expectancy calls for tools that allow us to analyze the difficulty that patients with multimorbidity present when performing healthcare-related tasks. To this end, we carried out a cross-cultural translation and adaptation into Spanish of the questionnaire "Healthcare Task Difficulty (HCTD) among Older Adults with Multimorbidity." METHODS: Direct translation and back translation were made, followed by a synthesis and adaptation by a third translator and a panel of experts in order to guarantee the conceptual, semantic, and content equivalence between the original questionnaire and the Spanish version. Additionally, an evaluation of the comprehension of the questionnaire in Spanish was carried out in a sample of elderly patients with multimorbidity. RESULTS: The Spanish version of the HCTD questionnaire (HCTD-E) was obtained. The overall difficulty of the translators to find an equivalent expression between both languages was low. In the synthesis and adaptation part, four discrepancies were resolved (two of them were adapted in order to use a terminology closer to our health system and the other two were completed with different examples). The comprehensibility analysis was conducted in a sample of ten elderly patients with multimorbidity, and they showed an excellent comprehensibility. CONCLUSIONS: This is the first cross-cultural adaptation to Spanish of the HCTD questionnaire. The methodology used through direct translation, back-translation and adaptation by a third translator and a panel of experts demonstrated a high level of comprehensibility of the HCTD-E, which was measured with cognitive interviews in a sample of patients.

OBJETIVO: El incremento de las enfermedades crónicas como consecuencia del aumento en la esperanza de vida, hace necesario disponer de herramientas que permitan analizar la dificultad que presentan los pacientes con multimorbilidad, a la hora de realizar tareas relacionadas con la asistencia sanitaria. Con este fin, se llevó a cabo una traducción y adaptación transcultural al español del cuestionario "Healthcare Task Difficulty (HCTD) among Older Adults with Multimorbidity". METODOS: Traducción directa y retrotraducción llevadas a cabo por dos traductores, seguidas de una síntesis y adaptación por parte de un tercer traductor. Posterior creación de un panel de expertos con el fin de garantizar la equivalencia conceptual, semántica y de contenido entre la versión original y la española. A continuación, se realizó una evaluación de la comprensión del cuestionario en español en una muestra de pacientes de edad avanzada con múltiples patologías. RESULTADOS: Se obtuvo la versión española del cuestionario HCTD (HCTD-E). La dificultad global encontrada por los traductores para hallar una expresión equivalente entre ambos idiomas fue baja. En la fase de síntesis y adaptación, se resolvieron 4 discrepancias con el fin de utilizar una terminología más cercana a nuestro sistema sanitario. El análisis de comprensibilidad se efectuó sobre una muestra de 10 pacientes, mayores y con multimorbilidad en seguimiento por Medicina Interna, el cual demostró una comprensibilidad excelente. CONCLUSIONES: Se trata de la primera adaptación transcultural al español del cuestionario HCTD. La metodología utilizada mediante traducción directa, retrotraducción y adaptación por parte de un tercer traductor y un panel de expertos, ha demostrado un alto nivel de comprensibilidad de la herramienta HCTD-E medida a través de entrevistas cognitivas realizadas en una muestra de pacientes.

Gender bias in clinical trials of biological agents for severe asthma: A systematic review.

Asthma is one of the most common chronic diseases characterized by sex disparities. Gender bias is a well-documented issue detected in the design of published clinical trials (CTs). International guidelines encourage researchers to analyze clinical data by sex, gender, or both where appropriate. The objective of this work was to evaluate gender bias in the published CTs of biological agents for the treatment of severe asthma. A systematic review of randomized controlled CTs of the biological agents (omalizumab, benralizumab, reslizumab, mepolizumab or dupilumab) for the treatment of severe asthma was conducted. The literature search was performed using PubMed and EMBASE without language restrictions. This study followed the corresponding international recommendations. We identified a total of 426 articles, of which 37 were finally included. Women represented 60.4% of patients included. The mean percentage of women in these trials was 59.9%, ranged from 40.8% to 76.7%. The separate analysis by sex of the main variable was only performed in 5 of the 37 publications included, and none of the trials analyzed secondary variables by sex. Only 1 of the articles discussed the results separately by sex. No study included the concept of gender in the text or analyzed the results separately by gender. The proportion of women included in CTs was higher compared to publications of other disciplines, where women were under-represented. The analysis of the main and secondary variables by sex or gender, even the discussion separately by sex, was insufficient. This gives rise to potential gender bias in these CTs.

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.