FARMACIA HOSPITALARIA最新文献

{"title":"The \"Trojan horse\" against antimicrobial resistance: Siderophore conjugates and public health.","authors":"Alina Dammar Herrera-Callo, Marco Roberto Chávez-Morán","doi":"10.1016/j.farma.2026.04.013","DOIUrl":"https://doi.org/10.1016/j.farma.2026.04.013","url":null,"abstract":"<p><strong>Objective: </strong>Antimicrobial resistance, particularly in carbapenemase-producing Enterobacterales such as KPC-type, represents a critical threat to public health in Latin America, associated with high mortality rates and increased healthcare costs. This systematic review aims to evaluate the therapeutic potential of siderophore-drug and siderophore-peptide conjugates against priority multidrug-resistant pathogens, including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, analyzing their efficacy, mechanisms of action, and implementation challenges.</p><p><strong>Method: </strong>A systematic search was conducted in PubMed, Scopus, and Web of Science databases up to August 2025, using key terms such as \"siderophore conjugates\", \"Trojan horse antibiotics\", \"antimicrobial resistance\", and \"Gram-negative bacteria\". Preclinical and clinical studies, reviews, and meta-analyses published between 2019 and 2025 were included, selecting 55 references based on relevance to the topic, currency, and methodological quality. This review corresponds to a narrative review with a systematic literature search, developed in accordance with PRISMA guidelines.</p><p><strong>Results: </strong>Siderophore conjugates, via the \"Trojan horse\" mechanism, effectively exploit bacterial iron uptake systems to deliver antimicrobial agents in a targeted manner. They overcome key resistance mechanisms such as β-lactamase production, porin alterations, and efflux pump activity, while reducing systemic toxicity and preserving commensal microbiota. Clinical evidence (e.g., cefiderocol) and preclinical studies confirm efficacy against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, with significant reductions in minimum inhibitory concentrations (MICs). However, critical challenges were identified: optimization of chemical stability and intracellular drug release, complexity in synthesis and industrial scaling under Good Manufacturing Practice (GMP) standards, and regulatory and logistical barriers in resource-limited settings.</p><p><strong>Conclusions: </strong>Siderophore conjugates offer a targeted therapeutic approach against multidrug-resistant pathogens by exploiting the bacteria's own iron-uptake systems. Available evidence ranges from clinical results with cefiderocol to preclinical developments with other platforms. Their application, however, faces challenges that span chemical optimization, manufacturing, regulation, and access in clinical settings.</p>","PeriodicalId":45860,"journal":{"name":"FARMACIA HOSPITALARIA","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148266549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PROA-KIDDDs study protocol: Evaluation of antimicrobial use and appropriateness in pediatric and neonatal care in Spain.","authors":"Paloma Suárez-Casillas, Marta Mejías-Trueba, José María Gutiérrez-Urbón, Walter A Goycochea-Valdivia, Elena Varela-Rubio, Olaf Neth, Maria Goretti López-Ramos, Maria Victoria Gil-Navarro, Ana Belén Guisado-Gil","doi":"10.1016/j.farma.2026.04.011","DOIUrl":"https://doi.org/10.1016/j.farma.2026.04.011","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the use of antimicrobials in the pediatric and neonatal population at a national level in order to identify consumption patterns, assess treatment appropriateness, and detect potential areas for improvement in therapeutic management.</p><p><strong>Method: </strong>We designed a retrospective, cross-sectional, multicenter observational study that included neonatal (<1 month) and pediatric (<15 years) inpatients with at least one active prescription of systemic antibacterials or antifungals. The study consists of two phases. The first phase involves the analysis of antimicrobial consumption through quarterly data collection, expressed as pediatric and neonatal defined daily doses (DDD) per 100 patient-days. A temporal trend analysis will be performed using segmented regression and calculation of the average quarterly percent change with 95% confidence intervals, identifying change points through the Monte Carlo permutation method. The second phase focuses on evaluating prescription appropriateness based on indication, antimicrobial selection, timing of administration, dose, frequency, route of administration, treatment duration, monitoring of efficacy and adverse effects, and documentation in the medical record. The review will be conducted by a hospital pharmacist and an infectious diseases specialist, with interobserver verification in 25% of cases. A sample size of 379 patients (270 pediatric and 109 neonatal) has been estimated for this phase. Differences between variables will be analyzed using Student's t-test, Mann-Whitney U test, Chi-squared test, or Fisher's exact test as appropriate. Inter-rater agreement will be assessed using Cohen's Kappa coefficient, and factors associated with differences in appropriateness will be analyzed through binary logistic regression and generalized lineal mixed models.</p><p><strong>Discussion: </strong>This study will allow the identification of antimicrobial consumption patterns and the evaluation of prescription appropriateness in pediatric and neonatal populations, providing objective and comparable information across centers. The findings will help strengthen Antimicrobial Stewardship Programs, serve as a solid basis for future research, and support the development of targeted national strategies, ultimately improving patient safety and helping to curb the progression of antimicrobial resistance.</p>","PeriodicalId":45860,"journal":{"name":"FARMACIA HOSPITALARIA","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148260012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Translated article] Real world outcomes of first-line pembrolizumab in metastatic non-small-cell lung cancer.","authors":"Amparo Burgos, Teresa Calleja, María Sacramento Díaz, Garbiñe Lizeaga, Cristina Ibáñez, Carmen María Valencia, Mónica Carbajales, David Conde, Juan Francisco Marín, Margarita Garrido, Raúl Díez, María José Martínez, María Larrosa, Estela Moreno","doi":"10.1016/j.farma.2026.02.019","DOIUrl":"https://doi.org/10.1016/j.farma.2026.02.019","url":null,"abstract":"<p><strong>Objective: </strong>To describe the effectiveness and safety of pembrolizumab in routine clinical practice as first-line treatment for advanced/metastatic non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50% and without EGFR or ALK alterations.</p><p><strong>Methods: </strong>Retrospective, multicenter observational study including patients diagnosed with advanced/metastatic NSCLC treated with pembrolizumab monotherapy as first-line therapy between January 2016 and July 2020. Clinical, treatment-related, and safety variables were collected. The primary effectiveness endpoints were overall survival (OS) and progression-free survival (PFS), estimated using the Kaplan-Meier method.</p><p><strong>Results: </strong>A total of 1005 patients from 42 Spanish hospitals were included, with a median age of 67 years (interquartile range [IQR]: 14); 256 were women. The predominant histology was non-squamous (725 patients). Median follow-up was 17.9 months (IQR: 24.1), and the median number of treatment cycles received was 8 (IQR: 21). Median PFS and OS were 8.7 months (95% confidence interval [CI]: 7.2-10.1) and 18.0 months (95% CI: 16.2-21.3), respectively. In the bivariate analysis, factors significantly associated with shorter OS included: age ≥ 75 years, body mass index (BMI) <25 kg/m², never smoking, performance status (PS-ECOG) ≥2, squamous histology, baseline liver or brain metastases, ≥2 metastatic sites at diagnosis, Lung Immune Prognostic Index (LIPI) 1-2, and prior exposure to proton pump inhibitors (PPIs), corticosteroids, and antibiotics (within the previous 10 days). Overall, 61.7% of patients experienced some degree of toxicity (G1-5), and 15.3% had G ≥ 3 toxicities. Treatment discontinuation due to toxicity occurred in 115 patients (12.7%). Patients who developed toxicity had a median OS of 28.3 months (95% CI: 23.9-34.5), compared to 6.5 months (95% CI: 5.1-9.2) in those without toxicity (p < 0.0001).</p><p><strong>Conclusions: </strong>In advanced/metastatic NSCLC with PD-L1 ≥ 50% and no EGFR/ALK alterations, first-line pembrolizumab demonstrates outcomes consistent with the pivotal trial and with published real-world evidence. The findings confirm that PS-ECOG ≥2 and prior PPI exposure are predictors of shorter OS, and that the development of toxicity during treatment is significantly associated with longer survival.</p>","PeriodicalId":45860,"journal":{"name":"FARMACIA HOSPITALARIA","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical intervention for the reduction of risks associated with medications in patients with liver cirrhosis in primary care.","authors":"Andrea Rodríguez Esquíroz, Amaya Echeverría Gorriti, Marta Marín Marín, Lorea Sanz Álvarez, Patricia García González, Javier Gorricho Mendivil, Juan Úriz Otano, Javier Garjón Parra, Inés Aguinaga Ontoso","doi":"10.1016/j.farma.2026.04.012","DOIUrl":"https://doi.org/10.1016/j.farma.2026.04.012","url":null,"abstract":"<p><strong>Introduction: </strong>The presence of cirrhosis may require adjustment of medication doses or substitution with safer alternatives. Inadequate treatment can lead to medication-related problems, which in most cases are preventable. The objectives are to describe the implementation of a safety strategy involving a comprehensive medication review for patients with cirrhosis, and to evaluate the acceptance rate of the intervention.</p><p><strong>Methods: </strong>It is a study of the implementation of a medication risk minimization strategy. It consisted of a medication review by hospital pharmacists, with clinical advice from a physician specializing in hepatology to patients in Primary Care.</p><p><strong>Results: </strong>307 patients were included, of whom 76.2% had at least one potentially inappropriate medication prescribed, with a safer alternative available in 87.2% of cases. Benzodiazepines and related drugs, proton pump inhibitors, and lipid-lowering drugs were the most frequently proposed, being benzodiazepines and related drugs the least modified by the physician. 48.1% of the 405 proposals were accepted.</p><p><strong>Conclusions: </strong>A high percentage of patients with cirrhosis were receiving inadequate treatments for their hepatic pathology, despite the availability of alternatives to minimize risks in most cases. Half of the pharmacists' recommendations were accepted and patient characteristics did not influence the acceptance rate of these proposals.</p>","PeriodicalId":45860,"journal":{"name":"FARMACIA HOSPITALARIA","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of immune checkpoint inhibitors for non-small cell lung cancer in a third level hospital.","authors":"Ana Álvarez-Yuste, María Pérez-Abánades, Ramón Colomer-Bosch, Irene Cuadrado-Berrocal, Jacobo Rogado-Revuelta, Tomás Gallego-Aranda, Ainhoa Aranguren-Oyarzábal","doi":"10.1016/j.farma.2026.04.015","DOIUrl":"https://doi.org/10.1016/j.farma.2026.04.015","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the effectiveness and cost-effectiveness of immune checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC) in real-world clinical practice.</p><p><strong>Methods: </strong>A retrospective, single-center observational study including NSCLC patients treated with atezolizumab, durvalumab, nivolumab, and pembrolizumab between 2015 and 2023. Demographic, clinical, and treatment data, as well as adverse events, were recorded. Statistical analysis was performed using the R Core Team (2024) software.</p><p><strong>Results: </strong>In stage IV, pembrolizumab demonstrated the longest median overall survival (OS) at 15.49 months, compared to nivolumab (10.26 months) and atezolizumab (9.24 months). In stage III, pembrolizumab reached an OS median of 34.64 months, nivolumab 17.03 months, and atezolizumab 10.62 months. Durvalumab reached an OS median of 30.18 months. In stage IV, the Incremental Cost-Effectiveness Ratio (ICER) of pembrolizumab versus atezolizumab was €517.92 per month of life gained, and the ICER of pembrolizumab versus nivolumab was €512.66 per month of life gained. In stage III with palliative intent, the ICER of pembrolizumab versus atezolizumab was €135.76 per month of life gained, and the ICER of pembrolizumab versus nivolumab was €152.26 per month of life gained.</p><p><strong>Conclusions: </strong>Although real-world survival outcomes are lower than those reported in pivotal clinical trials, immunotherapy is established as an efficient strategy for the National Health System. All analyzed drugs were cost-effective in the hospital setting studied, falling below the efficiency thresholds proposed by the WHO for Spain (<€65,180/year). The sustainability of these high-budget-impact treatments depends on precise patient selection based on biomarkers and the implementation of dosage optimization strategies. There is a need for local economic evaluations to guide clinical and management decision-making.</p>","PeriodicalId":45860,"journal":{"name":"FARMACIA HOSPITALARIA","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence on the impact of treatment optimization on the safety of patients with liver cirrhosis.","authors":"Andrea Rodríguez Esquíroz, Javier Garjón Parra, Amaya Echeverría Gorriti, Lorea Sanz Álvarez, Marta Marín Marín, Inés Aguinaga Ontoso","doi":"10.1016/j.farma.2026.03.015","DOIUrl":"https://doi.org/10.1016/j.farma.2026.03.015","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the impact of therapy optimization on medication-related safety in patients with liver cirrhosis.</p><p><strong>Method: </strong>Systematic review of clinical trials and before-and-after studies with time series analysis in CENTRAL, MEDLINE, and INAHTA databases. The certainty of the evidence was assessed using the GRADE approach, and the risk of bias was evaluated with the ROBUST-RCT tool.</p><p><strong>Results: </strong>Six articles were identified, all corresponding to a single randomized controlled trial (116 patients) that evaluated the effectiveness of a pharmacist-led intervention (medication reconciliation and individualized health education) compared to usual care. Although no significant differences were found in all-cause mortality or the crude relative risk of hospitalization, the adjusted incidence rate analysis revealed that the intervention significantly reduced unplanned hospitalizations by 48%. Furthermore, within the intervention group, each unit increase in the rate of high-risk medication-related problems was associated with more than three-fold higher odds of mortality, independently of disease severity.</p><p><strong>Conclusions: </strong>There is a current scarcity of high-quality studies in this field. Nevertheless, the available evidence suggests that pharmaceutical follow-up is an effective strategy to reduce preventable hospitalizations in outpatients with decompensated cirrhosis. Pharmacological safety is vital for survival, justifying the integration of the pharmacist into the clinical team.</p>","PeriodicalId":45860,"journal":{"name":"FARMACIA HOSPITALARIA","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Translated article] Possible severe gastrointestinal toxicity following the first cycle of mirvetuximab soravtansine in a patient with high-grade serous ovarian carcinoma.","authors":"Carlota Rodríguez-Tenreiro Rodríguez, Alicia Caso González, Marina Muñoz Villasur, Lucía Roncero Sánchez, Ana Lozano Blázquez","doi":"10.1016/j.farma.2026.05.001","DOIUrl":"https://doi.org/10.1016/j.farma.2026.05.001","url":null,"abstract":"","PeriodicalId":45860,"journal":{"name":"FARMACIA HOSPITALARIA","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the pharmacist in antimicrobial stewardship programs in critically ill patients.","authors":"Miguel Ángel Amor García, Irene Aquerreta González, Carla Bastida Fernández, Amaia Egüés Lugea, Sara Cobo Sacristán, Fernando Becerril Moreno, María Martín-Cerezuela, Esther Domingo Chiva, Tatiana Betancor García, Marta Albanell Fernández, Laura Doménech-Moral, Sara Ortiz Pérez, Aurora Fernández Polo","doi":"10.1016/j.farma.2026.04.014","DOIUrl":"https://doi.org/10.1016/j.farma.2026.04.014","url":null,"abstract":"<p><p>The design and implementation of antimicrobial stewardship programs for patients admitted to intensive care units must consider the specific characteristics of this population, including infection severity, organ dysfunction, and pharmacokinetic/pharmacodynamic alterations. The creation of a multidisciplinary team and the establishment of clear, targeted objectives are essential to improve treatment appropriateness, reduce the emergence of antimicrobial resistance, and ensure the sustainability of healthcare system. Pharmaceutical care contributes to the optimisation of antimicrobial use through antimicrobial therapy review, dose individualisation based on pharmacokinetic/pharmacodynamic parameters, and treatment monitoring, while also facilitating the development of systems for monitoring clinical outcomes, microbiology, and antimicrobial consumption.</p>","PeriodicalId":45860,"journal":{"name":"FARMACIA HOSPITALARIA","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milrinone in aneurysmal subarachnoid hemorrhage: A long way ahead.","authors":"Begoña Guardiola, Jesús Antonio Sánchez-Martín, Jon Pérez-Bárcena, Juan Antonio Llompart-Pou","doi":"10.1016/j.farma.2026.04.016","DOIUrl":"https://doi.org/10.1016/j.farma.2026.04.016","url":null,"abstract":"","PeriodicalId":45860,"journal":{"name":"FARMACIA HOSPITALARIA","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing strategies to mitigate psychotropic drug continuation post-ICU discharge: A critical perspective on the PSICU-ALTA protocol.","authors":"Parth Aphale, Himanshu Shekhar, Shashank Dokania","doi":"10.1016/j.farma.2026.04.001","DOIUrl":"https://doi.org/10.1016/j.farma.2026.04.001","url":null,"abstract":"","PeriodicalId":45860,"journal":{"name":"FARMACIA HOSPITALARIA","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}