[Antibiotic stewardship programs in the Spanish emergency services: PROA-URG Study]. / Programas de optimización del uso de antimicrobianos en los servicios de urgencias españoles: Estudio PROA-URG.

OBJECTIVE: Antimicrobial stewardship programs (ASP) have become a key tool in the adaptation of these drugs to the health system. The information available on the application and indicators used in these programs in emergency departments is scarce. The objective of this study is to know the extent of ASP implementation in the emergency departments, as well as the use of antimicrobials in these units. METHODS: Multicenter retrospective study. An invitation was sent to all participants of the REDFASTER-SEFH emergency pharmacist working group. A questionnaire was used consisting of 21 items, answered by a team made up of a pharmacist, emergency room specialist, infectious disease specialist and microbiologist. RESULTS: Eighteen hospitals completed the survey. Fourteen (77.8%) had an ASP manager. The DDD value per 1000 admissions ranged between 36.5 and 400.5 (median: 100.4 [IQR:57.2-157.3]). Both carbapenem and macrolide group presented wide variability in use. Six (33.3%) hospitals had an annual report on the specific resistance profile for urine and blood cultures. The percentage of multi-drug resistant strains in urine cultures was 12.5% and in blood cultures 12.2%. The percentage of adequacy in the bacteremia treatment was 81.0% (IQR:74.6-85.0%), while in urinary tract infections was 78.0% (IQR:71.5-88.0). CONCLUSIONS: Despite the existence of ASP members in emergency services, as well as the training activity and local guidelines is common. knowledge of the use of antimicrobials and resistances is limited. Future activities must be aimed at improving information about the ASP results in these units.

[Antimicrobial stewardship program in urinary tract infections due to multiresistant strains in the emergency department]. / Programa de optimización de antibioterapia en infección urinaria por cepas multirresistentes en el servicio de urgencias.

OBJECTIVE: Urinary tract infections (UTI) are a frequent reason for attendance at emergency department (ED). The present study evaluates the impact of a multidisciplinary program for the optimization of antibiotic therapy in patients with UTI caused by multi-drug resistant bacteria treated from the hospital ED. METHODS: Descriptive study of the implementation of a program in which emergency, microbiology and pharmacy departments participated. Antibiotic treatment of the patients who consulted the ED with positive urine cultures caused by multidrug-resistant bacteria was reviewed upon discharge. In those patients with inappropriate treatment, doctors and/or pharmacists of the next level of healthcare or patients in the case of home discharge were contacted. The impact of the program was evaluated based on new visits to the ED at 30 days after discharge, compared with the results obtained from the usual practice three months prior the intervention. RESULTS: During the first year, 2,474 urine cultures of patients with UTI were reviewed, 533 (21.7%) were caused by multidrug-resistant bacteria. Empirical treatment was inappropriate in 287 (53.4%), making treatment modifications in 243 of them. 73 (19.3%) patients returned to the ED 30 days after discharge, being lower than the results obtained in the three months prior intervention (27.9%; p=0.031), without significant differences in new visits associated with UTI. CONCLUSIONS: The implementation of a multidisciplinary program focused on multidrug resistant UTI at discharge form ED correct antibiotic therapy in a large number of patients, being a potentially tool to reduce the number of new ED visits.

Antimicrobial stewardship programs in the Intensive Care Unit in patients with infections caused by multidrug-resistant Gram-negative bacilli.

Antimicrobial stewardship programs (ASPs) have been shown to be effective and safe, contributing to reducing and adjusting antimicrobial use in clinical practice. Such programs not only reduce antibiotic selection pressure and therefore the selection of multidrug-resistant strains, but also reduce the potential deleterious effects for individual patients and even improve the prognosis by adjusting the choice of drug and dosage, and lessening the risk of adverse effects and interactions. Gram-negative bacilli (GNB), particularly multidrug-resistant strains (MDR-GNB), represent the main infectious problem in the Intensive Care Unit (ICU), and are therefore a target for ASPs. The present review provides an update on the relationship between ASPs and MDR-GNB.

[Risk factors associated with emergency service re-visits in frailty diabetic patients who consult for hypoglycaemia]. / Factores asociados a reconsultas a urgencias en pacientes frágiles con diabetes tipo 2 que consultan por hipoglucemia.

INTRODUCTION AND OBJECTIVES: Emergency department (ED) visits due to hypoglycaemia are frequent in elderly patients. The main objective of the study is to evaluate the risk factors associated to ED re-visits at 90days in elderly patients who visited ED with an episode of hypoglycaemia. MATERIAL AND METHODS: A retrospective observational study was designed, including elderly diabetic patients (>65years) attended in a fragility area of an ED for an episode of hypoglycaemia. To evaluate the risk factors associated to ED re-visits at 90days a multivariate analysis with logistic regression was performed, including those variables related to comorbidity and antidiabetic treatment with a P<0.2 in a previous univariate analysis. RESULTS: 106 patients were included. %HbA1c value was available in 87 (82.1%) patients. Ten (11.5%) patients presented a value of HbA1c ≤5.5%. Antidiabetic treatment was changed to 63 (59.4%) patients at discharge. Thirty-eight (36.1%) patients re-visited the ED at 90days, 9 for glycaemic alterations. The risk factors associated to 90days ED re-visit were: being man (OR: 3.62 [95%CI: 1.24-10.51)), treatment modified at discharge (OR: 0.31 [0.11-0.91]) and to present an HbA1c value ≤5.5% (OR: 5.33 [1.16-14.51]). CONCLUSIONS: Fragile patients with diabetes who visit ED for hypoglycaemia present, in high frequency, HbA1c values lower than those recommended, being associated to an increase of ED re-visit risk at 90days.

Antimicrobial stewardship programs in emergency departments: how do we measure antimicrobial use? A systematic review.

OBJECTIVE: The implementation of antimicrobial stewardship programs (ASPs) has become a usual practice in hospital settings. However, the method for monitoring antimicrobial use in accident and emergency departments (ED) is not yet adequately defined. Thus, the objective of this review is to describe antimicrobial use indicators used by ASPs implemented in ED. METHODS: A systematic review was performed based on studies found in the following academic research databases: MEDLINE, EMBASE, Web of Science, and Scopus (Period: January 2000 to December 2019). Controlled clinical trials, before-and-after studies, interrupted time series, and repeated measures studies assessing the impact of ASPs on antimicrobial use in ED were included; studies published in languages other than English or Spanish were excluded from this review. RESULTS: Twenty-six studies met the inclusion criteria and were included in this systematic review. In total, 15 (62.5%) studies described the ASP team members who collaborated with the ED staff. Most (21; 80.8%) studies used the percentage of patients with an antibiotic prescription as an indicator. Four (15.4%) studies included defined daily dose data. The antibiotic treatment duration was reported in four (15.4%) studies. Only two studies assessed the impact of the ASP using microbiological indicators, both of which used the incidence of infection with Clostridioides difficile as the indicator. CONCLUSIONS: The reports of experiences in implementing ASPs in ED show heterogeneous antimicrobial use indicators, which makes it difficult to compare results. Therefore, antimicrobial use indicators for ASPs must be standardised between hospital units.

Fosfomycin in infections caused by multidrug-resistant Gram-negative pathogens.

The alarming increase in antibiotic resistance rates reported for various pathogens has resulted in the use of alternative treatment policies. Given the fairly limited availability of new antimicrobial drugs, the reassessment of older antibiotics is now an interesting option. Fosfomycin, a bactericidal analog of phosphoenolpyruvate that has been previously been employed as an oral treatment for uncomplicated urinary tract infection, has recently raised interest among physicians worldwide. In general, the advanced resistance described in Gram-negative bacteria suggests that fosfomycin can be an appropriate treatment option for patients with highly resistant microbial infections. This review, which refers to key available data, focuses on the possibility of extending the use of fosfomycin beyond urinary tract infections and against multidrug-resistant Gram-negative bacteria.

Haemodialysis significantly reduces serum levetiracetam levels inducing epileptic seizures: Case report.

WHAT IS KNOWN AND OBJECTIVE: Levetiracetam is used in the treatment of some forms of epilepsy. In renal impairment and patients on chronic haemodialysis, dose adjustment is required. We report a case. CASE DESCRIPTION: This case report describes a woman on levetiracetam treatment who presented with generalized tonic-clonic seizures during a haemodialysis session. We report on treatment adjustment and on the impact of dialysis on levetiracetam levels. WHAT IS NEW AND CONCLUSION: Haemodialysis reduces serum levetiracetam concentration and can lead to subtherapeutic levels. Close monitoring is necessary when dialysis is used on patients receiving anticonvulsant drugs that are extensively eliminated by the procedure.

Ventilator-associated pneumonia by methicillin-susceptible Staphylococcus aureus: do minimum inhibitory concentrations to vancomycin and daptomycin matter?

The use of vancomycin minimum inhibitory concentration (MIC) as an outcome predictor in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia has become an important topic for debate in the last few years. Given these previous results, we decided to investigate whether MICs to vancomycin or daptomycin had any effect on the evolution of patients with ventilator-associated pneumonia (VAP) due to MSSA. An observational, retrospective, multicenter study was conducted among patients with MSSA VAP. We analyzed the relationship between vancomycin and daptomycin MICs and early clinical response (72 h), 30-day mortality, intensive care unit (ICU) length of stay (LOS), and duration on mechanical ventilation. Univariate and multivariate analyses were performed. Sixty-six patients from 12 centers were included. Twenty-six patients (39%) had an infection due to MSSA strains with a vancomycin MIC ≥1.5 µg/mL. Daptomycin MIC was determined in 58 patients, of whom 17 (29%) had an MIC ≥1.0 µg/mL. Ten patients (15%) did not respond to first-line treatment. Only daptomycin MIC ≥1.0 µg/mL had a significant association [odds ratio (OR): 30.00; 95% confidence interval (CI): 2.91-60.41] with early treatment failure. The 30-day mortality was 12% (n = 8). Any variable was associated with mortality in the multivariate analysis. None of the variables studied were associated with ICU LOS or duration on mechanical ventilation. In patients with MSSA VAP, vancomycin MIC does not influence the response to antibiotic treatment or the 30-day mortality. Daptomycin MIC was directly related to early treatment failure.

Aflibercept in exudative age related macular degeneration refractory to ranibizumab.

PURPOSE: The aim of this study is to determine the effectiveness, safety and cost of aflibercept in the treatment of wet age-related macular degeneration (ARMD) refractory to ranibizumab. METHODS: Retrospective observational study was conducted on patients diagnosed with wet ARMD, and previously treated with ranibizumab. Efficacy variables assessed were changes in visual acuity (BCVA) and anatomical improvements in the most affected eye. Factors associated with improvement of BCVA with aflibercept were also studied. Adverse events related to the aflibercept administration were recorded. Cost analysis data were collected from the hospital perspective, and only taking the direct medical costs into account. Cost-effectiveness analysis was calculated using the aflibercept treatment cost, and effectiveness calculated as BCVA gained. RESULTS: A total of 50 eyes corresponding to 46 patients were included. The median follow-up period was 4.6 months (range: 1.0-6.0). Improvement in visual acuity after the first 2 doses and at the end of the follow-up period was observed in 32.0 and 28.0% of treated eyes, respectively. None of the variables studied was associated with an improvement in the BCVA after treatment. No significant differences were found in the average monthly cost between treatments. CONCLUSIONS: Aflibercept is shown to be an effective treatment in a significant number of patients resistant to treatment with ranibizumab, presenting a cost similar to that generated during the final stages of treatment with ranibizumab.

Initial experience of use of tolvaptan in critically ill patients with fluid overload.

WHAT IS KNOWN AND OBJECTIVE: Positive volume balance is related with high mortality in critically ill patients. We describe our experience in the use of tolvaptan in patients with fluid overload. CASE SUMMARY: Six patients in the recovery phase from septic shock were included. All patients achieved an increase in diuresis after the first day, with a median fluid balance variation of -2362 (-485 to -3447) mL. At the end of treatment, median fluid balance variation was -9080 (-26,784 to -4395) mL. WHAT IS NEW AND CONCLUSION: Tolvaptan could be an option in critically ill patients with fluid overload and resistant or not treatable with conventional diuretics.

Clinical evaluation of rituximab treatment for neuromyelitis optica.

INTRODUCTION: Neuromyelitis optica is an inflammatory and usually relapsing demyelinating autoimmune disease of the central nervous system that targets the optic nerves and spinal cord. Rituximab has been used for different neurological diseases that are probably immune-mediated or involving humoural immunity. The objective of this study is to evaluate the efficacy and safety of rituximab as treatment for neuromyelitis optica in a tertiary hospital. METHODS: Retrospective study of patients with neuromyelitis optica treated with rituximab 1000mg on days 1 and 15, repeated every 6 to 8 months. We recorded EDSS score, relapse rate, overall condition, CD19+ count, presence of anti-NMO antibodies, and possible adverse reactions. RESULTS: Six patients were treated; all were women with a median age of 46 years (range, 38-58). Anti-NMO antibodies were detected in 3 patients (50%). Baseline EDSS was 4 (range 2.0-5.5). Two patients had previously been treated with an immunomodulatory drug. Median time from the first rituximab infusion to first relapse was 3.7 years (range 1.7-6.9). Two patients had infusion reactions after the first dose of rituximab. Four patients remained relapse-free and their EDSS score did not progress during rituximab treatment, one patient showed no clinical improvement, and one patient could not be evaluated. CONCLUSION: Rituximab can be considered an attractive therapeutic alternative for patients with neuromyelitis optica as there are no approved treatments for this disease. Further studies with rituximab are needed to establish the role of this drug in treating neuromyelitis optica.

[Analysis of the causes leading to withdrawal of the treatment with triple antiviral therapy for hepatitis C patients]. / Análisis de las causas de suspensión de tratamiento con triple terapia antiviral en pacientes con hepatitis C.

OBJECTIVE: To assess causes of suspension of hepatitis C treatment in patients receiving triple antiviral therapy (peginterferon+ ribavirin + protease inhibitor). METHODS: Retrospective observational study of patients who received triple antiretroviral therapy against hepatitis C between January 2012 - March 2013 and discontinued their treatment. RESULTS: Of 156 patients who initiated therapy, 41 discontinued treatment: Nineteen due to adverse events, being dermatological events in seven patients ( 36.8 %), intolerance in six(31.6%) and hematologic toxicity in four (15.8%) . Sixteen patients discontinued treatment for being ineffectiveness.Patients with higher inefficacy failure rate were "null-responders"(32.3% ) while the group of "relapsers" were the one with the highest rate of toxicity suspensions (15.6%). Two patients died during treatment for pneumonia. CONCLUSIONS: Triple therapy with boceprevir and telaprevir is associated with a significant number of treatment failures due to toxicity and ineffectiveness.

Objetivo: Evaluar las causas de suspensión de tratamientofrente a Hepatitis C que reciben triple terapia antiviral (peginterferon+ ribavirina + inhibidor de proteasa).Métodos: Estudio observacional retrospectivo de pacientes queiniciaron triple terapia antiviral entre enero 2012 - marzo 2013y suspendieron el tratamiento antes de completar el mismo.Resultados: De 156 pacientes que iniciaron triple terapia, 41interrumpieron el tratamiento: Diecinueve por toxicidad, siendodermatológica en siete pacientes (36,8%), intolerancia en seis(31,6%) y hematológica en cuatro (15,8%). Dieciséis pacientessuspendieron todo el tratamiento por ineficacia. El grupo depacientes con mayor porcentaje de fracasos por ineficacia fueronlos "no respondedores" (32,3%) mientras que el grupo depacientes "recidivantes" fueron el grupo con mayor porcentajede suspensiones por toxicidad (15,6%). Dos pacientes fallecierondurante el tratamiento por neumonía.Conclusiones: La triple terapia frente a VHC está asociada a unnúmero importante de fracasos terapéuticos tanto por toxicidadcomo por ineficacia.

Anidulafungin-induced alopecia.

OBJETIVE: To report a case of a woman in whom alopecia appeared after several months of treatment with anidulafungin. CASE SUMMARY: A 34-year-old woman with chronic femoral osteomyelitis with the presence of persistent suppuration, developed a Candida albicans infection, isolated in the fistula exudate cultures. After initial failures of single therapy with azoles, it was decided to administer fluconazole and anidulafungin 100 mg/d. One month after starting the treatment, the patient mentioned a greater hair loss than usual. At 3 months, the patient stopped taking the drug on noting the loss and easy falling out of her hair, with alopecia plaques 1 to 2 cm in size. At 2 months after stopping the anidulafungin, it was decided to restart combined antifungal treatment using micafungin and fluconazole; there was no mention of new or greater loss of hair. It was decided to change micafungin to anidulafungin again 90 days after starting treatment. In the first month of treatment, there appeared to be a reactivation in hair loss that later stabilized and improved. DISCUSSION: Drug-induced hair loss is an adverse reaction that has been identified during different hair growth phases. It has been described for the azoles group and has not been associated with candins until now. Results of the causality analysis, using the probability scale established by Naranjo, found the relationship as probable. CONCLUSIONS: Anidulafungin could be associated with hair loss. Physicians must be aware of this adverse effect in order to approach it properly and to detect possible nonadherence to treatment.

[Effectiveness and adequacy of tolvaptan prescription in hospitalized patients]. / Efectividad y adecuación de la prescripción de tolvaptán en pacientes hospitalizados.

PURPOSE: To analyse the effectiveness of the use of Tolvaptan and the adequacy of Tolvaptan prescription at a tertiary level hospital. METHODS: Prospective observational study of Tolvaptan prescrip - tion from October of 2010 to December of 2011. RESULTS: 30 patients (60.0% males) were included, 50.0% of which were diagnosed with heart failure and 30.0% with SIADH. Tolvaptan allowed achieving sodium levels higher than 135 mEq/L in 53.3% of the patients with a mean baseline value of 125.3±7.3 mEq/L. The median treatment duration was 5.0 days (interquartile range=3-45). A significant increase of uric acid associated to Tolvaptan treatment was observed. The prescription was in agreement to what has been established in GFT in 63.3% of the cases. CONCLUSIONS: Tolvaptan increases sodium levels by 7.5 mEq/L, both in SIADH-associated hyponatremia and in heart failure, with an appropriate safety profile.

Objetivo: Analizar la efectividad del uso de tolvaptán y la adecuación de su prescripción en un hospital de tercer nivel. Método: Estudio observacional prospectivo de las prescripciones de tolvaptán desde octubre de 2010 hasta diciembre de 2011. Resultados: Se incluyeron 30 pacientes (60,0% varones), 50,0% diagnosticados de insuficiencia cardíaca y 30,0% de SIADH. Tolvaptán permitió alcanzar niveles de sodio superiores a 135 mEq/L en el 53,3% de los pacientes que partían con una media de 125,3±7,3 mEq/L. La mediana de días de tratamiento fue de 5,0 (rango intercuartílico = 3-45). Se observó un incremento significativo de los niveles de ácido úrico asociado al tratamiento con tolvaptán. La prescripción se adecuó a lo establecido en la GFT en el 63,3% de los casos. Conclusiones: Tolvaptán incrementa un 7,5 mEq/L los niveles de sodio tanto en hiponatremia secundaria al SIADH como en insuficiencia cardiaca.

[Evaluation of the written informed consent form in clinical trials]. / Evaluación de la hoja de información al paciente y del consentimiento informado en ensayos clínicos.

PURPOSE: To assess the quality of the written informed consent form (WICF) in clinical trials. MATERIAL AND METHODS: Retrospective observational study was performed on 50 WICF of clinical trials started between 2010 and 2011. The quality of the content of the WICF was assessed using the "Guideline for Good Clinical Practice" contained in the CPMP/ICH/135/95 of the European Medicines Agency. Legibility indexes were applied to the WICF. RESULTS: The WICF was correct in all aspects in 10% of the clinical trial; five sections were correct in all WICF: "trial involves research", "trials goals", "participation is voluntary and the subject may withdraw at any time without penalty", "study personnel with access to medical records" and "documents that identify the patient are confidential". Aspects less present were "the subject's responsibilities" and "available alternatives". All WICF required clarification by the Ethics Committee (EC), with a mean of 4.24 (SD=1.87) changes per WICF. The WICF showed good results in the indices of readability. Almost all (98%) of WICF were considered with an acceptable readability. CONCLUSIONS: Compliance with different aspects that must appear in the WICF is high. Aspects to improve are the subject's responsibilities and available alternatives to the clinical trial. The complexity of reading the WICF is suitable for the average population. The review of the WICF by the EC guarantees the access to comprehensive and appropriate information.