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El aumento progresivo de las resistencias antibióticas apremia el tener estrategias para disminuir la presión sobre la microbiota. La duración del tratamiento antibiótico empírico es variable, a pesar de las recomendaciones de las guías. Se ha realizado una revisión bibliográfica de la evidencia científica publicada sobre la duración del tratamiento antibiótico empírico en las infecciones intraabdominales quirúrgicas con control de foco efectivo. Se analizan las guías americanas realizadas por Mazuski et al. de 2017 como eje central en las recomendaciones de la duración de tratamiento antibiótico empírico en infecciones intraabdominales con control del foco y se añade una búsqueda bibliográfica de todos los artículos que contuviesen las palabras claves en Pubmed y Google Scholar. Se recopilan 21 artículos referentes en la duración del tratamiento antibiótico empírico en la infección intraabdominal con control del foco. Con las guías americanas y estos artículos se ha elaborado una propuesta de duración del tratamiento antibiótico empírico en pacientes sin factores de riesgo entre 24 y 72 h. Y en los que presentan factores de riesgo se habría de individualizar el mismo con monitorización activa cada 24 h de fiebre, íleo paralítico y leucocitosis, ante una detección precoz de complicaciones o de necesidad de cambios en el espectro antibiótico. Los tratamientos cortos son igual de eficaces que los de duraciones más prolongadas y se asocian a menos tasa de efectos adversos, por tanto, ajustar y revaluar diariamente la duración del tratamiento antibiótico empírico es fundamental para una mejor praxis. A non-systematic review of the published scientific evidence has been carried out on the duration of empirical antibiotic treatment in surgical intra-abdominal infections with effective focus control. Given the progressive increase in antibiotic resistance, it is urgent to have strategies to reduce the pressure on the microbiota. The American guidelines made by Mazuski et al. of 2017, as the central axis in the recommendations of the duration of empirical antibiotic treatment in intra-abdominal infections with control of the focus and a bibliographic search of all the articles that contained the keywords in Pubmed and Google Scholar is added. 21 articles referring to the duration of empirical antibiotic treatment in intra-abdominal infection with control of the focus are collected. With the American guidelines and these articles, a proposal is prepared for the duration of empirical antibiotic treatment in patients without risk factors between 24 and 72 h. And in those who present risk factors, it should be individualized with active monitoring every 24 h of fever, paralytic ileus and leukocytosis, before an early detection of complications or the need for changes in antibiotic treatment. Short treatments are just as effective as those of longer durations and are associated with fewer adverse effects, therefore, daily adjusting and reassessing the duration of empirical antibiotic treatment is essential for better practice. info:eu-repo/semantics/publishedVersion

Background: Skeletal involvement of Cryptococcus neoformans is infrequent and usually associated with disseminated cryptococcosis or underlying predisposing conditions. We present an atypical case of osteoarticular cryptococcosis in an immunocompetent patient. Case presentation: We herein report a case of bone and soft tissue cryptococcal infection in a 42-year-old male from Pakistan with well-controlled diabetes without other associated immunodeficiencies treated with antifungal therapy without surgical debridement. Furthermore, the patient developed toxidermia due to fluconazole use, so a fluconazole desensitization was performed. Therapeutic management also included the performance of therapeutic drug monitoring of fluconazole plasma concentrations. Conclusion: To our knowledge, this is the first case of osteoarticular cryptococcosis treated with this treatment regimen. This strategy may be of interest to try to reduce hospital stay and associated complications.

Our aim was to describe the incidence and characteristics of immune-related adverse events (irAEs) in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and to evaluate their impact on outcome. All cases of NSCLC patients treated with ICIs in the second-line setting between December 2015 and May 2018 were evaluated. Seventy patients were included. Mean age was 65.9 years, and the majority of male (n = 53, 75.7%), with PS of 0-1 (n = 62, 88.6%) treated with nivolumab (n = 51; 72.9%). Thirty-one patients (44.3%) experienced an AE, 5 (7.1%) were grades 3-4. Median OS in patients with AE was 30.1 months (95% CI, 16.7-43.5) compared with 5.1 months (95% CI, 1.2-9.0) in cases without AE (log-rank test: p = 0.010). The adjusted HR for OS was 0.46 (95% CI, 0.25-0.86) for the irAE occurrence and 3.60 (95% CI, 1.56-8.32) for PS 2-3 group. The development of irAEs was associated with improved patient outcome.

Introduction: SARS-CoV-2 is a novel virus that causes coronavirus disease-19 (COVID-19). Antiviral and immunomodulatory agents have been proposed as potential treatments. Azithromycin exhibits both properties and therefore may play a role. Areas covered: This article reviews the pharmacology, pharmacokinetics, clinical efficacy, and safety of azithromycin in viral infections, with emphasis on COVID-19. A literature search of PUBMED was conducted on May 30th and updated on July 28th. Expert opinion: Azithromycin presents in vitro activity against SARS-CoV-2 and could act in different points of the viral cycle. Its immunomodulatory properties include the ability to downregulate cytokine production, maintain epithelial cell integrity or prevent lung fibrosis. Azithromycin use was associated with a reduction in mortality and ventilation days in other viral infections. These properties could be beneficial throughout the COVID-19. However, the evidence of its use is scarce and of low quality. Azithromycin has been assessed in retrospective observational studies mainly in combination with hydroxychloroquine, which has shown to provide no benefit. This macrolide presents a well-known safety profile. Upcoming clinical trials will determine the role of azithromycin in the COVID-19 (including the stage of the disease where it offers the greatest benefits and the effect of its combination with other drugs).

Hospital antibiotic consumption is measured using defined-daily-doses (DDD) divided by bed days. However,other denominators as discharges could provide a more accurate interpretation of consumption. The main objective was to analyze trends of antibiotic consumption among hospitals in Catalonia during the period 2008-2016, using both DDD/100 bed days and DDD/100 discharges.Retrospective, descriptive, and longitudinal study performed among acute care hospitals affiliated to VINCat Program. Antibiotic consumption was expressed using the Anatomical Therapeutic Chemical/DDD classification and trends with a mixed linear model. Trends after using both DDD/100 bed days and DDD/100 discharges were determined and compared.Overall antibiotic consumption from 2008 to 2016 increased by 10.24% (Whereas a significant upward trend in antibiotic consumption in DDD/100 bed days was noticed, DDD/100 discharges remained stable. The description of both indicators seems therefore essential for a correct interpretation of data.

Antibiotic allergy labels (AAL) are related to worse therapeutic results. Strategies to improve the management of these patients, such as the implementation of antibiotic desensitization, are essential for Antimicrobial Stewardship Programs (ASP). The aim of our study is to evaluate the efficacy and safety of antibiotic desensitization procedures for the management of patients with AAL. A retrospective study from 2015 to 2022 was performed to describe all antibiotic desensitization conducted in our institution, within the framework of ASP. A systematic literature review using electronic databases, such as PubMed, was also done to identify studies describing antibiotic desensitization between 2000 and 2022. Sixteen antibiotic desensitization protocols were carried out in our institution. In fourteen cases, the desensitization was successfully completed, and the antibiotic could be used to treat the infection. In the systematic review, twenty-two studies were included, with a total of 202 desensitization episodes . In 97% of them, the desensitization was completed successfully. No desensitization-related mortality was observed neither in our cohort nor in literature review. Antibiotic desensitization strategies should be considered a safe and effective tool that can be included in ASP for patients with a high risk of or confirmed allergy to penicillin.

Background: The impact of antimicrobials generic entry (GE) is controversial. Their introduction could provide an economic benefit yet may also increase their consumption, leading to a higher risk of resistance. Our aim was to analyze the impact of GE on trends of antimicrobial consumption in an acute-care hospital. Methods: A retrospective quasi-experimental interrupted time series analysis was conducted at a 400-bed tertiary hospital in Barcelona, Spain. All antimicrobials for systemic use for which a generic product entered the hospital from January 2000 to December 2019 were included. Antimicrobial consumption was expressed as DDD/100 bed days. Results: After GE, the consumption of cefotaxime (0.09, p &lt, 0.001), meropenem (0.54, p &lt, 0.001), and piperacillin-tazobactam (0.13, p &lt, 0.001) increased, whereas the use of clindamycin (−0.03, p &lt, 0.001) and itraconazole (−0.02, p = 0.01) was reduced. An alarming rise in cefepime (0.004), daptomycin (1.02), and cloxacillin (0.05) prescriptions was observed, despite not achieving statistical significance. On the contrary, the use of amoxicillin (−0.07), ampicillin (−0.02), cefixime (−0.06), fluconazole (−0.13), imipenem–cilastatin (−0.50) and levofloxacin (−0.35) decreased. These effects were noticed beyond the first year post GE. Conclusions: GE led to an increase in the consumption of broad-spectrum molecules. The potential economic benefit of generic antibiotics could be diluted by an increase in resistance. Antimicrobial stewardship should continue to monitor these molecules despite GE.

Introduction Aspergillus may cause different types of lung infections: invasive, chronic pulmonary or allergic bronchopulmonary aspergillosis. Pharmacological management with antifungals poses as a challenge. Patients diagnosed with pulmonary aspergillosis are complex, as well as the problems associated with antifungal agents. Areas covered This article reviews the pharmacology of antifungal agents in development and currently used to treat pulmonary aspergillosis, including the mechanisms of action, pharmacokinetics, pharmacodynamics, dosing, therapeutic drug monitoring and safety. Recommendations to manage situations that arise in daily clinical practice are provided. A literature search of PubMed was conducted on November 15th, 2020 and updated on March 30th, 2021. Expert opinion Recent and relevant developments in the treatment of pulmonary aspergillosis have taken place. Novel antifungals with new mechanisms of action that extend antifungal spectrum and improve pharmacokinetic-related aspects, drug-drug interactions and safety are under current study. For those antifungals already marketed, new data related to pharmacokinetics, pharmacodynamics, dose adjustments in special situations, therapeutic drug monitoring and safety are available. To maximize efficacy and reduce the risk of associated toxicities, it is essential to choose the most appropriate antifungal; optimize its dose, interval, route of administration and length of treatment; and prevent side effects.

BACKGROUND: Limited data regarding altered linezolid pharmacokinetics in patients with liver cirrhosis are available. The objective of this study was to evaluate the pharmacokinetics, efficacy and safety of linezolid in cirrhotic patients. METHODS: A case-control 1:1 study of patients undergoing linezolid therapeutic drug monitoring was conducted between January 2015 and June 2017. Cases with liver cirrhosis were matched with controls by age, body weight, comorbidities, renal function, and intensive care unit (ICU) admission. RESULTS: Fifty-two patients were included, 26 in each group. Patients with Child-Pugh Scores A, B, and C were 1 (3.8%), 13 (50.0%), and 12 (46.2%), respectively. Cases had higher median linezolid trough plasma concentrations than controls [20.6 (17.4) versus 2.7 (11.3); P < 0.001)] and more frequently achieved an optimal pharmacodynamic index [26 (100%) versus 16 (61.5%); P = 0.002]. In addition, potentially toxic concentrations and treatment discontinuation due to overexposure and hematological toxicity were also more frequently seen in cirrhotic patients. Overall clinical cure rate was high (67.4%), and in-hospital mortality was 28.8%. No differences in clinical outcomes were observed between both groups. CONCLUSIONS: Linezolid showed a high clinical cure rate. Nevertheless, plasma concentrations and treatment discontinuation due to hematological toxicity were higher in cirrhotic patients. Liver cirrhosis may influence linezolid pharmacokinetics and question the use of standard doses. Therapeutic drug monitoring of linezolid would be valuable in these patients.

The overall increase in the use of carbapenems could lead to the selection of carbapenem-resistant bacteria. The objectives of this study were to analyze carbapenem use from 2008 to 2015 and their prescription profile in 58 hospitals affiliated to the VINCat Programme (nosocomial infection vigilance system).Retrospective, longitudinal and descriptive study of carbapenem use. Consecutive case-series study, looking for carbapenem prescription characteristics, conducted in January 2016. Use was calculated in defined daily doses (DDD)/100 patient-days (PD); prescription profiles were assessed using a standardized survey.Carbapenem use increased 88.43%, from 3.37 DDD/100-PD to 6.35 DDD/100-PD (p0.001). A total of 631 patients were included in the prescription analysis. Carbapenems were prescribed empirically in 76.2% of patients, mainly for urinary tract and intra-abdominal infections due to suspicion of polymicrobial mixed infection (27.4%) and severity (25.4%).A worrying increase in carbapenem use was found in Catalonia. Stewardship interventions are required to prevent carbapenem overuse.

Iron deficiency affects exercise capacity because of the critical role iron plays in the optimal functioning of skeletal muscle metabolism. We hypothesized that intravenous iron may improve exercise tolerance, quality of life (QoL), and daily physical activity (DPA) in patients with chronic obstructive pulmonary disease (COPD).This was a placebo-controlled, single-blind, parallel-group, randomized clinical trial. Iron deficiency was defined as a ferritin level100ng/mL or a ferritin level between 100 and 299ng/mL with a transferrin saturation20%, with or without mild anaemia. Patients were randomized at a 2:1 ratio to receive intravenous ferric carboxymaltose or placebo. The primary objective was to investigate whether intravenous iron replacement improved endurance time from baseline by at least 33%. The secondary objectives were to evaluate impact on QoL using the COPD Assessment Test (CAT) and on DPA by accelerometry.We included 66 patients, 44 (66.7%) in the intervention group and 22 (33.3%) in the placebo group. Among patients receiving ferric carboxymaltose, 23 (52.3%) achieved the primary endpoint compared to 4 (18.2%) in the placebo group [p=0.009; relative risk 3.12, (95% CI, 1.19-8.12)]. CAT score decreased -3 (-6.0-1.3) points from baseline in the intervention group (p=0.007), in contrast to placebo group [-1 (-4.0-2.3) points, p=0.236] with no differences in DPA and adverse events in both groups.Iron replacement improved exercise capacity and QoL in stable COPD patients with iron deficiency. The treatment was well tolerated.EudraCT 2016-001238-89.

Background and importance Drug related problems (DRP) are common among hospitalised patients. During the COVID-19 pandemic, the number of inpatients increased and the pattern of drug use was varied which could lead to a higher number of potential DRP. Aim and objectives To describe DRP in patients admitted to COVID-19 wards during the COVID-19 pandemic peak. Material and methods A retrospective observational study was performed in a tertiary university hospital from 21 March to 30 April 2020. Patients included were those admitted to a COVID-19 ward and presenting a DRP (excluding emergency department and critical care units). Computerised physician order entry (CPOE) operates for all hospital beds. Medical prescriptions were revised daily by clinical pharmacists. When a potential DRP was detected, an annotation with a recommendation was made in the patient’s medical record. DRP were classified according to the Pharmaceutical Care Network Europe classification. Data collected were demographic, the drug class involved (anatomical chemical therapeutic (ATC)), DRP detected and degree of recommendation acceptance. Results Total patients with DRP: 291 (23.3%). Identified DRP: 393 (1.4 DRP/patient). 58.3% were men and median age was 63 (15.7) years. Conclusion and relevance Almost 25% of all patients had a DRP, presenting an incidence of 1.4 DRP/patient, higher than reported in previous series. 83% of evaluable recommendations were accepted. One- third of the recommendations were derived from a wrong dosage, and 15% from drug interactions. Hydroxychloroquine was the most frequently involved drug, probably because of the limited experience and wide spectrum of interactions, followed by antimicrobials such as ceftriaxone and azithromycin, used widely in respiratory tract infections. References and/or acknowledgements Conflict of interest No conflict of interest

Background: The first wave of COVID-19 pandemic may have significantly impacted antimicrobial consumption in hospitals. The objective of this study was to assess the evolution of antimicrobial consumption during this period. Methods: A retrospective quasi-experimental before–after study was conducted in a Spanish tertiary care hospital. The study compared two periods: pre-pandemic, from January 2018 to February 2020, and during the COVID-19 pandemic from March to June 2020. Antimicrobial consumption was analyzed monthly as defined daily doses (DDD)/100 bed-days and overall hospital and ICU consumption were evaluated. Results: An increase in the hospital consumption was noticed. Although only ceftaroline achieved statistical significance (p = 0.014), a rise was observed in most of the studied antimicrobials. A clear temporal pattern was detected. While an increase in ceftriaxone and azithromycin was observed during March, an increment in the consumption of daptomycin, carbapenems, linezolid, ceftaroline, novel cephalosporin/β-lactamase inhibitors or triazoles during April–May was noticed. In the ICU, these findings were more evident, namely ceftriaxone (p = 0.029), carbapenems (p = 0.002), daptomycin (p = 0.002), azithromycin (p = 0.030), and linezolid (p = 0.011) but followed a similar temporal pattern. Conclusion: An increase in the antimicrobial consumption during the first wave of COVID-19 pandemic was noticed, especially in the ICU. Availability of updated protocols and antimicrobial stewardship programs are essential to optimize these outcomes.

Azithromycin has shown antiviral and immunomodulatory actions that may be of interest in coronavirus disease-19 (COVID-19). The objective of this review was to summarize the potential usefulness of azithromycin in the COVID-19. Azithromycin has shown in vitro activity against SARS-CoV-2. The potential mechanisms of action include the impairment of virus binding and of membrane fusion, endocytosis, and lysosomal protease activation due to its lysosomotropic character. Among other immunomodulatory actions, azithromycin downregulates the production of proinflammatory cytokines, maintains epithelial cell integrity and may prevent lung fibrosis. These properties, which have been related to positive clinical outcomes in other settings as influenza pneumonia, may be beneficial throughout the course of COVID-19. However, scientific evidence is still scarce. Azithromycin has mostly been studied with hydroxychloroquine/chloroquine. In outpatients, this combination showed a reduction in time to clinical recovery or need for hospitalization without safety concerns. In hospitalized patients presented an increased risk of mortality and cardiovascular events. In the few studies that assessed the efficacy of azithromycin monotherapy, a reduction in the time to clinical recovery in outpatients and a trend towards a reduction in mortality in inpatients was observed. Data on critically ill patients are lacking. The quality of data was low, as most of the studies were observational and retrospective. Azithromycin may play a role in the treatment of COVID-19. Despite the paucity of data and associated limitations, azithromycin has shown promising results that deserve further study. The upcoming clinical trials will elucidate the role of this macrolide in COVID-19.

Our objective was to analyze in vitro the persistence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the packaging material of the drugs dispensed to hospital wards. Additionally, to evaluate if the protection with a double plastic bag prevents the contamination of the medication dispensed to an intensive care unit (ICU).On the first part, different materials containing different drugs within an ICU were sampled to confirm the lack of contamination by SARS-CoV-2. The confirmation of the virus was performed using real time reverse transcription polymerase chain reaction. As a control group, in the microbiology laboratory we inoculated the virus into the different surfaces containing the same drugs included in the first part. Samples were obtained with a sterile swab at 3, 6, 8, 10, 14, 21, and 30 days after inoculation and analyzed through real time reverse transcription polymerase chain reaction.None of the studied materials containing the drugs within an ICU was contaminated by SARS-CoV-2. In the second part, SARS-CoV-2 was found in all surfaces for up to 30 days.The use of double-bag unit-dose system to deliver medication in a pandemic seems effective to prevent the potential transmission of SARS-CoV-2. A striking SARS-CoV-2 RNA stability of up to 30 days was found in the surfaces containing the drugs.

Background The intravenous administration of antibiotics remains the route of choice at patient admission. Although the early-oral switch once the clinical stability has been achieved, has demonstrated to be effective and safe in other settings, its implementation in the pneumology ward has not been studied. Purpose To assess the effectiveness and safety of an early-oral antimicrobial switch protocol in the pulmonology ward. Material and methods Quasi-experimental study performed in a 400-bed tertiary hospital. The protocol was implemented in March 2018 and therefore two groups were identified: intervention group (March to August 2018) and control group (March to August 2017). All patients admitted to the pneumology ward were treated with intravenous antibiotics that, in turn, were available orally: therefore, amoxicillin/clavulanate, fluoroquinolones, trimethoprim-sulfamethoxazole, clindamycin and azithromycin were included. Results A total of 200 patients were included. Main clinical outcomes are summarised in table 1. Conclusion The implementation of an early-oral antimicrobial switch protocol in the pneumology ward is effective and safe. The early-oral antibiotic switch could decrease the days of catheterisation and the potential related adverse outcomes, with a shortening in the length of stay. References and/or acknowledgements None. No conflict of interest.

Background: Ampicillin resistant and glycopeptide susceptible Enterococcus faecium bloodstream infection (GSEF-BSI) incidence has risen. However, the treatment of choice remains unknown. Daptomycin use for the treatment of enterococcal infections has increased, despite effectiveness and safety concerns. The objective was to compare the effectiveness and safety of daptomycin and glycopeptides in the treatment of GSEF-BSI. Methods: This was a single-centre, retrospective observational cohort study performed at Hospital del Mar (Barcelona, Spain), from January 2006–May 2018. The primary outcome was clinical cure at the end of the therapy, and secondary outcomes included 14-day, 30-day, in-hospital mortality, and length of stay. Results: From a total of 192 patients with GSEF-BSI, 54 (28.1%) were treated with glycopeptides and 17 (8.9%) with daptomycin. Patients treated with daptomycin presented a lower clinical cure than patients treated with glycopeptides (58.8% vs. 83.3%, RR 0.416 (95% CI 0.189–0.915)). After controlling for confounding variables by means of multivariate analysis the significative difference was confirmed (aOR 4.313, 95% CI, 1.053–17.660). The need for treatment discontinuation due to adverse events was similar. Conclusions: Patients with GSEF-BSI treated with glycopeptides showed a higher clinical cure than those treated with daptomycin.

Background The incidence of ampicillin-resistant Enterococcus faecium bacteraemia is increasing. Vancomycin remains the first-line treatment in areas with a high prevalence of glycopeptide-susceptible isolates, but data comparing its clinical outcomes with other treatments are lacking. The objective of this study was to compare the effectiveness and safety of linezolid and glycopeptides for the treatment of glycopeptide-susceptible E. faecium bloodstream infection (GSEF-BSI). Methods This retrospective observational cohort study was conducted from January 2006 to May 2018 at the Hospital del Mar, Barcelona, Spain, and compared the clinical outcomes and safety of linezolid and glycopeptides in adult patients with GSEF-BSI. The main outcomes included clinical cure at the end of therapy, 30-day mortality, microbiological eradication and attributable length of stay (LOS). Propensity score matching was performed to reduce potential confounders among groups. Results In total, 105 patients with GSEF-BSI were included (linezolid, n=38; glycopeptides, n=67). After propensity score matched analysis, 56 (53.3%) patients, 28 in each cohort, entered the final analysis. No differences were observed in any of the main clinical outcomes among patients treated with linezolid or glycopeptides: clinical cure [16/28 (57.1%) vs 13/28 (46.4%), P=0.593], 30-day mortality [8/28 (28.6%) vs 12/28 (42.9%), P=0.403], microbiological eradication [22/28 (78.6%) vs 20/28 (71.4%), P=0.758] and median attributable LOS (18.0 vs 17.0 days, P=0.924). Adverse events were similar in both groups. Conclusions Linezolid and glycopeptides showed similar clinical effectiveness and safety in the treatment of GSEF-BSI. Linezolid could be an alternative to glycopeptides in the treatment of GSEF-BSI.

BACKGROUND The objective of this study was to assess the effect of intravenous human serum albumin administration (IV HSA) on nutrition markers, including non-serum-albumin plasma protein levels, in adult critically ill patients receiving parenteral nutrition (PN). METHODS This was a retrospective study of prospectively collected data. Patients included in an initial cohort were patients who initiated IV HSA within 24 hours of start of PN. A second cohort who did not received IV HSA during PN was manually selected, matching several variables. Subsequently, both cohorts were propensity-score matched, resulting in 2 final cohorts: the cohort receiving IV HSA (ALB) and the cohort not receiving IV HSA (NOALB). RESULTS A total of 42 patients, 21 in each cohort, entered the study. Both cohorts were similar in demographics, anthropometrics, comorbidities, diagnoses, PN composition, and severity of the disease, biochemistry, and nutrition markers. Patients in the ALB cohort received IV HSA at a dose of 30.0 g/day during 5 days. The ALB cohort presented higher values of final serum albumin level and serum albumin level change from baseline, but also presented lower values of final non-serum-albumin plasma protein levels and their change and lower final prealbumin. In addition, bilirubin in the ALB cohort increased, whereas it decreased in the NOALB cohort. CONCLUSION Patients receiving IV HSA and PN for several days increased serum albumin level, but decreased non-serum-albumin plasma protein levels. In addition, bilirubin clearance could be slightly impaired in these patients.

Background The emergence of multidrug-resistant microorganisms is a serious threat to global public health that requires action. Thus, the implementation of antimicrobial stewardship programmes aims to optimise antibiotic prescription and prevent antimicrobial resistance. Although these programmes are multidisciplinary, there is a lack of data about the specific role of pharmacists. Purpose To describe pharmacists’ activity in an antimicrobial stewardship team. Material and methods Retrospective descriptive study performed in a 400-bed tertiary hospital. Data from all pharmaceutical interventions referring to any antimicrobial prescription registered between January 2014 and December 2015 were collected. Vancomycin- and aminoglycosides-related interventions were excluded as they belong to another intervention area. Antimicrobial prescriptions were reviewed every day through an electronic prescription program. Pharmaceutical interventions were gathered and registered in six different groups: renal impairment adjustment, dose adjustment, frequency adjustment, drug-interactions and miscellaneous (adverse events, therapeutic drug monitoring, monitoring of biochemical parameters…). Acceptance by physicians was also evaluated. Categorical values were presented in percentages. Results A total of 1026 interventions were recorded. The 26.1% were renal impairment adjustments; 24.7% dose adjustments; 17.3% miscellaneous; 13.1% related to antimicrobial-spectrum; 9.7% interactions; and 9.2% frequency adjustments. From 1026 interventions, 80.4% were accepted, 11.6% rejected and 8 not evaluable. Conclusion Adjustments due to renal impairment and dose adjustments were the main actions performed. Interestingly, a 13.1% of interventions were related to the antimicrobial-spectrum, mainly in antibiotics of high ecological impact. Overall, recommendations by pharmacists were highly accepted among physicians. These data highlight the important role of hospital pharmacists in antimicrobial stewardship programmes. No conflict of interest

BACKGROUND: Linezolid is used at a standard dose of 600 mg/12 hours regardless of renal or hepatic function but very little data concerning its pharmacokinetics (PK), efficacy and safety in patients with liver cirrhosis is available. PURPOSE: The objectives were to describe the PK, efficacy and safety of linezolid in cirrhotic patients. MATERIAL AND METHODS: A prospective case-control 1:1 study conducted between January 2015 to June 2017. Cases were all cirrhotic patients treated with linezolid undergoing therapeutic drug monitoring (TDM). Controls were matched by age, actual bodyweight, comorbidities, renal function (glomerular filtration rate (GFR)) and severity. Subtherapeutic linezolid concentrations were defined as a through (Cmin) concentration 10 mg/L. Thrombocytopaenia was defined as a decrease in platelet count to

Background The incidence of Enterococcus faecium infections has increased over the past years and is currently the third major microorganism implicated in nosocomial bacteraemia. Nevertheless, the best treatment available is yet to be established, especially in vancomycin-susceptible E. faecium . In this setting, a correct dosage is essential, as inappropriate dosage has been associated with a higher risk of treatment failure. Purpose Our objective was to describe the dosage adequacy of antibiotics used in the treatment of E. faecium bacteraemia. Material and methods Retrospective observational study performed in a 400-bed university teaching hospital from June 2011 to June 2016. Patients with E. faecium isolation from at least one positive blood culture were included. Dosage adequacy was assessed by infectious-diseases-trained pharmacists, who reviewed antimicrobial prescriptions daily and recommended an appropriate dose adjustment in the first 24 to 72 hours of treatment. Inappropriate dosage was considered if it was out of therapeutic range according to plasmatic levels when available, or if an adjustment was needed according to weight or renal function (based on John Hopkins antibiotic guide and data sheet). Categorical variables were presented as percentages and continuous variables as mean (±SD). Results Seventy patients were included Sixty (85.7%) males, 17 (24.3%) critically ill, mean age 69.8 (±13.5) years. Thirty (42.3%) patients received an inappropriate dosage, 19 (63.3%) of them were underdosed. Conclusion Almost 43% of patients were inappropriately dosed in E. faecium bacteraemia, mainly because of underdosing. These data demonstrate the large proportion of inappropriate doses, which highlights the importance of an adequate review of medication and therapeutic drug monitoring in order to assure efficacy and prevent toxicities. No conflict of interest

OBJECTIVES: Interactions between antiretroviral treatment (ART) and comedications are a concern in HIV-infected patients. This study aimed to determine the frequency and severity of potential drug-drug interactions (PDDIs) with ART in our setting. METHODS: Observational study by a multidisciplinary team in 1259 consecutive HIV patients (March 2015-September 2016). Data on demographics, toxic habits, comorbidities, and current ART were collected. A structured questionnaire recorded concomitant medications (including occasional and over-the-counter drugs). PDDIs were classified into four categories: (1) no interactions, (2) mild (clinically non-significant), (3) moderate (requiring close monitoring or drug modification/dose adjustment), and (4) severe (contraindicated). STATISTICAL ANALYSIS: chi-square test, logistic regression analysis. RESULTS: In total, 881 (70%) patients took comedication, and 563 (44.7%) had ≥ PDDI. Forty-one comedicated patients (4.6%) had severe and 522 (59.2%) moderate PDDIs. Moderate PDDIs mainly involved cardiovascular (53.8%) and central nervous system (40.2%) drugs. Independent risk factors for PDDIs were ART containing a boosted protease inhibitor (odds ratio [OR]=9.11, 95% confidence interval [CI] 5.15-16.11; p = 0.0001) and/or non-nucleoside reverse transcriptase (NNRTI) (OR = 4.34, 95%CI 2.49-7.55; p = 0.0001), HCV co-infection (OR = 3.26, 95%CI 2.15-4.93; p = 0.0001), and use of two or more comedications (OR = 3.36, 95%CI 2.27-4.97; p = 0.0001). Adherence and effectiveness of ART were similar in patients with and without PDDIs. The team made 133 recommendations related to comedications (drug change or dose adjustment) or ART (drug switch or change in administration schedule). CONCLUSIONS: Systematic evaluation detected a significant percentage of PDDIs requiring an intervention in HIV patients on ART. Monitoring and advice about drug-drug interactions should be part of routine practice.

We evaluated the use of antimicrobials expressed as defined daily doses (DDDs) per 1,000 patient days and days of therapy (DOT) per 100 occupied bed-days in a intensive care unit (ICU) of a general hospital in Barcelona, Spain, before and after implementation of an antimicrobial stewardship (AMS) program (2007 to 2010 versus 2011 to 2015). The quarterly costs of antimicrobials used in the ICU and its weight in the overall hospital costs of antimicrobials were calculated. The effect of the applied AMS program on DDDs and DOT time series data was analyzed by means of intervention time series analysis. A total of 5,002 patients were included (1,971 for the first [before] period and 3,031 for the second [after] period). The percentage of patients treated with one or more antimicrobials decreased from 88.6 to 77.2% ( P < 0.001). DDDs decreased from 246.8 to 192.3 (mean difference, −54.5; P = 0.001) and DOT from 66.7 to 54.6 (mean difference, −12.1; P = 0.066). The mean cost per trimester decreased from €115,543 to €73,477 (mean difference, −42,065.4 euros; P < 0.001), and the percentage of ICU antimicrobials cost with respect to the total cost of hospital antimicrobials decreased from 28.5 to 22.8% (mean difference, −5.59; P = 0.023). Implementation of an AMS program in the ICU was associated with a marked reduction in the use of antimicrobials, with cost savings close to one million euros since its implementation. An AMS program can have a significant impact on optimizing antimicrobial use in critical care practice.

Six cases of patients diagnosed with urinary tract infection (UTI) successfully treated with micafungin are reported. Four were infected with fluconazole-resistant Candida spp. and two (with hepatic injury) were infected with fluconazole-sensitive Candida spp. Traditionally, echinocandins have not been considered for the treatment of UTIs. However, despite its low urinary excretion rate, therapeutic drug monitoring of micafungin urinary levels could be helpful in order to achieve optimal pharmacokinetic/pharmacodynamic (PK/PD) indices for treating UTIs caused by Candida spp. resistant to fluconazole.

Background The recent approval of the new direct acting antivirals (DAAs) has extended treatment options in hepatitis C virus (HCV) genotype 1 infected patients with compensated liver disease. Purpose To evaluate which factors can influence the selection of DAAs in genotype 1 HCV patients in our setting. Material and methods Retrospective study including genotype 1 HCV patients treated with interferon free DAAs from December 2014 to September 2015. Data collected: demographics, genotype 1 subtype, HIV infection, presence of liver cirrhosis (LC), prior treatment status (naive or pretreated) and other concomitant drugs. DAAs were classified­ as follows: sofosbuvir+simeprevir±ribavirin (SOF/SMV); sofosbuvir+daclatasvir±ribavirin (SOF/DCV); sofosbuvir/ledipasvir±ribavirin (SOF/LDV); ombitasvir/paritaprevir/ritonavir+dasabuvir±RBV (OBV/PTV/r/DSV). The χ 2 test and the Mann-Whitney U test were used for categorical and quantitative variables, respectively. Results We included 124 patients: 79 (63.7%) male; mean age 60.8 (±SD 11.5) years; 35 (28.2%) genotype 1a; 26 (21%) HIV/HCV coinfected; 79 (63.7%) LC; 65 (52.4%) naive; and 56 (45.2%) with polypharmacy (>3 drugs, median value). DAA regimen selected: 34 (27.4%) SOF/SMV; 14 (11.3%) SOF/DCV; 34 (27.4%) SOF/LDV and 42 (33.9%) OBV/PTV/r/DSV. There were statistically significant differences in the frequency distribution of the different selected DAAs (table 1) A tendency was observed when comparing different genotype subtypes (p = 0.094) or presence of polypharmacy (p = 0.088). Conclusion HIV/HCV coinfected and cirrhotic patients were more likely to be treated with SOF/LDV while HCV monoinfected and non-cirrhotic patients with likely to receive OBV/PTV/r/DSV. Pretreated patients were more likely to be treated with SOF/SMV while those naive with more likely to receive OBV/PTV/r/DSV. The major potential for drug-drug interactions of OBV/PTV/r/DSV and its lower experience in advanced liver disease and previous triple therapy failure could have influenced these findings. References and/or Acknowledgements Pawlotsky JM. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol 2015 No conflict of interest.

Background Despite current highly active antiretroviral therapy (HAART), some patients still do not achieve an undetectable viral load, and it is important to identify treatment failure (TF) associated factors. Purpose To determine the incidence and risk factors for TF in a cohort of HIV infected patients. Material and methods Cross sectional study in an initial cohort of 1562 HIV infected patients from June 2014 to July 2015. 1259 were finally included and interviewed, to collect the following data: demographics, current ART and adherence, concomitant medications and drug interactions (DI) (according to the University of Liverpool database). TF was defined as confirmed HIV RNA >50 copies/mL. A logistic regression analysis was used to identify variables independently related to TF. Results Patients included: 1259 (80.6%); patients excluded: 303 (19.4%) due to lack of data or lost to follow-up. Univariate analysis Patients with and without TF: 151 (12.0%) versus 1108 (88.0%), male (82.1% vs 80.1%, p = 0.587), age (42.9 vs 48.0 years, p + T cell count (526.0 vs 716.3 cells/µL, p HAART: non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI) (35.8% vs 55.0%, p Adherence 90 (8.1%), p Goodness-of-fit: Hosmer and Lemershow test (p = 0.889). Discriminative ability: AUC 0.744 (95% 0.702 to 0.787), p Conclusion Risk factors related to treatment failure were younger age, alcohol or drug use, poor adherence and use of HAART not including an NNRTI. Despite advances in HIV treatment, poor adherence is still the most important factor for treatment failure and justifies the need for multidisciplinary management of these high risk patients. No conflict of interest.

Background Monoclonal antibody drugs (mAb) are a relative new innovation and have been established as one of the most successful therapeutic strategies in several pathologies. The novel mechanism of action, based on modulation of the immune system, is associated with higher cure rates. Consequently, mAb are considered an attractive therapeutic option and are the subject of study in several clinical trials (CT). Purpose To assess the impact of mAb CT related to total CT managed at the pharmacy department, and different services involved in them. Material and methods Retrospective observational study performed in a tertiary university hospital from January 2014 to September 2015. Data collected: total CT and mAb CT (mAb-CT) by department; mAb-CT/total mAb-CT by department; mAb-CT phase. Reference sources were an internal database, the EU Clinical Trials Register and the American Clinical Trials Database. Results Conclusion More than half of clinical trials from dermatology, rheumatology and cardiology services are evaluating mAb. Considering total mAb-CT, oncology and haematology services are involved in approximately 60% of them. Approval of these mAb is imminent, as more than two-thirds of CT are phase III and will be commercialised soon. Benefit of mAb has been linked to certain pathologies. Consequently, some services with intense research activity have a reduced number of mAb-CT. No conflict of interest.

Background Interferon free treatments (IFT) for chronic hepatitis C (CHC) consist of more feasible and better tolerated regimens that could help to improve adherence. Nevertheless, little is known about adherence to these treatments in clinical practice. Purpose To evaluate adherence to IFT in clinical practice and non-adherence risk factors. Material and methods Patients completing IFT for CHC in a tertiary hospital were included (December 2014 to September 2015). Baseline characteristics including concomitant medications were recorded. Adherence was calculated as a percentage from pill count records performed in each drug dispensing visit (every 4 weeks) and at the end of treatment. Ribavirin dose reductions were not considered as lack of adherence. Bivariate analysis of baseline characteristics in patients with and without 100% adherence was performed. Fisher’s test and the Mann-Whitney U test were used for categorical and continuous variables, respectively. Results 78 patients were included: median age was 59 years, 55 (70.5%) were male, 48 (61.5%) with genotype 1b, 15 (19.2%) with HIV coinfection, 53 (67.9%) with cirrhosis and 36 (46.2%) were naive. Mean number of concomitant drugs was 3.31 (SD 2.7). 69 (88.5%) patients received 12 weeks of treatment. No differences were found in demographics, genotype, HIV coinfection, previous antiviral treatment or number of concomitant medications between patients with and without 100% adherence. Conclusion Observed adherence rates to all IFT in clinical practice were superior to 90%. None of the analysed factors seemed to influence patient adherence, probably due to the low number of patients and the excellent rates of adherence observed. References and/or Acknowledgements Pawlotsky JM. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol 2015 No conflict of interest.