Antimicrobial consumption among 66 acute care hospitals in Catalonia: impact of the COVID-19 pandemic

Background: antimicrobials have been widely used during the COVID-19 pandemic. This study aimed to analyze the impact of the COVID-19 pandemic on the antimicrobial consumption of 66 hospitals in Catalonia. Methods: adult antibacterial and antimycotic consumption was calculated as defined daily doses (DDD)/100 bed-days and DDD/100 discharges. Firstly, overall and ICU consumption in 2019 and 2020 were compared. Secondly, observed ICU 2020 consumptions were compared with non-COVID-19 2020 estimated consumptions (based on the trend from 2008-2019). Results: overall, antibacterial consumption increased by 2.31% and 4.15% DDD/100 bed-days and DDD/100 discharges, respectively. Azithromycin (105.4% and 109.08% DDD/100 bed-days and DDD/100 discharges, respectively) and ceftriaxone (25.72% and 27.97% DDD/100 bed-days and DDD/100 discharges, respectively) mainly accounted for this finding. Likewise, antifungal consumption increased by 10.25% DDD/100 bed-days and 12.22% DDD/100 discharges, mainly due to echinocandins or amphotericin B. ICU antibacterial and antimycotic consumption decreased by 1.28% and 4.35% DDD/100 bed-days, respectively. On the contrary, antibacterial and antifungal use, expressed in DDD/100 discharges, increased by 23.42% and 19.58%. Azithromycin (275.09%), ceftriaxone (55.11%), cefepime (106.35%), vancomycin (29.81%), linezolid (31.28%), amphotericin B (87.98%), and voriconazole (96.17%) use changed the most. Observed consumption of amphotericin B, azithromycin, caspofungin, ceftriaxone, vancomycin, and voriconazole were higher than estimated values. Conclusions: the consumption indicators for most antimicrobials deviated from the expected trend pattern. A worrisome increase in antibacterial and antifungal consumption was observed in ICUs in Catalonia

Evolution of Antimicrobial Consumption During the First Wave of COVID-19 Pandemic

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

Risk Factors for Amoxicillin-Clavulanate Resistance in Community-Onset Urinary Tract Infections Caused by Escherichia coli or Klebsiella pneumoniae : The Role of Prior Exposure to Fluoroquinolones

Background: High rates of amoxicillin-clavulanate (AMC) resistance among Enterobacterales isolated from urinary tract infections (UTIs) were observed in our area. The aim of this study was to identify risk factors associated with AMC resistance in patients with community-onset UTI in emergency departments (EDs). Methods: A retrospective study was performed of all ED patients with positive urine cultures for Escherichia coli or Klebsiella pneumoniae in a Spanish tertiary-care hospital. Results: 330 urine cultures in all were included: 261 (79.1%) for E. coli and 69 (20.90%) for K. pneumonia. Rates of AMC resistance were 14.94% and 34.78%, respectively. UTI was clinically confirmed in 212 (64.24%) cases. Previous antimicrobial exposure was independently associated with AMC resistance development in E. coli and K. pneumoniae urinary isolates (OR = 2.94, 95% CI = 1.55-5.58). Analyses of infected patients revealed that previous exposure to fluoroquinolones (OR = 3.33, 95% CI = 1.10-10.12, p = 0.034) and to AMC (OR = 5.68, 95% CI = 1.97-16.44, p = 0.001) was significantly associated with isolation of AMC-resistant strains. Conclusions: Prior antibiotic exposure, particularly to AMC or fluoroquinolones, was the only independent risk factor associated with development of AMC resistance in E. coli and K. pneumoniae urinary isolates from patients attending the ED

Epidemiología, factores de riesgo y tratamiento de las bacteriemias producidas por enterococcus faecium

Enterococcus faecium es tracta d'un microorganisme comensal amb capacitat per a provocar infeccions com la bacterièmia. La incidència de bacterièmia per aquest microorganisme s'ha incrementat durant els darrers anys, presentant una elevada mortalitat. No obstant, malgrat aquestes dades no existeix evidència suficient que avali l'elecció del tractament més apropiat. L'objectiu principal d'aquesta tesi, elaborada per compendi de publicacions, consisteix a estudiar l'efectivitat i la seguretat dels diferents tractaments antibiòtics disponibles (vancomicina, linezolid i daptomicina) en el tractament de la bacterièmia per E. faecium sensible a la vancomicina. En el primer treball es va observar que el linezolid podria ser una alternativa efectiva i segura a la vancomicina en el tractament d'aquesta entitat. En el segon treball, la daptomicina va presentar un major risc de fracàs terapèutic en comparació amb la vancomicina, per la qual cosa hauria de ser utilitzat amb precaució i un estricte monitoratge. Finalment, són necessaris assajos clínics que confirmin l'observat en aquests estudis observacionals. Fins a disposar d'aquesta evidència, linezolid podria considerar-se una alternativa a vancomicina, mentre que la daptomicina hauria de ser utilitzada com a fàrmac de segona línia.Enterococcus faecium se trata de un microorganismo comensal con capacidad para provocar infecciones como bacteriemia. La incidencia en la bacteriemia por este microorganismo se ha incrementado durante los últimos años, presentando una elevada mortalidad. Sin embargo, a pesar de estos datos no existe evidencia suficiente que avale la elección del tratamiento más apropiado. El objetivo principal de esta tesis, elaborada por compendio de publicaciones, consiste en estudiar la efectividad y seguridad de los diferentes tratamientos antibióticos disponibles (vancomicina, linezolid y daptomicina) en el tratamiento de la bacteriemia por E. faecium sensible a la vancomicina. En el primer trabajo se observó que linezolid podría ser una alternativa efectiva y segura a vancomicina en el tratamiento de esta entidad. En el segundo trabajo daptomicina presentó un mayor riesgo de fracaso terapéutico en comparación con vancomicina, por lo que debería ser utilizado con precaución y una estricta monitorización. Finalmente, son necesarios ensayos clínicos que confirmen lo observado en estos estudios observacionales. Hasta disponer de esa evidencia, linezolid podría considerarse una alternativa a vancomicina, mientras que daptomicina debería ser utilizado como fármaco de segunda línea.Enterococcus faecium is a commensal microorganism with the ability to cause infections as bacteraemia. The incidence in the bacteraemia of this microorganism has increased in recent years, showing a high mortality. Despite these data, there is a lack of evidence to support the choice of the most appropriate treatment. The main objective of this thesis, presented as a compendium of publications, is to study the effectiveness and safety of the different antibiotic treatments (vancomycin, linezolid and daptomycin) in the treatment of the bacteraemia caused by vancomycin susceptible E. faecium. In the first study, linezolid appeared as an effective and safe alternative to vancomycin. In the second, daptomycin presented a higher risk of therapeutic failure compared to vancomycin, so it should be used with caution and strict monitoring. Finally, randomised clinical trials are necessary to confirm what has been observed in these observational studies. Until this evidence is available, linezolid could be considered an alternative to vancomycin, while daptomycin should be used as a second-line therapy

Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in critically-ill patients: systematic review

INTRODUCTION: Community-acquired pneumonia (CAP) is associated with high morbidity and mortality rates. Despite methicillin-resistant Staphylococcus aureus (MRSA) having often been associated with nosocomial pneumonia, the condition of some MRSA CAP patients is severe enough to warrant their being admitted to ICU. OBJECTIVE: The purpose of this study is to conduct a systematic review of the literature on antibiotic treatment of MRSA CAP in critically-ill patients. MATERIAL AND METHODS: An online search was conducted for locating articles on MRSA CAP in critically ill patients. Relevant publications were identified in PUBMED, the BestPractice database, UpToDate database and the Cochrane Library for articles published in English within the December 2001 - April 2016 time frame. RESULTS: A total of 70 articles were found to have been published, 13 (18.8%) having been included and 57 (81.4%) excluded. Cohort studies were predominant, having totaled 16 in number (20.7%) as compared to one sole cross-sectional study (3.5%). CONCLUSIONS: The experience in the treatment of MRSA CAP in patients requiring admission to ICU is quite limited. Vancomycin or linezolid seem to be the treatments of choice for MRSA CAP, although there not be any specific recommendation in this regard. It may be useful to use alternative routes, such as administration via aerosolized antibiotics, continuous infusion or in association with other antibiotic

Daptomycin versus glycopeptides for the treatment of Enterococcus faecium bacteraemia: a cohort study

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

Real-world effectiveness and persistence of reference etanercept versus biosimilar etanercept GP2015 among rheumatoid arthritis patients: A cohort study

Although several randomized clinical trials have confirmed that there is no difference in efficacy between etanercept and its biosimilar versions in the treatment of rheumatoid arthritis (RA), limited real-world evidence is available. We conducted a cohort study to compare the effectiveness and treatment persistence between the reference etanercept (ETN) and the biosimilar GP2015 in RA patients in a real-life setting. Adults with a diagnosis of RA who initiated treatment with ETN or GP2015, between January 2007 and December 2019, were included. The follow-up period was 52 weeks. The primary outcome was the mean of change in the DAS28-CRP values and the adjusted mean difference from baseline to 52 weeks between ETN and GP2015. Other effectiveness endpoints assessed were the rate of patients who achieved remission or low disease activity (LDA) at week 52, who showed a reduction of DAS28-CRP value greater than or equal to 1.2 from baseline to week 52 and rate of good responder patients (those meeting both effectiveness measures) at week 52. Treatment effectiveness over time (baseline, 26 and 52 weeks) was compared between the ETN and GP2015 groups using mixed effects models. Treatment persistence (probability of maintaining the same treatment over time) was also evaluated and shown using Kaplan-Meier survival curves. A total of 115 RA patients were included (ETN, n = 90; GP2015, n = 25). No differences were observed in the primary outcome: DAS28-CRP score decreased from baseline to week 52 [5.1 to 2.7 (mean of change -2.37) in ETN group and 5.0 to 2.2 (mean of change -2.84) in GP2015 group, p-value = 0.372] and the adjusted mean difference was -0.37 (-1.03 to 0.29). No differences were also observed in the other effectiveness endpoints assessed among patients treated with ETN or GP2015: rate of patients who achieved remission (54.1% vs. 66.7%, p-value = 0.303) and LDA (71.6% vs. 80.9%, p-value = 0.391) at week 52, reduction of DAS28-CRP value greater than or equal to 1.2 from baseline to week 52 (75.6% vs. 80.9%, p-value = 0.613) and rate of good responder patients (58.1% vs. 76.1%, p-value = 0.202). Drug survival was 82% and 80% for ETN and GP2015, respectively (log-rank p-value = 0.804). Etanercept and its biosimilar GP2015 show similar effectiveness and treatment persistence in RA patients in a real-life setting

Azithromycin in the treatment of COVID-19: a review

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)