Elena Espejo

Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial

Introduction Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. Methods and analysis A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. Ethics and dissemination The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study. Trial registration number NCT01898338.

Clinical presentation of acute Q fever in Spain: seasonal and geographical differences

OBJECTIVES The aims of this study were to improve our understanding of the clinical forms of presentation of acute Q fever in Spain and to determine any possible relationships with geographical and seasonal factors. METHODS This was a retrospective study of 183 cases of acute Q fever from three Spanish regions, Catalonia, Canary Islands, and La Rioja. RESULTS The main clinical form of presentation was hepatitis (49.2%), followed by isolate febrile syndrome (31.7%) and pneumonia (19.1%). The proportion of cases presenting as pneumonia was significantly higher in La Rioja (40.7%) than in Catalonia (18.3%) or the Canary Islands (12.9%) (p=0.001). In Catalonia and the Canary Islands, most cases (52.1% and 57.6%, respectively) were diagnosed between March and June, whereas in La Rioja, most cases (51.8%) occurred between November and February. Overall, the proportion of cases presenting as pneumonia was significantly higher in the period from November to February (32.6%) than in the periods March-June (16.0%) and July-October (13.0%) (p=0.01). CONCLUSIONS Our results suggest the existence of seasonal differences in the presentation of acute Q fever in Spain, with a higher proportion of pneumonic forms in the colder months. Furthermore, we confirmed the existence of geographical differences, with a higher proportion of pneumonic forms in the region of La Rioja, in the north of the country.

Epidemiology and risk factors for infections due to AmpC β-lactamase-producing Escherichia coli

OBJECTIVES To describe the prevalence and risk factors for infection due to AmpC β-lactamase-producing Escherichia coli (AmpC-EC). METHODS For the prevalence study, all clinical isolates of E. coli with reduced susceptibility to third-generation cephalosporins were prospectively included from June 2010 to November 2011. For risk factor analysis, a case-control study was conducted. Cases were patients with an infection due to AmpC-EC. Controls were patients infected with cephalosporin-susceptible E. coli, matched 1 : 2. Detection of blaAmpC genes was done with a multiplex AmpC-PCR, and hyperproduction of E. coli chromosomal blaAmpC by quantitative RT-PCR. Alteration of the blaAmpC promoter was studied by PCR and sequencing. RESULTS We identified 243 (1.1%) AmpC-EC strains out of 21 563 clinical isolates. Three cases with strains carrying ESBLs, 18 strains that were considered due to colonization and 8 cases lost to clinical follow-up were excluded. Finally, 214 cases were included in the analysis. Ninety-one cases (42.5%) and 269 (62.8%) controls were strictly community acquired (P < 0.001). Thirty-five (16.3%) cases and 186 controls (43.5%) did not have any identifiable risk factor (P < 0.001). Among cases, 158 (73.8%) were found to harbour an acquired AmpC (73.4% CMY-2). Previous use of fluoroquinolones [OR 2.6 (95% CI 1.12-3.36); P = 0.008] was independently associated with AmpC-EC in the multivariate analysis. CONCLUSIONS Prevalence of AmpC in E. coli remains low in our area. Plasmid acquisition (CMY type) represents the main mechanism of AmpC production. A high proportion of community-acquired isolates and patients with no identifiable risk factors were found. Previous use of fluoroquinolones was identified as a risk factor.

Clinical characteristics, treatment and outcomes of MRSA bacteraemia in the elderly.

OBJECTIVES To compare clinical and microbiological characteristics, treatment and outcomes of MRSA bacteraemia among elderly and younger patients. MATERIAL AND METHODS Prospective study conducted at 21 Spanish hospitals including patients with MRSA bacteraemia diagnosed between June/2008 and December/2009. Episodes diagnosed in patients aged 75 or more years old (≥75) were compared with the rest of them (<75). RESULTS Out of 579 episodes of MRSA bacteraemia, 231 (39.9%) occurred in patients ≥75. Comorbidity was significantly higher in older patients (Charlson score ≥4: 52.8 vs. 44%; p = .037) as was the severity of the underlying disease (McCabe ≥1: 61.9 vs. 43.4%; p < .001). In this group the acquisition was more frequently health-care related (43.3 vs. 33.9%, p = .023), mostly from long-term care centers (12.1 vs. 3.7%, p < .001). An unknown focus was more frequent among ≥75 (19.9 vs. 13.8%; p = .050) while severity at presentation was similar between groups (Pitt score ≥3: 31.2 vs. 27.6%; p = .352). The prevalence of vancomycin resistant isolates was similar between groups, as was the appropriateness of empirical antibiotic therapy. Early (EM) and overall mortality (OM) were significantly more frequent in the ≥75 group (EM: 12.1 vs. 6%; p = .010 OM: 42.9 vs. 23%; p < .001). In multivariate analysis age ≥75 was an independent risk factor for overall mortality (aOR: 2.47, CI: 1.63-3.74; p < .001). CONCLUSION MRSA bacteraemia was frequent in patients aged ≥75 of our cohort. This group had higher comorbidity rates and the source of infection was more likely to be unknown. Although no differences were seen in severity or adequacy of empiric therapy, elderly patients showed a higher overall mortality.

Cost of organ/space infection in elective colorectal surgery. Is it just a problem of rates?

Organ/space (O/S) infection in colorectal surgery remains a major health problem. In Catalonia, the VINCat Program has monitored 24,832 procedures during 2007-2014, showing a steady rate of O/S infection over the years, 8.2% (95% CI 7.9 - 8.6). Improving awareness of stakeholders could be an easy strategy for assembling quality programs within health systems.

Prospective Cohort Study of Single-Day Doxycycline Therapy for Mediterranean Spotted Fever

Original Article 1 Length of the paper: 2032 words 2 Length of the abstract: 250 words 3 4 5 Title: Single-day doxycycline therapy for Mediterranean spotted fever: a prospective 6 cohort study 7 Running title: One-day doxycycline therapy for Mediterranean spotted fever 8 9 Authors: Elena Espejo, Marta Andrés, Maria-Consol Garcia, Anna Fajardo, Josefa 10 Pérez, Feliu Bella. 11 1 Infectious Diseases Unit, Internal Medicine Service, Hospital de Terrassa (Consorci 12 Sanitari de Terrassa), Ctra. Torrebonica s/n, 08227 Terrassa, Spain. 13 2 Internal Medicine Service, Hospital de Terrassa (Consorci Sanitari de Terrassa), Ctra. 14 Torrebonica s/n, 08227 Terrassa, Spain. 15 3 Microbiology Laboratory, Catlab, Vial Sant Jordi s/n, Pol. Ind. Can Mitjans, 08232 16 Viladecavalls, Spain. 17 18 19 20 Corresponding author: 21 Elena Espejo 22 Infectious Diseases Unit. Hospital de Terrassa (Consorci Sanitari de Terrassa). 23 Ctra. Torrebonica s/n. 08227 Terrassa, Spain 24 e-mail: 12088eea@comb.cat 25 Telephone: 34-937839488 26 Fax: 34-937003614 27 28 AAC Accepted Manuscript Posted Online 27 August 2018 Antimicrob. Agents Chemother. doi:10.1128/AAC.00978-18 Copyright