Publications by authors named "Miguel Montejo"

84 Publications

Efficacy and safety of oral fosfomycin for asymptomatic bacteriuria in kidney transplant recipients: Results from a Spanish multicenter cohort.

Antimicrob Agents Chemother 2021 Feb 8. Epub 2021 Feb 8.

Unit of Infectious Diseases, University Hospital "12 de Octubre", Instituto de Investigación Biomédica Hospital "12 de Octubre" (imas12), Madrid, Spain.

Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR]: 1.1 - 10.5). Most episodes (96.4% [132/137]) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum β-lactamase-producing [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [95%CI]: 31.9 - 48.9) for the whole cohort and 42.3% (95%CI: 31.2 - 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR]: 2.42; 95%CI: 1.11 - 5.29; -value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 - 41.35; -value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.
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http://dx.doi.org/10.1128/AAC.02267-20DOI Listing
February 2021

Oral decontamination with colistin plus neomycin in solid organ transplant recipients colonized by multidrug-resistant Enterobacterales: a multicentre, randomized, controlled, open-label, parallel-group clinical trial.

Clin Microbiol Infect 2020 Dec 24. Epub 2020 Dec 24.

Quality Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.

Objectives: To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients.

Methods: Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed.

Results: MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24-2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea.

Conclusions: DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.
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http://dx.doi.org/10.1016/j.cmi.2020.12.016DOI Listing
December 2020

Invasive Fusariosis in Nonneutropenic Patients, Spain, 2000-2015.

Emerg Infect Dis 2021 Jan;27(1)

Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000-2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000-2009 to 0.22 cases per 100,000 admissions in 2010-2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.
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http://dx.doi.org/10.3201/eid2701.190782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774531PMC
January 2021

Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients.

Cell Rep Med 2020 Nov 3;1(8):100130. Epub 2020 Nov 3.

Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.

Hemagglutination-inhibitory antibodies are usually highly strain specific with little effect on infection with drifted or shifted strains. The significance of broadly cross-reactive non-HAI anti-influenza antibodies against conserved domains of virus glycoproteins, such as the hemagglutinin (HA) stalk, is of great interest. We characterize a cohort of 40 H1N1pmd09 influenza-infected patients and identify lower respiratory symptoms (LRSs) as a predictor for development of pneumonia. A binomial logistic regression of log10 pre-existing antibody values shows that the probability of LRS occurrence decreased with increased anti-HA full-length and stalk antibody ELISA titers. However, a multilevel logistic regression model adjusted by other potential serocorrelates demonstrates that only antibodies directed against the stalk of HA correlate with protection from lower respiratory infection, limiting disease progression. Our predictive model indicates that a threshold of protective immunity based on broadly cross-reactive HA stalk antibodies could be feasible.
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http://dx.doi.org/10.1016/j.xcrm.2020.100130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691380PMC
November 2020

Efficacy of β-lactam/β-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

Transpl Infect Dis 2020 Nov 22:e13520. Epub 2020 Nov 22.

Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.

Background: Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear.

Methods: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively.

Results: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes.

Conclusions: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
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http://dx.doi.org/10.1111/tid.13520DOI Listing
November 2020

Effect of Influenza Vaccination Inducing Antibody Mediated Rejection in Solid Organ Transplant Recipients.

Front Immunol 2020 6;11:1917. Epub 2020 Oct 6.

National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.

Introduction: Our goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR).

Methods: Serum anti-Human Leukocyte Antigen (HLA) antibodies were determined using class I and class II antibody-coated latex beads (FlowPRA Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch.

Results: We studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%; = 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA.

Conclusion: Our results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR.
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http://dx.doi.org/10.3389/fimmu.2020.01917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574595PMC
October 2020

Pretransplant CMV-Specific T-Cell Immunity But Not Dose of Antithymocyte Globulin Is Associated With Recovery of Specific Immunity After Kidney Transplantation.

J Infect Dis 2021 Apr;223(7):1205-1213

Maimónides Institute for Biomedical Research of Cordoba (IMIBIC), Reina Sofía University Hospital, University of Cordoba, Cordoba, Spain.

Background: This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG.

Methods: CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-γ [IFN-γ] ≥ 0.2 IU/mL) indicated a positive CMV-CMI.

Results: A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-γ level (>12 IU/mL vs ≤12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1-53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-γ level ≤12 IU/mL.

Conclusions: More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-γ level, but not the ATG dose, shows a strong association with the kinetics of this recovery.
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http://dx.doi.org/10.1093/infdis/jiaa503DOI Listing
April 2021

Four weeks versus six weeks of ampicillin plus ceftriaxone in Enterococcus faecalis native valve endocarditis: A prospective cohort study.

PLoS One 2020 3;15(8):e0237011. Epub 2020 Aug 3.

Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Enterococcus faecalis infective endocarditis (EFIE) is a severe disease of increasing incidence. The objective was to analyze whether the outcome of patients with native valve EFIE (NVEFIE) treated with a short course of ampicillin plus ceftriaxone (4wAC) was similar to patients treated according to international guidelines (6wAC). Between January 2008 and June 2018, 1,978 consecutive patients with definite native valve IE were prospectively included in a national registry. Outcomes of patients with NVEFIE treated with 4wAC were compared to those of patients who received 6wAC. Three hundred and twenty-two patients (16.3%) had NVEFIE. One hundred and eighty-three (56.8%) received AC. Thirty-nine patients (21.3%) were treated with 4wAC for four weeks and 70 patients (38.3%) with 6wAC. There were no differences in age or comorbidity. Patients treated 6wAC presented a longer duration of symptoms before diagnosis (21 days, IQR 7-60 days vs. 7 days, IQR 1-22 days; p = 0.002). Six patients presented perivalvular abscess and all of these received 6wAC. Surgery was performed on 14 patients (35.9%) 4wAC and 34 patients (48.6%) 6wAC (p = 0.201). In-hospital mortality, one-year mortality and relapses among 4wAC and 6wAC patients were 10.3% vs. 11.4% (p = 0.851); 17.9% vs. 21.4% (p = 0.682) and 5.1% vs. 4.3% (p = 0.833), respectively. In conclusion, a four-week course of AC may be considered as an alternative regimen in NVEFIE, notably in patients with shorter duration of symptoms and those without perivalvular abscess. These results support the performance of a randomized clinical trial to evaluate the efficacy of this short regimen.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237011PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398509PMC
October 2020

Daptomycin plus Fosfomycin versus Daptomycin Alone for Methicillin-Resistant Staphylococcus aureus Bacteremia and Endocarditis. A Randomized Clinical Trial.

Clin Infect Dis 2020 Jul 29. Epub 2020 Jul 29.

Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut Investigacions Biomèdiques de Bellvitge (IDIBELL), University of Barcelona, Barcelona, Spain.

Background: We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis.

Methods: A randomized (1:1) phase III superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg of daptomycin intravenously per kilogram daily plus 2 g of fosfomycin intravenously every six hours, or 10 mg of daptomycin intravenously per kilogram daily. Primary endpoint was treatment success six weeks after the end of therapy.

Results: Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at six weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs. 42.0%; relative risk: 1.29, 95%CI 0.93 to 1.8, p=0.135). At six weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs. 9 patients, p=0.003) and lower complicated bacteremia (16.2% vs. 32.1%; p=0.022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in four of 81 patients (4.9%) receiving daptomycin alone (p=0.018).

Conclusion: Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events.
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http://dx.doi.org/10.1093/cid/ciaa1081DOI Listing
July 2020

Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts.

Crit Care 2020 03 26;24(1):117. Epub 2020 Mar 26.

Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia.

Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3).

Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02).

Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.
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http://dx.doi.org/10.1186/s13054-020-2793-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099832PMC
March 2020

A New Clinical and Immunovirological Score for Predicting the Risk of Late Severe Infection in Solid Organ Transplant Recipients: The CLIV Score.

J Infect Dis 2020 07;222(3):479-487

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre," Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain.

Background: We aimed at constructing a composite score based on Epstein-Barr virus DNAemia (EBVd) and simple clinical and immunological parameters to predict late severe infection (LI) beyond month 6 in solid organ transplantation (SOT) recipients.

Methods: Kidney and liver transplant recipients between May 2014 and August 2016 at 4 participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole blood EBVd were determined at months 1, 3, and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI.

Results: Overall, 309 SOT recipients were followed-up for a median of 1000 days from transplant (interquartile range, 822-1124). Late severe infection occurred in 104 patients (33.6%). The CLIV Score consisted of the following variables at month 6: high-level EBVd (>1500 IU/mL) and recurrent infection during the previous months (6 points); recipient age ≥70 years and chronic graft dysfunction (5 points); cytomegalovirus mismatch (4 points); and CD8+ T-cell count <400 cells/μL (2 points). The area under receiver operating characteristics curve was 0.77 (95% confidence interval, 0.71-0.84). The risk of LI at day 1000 was as follows: score 0, 12.6%; score 2-5, 25.5%; score 6-9, 52.7%; score ≥10, 73.5%.

Conclusions: While waiting for further external validation, the CLIV Score based on clinical and immune-virological parameters is potentially useful to stratify the risk of LI after SOT.
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http://dx.doi.org/10.1093/infdis/jiaa090DOI Listing
July 2020

A Contemporary Picture of Enterococcal Endocarditis.

J Am Coll Cardiol 2020 02;75(5):482-494

Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, Spain. Electronic address:

Background: Enterococcal endocarditis (EE) is a growing entity in Western countries. However, quality data from large studies is lacking.

Objectives: The purpose of this study was to describe the characteristics and analyze the prognostic factors of EE in the GAMES cohort.

Methods: This was a post hoc analysis of a prospectively collected cohort of patients from 35 Spanish centers from 2008 to 2016. Characteristics and outcomes of 516 cases of EE were compared with those of 3,308 cases of nonenterococcal endocarditis (NEE). Logistic regression and Cox proportional hazards regression analysis were performed to investigate risk factors for in-hospital and 1-year mortality, as well as relapses.

Results: Patients with EE were significantly older; more frequently presented chronic lung disease, chronic heart failure, prior endocarditis, and degenerative valve disease; and had higher median age-adjusted Charlson score. EE more frequently involved the aortic valve and prosthesis (64.3% vs. 46.7%; p < 0.001; and 35.9% vs. 28.9%; p = 0.002, respectively) but less frequently pacemakers/defibrillators (1.5% vs. 10.5%; p < 0.001), and showed higher rates of acute heart failure (45% vs. 38.3%; p = 0.005). Cardiac surgery was less frequently performed in EE (40.7% vs. 45.9%; p = 0.024). No differences in in-hospital and 1-year mortality were found, whereas relapses were significantly higher in EE (3.5% vs. 1.7%; p = 0.035). Increasing Charlson score, LogEuroSCORE, acute heart failure, septic shock, and paravalvular complications were risk factors for mortality, whereas prior endocarditis was protective and persistent bacteremia constituted the sole risk factor for relapse.

Conclusions: Besides other baseline and clinical differences, EE more frequently affects prosthetic valves and less frequently pacemakers/defibrillators. EE presents higher rates of relapse than NEE.
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http://dx.doi.org/10.1016/j.jacc.2019.11.047DOI Listing
February 2020

An evidence-based bundle improves the quality of care and outcomes of patients with candidaemia.

J Antimicrob Chemother 2020 03;75(3):730-737

Hospital Clínic, IDIBAPS (Institut d'Investigacions biomèdiques Agust Pi i Sunyer), Universitat de Barcelona, Barcelona, Spain.

Background: Candidaemia is a leading cause of bloodstream infections in hospitalized patients all over the world. It remains associated with high mortality.

Objectives: To assess the impact of implementing an evidence-based package of measures (bundle) on the quality of care and outcomes of candidaemia.

Methods: A systematic review of the literature was performed to identify measures related to better outcomes in candidaemia. Eight quality-of-care indicators (QCIs) were identified and a set of written recommendations (early treatment, echinocandins in septic shock, source control, follow-up blood culture, ophthalmoscopy, echocardiography, de-escalation, length of treatment) was prospectively implemented. The study was performed in 11 tertiary hospitals in Spain. A quasi-experimental design before and during bundle implementation (September 2016 to February 2018) was used. For the pre-intervention period, data from the prospective national surveillance were used (May 2010 to April 2011).

Results: A total of 385 and 263 episodes were included in the pre-intervention and intervention groups, respectively. Adherence to all QCIs improved in the intervention group. The intervention group had a decrease in early (OR 0.46; 95% CI 0.23-0.89; P = 0.022) and overall (OR 0.61; 95% CI 0.4-0.94; P = 0.023) mortality after controlling for potential confounders.

Conclusions: Implementing a structured, evidence-based intervention bundle significantly improved patient care and early and overall mortality in patients with candidaemia. Institutions should embrace this objective strategy and use the bundle as a means to measure high-quality medical care of patients.
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http://dx.doi.org/10.1093/jac/dkz491DOI Listing
March 2020

Candidemia in solid organ transplant recipients in Spain: Epidemiological trends and determinants of outcome.

Transpl Infect Dis 2019 Dec 26;21(6):e13195. Epub 2019 Oct 26.

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid, Spain.

Background: Despite being considered a high-risk population for invasive fungal disease, specific features of candidemia among solid organ transplant (SOT) recipients remain poorly characterized.

Methods: We compiled prospective data from two multicenter studies on candidemia performed over two consecutive periods in Spain: the CANDIPOP Study (2010-2011) and the CANDI-Bundle Study (2016-2018). Episodes diagnosed in adult SOT recipients in 10 participating centers were included. Risk factors for clinical failure (all-cause 7-day mortality and/or persistent candidemia for ≥72 hours) and 30-day mortality were investigated by univariate analysis.

Results: We included 55 episodes of post-transplant candidemia (32 and 23 of which occurred during the first and second periods). Kidney (38.2%) and liver recipients (30.9%) were the most common populations. Candida albicans accounted for 27.3% of episodes. The proportion of C glabrata increased over time (18.8% vs 30.4% for the first and second periods). There were no differences in the rate of fluconazole non-susceptible isolates (50.0% vs 60.0%, respectively). Clinical failure and 30-day mortality occurred in 25.5% and 27.3% of episodes and were associated with the severity of candidemia (Pitt score and severe sepsis/septic shock). Kidney transplantation (unadjusted odds ratio [uOR]: 0.17; 95% confidence interval [CI]: 0.03-0.85; P-value = .020), early catheter removal (uOR: 0.15; 95% CI: 0.03-0.76; P-value = .013), and appropriate early antifungal therapy (uOR: 0.14; 95% CI: 0.02-0.89; P-value = .041) were protective for 30-day mortality.

Conclusions: High rates of non-albicans species and fluconazole non-susceptibility must be taken into account to optimize therapeutic management and outcomes in SOT recipients with candidemia.
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http://dx.doi.org/10.1111/tid.13195DOI Listing
December 2019

Oral fosfomycin for the treatment of lower urinary tract infections among kidney transplant recipients-Results of a Spanish multicenter cohort.

Am J Transplant 2020 02 28;20(2):451-462. Epub 2019 Oct 28.

Unit of Infectious Diseases, University Hospital, "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), School of Medicine, Universidad Complutense, Madrid, Spain.

Oral fosfomycin may constitute an alternative for the treatment of lower urinary tract infections (UTIs) in kidney transplant recipients (KTRs), particularly in view of recent safety concerns with fluroquinolones. Specific data on the efficacy and safety of fosfomycin in KTR are scarce. We performed a retrospective study in 14 Spanish hospitals including KTRs treated with oral fosfomycin (calcium and trometamol salts) for posttransplant cystitis between January 2005 and December 2017. A total of 133 KTRs developed 143 episodes of cystitis. Most episodes (131 [91.6%]) were produced by gram-negative bacilli (GNB), and 78 (54.5%) were categorized as multidrug resistant (including extended-spectrum β-lactamase-producing Enterobacteriaceae [14%] or carbapenem-resistant GNB [3.5%]). A median daily dose of 1.5 g of fosfomycin (interquartile range [IQR]: 1.5-2) was administered for a median of 7 days (IQR: 3-10). Clinical cure (remission of UTI-attributable symptoms at the end of therapy) was achieved in 83.9% (120/143) episodes. Among those episodes with follow-up urine culture, microbiological cure at month 1 was achieved in 70.2% (59/84) episodes. Percutaneous nephrostomy was associated with a lower probability of clinical cure (adjusted odds ratio: 10.50; 95% confidence interval: 0.98-112.29; P = 0.052). In conclusion, fosfomycin is an effective orally available alternative for treating cystitis among KTRs.
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http://dx.doi.org/10.1111/ajt.15614DOI Listing
February 2020

Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing.

PLoS One 2019 18;14(7):e0219701. Epub 2019 Jul 18.

Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Institute for Global Health, (ISGlobal), Barcelona, Spain.

Objetives: The aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance.

Methods: Using Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016.

Results: Among 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in <20% of the sequenced population, being located in the UL97 gene and conferring high-level resistance to ganciclovir. The presence of DRM by NGS was associated with lung transplantation (p = 0.050), the administration of prophylaxis (p = 0.039), a higher mean time between transplantation and suspicion of resistance (p = 0.038) and longer antiviral treatment duration before suspicion (p = 0.024). However, the latter was the only factor independently associated with the presence of DRM by NGS in the multivariate analysis (OR 2.24, 95% CI 1.03 to 4.87).

Conclusions: NGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219701PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638921PMC
March 2020

Biofilm formation by multidrug resistant Enterobacteriaceae strains isolated from solid organ transplant recipients.

Sci Rep 2019 06 20;9(1):8928. Epub 2019 Jun 20.

Instituto de Investigación Valdecilla-IDIVAL, Avd. Cardenal Herrera Oria, 39011, Santander, Spain.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant bacteria (MDR). In this study, the biofilm-forming capability of 209 MDR strains (Escherichia coli n = 106, Klebsiella pneumoniae n = 78, and Enterobacter spp. n = 25) isolated from rectal swabs in the first 48 hours before or after kidney (93 patients), liver (60 patients) or kidney/pancreas transplants (5 patients) were evaluated by using a microplate assay. Thirty-nine strains were isolated before transplant and 170 strains were isolated post-transplant. Overall, 16% of E. coli strains, 73% of K. pneumoniae strains and 4% Enterobacter strains showed moderate or strong biofilm production. Nine strains isolated from infection sites after transplantation were responsible of infections in the first month. Of these, 4 K. pneumoniae, 1 E. coli and 1 Enterobacter spp. strains isolated pre-transplant or post-transplant as colonizers caused infections in the post-transplant period. Our results suggest that in vitro biofilm formation could be an important factor for adhesion to intestine and colonization in MDR K. pneumoniae strains in SOT recipients, but this factor appears to be less important for MDR E. coli and Enterobacter spp.
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http://dx.doi.org/10.1038/s41598-019-45060-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586660PMC
June 2019

Role of age and comorbidities in mortality of patients with infective endocarditis.

Authors:
Carlos Armiñanzas Concepción Fariñas-Alvarez Jesús Zarauza Patricia Muñoz Víctor González Ramallo Manuel Martínez Sellés José Mª Miró Meda Juan Manuel Pericás Miguel Ángel Goenaga Guillermo Ojeda Burgos Regino Rodríguez Álvarez Laura Castelo Corral Juan Gálvez-Acebal Francisco Javier Martínez Marcos Maria Carmen Fariñas Fernando Fernández Sánchez Mariam Noureddine Gabriel Rosas Javier de la Torre Lima José Aramendi Elena Bereciartua María José Blanco Roberto Blanco María Victoria Boado Marta Campaña Lázaro Alejandro Crespo Josune Goikoetxea José Ramón Iruretagoyena Josu Irurzun Zuazabal Leire López-Soria Miguel Montejo Javier Nieto David Rodrigo David Rodríguez Regino Rodríguez Yolanda Vitoria Roberto Voces Mª Victoria García López Radka Ivanova Georgieva Guillermo Ojeda Isabel Rodríguez Bailón Josefa Ruiz Morales Ana María Cuende Tomás Echeverría Ana Fuerte Eduardo Gaminde Miguel Ángel Goenaga Pedro Idígoras José Antonio Iribarren Alberto Izaguirre Yarza Xabier Kortajarena Urkola Carlos Reviejo Rafael Carrasco Vicente Climent Patricio Llamas Esperanza Merino Joaquín Plazas Sergio Reus Nemesio Álvarez José María Bravo-Ferrer Laura Castelo José Cuenca Pedro Llinares Enrique Miguez Rey María Rodríguez Mayo Efrén Sánchez Dolores Sousa Regueiro Francisco Javier Martínez Mª Del Mar Alonso Beatriz Castro Dácil García Rosado Mª Del Carmen Durán Mª Antonia Miguel Gómez Juan Lacalzada Ibrahim Nassar Antonio Plata Ciezar José Mª Reguera Iglesias Víctor Asensi Álvarez Carlos Costas Jesús de la Hera Jonnathan Fernández Suárez Lisardo Iglesias Fraile Víctor León Arguero José López Menéndez Pilar Mencia Bajo Carlos Morales Alfonso Moreno Torrico Carmen Palomo Begoña Paya Martínez Ángeles Rodríguez Esteban Raquel Rodríguez García Mauricio Telenti Asensio Manuel Almela Juan Ambrosioni Manuel Azqueta Mercè Brunet Marta Bodro Ramón Cartañá Carlos Falces Guillermina Fita David Fuster Cristina García de la Mària Marta Hernández-Meneses Jaume Llopis Pérez Francesc Marco José M Miró Asunción Moreno David Nicolás Salvador Ninot Eduardo Quintana Carlos Paré Daniel Pereda Juan M Pericás José L Pomar José Ramírez Irene Rovira Elena Sandoval Marta Sitges Dolors Soy Adrián Téllez José M Tolosana Bárbara Vidal Jordi Vila Iván Adán Javier Bermejo Emilio Bouza Daniel Celemín Gregorio Cuerpo Caballero Antonia Delgado Montero Ana Fernández Cruz Ana García Mansilla Mª Eugenia García Leoni Víctor González Ramallo Martha Kestler Hernández Amaia Mari Hualde Mercedes Marín Manuel Martínez-Sellés Mª Cruz Menárguez Patricia Muñoz Cristina Rincón Hugo Rodríguez-Abella Marta Rodríguez-Créixems Blanca Pinilla Ángel Pinto Maricela Valerio Pilar Vázquez Eduardo Verde Moreno Isabel Antorrena Belén Loeches Alejandro Martín Quirós Mar Moreno Ulises Ramírez Verónica Rial Bastón María Romero Araceli Saldaña Jesús Agüero Balbín Cristina Amado Carlos Armiñanzas Castillo Ana Arnaiz García Manuel Cobo Belaustegui María Carmen Fariñas Concepción Fariñas-Álvarez Rubén Gómez Izquierdo Iván García Claudia González-Rico Manuel Gutiérrez-Cuadra José Gutiérrez Díez Marcos Pajarón José Antonio Parra Aurelio Sarralde Ramón Teira Jesús Zarauza Fernando Domínguez Pablo García Pavía Jesús González Beatriz Orden Antonio Ramos Tomasa Centella José Manuel Hermida José Luis Moya Pilar Martín-Dávila Enrique Navas Enrique Oliva Alejandro Del Río Soledad Ruiz Carmen Hidalgo Tenorio Manuel Almendro Delia Omar Araji José Miguel Barquero Román Calvo Jambrina Marina de Cueto Juan Gálvez Acebal Irene Méndez Isabel Morales Luis Eduardo López-Cortés Arístides de Alarcón Emilio García Juan Luis Haro José Antonio Lepe Francisco López Rafael Luque Luis Javier Alonso Pedro Azcárate José Manuel Azcona Gutiérrez José Ramón Blanco Lara García-Álvarez José Antonio Oteo Mercedes Sanz Natividad de Benito Mercé Gurguí Cristina Pacho Roser Pericas Guillem Pons M Álvarez A L Fernández Amparo Martínez A Prieto Benito Regueiro E Tijeira Marino Vega Andrés Canut Blasco José Cordo Mollar Juan Carlos Gainzarain Arana Oscar García Uriarte Alejandro Martín López Zuriñe Ortiz de Zárate José Antonio Urturi Matos Gloria García Domínguez Antonio Sánchez-Porto José Mª Arribas Leal Elisa García Vázquez Alicia Hernández Torres Ana Blázquez Gonzalo de la Morena Valenzuela Ángel Alonso Javier Aramburu Felicitas Elena Calvo Anai Moreno Rodríguez Paola Tarabini-Castellani Eva Heredero Gálvez Carolina Maicas Bellido José Largo Pau Mª Antonia Sepúlveda Pilar Toledano Sierra Sadaf Zafar Iqbal-Mirza Eva Cascales Alcolea Pilar Egea Serrano José Joaquín Hernández Roca Ivan Keituqwa Yañez Ana Peláez Ballesta Víctor Soriano Eduardo Moreno Escobar Alejandro Peña Monje Valme Sánchez Cabrera David Vinuesa García María Arrizabalaga Asenjo Carmen Cifuentes Luna Juana Núñez Morcillo Mª Cruz Pérez Seco Aroa Villoslada Gelabert Carmen Aured Guallar Nuria Fernández Abad Pilar García Mangas Marta Matamala Adell Mª Pilar Palacián Ruiz Juan Carlos Porres Begoña Alcaraz Vidal Nazaret Cobos Trigueros María Jesús Del Amor Espín José Antonio Giner Caro Roberto Jiménez Sánchez Amaya Jimeno Almazán Alejandro Ortín Freire Monserrat Viqueira González Pere Pericás Ramis Mª Ángels Ribas Blanco Enrique Ruiz de Gopegui Bordes Laura Vidal Bonet Mª Carmen Bellón Munera Elena Escribano Garaizabal Antonia Tercero Martínez Juan Carlos Segura Luque

Eur J Intern Med 2019 Jun 21;64:63-71. Epub 2019 Mar 21.

Complejo Hospitalario Universitario de Albacete Albacete, Spain.

Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality.

Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk.

Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality.

Conclusion: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group.
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http://dx.doi.org/10.1016/j.ejim.2019.03.006DOI Listing
June 2019

Antimicrobial management of Tropheryma whipplei endocarditis: the Spanish Collaboration on Endocarditis (GAMES) experience.

J Antimicrob Chemother 2019 06;74(6):1713-1717

Departamento de Enfermedades Infecciosas, Hospital Universitario San Pedro-Centro de investigación Biomédica de La Rioja (CIBIR), Logroño, Spain.

Objectives: Tropheryma whipplei has been detected in 3.5% of the blood culture-negative cases of endocarditis in Spain. Experience in the management of T. whipplei endocarditis is limited. Here we report the long-term outcome of the treatment of previously reported patients who were diagnosed with infective endocarditis (IE) caused by T. whipplei from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) and discuss potential options for antimicrobial therapy for IE caused by T. whipplei.

Patients And Methods: Seventeen patients with T. whipplei endocarditis were recruited between 2008 and 2014 in 25 Spanish hospitals. Patients were classified according to the therapeutic regimen: ceftriaxone and trimethoprim/sulfamethoxazole, doxycycline + hydroxychloroquine and other treatment options.

Results: Follow-up data were obtained from 14 patients. The median follow-up was 46.5 months. All patients completed the antibiotic treatment prescribed, with a median duration of 13 months. Six patients were treated with ceftriaxone and trimethoprim/sulfamethoxazole (median duration 13 months), four with doxycycline + hydroxychloroquine (median duration 13.8 months) and four with other treatment options (median duration 22.3 months). The follow-up after the end of the treatments was between 5 and 84 months (median 24 months).

Conclusions: All treatment lines were effective and well tolerated. Therapeutic failures were not detected during the treatment. None of the patients died or experienced a relapse during the follow-up. Only six patients received antibiotic treatment in accordance with guidelines. These data suggest that shorter antimicrobial treatments could be effective.
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http://dx.doi.org/10.1093/jac/dkz059DOI Listing
June 2019

A 5-Year Prospective Multicenter Evaluation of Influenza Infection in Transplant Recipients.

Clin Infect Dis 2018 10;67(9):1322-1329

Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.

Background: Seasonal influenza infection may cause significant morbidity and mortality in transplant recipients. The purpose of this study was to assess the epidemiology of symptomatic influenza infection posttransplant and determine risk factors for severe disease.

Methods: Twenty centers in the United States, Canada, and Spain prospectively enrolled solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT) recipients with microbiologically confirmed influenza over 5 consecutive years (2010-2015). Demographics, microbiology data, and outcomes were collected. Serial nasopharyngeal swabs were collected at diagnosis and upto 28 days, and quantitative polymerase chain reaction for influenza A was performed.

Results: We enrolled 616 patients with confirmed influenza (477 SOT; 139 HSCT). Pneumonia at presentation was in 134 of 606 (22.1%) patients. Antiviral therapy was given to 94.1% for a median of 5 days (range, 1-42 days); 66.5% patients were hospitalized and 11.0% required intensive care unit (ICU) care. The receipt of vaccine in the same influenza season was associated with a decrease in disease severity as determined by the presence of pneumonia (odds ratio [OR], 0.34 [95% confidence interval {CI}, .21-.55], P < .001) and ICU admission (OR, 0.49 [95% CI, .26-.90], P = .023). Similarly, early antiviral treatment (within 48 hours) was associated with improved outcomes. In patients with influenza A, pneumonia, ICU admission, and not being immunized were also associated with higher viral loads at presentation (P = .018, P = .008, and P = .024, respectively).

Conclusions: Annual influenza vaccination and early antiviral therapy are associated with a significant reduction in influenza-associated morbidity, and should be emphasized as strategies to improve outcomes of transplant recipients.
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http://dx.doi.org/10.1093/cid/ciy294DOI Listing
October 2018

Lack of evidence of association between IFNG and IL28B polymorphisms and QuantiFERON-CMV test results in seropositive transplant patients.

Hum Immunol 2018 Jun 29;79(6):499-505. Epub 2018 Mar 29.

Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Reina Sofía University Hospital/University of Cordoba, (REIPI RD12/0015 and REIPI RD16/0016/0008), Cordoba, Spain.

The aim of this study was to analyze the relationship between the IFNG +874 T/A and IL28B (rs12979860) C/T polymorphisms and the secretion of IFNG by CD8+ T cells after stimulation with cytomegalovirus (CMV) peptides, measured using QuantiFERON-CMV (QF-CMV) assay. A total of 184 CMV-seropositive solid organ transplant patients (108 kidney, 68 liver and 8 lung) were recruited. Of them, 151 patients were QF-CMV Reactive (IFNG ≥ 0.2 UI/mL) and 33 were Non-reactive. Genotype frequencies in the study population were TT (26.6%), AT (50.0%) and AA (23.4%) for IFNG +874 and CC (52.7%), CT (39.1%) and TT (8.2%) for IL28B (rs12979860). These frequencies did not significantly differ between QF-CMV Reactive and Non-reactive patients. Nor were any significant differences observed in the quantitative IFNG level among the genotypes in either the IFNG or the IL28 genes. When we analyzed whether these polymorphisms had any impact on the risk of CMV replication after transplantation, the adjusted analysis showed no association. In summary, our results showed that IFNG +874 T/A and IL28B (rs12979860) C/T polymorphisms are not associated with the IFNG response to CMV measured by the QuantiFERON-CMV assay, although these results should be confirmed with a higher number of patients.
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http://dx.doi.org/10.1016/j.humimm.2018.03.009DOI Listing
June 2018

Prognostic implications of a negative echocardiography in patients with infective endocarditis.

Eur J Intern Med 2018 06 4;52:40-48. Epub 2018 Feb 4.

Servicio de Cardiología, Hospital General Universitario Gregorio Marañón, CIBERCV, Madrid, Spain; Universidad Complutense and Universidad Europea, Madrid, Spain. Electronic address:

Background: Echocardiography plays an important role in infective endocarditis (IE) diagnosis according with the modified Duke criteria. We evaluated the implications of a positive echocardiography in the prognosis of a cohort of patients with IE.

Methods: Prospective multicentre study in 31 Spanish centres. From January 2008 to September 2016, 3467 patients were included (2765 definite IE, 702 possible IE). The main outcome was in-hospital mortality. Echocardiography diagnosis was based on modified Duke criteria for the diagnosis of IE.

Results: Median age was 69 years (interquartile range: 57-77 years). Comorbidity was high (mean Charlson index 4.7 ± 2.8). Transoesophageal echocardiography was performed in 2680 (77.3%). The overall inhospital mortality rate was 26.7%. Univariate analysis showed that, in patients with definite IE, inhospital mortality was similar in patients with positive and negative echocardiography (27.7% vs. 24.6%, respectively, p = 0.121). In possible IE these figures were 27.5% vs. 16.7%, respectively, p < 0.001. Complications (cardiac and extracardiac [embolic, immunological, and septic shock]) were more frequent with positive than with negative echocardiography, regardless of clinical suspicion (definite IE 35.5% vs. 16.8%, respectively, p < 0.001; possible IE 20.8% vs. 7.6%, respectively, p < 0.001). Positive echocardiography was a predictor of inhospital death by logistic regression modelling, after adjusting for confounders, definite IE (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.02-1.76, p = 0.036), possible IE (OR 1.59, 95% CI 1.02-2.45, p = 0.036).

Conclusions: A positive echocardiography in patients with IE is associated with increased inhospital mortality, in addition to other clinical factors and comorbidities.
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http://dx.doi.org/10.1016/j.ejim.2018.01.033DOI Listing
June 2018

Epidemiology and prognosis of candidaemia in elderly patients.

Mycoses 2017 Dec 23;60(12):808-817. Epub 2017 Aug 23.

Micology Department, Instituto de Salud Carlos III, Mahadahonda, Spain.

The aim of the study was to analyse the epidemiology and prognosis of candidaemia in elderly patients. We performed a comparison of clinical presentation of candidaemia according to age and a study of hazard factors within a prospective programme performed in 29 hospitals. One hundred and seventy-six episodes occurred in elderly patients (>75 years), 227 episodes in middle-aged patients (61-75 years) and 232 episodes in younger patients (16-60 years). Central venous catheter, parenteral nutrition, neutropenia, immunosuppressive therapy and candidaemia caused by Candida parapsilosis were less frequent in elderly patients. These patients received inadequate antifungal therapy (57.3%) more frequently than middle-aged and younger patients (40.5% P < .001). Mortality during the first week (20%) and 30 days (42%) was higher in elderly patients. The variables independently associated with mortality in elderly patients during the first 7 days were acute renal failure (OR: 2.64), Pitt score (OR: 1.57) and appropriate antifungal therapy (OR: 0.132). Primary candidaemia (OR: 2.93), acute renal failure (OR: 3.68), Pitt score (OR: 1.38), appropriate antifungal therapy (OR: 0.3) and early removal of the central catheter (OR: 0.47) were independently associated with 30-day mortality.In conclussion, inadequate antifungal treatment is frequently prescribed to elderly patients with candidaemia and is related with early and late mortality.
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http://dx.doi.org/10.1111/myc.12677DOI Listing
December 2017

Efficacy of β-Lactam/β-Lactamase Inhibitor Combinations for the Treatment of Bloodstream Infection Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Hematological Patients with Neutropenia.

Antimicrob Agents Chemother 2017 08 25;61(8). Epub 2017 Jul 25.

Infectious Diseases Department, Bellvitge University Hospital, IDIBELL, University of Barcelona, Spain.

β-Lactam/β-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-β-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients.
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http://dx.doi.org/10.1128/AAC.00164-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527609PMC
August 2017

A case-control study of non-AIDS-defining cancers in a prospective cohort of HIV-infected patients.

Med Clin (Barc) 2018 04 18;150(8):291-296. Epub 2017 May 18.

Servicio de Enfermedades Infecciosas, Hospital Universitario Donostia, San Sebastián, Guipúzcoa, España.

Introduction: We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality.

Methods: All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected.

Results: Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7,067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1,000 people-year. In addition to aging and smoking, time on ART (OR 1.11; 95% CI 1.05-1.17) and PI use (OR 1.72; 95% CI 1.0-2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99-1.0; P=.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08-3.92) were associated with higher mortality.

Conclusions: Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.
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http://dx.doi.org/10.1016/j.medcli.2017.03.032DOI Listing
April 2018

Impact of age and cytomegalovirus on CD8 T-cell compartment remodeling after solid organ transplantation: A one-year follow-up study.

Exp Gerontol 2017 09 29;95:98-106. Epub 2017 Apr 29.

Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain; Immunology Department, Reina Sofia University Hospital, Cordoba, Spain.

Cytomegalovirus (CMV), a member of the β-herpesvirus family, is a major complicating infection in transplant patients. CMV latency has a long-term impact on CD8 T-cell differentiation. It is unclear, however, whether this effect can be detected in one-year period. To investigate this, we analyzed the remodeling of the CD8 T-cell compartment during the first year after solid organ transplantation. A total of 55 kidney or lung transplant patients were recruited. CD8 T-cell subsets were prospectively analyzed at pretransplant, at 3 or 6months and 12months after transplantation (mo post-Tx). A significant increase in the frequency of CD27CD28CD8 T cells (from 32.8% to 42.3%; p=0.014) was observed from pretransplant to 12mo post-Tx. Further analysis, however, showed that the largest expansion was observed from 3/6 to 12mo post-Tx whereas small non-significant variations were observed from pretransplant to 3/6mo post-Tx. The adjusted analysis showed that age and CMV seropositivity were statistically associated with the baseline frequency of CD27CD28CD8 T cells. Additionally, CMV replication was related to the posttransplant expansion of this subpopulation, since it was not observed in patients without CMV viremia (24% vs. 4.2%). The results indicate that the expanded frequency associated with late CMV replication is additive to the baseline frequency related to aging and CMV seropositivity. If the expanded frequency remains at this high level for a long period it might have clinical consequences related to the control of future reactivations of CMV or of other related viruses.
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http://dx.doi.org/10.1016/j.exger.2017.04.011DOI Listing
September 2017

Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance.

J Clin Virol 2017 05 21;90:57-63. Epub 2017 Mar 21.

Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Barcelona Institute for Global Health, Barcelona, (ISGlobal), Spain. Electronic address:

Background: Current guidelines recommend that treatment of resistant cytomegalovirus (CMV) in solid organ transplant (SOT) recipients must be based on genotypic analysis. However, this recommendation is not systematically followed.

Objectives: To assess the presence of mutations associated with CMV resistance in SOT recipients with suspected resistance, their associated risk factors and the clinical impact of resistance.

Study Design: Using Sanger sequencing we prospectively assessed the presence of resistance mutations in a nation-wide prospective study between September 2013-August 2015.

Results: Of 39 patients studied, 9 (23%) showed resistance mutations. All had one mutation in the UL 97 gene and two also had one mutation in the UL54 gene. Resistance mutations were more frequent in lung transplant recipients (44% p=0.0068) and in patients receiving prophylaxis ≥6 months (57% vs. 17%, p=0.0180). The mean time between transplantation and suspicion of resistance was longer in patients with mutations (239 vs. 100days, respectively, p=0.0046) as was the median treatment duration before suspicion (45 vs. 16days, p=0.0081). There were no significant differences according to the treatment strategies or the mean CMV load at the time of suspicion. Of note, resistance-associated mutations appeared in one patient during CMV prophylaxis and also in a seropositive organ recipient. Incomplete suppression of CMV was more frequent in patients with confirmed resistance.

Conclusions: Our study confirms the need to assess CMV resistance mutations in any patient with criteria of suspected clinical resistance. Early confirmation of the presence of resistance mutations is essential to optimize the management of these patients.
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http://dx.doi.org/10.1016/j.jcv.2017.03.014DOI Listing
May 2017

Favorable longterm outcomes of liver transplant recipients treated de novo with once-daily tacrolimus: Results of a single-center cohort.

Liver Transpl 2016 10;22(10):1391-400

Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain.

The once-daily prolonged-release formulation of tacrolimus has been recently related with significant graft and patient mid-term survival advantages; however, practical information on the de novo administration after liver transplantation and longterm outcomes is currently lacking. This study is a 5-year retrospective analysis of a single-center cohort of liver transplant recipients treated de novo with once-daily tacrolimus (April 2008/August 2011). The study cohort consisted of 160 patients, including 23 with pretransplant renal dysfunction, with a median follow-up of 57.6 months (interquartile range, 46.6-69.0). Tacrolimus target trough levels were 5-10 ng/mL during the first 3 months after transplant, reducing progressively to <7 ng/mL after the first posttransplant year. Once-daily tacrolimus was withdrawn in 35 (21.8%) patients during follow-up, mostly due to renal dysfunction and/or metabolic syndrome. The biopsy-proven acute rejection rate was 12.5% with no cases of steroid-resistant rejection. The cumulative incidence of de novo diabetes, hypertension, and dyslipidemia were 16.9%, 31.2%, and 6.5%, respectively. Hepatocellular carcinoma recurrence rate was 2.8%. Renal function remained stable after the sixth month after transplant with a mean estimated glomerular filtration rate of 77.7 ± 19.6 mL/minute/1.73 m(2) at 5 years. None of our patients developed chronic kidney disease stage 4 or 5. Patient survival at 1, 3, and 5 years was 96.3%, 91.9%, and 88.3%, respectively. Overall survival of patients with Model for End-Stage Liver Disease (MELD) score > 25 points was not significantly different. In conclusion, our study suggests that immunosuppression based on de novo once-daily tacrolimus is feasible in routine clinical practice, showing favorable outcomes and outstanding longterm survival even in patients with high MELD scores. Liver Transplantation 22 1391-1400 2016 AASLD.
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http://dx.doi.org/10.1002/lt.24514DOI Listing
October 2016