Publications by authors named "Francesc Marco"

144 Publications

Clinical Characteristics and Outcome of Bloodstream Infections in HIV-Infected Patients with Cancer and Febrile Neutropenia: A Case-Control Study.

Infect Dis Ther 2021 Apr 11. Epub 2021 Apr 11.

Infectious Diseases Department, Hospital Clinic-IDIBAPS, Carrer de Villarroel 170, 08036, Barcelona, Spain.

Introduction: We aimed to compare the clinical characteristics and outcomes of bloodstream infections (BSI) in cancer patients presenting febrile neutropenia with and without HIV infection, and analyze the prognostic factors for mortality.

Methods: BSI episodes in febrile neutropenic patients following chemotherapy were prospectively collected (1997-2018). A case (HIV-infected)-control (non-HIV-infected) sub-analysis was performed (1:2 ratio), matching patients by age, gender, baseline disease, and etiological microorganism.

Results: From 1755 BSI episodes in neutropenic cancer patients, 60 (3.4%) occurred in those with HIV. HIV characteristics: 51.7% were men who have sex with men; 58.3% had < 200 CD4; 51.7% had a detectable HIV-1 RNA viral load before the BSI episode; 70.0% met AIDS-defining criteria; and 93.3% were on antiretroviral therapy, with a protease inhibitor-based regimen being the most common (53.0%). HIV-infected patients were younger, more frequently male and more commonly presenting chronic liver disease (p < 0.001 for all). BSI due to Enterococcus spp. was significantly more frequent among patients with HIV (p = 0.017) with no differences in other pathogens. HIV-infected patients with cancer presented with shock more frequently (p = 0.014) and had higher mortality (31.7% vs. 18.1%, p = 0.008). In the case-control analysis, cases (HIV-infected) had chronic liver disease (p = 0.003) more frequently, whereas acute leukemia (p = 0.013) and hematopoietic stem-cell transplant (p = 0.023) were more common among controls. There was a non-significant trend for cases to have higher mortality (p = 0.084). However, in multivariate analysis, HIV infection was not associated with mortality (p = 0.196).

Conclusion: HIV-infected patients with cancer developing febrile neutropenia and BSI have different epidemiological and clinical profiles, and experience higher mortality. However, HIV infection by itself was not associated with mortality.
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http://dx.doi.org/10.1007/s40121-021-00445-3DOI Listing
April 2021

Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis.

J Antimicrob Chemother 2021 Apr 9. Epub 2021 Apr 9.

Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); University of Barcelona, Barcelona, Spain.

Objectives: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits.

Methods: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400.

Results: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains.

Conclusions: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE.
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http://dx.doi.org/10.1093/jac/dkab069DOI Listing
April 2021

High prevalence and mortality due to Histoplasma capsulatum in the Brazilian Amazon: An autopsy study.

PLoS Negl Trop Dis 2021 Apr 5;15(4):e0009286. Epub 2021 Apr 5.

Department of Pathology, ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.

Background: Histoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions.

Methodology: We conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization of Histoplasma strains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation.

Principal Findings: Evidence of Histoplasma infection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patients Histoplasma DNA was detected by PCR in patients with no histological lesions. Histoplasma infection was detected in 38% of HIV-positive patients and was a major contributor to death in 22% of them. Lungs, liver and spleen were affected in all cases of disseminated histoplasmosis. Phylogenetic analysis of the strains suggested a high diversity of Histoplasma species circulating in the Brazilian Amazon. Histoplasmosis was clinically missed in 75% of the disseminated infections. In conclusion, substantial mortality is associated with disseminated histoplasmosis among HIV-positive patients in the Brazilian Amazon.

Conclusions: The high incidence of histoplasmosis, the low index of clinical suspicion, and the severity of the disseminated disease highlight the need of proactively implementing sensitive routine screening methods for this pathogen in endemic areas. Antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas.
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http://dx.doi.org/10.1371/journal.pntd.0009286DOI Listing
April 2021

Antibiotic-resistant microorganisms in patients with bloodstream infection of intraabdominal origin: risk factors and impact on mortality.

Infection 2021 Mar 16. Epub 2021 Mar 16.

Department of Infectious Diseases, Hospital Clínic de Barcelona - IDIBAPS, Barcelona, Spain.

Background: Knowledge of resistance patterns is essential to choose empirical treatment. We aimed to determine the risk factors for antibiotic-resistant microorganisms (ARM) in intraabdominal infections (IAI) and their impact on mortality.

Methods: Retrospective cohort study of patients with bacteremia from IAI origin in a single hospital between January 2006 and July 2017.

Results: A total of 1485 episodes were recorded, including 381 (25.6%) due to ARM. Independent predictors of ARM were cirrhosis (OR 2; [95% CI 1.15-3.48]), immunosuppression (OR 1.49; 1.12-1.97), prior ceftazidime exposure (OR 3.7; 1.14-11.9), number of prior antibiotics (OR 2.33; 1.61-3.35 for 1 antibiotic), biliary manipulation (OR 1.53; 1.02-2.96), hospital-acquisition (OR 2.77; 1.89-4) and shock (OR 1.48; 1.07-2). Mortality rate of the whole cohort was 11.1%. Age (OR 1.03; 1.01-1.04), cirrhosis (OR 2.32; 1.07-4.38), urinary catheter (OR 1.99; 1.17-3.38), ultimately (OR 2.28; 1.47-3.51) or rapidly (OR 13.3; 7.12-24.9) fatal underlying disease, nosocomial infection (OR 2.76; 1.6-4.75), peritonitis (OR 1.95, 1.1-3.45), absence of fever (OR 2.17; 1.25-3.77), shock (OR 5.96; 3.89-9.13), and an ARM in non-biliary infections (OR 2.14; 1.19-3.83) were independent predictors of 30-day mortality. Source control (OR 0.24; 0.13-0.44) and 2015-2017 period (OR 0.29; 0.14-0.6) were protective.

Conclusion: Biliary manipulation and septic shock are predictors of ARM. The presence of an ARM from a non-biliary focus is a poor-prognosis indicator. Source control continues to be of paramount importance.
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http://dx.doi.org/10.1007/s15010-021-01592-yDOI Listing
March 2021

Factors Associated With Short-Term Eradication of Rectal Colonization by KPC-2 Producing in an Outbreak Setting.

Front Microbiol 2021 1;12:630826. Epub 2021 Feb 1.

Service of Infectious Diseases, Hospital Clínic de Barcelona, Barcelona, Spain.

KPC-producing (KPCKP) is a threat for patients admitted to healthcare institutions. To assess the efficacy of several decolonization strategies for KPCKP rectal carriage. Observational study performed in a 750-bed university center from July to October 2018 on the efficacy of a 10-day non-absorbable oral antibiotic (NAA) regimen (colistin 10 mg/ml, amikacin 8 mg/ml, and nystatin 30 mg/ml, 10 ml/6 h) vs. the same regimen followed by a probiotic (Vivomixx®) for 20 days in adult patients with KPCKP rectal colonization acquired during an outbreak. Seventy-three patients colonized by KPCKP were included, of which 21 (29%) did not receive any treatment and 52 (71.2%) received NAA either alone ( = 26, 35.6%) or followed by a probiotic ( = 26, 35.6%). Eradication was observed in 56 (76.7%) patients and the only variable significantly associated with it was not receiving systemic antibiotics after diagnosis of rectal carriage [22/24 (91.6%) vs. 34/49 (69.3%), = 0.04]. Eradication in patients receiving NAA plus probiotic was numerically but not significantly higher than that of controls [23/26 (88.4%) vs. 15/21 (71.4%), = 0.14] and of those receiving only NAA (OR = 3.4, 95% CI = 0.78-14.7, = 0.09). In an outbreak setting, rectal carriage of KPCKP persisted after a mean of 36 days in about one quarter of patients. The only factor associated with eradication was not receiving systemic antibiotic after diagnosis. A 10-day course of NAA had no impact on eradication. Probiotics after NAA may increase the decolonization rate, hence deserving further study.
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http://dx.doi.org/10.3389/fmicb.2021.630826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882481PMC
February 2021

Salvage Treatment with Cefiderocol Regimens in Two Intravascular Foreign Body Infections by MDR Gram-Negative Pathogens, Involving Non-Removable Devices.

Infect Dis Ther 2021 Mar 8;10(1):575-581. Epub 2021 Jan 8.

Department of Infectious Diseases, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Introduction: The objective of this study was to describe two challenging cases of intravascular foreign body infections caused by multidrug-resistant Gram-negative pathogens requiring complex antimicrobial regimens including cefiderocol and successfully treated without implant removal.

Methods: Clinical charts and microbiological reports of the clinical cases.

Results: Case 1 included a left ventricular assist device (HEARTMATE 3™Abbot) infection due to Achromobacter xylosoxidans, while case 2 included a portal prosthesis infection due to Pseudomonas aeruginosa. As the pathogens were multidrug-resistant (MDR), both cases required antimicrobial regimens with cefiderocol; treatment was successful without implant removal. Importantly, case 1 presented a probable, drug-induced thrombocytopenia, a non-previously described side effect related to cefiderocol.

Conclusion: Cefiderocol may be an additional, promising drug to the available arsenal, even for challenging foreign body infections caused by MDR Gram-negative pathogens.
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http://dx.doi.org/10.1007/s40121-020-00385-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955010PMC
March 2021

Dissemination of NDM-producing Klebsiella pneumoniae and Escherichia coli high-risk clones in Catalan healthcare institutions.

J Antimicrob Chemother 2021 Jan;76(2):345-354

Laboratory of Antimicrobial Resistance, ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.

Objectives: To characterize the clonal spread of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates between different healthcare institutions in Catalonia, Spain.

Methods: Antimicrobial susceptibility was tested by disc diffusion. MICs were determined by gradient diffusion or broth microdilution. Carbapenemase production was confirmed by lateral flow. PCR and Sanger sequencing were used to identify the allelic variants of resistance genes. Clonality studies were performed by PFGE and MLST. Plasmid typing, conjugation assays, S1-PFGE plus Southern blotting and MinION Oxford Nanopore sequencing were used to characterize resistance plasmids.

Results: Twenty-nine carbapenem-resistant isolates recovered from three healthcare institutions between January and November 2016 were included: 14 K. pneumoniae isolates from a tertiary hospital in the south of Catalonia (hospital A); 2 K. pneumoniae isolates from a nearby healthcare centre; and 12 K. pneumoniae isolates and 1 E. coli isolate from a tertiary hospital in Barcelona (hospital B). The majority of isolates were resistant to all antimicrobial agents, except colistin, and all were NDM producers. PFGE identified a major K. pneumoniae clone (n = 27) belonging to ST147 and co-producing NDM-1 and CTX-M-15, with a few isolates also harbouring blaOXA-48. Two sporadic isolates of K. pneumoniae ST307 and E. coli ST167 producing NDM-7 were also identified. blaNDM-1 was carried in two related IncR plasmid populations and blaNDM-7 in a conjugative 50 kb IncX3 plasmid.

Conclusions: We report the inter-hospital dissemination of XDR high-risk clones of K. pneumoniae and E. coli associated with the carriage of small, transferable plasmids harbouring blaNDM genes.
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http://dx.doi.org/10.1093/jac/dkaa459DOI Listing
January 2021

Adherence to Human Colon Cells by Multidrug Resistant Strains Isolated From Solid Organ Transplant Recipients With a Focus on .

Front Cell Infect Microbiol 2020 16;10:447. Epub 2020 Sep 16.

Instituto de Investigación Valdecilla-IDIVAL, Santander, Spain.

Enterobacteria species are common causes of hospital-acquired infections, which are associated with high morbidity and mortality rates. Immunocompromised patients such as solid organ transplant (SOT) recipients are especially at risk because they are frequently exposed to antibiotics in the course of their treatments. In this work, we used a collection of 106 , 78 , 25 spp., and 24 spp. multidrug resistant strains isolated from transplant patients (hepatic, renal or renal/pancreatic) in order to examine their ability to adhere to HT-29 human colon cells, and to determine if some adhesive characteristics are associated with prevalence and persistence of these strains. A total of 33 (31%), 21 (27%), 7 spp. (28%), and 5 spp. (21%), adhered to the colon epithelial cells. Two main adherence patterns were observed in the four species analyzed, diffuse adherence, and aggregative adherence. Under transmission electronic microscopy (TEM), most bacteria lacked visible fimbria on their surface, despite their strong adherence to epithelial cells. None of the strains studied was able to induce any cytotoxic effect on HT-29 cells although some of them strongly colonizing both cells and glass coverslips at high density. Some of the strains failed to adhere to the epithelial cells but adhered strongly to the cover-slide, which shows that microscopy studies are mandatory to elucidate the adherence of bacteria to epithelial cells , and that quantitative assays using colony forming unit (CFUs) counting need to be supplemented with pictures to determine definitively if a bacterial strain adheres or not to animal cells . We report here, for the first time, the aggregative adherence pattern of two multidrug resistant (MDR) strains isolated from human patients; importantly, biofilm formation in is totally dependent on the temperature; strong biofilms were formed at room temperature (RT) but not at 37°C, which can play an important role in the colonization of hospital surfaces. In conclusion, our results show that there is a great variety of adhesion phenotypes in multidrug-resistant strains that colonize transplanted patients.
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http://dx.doi.org/10.3389/fcimb.2020.00447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525035PMC
September 2020

Cloxacillin or fosfomycin plus daptomycin combinations are more active than cloxacillin monotherapy or combined with gentamicin against MSSA in a rabbit model of experimental endocarditis.

J Antimicrob Chemother 2020 12;75(12):3586-3592

Hospital Clínic - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Background: In vitro and in vivo activity of daptomycin alone or plus either cloxacillin or fosfomycin compared with cloxacillin alone and cloxacillin plus gentamicin were evaluated in a rabbit model of MSSA experimental endocarditis (EE).

Methods: Five MSSA strains were used in the in vitro time-kill studies at standard (105-106 cfu/mL) and high (108 cfu/mL) inocula. In the in vivo EE model, the following antibiotic combinations were evaluated: cloxacillin (2 g/4 h) alone or combined with gentamicin (1 mg/kg/8 h) or daptomycin (6 mg/kg once daily); and daptomycin (6 mg/kg/day) alone or combined with fosfomycin (2 g/6 h).

Results: At standard and high inocula, daptomycin plus fosfomycin or cloxacillin were bactericidal against 4/5 and 5/5 strains, respectively, while cloxacillin plus gentamicin was bactericidal against 3/5 strains at standard inocula but against none at high inocula. Fosfomycin, cloxacillin, gentamicin and daptomycin MIC/MBCs of the MSSA-678 strain used in the EE model were: 8/64, 0.25/0.5, 0.25/0.5 and 1/8 mg/L, respectively. Adding gentamicin to cloxacillin significantly reduced bacterial density in vegetations compared with cloxacillin monotherapy (P = 0.026). Adding fosfomycin or cloxacillin to daptomycin [10/11 (93%) and 8/11 (73%), respectively] significantly improved the efficacy of daptomycin in sterilizing vegetations [0/11 (0%), P < 0.001 for both combinations] and showed better activity than cloxacillin alone [0/10 (0%), P < 0.001 for both combinations] and cloxacillin plus gentamicin [3/10 (30%), P = 0.086 for cloxacillin plus daptomycin and P = 0.008 for fosfomycin plus daptomycin]. No recovered isolates showed increased daptomycin MIC.

Conclusions: The addition of cloxacillin or fosfomycin to daptomycin is synergistic and rapidly bactericidal, showing better activity than cloxacillin plus gentamicin for treating MSSA EE, supporting their clinical use.
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http://dx.doi.org/10.1093/jac/dkaa354DOI Listing
December 2020

Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study.

Clin Microbiol Infect 2021 Jan 31;27(1):83-88. Epub 2020 Jul 31.

Department of Infectious Diseases, Hospital Clinic of Barcelona, IDIBAPS, Barcelona, Spain.

Objectives: To describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19).

Methods: We performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records.

Results: Of a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes.

Conclusions: Co-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies.
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http://dx.doi.org/10.1016/j.cmi.2020.07.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836762PMC
January 2021

Evaluation of Vitek-MS™ and Microflex LT™ commercial systems for identification of Acinetobacter calcoaceticus-baumannii complex.

Enferm Infecc Microbiol Clin 2021 Jan 16;39(1):9-13. Epub 2020 Apr 16.

Unit of Microbiology, University Hospital Reina Sofia, Cordoba, Spain; Department of Microbiology, University of Cordoba, Cordoba, Spain; Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Spain.

Introduction: Acinetobacter is a genus that comprises a group of opportunistic pathogens responsible for a variety of nosocomial infections. The Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex includes some species of clinical importance, mainly A. baumannii, A. pittii and A. nosocomialis, which share phenotypic similarities that make it very difficult to distinguish between them using a phenotypic approach. The aim of this study was to evaluate two commercial matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems for the identification of different Acinetobacter species, with a special focus among those belonging to the Acb complex.

Methods: One hundred and fifty-six Acinetobacter spp. clinical strains, identified by amplified ribosomal DNA restriction analysis (ARDRA) and rpoB gene sequencing, were analysed by two different MALDI-TOF systems.

Results: Considering only the 144 strains of the Acb complex evaluated in this study, the Vitek-MS™ and Microflex LT™ systems correctly identified 129 (89.6%) and 143 (99.3%) strains, respectively.

Conclusion: After analysing 156 strains belonging to Acinetobacter spp., both Vitek-MS™ and Microflex LT™ proved to be rapid and accurate systems for the identification of Acb complex species showing a good correlation. However, both manufacturers should improve their databases to include new species in them.
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http://dx.doi.org/10.1016/j.eimc.2020.02.028DOI Listing
January 2021

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

Assessment of a Loop-Mediated Isothermal Amplification (LAMP) Assay for the Rapid Detection of Pathogenic Bacteria from Respiratory Samples in Patients with Hospital-Acquired Pneumonia.

Microorganisms 2020 Jan 11;8(1). Epub 2020 Jan 11.

Department of Clinical Microbiology, CDB, Hospital Clínic of Barcelona, University of Barcelona, 08036 Barcelona, Spain.

Rapid identification of the causative agent of hospital-acquired pneumonia (HAP) will allow an earlier administration of a more appropriate antibiotic and could improve the outcome of these patients. The aim of this study was to develop a rapid protocol to identify the main microorganisms involved in HAP by loop-mediated isothermal amplification (LAMP) directly from respiratory samples. First of all, a rapid procedure (<30 min) to extract the DNA from bronchoalveolar lavage (BAL), endotracheal aspirate (EA) or bronchoaspirate (BAS) was set up. A specific LAMP for , , , and was performed with the extracted solution at 65 °C for 30-40 min. Overall, 58 positive BAL and 83 EA/BAS samples were tested. The limits of detection varied according to the microorganism detected. Validation of the LAMP assay with BAL samples showed that the assay was 100% specific and 86.3% sensitive (positive predictive value of 100% and a negative predictive value of 50%) compared with culture. Meanwhile for BAS/EA samples, the assay rendered the following statistical parameters: 100% specificity, 94.6% sensitivity, 100% positive predictive value and 69.2% negative predictive value. The turnaround time including sample preparation and LAMP was circa 1 h. LAMP method may be used to detect the most frequent bacteria causing HAP. It is a simple, cheap, sensitive, specific and rapid assay.
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http://dx.doi.org/10.3390/microorganisms8010103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022425PMC
January 2020

Relationship between Vancomycin MIC and Virulence Gene Expression in Clonal Complexes of Methicillin-Susceptible Staphylococcus aureus Strains Isolated from Left-Sided Endocarditis.

Antimicrob Agents Chemother 2020 02 21;64(3). Epub 2020 Feb 21.

Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain

Higher vancomycin MICs have been associated with more complicated courses and higher mortality rates in patients with bacteremia and infective endocarditis (IE). The aim of this study was to investigate whether the strains belonging to the cohort of 93 patients from a previously published study in which patients with strains with vancomycin MICs of ≥1.5 μg/ml presented higher mortality rates and systemic emboli than patients with strains with vancomycin MICs of <1.5 μg/ml had specific patterns of virulence factors, clonal complex (CC) types, or the ability to form biofilms. Vancomycin MICs were determined by Etest, and the isolates underwent typing to infer the CC, biofilm studies, a thrombin-induced platelet microbicidal assay, and multiplex PCR for the presence of virulence genes. We found no differences in genes encoding adhesins, toxins, or other putative virulence genes according to the vancomycin MIC group. CC30, CC34, and CC45 represented nearly half of the isolates, and there was no association with the vancomycin MIC. subgroups I and III predominated, with no association with the vancomycin MIC. Isolates with higher vancomycin MICs exhibited a poorer ability to form biofilms with and without the presence of vancomycin (2.03 versus 2.48 [ < 0.001], respectively, for isolates with higher vancomycin MICs and 2.60 versus 2.87 [ = 0.022], respectively, for isolates with lower vancomycin MICs). In the multivariable analysis, and were risk factors for major emboli (adjusted odds ratio [aOR] = 7.5 and 95% confidence interval [CI] = 1.2 to 46.6 for , and aOR = 3.9 and 95% CI = 1.1 to 14.1 for ), whereas no genotypic predictors of in-hospital mortality were found. No clear associations between genes encoding virulence factors, type, clonal complexes, mortality, and major embolic events according to vancomycin MIC group were found.
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http://dx.doi.org/10.1128/AAC.01579-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038266PMC
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

Changing epidemiology of bloodstream infection in a 25-years hematopoietic stem cell transplant program: current challenges and pitfalls on empiric antibiotic treatment impacting outcomes.

Bone Marrow Transplant 2020 03 30;55(3):603-612. Epub 2019 Sep 30.

Infectious Diseases Department, Hospital Clínic-IDIBAPS, Barcelona, Spain.

We aimed to describe epidemiology changes in bloodstream infections (BSI) episodes in hematopoietic stem cell transplant (HSCT) recipients throughout a 25-year period (1993-2017), comparing five-year time spans, and we evaluate their impact on inappropriate empirical antibiotic treatment (IEAT) and mortality. During the study period, 1164 BSI episodes were documented in patients undergoing HSCT (71.6% allogenic and 29% autologous). A significant decrease in gram-positive cocci (GPC) and increase in gram-negative bacilli (GNB) were observed (p < 0.001). Among GP, coagulase-negative staphylococci (CoNS) significantly decreased whereas rising E. faecium BSI was documented. Among GNB, E. coli, Pseudomonas aeruginosa and K. pneumoniae rates increased. Multidrug-resistant (MDR) GNB, especially ESBL-E. coli and MDR-P. aeruginosa, emerged in 2008 and has gradually increased. IEAT against MDR-P. aeruginosa, but not in other MDR-GNB, augmented throughout the study period. Overall, 30-day and related mortality rates were 12.7% and 7.7% respectively, both increasing over time (p < 0.001 and p = 0.025). In GNB, 30-day and related mortality were 18.5% and 12.8%, respectively, increasing over time (p < 0.001 and p = 0.004). To conclude, important BSI epidemiological changes were described in a 25-year period. Concerning increase in IEAT for P. aeruginosa infections and rising 30-day mortality rate were documented.
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http://dx.doi.org/10.1038/s41409-019-0701-3DOI Listing
March 2020

Impact of Cefotaxime Non-susceptibility on the Clinical Outcomes of Bacteremic Pneumococcal Pneumonia.

J Clin Med 2019 Aug 1;8(8). Epub 2019 Aug 1.

Department of Infectious Disease, Hospital Clinic of Barcelona, 08036 Barcelona, Spain.

Background: We aimed to analyze the impact of cefotaxime non-susceptibility on the 30-day mortality rate in patients receiving a third-generation cephalosporin for pneumococcal bacteremic pneumonia.

Methods: We conducted a retrospective observational study of prospectively collected data from the Hospital Clinic of Barcelona. All adult patients with monomicrobial bacteremic pneumonia due to and treated with a third-generation cephalosporin from January 1991 to December 2016 were included. Risk factors associated with 30-day mortality were evaluated by univariate and multivariate analyses.

Results: During the study period, 721 eligible episodes were identified, and data on the susceptibility to cefotaxime was obtainable for 690 episodes. Sixty six (10%) cases were due to a cefotaxime non-susceptible strain with a 30-day mortality rate of 8%. Variables associated with 30-day mortality were age, chronic liver disease, septic shock, and the McCabe score. Infection by a cefotaxime non-susceptible did not increase the mortality rate.

Conclusion: Despite the prevalence of cefotaxime, non-susceptible has increased in recent years. We found no evidence to suggest that patients hospitalized with bacteremic pneumonia due to these strains had worse clinical outcomes than patients with susceptible strains.
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http://dx.doi.org/10.3390/jcm8081150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722634PMC
August 2019

Perioperative prophylaxis with ertapenem reduced infections caused by extended-spectrum betalactamase-producting Enterobacteriaceae after kidney transplantation.

BMC Nephrol 2019 07 22;20(1):274. Epub 2019 Jul 22.

Department of Infectious Diseases, Hospital Clinic - IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain.

Backgound: In recent years we have witnessed an increase in infections due to multidrug-resistant organisms in kidney transplant recipients (KTR). In our setting, we have observed a dramatic increase in infections caused by extended-spectrum betalactamase-producing (ESBL) Enterobacteriaceae in KTR. In 2014 we changed surgical prophylaxis from Cefazolin 2 g to Ertapenem 1 g.

Methods: We compared bacterial infections and their resistance phenotype during the first post-transplant month with an historical cohort collected during 2013 that had received Cefazolin.

Results: During the study period 110 patients received prophylaxis with Cefazolin and 113 with Ertapenem. In the Ertapenem cohort we observed a non-statistically significant decrease in the percentage of early bacterial infection from 57 to 47%, with urine being the most frequent source in both. The frequency of infections caused by Enterobacteriaceae spp. decreased from 64% in the Cefazolin cohort to 36% in the Ertapenem cohort (p = 0.005). In addition, percentage of ESBL-producing strains decreased from 21 to 8% of all Enterobacteriaceae isolated (p = 0.015). After adjusted in multivariate Cox regression analysis, male sex (HR 0.16, 95%CI: 0.03-0.75), cefazolin prophylaxis (HR 4.7, 95% CI: 1.1-22.6) and acute rejection (HR 14.5, 95% CI: 1.3-162) were associated to ESBL- producing Enterobacteriaceae infection.

Conclusions: Perioperative antimicrobial prophylaxis with a single dose of Ertapenem in kidney transplant recipients reduced the incidence of early infections due to ESBL-producing Enterobacteriaceae without increasing the incidence of other multidrug-resistant microorganisms or C. difficile.
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http://dx.doi.org/10.1186/s12882-019-1461-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647261PMC
July 2019

Inappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug Resistance.

Clin Infect Dis 2020 03;70(6):1068-1074

Infectious Diseases Department, Hospital Clínic-Institut d'investigacions Biomèdiques August Pi i Sunyer.

Background: We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality.

Methods: This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006-2017). Episodes receiving IEAT were compared with episodes receiving appropriate empirical therapy. Adherence to Infectious Diseases Society of America (IDSA) recommendations was evaluated. Multivariate analysis was performed to identify independent risk factors for mortality in Pseudomonas aeruginosa episodes.

Results: Of 1615 episodes, including Escherichia coli (24%), coagulase-negative staphylococci (21%), and P. aeruginosa (16%), 394 (24%) received IEAT despite IDSA recommendations being followed in 87% of cases. Patients with multidrug-resistant gram-negative bacilli (MDR-GNB), accounting for 221 (14%) of all isolates, were more likely to receive IEAT (39% vs 7%, P < .001). Overall mortality was higher in patients with GNB BSI who received IEAT (36% vs 24%, P = .004); when considering individual microorganisms, only patients with infection caused by P. aeruginosa experienced a significant increase in mortality when receiving IEAT (48% vs 31%, P = .027). Independent risk factors for mortality in PA BSI (odds ratio [95% confidence interval] were IEAT (2.41 [1.19-4.91]), shock at onset (4.62 [2.49-8.56]), and pneumonia (3.01 [1.55-5.83]).

Conclusions: IEAT is frequent in high-risk patients with FN and BSI, despite high adherence to guidelines. This inappropriate treatment primarily impacts patients with P. aeruginosa-related BSI mortality and in turn is the only modifiable factor to improve outcomes.
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http://dx.doi.org/10.1093/cid/ciz319DOI Listing
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

Endocarditis Caused by Highly Penicillin-Resistant Viridans Group Streptococci: Still Room for Vancomycin-Based Regimens.

Antimicrob Agents Chemother 2019 08 25;63(8). Epub 2019 Jul 25.

Division of Infectious Diseases, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Optimal treatment options remain unknown for infective endocarditis (IE) caused by penicillin-resistant (PEN-R) viridans group streptococcal (VGS) strains. The aims of this study were to report two cases of highly PEN-R VGS IE, perform a literature review, and evaluate various antibiotic combinations and The following combinations were tested by time-kill studies and in the rabbit experimental endocarditis (EE) model: PEN-gentamicin, ceftriaxone-gentamicin, vancomycin-gentamicin, daptomycin-gentamicin, and daptomycin-ampicillin. Case 1 was caused by (PEN MIC, 4 μg/ml) and was treated with vancomycin plus cardiac surgery. Case 2 was caused by (PEN MIC, 8 μg/ml) and was treated with 4 weeks of vancomycin plus gentamicin, followed by 2 weeks of vancomycin alone. Both patients were alive and relapse-free after ≥6 months follow-up. For the studies, except for daptomycin-ampicillin, all combinations demonstrated both synergy and bactericidal activity against the isolate. Only PEN-gentamicin, daptomycin-gentamicin, and daptomycin-ampicillin demonstrated both synergy and bactericidal activity against the strain. Both strains developed high-level daptomycin resistance (HLDR) during daptomycin passage. In the EE studies, PEN alone failed to clear from vegetations, while ceftriaxone and vancomycin were significantly more effective ( < 0.001). The combination of gentamicin with PEN or vancomycin increased bacterial eradication compared to that with the respective monotherapies. In summary, two patients with highly PEN-R VGS IE were cured using vancomycin-based therapy. , regimens of gentamicin plus either β-lactams or vancomycin were more active than their respective monotherapies. Further clinical studies are needed to confirm the role of vancomycin-based regimens for highly PEN-R VGS IE. The emergence of HLDR among these strains warrants caution in the use of daptomycin therapy for VGS IE.
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http://dx.doi.org/10.1128/AAC.00516-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658762PMC
August 2019

Mortality due to Cryptococcus neoformans and Cryptococcus gattii in low-income settings: an autopsy study.

Sci Rep 2019 05 16;9(1):7493. Epub 2019 May 16.

ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.

Cryptococcosis is a major opportunistic infection and is one of the leading causes of death in adults living with HIV in sub-Saharan Africa. Recent estimates indicate that more than 130,000 people may die annually of cryptococcal meningitis in this region. Although complete diagnostic autopsy (CDA) is considered the gold standard for determining the cause of death, it is seldom performed in low income settings. In this study, a CDA was performed in 284 deceased patients from Mozambique (n = 223) and Brazil (n = 61). In depth histopathological and microbiological analyses were carried out in all cases dying of cryptococcosis. We determined the cryptococcal species, the molecular and sero-mating types and antifungal susceptibility. We also described the organs affected and reviewed the clinical presentation and patient management. Among the 284 cases included, 17 fatal cryptococcal infections were diagnosed. Cryptococcus was responsible for 16 deaths among the 163 HIV-positive patients (10%; 95%CI: 6-15%), including four maternal deaths. One third of the cases corresponded to C. gattii (VGI and VGIV molecular types, Bα and Cα strains) and the remaining infections typed were caused by C. neoformans var. Grubii (all VNI and Aα strains). The level of pre-mortem clinical suspicion was low (7/17, 41%), and 7/17 patients (41%) died within the first 72 hours of admission. Cryptococcosis was responsible for a significant proportion of AIDS-related mortality. The clinical diagnosis and patient management were inadequate, supporting the need for cryptococcal screening for early detection of the disease. This is the first report of the presence of C. gattii infection in Mozambique.
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http://dx.doi.org/10.1038/s41598-019-43941-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522501PMC
May 2019

Evaluation of the Magicplex™ Sepsis Real-Time Test for the Rapid Diagnosis of Bloodstream Infections in Adults.

Front Cell Infect Microbiol 2019 12;9:56. Epub 2019 Mar 12.

Department of Microbiology, ISGlobal, Barcelona Centre for International Health Research, Hospital Clinic, University of Barcelona, Barcelona, Spain.

Sepsis is a serious health condition worldwide, affecting more than 30 million people globally each year. Blood culture (BC) is generally used to diagnose sepsis because of the low quantity of microbes occurring in the blood during such infections. However, ~50% of bloodstream infections (BSI) give negative BC, this figure being higher for sepsis, which delays the start of appropriate antimicrobial therapy. This prospective study evaluated a multiplex real-time polymerase chain reaction, the Magicplex Sepsis test (MP), for the detection of pathogens from whole blood, comparing it to routine BC. We analyzed 809 blood samples from 636 adult patients, with 132/809 (16.3%) of the samples positive for one or more relevant microorganism according to BC and/or MP. The sensitivity and specificity of MP were 29 and 95%, respectively, while the level of agreement between BC and MP was 87%. The rate of contaminated samples was higher for BC (10%) than MP (4.8%) ( < 0.001). Patients with only MP-positive samples were more likely to be on antimicrobial treatment (47%) than those with only BC-positive samples (18%) ( = 0.002). In summary, the MP test could be useful in some clinical setting, such as among patients on antibiotic therapy. Nevertheless, a low sensitivity demonstrated impairs its use as a part of a routine diagnostic algorithm.
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http://dx.doi.org/10.3389/fcimb.2019.00056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423426PMC
November 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

Recommendations of the Spanish Antibiogram Committee (COESANT) for selecting antimicrobial agents and concentrations for in vitro susceptibility studies using automated systems.

Enferm Infecc Microbiol Clin 2020 04 14;38(4):182-187. Epub 2019 Mar 14.

Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain; Unidad de Gestión Clínica de Microbiología, Hospital Reina Sofía, Departamento de Microbiología, Universidad de Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.

Automated antimicrobial susceptibility testing devices are widely implemented in clinical microbiology laboratories in Spain, mainly using EUCAST (European Committee on Antimicrobial Susceptibility Testing) breakpoints. In 2007, a group of experts published recommendations for including antimicrobial agents and selecting concentrations in these systems. Under the patronage of the Spanish Antibiogram Committee (Comité Español del Antibiograma, COESANT) and the Study Group on Mechanisms of Action and Resistance to Antimicrobial Agents (GEMARA) from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), and aligned with the Spanish National Plan against Antimicrobial Resistance (PRAN), a group of experts have updated this document. The main modifications from the previous version comprise the inclusion of new antimicrobial agents, adaptation of the ranges of concentrations to cover the EUCAST breakpoints and epidemiological cut-off values (ECOFFs), and the inference of new resistance mechanisms. This proposal should be considered by different manufacturers and users when designing new panels or cards. In addition, recommendations for selective reporting are also included. With this approach, the implementation of EUCAST breakpoints will be easier, increasing the quality of antimicrobial susceptibility testing data and their microbiological interpretation. It will also benefit epidemiological surveillance studies as well as the clinical use of antimicrobials aligned with antimicrobial stewardship programs.
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http://dx.doi.org/10.1016/j.eimc.2019.01.017DOI Listing
April 2020

Cutaneous infection by Phaeoacremonium parasiticum.

Rev Iberoam Micol 2019 Apr - Jun;36(2):90-92. Epub 2019 Mar 8.

Department of Microbiology, Hospital Clínic, Universitat de Barcelona, ISGLOBAL, Barcelona, Spain.

Background: Phaeoacremonium parasiticum is considered a rare infectious agent that is part of a heterogeneous group of fungi causing phaeohyphomycosis. This organism is capable of producing subcutaneous infections, eumycetomas, osteomyelitis, arthritis, myositis and also disseminated diseases, such as fungemia and endocarditis.

Case Report: We describe a case of cutaneous infection by P. parasiticum in a kidney transplant patient. The identification of this microorganism was performed by microbiological and histopathological studies and confirmed with the sequence of the gene encoding β-tubulin and a real time panfungal PCR targeting 18S ribosomal RNA gene. The microorganism was correctly identified by phenotypic and molecular methods. The patient was treated with oral antifungal therapy and a debulking surgery and evolved without any complication.

Conclusions: The diagnosis of this infection is difficult and usually affects kidney transplant patients, but the reasons of this association are still unknown.
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http://dx.doi.org/10.1016/j.riam.2018.10.003DOI Listing
February 2020

Emergence of Resistance to Quinolones and β-Lactam Antibiotics in Enteroaggregative and Enterotoxigenic Causing Traveler's Diarrhea.

Antimicrob Agents Chemother 2019 02 29;63(2). Epub 2019 Jan 29.

Institute of Global Health of Barcelona, Barcelona, Spain

The objective of this study was to assess the antimicrobial resistance of enteroaggregative (EAEC) and enterotoxigenic (ETEC) strains causing traveler's diarrhea (TD) and to investigate the molecular characterization of antimicrobial resistance genes to third-generation cephalosporins, cephamycins, and quinolones. Overall, 39 EAEC and 43 ETEC clinical isolates were studied. The susceptibilities of EAEC and ETEC against ampicillin, amoxicillin-clavulanic acid, cefotaxime, imipenem, chloramphenicol, tetracycline, co-trimoxazole, nalidixic acid, ciprofloxacin, azithromycin, and rifaximin were determined. All genes encoding resistance determinants were detected by PCR or PCR plus DNA sequencing. The epidemiology of selected EAEC and ETEC strains was studied using multilocus sequence typing (MLST). The resistance to quinolones of EAEC and ETEC strains causing TD has significantly increased over the last decades, and high percentages have been found especially in patients traveling to India and sub-Saharan Africa. Sequence type 38 (ST38) and ST131, carrying the and genes, respectively, are highly prevalent among extended-spectrum β-lactamase (ESBL)-producing EAEC and ETEC strains. The cephamycinase ACT-20 is described in the present study for the first time in EAEC and ETEC strains causing TD in patients who had traveled to Central America. The percentages of resistance to azithromycin in EAEC and ETEC isolates from patients to Southeast Asia/India and Africa are above 25%. Meanwhile, rifaximin is still active against EAEC and ETEC, with the prevalence of resistant strains not being high. In conclusion, fluoroquinolones should no longer be considered the drugs of choice for the prevention or treatment in TD for travelers traveling to India and Africa. Azithromycin and rifaximin are still a good alternative to treat TD caused by EAEC or ETEC.
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http://dx.doi.org/10.1128/AAC.01745-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355616PMC
February 2019

Clinical characteristics and prognosis of infections caused by OXA-48 carbapenemase-producing Enterobacteriaceae in patients treated with ceftazidime-avibactam.

Int J Antimicrob Agents 2019 Apr 22;53(4):520-524. Epub 2018 Nov 22.

Department of Infectious Diseases, Hospital Clinic, Barcelona, University of Barcelona, IDIBAPS, Spain.

Background: Ceftazidime-avibactam has in vitro activity against Gram-negative bacilli that produce Class A, C and some D β-lactamases, and has been successfully used in the treatment of infections caused by cephalosporin and carbapenem-resistant Enterobacteriaceae. However, actual experience in the treatment of OXA-48 carbapenemase-producing Enterobacteriaceae (CPE) is limited.

Objective: To review the characteristics and prognosis of OXA-48 CPE infections treated with ceftazidime-avibactam since introduction of the drug to the current centre during the period October 2014 to December 2016.

Methods: Retrospective assessment of episodes of infection caused by OXA-48 CPE treated with ceftazidime-avibactam, analysing data collected from infection diagnosis until 90 days after the end of treatment.

Results: Twenty-four episodes were analysed. Ceftazidime-avibactam was given as the initial definitive treatment in 15 (62.5%) and as salvage therapy in nine (37.5%). Intraabdominal (seven, 29%), urinary (six, 25%) and respiratory (five, 21%) were the most common sources. The 30-day and 90-day mortality rates were 8.3% and 20.8%, respectively. Clinical cure at 30 days was achieved in 62.5% of episodes. Four (16.7%) patients had adverse events, two of them were related to impaired renal function. Among patients who finished the treatment with ceftazidime-avibactam, seven (35%) were diagnosed with infection recurrence within 90 days of the end of treatment.

Conclusions: From experience, ceftazidime-avibactam is an effective drug for treating infections due to OXA-48 CPE. From these results a better safety profile than the current best available therapy could be expected.
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http://dx.doi.org/10.1016/j.ijantimicag.2018.11.015DOI Listing
April 2019

Serotypes and genotypes of S. pneumoniae isolates from adult invasive disease in Spain: A 5-year prospective surveillance after pediatric PCV13 licensure. The ODIN study.

Vaccine 2018 12 16;36(52):7993-8000. Epub 2018 Nov 16.

Medical Department, Pfizer, Madrid, Spain.

Serotypes/genotypes causing invasive pneumococcal disease (IPD) in adults are determined by vaccination strategies. The aim of this study was to assess the epidemiology of IPD in adults (≥18 years) after PCV13 introduction for children: serotypes, clonal complexes, antibiotic non-susceptibility and clinical presentations. We performed a prospective, clinical surveillance of hospitalized culture-confirmed IPDs in adults in nine Spanish hospitals (August 2010-June 2015). A total of 1087 culture-confirmed IPD episodes were included, of which 772 (71.0%) had bacteremic pneumonia (401 complicated/371 uncomplicated pneumonia), 122 (11.2%) meningitis, 102 (9.4%) non-focal bacteremia, 34 (3.1%) peritonitis and 57 (5.3%) others. The most common serotypes were: 3 (12.7%), 19A (8.5%), 8 (7.7%), 7F (6.3%), 1 (4.2%), 6C (4.2%), 11A (4.2%), 22F (4.2%) and 14 (4.0%). Vaccine types (PCV13 + 6C) caused 49.8% of IPD episodes, with a significant decrease over the 5-year period, and significant decreases in serotypes 6C and 7F. The most common genotypes were: CC180 (8.4%), CC191 (6.0%), and CC53 (5.0%). Vaccine types caused 53.9% (414/768) pneumonia episodes and 58.9% (235/399) complicated pneumonia, 53.4% IPD in adults <50 years (143/268), and 54.7% IPD in immunocompetent patients (337/616). Overall non-susceptibility was 25.9% to penicillin (1.1% for parenteral criteria), 24.9% to erythromycin and 2.7% to levofloxacin. CONCLUSIONS: Although the percentage of vaccine-types causing IPDs in adults significantly decreased, it remained high. Associations of vaccine types with pneumonia (with complicated pneumonia for specific serotypes), and immunocompetent patients point to the burden of IPD caused by PCV13 serotypes.
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http://dx.doi.org/10.1016/j.vaccine.2018.10.098DOI Listing
December 2018