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1. Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients

Author

Gutierrez-Gutierrez, B., Perez-Nadales, E., Perez-Galera, S., Fernandez-Ruiz, M., Carratala, J., Oriol, I., Cordero, E., Lepe, J. A., Tan, B. H., Corbella, L., Paul, M., Natera, A. M., David, M. D., Montejo, M., Iyer, R. N., Pierrotti, L. C., Merino, E., Steinke, S. M., Rana, M. M., Munoz, P., Mularoni, A., van Delden, C., Grossi, P. A., Seminari, E. M., Gunseren, F., Lease, E. D., Roilides, E., Fortun, J., Arslan, H., Coussement, J., Tufan, Z. K., Pilmis, B., Rizzi, M., Loeches, B., Eriksson, B. M., Abdala, E., Soldani, F., Lowman, W., Clemente, W. T., Bodro, M., Farinas, M. C., Kazak, E., Martinez-Martinez, L., Aguado, J. M., Torre-Cisneros, J., Pascual, A., Rodriguez-Bano, J., Sabe, N., Camoez, M., Martin-Gandul, C., Bernal, G., Kee, T. Y. S., Lopez-Medrano, F., Juan, R. S., Koppel, F., Bar-Sinai, N., Caston, J. J., Cano, A., Gracia-Ahufinger, I., Rodriguez, R., Lopez-Soria, L., Azurmendi, M., Pinheiro, M., Freire, M., Banks, I., Lopes, F., David-Neto, E., Balibrea, N., Franco, A., Avery, R., Ostrander, D., Minero, M. V., Carrillo, C. S., Rodriguez-Ferrero, M. L., Monaco, F., Campanella, M., Mueller, N. J., Manuel, O., Khanna, N., Rovelli, C., Balsamo, M. L., Colombo, A., Leoni, C., Pyrpasopoulou, A., Mouloudi, E., Iosifidis, E., Martin-Davila, P., Gioia, F., Escudero, R., Demirkaya, M. H., Dewispelaere, L., Kalem, A. K., Hasanoglu, I., Guner, R., Lortholary, O., Scemla, A., Calvi, E. G., Gervasi, E., Binda, F., Oliva, M. L., Dimopoulos, N., Magalhaes, M. R., Song, A. T. W., D'Albuquerque, L. A. C., Chiesi, S., Salerno, N. D., Mourao, P. H. O., Moreno, A., Linares, L., Almela, M., Rico, C. G., Rodrigo, E., Martinez, M. F., Falcone, M., Tumbarello, M., Strabelli, T. M. V., Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, European Commission, Sociedad Andaluza de Trasplante de Órganos y Tejidos, and Ministerio de Ciencia e Innovación (España)

Subjects
Ertapenem, medicine.medical_specialty, Urinary system, UTI, Bacteremia, Bloodstream infection, BSI, Logistic regression, Extended-spectrum-b-lactamase-producing Enterobacterales, Meropenem, beta-Lactamases, Cohort Studies, chemistry.chemical_compound, Internal medicine, polycyclic compounds, medicine, Humans, Pharmacology (medical), Propensity Score, Kidney transplant, Retrospective Studies, Pharmacology, Urinary tract infection, business.industry, ESBL-E, Anti-Bacterial Agents, Kidney Transplantation, Urinary Tract Infections, bacterial infections and mycoses, medicine.disease, Infectious Diseases, chemistry, Propensity score matching, Cohort, business, medicine.drug, Cohort study
Abstract

REIPI/ESGICH/ESGBIS/INCREMENT-SOT Group., There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages., This work was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III (ISCIII), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001, RD16/0016/0002, RD16/0016/0008; RD16/0016/00010) and was cofinanced by the European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014‐2020; ESCMID Study Group for Infections in Compromised Hosts (ESGICH grant to J.M.A.); Sociedad Andaluza de Trasplante de Órgano Sólido (SATOT grant to L.M.-M.); ESCMID Study Group for Bloodstream Infections and Sepsis (ESGBIS); and ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS). B.G.-G. (PI 18/01849) and E.P.-N. (PI 16/01631) have received research funds from the Spanish Ministry of Science and Innovation, ISCIII; M.F.-R. holds a research contract “Miguel Servet” (CP 18/00073) from the Spanish Ministry of Science and Innovation, ISCIII.

Published
2021

2. Invasive Fusariosis in Nonneutropenic Patients, Spain, 2000–2015

Author

Perez-Nadales E, Alastruey-Izquierdo A, Linares-Sicilia M, Soto-Debran J, Abdala E, Garcia-Rodriguez J, Montejo M, Munoz P, Lleti M, Rezusta A, de Pipaon M, Yanez L, Merino E, Campos-Herrero M, Costa-Mateo J, Fortun J, Garcia-Lozano T, Garcia-Vidal C, Fernandez-Ruiz M, Sanchez-Reus F, Castro-Mendez C, Guerrero-Lozano I, Soler-Palacin P, Aguado J, Martinez-Martinez L, Torre-Cisneros J, Nucci M, Spanish Fusariosis Study Grp, Biomedicina, Biotecnología y Salud Pública, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, European Regional Development Fund, and European Regional Development Fund (ERDF/FEDER)

Subjects
Antifungal Agents, Epidemiology, fusariosis, lcsh:Medicine, HEMATOLOGIC MALIGNANCIES, Fusarium, CME, health care economics and organizations, Neutropènia, musculoskeletal, neural, and ocular physiology, Mortality rate, Incidence (epidemiology), Observational Studies as Topic, Infectious Diseases, fungal infections, DISEASES, Synopsis, Microbiology (medical), Fusariosis, medicine.medical_specialty, Neutropenia, education, Invasive Fusariosis in Nonneutropenic Patients, Spain, 2000–2015, macromolecular substances, lcsh:Infectious and parasitic diseases, FUNGAL-INFECTIONS, Internal medicine, medicine, Mortalitat, Humans, lcsh:RC109-216, Risk factor, Mortality, Epidemiologia, Proportional hazards model, business.industry, lcsh:R, Retrospective cohort study, invasive fusariosis, MASS-SPECTROMETRY, medicine.disease, mortality, CELL TRANSPLANT RECIPIENTS, mycotic diseases, nervous system, Spain, incidence, fungi, business
Abstract

Invasive fusariosis has a global increasing incidence and has emerged as a severe infection in nonneutropenic patients., 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.

Published
2021

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

Author

Cardozo, C., Cuervo, G., Salavert, M., Merino, P., Gioia, F., Fernandez-Ruiz, M., Lopez-Cortes, L. E., Escola-Verge, L., Montejo, M., Munoz, P., Aguilar-Guisado, M., Puerta-Alcalde, P., Tasias, M., Ruiz-Gaitan, A., Gonzalez, F., Puig-Asensio, M., Vena, A., Marco, F., Peman, J., Fortun, J., Aguado, J. M., Almirante, B., Soriano, A., Carratala, J., Garcia-Vidal, C., Martinez, J. A., Morata, L., Rodriguez-Nunez, O., Guerrero, M. A., Ayats, J., Grau, I., Calabuig, E., Castro, I., Cuellar, S., Martin-Davila, P., Gomez-Garcia De La Pedrosa, E., Perez-Ayala, A., Losada, I., Navarro, M. D., Suarez, A. I., Martin-Gomez, M. T., Rodriguez-Alvarez, R., Lopez-Soira, L., Bouza, E., Guinea, J., Martin, C., Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Red Española de Investigación en Patología Infecciosa, and Generalitat de Catalunya

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Evidence-based practice, IMPACT, 030106 microbiology, MEDLINE, Blood culture, Humans, Prospective Studies, Quality of Health Care, Spain, Candidemia, Shock, Septic, 03 medical and health sciences, 0302 clinical medicine, Intervention (counseling), Septic shock, medicine, MANAGEMENT, EPIDEMIOLOGY, Pharmacology (medical), CANDIDIASIS, 030212 general & internal medicine, Quality of care, Mortality, Pharmacology, medicine.diagnostic_test, business.industry, Septic, Follow-up, ESCMID-ASTERISK GUIDELINE, MORTALITY, Confounding, SEPTIC SHOCK, ANTIFUNGAL THERAPY, Shock, FLUCONAZOLE, medicine.disease, CANDIDEMIA, Infectious Diseases, Bundle, Emergency medicine, business, Evidence-based practice Introduction
Abstract

GEMICOMED (SEIMC) and the Spanish CANDI-Bundle Group., [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., This study was funded by a research grant from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (FIS PI15/00744). This study is also co-financed by the European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD06/0008). The funding institutions had no role in the design or performance of the research. C.G.-V. is a recipient of an INTENSIFICACIÓ Grant from the ‘Strategic plan for research and innovation in health-PERIS 2016–2020’ and forms part of the FungiCLINIC Research group (AGAUR-Project 2017SGR1432 of the Catalan Health Agency).

Published
2020

4. Perspectives on Scedosporium species and Lomentospora prolificans in lung transplantation: Results of an international practice survey from ESCMID fungal infection study group and study group for infections in compromised hosts, and European Confederation of Medical Mycology

Author

Rammaert, B., Puyade, M., Cornely, O. A., Seidel, D., Grossi, P., Husain, S., Picard, C., Lass-Florl, C., Manuel, O., Le Pavec, J., Lortholary, O., Nagel, C., Westall, G., Morrissey, O., Chambers, D., Eschertzhuber, S., Coussement, J., Knoop, C., Vos, R., Dupont, L., Dumonceaux, M., Campos, S. V., Kabbani, D., Cervera, C., Luong, M. -L., Blanchard, E., Senechal, A., Pavec, J. L., Brugiere, O., Boussaud, V., Guillemain, R., Bervar, J. -F., Claustre, J., Haloun, A., Hirschi, S., Reynaud, M., Kneidinger, N., Gottlieb, J., Roilides, E., Zarrinfar, H., Rosso, L., Morlacchi, L. C., Dell'Amore, A., Loy, M., Santos, C. O. D., Rello, J., Monforte, V., Martin-Gomez, M. T., Medrano, F. L., Fernandez-Ruiz, M., Sole, A., Cifrian, J. M., Neofytos, D., Mueller, N., Benden, C., Brill, A. K., Kiyan, E., Gould, K., Gkrania-Klotsas, E., David, M., Weigt, S., Kwak, E. J., Silveira, F., Hadjiliadis, D., Baddley, J., Danziger-Isakov, L., Bhorade, S., Ison, M., Wolfe, C., Aslam, S., Budem, M., Musetti, A., Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases - CECAD [Cologne, Germany] (Institute for Genetics), University of Cologne, German Centre for Infection Research (DZIF), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), University Health Network, Hôpital Foch [Suresnes], Leopold Franzens Universität Innsbruck - University of Innsbruck, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre Chirurgical Marie Lannelongue (CCML), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), The authors thank all the people who helped to collect mycological data and to contact transplant centers: Alejandro Mario Bertolotti (Buenos Aires, Argentina), Claire Heney (Brisbane, Australia), Carlota Montesinos (Brussels, Belgium), Katrien Lagrou (Leuven, Belgium), Youri Gluczynski (Yvoir, Belgium), Sandrine Houze (Paris, France), Eric Dannaoui (Paris, France), Florent Morio (Nantes, France), Murielle Cornet (Grenoble, France), Valérie Bru (Strasbourg, France), Stéphane Ranque (Marseille, France), Emilie Cardot (Suresnes, France), Ludwig Sedlacek (Hannover, Germany), Maurizio Sanguinetti (Roma, Italy), Ana Alastruey (Madrid, Spain), Konrad Muehlethaler (Bern, Switzerland), Kevin Alby (Philadelphia, USA), Malcom Richardson (Manchester, UK), the members of the ESCMID Fungal Infection Study Group (EFISG) and Study Group for Infections in Compromised Hosts (ESGICH) and European Confederation of Medical Mycology (ECMM) who helped to promote the study, Jeffrey Arsham for editing our original English language manuscript., The SCEDO‐LUNG collaborative group collected the data., University of Insubria, Varese, University of Innsbruck, Centre chirurgical Marie Lannelongue, Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]

Subjects
Internationality, [SDV]Life Sciences [q-bio], invasive fungal disease, lomentosporiosis, scedosporiosis, solid organ transplantation, Ascomycota, Humans, Lung Transplantation, Mycoses, Prospective Studies, Respiratory Tract Infections, Scedosporium, Surveys and Questionnaires, Disease Management, Immunocompromised Host, MESH: Mycoses/epidemiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Mycoses/etiology, MESH: Surveys and Questionnaires, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Respiratory Tract Infections/etiology, MESH: Humans, MESH: Respiratory Tract Infections/microbiology, MESH: Scedosporium/isolation & purification, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Lung Transplantation/adverse effects, MESH: Prospective Studies, MESH: Disease Management, MESH: Internationality, MESH: Ascomycota/isolation & purification, MESH: Immunocompromised Host
Abstract

International audience; Background: Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients.Methods: We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a large number of lung transplant centers through an international practice survey from October 2016 to March 2017.Results: A total of 51 respondents from 45 lung transplant centers (17 countries, 4 continents) answered the survey (response rate 58%). S/L colonization was estimated to be detected in candidates by 48% of centers. Only 18% of the centers used a specific medium to detect S/L colonization. Scedosporium spp. colonization was a contraindication to transplantation in 10% of centers whereas L prolificans was a contraindication in 31%; 22% of centers declared having had 1-5 recipients infected with S/L in the past 5 years.Conclusions: This survey gives an overview of the current practices regarding S/L colonization and infection in lung transplant centers worldwide and underscores the need of S/L culture procedure standardization before implementing prospective studies.

Published
2019
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5. Candidemia in solid organ transplant recipients in Spain: Epidemiological trends and determinants of outcome

Author

Fernandez-Ruiz, M., Cardozo, C., Salavert, M., Aguilar-Guisado, M., Escola-Verge, L., Munoz, P., Gioia, F., Montejo, M., Merino, P., Cuervo, G., Garcia-Vidal, C., Aguado, J. M., Padilla, B., Guinea, J., Pano-Pardo, J. R., Garcia-Rodriguez, J., Garcia Cerrada, C., Fortun, J., Martin-Davila, P., Gomez-Garcia de la Pedrosa, E., Ryan, P., Campelo, C., de los Santos Gil, I., Buendia, V., Perez Gorricho, B., Alonso, M., Sanz Sanz, F., Gonzalez Romo, F., Gorgolas, M., Gadea, I., Delgado-Iribarren, A., Ramos, A., Romero, Y., Sanchez Romero, I., Zaragoza, O., Cuenca-Estrella, M., Rodriguez-Bano, J., Suarez, A. I., Loza, A., Aller Garcia, A. I., Martin-Mazuelos, E., Ruiz Perez de Pipaon, M., Garnacho, J., Ortiz, C., Chavez, M., Maroto, F. L., Peman, J., Blanquer, J., Navarro, D., Camarena, J. J., Zaragoza, R., Abril, V., Gimeno, C., Hernandez, S., Ezpeleta, G., Bereciartua, E., Hernandez Almaraz, J. L., Rivas, R. A., Ayarza, R., Planes, A. M., Ruiz-Camps, I., Almirante, B., Mensa, J., Almela, M., Gurgui, M., Sanchez-Reus, F., Martinez-Montauti, J., Sierra, M., Horcajada, J. P., Sorli, L., Gomez, J., Gene, A., Urrea, M., Valerio, M., Diaz-Martin, A., Puchades, F., Mularoni, A., Puerta-Alcalde, P., Morata, L., Rodriguez-Nunez, O., Guerrero, M. A., Carratala, J., Sabe, N., Ayats, J., Grau, I., Calabuig, E., Castro, I., Cuellar, S., Perez-Ayala, A., Losada, I., Suarez, M. I., Martin-Gomez, M. T., Rodriguez-Alvarez, R., Lopez-Soira, L., Vena, A., Bouza, E., Martin, C., Gilead Sciences, Astellas Pharma, Pfizer, Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, Fundación SEIMC-GESIDA, Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, and Instituto de Salud Carlos III

Subjects
Male, Antifungal Agents, Epidemiology, candidemia, epidemiology, outcome, solid organ transplantation, treatment, Adult, Aged, Candida albicans, Candida glabrata, Candidemia, Drug Resistance, Fungal, Female, Fluconazole, Hospital Mortality, Humans, Microbial Sensitivity Tests, Middle Aged, Multicenter Studies as Topic, Organ Transplantation, Prospective Studies, Risk Factors, Spain, Transplant Recipients, Drug Resistance, Solid organ transplantation, Kidney transplantation, Outcome, education.field_of_study, Univariate analysis, Infectious Diseases, Fungal, medicine.drug, medicine.medical_specialty, Population, Internal medicine, medicine, education, Transplantation, business.industry, Septic shock, Odds ratio, medicine.disease, Confidence interval, Treatment, business
Abstract

CANDIPOP Project, the CANDI‐Bundle Group GEIRAS‐GEMICOMED (SEIMC) REIPI., [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., The CANDIPOP Project was supported by non‐restrictive research grants from Gilead Sciences, MSD, Astellas Pharma, and Pfizer. This study was cofounded by Fundación SEIMC‐GESIDA, by the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III (co‐financed by the European Development Regional Fund [ERDF] >A way to achieve Europe>), and by the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015). The CANDI‐Bundle Study was supported by “Plan Nacional de I + D+I” and Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias [FIS] PI15/00744), Subdirección General de Redes y Centros de Investigación Cooperativa, Spanish Ministry of Science, Innovation and Universities, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016). MFR holds a research contract “Miguel Servet” (CP 18/00073) from the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III.

Published
2019

6. T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: A prospective pilot study

Author

Munoz, P., Vena, A., Machado, M., Gioia, F., Martinez-Jimenez, M. C., Gomez, E., Origuen, J., Orellana, M. A., Lopez-Medrano, F., Fernandez-Ruiz, M., Merino, P., Gonzalez-Romo, F., Frias, I., Perez-Granda, M. -J., Aguado, J. M., Fortun, J., Bouza, E., Navarro, R., Sanchez, C., and Ruiz, M. F.

Subjects
0301 basic medicine, Microbiology (medical), Antifungal, Adult, Male, medicine.medical_specialty, Antifungal Agents, beta-Glucans, medicine.drug_class, 030106 microbiology, Pilot Projects, 03 medical and health sciences, Internal medicine, Clinical endpoint, Medicine, Humans, Pharmacology (medical), In patient, Blood culture, Candidiasis, Invasive, Prospective Studies, Prospective cohort study, Candida albicans, Antibodies, Fungal, Aged, Pharmacology, biology, medicine.diagnostic_test, business.industry, Candidiasis, Invasive candidiasis, Middle Aged, medicine.disease, biology.organism_classification, Magnetic Resonance Imaging, Infectious Diseases, Blood Culture, Serological biomarkers, Female, business
Abstract

Objectives We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy. Methods Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome). Results Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA [3/14 (21.4%) versus 8/35 (22.9%), P = 1] and BDG [8/14 (57.1%) versus 17/35 (48.6%), P = 0.75] results were similar in poor- and good-outcome patients. Conversely, a positive T2MR was associated with a higher risk of poor outcome [5/14 (35.7%) versus 0/35 (0.0%) P = 0.0001]. Specificity and positive predictive value of a positive T2MR for predicting poor outcome were both 100%, with a negative predictive value of 79.6%. After testing the combinations of biomarkers/standard cultures and T2MR/standard cultures, the combination of T2MR/standard cultures showed a high capacity to discriminate patients with poor outcome from those with good clinical evolution. Conclusions T2MR may be of significant utility to identify patients who may benefit from maintaining antifungal therapy.

Published
2018

7. Nocardia Infection in Solid Organ Transplant Recipients: A Multicenter European Case-control Study

Author

Coussement, J., Lebeaux, D., Delden, C. van, Guillot, H., Freund, R., Marbus, S., Melica, G., Wijngaerden, E. van, Douvry, B., Laecke, S. van, Vuotto, F., Tricot, L., Fernandez-Ruiz, M., Dantal, J., Hirzel, C., Jais, J.P., Rodriguez-Nava, V., Lortholary, O., Jacobs, F., European Study Grp Nocardia Solid, Department Infections Diseases, Université Libre de Bruxelles [Bruxelles] (ULB), Centre Infectiologie, CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Transplantation Infection Disease Unity, Hôpitaux Universitaires de Genève (HUG), Swiss Transplant Cohort Study, University of Basel (Unibas), Service Maladies Infectieuses et Tropicales, Hôpital Universitaire Pitié Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP - HP), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Biostatistique, Centre Hospitalier Universitaire de Clermont-Ferrand, Medical Center, Department of Infectious Diseases, Leiden University, Immunologie Clinique et Maladies Infectieuses, Hopital Henri Mondor (APHP), Département Génétique Internal Médecine, Hôpital Universitaire Leuven, Service Pneumologie et Transplantation Pulmonaire, Hôpital Foch [Suresnes], Renal Division, Freiburg University Medical Center, Unité Maladies Infectieuses, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service Néphrologie Transplantation Rénale, Unit Infectious Diseases, Hospital 12 de Octubre, Institut Transplantation Urologie et Néphrologie, Centre hospitalier universitaire de Nantes (CHU Nantes), Swiss Transplantation Cohort Study, Department Infectious Diseases, University Hospital of Bern, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centrer Infectiologie, Department of Infectious Diseases, University of Gothenburg (GU), Societe de Pathologie Infectieuse de Langue Francaise, Prix Fonds Carine Vyghen pour le don d'organes, Swiss National Science Foundation, Swiss University Hospitals (G15) and transplant centers, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Universiteit Leiden, Hôpital Henri Mondor, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Université Libre de Bruxelles [Bruxelles] ( ULB ), Hôpital Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris ( AP-HP ), Institut Imagine, Hôpitaux Universitaires de Genève ( HUG ), University of Basel ( Unibas ), Hôpital Universitaire Pitié Salpêtrière, Assistance Publique - Hôpitaux de Paris ( AP - HP ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hopital Henri Mondor ( APHP ), Centre Hospitalier Régional Universitaire de Lille ( CHRU de Lille ), Centre Hospitalier Universitaire de Nantes, Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), and University of Gothenburg ( GU )

Subjects
Male, 0301 basic medicine, Opportunistic infection, opportunistic infection, greffe d'organe, Transplants, organ transplant, Organ transplantation, Nocardia, Risk Factors, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Medicine, ddc:616, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, ddc:618, [ SDV.MHEP.ME ] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Nocardiosis, Middle Aged, opportunistic infections, 3. Good health, Europe, Infectious Diseases, nocardiaceae, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Nocardia Infections, Adult, Microbiology (medical), medicine.medical_specialty, Calcineurin Inhibitors, 030106 microbiology, 610 Medicine & health, 03 medical and health sciences, Internal medicine, Trimethoprim, Sulfamethoxazole Drug Combination, Humans, Intensive care medicine, Aged, Retrospective Studies, nocardiosis, business.industry, Retrospective cohort study, biology.organism_classification, medicine.disease, Transplant Recipients, infection, Tacrolimus, Transplantation, Logistic Models, Case-Control Studies, business
Abstract

Background. Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplant (SOT). The aim of this study was to identify risk factors for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients.Methods. We performed a retrospective case-control study of adult patients diagnosed with nocardiosis after SOT between 2000 and 2014 in 36 European (France, Belgium, Switzerland, the Netherlands, Spain) centers. Two control subjects per case were matched by institution, transplant date, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors for nocardiosis.Results. One hundred and seventeen cases of nocardiosis and 234 control patients were included. Nocardiosis occurred at a median of 17.5 (range, 2-244) months after transplant. In multivariable analysis, high calcineurin inhibitor trough levels in the month before diagnosis (odds ratio [OR], 6.11; 95% confidence interval [CI], 2.58-14.51), use of tacrolimus (OR, 2.65; 95% CI, 1.17-6.00) and corticosteroid dose (OR, 1.12; 95% CI, 1.03-1.22) at the time of diagnosis, patient age (OR, 1.04; 95% CI, 1.02-1.07), and length of stay in the intensive care unit after SOT (OR, 1.04; 95% CI, 1.00-1.09) were independently associated with development of nocardiosis; low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis. Nocardia farcinica was more frequently associated with brain, skin, and subcutaneous tissue infections than were other Nocardia species. Among the 30 cases with central nervous system nocardiosis, 13 (43.3%) had no neurological symptoms.Conclusions. We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.

Published
2016
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8. Invasive aspergillosis due to Aspergillus section Usti: a multicenter retrospective study

Author

Eléna Charpentier, Frédéric Gabriel, Frédéric Lamoth, Maria Aigner, Emmanouil Glampedakis, Michela Paolucci, Felix Bongomin, Malcolm Richardson, C. Bonnal, Russel Edward Lewis, Arnaud Fekkar, Christophe Hennequin, Stéphane Bretagne, Patrice Le Pape, Arnaud Riat, Reinhard Zbinden, Veronique Erard, Pierre-Yves Bochud, Marie-Elisabeth Bougnoux, Ahmet Çağkan İnkaya, Olga V Shadrivova, Sophie Brun, Nina Khanna, Dionysios Neofytos, Anne-Pauline Bellanger, Eric Dannaoui, Florent Morio, Peter W Schreiber, Sevtap Arikan-Akdagli, Mario Fernández-Ruiz, Alix T. Coste, Nikolai Klimko, Sophie Cassaing, Glampedakis E., Cassaing S., Fekkar A., Dannaoui E., Bougnoux M.-E., Bretagne S., Neofytos D., Schreiber P.W., Hennequin C., Morio F., Shadrivova O., Bongomin F., Fernandez-Ruiz M., Bellanger A.P., Arikan-Akdagli S., Erard V., Aigner M., Paolucci M., Khanna N., Charpentier E., Bonnal C., Brun S., Gabriel F., Riat A., Zbinden R., Le Pape P., Klimko N., Lewis R.E., Richardson M., Inkaya A.C., Coste A.T., Bochud P.-Y., Lamoth F., Hôpital Lausanne, Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité de Parasitologie-Mycologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hop Univ Geneve, Serv Malad Infect, Geneva, Switzerland, Department of Infectious Diseases and Hospital Epidemiology [Zurich], University hospital of Zurich [Zurich], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Saint-Petersburg, University of Manchester [Manchester], Unit Infectious Diseases, Hospital 12 de Octubre, Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Ankara University School of Medicine [Turkey], University of Fribourg, Universität Innsbruck [Innsbruck], Department of Hematology and Oncology 'L. e A. Seragnoli', St. Orsola University Hospital, University Hospital Basel [Basel], Service de Parasitologie Mycologie[Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Parasitologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, CHU Bordeaux [Bordeaux], Hôpitaux Universitaire de Genève, Laboratoire de parasitologie et de mycologie médicale [CHU Nantes], Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, and Université de Lausanne (UNIL)

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Posaconazole, Antifungal Agents, Aspergillosi, Aspergillus puniceus, 030106 microbiology, Aspergillus calidoustus, Aspergillus pseudodeflectus, Aspergillosis, 03 medical and health sciences, Aspergillus ustus, Retrospective Studie, Internal medicine, Amphotericin B, medicine, Antifungal Agent, Humans, Retrospective Studies, Voriconazole, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, ddc:616, business.industry, Mortality rate, Retrospective cohort study, Aspergillus insuetus, medicine.disease, Aspergillu, 3. Good health, 030104 developmental biology, Infectious Diseases, Aspergillus, business, Invasive Fungal Infections, medicine.drug, Human
Abstract

Background Aspergillus spp. of section Usti (A. ustus) represent a rare cause of invasive aspergillosis (IA). This multicenter study describes the epidemiology and outcome of A. ustus infections. Methods Patients with A. ustus isolated from any clinical specimen were retrospectively identified in 22 hospitals from 8 countries. When available, isolates were sent for species identification (BenA/CaM sequencing) and antifungal susceptibility testing. Additional cases were identified by review of the literature. Cases were classified as proven/probable IA or no infection, according to standard international criteria. Results Clinical report forms were obtained for 90 patients, of whom 27 had proven/probable IA. An additional 45 cases were identified from literature review for a total of 72 cases of proven/probable IA. Hematopoietic cell and solid-organ transplant recipients accounted for 47% and 33% cases, respectively. Only 8% patients were neutropenic at time of diagnosis. Ongoing antimold prophylaxis was present in 47% of cases. Pulmonary IA represented 67% of cases. Primary or secondary extrapulmonary sites of infection were observed in 46% of cases, with skin being affected in 28% of cases. Multiple antifungal drugs were used (consecutively or in combination) in 67% of cases. The 24-week mortality rate was 58%. A. calidoustus was the most frequent causal agent. Minimal inhibitory concentrations encompassing 90% isolates (MIC90) were 1, 8, >16, and 4 µg/mL for amphotericin B, voriconazole, posaconazole, and isavuconazole, respectively. Conclusions Aspergillus ustus IA mainly occurred in nonneutropenic transplant patients and was frequently associated with extrapulmonary sites of infection. Mortality rate was high and optimal antifungal therapy remains to be defined.

Published
2019
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9. Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Author

Álvaro Pascual, Domingo Hernández, Francisco López-Medrano, Pilar Martín-Dávila, Rafael Cantón, M.J. Goyanes, Belén Gutiérrez-Gutiérrez, Elisa Vidal, A. Solé-Jover, J. Fortún, Patricia Muñoz, Julián Torre-Cisneros, Rafael López-Andújar, Oscar Len, A. Román-Broto, Antonio Oliver, Valentín Cuervas-Mons, Miguel Montejo, Mario Fernández-Ruiz, Joan Gavaldà, Emilia Cercenado, Carlota Gudiol, A. Moreno, Elena Pérez-Nadales, Juan José Castón, Elisa Cordero, Rafael San-Juan, Daniel Serón, Carlos Cervera, J.T. Silva, María G. Crespo-Leiro, Luis Martínez-Martínez, Benito Almirante, José María Aguado, Luis Almenar, M.C. Fariñas, Maricela Valerio, J. Elizalde-Fernández, José Miguel Cisneros, Jordi Carratalà, Universidad de Cantabria, Universitat de Barcelona, [Aguado, J. M.] Univ Complutense, Univ Hosp 12 Octubre, Infect Dis Unit, Inst Invest Hosp 12 Octubre i +72, Madrid, Spain, [Fernandez-Ruiz, M.] Univ Complutense, Univ Hosp 12 Octubre, Infect Dis Unit, Inst Invest Hosp 12 Octubre i +72, Madrid, Spain, [Lopez-Medrano, F.] Univ Complutense, Univ Hosp 12 Octubre, Infect Dis Unit, Inst Invest Hosp 12 Octubre i +72, Madrid, Spain, [San-Juan, R.] Univ Complutense, Univ Hosp 12 Octubre, Infect Dis Unit, Inst Invest Hosp 12 Octubre i +72, Madrid, Spain, [Silva, J. T.] Univ Extremadura, Fdn Formac & Invest Profes Salud Extremadura Fund, Univ Hosp Badajoz, Dept Infect Dis, Badajoz, Spain, [Cordero, E.] Univ Seville, Clin Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville, IBiS,Univ Hosp Virgen Rocio,CSIC, Seville, Spain, [Cisneros, J. M.] Univ Seville, Clin Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville, IBiS,Univ Hosp Virgen Rocio,CSIC, Seville, Spain, [Fortun, J.] Univ Hosp Ramon & Cajal, Dept Infect Dis, Madrid, Spain, [Martin-Davila, P.] Univ Hosp Ramon & Cajal, Dept Infect Dis, Madrid, Spain, [Gudiol, C.] Univ Barcelona, Dept Infect Dis, Hosp Univ Bellvitge, Inst Invest Biomed Bellvitge IDIBELL, Barcelona, Spain, [Carratala, J.] Univ Barcelona, Dept Infect Dis, Hosp Univ Bellvitge, Inst Invest Biomed Bellvitge IDIBELL, Barcelona, Spain, [Martinez-Martinez, L.] Univ Cordoba, Reina Sofia Univ Hosp, Clin Unit Microbiol, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Andalusia, Spain, [Vidal, E.] Univ Cordoba, Reina Sofia Univ Hosp, Clin Unit Infect Dis, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Andalusia, Spain, [Caston, J. J.] Univ Cordoba, Reina Sofia Univ Hosp, Clin Unit Infect Dis, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Andalusia, Spain, [Perez-Nadales, E.] Univ Cordoba, Reina Sofia Univ Hosp, Clin Unit Infect Dis, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Andalusia, Spain, [Torre-Cisneros, J.] Univ Cordoba, Reina Sofia Univ Hosp, Clin Unit Infect Dis, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Andalusia, Spain, [Almenar, L.] Hosp Univ La Fe, Cardiol Dept, Heart Failure & Heart Transplant Unit, Valencia, Spain, [Almirante, B.] Univ Autonoma Barcelona, Dept Infect Dis, Hosp Univ Vail Hebron, Barcelona, Spain, [Gavalda, J.] Univ Autonoma Barcelona, Dept Infect Dis, Hosp Univ Vail Hebron, Barcelona, Spain, [Len, O.] Univ Autonoma Barcelona, Dept Infect Dis, Hosp Univ Vail Hebron, Barcelona, Spain, [Canton, R.] Univ Hosp Ramon & Cajal, Microbiol Dept, IRYCIS, Madrid, Spain, [Cercenado, E.] Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Hosp Gregorio Maranon, Clin Microbiol & Infect Dis, Madrid, Spain, [Goyanes, M. J.] Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Hosp Gregorio Maranon, Clin Microbiol & Infect Dis, Madrid, Spain, [Valerio, M.] Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Hosp Gregorio Maranon, Clin Microbiol & Infect Dis, Madrid, Spain, [Munoz, P.] Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Hosp Gregorio Maranon, Clin Microbiol & Infect Dis, Madrid, Spain, [Cercenado, E.] CIBERES C606 06 0058, Enfermedades Resp, Madrid, Spain, [Goyanes, M. J.] CIBERES C606 06 0058, Enfermedades Resp, Madrid, Spain, [Valerio, M.] CIBERES C606 06 0058, Enfermedades Resp, Madrid, Spain, [Munoz, P.] CIBERES C606 06 0058, Enfermedades Resp, Madrid, Spain, [Cercenado, E.] Univ Complutense Madrid, Sch Med, Med Dept, Madrid, Spain, [Goyanes, M. J.] Univ Complutense Madrid, Sch Med, Med Dept, Madrid, Spain, [Valerio, M.] Univ Complutense Madrid, Sch Med, Med Dept, Madrid, Spain, [Munoz, P.] Univ Complutense Madrid, Sch Med, Med Dept, Madrid, Spain, [Cervera, C.] Univ Alberta, Div Infect Dis, Dept Med, Edmonton, AB, Canada, [Crespo-Leiro, M. G.] Complexo Hosp Univ A Coruna, Cardiol Dept, La Coruna, Spain, [Cuervas-Mons, V.] Hosp Clin Puerto Hierro, Liver Transplantat Internal Med, Madrid, Spain, [Elizalde-Fernandez, J.] Hosp Navarra, Intens Care Unit, Pamplona, Spain, [Farinas, M. C.] Univ Cantabria, Univ Hosp Marques Valdecilla, Unit Infect Dis, Santander, Spain, [Gutierrez-Gutierrez, B.] Univ Seville, Clin Unit Infect Dis & Microbiol, Unidad Gest Clin Enfermedades Infecciosas & Micro, Inst Biomed Sevilla,Hosp Univ Virgen Macarena,IBi, Seville, Spain, [Pascual, A.] Univ Seville, Clin Unit Infect Dis & Microbiol, Unidad Gest Clin Enfermedades Infecciosas & Micro, Inst Biomed Sevilla,Hosp Univ Virgen Macarena,IBi, Seville, Spain, [Hernandez, D.] Univ Malaga, Dept Nephrol, Carlos Haya Reg Univ Hosp, Inst Biomed Res Malaga IBIMA, Malaga, Spain, [Lopez-Andujar, R.] Hosp Univ & Politecn La Fe, Gen Surg Serv, Hepatobiliopancreat Surg & Transplantat Unit, Valencia, Spain, [Montejo, M.] Univ Hosp Cruces, Unit Infect Dis, Bilbao, Spain, [Moreno, A.] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain, [Oliver, A.] Hosp Son Espases, Inst Invest Sanitaria Palma IdISPa, Dept Microbiol, Palma de Mallorca, Spain, [Oliver, A.] Hosp Son Espases, Inst Invest Sanitaria Palma IdISPa, Res Unit, Palma de Mallorca, Spain, [Roman-Broto, A.] Univ Autonoma Barcelona, Hosp Univ Vall Hebron, Lung Transplant Unit, Barcelona, Spain, [Seron, D.] Hosp Univ Vall Hebron, Nephrol Dept, Barcelona, Spain, [Sole-Jover, A.] Hosp Univ La Fe, Dept Pneumol, Lung Transplant Unit, Valencia, Spain, Spanish Ministry of Economy and Competitiveness, Institute de Salud Carlos III, and Fundacion pars la Formacion e Investigacion de los Profesionales de la Salud de Extremadura (FundeSalud), Institute de Salud Carlos III

Subjects
0301 basic medicine, medicine.medical_treatment, Antibiotics, Carbapenem-resistant enterobacteriaceae, Communicable diseases, Organ transplantation, Lactamase-producing enterobacteriaceae, Postoperative Complications, Solid organ transplantation, Medicine, Blood-stream infections, Kidney transplantation, Transplantation of organs, Carbapenem-resistant Gram-negative bacilli, High-risk patients, Multidrug resistant Gram-negative bacilli, Disease Management, Drug Resistance, Multiple, Tissue Donors, Anti-Bacterial Agents, Pseudomonas-aeruginosa bacteremia, medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Urinary-tract-infections, 03 medical and health sciences, Surgical prophylaxis, Acinetobacter-baumannii infections, Pseudomonas, Ventilator-associated pneumonia, Lung transplantation, Humans, Extended-spectrum β-lactamases, Intensive care medicine, Contraindication, Transplantation, business.industry, Bacils, Extensively-drug-resistant, Organ Transplantation, Malalties infeccioses, medicine.disease, Transplant Recipients, Trasplantament d'òrgans, Bacillus (Bacteria), Spectrum beta-lactamases, Intensive-care-unit, business, Gram-Negative Bacterial Infections
Abstract

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection. J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III.

Published
2017

10. Impact of fluconazole susceptibility on the outcome of patients with candidaemia: data from a population-based surveillance

Author

M. Fernández-Ruiz, J. Guinea, D. Lora-Pablos, Ó. Zaragoza, M. Puig-Asensio, B. Almirante, M. Cuenca-Estrella, J.M. Aguado, B. Padilla, P. Muñoz, J.R. Paño Pardo, J. García-Rodríguez, C.G. Cerrada, J. Fortún, P. Martín, E. Gómez, P. Ryan, C. Campelo, I. de los Santos Gil, V. Buendía, B.P. Gorricho, M. Alonso, F.S. Sanz, P. Merino, F. González Romo, M. Gorgolas, I. Gadea, J.E. Losa, A. Delgado-Iribarren, A. Ramos, Y. Romero, I.S. Romero, O. Zaragoza, J. Rodríguez-Baño, A.I. Suarez, A. Loza, A.I. Aller García, E. Martín-Mazuelos, M.R. Pérez de Pipaón, J. Garnacho, C. Ortiz, M. Chávez, F.L. Maroto, M. Salavert, J. Pemán, J. Blanquer, D. Navarro, J.J. Camarena, R. Zaragoza, V. Abril, C. Gimeno, S. Hernández, G. Ezpeleta, E. Bereciartua, J.L. Hernández Almaraz, M. Montejo, R.A. Rivas, R. Ayarza, A.M. Planes, I.R. Camps, J. Mensa, M. Almela, M. Gurgui, F. Sánchez-Reus, J. Martínez-Montauti, M. Sierra, J.P. Horcajada, L. Sorli, J. Gómez, A. Gené, M. Urrea, A. Mularoni, M. Valerio, A. Díaz-Martín, F. Puchades, Gilead Sciences, MSD, Astellas Pharma, Pfizer, Fundación SEIMC-GESIDA, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Red Española de Investigación en Patología Infecciosa, Fundación Mutua Madrileña, MicoLab, Merck Sharp & Dohme de España, Hikma Pharmaceuticals, United Medical Corporation, Novartis, bioMérieux, Schering-Plough, Fundación Francisco Soria Melguizo, Ferrer International, Ministerio de Asuntos Exteriores y Cooperación (España), Ministerio de Educación y Cultura (España), Ministerio de Sanidad, Servicios Sociales e Igualdad (España), Fundación Ramón Areces, [Fernandez-Ruiz, M.] Univ Complutense, Inst Invest Hosp Octubre i 12 12, Hosp Univ Octubre 12, Unit Infect Dis, Madrid, Spain, [Aguado, J. M.] Univ Complutense, Inst Invest Hosp Octubre i 12 12, Hosp Univ Octubre 12, Unit Infect Dis, Madrid, Spain, [Guinea, J.] Univ Complutense, Hosp Gen Univ Gregorio Maranon, Dept Clin Microbiol & Infect Dis, Madrid, Spain, [Lora-Pablos, D.] Hosp Univ Octubre 12, Inst Invest Hosp Octubre i 12 12, Unit Clin Res, Madrid, Spain, [Lora-Pablos, D.] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain, [Zaragoza, O.] Inst Salud Carlos III, Spanish Natl Ctr Microbiol, Dept Mycol, Madrid, Spain, [Cuenca-Estrella, M.] Inst Salud Carlos III, Spanish Natl Ctr Microbiol, Dept Mycol, Madrid, Spain, [Puig-Asensio, M.] Univ Autonoma Barcelona, Dept Med, Hosp Univ Vall dHebron, Dept Infect Dis, Barcelona, Spain, [Almirante, B.] Univ Autonoma Barcelona, Dept Med, Hosp Univ Vall dHebron, Dept Infect Dis, Barcelona, Spain, Gilead, Astellas, Fundacion SEIMC-GESIDA, Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III - European Development Regional Fund (ERDF) 'A Way to Achieve Europe'), Spanish Network for the Research in Infectious Diseases, Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, MICOLAB, Mutua Madrilena Foundation, Spanish Health Research Fund (FIS), Merck Sharp Dohme, Hickma Pharmaceutica, United Medical, bioMerieux, Schering Plough, Soria Melguizo SA, Europea Union, ALBAN program, Spanish Agency for International Cooperation, Spanish Ministry of Culture and Education, Spanish Health Research Fund, Instituto de Salud Carlos III (Spanish Ministry of Economy and Competitiveness), Ramon Areces Foundation, and Mutua Madrileria Foundation

Subjects
0301 basic medicine, Male, Antifungal Agents, Nonneutropenic patients, Dose/mic ratio, 0302 clinical medicine, 030212 general & internal medicine, Blood-stream infection, Fluconazole, Outcome, Candida, Aged, 80 and over, education.field_of_study, Diseases society, General Medicine, Middle Aged, PK/PD parameters, Infectious Diseases, Treatment Outcome, Propensity score analysis, Female, medicine.drug, Microbiology (medical), medicine.medical_specialty, Therapeutic response, 030106 microbiology, Population, Population based, Microbial Sensitivity Tests, 03 medical and health sciences, Minimum inhibitory concentration, Candidaemia, Pharmacokinetics, Drug Resistance, Fungal, Internal medicine, Interpretive breakpoints, medicine, Humans, education, Aged, business.industry, Candidemia, Odds ratio, Confidence interval, Surgery, Cross-Sectional Studies, Susceptibility, Pharmacodynamics, Critically-ill patients, business, Antifungal susceptibility
Abstract

CANDIPOP Project: B. Padilla, P. Muñoz, J. Guinea, J. R. Paño Pardo, J. García-Rodríguez, C. G. Cerrada, J. Fortún, P. Martín, E. Gómez, P. Ryan, C. Campelo, I. de los Santos, Gil, V. Buendía, B. P. Gorricho, M. Alonso, F. S. Sanz, J. M. Aguado, P. Merino, F. González Romo, M. Gorgolas, I. Gadea, J. E. Losa, A. Delgado-Iribarren, A. Ramos, Y. Romero, I. S. Romero, O. Zaragoza, M. Cuenca-Estrella, J. Rodríguez-Baño, A. I. Suarez, A. Loza, A. I. Aller García, E. Martín-Mazuelos, M. R. Pérez de Pipaón, J. Garnacho, C. Ortiz, M. Chávez, F. L. Maroto, M. Salavert, J. Pemán, J. Blanquer, D. Navarro, J. J. Camarena, R. Zaragoza, V. Abril, C. Gimeno, S. Hernández, G. Ezpeleta, E. Bereciartua, J. L. Hernández Almaraz, M. Montejo, R. A. Rivas, R. Ayarza, A. M. Planes, I. R. Camps, B. Almirante, J. Mensa, M. Almela, M. Gurgui, F. Sánchez-Reus, J. Martínez-Montauti, M. Sierra, J. P. Horcajada, L.Sorli, J. Gómez, A. Gené, M. Urrea, A. Mularoni, M.Valerio, A. Díaz-Martín, F. Puchades., [Objectives] The clinical correlation of fluconazole antifungal susceptibility testing (AST) for Candida isolates and its integration with pharmacokinetics/pharmacodynamics (PK/PD) parameters is unclear. We analysed the impact of fluconazole minimum inhibitory concentration (MIC) values, 24-hour area under the concentration–time curve (AUC24) and AUC24/MIC ratio on the outcome of candidemic patients., [Methods] We included 257 episodes of candidaemia treated with fluconazole monotherapy for ≥72 hours from a population-based surveillance conducted in 29 hospitals (CANDIPOP Project). AST was centrally performed by European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) microdilution methods. Primary outcome was clinical failure (30-day mortality and/or persistent candidaemia for ≥72 hours from initiation of therapy). Secondary outcomes included early (3–7 days) and late (3–30 days) mortality., [Results] Rates of clinical failure, early and late mortality among evaluable episodes were 32.3% (80/248), 3.1% (8/257) and 23.4% (59/248). There was no relationship between fluconazole MIC values or PK/PD parameters and clinical failure. Although MIC values ≥2 mg/L by EUCAST (positive predictive value 32.1%, negative predictive value 68.7%) and ≥0.5 mg/L by CLSI (positive predictive value 34.8%, negative predictive value 74.4%) appeared to be optimal for predicting clinical failure, no significant associations remained after multivariate adjustment (odds ratio 1.67; 95% confidence interval 0.48–5.79; p 0.423). Lack of association was consistent for alternative thresholds (including proposed clinical breakpoints). The only association found for secondary outcomes was between an AUC24/MIC ratio >400 h by CLSI and early mortality (odds ratio 0.18; 95% confidence interval 0.04–0.98; p 0.026)., [Conclusions] High fluconazole MIC values did not negatively impact outcome of patients with candidaemia treated with fluconazole. No effect of PK/PD targets on the risk of clinical failure was found., Supported in part by nonrestrictive research grants from Gilead, MSD, Astellas and Pfizer. This study was cofunded by Fundación SEIMC-GESIDA; the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (cofinanced by the European Development Regional Fund (ERDF) ‘A Way to Achieve Europe’); and the Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). MFR holds a ‘Juan Rodés’ clinical research contract (JR14/00036) and JG a ‘Miguel Servet’ contract (CPII15/00006), both from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III. MFR has received honoraria for talks on behalf of Pfizer and Gilead Sciences. JG has received grant support from Astellas Pharma, MICOLAB, the Mutua Madrileña Foundation and the Spanish Health Research Fund (FIS). He has been paid for talks on behalf of Gilead Sciences, Merck Sharp & Dohme, Pfizer, Astellas Pharma, Hickma Pharmaceutica and United Medical. BA has received grant support from Gilead Sciences, Pfizer and the Instituto de Salud Carlos III. He has received honoraria for talks on behalf of Gilead Sciences, Merck Sharp & Dohme, Pfizer, Astellas Pharma and Novartis. BP has received honoraria for talks on behalf of Gilead Sciences, Merck Sharp & Dohme, Pfizer, Astellas Pharma and Novartis. MCE has received grant support from Astellas Pharma, bioMérieux, Gilead Sciences, Merck Sharp & Dohme, Pfizer, Schering Plough, Soria Melguizo SA, Ferrer International, the Europea Union, the ALBAN program, the Spanish Agency for International Cooperation, the Spanish Ministry of Culture and Education, the Spanish Health Research Fund, the Instituto de Salud Carlos III (Spanish Ministry of Economy and Competitiveness), the Ramon Areces Foundation and the Mutua Madrileña Foundation.

Published
2017

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