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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. Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales: The impact of cytomegalovirus disease and lymphopenia

Author

Perez-Nadales, E., Gutierrez-Gutierrez, B., Natera, A. M., Abdala, E., Reina Magalhaes, M., Mularoni, A., Monaco, F., Camera Pierrotti, L., Pinheiro Freire, M., Iyer, R. N., Mehta Steinke, S., Grazia Calvi, E., Tumbarello, M., Falcone, M., Fernandez-Ruiz, M., Costa-Mateo, J. M., Rana, M. M., Mara Varejao Strabelli, T., Paul, M., Carmen Farinas, M., Clemente, W. T., Roilides, E., Munoz, P., Dewispelaere, L., Loeches, B., Lowman, W., Hock Tan, B., Escudero-Sanchez, R., Bodro, M., Antonio Grossi, P., Soldani, F., Gunseren, F., Nestorova, N., Pascual, A., Martinez-Martinez, L., Aguado, J., Rodriguez-Bano, J., Torre-Cisneros, J., Wan Song, A. T., Andraus, W., Carneiro D'Albuquerque, L. A., David-Neto, E., Jota de Paula, F., Rossi, F., Ostrander, D., Avery, R., Rizzi, M., Losito, A. R., Raffaelli, F., Del Giacomo, P., Tiseo, G., Lora-Tamayo, J., San-Juan, R., Gracia-Ahufinger, I., Caston, J., Ruiz, Y. A., Altman, D. R., Campos, S. V., Bar-Sinai, N., Koppel, F., Arnaiz de las Revillas Almajano, F., Gonzalez Rico, C., Fernandez Martinez, M., Mourao, P. H. O., Neves, F. A., Ferreira, J., Pyrpasopoulou, A., Iosifidis, E., Romiopoulos, I., Minero, M. V., Sanchez-Carrillo, C., Lardo, S., Coussement, J., Dodemont, M., Jiayun, K., Martin-Davila, P., Fortun, J., Almela, M., Moreno, A., Linares, L., Gasperina, D. D., Balsamo, M. L., Rovelli, C., Concia, E., Chiesi, S., Salerno, D. N., Ogunc, D., Pilmis, B., Seminari, E. M., Carratala, J., Dominguez, A., Cordero, E., Lepe, J. A., Montejo, M., Merino de Lucas, E., Eriksson, B. M., van Delden, C., Manuel, O., Arslan, H., Kocak Tufan, Z., Kazak, E., David, M., Lease, E., Cornaglia, G., Akova, M., European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, and Universidad de Cantabria

Subjects
medicine.medical_specialty, Combination therapy, infectious disease, 030230 surgery, Settore MED/17 - MALATTIE INFETTIVE, Logistic regression, clinical research/practice, 03 medical and health sciences, 0302 clinical medicine, infection and infectious agents - bacterial, Internal medicine, medicine, Immunology and Allergy, Pharmacology (medical), organ transplantation in general, Infection and infectious agents - bacterial, Transplantation, Infectious disease, Receiver operating characteristic, business.industry, Hazard ratio, Confidence interval, Organ transplantation in general, antibiotic drug resistance, Cohort, Clinical research/practice, Antibiotic drug resistance, business, Cohort study
Abstract

Treatment of carbapenemase‐producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase‐producing Enterobacterales bloodstream infections. A multinational, retrospective (2004‐2016) cohort study (INCREMENT‐SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30‐day all‐cause mortality. The INCREMENT‐SOT‐CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT‐CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT‐CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76‐0.88) and classified patients into 3 strata: 0‐7 (low mortality), 8‐11 (high mortality), and 12‐17 (very‐high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very‐high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13‐7.06, P = .03) and high (HR 9.93, 95% CI 2.08‐47.40, P = .004) mortality risk strata. A score‐based algorithm is provided for therapy guidance., This work was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0008; RD16/0016/0001, RD16/0016/0002, RD16/0016/00010] ‐ co‐financed by 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 JMA]; Sociedad Andaluza de Trasplante de Órgano Sólido [SATOT grant to LMM]; ESCMID Study Group for Bloodstream Infections and Sepsis (ESGBIS); and ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS).

Published
2020

4. 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

5. 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

6. 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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7. 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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8. 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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