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Studies comparing gradient diffusion strips (GDSs) and the EUCAST E.Def 9.4 microdilution method are scarce, thwarted by a low number of isolates, and restricted to selected antifungal agents.We evaluated the performance of GDSs to detect azole resistance in A. fumigatus, including cryptic species.A. fumigatus sensu stricto (n = 89) and cryptic species (n = 52) were classified as susceptible or resistant to itraconazole, voriconazole, posaconazole and isavuconazole (EUCAST E.Def 9.4; clinical breakpoints v10). A. fumigatus sensu stricto azole-resistant isolates had the following cyp51A gene mutations: TRFor A. fumigatus sensu stricto, itraconazole MICs1.5 mg/L, voriconazole0.38 mg/L, posaconazole0.75 mg/L, and isavuconazole0.5 mg/L correctly separated resistant from susceptible isolates with two exceptions. Considering the aforementioned cut-off MICs, sensitivity/specificity values of GDSs to detect azole resistance were: itraconazole (97%/100%), voriconazole (97%/100%), posaconazole (97%/100%) and isavuconazole (93.3%/100%). For cryptic species isolates, voriconazole MICs1 mg/L and isavuconazole0.75 mg/L separated resistant isolates from susceptible isolates with 15 and 27 exceptions, respectively. Considering the aforementioned cut-off MICs, sensitivity/specificity values were as follows: voriconazole (68.1%/100%) and isavuconazole (25%/100%). For itraconazole and posaconazole, it was not possible to establish cut-off values.We set tentative cut-off MIC values to correctly spot resistant Aspergillus fumigatus sensu stricto isolates using GDSs. The performance against cryptic species was poor.

Previous studies show high agreement between MIC spectrophotometric readings and visual inspection of azoles and amphotericin B against Aspergillus fumigatus isolates. Here, we tested and compared the in vitro activity of a novel antifungal, olorofim, against Aspergillus spp., Scedosporium spp., and Lomentospora prolificans by visual inspection and spectrophotometric readings. Clinical isolates of Aspergillus (n = 686) and Scedosporium (n = 36) spp. and L. prolificans (n = 13) were tested. Olorofim MICs were evaluated—following the EUCAST E.Def 9.4 procedure—by visual inspection or spectrophotometric readings (combinations of either ≥90% or ≥95% fungal growth inhibition endpoints compared to drug-free control endpoints and different wavelengths [405 nm, 450 nm, 492 nm, 540 nm, and 620 nm]). We observed high in vitro activity of olorofim against all tested Aspergillus spp. (MICs up to 0.06 mg/L), except for A. calidoustus, and against L. prolificans and Scedosporium spp. (MICs up to 0.125 mg/L). The combination of ≥90% fungal growth inhibition endpoints at wavelengths of ≥492 nm resulted in high essential agreements with A. fumigatus and lesser agreement with non-fumigatus Aspergillus, Scedosporium spp., and L. prolificans, although the number of isolates studied was low. This single-center study shows high agreement among olorofim MICs against A. fumigatus by visual inspection and spectrophotometric readings (≥90% fungal growth inhibition endpoints and wavelengths of ≥492 nm) and encouraging results against non-fumigatus Aspergillus spp., Scedosporium spp., and L. prolificans.

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Introduction Infective endocarditis (IE) still carries high morbidity and mortality and frequently requires surgery. The benefit of mitral valve repair (MVr) in the setting of IE is yet to be proven. The goal of this study was to assess the results of MVr in patients with IE after a minimum follow-up of 1 year. Methods This study is based on a Spanish nationwide prospective registry that included patients operated on for native mitral valve IE. The collaborating Institutions pooled their pre-, peri-, and postoperative data into the database of the GAMES group [Grupo de Apoyo al Manejo de la EndocarditiS (Group for support and management of infective endocarditis)]. Results Data from 27 hospitals were recorded and 3524 cases of active IE identified between 2008 and 2016. There were 1513 cases of mitral IE, of which 898 involved native valves. Of these, 437 patients underwent surgical treatment, and 369 completed the 1-year follow-up. The valve was repaired in 68 cases (18.4%). Preoperative groups were comparable (EuroSCORE MVr 7.7 vs MVR 8.0; p = ns). Mortality in the repair group was inferior to that in the replacement group (16.2% vs 27.2%, p = 0.058). At 1 year, mortality remained higher in the replacement group: 3.7% vs 2.9%. Relapse of the infection was slightly more frequent in the repair group (7.1% vs 3.7%; p = ns), although this did not lead to higher rates of reintervention (MVr/MVR: 2.9% vs 4.9%). Conclusion MVr is an attractive option for specific patients with IE and does not seem to negatively impact on relapses.

For the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) investigators: Hospital Costa del Sol, Marbella: Fernando Fernández Sánchez, Mariam Noureddine, Gabriel Rosas, Javier de la Torre Lima. Hospital Universitario de Cruces, (Bilbao): Roberto Blanco, María Victoria Boado, Marta Campaña Lázaro, Alejandro Crespo, Josune Goikoetxea, José Ramón Iruretagoyena, Josu Irurzun Zuazabal, Leire López-Soria, Miguel Montejo, Javier Nieto, David Rodrigo, Regino Rodríguez, Yolanda Vitoria, Roberto Voces. Hospital Universitario Virgen de la Victoria, Málaga: María (Mª) Victoria García López, Radka Ivanova Georgieva, Guillermo Ojeda, Isabel Rodríguez Bailón, Josefa Ruiz Morales. Hospital Universitario Donostia-Policlínica Gipuzkoa, San Sebastián: Ana María Cuende, Tomás Echeverría, Ana Fuerte, Eduardo Gaminde, Miguel Ángel Goenaga, Pedro Idígoras, José Antonio Iribarren, Alberto Izaguirre Yarza, Xabier Kortajarena Urkola, Carlos Reviejo. Hospital General Universitario de Alicante, Alicante: Rafael Carrasco, Vicente Climent, Patricio Llamas, Esperanza Merino, Joaquín Plazas, Sergio Reus. Complejo Hospitalario Universitario A Coruña, A Coruña: Nemesio Álvarez, José María Bravo-Ferrer, Laura Castelo, José Cuenca, Pedro Llinares, Enrique Miguez Rey, María Rodríguez Mayo, Efrén Sánchez, Dolores Sousa Regueiro. Complejo Hospitalario Universitario de Huelva, Huelva: Francisco Javier Martínez. Hospital Universitario de Canarias, Canarias: Mª del Mar Alonso, Beatriz Castro, Dácil García Rosado, Mª del Carmen Durán, Mª Antonia Miguel Gómez, Juan Lacalzada, Ibrahim Nassar. Hospital Regional Universitario de Málaga, Málaga: Antonio Plata Ciezar, José Mª Reguera Iglesias. Hospital Universitario Central Asturias, Oviedo: Víctor Asensi Álvarez, Carlos Costas, Jesús de la Hera, Jonnathan Fernández Suárez, Lisardo Iglesias Fraile, Víctor León Arguero, José López Menéndez, Pilar Mencia Bajo, Carlos Morales, Alfonso Moreno Torrico, Carmen Palomo, Begoña Paya Martínez, Ángeles Rodríguez Esteban, Raquel Rodríguez García, Mauricio Telenti Asensio. Hospital Clínic-IDIBAPS, Universidad de Barcelona, Barcelona: Manuel Almela, Juan Ambrosioni, Manuel Azqueta, Mercè Brunet, Marta Bodro, Ramón Cartañá, Carlos Falces, Guillermina Fita, David Fuster, Cristina García de la Mària, Laura García-Valls, Marta Hernández-Meneses, Jaume Llopis Pérez, Francesc Marco, José M. Miró, Asunción Moreno, David Nicolás, Salvador Ninot, Eduardo Quintana, Carlos Paré, Daniel Pereda, Juan M. Pericás, José L. Pomar, José Ramírez, Irene Rovira, Elena Sandoval, Marta Sala, Marta Sitges, Dolors Soy, Adrián Téllez, José M. Tolosana, Bárbara Vidal, Jordi Vila. Hospital General Universitario Gregorio Marañón, Madrid: Iván Adán, Javier Bermejo, Emilio Bouza, Daniel Celemín, Gregorio Cuerpo Caballero, Antonia Delgado Montero, Ana Fernández Cruz, Ana García Mansilla, Mª Eugenia García Leoni, Víctor González Ramallo, Martha Kestler Hernández, Amaia Mari Hualde, Mercedes Marín, Manuel Martínez-Sellés, Mª Cruz Menárguez, Patricia Muñoz, Cristina Rincón, Hugo Rodríguez-Abella, Marta Rodríguez-Créixems, Blanca Pinilla, Ángel Pinto, Maricela Valerio, Pilar Vázquez, Eduardo Verde Moreno. Hospital Universitario La Paz, Madrid: Isabel Antorrena, Belén Loeches, Alejandro Martín Quirós, Mar Moreno, Ulises Ramírez, Verónica Rial Bastón, María Romero, Araceli Saldaña. Hospital Universitario Marqués de Valdecilla, Santander: Jesús Agüero Balbín, Carlos Armiñanzas Castillo, Ana Arnaiz, Francisco Arnaiz de las Revillas, Manuel Cobo Belaustegui, María Carmen Fariñas, Concepción Fariñas-Álvarez, Rubén Gómez Izquierdo, Iván García, Claudia González Rico, Manuel Gutiérrez-Cuadra, José Gutiérrez Díez, Marcos Pajarón, José Antonio Parra, Ramón Teira, Jesús Zarauza. Hospital Universitario Puerta de Hierro, Madrid: Fernando Domínguez, Pablo García Pavía, Jesús González, Beatriz Orden, Antonio Ramos. Hospital Universitario Ramón y Cajal, (Madrid): Tomasa Centella, José Manuel Hermida, José Luis Moya, Pilar Martín-Dávila, Enrique Navas, Enrique Oliva, Alejandro del Río, Jorge Rodríguez-Roda Stuart, Soledad Ruiz Rodríguez. Hospital Universitario Virgen de las Nieves, Granada: Carmen Hidalgo Tenorio. Hospital Universitario Virgen Macarena, Sevilla: Manuel Almendro Delia, Omar Araji, José Miguel Barquero, Román Calvo Jambrina, Marina de Cueto, Juan Gálvez Acebal, Irene Méndez, Isabel Morales, Luis Eduardo López-Cortés. Hospital Universitario Virgen del Rocío, Sevilla: Arístides de Alarcón, Emilio García, Juan Luis Haro, José Antonio Lepe, Francisco López, Rafael Luque. Hospital San Pedro, Logroño: Luis Javier Alonso, Pedro Azcárate, José Manuel Azcona Gutiérrez, José Ramón Blanco, Lara García-Álvarez, José Antonio Oteo, Mercedes Sanz. Hospital de la Santa Creu i Sant Pau, Barcelona: Natividad de Benito, Mercé Gurguí, Cristina Pacho, Roser Pericas, Guillem Pons. Complejo Hospitalario Universitario de Santiago de Compostela, A Coruña: M. Álvarez, A. L. Fernández, Amparo Martínez, A. Prieto, Benito Regueiro, E. Tijeira, Marino Vega. Hospital Santiago Apóstol, Vitoria: Andrés Canut Blasco, José Cordo Mollar, Juan Carlos Gainzarain Arana, Oscar García Uriarte, Alejandro Martín López, Zuriñe Ortiz de Zárate, José Antonio Urturi Matos. Hospital SAS Línea de la Concepción, Cádiz: Gloria García Domínguez, Antonio Sánchez-Porto. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia: José Mª Arribas Leal, Elisa García Vázquez, Alicia Hernández Torres, Ana Blázquez, Gonzalo de la Morena Valenzuela. Hospital de Txagorritxu, Vitoria: Ángel Alonso, Javier Aramburu, Felicitas Elena Calvo, Anai Moreno Rodríguez, Paola Tarabini-Castellani. Hospital Virgen de la Salud, Toledo: Eva Heredero Gálvez, Carolina Maicas Bellido, José Largo Pau, Mª Antonia Sepúlveda, Pilar Toledano Sierra, Sadaf Zafar Iqbal-Mirza. Hospital Rafael Méndez, Lorca-Murcia: Eva Cascales Alcolea, Pilar Egea Serrano, José Joaquín Hernández Roca, Ivan Keituqwa Yañez, Ana Peláez Ballesta, Víctor Soriano. Hospital Universitario San Cecilio, Granada: Eduardo Moreno Escobar, Alejandro Peña Monje, Valme Sánchez Cabrera, David Vinuesa García. Hospital Son Llátzer, Palma de Mallorca: María Arrizabalaga Asenjo, Carmen Cifuentes Luna, Juana Núñez Morcillo, Mª Cruz Pérez Seco, Aroa Villoslada Gelabert. Hospital Universitario Miguel Servet, Zaragoza: Carmen Aured Guallar, Nuria Fernández Abad, Pilar García Mangas, Marta Matamala Adell, Mª Pilar Palacián Ruiz, Juan Carlos Porres. Hospital General Universitario Santa Lucía, Cartagena: Begoña Alcaraz Vidal, Nazaret Cobos Trigueros, María Jesús Del Amor Espín, José Antonio Giner Caro, Roberto Jiménez Sánchez, Amaya Jimeno Almazán, Alejandro Ortín Freire, Monserrat Viqueira González. Hospital Universitario Son Espases, Palma de Mallorca: Pere Pericás Ramis, Mª Ángels Ribas Blanco, Enrique Ruiz de Gopegui Bordes, Laura Vidal Bonet. Complejo Hospitalario Universitario de Albacete, Albacete: Mª Carmen Bellón Munera, Elena Escribano Garaizabal, Antonia Tercero Martínez, Juan Carlos Segura Luque., [Background] Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious for treating infective endocarditis (IE). However, the 2001 Infectious Diseases Society of America (IDSA) criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT). [Methods] Retrospective analysis of data from a multicenter, prospective cohort study of 2000 consecutive IE patients in 25 Spanish hospitals (2008–2012) was performed. [Results] A total of 429 patients (21.5%) received OPAT, and only 21.7% fulfilled IDSA criteria. Males accounted for 70.5%, median age was 68 years (interquartile range [IQR], 56–76), and 57% had native-valve IE. The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). Median length of antibiotic treatment was 42 days (IQR, 32–54), and 44% of patients underwent cardiac surgery. One-year mortality was 8% (42% for HBAT; P < .001), 1.4% of patients relapsed, and 10.9% were readmitted during the first 3 months after discharge (no significant differences compared with HBAT). Charlson score (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.04–1.42; P = .01) and cardiac surgery (OR, 0.24; 95% CI, .09–.63; P = .04) were associated with 1-year mortality, whereas aortic valve involvement (OR, 0.47; 95% CI, .22–.98; P = .007) was the only predictor of 1-year readmission. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission. [Conclusions] OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA. OPAT criteria should therefore be expanded., This work was supported by the Ministerio de Economia and Competitividad (Madrid, Spain) (FIS NCT00871104, Instituto de Salud Carlos III). J. M. P. received a “Rio Hortega” research grant from Instituto de Salud Carlos III and the Ministerio de Economia and Competitividad (Madrid, Spain) and the European Society for Clinical Microbiology and Infectious Diseases and Federation of European Microbiological Societies Research Fellowship 2016. Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (Madrid, Spain) provided J. M. M. with a personal intensification research grant (INT15/00168) during 2016 and a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques Pi i Sunyer for the period 2017–2019.

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

Summary Objective To assess the current clinical features and determinants of outcome of Candida tropicalis bloodstream infection (BSI). Methods A population-based surveillance on Candida BSI was conducted from May 2010 to April 2011 in 29 Spanish hospitals. Antifungal susceptibility testing (EUCAST methodology) was centrally performed. The characteristics and outcome of C. tropicalis BSI episodes were compared with those due to other species. Results Fifty-nine out of 752 episodes (7.8%) were due to C. tropicalis (annual incidence: 0.62 cases per 100,000 population). Resistance to fluconazole and voriconazole was found in 23.2% and 26.8% of isolates. Breakthrough BSI occurred in 10.5% of episodes. Risk factors for C. tropicalis BSI were age (odds ratio [OR]: 1.01; P -value = 0.05), underlying leukaemia (OR: 4.77; P -value = 0.001) and chronic lung disease (OR: 2.62; P -value = 0.002). There were no differences in clinical failure (persistent BSI for ≥72 h after initiation of therapy and/or 30-day all-cause mortality) between C. tropicalis (39.6%) and non- C. tropicalis groups (45.6%). The appropriateness of antifungal therapy or the fluconazole MIC values had no significant impact on outcome, whereas early central venous catheter removal exerted a protective effect. Conclusions C. tropicalis BSI was associated with advanced age, haematological malignancy and respiratory comorbidity. We found no correlation between the unexpectedly high resistance rate to azoles observed and outcome.

The aim of the study was to draw a comparison between the characteristics of infective endocarditis (IE) in patients with cancer and those of IE in noncancer patients.Patients with IE, according to the modified Duke criteria, were prospectively included in the GAMES registry between January 2008 and February 2014 in 30 hospitals. Patients with active cancer were compared with noncancer patients.During the study period, 161 episodes of IE fulfilled the inclusion criteria. We studied 2 populations: patients whose cancer was diagnosed before IE (73.9%) and those whose cancer and IE were diagnosed simultaneously (26.1%). The latter more frequently had community-acquired IE (67.5% vs 26.4%, P

Objectives To determine the epidemiology of Candida bloodstream infections, variables influencing mortality, and antifungal resistance rates in ICUs in Spain. Design Prospective, observational, multicenter population-based study. Setting Medical and surgical ICUs in 29 hospitals distributed throughout five metropolitan areas of Spain. Patients Adult patients (≥ 18 yr) with an episode of Candida bloodstream infection during admission to any surveillance area ICU from May 2010 to April 2011. Interventions Candida isolates were sent to a reference laboratory for species identification by DNA sequencing and susceptibility testing using the methods and breakpoint criteria promulgated by the European Committee on Antimicrobial Susceptibility Testing. Prognostic factors associated with early (0-7 d) and late (8-30 d) mortality were analyzed using logistic regression modeling. Measurements and main results We detected 773 cases of candidemia, 752 of which were included in the overall cohort. Among these, 168 (22.3%) occurred in adult ICU patients. The rank order of Candida isolates was as follows: Candida albicans (52%), Candida parapsilosis (23.7%), Candida glabrata (12.7%), Candida tropicalis (5.8%), Candida krusei (4%), and others (1.8%). Overall susceptibility to fluconazole was 79.2%. Cumulative mortality at 7 and 30 days after the first episode of candidemia was 16.5% and 47%, respectively. Multivariate analysis showed that early appropriate antifungal treatment and catheter removal (odds ratio, 0.27; 95% CI, 0.08-0.91), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.11; 95% CI, 1.04-1.19), and abdominal source (odds ratio, 8.15; 95% CI, 1.75-37.93) were independently associated with early mortality. Determinants of late mortality were age (odds ratio, 1.04; 95% CI, 1.01-1.07), intubation (odds ratio, 7.24; 95% CI, 2.24-23.40), renal replacement therapy (odds ratio, 6.12; 95% CI, 2.24-16.73), and primary source (odds ratio, 2.51; 95% CI, 1.06-5.95). Conclusions Candidemia in ICU patients is caused by non-albicans species in 48% of cases, C. parapsilosis being the most common among these. Overall mortality remains high and mainly related with host factors. Prompt adequate antifungal treatment and catheter removal could be critical to decrease early mortality.

A prospective, multicentre, population-based surveillance programme for Candida bloodstream infections was implemented in five metropolitan areas of Spain to determine its incidence and the prevalence of antifungal resistance, and to identify predictors of death. Between May 2010 and April 2011, Candida isolates were centralized to a reference laboratory for species identification by DNA sequencing and for susceptibility testing by EUCAST reference procedure. Prognostic factors associated with early (0–7 days) and late (8–30 days) death were analysed using logistic regression modelling. We detected 773 episodes: annual incidence of 8.1 cases/100 000 inhabitants, 0.89/1000 admissions and 1.36/10 000 patient-days. Highest incidence was found in infants younger than 1 year (96.4/100 000 inhabitants). Candida albicans was the predominant species (45.4%), followed by Candida parapsilosis (24.9%), Candida glabrata (13.4%) and Candida tropicalis (7.7%). Overall, 79% of Candida isolates were susceptible to fluconazole. Cumulative mortality at 7 and 30 days after the first episode of candidaemia was 12.8% and 30.6%, respectively. Multivariate analysis showed that therapeutic measures within the first 48 h may improve early mortality: antifungal treatment (OR 0.51, 95% CI 0.27–0.95) and central venous catheter removal (OR 0.43, 95% CI 0.21–0.87). Predictors of late death included host factors (e.g. patients' comorbid status and signs of organ dysfunction), primary source (OR 1.63, 95% CI 1.03–2.61), and severe sepsis or septic shock (OR 1.77, 95% CI 1.05–3.00). In Spain, the proportion of Candida isolates non-susceptible to fluconazole is higher than in previous reports. Early mortality may be improved with strict adherence to guidelines.

We report the molecular identifications and antifungal susceptibilities of the isolates causing fungemia collected in the CANDIPOP population-based study conducted in 29 Spanish hospitals. A total of 781 isolates (from 767 patients, 14 of them having mixed fungemia) were collected. The species found most frequently were Candida albicans (44.6%), Candida parapsilosis (24.5%), Candida glabrata (13.2%), Candida tropicalis (7.6%), Candida krusei (1.9%), Candida guilliermondii (1.7%), and Candida lusitaniae (1.3%). Other Candida and non- Candida species accounted for approximately 5% of the isolates. The presence of cryptic species was low. Compared to findings of previous studies conducted in Spain, the frequency of C. glabrata has increased. Antifungal susceptibility testing was performed by using EUCAST and CLSI M27-A3 reference procedures; the two methods were comparable. The rate of fluconazole-susceptible isolates was 80%, which appears to be a decrease compared to findings of previous studies, explained mainly by the higher frequency of C. glabrata . Using the species-specific breakpoints and epidemiological cutoff values, the rate of voriconazole and posaconazole in vitro resistance was low (C. tropicalis , using the EUCAST procedure, the rate of azole resistance was around 20%. There was a correlation between the previous use of azoles and the presence of fluconazole-resistant isolates. Resistance to echinocandins was very rare (2%), and resistance to amphotericin B also was very uncommon. The sequencing of the hot spot (HS) regions from FKS1 or FKS2 genes in echinocandin-resistant isolates revealed previously described point mutations. The decrease in the susceptibility to fluconazole in Spanish isolates should be closely monitored in future studies.

Solid organ transplant recipients (SOTR) are at risk of serious influenza-related complications. The impact of respiratory co-infection in SOTR with 2009 pandemic influenza A(H1N1) is unknown. A multicentre prospective study of consecutive cases of pandemic influenza A(H1N1) in SOTR was carried out to assess the clinical characteristics and outcome and the risk factors for co-infection. Overall, 51 patients were included. Median time from transplant was 3.7years, 5.9% of the cases occurred perioperatively and 7.8% were hospital-acquired. Pneumonia was diagnosed in 15 (29.4%) patients. Ten cases were severe (19.6%): 13.7% were admitted to intensive care units, 5.9% suffered septic shock, 5.9% developed acute graft rejection and 7.8% died. Co-infection was detected in 15 patients (29.4%): eight viral, six bacterial and one fungal. Viral co-infection did not affect the outcome. Patients with non-viral co-infection had a worse outcome: longer hospital stay (26.2±20.7 vs. 5.5±10.2) and higher rate of severe diseases (85.7% vs. 2.3%) and mortality (42.8% vs. 2.3%). Independent risk factors for non-viral co-infection were: diabetes mellitus and septic shock. Other factors associated with severe influenza were: delayed antiviral therapy, diabetes mellitus, time since transplantation

The guidelines on the treatment of invasive fungal disease by Aspergillus spp. and other fungi issued by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) are presented. These recommendations are focused on four clinical categories: oncology-haematology patients, solid organ transplant recipients, patients admitted to intensive care units, and children. An extensive review is made of therapeutical advances and scientific evidence in these settings. These guidelines have been prepared according the SEIMC consensus rules by a working group composed of specialists in infectious diseases, clinical microbiology, critical care medicine, paediatrics and oncology-haematology. Specific recommendations on the prevention of fungal infections in these patients are included.

The rate of compliance with antifungal drug use guidelines by transplant physicians is mostly unknown. We performed a nationwide electronic survey to assess antifungal use by different types of transplant physicians. Sixty-one percent (53/87) of the transplant programs responded (accounting for 85% of heart transplant procedures, 65% of kidney transplantations, and 71.5% of liver transplantations). Antifungal prophylaxis was used in 41.5% programs (liver 93.3%, heart 30.8%, and kidney 16%). Prophylaxis was universal in 32% of the programs and targeted only to selected patients in 68%, mainly indicated after re-transplantation (73.3%), re-intervention (66.7%) and hemodialysis (60%). Main drugs for universal prophylaxis were fluconazole and itraconazole (42.9% each), while fluconazole (60%), L-amphotericin B (AMB), and caspofungin (13.4% each) were preferred for targeted prophylaxis. Overall, 84.9% of the programs used galactomannan for the diagnosis of invasive aspergillosis (only 34% in BAL) and 66.6% used voriconazole as first-line monotherapy. Combination first-line therapy for invasive aspergillosis was used by 31.3%, mainly with voriconazole with caspofungin (40%) or anidulafungin (26.7%) or L-AMB-caspofungin (26.7%). Adherence of transplant physicians to current recommendations on antifungal treatment and prophylaxis is poor. An international consensus that responds to differences in patients and centers and emphasizes patient safety is clearly needed.

This study was partially financed by the CIBER de Enfermedades Respiratorias (CIBERES) from the ISCIII (CB06/06/0058) and by Fundación BBVA-FundacioóCarolina (research fellowship of Maricela Valerio)., Muñoz, P; Kestler, M; De Alarcon, A; Miro, JM; Bermejo, J; Rodriguez-Abella, H; Farinas, MC; Belaustegui, MC; Mestres, C; Llinares, P; Goenaga, M; Navas, E; Oteo, JA; Tarabini, P; Bouza, E.

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.

International audience; Background : Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality.Methods and results : Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement.Patients who received bioprostheses were older (62 vs 54 years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p = 0.0009) and 25.3% vs 16.6% (p < .0001), respectively.In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10 years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60).Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298).Conclusions :Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction.

We aimed to develop a simple prediction score to identify fluconazole non-susceptible (Flu-NS) candidaemia using simple clinical criteria. A derivation cohort was extracted from the CANDIPOP study, a prospective, multicentre, population-based surveillance programme on candidaemia conducted in 29 hospitals in Spain from April 2010 to May 2011. The score was validated with an external, multicentre cohort of adults with candidaemia in six tertiary hospitals in three countries. The prediction score was based on three variables selected by a logistic regression model together with the severity of disease. In total, 617 and 297 cases of candidaemia were included in the derivation and validation cohorts, respectively; of these, 134 (21.7%) and 57 (19.2%) were caused by Flu-NS strains. Factors independently associated with Flu-NS were transplant recipient status (adjusted odds ratio (AOR) 2.13; 95% CI 1.01–4.55; p 0.047), hospitalization in a unit with a high prevalence (≥15%) of Flu-NS strains (7.53; 4.68–12.10; p

Aims Surgery for infective endocarditis (IE) is associated with high mortality. Our objectives were to describe the experience with surgical treatment for IE in Spain, and to identify predictors of in-hospital mortality. Methods Prospective cohort of 1000 consecutive patients with IE. Data were collected in 26 Spanish hospitals. Results Surgery was performed in 437 patients (43.7%). Patients treated with surgery were younger and predominantly male. They presented fewer comorbid conditions and more often had negative blood cultures and heart failure. In-hospital mortality after surgery was lower than in the medical therapy group (24.3 vs 30.7%, p = 0.02). In patients treated with surgery, endocarditis involved a native valve in 267 patients (61.1%), a prosthetic valve in 122 (27.9%), and a pacemaker lead with no clear further valve involvement in 48 (11.0%). The most common aetiologies were Staphylococcus (186, 42.6%), Streptococcus (97, 22.2%), and Enterococcus (49, 11.2%). The main indications for surgery were heart failure and severe valve regurgitation. A risk score for in-hospital mortality was developed using 7 prognostic variables with a similar predictive value (OR between 1.7 and 2.3): PALSUSE: prosthetic valve, age ≥ 70, large intracardiac destruction, Staphylococcus spp, urgent surgery, sex [female], EuroSCORE ≥ 10. In-hospital mortality ranged from 0% in patients with a PALSUSE score of 0 to 45.4% in patients with PALSUSE score > 3. Conclusions The prognosis of IE surgery is highly variable. The PALSUSE score could help to identify patients with higher in-hospital mortality. 4.036 JCR (2014) Q1, 29/123 Cardiac and cardiovascular systems UEM

International audience; IMPORTANCE: There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). OBJECTIVE: To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. INTERVENTIONS: Valve replacement during index hospitalization (early surgery) vs medical therapy. MAIN OUTCOMES AND MEASURES: In-hospital and 1-year mortality. RESULTS: Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P = .007) quintiles of surgical propensity. CONCLUSIONS AND RELEVANCE: Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.

International audience; Enterococci are reportedly the third most common group of endocarditis-causing pathogens but data on enterococcal infective endocarditis (IE) are limited. The aim of this study was to analyse the characteristics and prognostic factors of enterococcal IE within the International Collaboration on Endocarditis. In this multicentre, prospective observational cohort study of 4974 adults with definite IE recorded from June 2000 to September 2006, 500 patients had enterococcal IE. Their characteristics were described and compared with those of oral and group D streptococcal IE. Prognostic factors for enterococcal IE were analysed using multivariable Cox regression models. The patients' mean age was 65 years and 361/500 were male. Twenty-three per cent (117/500) of cases were healthcare related. Enterococcal IE were more frequent than oral and group D streptococcal IE in North America. The 1-year mortality rate was 28.9% (144/500). E. faecalis accounted for 90% (453/500) of enterococcal IE. Resistance to vancomycin was observed in 12 strains, eight of which were observed in North America, where they accounted for 10% (8/79) of enterococcal strains, and was more frequent in E. faecium than in E. faecalis (3/16 vs. 7/364 , p 0.01). Variables significantly associated with 1-year mortality were heart failure (HR 2.4, 95% CI 1.7--3.5, p

International audience; CONTEXT: Infection of implantable cardiac devices is an emerging disease with significant morbidity, mortality, and health care costs. OBJECTIVES: To describe the clinical characteristics and outcome of cardiac device infective endocarditis (CDIE) with attention to its health care association and to evaluate the association between device removal during index hospitalization and outcome. DESIGN, SETTING, AND PATIENTS: Prospective cohort study using data from the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), conducted June 2000 through August 2006 in 61 centers in 28 countries. Patients were hospitalized adults with definite endocarditis as defined by modified Duke endocarditis criteria. MAIN OUTCOME MEASURES: In-hospital and 1-year mortality. RESULTS: CDIE was diagnosed in 177 (6.4% [95% CI, 5.5%-7.4%]) of a total cohort of 2760 patients with definite infective endocarditis. The clinical profile of CDIE included advanced patient age (median, 71.2 years [interquartile range, 59.8-77.6]); causation by staphylococci (62 [35.0% {95% CI, 28.0%-42.5%}] Staphylococcus aureus and 56 [31.6% {95% CI, 24.9%-39.0%}] coagulase-negative staphylococci); and a high prevalence of health care-associated infection (81 [45.8% {95% CI, 38.3%-53.4%}]). There was coexisting valve involvement in 66 (37.3% [95% CI, 30.2%-44.9%]) patients, predominantly tricuspid valve infection (43/177 [24.3%]), with associated higher mortality. In-hospital and 1-year mortality rates were 14.7% (26/177 [95% CI, 9.8%-20.8%]) and 23.2% (41/177 [95% CI, 17.2%-30.1%]), respectively. Proportional hazards regression analysis showed a survival benefit at 1 year for device removal during the initial hospitalization (28/141 patients [19.9%] who underwent device removal during the index hospitalization had died at 1 year, vs 13/34 [38.2%] who did not undergo device removal; hazard ratio, 0.42 [95% CI, 0.22-0.82]). CONCLUSIONS: Among patients with CDIE, the rate of concomitant valve infection is high, as is mortality, particularly if there is valve involvement. Early device removal is associated with improved survival at 1 year.

Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.

A prospective, population-based surveillance on candidaemia was implemented in five metropolitan areas of Spain from May 2010 to April 2011. We aimed to describe the distribution and susceptibility pattern of Candida species, and to evaluate risk factors for mortality in patients with oncological (solid tumours) and haematological malignancies. Adults (≥16 years) with cancer were included in the present report. Impact of therapeutic strategies on 7- and 30-day mortality were analysed by logistic regression, adjusting for propensity score by inverse weighting probability of receiving early antifungal treatment and catheter removal. We included 238 (32.6%) patients (195 oncological, 43 haematological). Compared with oncological patients, haematological patients were more likely to have received chemotherapy (53.5% versus 17.4%, p

Streptococcus pneumoniae is an infrequent cause of severe infectious endocarditis (IE). The aim of our study was to describe the epidemiology, clinical and microbiological characteristics, and outcome of a series of cases of S. pneumoniae IE diagnosed in Spain and in a series of cases published since 2000 in the medical literature. We prospectively collected all cases of IE diagnosed in a multicenter cohort of patients from 27 Spanish hospitals (n = 2539). We also performed a systematic review of the literature since 2000 and retrieved all cases with complete clinical data using a pre-established protocol. Predictors of mortality were identified using a logistic regression model. We collected 111 cases of pneumococcal IE: 24 patients from the Spanish cohort and 87 cases from the literature review. Median age was 51 years, and 23 patients (20.7%) were under 15 years. Men accounted for 64% of patients, and infection was community-acquired in 96.4% of cases. The most important underlying conditions were liver disease (27.9%) and immunosuppression (10.8%). A predisposing heart condition was present in only 18 patients (16.2%). Pneumococcal IE affected a native valve in 93.7% of patients. Left-sided endocarditis predominated (aortic valve 53.2% and mitral valve 40.5%). The microbiological diagnosis was obtained from blood cultures in 84.7% of cases. In the Spanish cohort, nonsusceptibility to penicillin was detected in 4.2%. The most common clinical manifestations included fever (71.2%), a new heart murmur (55%), pneumonia (45.9%), meningitis (40.5%), and Austrian syndrome (26.1%). Cardiac surgery was performed in 47.7% of patients. The in-hospital mortality rate was 20.7%. The multivariate analysis revealed the independent risk factors for mortality to be meningitis (OR, 4.3; 95% CI, 1.4–12.9; P

Introduction. Invasive infections caused by Candida spp. in critically ill patients may significantly worsen their prognosis, so it is of great importance to establish an early detection and a suitable therapeutic strategy. The objective of this study was to define the differential role of echinocandins in treating certain critical patient profiles. Methodology. A scientific committee of 9 experts in infectious diseases, critical care, microbiology, and hospital pharmacy reviewed the existing evidence on the treatment of candidemia and invasive candidiasis in critically ill patients. After that, a questionnaire with 35 items was elaborated to be agreed by 26 specialists in the aforementioned disciplines using a modified Delphi method. Results. After two rounds of evaluation, a consensus was reached in terms of agreement in 66% of the items. Some of the consensuses achieved included: it is not necessary to adjust the dose of echinocandins during renal replacement therapy; the echinocandins are the empirical and/or directed treatment of choice for candidemia and invasive candidiasis associated with biofilms; these drugs may be used in the antifungal prophylaxis of high-risk liver transplantation. In the absence of additional clinical data, it should be noted that micafungin is the echinocandin with the most available scientific evidence. Conclusions. The experts consulted showed a high degree of agreement on some of the most controversial aspects regarding the management of candidemia and invasive candidiasis in critical patients, which could inform of practical recommendations for their treatment.