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1. Analysis of the factors predicting clinical response to tocilizumab therapy in patients with severe COVID-19

Author

Rafael San-Juan, Mario Fernández-Ruiz, Francisco López-Medrano, Octavio Carretero, Antonio Lalueza, Guillermo Maestro de la Calle, María Asunción Pérez-Jacoiste Asín, Héctor Bueno, José Manuel Caro-Teller, Mercedes Catalán, Cristina de la Calle, Rocío García-García, Carlos Gómez, Rocío Laguna-Goya, Manuel Lizasoáin, Joaquín Martínez-López, Julia Origüen, Ángel Sevillano, Eduardo Gutiérrez, Borja de Miguel, Fernando Aguilar, Patricia Parra, Mar Ripoll, Tamara Ruiz-Merlo, Hernando Trujillo, José Luis Pablos, Estela Paz-Artal, Carlos Lumbreras, and José María Aguado

Subjects
Microbiology (medical), ALT, alanine transaminase, Infectious and parasitic diseases, RC109-216, clinical response, Antibodies, Monoclonal, Humanized, NAT, nucleic acid testing, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, Article, tocilizumab, RT-PCR, reverse transcription polymerase chain reaction, AST, aspartate transaminase, LPV/r, lopinavir/ritonavir, Humans, IL-6, interleukin-6, ARDS, acute respiratory distress syndrome, IQR, interquartile range, Retrospective Studies, COVID-19, coronavirus disease 2019, LDH, lactate dehydrogenase, SARS-CoV-2, TCZ, tocilizumab, COVID-19, HCQ, hydroxychloroquine, General Medicine, ICU, intensive care unit, COVID-19 Drug Treatment, early initiation, predictors, IMV, invasive mechanical ventilation, Infectious Diseases, CRP, C-reactive protein, IFN-β, interferon-β, OTR, oxygen therapy requirements, SCI, Significant clinical improvement, ePO2/FiO2, estimated arterial oxygen/fraction of inspired oxygen ratio
Abstract

Background: Controversy remains about the efficacy of tocilizumab (TCZ) for the treatment of severe COVID-19. We aimed to analyze the profile of TCZ-respondent patients. Methods: We retrospectively analyzed a cohort of patients with severe COVID-19 who received off-label TCZ after recommendation by a local committee and were admitted to the University Hospital “12 de Octubre” until May 2020. The primary end point was a significant clinical improvement (SCI) on day 14 after administration of TCZ. Factors independently related to SCI were analyzed by multivariate logistic regression models. Results: Of 428 (63.3%) patients treated with TCZ, 271 (63.3%) experienced SCI. After adjustment for factors related to unfavorable outcomes, TCZ administration within the first 48 hours from admission (odds ratio [OR]: 1.98, 95% confidence Interval [95% CI]: 1.1–3.55; P = 0.02) and ALT levels >100 UI/L at day 0 (OR: 3.28; 95% CI: 1.3–8.1; P = 0.01) were independently related to SCI. The rate of SCI significantly decreased according to the time of TCZ administration: 70.2% in the first 48 hours from admission, 58.5% on days 3-7, and 45.1% after day 7 (P = 0.03 and P = 0.001, respectively). Conclusion: TCZ improves the prognosis of patients with COVID-19 the most if treatment starts within the first 48 hours after admission.

Published
2022

2. Remdesivir and survival outcomes in critically ill patients with COVID-19: A multicentre observational cohort study

Author

Catia Cillóniz, Anna Motos, Tatiana Castañeda, Albert Gabarrús, Ferran Barbé, Antoni Torres, Víctor D. Gumucio-Sanguino, Rafael Mañez, Jordi Solé-Violan, Felipe Rodríguez de Castro, Fernando Suarez-Sipmann, Ruth Noemí Jorge García, María Mora Aznar, Mateu Torres, María Martinez, Cynthia Alegre, Jordi Riera, Sofía Contreras, Juan Manuel Pericas, Ricard Ferrer, Jesús Caballero, Javier Trujillano, Montse Vallverdú, Miguel León, Mariona Badía, Begoña Balsera, Lluís Servià, Judit Vilanova, Silvia Rodríguez, Neus Montserrat, Silvia Iglesias, Javier Prados, Sula Carvalho, Mar Miralbés, Josman Monclou, Gabriel Jiménez, Jordi Codina, Estela Val, Pablo Pagliarani, Jorge Rubio, Dulce Morales, Andrés Pujol, Àngels Furro, Beatriz García, Gerard Torres, Javier Vengoechea, David de Gonzalo-Calvo, Jessica González, Silvia Gomez, José M. Gómez, Nieves Franco, José Barberán, Guillermo M Albaiceta, Lorena Forcelledo Espina, Emilio García Prieto, Paula Martín Vicente, Cecilia del Busto Martínez, Pablo Vidal-Cortés, José Luis García Garmendia, María Aguilar Cabello, Carmen Eulalia Martínez Fernández, Nieves Carbonell, María Luisa Blasco Cortés, Ainhoa Serrano Lázaro, Mar Juan Díaz, Aaron Blandino Ortiz, Rosario Menendez, Luis Jorge Valdivia, María Victoria Boado, Susana Sancho Chinesta, Maria del Carmen de la Torre, Ignacio Martínez Varela, María Teresa Bouza Vieiro, Inés Esmorís Arijón, David Campi Hermoso, Rafaela Nogueras Salinas, Teresa Farre Monjo, Ramon Nogue Bou, Gregorio Marco Naya, Carme Barberà, Núria Ramon Coll, Mercedes Catalán-González, Juan Carlos Montejo-González, Gloria Renedo Sanchez-Giron, Juan Bustamante-Munguira, Elena Bustamante-Munguira, Ramon Cicuendez Avila, Nuria Mamolar Herrera, Raquel Almansa, Alicia Ortega, Jesús Bermejo-Martin, Víctor Sagredo, Jose Añon, Alexander Agrifoglio, Lucia Cachafeiro, Emilio Maseda, Lorenzo Socias, Mariana Andrea Novo, Albert Figueras, Maria Teresa Janer, Laura Soliva, Marta Ocón, Luisa Clar, J Ignacio Ayestarán, Yhivian Peñasco, Sandra Campos Fernández, Mireia Serra-Fortuny, Eva Forcadell-Ferreres, Immaculada Salvador-Adell, Neus Bofill, Berta Adell-Serrano, Josep Pedregosa Díaz, Núria Casacuberta-Barberà, Luis Urrelo-Cerrón, Àngels Piñol-Tena, Ferran Roche-Campo, Amalia Martínez de la Gándara, Pablo Ryan Murúa, Covadonga Rodríguez Ruíz, Laura Carrión García, Juan I Lazo Álvarez, José Ángel Lorente, Ana Loza-Vázquez, Desire Macias Guerrero, Arturo Huerta, Daniel Tognetti, Carlos García Redruello, David Mosquera Rodríguez, Eva María Menor Fernández, Sabela Vara Adrio, Vanesa Gómez Casal, Marta Segura Pensado, María Digna Rivas Vilas, Amaia García Sagastume, Raul de Pablo Sánchez, David Pestaña Laguna, Tommaso Bardi, Rosario Amaya Villar, Carmen Gómez Gonzalez, Maria Luisa Gascón Castillo, José Garnacho-Montero, María Luisa Cantón-Bulnes, Judith Marin-Corral, Cristina Carbajales Pérez, Joan Ramon Masclans, Ana Salazar Degracia, Judit Bigas, Rosana Muñoz-Bermúdez, Clara Vilà-Vilardel, Francisco Parrilla, Irene Dot, Ana Zapatero, Yolanda Díaz, María Pilar Gracia, Purificación Pérez, Andrea Castellví, Cristina Climent, Lidia Serra, Laura Barbena, Iosune Cano, Pilar Ricart, Alba Herraiz, Pilar Marcos, Laura Rodríguez, Maria Teresa Sariñena, Ana Sánchez, Alejandro Úbeda, María Cruz Martin Delgado, Elena Gallego, Juan Fernando Masa Jimenez, Gemma Gomà, Emi Díaz, Mercedes Ibarz, Diego De Mendoza, Enric Barbeta, Victoria Alcaraz-Serrano, Joan Ramon Badia, Manuel Castella, Leticia Bueno, Adrian Ceccato, Andrea Palomeque, Laia Fernandez Barat, Pamela Conde, Javier Fernández, Albert Gabarrus, Karsa Kiarostami, Alexandre López-Gavín, Cecilia L Mantellini, Carla Speziale, Nil Vázquez, Hua Yang, Minlan Yang, Carlos Ferrando, Pedro Castro, Marta Arrieta, Jose Maria Nicolas, Rut Andrea, Marta Barroso, Raquel Pérez, Sergio Álvarez, Dario Garcia-Gasulla, Adrián Tormos, Luis Tamayo Lomas, Cesar Aldecoa, Rubén Herrán-Monge, José Ángel Berezo García, Pedro Enríquez Giraudo, Pablo Cardinal Fernández, Alberto Rubio López, Orville Báez Pravia, Juan López Messa, Leire Pérez Bastida, Antonjo Alvarez Ruiz, José Trenado, Anna Parera Pous, Cristóbal Galbán, Ana López Lago, Eva Saborido Paz, Patricia Barral Segade, Ana Balan Mariño, Manuel Valledor Mendez, Raúl de Frutos, Luciano Aguilera, Felipe Pérez-García, Esther López-Ramos, Ángela Leonor Ruiz-García, Belén Beteré, Rafael Blancas, Cristina Dólera, Gloria Perez Planelles, Enrique Marmol Peis, Maria Dolores Martinez Juan, Miriam Ruiz Miralles, Eva Perez Rubio, Maria Van der Hofstadt Martin-Montalvo, Ángel Sánchez-Miralles, Tatiana Villada Warrington, Juan Carlos Pozo-Laderas, Angel Estrella, Sara Guadalupe Moreno Cano, Federico Gordo, Basilisa Martinez Palacios, Maite Nieto, Maria Teresa Nieto, Sergio Ossa, Ana Ortega, Miguel Sanchez, and Bitor Santacoloma

Subjects
Microbiology (medical), Infectious Diseases
Published
2022

3. Effectiveness of anakinra for tocilizumab-refractory severe COVID-19: A single-centre retrospective comparative study

Author

Estela Paz-Artal, Borja de Miguel, Octavio Carretero, Guillermo Maestro de la Calle, Carlos Mario Gómez Gómez, Mar Ripoll, Rocío García-García, Marcos Sánchez-Fernández, Rafael San Juan, Antonio Lalueza, Carlos Lumbreras, José L. Pablos, José María Aguado, Jaime Lora-Tamayo, Mario Fernández-Ruiz, Joaquin Martinez-Lopez, Cristina de la Calle, Fernando Aguilar, José Manuel Caro-Teller, Angel Sevillano, Julia Origüen, María Asunción Pérez-Jacoiste Asín, Mercedes Catalán, Francisco López-Medrano, Héctor Bueno, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), and Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)

Subjects
0301 basic medicine, Male, Infectious and parasitic diseases, RC109-216, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, Hospital Mortality, Treatment Failure, skin and connective tissue diseases, Outcome, General Medicine, Tocilizumab, Middle Aged, Single centre, Infectious Diseases, Anakinra, Treatment Outcome, Christian ministry, Female, Cytokine Release Syndrome, medicine.drug, Microbiology (medical), musculoskeletal diseases, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Library science, Antibodies, Monoclonal, Humanized, Article, Immunomodulation, 03 medical and health sciences, Political science, medicine, Humans, Aged, Retrospective Studies, Salvage Therapy, SARS-CoV-2, COVID-19, Interleukin 1 Receptor Antagonist Protein, chemistry, Spain, Case-Control Studies, Therapy
Abstract

A subgroup of patients with SARS-CoV-2 infection was thought to have developed cytokine release syndrome and were treated with tocilizumab; however, a significant percentage of patients evolved. This study aimed to determine the usefulness of anakinra as a rescue treatment for patients with tocilizumab-refractory COVID-19 disease. A prospective cohort of patients with COVID-19 pneumonia who received anakinra as salvage therapy after failure of tocilizumab were compared (1:1) with selected controls in a historical cohort of patients treated with tocilizumab. Cases and controls were matched by age, comorbidities, pulse oximetry oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at baseline, and time elapsed since the initiation of treatment with tocilizumab. The primary outcome was the improvement in clinical status measured by a 6-point ordinal scale, from baseline to day 21. The study included 20 cases and 20 controls (mean age 65.3 ± 12.8 years, 65% males). No differences were found in the clinical improvement rates at 7, 14 and 21 days of follow-up. The in-hospital mortality rate for patients receiving anakinra was 55% vs. 45% in the control group (P = 0.527). Treatment with anakinra was not useful in improving the prognosis of patients with tocilizumab-refractory severe COVID-19. This work was supported by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COV20/00181) — co‐financed by European Development Regional Fund “A way to achieve Europe”. M.F.R. holds a research contract “Miguel Servet” (CP18/00073) from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III. Sí

Published
2021

4. Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: a single-center retrospective study

Author

Octavio Carretero, Carlos Lage Gómez, Borja de Miguel, Héctor Bueno, Eduardo Gutiérrez, Joaquin Martinez-Lopez, Julia Origüen, Rafael San Juan, José L. Pablos, Guillermo Chiara-Graciani, José María Aguado, José Tiago Silva, Mercedes Catalán, Hernando Trujillo, Daniel García-Ruiz de Morales, Cristina de la Calle, María Asunción Pérez-Jacoiste Asín, Rocío García-García, Carlos Lumbreras, José Manuel Caro, Antonio Lalueza, Mar Ripoll, Miguel Saro-Buendía, Guillermo Maestro de la Calle, Estela Paz-Artal, Angel Sevillano, Fernando Aguilar, Mario Fernández-Ruiz, Ángel Marrero-Sánchez, and Francisco López-Medrano

Subjects
0301 basic medicine, Microbiology (medical), Male, medicine.medical_specialty, Combination therapy, Secondary infection, 030106 microbiology, Infectious and parasitic diseases, RC109-216, Single Center, immunomodulation, Antibodies, Monoclonal, Humanized, Gastroenterology, Methylprednisolone, Article, corticosteroids, 03 medical and health sciences, chemistry.chemical_compound, tocilizumab, 0302 clinical medicine, Tocilizumab, Internal medicine, medicine, Humans, 030212 general & internal medicine, Aged, Retrospective Studies, Aged, 80 and over, therapy, business.industry, SARS-CoV-2, Hazard ratio, COVID-19, Retrospective cohort study, General Medicine, Odds ratio, Middle Aged, mortality, Confidence interval, COVID-19 Drug Treatment, Infectious Diseases, chemistry, outcome, Drug Therapy, Combination, Female, business, medicine.drug
Abstract

BackgroundThe role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear.MethodsWe conducted a retrospective single-center study including consecutive patients ≥65 years that developed severe COVID-19 between March 3 and May 1, 2020 and were treated with corticosteroids at various doses (methylprednisolone [0.5 mg/Kg/12 hours to 250 mg/24 hours]), either alone (“CS group”) or associated to intravenous tocilizumab (400-600 mg, one to three doses) (“CS-TCZ group”). Primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2-point decrease on a six-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied.ResultsOverall, 181 and 80 patients were included in the CS and CS-TCZ groups. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17 – 0.68;P-value = 0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21 – 0.68;P-value = 0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21 – 0.72;P-value = 0.003). Clinical improvement by day +14 was higher in the CS-TCZ group in the IPTW analysis only (OR: 2.26; 95% CI: 1.49 – 3.41;P-value ConclusionsThe combination of corticosteroids and TCZ was associated with better outcomes among patients ≥65 years with severe COVID-19.

Published
2021

5. Tocilizumab for the treatment of adult patients with severe COVID‐19 pneumonia: A single‐center cohort study

Author

Carlos Lumbreras, Rafael San Juan, Rocío Laguna-Goya, Joaquin Martinez-Lopez, José María Aguado, María Asunción Pérez-Jacoiste Asín, José Manuel Caro-Teller, Guillermo Maestro de la Calle, Manuel Lizasoain, Francisco López-Medrano, José L. Pablos, Mar Ripoll, Cristina de la Calle, Mario Fernández-Ruiz, Héctor Bueno, Julia Origüen, Carlos Mario Gómez Gómez, Hernando Trujillo, Mercedes Catalán, and Rocío García-García

Subjects
Male, immunomodulation, Severity of Illness Index, SARS‐CoV‐2, Body Temperature, chemistry.chemical_compound, 0302 clinical medicine, Heart Rate, Medicine, 030212 general & internal medicine, Research Articles, Middle Aged, C-Reactive Protein, Infectious Diseases, Administration, Intravenous, Female, 030211 gastroenterology & hepatology, Cytokine Release Syndrome, Research Article, Cohort study, Adult, medicine.medical_specialty, Antibodies, Monoclonal, Humanized, Antiviral Agents, tocilizumab, 03 medical and health sciences, Tocilizumab, Respiratory Rate, COVID‐19, Internal medicine, Virology, Severity of illness, pneumonia, Humans, Immunologic Factors, Adverse effect, Retrospective Studies, L-Lactate Dehydrogenase, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, Interferon-beta, Odds ratio, medicine.disease, Receptors, Interleukin-6, Survival Analysis, COVID-19 Drug Treatment, Pneumonia, chemistry, Concomitant, business
Abstract

Coronavirus disease 2019 (COVID‐19) can lead to a massive cytokine release. The use of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6‐point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6‐point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon‐β (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06‐0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06‐0.99; P = .048) were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C‐reactive protein levels dropped by day 2. There were no TCZ‐attributable adverse events. In this observational single‐center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID‐19 pneumonia., Highlights COVID‐19 can lead to a hyperinflammatory state that mirrors the cytokine release syndrome.The off‐labeluse of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab has been proposed to abrogate this deleterious inflammatory response, although the supporting evidence is scarce.In the present single‐centre study comprising 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous tocilizumab between March 16 and 27, 2020, the rates of clinical improvement (defined by discharge to home and/or a decrease of = 2 points on a six‐point ordinal scale) were 44.3% (39/88) and 73.9% (65/88) by days 7 and 14, respectively.The previous or concomitant use of interferon‐β and baseline serum lactate dehydrogenase levels >450 U/L were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8%, with no tocilizumab‐attributable adverse events.

Published
2020
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6. A non-compulsory stewardship programme for the management of antifungals in a university-affiliated hospital

Author

Carlos Lumbreras, José María Aguado, J.M. Ferrari, Fernando Chaves, A. Herreros de Tejada, R. San Juan, J.C. Montejo, Manuel Lizasoain, Francisco López-Medrano, and Mercedes Catalán

Subjects
Microbiology (medical), medicine.medical_specialty, Antifungal Agents, Hospitals, University, resistance, Route of administration, chemistry.chemical_compound, stewardship, Drug Resistance, Fungal, Internal medicine, cost, Humans, Medicine, Antimicrobial stewardship, Medical prescription, Intensive care medicine, Candida, Voriconazole, Antifungals, Chi-Square Distribution, business.industry, Incidence (epidemiology), Candidiasis, General Medicine, Antimicrobial, Prescriptions, Treatment Outcome, Infectious Diseases, chemistry, Caspofungin, Pharmacy Service, Hospital, business, Fluconazole, medicine.drug
Abstract

Antimicrobial stewardship programmes promote excellence in the use of antimicrobials by selecting the appropriate antimicrobial agent and the correct dose, route of administration and duration of treatment. However, there is limited experience with such programmes targeting antifungal treatments. We present the results of a non-compulsory programme for the control of antifungals. For 12 months, prescriptions of oral voriconazole or intravenous voriconazole, caspofungin and liposomal amphotericin B were reviewed, and non-compulsory recommendations were made. The incidence and outcome of fungal infections were examined. The results for the dispensed defined daily doses (DDDs) and expenditure on antifungals were compared with those for the previous 12 months. The number of antifungal treatments reviewed was 662. A recommendation to change treatment was made in 29% of the cases, including a change from intravenous to oral treatment (15%), cessation of antifungal treatment (8%), and a change to fluconazole (6%). The DDDs of intravenous voriconazole and caspofungin were reduced by 31.4% and 20.2%, respectively. The DDDs of oral voriconazole and dispensed vials of liposomal amphotericin B were increased by 8.2% and 13.9%, respectively. Expenditure on antifungals was reduced by US$370681.78 (11.8% reduction). The programme was not related to significant increases in the incidence of candidaemia, percentage of persistent/relapsing candidaemia cases, percentage of fluconazole-resistant Candida species, incidence of infections by filamentous fungi, or 12-month mortality in patients with filamentous fungal infections. In conclusion, a stewardship programme targeting antifungals achieved a reduction in antifungal expenditure without reducing the quality of care provided.

Published
2013
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7. Prospective study in critically ill non-neutropenic patients: diagnostic potential of (1,3)-β-D-glucan assay and circulating galactomannan for the diagnosis of invasive fungal disease

Author

Mercedes Catalán, Juan Carlos Montejo, M. A. Finkelman, José Pontón, Joshi Acosta, A. del Palacio-Peréz-Medel, María-Dolores Moragues, A. del Palacio, and J. De-La-Cruz-Bértolo

Subjects
Adult, Male, Microbiology (medical), medicine.medical_specialty, beta-Glucans, Critical Illness, Neutropenia, Aspergillosis, Gastroenterology, Mannans, Galactomannan, chemistry.chemical_compound, Sepsis, Intensive care, Internal medicine, medicine, Humans, Blood culture, Prospective Studies, Prospective cohort study, Aged, Aged, 80 and over, Leukopenia, medicine.diagnostic_test, business.industry, Galactose, General Medicine, Middle Aged, medicine.disease, Surgery, Infectious Diseases, Mycoses, ROC Curve, chemistry, Female, Proteoglycans, Zygomycosis, medicine.symptom, business
Abstract

Diagnosis of invasive fungal disease (IFD) in patients under intensive care is challenging. Circulating biomarkers, (1,3)-β-D-glucan (BG) and galactomannan (GM), were prospectively assessed in 98 critically ill patients at risk of IFD. There were 11 cases of invasive aspergillosis (IA; 4 proven and 7 probable), 9 cases of proven invasive candidiasis (IC), 1 case of mixed proven IC and probable IA, 1 case of proven zygomycosis, and 1 case of mixed mycelial proven IFD. In all IA cases there was no significant difference when the area under the receiver operating characteristic curve (AUC) of GM (0.873 [95%CI, 0.75-0.99]) and BG (0.856 [95% CI, 0.71-0.99]) were compared (p = 0.871). The AUC for BG in IC and for the rest of the IFD cases was 0.605 (95% CI, 0.39-0.82) and 0.768 (95% CI, 0.63-0.90) respectively. Positive BG (40%) predated blood culture (n = 3) and abdominal pus (n = 1) a mean of 3.25 days before Candida was grown. In patients with IFD caused by molds, BG appeared a mean of 5.65 days before culture results. For the diagnosis of patients at risk of IC, BG has shown a high NPV (94.5%), with positive results also predating blood cultures in 30% of patients. In conclusion, early BG results permit a timely initiation of antifungal therapy in patients at risk of IFD.

Published
2011

8. Aislamiento de Aspergillus lentulus en España en un paciente crítico con enfermedad pulmonar obstructiva crónica

Author

José Pontón, Amalia del Palacio, Sonia Brena, María Dolores Moragues, Almudena Alhambra, Juan Carlos Montejo, and Mercedes Catalán

Subjects
Voriconazole, medicine.medical_specialty, COPD, biology, Exacerbation, Itraconazole, business.industry, biology.organism_classification, medicine.disease, Microbiology, Surgery, Aspergillus fumigatus, chemistry.chemical_compound, Infectious Diseases, chemistry, Amphotericin B, Internal medicine, medicine, Aspergillus lentulus, Caspofungin, business, medicine.drug
Abstract

Aspergillus lentulus was first described in the year 2005, and since it cannot be phenotypically distinguished from Aspergillus fumigatus, it is conceivable that earlier descriptions (before 2005) could be attributed to this new species. Currently invasive infections caused by A. lentulus are rare and very few cases have been previously published in neutropenic patients, all of them with fatal outcome. Here we report a critically ill non neutropenic patient with chronic obstructive pulmonary disease (COPD) who was admitted to the medical intensive care unit with an exacerbation of COPD and who had been treated with long term corticosteroids. A. fumigatus was cultured from two bronchial aspirates and in a third bronchial aspirate both A. lentulus and A. fumigatus were isolated. On two consecutive days detection of galactomannan in serum was negative whilst detection of (1-3) beta-D glucan was positive (> 518 pg/ml). Minimal inhibitory concentrations (MIC) for itraconazole, voriconazole, caspofungin and amphotericin B were high for this strain of A. lentulus. Given the high MIC values of A. lentulus to available antifungals, the accurate identification of this new species is warranted. To our knowledge, this is the first report of the isolation of A. lentulus in a non-neutropenic critically ill patient, although we note that since it was isolated only once from respiratory specimens, its implication as an etiologic agent of infection for this patient remains to be established.

Published
2008

9. Utilidad clínica de la anidulafungina en el tratamiento de las candidiasis esofágicas, candidemias y candidiasis invasoras

Author

Mercedes Catalán González, Cristóbal León Gil, and Juan Carlos Montejo González

Subjects
Aspergillus, Echinocandin, biology, business.industry, Salvage therapy, bacterial infections and mycoses, biology.organism_classification, medicine.disease, Microbiology, Esophageal candidiasis, Infectious Diseases, In vivo, Amphotericin B, medicine, Anidulafungin, business, Fluconazole, medicine.drug
Abstract

Anidulafungin is a new echinocandin that appears to have several advantages over existing antifungals. It is unique because it slowly degrades in humans, undergoing a process of biotransformation rather than being metabolized. It exhibits high in vitro and in vivo activities against Candida spp. and Aspergillus spp. In several clinical studies investigating Candida esophagitis; candidemia and invasive candidiasis, the clinical efficacy of this echinocandin was similar, or even superior, to that of established antifungals in candidemia. Antifungal activity against strains no longer susceptible to conventional antifungal agents, such as fluconazole and amphotericin B suggests that anidulafungin can be used as salvage therapy in life-threatening fungal infections. The limited toxicity profile, minimal drug-drug interactions and the fact that does not require dosage adjustment in subjects with hepatic or renal impairment, establishes this echinocandin as an attractive new option for the treatment of invasive fungal infections.

Published
2008

10. Nueva aportación en terapia antifúngica: Anidulafungina. Aspectos farmacológicos de la anidulafungina

Author

Mercedes Catalán González and Juan Carlos Montejo González

Subjects
Infectious Diseases, business.industry, medicine, Anidulafungina, medicine.disease, business, Microbiology, Humanities, Fungemia
Abstract

La anidulafungina es una nueva equinocandina que inhibe la sintesis de s-1,3-D-glucano sintasa e interrumpe la sintesis de la pared celular del hongo. Presenta una marcada actividad frente a Candida spp. y Aspergillus spp., incluyendo las especies resistentes a anfotericina B y triazoiles. Debido a su limitada biodisponibilidad oral unicamente se administra en la clinica por via parenteral. La anidulafungina sufre un proceso de degradacion espontanea en la sangre, no precisando de metabolizacion hepatica y siendo eliminada por via fecal en su mayoria como metabolitos inactivos. La eliminacion urinaria del farmaco es inferior al 1%. No precisa ajuste de dosis en insuficiencia hepatica ni renal. La anidulafungina es generalmente bien tolerada. Los efectos adversos notificados no se relacionan ni con la dosis ni con el tipo de infusion. La mayoria de los efectos adversos son flebitis, cefalea, nauseas, vomitos y fiebre. El limitado perfil de toxicidad y las minimas interacciones con otros farmacos (ciclosporina, tacrolimus y corticoesteroides) hacen de la anidulafungina una nueva opcion terapeutica para las infecciones fungicas invasoras, especialmente en pacientes receptores de trasplantes.

Published
2008

11. Antifúngicos sistémicos. Farmacodinamia y farmacocinética

Author

Juan Carlos Montejo and Mercedes Catalán

Subjects
Voriconazole, business.industry, Itraconazole, Critically ill, Pharmacology, Microbiology, Flucytosine, chemistry.chemical_compound, Infectious Diseases, chemistry, Pharmacodynamics, Amphotericin B, medicine, Caspofungin, business, Fluconazole, medicine.drug
Abstract

Invasive fungal infections are important causes of morbidity and mortality in critically ill non neutropenic patients. For many years, amphotericin B and flucytosine have been the only available antifungal agents for invasive fungal infections. Fortunately, the antifungal armamentarium has increased during the past two decades with the addition of several new agents. In addition to itraconazole and fluconazole, lipid formulations of amphotericin B, voriconazole, and caspofungin have been recently licensed. These various antifungal agents differ in their pharmacokinetic and pharmacodynamic profile.

Published
2006

12. Medidas de prevención de la candidiasis invasora en el paciente crítico no neutropénico

Author

Amalia del Palacio, Mercedes Catalán, and Juan Carlos Montejo

Subjects
Gynecology, medicine.medical_specialty, Infectious Diseases, Critically ill, business.industry, medicine, Invasive candidiasis, business, medicine.disease, Microbiology
Abstract

Resumen La prevencion de la candidiasis invasora (CI) en el enfermo critico no neutropenico debe sustentarse en recomendaciones basadas en la evidencia: medidas higienicas de manos; optimizacion en los cuidados de cateteres vasculares centrals y utilizacion racional de antibioticos de amplio espectro. Otras intervenciones concomitantes con la finalidad de disminuir los factores de riego son importantes para reducir la incidencia de la CI.

Published
2006

13. Impact of early oseltamivir treatment on outcome in critically ill patients with 2009 pandemic influenza A

Author

José Albofedo-Sánchez, M. Blasco Navalpotro, Paloma Dorado Regil, S. Tormo, Luis Regalado, Eduardo Palencia, A. Tellería, Raul José González, J.M. Añón, Antonio Jareño, Jose Ramon Iruretagoyena Amiano, Elena Gallego, Angel Arenzana, Cecilia Hermosa, Laura Macaya, Luis Álvarez–Rocha, R. Granada, Antonio Albaya, Carlos Velayos, Dolores Ocaña Fernández, Ignacio Amestarán, Josep Ballus, Emilio Robles-Musso, José Mª Molina, Sonia Gómez-Rosado, Carlos Pey, Fernándo Bueno, Luis Miguel Prado López, Iñaki Catalán, Rosa María Díaz, Ana Trujillo, B. Santamaría, Virgilio Paricio, Antonia Socias, José Luis Ballesteros, Julio Canabal, J.C. Pozo, César Pérez–Calvo, Mónica Magret, B. Suberviola, P. Ugarte, Joaquim Ramón Cervelló, S Barbadillo, Loreto Vidaur, Pedro Ibañez, Bárbara Baladín, Pilar Luque, J Nolla, José Cuñat, Juan C. Figueira, Fernando Barcenilla, S. Garrido Ramírez de Arellano, Sisón, Fernando Arméstar, Arantxa Lander, M. Martín, Inés Navarrete, Antonio Cárdenas, M. Cruz Soriano, Miguel Angel Díaz Castellanos, Diego de Mendoza, Javier Pérez, Francisco del Río, Medhi Zaheri Beryanaki, Miguel González, I. Jimenez Urra, David Hernandez, Sandra Trefler, Lisardo Iglesias, Antonio Álvarez Terrero, JJ Díaz, Marta Ortíz, Francisco Álvarez-Lerma, A. Liétor, Concepción Vaquero, Susana Altaba, Isidro Prieto, M. Badia, Ángel Sánchez-Miralles, Almudena Simón, Nerea López de Arbina, Mª Jesús Huertos, Zoran Josic, M. I. Marquina Lacueva, Santiago Macias, J. Nava, C. Ferri, José A. Pastor, Rafael Sierra, Antoli Ribas, Quiroga, Ignacio Martin-Loeches, Eleuterio Merayo, Santiago Freita, Nieves Carrasco, L. Macaya Redin, Ana María Rojo López, F. Felices Abad, Patricia Albert, Leonardo Lorente, Rafael Caballero, Sergio Ruiz-Santana, Javier Martins, José M. Bonell, Eva Vilaboy, Juan B. López Messa, Xavier Balanzó, José Luna, Cristóbal León, Abilio Arrascaeta, M. C. Martín, Joaquim Páez, Ana Loza, Juliá-Narváez José, José Garnacho-Montero, Jordi Almirall, Zulema Ferreras, Elena Arnau, L. Cabre, Guillermo Sevilla, S. García, José Eugenio Guerrero, R. Guerrero, Enrique Marquez, José Luis Monzón, Yolanda Fernández, A. del Castillo, Thiago Lisboa, Teresa Recio, Asunción Marques, Ignacio Sánchez, Lluis Llopart, M. Rodriguez, José Pomares, Marcío Borges-Sa, José Blanquer, Juan Carlos Montejo, Mercedes Díaz, Carmen González, Rosa Mª Catalán, Fernández del Cabo, Rafael Mañez, Enrique Ferres, Bernardo Gil Rueda, Alejandro Algora, Jesús Blanco Varela, L. Canadell, Jordi Rello, Alberto Manzano, A. Andaluz Ojeda, Jaime Benitez Peyrat, Félix Goñi, Rafael Zaragoza, Miquel Ferrer, Eduard Mesalles, A. Alonso, Alberto Fernández-Zapata, Frutos Del Nogal Sáez, Alejandro Rodríguez, Águeda García-Rodríguez, Ignacio González, Antonio Pasilla, A. Vazquez, Zulema Paez, Assumpta Rovira, Alberto Sandiumenge, M. F. Esteban, Dolores Ocaña, Josu Insansti, José F. Prieto, Pedro Cobo, Manuel Alvarez, Luis Arnaiz, Javier Cebrian, Carlos Castillo Arenal, Ricard Jordà Marcos, Manuel Luis Avellanas, Emili Diaz, Santiago Alberto Picos, Juan Carlos Vergara, Montserrat Valverdú-Vidal, J. J. Cáceres, Enrique Maraví-Poma, Diego López, Juan Bonastre, Esteban Fernández, P. Galdós, Sofía Martínez, Bernabé Alvarez-Sánchez, Fabiola Tena Ezpeleta, Ana de Pablo, R. Ramos, Eva Maria Saborido, Roberto Reig Valero, Enrique Cerdá, S. Sánchez-Alonso, Mercedes Catalán, Victor Jose López-Ciudad, M. Ortiz Piquer, Mariano Martínez, Amparo Paredes, Belén Agrela Romero, Jordi Vallés, M. Palamo, Jos M. Latour, J. González de Molina, Francisco Gurri, Jose Mª Montón, Juan José Díaz, Ana Díaz Lamas, Álvaro García, Josep Mª Sirvent, Jose Ángel Berezo, Mª José García-Ramos, Sergio Manuel Butí, Federico Gordo, Lorenzo Socias, Manuel Rodríguez-Carvajal, Mª Lourdes Cordero, Mercedes Palomar, Fernando García-López, Cecilia Carbayo, Pilar Martínez, R. Hinojosa, Dolores Vila, Francisco Lobato, Francisco Fernández, Juan Cortez, Pedro Olaechea, M. Ángel García, Mª Jesús López Pueyo, Antoni Torres, Beatriz Galván, Mª Carmen García-Torrejón, J. A. Cambronero, Bárbara Balandin Moreno, A. Canabal, Sergio F. Martínez, Nagore González, A. Belenger, Francisco Mariscal, P. Marco, Luis Marina, Francisco García, Mª Luisa Gómez Grande, S. Sánchez-Morcillo, Javier Fierro, and C. Guía

Subjects
Microbiology (medical), Adult, Male, medicine.medical_specialty, Oseltamivir, Time Factors, medicine.drug_class, medicine.medical_treatment, Critical Illness, Antiviral Agents, law.invention, chemistry.chemical_compound, Influenza A Virus, H1N1 Subtype, law, Internal medicine, Influenza, Human, medicine, Humans, Pharmacology (medical), Prospective Studies, Prospective cohort study, Pharmacology, Mechanical ventilation, Neuraminidase inhibitor, business.industry, Middle Aged, medicine.disease, Intensive care unit, Surgery, Pneumonia, Infectious Diseases, Treatment Outcome, chemistry, Propensity score matching, Cohort, Female, business
Abstract

Received 8 October 2010; returned 9 November 2010; revised 2 December 2010; accepted 6 December 2010Objectives: The impact of oseltamivir on mortality in critically ill patients with 2009 pandemic influenza A(2009 H1N1) is not clear. The main objective of this study was to investigate the relationship between thetiming of antiviral administration and intensive care unit (ICU) outcomes.Methods: Prospective, observational study of a cohort of ICU patients with confirmed 2009 H1N1 infection.Clinical data, treatment and outcome were compared between patients receiving early treatment (ET) withoseltamivir, initiated within 2 days, and patients administered late treatment (LT), initiated after this timepoint.Multivariate analysis and propensity score were used to determine the effect of oseltamivir on ICU mortality.Results: Six hundred and fifty-seven patients were enrolled. Four hundred and four (61.5%) patients requiredmechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy andwere included in the study group. All patients received oseltamivir for a median duration of 10 days (interquar-tile range 8–14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groupswere comparable in terms of main clinical variables. ICU length of stay (22.7+16.7 versus 18.4+14.2 days;P¼0.03), hospital length of stay (34.0+20.3 versus 27.2+18.2 days; P¼0.001) and MV days (17.4+15.2versus 14.0+12.4; P¼0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than inET (21.5%; OR¼1.9; 95% CI 1.06–3.41). A multivariate model identified ET (OR¼0.44; 95% CI 0.21–0.87) asan independent variable associated with reduced ICU mortality. These results were confirmed by propensityscore analysis (OR¼0.44; 95% CI 0.22–0.90; P,0.001).Conclusions: Our findings suggest that early oseltamivir administration was associated with favourableoutcomes among critically ill ventilated patients with 2009 H1N1 virus infection.Keywords: antiviral treatment, prognosis, pneumonia

Published
2011

14. A prospective comparison of galactomannan in bronchoalveolar lavage fluid for the diagnosis of pulmonary invasive aspergillosis in medical patients under intensive care: comparison with the diagnostic performance of galactomannan and of (1→ 3) – β – d-glucan chromogenic assay in serum samples

Author

Juan Carlos Montejo, D. Lora, A. del Palacio, A. del Palacio-Peréz-Medel, Joshi Acosta, Mercedes Catalán, M. S. Cuetara, José Pontón, and María-Dolores Moragues

Subjects
Microbiology (medical), Adult, Male, Serum, medicine.medical_specialty, beta-Glucans, Critical Care, Critical Illness, fungal pneumonia, Aspergillosis, Gastroenterology, intensive care unit, Mannans, Galactomannan, chemistry.chemical_compound, Blood serum, Internal medicine, Intensive care, medicine, Pneumocystosis, Humans, bronchoalveolar lavage, Prospective Studies, Aged, Invasive Pulmonary Aspergillosis, medicine.diagnostic_test, business.industry, Respiratory disease, Galactose, General Medicine, Middle Aged, Fungal pneumonia, medicine.disease, (1→3)–β–d-glucan, Infectious Diseases, Bronchoalveolar lavage, chemistry, ROC Curve, galactomannan, Immunology, Female, Proteoglycans, business, Bronchoalveolar Lavage Fluid
Abstract

Diagnosis of fungal pneumonia (FP) in critically ill patients is challenging. Circulating biomarkers for the diagnosis of FP have limitations and the combination of different assays in serum samples and directly from the target organ may further improve the diagnosis of FP. We prospectively assessed the diagnostic utility of paired galactomannan (GM) in bronchoalveolar lavage fluid (BAL) and serum GM and (1→3)–β–d-glucan (BG) assays in critically ill patients at risk of FP. Patients with FP were classified according to European Organisation for Research and Treatment of Cancer-Mycoses Study Group criteria, with modifications. Out of 847 admissions, 51 patients were eligible. There were nine invasive aspergillosis (IA) cases (four proven, five probable), three proven Pneumocysitis jirovecii pneumonia (PJP) cases and one mixed FP case (probable IA and proven PJP). The diagnostic accuracy as given by the area under the receiver operating characteristic curve in IA cases (proven and probable) for GM in BAL was 0.98 (95% CI, 0.94–1.00), whilst for GM and BG in serum it was 0.85 (95% CI, 0.74–0.96) and 0.815 (95% CI, 0.66–0.96), respectively. For IA cases (proven and probable) AUC for GM in BAL was significantly higher than GM and BG in serum (p 0.025 and p 0.032, respectively). In one of four proven and one of six probable IA cases, GM in serum remained negative, whereas GM in BAL was positive. In patients with IA, GM (90%) and BG (80%) appeared a mean of 4.3 days (range, 1–10 days) before Aspergillus was cultured. GM detection in BAL appears to improve the diagnosis of IA in critical patients.

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15. Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: A CHAID decision-tree analysis

Author

Alejandro H. Rodríguez, Francesc X. Avilés-Jurado, Emili Díaz, Philipp Schuetz, Sandra I. Trefler, Jordi Solé-Violán, Lourdes Cordero, Loreto Vidaur, Ángel Estella, Juan C. Pozo Laderas, Lorenzo Socias, Juan C. Vergara, Rafael Zaragoza, Juan Bonastre, José E. Guerrero, Borja Suberviola, Catia. Cilloniz, Marcos I. Restrepo, Ignacio Martín-Loeches, Pedro Cobo, Javier Martins, Cecilia Carbayo, Emilio Robles-Musso, Antonio Cárdenas, Javier Fierro, Dolores Ocaña Fernández, Rafael Sierra, Mª Jesús Huertos, Mª Luz Carmona Pérez, Juan Carlos Pozo Laderas, R. Guerrero, Juan Carlos Robles, Melissa Echevarría León, Alberto Bermejo Gómez, Enrique Márquez, Manuel Rodríguez-Carvajal, José Pomares, José Luis Ballesteros, Olga Moreno Romero, Yolanda Fernández, Francisco Lobato, José F. Prieto, José Albofedo-Sánchez, Pilar Martínez, María Victoria de la Torre, María Nieto, Estefanía Camara Sola, Miguel Angel Díaz Castellanos, Guillermo Sevilla Soler, Carlos Ortiz Leyba, José Garnacho-Montero, Rafael Hinojosa, Esteban Fernández, Ana Loza, Cristóbal León, Samuel González López, Angel Arenzana, Dolores Ocaña, Inés Navarrete, Medhi Zaheri Beryanaki, Ignacio Sánchez, Manuel Pérez Alé, Ana Mª Poullet Brea, Juan Francisco Machado Casas, Carlos Serón, Manuel Luis Avellanas, Arantxa Lander, S. Garrido Ramírez de Arellano, M.I. Marquina Lacueva, Pilar Luque, Elena Plumed Serrano, Juan Francisco Martín Lázaro, Carlos Sánchez Polo, Isabel Gutiérrez Cia, Belén Jiménez Bartolomé, Carlos López Nuñez, Ignacio González, José Ignacio Tomás Marsilla, Clara Jaques Andrés, Pablo Gtiérrez Ibañes, Pilar Araujo Aguilar, Jose Mª Montón, Paloma Dorado Regil, Lisardo Iglesias, Carmen Pascual González, Brígida Quindós Fernández, Lorena Martín Iglesias, Lucía Viña Soria, Raquel Yano Escudero, Mª del Rosario Mtnez Revuelta, null Quiroga, Águeda García-Rodríguez, Marta Martín Cuadrado, Ana Luz Balán Mariño, Pedro Ibánez, Marcío Borges-Sa, A. Socias, A. Del Castillo, Ricard Jordà Marcos, Cristina Muñoz, José M. Bonell, Ignacio Amestarán, M. Angeles González López, Cecilia Vilanova Pàmies, José Ma. Bonell Goytisolo, José Antonio Morales Carbonero, Rossana Pérez Senoff, Marta Generelo López de Medrano, Sergio Ruiz-Santana, Juan José Díaz, Catalina Sánchez Ramírez, Montse Sisón, David Hernández, Ana Trujillo, Luis Regalado, Sonia Rodríguez Fndez, Leonardo Lorente, Judith Cabrera Rivero, Mª Luisa Mora Quintero, Mar Martín, Sergio Martínez, J.J. Cáceres, Manuel Sanchez Palacio, null Marcos, D. García Rodríguez, María Ripoll Leria, P. Ugarte, Fernando García-López, Rafael Sánchez Iniesta, Angel Álvaro Alonso, Antonio Padilla, Basi Martínez Palacios, Mª Luisa Gómez Grande, Ma. Carmen Martín Rodríguez, Hasania Adbel-Hadi Álvarez, Alfonso Ambros Checa, Higinio Martín Hernández, Antonio Albaya, Alberto Silva Obregón, Carlos Marian Crespo, Carlos Armendariz Estrella, Carmen Benito Puncel, Eduardo Quirós Oyargue, Alfonso Canabal, Luis Marina, Ismael López de Toro, Almudena Simón, José María Añón, Juan B. López Messa, Mª Jesús López Pueyo, Ortíz María del valle Sergio Ossa Echeverri, Zulema Ferreras, Juan C. Ballesteros Herraez, Santiago Macias, José Ángel Berezo, Jesús Blanco Varela, Pablo Blanco Schweizer, Angela González Salamanca, Luis Tamayo Lomas, Andaluz Ojeda Anzález, Ramón Cicuéndez Avila, Pérez G. Francisco Javier, Antonio Álvarez Terrero, Fabiola Tena Ezpeleta, Christian Sala, Oliverio López, Zulema Paez, Álvaro García, Demetrio Carriedo Ule, Miriam Riesco Crespo, Jesús Pino Rebolledo, Nicolás Hidalgo Andrés, Ana Carolina Caballero Zirena, Belén Román García, Juan Bautista López Messa, María del Valle Ortiz, Sergio Ossa Echeverri, Rosa Mª Catalán, Miquel Ferrer, Antoni Torres, Catia Cilloniz, Sandra Barbadillo Ansorregui, Lluís Cabré, Ignacio Baeza, Assumpta Rovira, Francisco Álvarez-Lerma, Antonia Vázquez, Joan Nolla, Francisco Fernández, Joaquim Ramón Cervelló, Raquel Iglesia, Rafael Mañéz, J. Ballús, Rosa Mª Granada, Jordi Vallés, Marta Ortíz, C. Guía, Joaquim Páez, Jordi Almirall, Xavier Balanzo, Estel Güell, Juan Carlos Yebenes, Jordi Rello, Elena Arnau, Marcos Pérez, César Laborda, Jesica Souto, Leonel Lagunes, Iñaki Catalán, Josep Mª Sirvent, Nerea López de Arbina, Anna Baró Serra, Adriana Sánchez, Silvia M. Cuenca, Mariona Badía, Begonia Baseda-Garrido, Montserrat Valverdú-Vidal, Fernando Barcenilla, Mercedes Palomar, Xavier Nuvials, Pedro Garrido Benedicto, Ferran Roche Campo, M.F. Esteban, José Luna, Gaspar Masdeu Eixarch, Angels Pascual Diago, Juan Mª Nava, J. González de Molina, Josep Trenado, Ricard Ferrer, Zoran Josic, Montserrat Casanovas, Francisco Gurri, Paula Rodríguez, Alejandro Rodríguez, Laura Claverias, Sandra Trefler, María Bodí, Mónica Magret, Cristina Ferri, Rosa María Díaz, Eduard Mesalles, Fernando Arméstar, Diego de Mendoza, Carmen Lomas Fernández, José Julián Berrade, Alfonso Bonet Saris, Marina Pechkova, Cristina Mora Jiménez, Santiago Picos Gil, José Juliá-Narváez, Manuel Robles Marcos, Vanessa Farje Mallqui, Mª. Angeles Santiago Triviño, Pablo Martínez García, Alberto Fernández-Zapata, Teresa Recio, Abilio Arrascaeta, Mª José García-Ramos, Elena Gallego, Esther Saiz Rodrigo, Fernándo Bueno, Mercedes Díaz, Noemí Gil Pérez, David López Hormigo, Juan Diego Jiménez Delgado, Pérez Frutos, M.J. Rivera Pinna, Mª Lourdes Cordero, José A. Pastor, Luis Álvarez-Rocha, Alexandra Ceniceros Barros, Alejandra Virgós Pedreira, Dolores Vila, Carmen Fernández González, Javier Blanco Pérez, M. Ortiz Piquer, Eleuterio Merayo, Victor Jose López-Ciudad, Juan Cortes Cañones, Eva Vilaboy, José Villar Chao, Francisco Savira Cid López, Pablo Vidal Cortés, Marcos A. Pérez Veloso, Eva Maria Saborido, Enrique Alemparte Pardavila, Ana Ortega Montes, Raul José González, Santiago Freita, Enrique Alemparte, Ana Ortega, Ana María López, Julio Canabal, Enrique Ferres, Santiago Freitas Ramos, Lucas Lage Cendón, Vanesa Gómez Casal, Sabela Vara Adrio, Eva Menor Fernández, Susana González Prado, Antonio Varela Franco, José Luis Monzón, Félix Goñi, Frutos Del Nogal Sáez, M. Blasco Navalpotro, Ricardo Díaz Abad, José Luis Flordelis Lasierra, Mª Carmen García-Torrejón, César Pérez–Calvo, Diego López, Luis Arnaiz, S. Sánchez-Alonso, Carlos Velayos, Francisco del Río, Miguel Ángel González, Mercedes Nieto, Carmen Sánchez Cesteros, María Cruz Martín, José Mª Molina, Juan Carlos Montejo, Mercedes Catalán, Patricia Albert, Ana de Pablo, José Eugenio Guerrero, María Zurita, Jaime Benitez Peyrat, Miriam Díaz Cámara, Enrique Cerdá, Manuel Alvarez, Carlos Pey, Eva Manteiga Riestra, Concepción Martinez-Fidalgo, Montse Rodríguez, Eduardo Palencia, Rafael Caballero, Concepción Vaquero, Francisco Mariscal, S. García, Rico Cepeda, Nieves Carrasco, Isidro Prieto, A. Liétor, R. Ramos, Rosario Cuadra Casas, Cruz Soriano Cuesta, Susana Sánchez Alonso, Beatriz Galván, Juan C. Figueira, M. Cruz Soriano, Bélen Civantos Martín, Alejgandro Robles Caballero, P. Galdós, Bárbara Balandin Moreno, Sara Alcántara Carmona, Fernández del Cabo, Cecilia Hermosa, Federico Gordo, Alejandro Algora, Amparo Paredes, Teodoro Grau Carmona, J.A. Cambroner, Esther López Ramos, Yaiza Ortiz de Zárate, Sonia Gómez-Rosado, Margarita Mas Lodo, Nieves Franco Garrobo, Silvia Álvarez Hernández, Teresa Honrubia, Luis Miguel Prado López, A. Esteban, J.A. Lorente, N. Nin, Carlos Jaramillo Sotomayor, Esperanza Molero Silvero, Eduardo Morales Fdez. de la Reguera, Rosa Mª de la Casa Monje, Fátima Martín Serrano, Mª Victoria Trasmonte Martínez, M. Cruz Martín Delgado, Sofía Martínez, F. Felices Abad, Isabel Cremades Navalon, Martín Vigil Velis, Mariano Martínez, Domingo Martínez Baño, Enriqueta Andreu, Sergio Manuel Butí, Bernardo Gil Rueda, Francisco García, Noemí Llamas Fernández, Luis Herrera Para, Alejandro Ortín Freire, Mª Rosa Nvarro Ruiz, C.R. Hernández Romero, Enrique Maraví-Poma, I. Jimenez Urra, Laura Macaya Redin, A. Tellería, Josu Insansti, Noelia Artesero Garcia, Laura Macaya, Joaquín Lobo Palanco, Nagore González, Pilar Marco, Estibaliz Salas, Ruth Salaberría Udabe, B. Santamaría, Tomás Rodríguez, Juan Carlos Vergara, Jose Ramon Iruretagoyena Amiano, Iratí Garrido Santos, Alberto Manzano, Carlos Castillo Arenal, Pedro María Olaechea, Alejandro Martín López, Fernando Fonseca San Miguel, José Blanquer, Nieves Carbonell, José Ferreres Franco, Roberto Reig Valero, A. Belenger, Susana Altaba, Bernabé Álvarez–Sánchez, José Canovas Robles, Jaime Sánchez Francisco, Mar Ruiz Sánchez, Santiago Alberto Picos, Abilio Arrascaeta Llanes, Eugenio Herrero Gutiérrez, Alberto Fernández Zapata, Ángel Sánchez-Miralles, José Luis Antón Pascual, M. Palamo, Javier Cebrian, José Cuñat, Mónica Gordón Sahuquillo, Belén Romero, Santiago Borrás Pallé, Javier de León Belmar, Constantino Tormo, Susana Sancho Chinesta, Virgilio Paricio, Asunción Marques, S. Sánchez-Morcillo, S. Tormo, J. Latour, M. Ángel García, Manuel Palomo, Francisco Tarín Royo, Pedro Manzano Hinojosa, Mª Salomé Sánchez Pino, Concha Maragues Ribes, Rubén González Luis, Antoli Ribas, and Universitat de Barcelona

Subjects
Male, Procalcitonin, 0302 clinical medicine, Community-acquired pneumonia, Septic shock, Prospective Studies, 030212 general & internal medicine, Coinfection, Bacterial Infections, Middle Aged, Prognosis, Intensive Care Units, Infectious Diseases, Female, Pèptids, Adult, Calcitonin, Microbiology (medical), medicine.medical_specialty, Icu patients, Calcitonin Gene-Related Peptide, CHAID analysis, Respiratory coinfection, Sensitivity and Specificity, Influenzavirus, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Influenza, Human, parasitic diseases, medicine, Humans, Influenza viruses, Protein Precursors, Intensive care medicine, Influenza A(H1N1)pmd, business.industry, Decision Trees, 030208 emergency & critical care medicine, Influenza a, medicine.disease, CHAID, Observational study, business, Peptides, Biomarkers
Abstract

Objectives: To define which variables upon ICU admission could be related to the presence of coinfection using CHAID (Chi-squared Automatic Interaction Detection) analysis. Methods: A secondary analysis from a prospective, multicentre, observational study (2009 -2014) in ICU patients with confirmed A(H1N1)pdm09 infection. We assessed the potential of biomarkers and clinical variables upon admission to the ICU for coinfection diagnosis using CHAID analysis. Performance of cut-off points obtained was determined on the basis of the bi-nominal distributions of the true (+) and true (-) results. Results: Of the 972 patients included, 196 (20.3%) had coinfection. Procalcitonin (PCT; ng/mL 2.4 vs. 0.5, p < 0.001), but not C-reactive protein (CRP; mg/dL 25 vs. 38.5; p = 0.62) was higher in patients with coinfection. In CHAID analyses, PCT was the most important variable for coinfection. PCT < 0.29 ng/mL showed high sensitivity (Se = 88.2%), low Sp (33.2%) and high negative predictive value (NPV = 91.9%). The absence of shock improved classification capacity. Thus, for PCT < 0.29 ng/mL, the Se was 84%, the Sp 43% and an NPV of 94% with a post-test probability of coinfection of only 6%. Conclusion: PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

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