44 results on '"Origüen, J."'
Search Results
2. Comparison of the clinical course of Clostridium difficile infection in glutamate dehydrogenase-positive toxin-negative patients diagnosed by PCR to those with a positive toxin test
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Origüen, J., Corbella, L., Orellana, M.Á., Fernández-Ruiz, M., López-Medrano, F., San Juan, R., Lizasoain, M., Ruiz-Merlo, T., Morales-Cartagena, A., Maestro, G., Parra, P., Villa, J., Delgado, R., and Aguado, J.M.
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- 2018
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3. Geographical variation in therapy for bloodstream infections due to multidrug-resistant Enterobacteriaceae: a post-hoc analysis of the INCREMENT study
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del Toro, M.D., Gálvez, J., Falcone, M., Russob, A., Karaiskos, I., Trecarichi, E.M., Losito, A.R., García-Vázquez, E., Gómez, J., Roilides, E., Iosifidis, E., Pournaras, S., Prim, N., Navarro, F., Mirelis, B., Origüen, J., Juan, R. San, Fernández-Ruiz, M., Almela, M., de la Calle, C., Martínez, J.A., Morata, L., Larrosa, N., Puig-Asensio, M., Bou, G., Molina, J., González, V., Bermejo, J., Rucci, V., de Gopegui, E. Ruiz, Marinescu, C.I., Fariñas, M.C., Cano, M.E., Gozalo, M., Paño-Pardo, J.R., Mora-Rillo, Marta, Gómez-Zorrilla, S., Tubau, F., Tsakris, A., Zarkotou, O., Antoniadou, A., Poulakou, G., Souli, M., Lowman, W., Virmani, D., Torre-Cisneros, Julian, Machuca, I., Gracia-Ahufinger, Irene, Azap, Ö.K., Helvaci, Ö., Sahin, A.O., Cantón, R., Pintado, V., Bartoletti, M., Giannella, M., Peter, S., Hamprecht, A., Badia, C., Xercavins, M., Fontanals, D., Jové, E., Harris, Patrick N.A., Pezzani, M. Diletta, Gutiérrez-Gutiérrez, Belén, Viale, Pierluigi, Hsueh, Po-Ren, Ruiz-Garbajosa, Patricia, Venditti, Mario, Tumbarello, Mario, Navarro-Francisco, Carolina, Calbo, Esther, Akova, Murat, Giamarellou, Helen, Oliver, Antonio, Almirante, Benito, Gasch, Oriol, Martínez-Martínez, Luis, Schwaber, Mitchell J., Daikos, George, Pitout, Johann, Peña, Carmen, Hernández-Torres, Alicia, Doi, Yohei, Pérez, Federico, Tuon, Felipe Francisco, Tacconelli, Evelina, Carmeli, Yehuda, Bonomo, Robert A., Pascual, Álvaro, Paterson, David L., and Rodríguez-Baño, Jesús
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- 2017
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4. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study
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del Toro, M D, Gálvez, J, Falcone, M, Russo, A, Giamarellou, H, Trecarichi, E M, Losito, A R, García-Vázquez, E, Hernández, A, Gómez, J, Bou, G, Iosifidis, E, Prim, N, Navarro, F, Mirelis, B, Skiada, A, Origüen, J, Juan, R San, Fernández-Ruiz, M, Larrosa, N, Puig-Asensio, M, Cisneros, J M, Molina, J, González, V, Rucci, V, de Gopegui, E Ruiz, Marinescu, C I, Martínez-Martínez, L, Fariñas, M C, Cano, M E, Gozalo, M, Mora-Rillo, M, Francisco, C Navarro-San, Peña, C, Gómez-Zorrilla, S, Tubau, F, Tsakris, A, Zarkotou, O, Antoniadou, A, Poulakou, G, Pitout, J, Virmani, D, Torre-Cisneros, J, Guzmán-Puche, J, Helvaci, Ö, Sahin, A O, Pintado, V, Ruiz, P, Bartoletti, M, Giannella, M, Tacconelli, E, Riemenschneider, F, Calbo, E, Badia, C, Xercavins, M, Gasch, O, Fontanals, D, Jové, E, Gutiérrez-Gutiérrez, Belén, Salamanca, Elena, de Cueto, Marina, Hsueh, Po-Ren, Viale, Pierluigi, Paño-Pardo, José Ramón, Venditti, Mario, Tumbarello, Mario, Daikos, George, Cantón, Rafael, Doi, Yohei, Tuon, Felipe Francisco, Karaiskos, Ilias, Pérez-Nadales, Elena, Schwaber, Mitchell J, Azap, Özlem Kurt, Souli, Maria, Roilides, Emmanuel, Pournaras, Spyros, Akova, Murat, Pérez, Federico, Bermejo, Joaquín, Oliver, Antonio, Almela, Manel, Lowman, Warren, Almirante, Benito, Bonomo, Robert A, Carmeli, Yehuda, Paterson, David L, Pascual, Alvaro, and Rodríguez-Baño, Jesús
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- 2017
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5. Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial
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Origüen, J., López-Medrano, F., Fernández-Ruiz, M., Polanco, N., Gutiérrez, E., González, E., Mérida, E., Ruiz-Merlo, T., Morales-Cartagena, A., Pérez-Jacoiste Asín, M.A., García-Reyne, A., San Juan, R., Orellana, M.á., Andrés, A., and Aguado, J.M.
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- 2016
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6. Influence of immunosuppressive therapy in the development of cytomegalovirus disease in patients with inflammatory bowel disease: O450
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Garcia-Reyne, A., Martin, D., Fernandez-Ruiz, M., Origüen, J., Herrero-Martinez, J. M, de Dios, B., Casis, B., Lizasoain, M., Martínez-Montiel, P., Aguado, J. M., and Lumbreras, C.
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- 2012
7. Predictors of outcome in patients with severe sepsis or septic shock due to extended-spectrum β-lactamase-producing Enterobacteriaceae
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Russo, A., primary, Falcone, M., additional, Gutiérrez-Gutiérrez, B., additional, Calbo, E., additional, Almirante, B., additional, Viale, P.L., additional, Oliver, A., additional, Ruiz-Garbajosa, P., additional, Gasch, O., additional, Gozalo, M., additional, Pitout, J., additional, Akova, M., additional, Peña, C., additional, Cisneros, J.M., additional, Hernández-Torres, A., additional, Farcomeni, A., additional, Prim, N., additional, Origüen, J., additional, Bou, G., additional, Tacconelli, E., additional, Tumbarello, M., additional, Hamprecht, A., additional, Karaiskos, I., additional, de la Calle, C., additional, Pérez, F., additional, Schwaber, M.J., additional, Bermejo, J., additional, Lowman, W., additional, Hsueh, P.-R., additional, Mora-Rillo, M., additional, Rodriguez-Gomez, J., additional, Souli, M., additional, Bonomo, R.A., additional, Paterson, D.L., additional, Carmeli, Y., additional, Pascual, A., additional, Rodríguez-Baño, J., additional, and Venditti, M., additional
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- 2018
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8. Geographical variation in therapy for bloodstream infections due to multidrug-resistant Enterobacteriaceae: a post-hoc analysis of the INCREMENT study
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Harris, P.N.A. Pezzani, M.D. Gutiérrez-Gutiérrez, B. Viale, P. Hsueh, P.-R. Ruiz-Garbajosa, P. Venditti, M. Tumbarello, M. Navarro-Francisco, C. Calbo, E. Akova, M. Giamarellou, H. Oliver, A. Almirante, B. Gasch, O. Martínez-Martínez, L. Schwaber, M.J. Daikos, G. Pitout, J. Peña, C. Hernández-Torres, A. Doi, Y. Pérez, F. Tuon, F.F. Tacconelli, E. Carmeli, Y. Bonomo, R.A. Pascual, Á. Paterson, D.L. Rodríguez-Baño, J. del Toro, M.D. Gálvez, J. Falcone, M. Russo, A. Karaiskos, I. Trecarichi, E.M. Losito, A.R. García-Vázquez, E. Gómez, J. Roilides, E. Iosifidis, E. Pournaras, S. Prim, N. Navarro, F. Mirelis, B. Origüen, J. Juan, R.S. Fernández-Ruiz, M. Almela, M. de la Calle, C. Martínez, J.A. Morata, L. Larrosa, N. Puig-Asensio, M. Bou, G. Molina, J. González, V. Bermejo, J. Rucci, V. de Gopegui, E.R. Marinescu, C.I. Fariñas, M.C. Cano, M.E. Gozalo, M. Paño-Pardo, J.R. Mora-Rillo, M. Gómez-Zorrilla, S. Tubau, F. Tsakris, A. Zarkotou, O. Antoniadou, A. Poulakou, G. Souli, M. Lowman, W. Virmani, D. Torre-Cisneros, J. Machuca, I. Gracia-Ahufinger, I. Azap, Ö.K. Helvaci, Ö. Sahin, A.O. Cantón, R. Pintado, V. Bartoletti, M. Giannella, M. Peter, S. Hamprecht, A. Badia, C. Xercavins, M. Fontanals, D. Jové, E. ESGBIS/REIPI/INCREMENT Group
- Abstract
We describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Patients (n = 1482) in 12 countries from an observational study of BSI caused by ESBL-E or CPE were included. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of β-lactam/β-lactamase inhibitors (BLBLIs) or carbapenems, targeted use of BLBLIs for ESBL-E and use of targeted combination therapy for CPE. Compared with Spain, BLBLI use for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14–0.81), Greece (aOR 0.49, 95% CI 0.26–0.94) and Canada (aOR 0.31, 95% CI 0.11–0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11–2.25) and Turkey (aOR 2.09, 95% CI 1.14–3.81). Empirical carbapenem use was more likely in sites from Taiwan (aOR 1.73, 95% CI 1.03–2.92) and USA (aOR 1.89, 95% CI 1.05–3.39) and less likely in Italy (aOR 0.44, 95% CI 0.28–0.69) and Canada (aOR 0.10, 95% CI 0.01–0.74). Targeted BLBLIs for ESBL-E was more likely in Italian sites. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. Better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts. © 2017 Elsevier B.V. and International Society of Chemotherapy
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- 2017
9. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study
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Gutiérrez-Gutiérrez, B. Salamanca, E. de Cueto, M. Hsueh, P.-R. Viale, P. Paño-Pardo, J.R. Venditti, M. Tumbarello, M. Daikos, G. Cantón, R. Doi, Y. Tuon, F.F. Karaiskos, I. Pérez-Nadales, E. Schwaber, M.J. Azap, Ö.K. Souli, M. Roilides, E. Pournaras, S. Akova, M. Pérez, F. Bermejo, J. Oliver, A. Almela, M. Lowman, W. Almirante, B. Bonomo, R.A. Carmeli, Y. Paterson, D.L. Pascual, A. Rodríguez-Baño, J. del Toro, M.D. Gálvez, J. Falcone, M. Russo, A. Giamarellou, H. Trecarichi, E.M. Losito, A.R. García-Vázquez, E. Hernández, A. Gómez, J. Bou, G. Iosifidis, E. Prim, N. Navarro, F. Mirelis, B. Skiada, A. Origüen, J. Juan, R.S. Fernández-Ruiz, M. Larrosa, N. Puig-Asensio, M. Cisneros, J.M. Molina, J. González, V. Rucci, V. de Gopegui, E.R. Marinescu, C.I. Martínez-Martínez, L. Fariñas, M.C. Cano, M.E. Gozalo, M. Mora-Rillo, M. Francisco, C.N.-S. Peña, C. Gómez-Zorrilla, S. Tubau, F. Tsakris, A. Zarkotou, O. Antoniadou, A. Poulakou, G. Pitout, J. Virmani, D. Torre-Cisneros, J. Guzmán-Puche, J. Helvaci, Ö. Sahin, A.O. Pintado, V. Ruiz, P. Bartoletti, M. Giannella, M. Tacconelli, E. Riemenschneider, F. Calbo, E. Badia, C. Xercavins, M. Gasch, O. Fontanals, D. Jové, E. REIPI/ESGBIS/INCREMENT Investigators REIPI/ESGBIS/INCREMENT Investigators
- Abstract
Background The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. Methods In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0–7 [low mortality score] vs 8–15 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. Findings Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38·5%] of 343 patients died vs 57 [60·6%] of 94; absolute difference 22·1% [95% CI 11·0–33·3]; adjusted hazard ratio [HR] 0·45 [95% CI 0·33–0·62]; p
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- 2017
10. Geographical variation in therapy for bloodstream infections due to multidrug-resistant Enterobacteriaceae: a post-hoc analysis of the INCREMENT study
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Harris, Patrick N.A., primary, Pezzani, M. Diletta, additional, Gutiérrez-Gutiérrez, Belén, additional, Viale, Pierluigi, additional, Hsueh, Po-Ren, additional, Ruiz-Garbajosa, Patricia, additional, Venditti, Mario, additional, Tumbarello, Mario, additional, Navarro-Francisco, Carolina, additional, Calbo, Esther, additional, Akova, Murat, additional, Giamarellou, Helen, additional, Oliver, Antonio, additional, Almirante, Benito, additional, Gasch, Oriol, additional, Martínez-Martínez, Luis, additional, Schwaber, Mitchell J., additional, Daikos, George, additional, Pitout, Johann, additional, Peña, Carmen, additional, Hernández-Torres, Alicia, additional, Doi, Yohei, additional, Pérez, Federico, additional, Tuon, Felipe Francisco, additional, Tacconelli, Evelina, additional, Carmeli, Yehuda, additional, Bonomo, Robert A., additional, Pascual, Álvaro, additional, Paterson, David L., additional, Rodríguez-Baño, Jesús, additional, del Toro, M.D., additional, Gálvez, J., additional, Falcone, M., additional, Russob, A., additional, Karaiskos, I., additional, Trecarichi, E.M., additional, Losito, A.R., additional, García-Vázquez, E., additional, Gómez, J., additional, Roilides, E., additional, Iosifidis, E., additional, Pournaras, S., additional, Prim, N., additional, Navarro, F., additional, Mirelis, B., additional, Origüen, J., additional, Juan, R. San, additional, Fernández-Ruiz, M., additional, Almela, M., additional, de la Calle, C., additional, Martínez, J.A., additional, Morata, L., additional, Larrosa, N., additional, Puig-Asensio, M., additional, Bou, G., additional, Molina, J., additional, González, V., additional, Bermejo, J., additional, Rucci, V., additional, de Gopegui, E. Ruiz, additional, Marinescu, C.I., additional, Fariñas, M.C., additional, Cano, M.E., additional, Gozalo, M., additional, Paño-Pardo, J.R., additional, Mora-Rillo, Marta, additional, Gómez-Zorrilla, S., additional, Tubau, F., additional, Tsakris, A., additional, Zarkotou, O., additional, Antoniadou, A., additional, Poulakou, G., additional, Souli, M., additional, Lowman, W., additional, Virmani, D., additional, Torre-Cisneros, Julian, additional, Machuca, I., additional, Gracia-Ahufinger, Irene, additional, Azap, Ö.K., additional, Helvaci, Ö., additional, Sahin, A.O., additional, Cantón, R., additional, Pintado, V., additional, Bartoletti, M., additional, Giannella, M., additional, Peter, S., additional, Hamprecht, A., additional, Badia, C., additional, Xercavins, M., additional, Fontanals, D., additional, and Jové, E., additional
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- 2017
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11. A Predictive Model of Mortality in Patients With Bloodstream Infections due to Carbapenemase-Producing Enterobacteriaceae
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Gutiérrez Gutiérrez, Belén, Salamanca, Elena, de Cueto, Marina, Pascual, Alvaro, Rodríguez Baño, Jesús, Hsueh, Po Ren, Viale, Pierluigi, Paño Pardo, José Ramón, Venditti, Mario, Tumbarello, Mario, Daikos, George, Pintado, Vicente, Doi, Yohei, Tuon, Felipe Francisco, Karaiskos, Ilias, Machuca, Isabel, Schwaber, Mitchell J., Azap, Özlem Kurt, Souli, Maria, Roilides, Emmanuel, Pournaras, Spyros, Akova, Murat, Pérez, Federico, Bonomo, Robert A., Bermejo, Joaquín, Oliver, Antonio, Almela, Manel, Lowman, Warren, Almirante, Benito, Carmeli, Yehuda, Paterson, David L., Falcone, M., Russo, A., Giamarellou, H., Trecarichi, Enrico Maria, Losito, Angela Raffaella, García Vázquez, E., Hernández, A., Gómez, J., Iosifidis, E., Prim, N., Navarro, F., Mirelis, B., Origüen, J., San Juan, R., Fernández Ruiz, M., Larrosa, N., Puig Asensio, M., Cisneros, J. M., Molina, J., González, V., Rucci, V., Ruiz de Gopegui, E., Marinescu, C. I., Martínez Martínez, L., Fariñas, M. C., Cano, M. E., Gozalo, M., Mora Rillo, M., Navarro San Francisco, C., Peña, C., Gómez Zorrilla, S., Tubau, F., Tsakris, A., Zarkotou, O., Azap, Ö. K., Pitout, J., Virmani, D., Torre Cisneros, J., Natera, C., Helvaci, Ö., Sahin, A. O., Cantón, R., Ruiz, P., Bartoletti, M., Giannella, M., Taconelli, E., Riemenschneider, F., Calbo, E., Badia, C., Xercavins, M., Gasch, E., Fontanals, D., and Jové, E.
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,carbapenems ,klebsiella pneumoniae ,pneumoniae carbapenemase ,030106 microbiology ,Bacteremia ,Comorbidity ,Logistic regression ,Settore MED/17 - MALATTIE INFETTIVE ,Sensitivity and Specificity ,beta-Lactamases ,Decision Support Techniques ,03 medical and health sciences ,0302 clinical medicine ,Bacterial Proteins ,Enterobacteriaceae ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Aged ,Anti-Bacterial Agents ,Enterobacteriaceae Infections ,Female ,Logistic Models ,Middle Aged ,Retrospective Studies ,Receiver operating characteristic ,business.industry ,Medicine (all) ,Retrospective cohort study ,General Medicine ,medicine.disease ,Surgery ,Predictive value of tests ,Observational study ,business - Abstract
Objective To develop a score to predict mortality in patients with bloodstream infections (BSIs) due to carbapenemase-producing Enterobacteriaceae (CPE). Patients and Methods A multinational retrospective cohort study (INCREMENT project) was performed from January 1, 2004, through December 31, 2013. Patients with clinically relevant monomicrobial BSIs due to CPE were included and randomly assigned to either a derivation cohort (DC) or a validation cohort (VC). The variables were assessed on the day the susceptibility results were available, and the predictive score was developed using hierarchical logistic regression. The main outcome variable was 14-day all-cause mortality. The predictive ability of the model and scores were measured by calculating the area under the receiver operating characteristic curve. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for different cutoffs of the score. Results The DC and VC included 314 and 154 patients, respectively. The final logistic regression model of the DC included the following variables: severe sepsis or shock at presentation (5 points); Pitt score of 6 or more (4 points); Charlson comorbidity index of 2 or more (3 points); source of BSI other than urinary or biliary tract (3 points); inappropriate empirical therapy and inappropriate early targeted therapy (2 points). The score exhibited an area under the receiver operating characteristic curve of 0.80 (95% CI, 0.74-0.85) in the DC and 0.80 (95% CI, 0.73-0.88) in the VC. The results for 30-day all-cause mortality were similar. Conclusion A validated score predictive of early mortality in patients with BSIs due to CPE was developed. Trial Registration clinicaltrials.gov Identifier: NCT01 764490.
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- 2016
12. Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: A multinational pre-registered cohort study
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Gutiérrez-Gutiérrez, B. Bonomo, R.A. Carmeli, Y. Paterson, D.L. Almirante, B. Martínez-Martínez, L. Oliver, A. Calbo, E. Peña, C. Akova, M. Pitout, J. Origüen, J. Pintado, V. García-Vázquez, E. Gasch, O. Hamprecht, A. Prim, N. Tumbarello, M. Bou, G. Viale, P. Tacconelli, E. Almela, M. Pérez, F. Giamarellou, H. Cisneros, J.M. Schwaber, M.J. Venditti, M. Lowman, W. Bermejo, J. Hsueh, P.-R. Mora-Rillo, M. Gracia-Ahulfinger, I. Pascual, A. Rodríguez-Baño, J. Karaiskos, I. Trecarichi, E.M. Losito, A.R. Hernández, A. Gómez, J. Navarro, F. Mirelis, B. Larrosa, N. Puig, M. Rucci, V. Bartoletti, M. Giannella, M. Riemenschneider, F. Badia, C. Xercavins, M. Gálvez, J. de Cueto, M. Salamanca, E. Falcone, M. Russo, A. Daikos, G. Roilides, E. Iosifidis, E. Doi, Y. Tuon, F.F. San Juan, R. Fernández-Ruiz, M. Molina, J. González, V. Ruiz de Gopegui, E. Marinescu, C.I. Fariñas, M.C. Cano, M.E. Gozalo, M. Paño-Pardo, J.R. Navarro-San Francisco, C. Gómez-Zorrilla, S. Tubau, F. Pournaras, S. Tsakris, A. Zarkotou, O. Azap, Ö.K. Souli, M. Antoniadou, A. Poulakou, G. Virmani, D. Machuca, I. Pérez-Nadales, E. Torre-Cisneros, J. Helvaci, Ö. Sahin, A.O. Cantón, R. Ruiz, P. Fontanals, D. Jové, E. REIPI/ESGBIS/INCREMENT Group
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polycyclic compounds ,bacterial infections and mycoses - Abstract
Objectives: Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E. Methods: A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality. Results: The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rateswere 90.6% with ertapenem and 75.5% with other carbapenems (P=0.06) in the ETC and 89.8% and 82.6% (P=0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P=0.01) in the ETC and 9.3% and 17.1% (P=0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24-20.08; P=0.58) and 1.04 (0.44- 2.50; P=0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43-3.29; P=0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43-2.03; P=0.86) and for the propensity-matched cohorts it was 1.05 (0.46-2.44; P=0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems. Conclusions: Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock. © The Author 2016.
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- 2016
13. A Predictive Model of Mortality in Patients With Bloodstream Infections due to Carbapenemase-Producing Enterobacteriaceae
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Gutiérrez-Gutiérrez, B. Salamanca, E. de Cueto, M. Pascual, A. Rodríguez-Baño, J. Hsueh, P.-R. Viale, P. Paño-Pardo, J.R. Venditti, M. Tumbarello, M. Daikos, G. Pintado, V. Doi, Y. Tuon, F.F. Karaiskos, I. Machuca, I. Schwaber, M.J. Azap, Ö.K. Souli, M. Roilides, E. Pournaras, S. Akova, M. Pérez, F. Bonomo, R.A. Bermejo, J. Oliver, A. Almela, M. Lowman, W. Almirante, B. Carmeli, Y. Paterson, D.L. Falcone, M. Russo, A. Giamarellou, H. Trecarichi, E.M. Losito, A.R. García-Vázquez, E. Hernández, A. Gómez, J. Iosifidis, E. Prim, N. Navarro, F. Mirelis, B. Origüen, J. San Juan, R. Fernández-Ruiz, M. Larrosa, N. Puig-Asensio, M. Cisneros, J.M. Molina, J. González, V. Rucci, V. Ruiz de Gopegui, E. Marinescu, C.I. Martínez-Martínez, L. Fariñas, M.C. Cano, M.E. Gozalo, M. Mora-Rillo, M. Navarro-San Francisco, C. Peña, C. Gómez-Zorrilla, S. Tubau, F. Tsakris, A. Zarkotou, O. Pitout, J. Virmani, D. Torre-Cisneros, J. Natera, C. Helvaci, Ö. Sahin, A.O. Cantón, R. Ruiz, P. Bartoletti, M. Giannella, M. Taconelli, E. Riemenschneider, F. Calbo, E. Badia, C. Xercavins, M. Gasch, E. Fontanals, D. Jové, E.
- Abstract
Objective To develop a score to predict mortality in patients with bloodstream infections (BSIs) due to carbapenemase-producing Enterobacteriaceae (CPE). Patients and Methods A multinational retrospective cohort study (INCREMENT project) was performed from January 1, 2004, through December 31, 2013. Patients with clinically relevant monomicrobial BSIs due to CPE were included and randomly assigned to either a derivation cohort (DC) or a validation cohort (VC). The variables were assessed on the day the susceptibility results were available, and the predictive score was developed using hierarchical logistic regression. The main outcome variable was 14-day all-cause mortality. The predictive ability of the model and scores were measured by calculating the area under the receiver operating characteristic curve. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for different cutoffs of the score. Results The DC and VC included 314 and 154 patients, respectively. The final logistic regression model of the DC included the following variables: severe sepsis or shock at presentation (5 points); Pitt score of 6 or more (4 points); Charlson comorbidity index of 2 or more (3 points); source of BSI other than urinary or biliary tract (3 points); inappropriate empirical therapy and inappropriate early targeted therapy (2 points). The score exhibited an area under the receiver operating characteristic curve of 0.80 (95% CI, 0.74-0.85) in the DC and 0.80 (95% CI, 0.73-0.88) in the VC. The results for 30-day all-cause mortality were similar. Conclusion A validated score predictive of early mortality in patients with BSIs due to CPE was developed. Trial Registration clinicaltrials.gov Identifier: NCT01 764490. © 2016 Mayo Foundation for Medical Education and Research
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- 2016
14. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study
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Gutiérrez-Gutiérrez, Belén, primary, Salamanca, Elena, additional, de Cueto, Marina, additional, Hsueh, Po-Ren, additional, Viale, Pierluigi, additional, Paño-Pardo, José Ramón, additional, Venditti, Mario, additional, Tumbarello, Mario, additional, Daikos, George, additional, Cantón, Rafael, additional, Doi, Yohei, additional, Tuon, Felipe Francisco, additional, Karaiskos, Ilias, additional, Pérez-Nadales, Elena, additional, Schwaber, Mitchell J, additional, Azap, Özlem Kurt, additional, Souli, Maria, additional, Roilides, Emmanuel, additional, Pournaras, Spyros, additional, Akova, Murat, additional, Pérez, Federico, additional, Bermejo, Joaquín, additional, Oliver, Antonio, additional, Almela, Manel, additional, Lowman, Warren, additional, Almirante, Benito, additional, Bonomo, Robert A, additional, Carmeli, Yehuda, additional, Paterson, David L, additional, Pascual, Alvaro, additional, Rodríguez-Baño, Jesús, additional, del Toro, M D, additional, Gálvez, J, additional, Falcone, M, additional, Russo, A, additional, Giamarellou, H, additional, Trecarichi, E M, additional, Losito, A R, additional, García-Vázquez, E, additional, Hernández, A, additional, Gómez, J, additional, Bou, G, additional, Iosifidis, E, additional, Prim, N, additional, Navarro, F, additional, Mirelis, B, additional, Skiada, A, additional, Origüen, J, additional, Juan, R San, additional, Fernández-Ruiz, M, additional, Larrosa, N, additional, Puig-Asensio, M, additional, Cisneros, J M, additional, Molina, J, additional, González, V, additional, Rucci, V, additional, de Gopegui, E Ruiz, additional, Marinescu, C I, additional, Martínez-Martínez, L, additional, Fariñas, M C, additional, Cano, M E, additional, Gozalo, M, additional, Mora-Rillo, M, additional, Francisco, C Navarro-San, additional, Peña, C, additional, Gómez-Zorrilla, S, additional, Tubau, F, additional, Tsakris, A, additional, Zarkotou, O, additional, Antoniadou, A, additional, Poulakou, G, additional, Pitout, J, additional, Virmani, D, additional, Torre-Cisneros, J, additional, Guzmán-Puche, J, additional, Helvaci, Ö, additional, Sahin, A O, additional, Pintado, V, additional, Ruiz, P, additional, Bartoletti, M, additional, Giannella, M, additional, Tacconelli, E, additional, Riemenschneider, F, additional, Calbo, E, additional, Badia, C, additional, Xercavins, M, additional, Gasch, O, additional, Fontanals, D, additional, and Jové, E, additional
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- 2017
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15. Reply to “Old Habits Die Hard: Screening for and Treating Asymptomatic Bacteriuria After Kidney Transplantation”
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Origüen, J., primary, López-Medrano, F., additional, Fernández-Ruiz, M., additional, and María Aguado, J., additional
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- 2016
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16. Progressive increase of resistance in Enterobacteriaceae urinary isolates from kidney transplant recipients over the past decade: narrowing of the therapeutic options
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Origüen, J., primary, Fernández-Ruiz, M., additional, López-Medrano, F., additional, Ruiz-Merlo, T., additional, González, E., additional, Morales, J.M., additional, Fiorante, S., additional, San-Juan, R., additional, Villa, J., additional, Orellana, M.Á., additional, Andrés, A., additional, and Aguado, J.M., additional
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- 2016
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17. Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study
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Gutiérrez-Gutiérrez B, Ra, Bonomo, Carmeli Y, Dl, Paterson, Benito Almirante, Martínez-Martínez L, Oliver A, Calbo E, Peña C, Akova M, Pitout J, Origüen J, Pintado V, García-Vázquez E, Gasch O, Hamprecht A, Prim N, Tumbarello M, Bou G, and Viale P
18. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study
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Manel Almela, Angela Raffaella Losito, Deepali Virmani, Silvia Gómez-Zorrilla, Alicia Hernandez, Maria Souli, George L. Daikos, F. Riemenschneider, V. Rucci, José Molina, Carmen Peña, C. I. Marinescu, Mireia Puig-Asensio, Mónica Gozalo, José Miguel Cisneros, E. Ruiz de Gopegui, A. O. Sahin, Joaquín Bermejo, R. San Juan, Esther Calbo, Mario Fernández-Ruiz, Emmanuel Roilides, Warren Lowman, Evelina Tacconelli, Maddalena Giannella, Julia Origüen, Antonio Oliver, M.D. del Toro, Elena Salamanca, Garyphallia Poulakou, Nieves Larrosa, Jorge Galvez, Özlem Kurt Azap, Po-Ren Hsueh, Pierluigi Viale, Elias Iosifidis, Felipe Francisco Tuon, Ilias Karaiskos, Marina de Cueto, V. González, M.C. Fariñas, Belén Gutiérrez-Gutiérrez, M. Xercavins, E. Jové, Athanassios Tsakris, M. E. Cano, Oriol Gasch, Alessandro Russo, Johann D. D. Pitout, Anna Skiada, Michele Bartoletti, Mario Tumbarello, Vicente Pintado, Mitchell J. Schwaber, C. Navarro-San Francisco, O. Zarkotou, Benito Almirante, Murat Akova, E. García-Vázquez, Yohei Doi, Beatriz Mirelis, Álvaro Pascual, Jesús Rodríguez-Baño, David L. Paterson, Federico Perez, N. Prim, Cristina Badia, Luis Martínez-Martínez, J. Gómez, Elena Pérez-Nadales, Julia Guzmán-Puche, José Ramón Paño-Pardo, Mario Venditti, Yehuda Carmeli, J. Torre-Cisneros, Ö. Helvaci, D. Fontanals, Enrico Maria Trecarichi, Helen Giamarellou, Marco Falcone, Ferran Navarro, Robert A. Bonomo, Rafael Cantón, Anastasia Antoniadou, Germán Bou, Spyros Pournaras, Fe Tubau, Marta Mora-Rillo, Patricia Cordero Ruiz, Gutiérrez-Gutiérrez, Belén, Salamanca, Elena, de Cueto, Marina, Hsueh, Po-Ren, Viale, Pierluigi, Paño-Pardo, José Ramón, Venditti, Mario, Tumbarello, Mario, Daikos, George, Cantón, Rafael, Doi, Yohei, Tuon, Felipe Francisco, Karaiskos, Ilia, Pérez-Nadales, Elena, Schwaber, Mitchell J, Azap, Özlem Kurt, Souli, Maria, Roilides, Emmanuel, Pournaras, Spyro, Akova, Murat, Pérez, Federico, Bermejo, Joaquín, Oliver, Antonio, Almela, Manel, Lowman, Warren, Almirante, Benito, Bonomo, Robert A, Carmeli, Yehuda, Paterson, David L, Pascual, Alvaro, Rodríguez-Baño, Jesú, del Toro, M.D., Gálvez, J., Falcone, M., Russo, A., Giamarellou, H., Trecarichi, E.M., Losito, A.R., García-Vázquez, E., Hernández, A., Gómez, J., Bou, G., Iosifidis, E., Prim, N., Navarro, F., Mirelis, B., Skiada, A., Origüen, J., Juan, R San, Fernández-Ruiz, M., Larrosa, N., Puig-Asensio, M., Cisneros, J.M., Molina, J., González, V., Rucci, V., de Gopegui, E Ruiz, Marinescu, C.I., Martínez-Martínez, L., Fariñas, M.C., Cano, M.E., Gozalo, M., Mora-Rillo, M., Francisco, C Navarro-San, Peña, C., Gómez-Zorrilla, S., Tubau, F., Tsakris, A., Zarkotou, O., Antoniadou, A., Poulakou, G., Pitout, J., Virmani, D., Torre-Cisneros, J., Guzmán-Puche, J., Helvaci, Ã ., Sahin, A.O., Pintado, V., Ruiz, P., Bartoletti, M., Giannella, M., Tacconelli, E., Riemenschneider, F., Calbo, E., Badia, C., Xercavins, M., Gasch, O., Fontanals, D., and Jové, E.
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Male ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Combination therapy ,030106 microbiology ,Bacteremia ,Settore MED/17 - MALATTIE INFETTIVE ,beta-Lactamases ,03 medical and health sciences ,Pharmacotherapy ,Drug Therapy ,Bacterial Proteins ,Risk Factors ,medicine ,Humans ,Propensity Score ,Aged ,Retrospective Studies ,business.industry ,Hazard ratio ,Retrospective cohort study ,Odds ratio ,Anti-Bacterial Agents ,Drug Therapy, Combination ,Female ,Klebsiella Infections ,Klebsiella pneumoniae ,medicine.disease ,Infectious Diseases ,Infectious Diseases, bloodstream infection, carbapenemase-prodicing Enterobacteriaceae ,N/A ,Combination ,Propensity score matching ,Cohort ,business - Abstract
Background The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. Methods In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0â7 [low mortality score] vs 8â15 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. Findings Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38·5%] of 343 patients died vs 57 [60·6%] of 94; absolute difference 22·1% [95% CI 11·0â33·3]; adjusted hazard ratio [HR] 0·45 [95% CI 0·33â0·62]; p
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- 2017
19. Comparison of Predictors and Mortality Between Bloodstream Infections Caused by ESBL-Producing Escherichia coli and ESBL-Producing Klebsiella pneumoniae
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Germán Bou, Alicia Hernandez-Torres, Álvaro Pascual, Antonio Oliver, Julia Origüen, Belén Gutiérrez-Gutiérrez, Benito Almirante, Carolina Navarro-San Francisco, Carmen Peña, Joaquín Bermejo, Vered Schechner, Maria Tumbarello, Esther Calbo, Oded Scheuerman, Axel Hamprecht, Federico Perez, Mario Venditti, Robert A. Bonomo, Cristina de la Calle, Oriol Gasch, Johann D. D. Pitout, Mónica Gozalo, Patricia Ruiz-Garbajosa, Warren Lowman, Murat Akova, Evelina Tacconelli, Mitchell J. Schwaber, Jesús Rodríguez-Baño, David L. Paterson, Po-Ren Hsueh, Pier-Luigy Viale, Núria Prim, Yehuda Carmeli, José Molina, Ilias Karaiskos, and Scheuerman O, Schechner V, Carmeli Y, Gutiérrez-Gutiérrez B, Calbo E, Almirante B, Viale P, Oliver A, Ruiz-Garbajosa P, Gasch O, Gozalo M, Pitout J, Akova M, Peña C, Molina J, Hernández-Torres A, Venditti M, Prim N, Origüen J, Bou G, Tacconelli E, Tumbarello M, Hamprecht A, Karaiskos I, de la Calle C, Pérez F, Schwaber MJ, Bermejo J, Lowman W, Hsueh PR, Navarro-San Francisco C, Bonomo RA, Paterson DL, Pascual A, Rodríguez-Baño J
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Male ,0301 basic medicine ,Epidemiology ,Klebsiella pneumoniae ,Bacteremia ,Polymerase Chain Reaction ,law.invention ,Tertiary Care Centers ,0302 clinical medicine ,Risk Factors ,law ,Genotype ,Risk of mortality ,polycyclic compounds ,Medicine ,030212 general & internal medicine ,Escherichia coli Infections ,Cross Infection ,biology ,Middle Aged ,Hospital Records ,Prognosis ,Intensive care unit ,Infectious Diseases ,ESBL Klebsiella penumoniae bloodstream infections ,Female ,Adult ,Microbiology (medical) ,medicine.medical_specialty ,030106 microbiology ,Infections ,beta-Lactamases ,03 medical and health sciences ,Internal medicine ,Escherichia coli ,Humans ,Aged ,Retrospective Studies ,business.industry ,Retrospective cohort study ,Odds ratio ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,biology.organism_classification ,bacterial infections and mycoses ,Klebsiella Infections ,Logistic Models ,ESBL ,bacteria ,business ,human activities - Abstract
OBJECTIVETo compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypesMETHODSAs part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression.RESULTSThe study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction amplification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia >14 days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4%; odds ratio, 1.64; P=.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non–CTX-M ESBLs were detected.CONCLUSIONSClinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected.CLINICAL TRIALS IDENTIFIERClinicalTrials.gov. Identifier: NCT01764490.Infect Control Hosp Epidemiol 2018;39:660–667
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- 2018
20. Predictors of outcome in patients with severe sepsis or septic shock due to extended-spectrum β-lactamase-producing Enterobacteriaceae
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Robert A. Bonomo, Mónica Gozalo, Evelina Tacconelli, Axel Hamprecht, Julia Origüen, Benito Almirante, Increment investigators, Warren Lowman, Marco Falcone, Po-Ren Hsueh, Germán Bou, C. de la Calle, Belén Gutiérrez-Gutiérrez, Pierluigi Viale, Alessandro Russo, Yehuda Carmeli, Marta Mora-Rillo, Maria Souli, Mario Tumbarello, Reipi, Alessio Farcomeni, Mitchell J. Schwaber, José Miguel Cisneros, Esgbis, Alicia Hernandez-Torres, Murat Akova, Jesús Rodríguez-Baño, David L. Paterson, Federico Perez, Jorge Rodriguez-Gómez, Mario Venditti, Patricia Ruiz-Garbajosa, Esther Calbo, Antonio Oliver, Oriol Gasch, Johann D. D. Pitout, N. Prim, Ilias Karaiskos, Álvaro Pascual, Carmen Peña, Joaquín Bermejo, Russo, A., Falcone, M., Gutiérrez-Gutiérrez, B., Calbo, E., Almirante, B., Viale, P.L., Oliver, A., Ruiz-Garbajosa, P., Gasch, O., Gozalo, M., Pitout, J., Akova, M., Peña, C., Cisneros, J.M., Hernández-Torres, A., Farcomeni, A., Prim, N., Origüen, J., Bou, G., Tacconelli, E., Tumbarello, M., Hamprecht, A., Karaiskos, I., de la Calle, C., Pérez, F., Schwaber, M.J., Bermejo, J., Lowman, W., Hsueh, P.-R., Mora-Rillo, M., Rodriguez-Gomez, J., Souli, M., Bonomo, R.A., Paterson, D.L., Carmeli, Y., Pascual, A., Rodríguez-Baño, J., and Venditti, M.
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0301 basic medicine ,Male ,Klebsiella pneumoniae ,ß-lactam/ß-lactamase inhibitor ,extended-spectrum ß-lactamases ,sepsis ,carbapenems ,septic shock ,ß-lactam/ß-lactamase inhibitors ,Aged ,Aged, 80 and over ,Anti-Bacterial Agents ,Drug Therapy, Combination ,Enterobacteriaceae ,Enterobacteriaceae Infections ,Female ,Humans ,Middle Aged ,Prognosis ,Retrospective Studies ,Sepsis ,Survival Analysis ,Treatment Outcome ,beta-Lactamase Inhibitors ,beta-Lactamases ,beta-Lactams ,Decision Support Techniques ,0302 clinical medicine ,Clinical endpoint ,80 and over ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,biology ,extended-spectrum ß-lactamase ,General Medicine ,Infectious Diseases ,Combination ,sepsi ,Settore SECS-S/01 - Statistica ,Microbiology (medical) ,medicine.medical_specialty ,030106 microbiology ,Infectious Disease ,carbapenem ,03 medical and health sciences ,Drug Therapy ,Internal medicine ,In patient ,business.industry ,Proportional hazards model ,Septic shock ,bacterial infections and mycoses ,medicine.disease ,biology.organism_classification ,Bacteremia ,business - Abstract
Purpose There are few data in the literature regarding sepsis or septic shock due to extended-spectrum β-lactamases (ESBL)-producing Enterobacteriaceae (E). The aim of this study was to assess predictors of outcome in septic patients with bloodstream infection (BSI) caused by ESBL-E. Methods Patients with severe sepsis or septic shock and BSI due to ESBL-E were selected from the INCREMENT database. The primary endpoint of the study was the evaluation of predictors of outcome after 30 days from development of severe sepsis or septic shock due to ESBL-E infection. Three cohorts were created for analysis: global, empirical-therapy and targeted-therapy cohorts. Results 367 septic patients were analysed. Overall mortality was 43.9% at 30 days. Escherichia coli (62.4%) and Klebsiella pneumoniae (27.2%) were the most frequent isolates. β-lactam/β-lactamase inhibitor (BLBLI) combinations were the most empirically used drug (43.6%), followed by carbapenems (29.4%). Empirical therapy was active in vitro in 249 (67.8%) patients, and escalation of antibiotic therapy was reported in 287 (78.2%) patients. Cox regression analysis showed that age, Charlson Comorbidity Index, McCabe classification, Pitt bacteremia score, abdominal source of infection and escalation of antibiotic therapy were independently associated with 30-day mortality. No differences in survival were reported in patients treated with BLBLI combinations or carbapenems in empirical or definitive therapy. Conclusions BSI due to ESBL-E in patients who developed severe sepsis or septic shock was associated with high 30-day mortality. Comorbidities, severity scores, source of infection and antibiotic therapy escalation were important determinants of unfavorable outcome.
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- 2018
21. Geographical variation in therapy for bloodstream infections due to multidrug-resistant enterobacteriaceae: a post hoc analysis of the INCREMENT study
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Patrick N.A. Harris, M. Diletta Pezzani, Belén Gutiérrez-Gutiérrez, Pierluigi Viale, Po-Ren Hsueh, Patricia Ruiz-Garbajosa, Mario Venditti, Mario Tumbarello, Carolina Navarro-Francisco, Esther Calbo, Murat Akova, Helen Giamarellou, Antonio Oliver, Benito Almirante, Oriol Gasch, Luis Martínez-Martínez, Mitchell J. Schwaber, George Daikos, Johann Pitout, Carmen Peña, Alicia Hernández-Torres, Yohei Doi, Federico Pérez, Felipe Francisco Tuon, Evelina Tacconelli, Yehuda Carmeli, Robert A. Bonomo, Álvaro Pascual, David L. Paterson, Jesús Rodríguez-Baño, M.D. del Toro, J. Gálvez, M. Falcone, A. Russob, I. Karaiskos, E.M. Trecarichi, A.R. Losito, E. García-Vázquez, J. Gómez, E. Roilides, E. Iosifidis, S. Pournaras, N. Prim, F. Navarro, B. Mirelis, J. Origüen, R. San Juan, M. Fernández-Ruiz, M. Almela, C. de la Calle, J.A. Martínez, L. Morata, N. Larrosa, M. Puig-Asensio, G. Bou, J. Molina, V. González, J. Bermejo, V. Rucci, E. Ruiz de Gopegui, C.I. Marinescu, M.C. Fariñas, M.E. Cano, M. Gozalo, J.R. Paño-Pardo, Marta Mora-Rillo, S. Gómez-Zorrilla, F. Tubau, A. Tsakris, O. Zarkotou, A. Antoniadou, G. Poulakou, M. Souli, W. Lowman, D. Virmani, Julian Torre-Cisneros, I. Machuca, Irene Gracia-Ahufinger, Ö.K. Azap, Ö. Helvaci, A.O. Sahin, R. Cantón, V. Pintado, M. Bartoletti, M. Giannella, S. Peter, A. Hamprecht, C. Badia, M. Xercavins, D. Fontanals, E. Jové, Universidad de Cantabria, Harris, Patrick N.A., Pezzani, M. Diletta, Gutiérrez-Gutiérrez, Belén, Viale, Pierluigi, Hsueh, Po-Ren, Ruiz-Garbajosa, Patricia, Venditti, Mario, Tumbarello, Mario, Navarro-Francisco, Carolina, Calbo, Esther, Akova, Murat, Giamarellou, Helen, Oliver, Antonio, Almirante, Benito, Gasch, Oriol, Martínez-Martínez, Lui, Schwaber, Mitchell J., Daikos, George, Pitout, Johann, Peña, Carmen, Hernández-Torres, Alicia, Doi, Yohei, Pérez, Federico, Tuon, Felipe Francisco, Tacconelli, Evelina, Carmeli, Yehuda, Bonomo, Robert A., Pascual, Álvaro, Paterson, David L., Rodríguez-Baño, Jesú, del Toro, M.D., Gálvez, J., Falcone, M., Russo, A., Karaiskos, I., Trecarichi, E.M., Losito, A.R., García-Vázquez, E., Gómez, J., Roilides, E., Iosifidis, E., Pournaras, S., Prim, N., Navarro, F., Mirelis, B., Origüen, J., Juan, R. San, Fernández-Ruiz, M., Almela, M., de la Calle, C., Martínez, J.A., Morata, L., Larrosa, N., Puig-Asensio, M., Bou, G., Molina, J., González, V., Bermejo, J., Rucci, V., de Gopegui, E. Ruiz, Marinescu, C.I., Fariñas, M.C., Cano, M.E., Gozalo, M., Paño-Pardo, J.R., Mora-Rillo, Marta, Gómez-Zorrilla, S., Tubau, F., Tsakris, A., Zarkotou, O., Antoniadou, A., Poulakou, G., Souli, M., Lowman, W., Virmani, D., Torre-Cisneros, Julian, Machuca, I., Gracia-Ahufinger, Irene, Azap, Ã .K., Helvaci, Ã ., Sahin, A.O., Cantón, R., Pintado, V., Bartoletti, M., Giannella, M., Peter, S., Hamprecht, A., Badia, C., Xercavins, M., Fontanals, D., and Jové, E.
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Male ,0301 basic medicine ,Carbapenem ,Global Health ,Logistic regression ,0302 clinical medicine ,Drug Resistance, Multiple, Bacterial ,Antimicrobial stewardship ,Pharmacology (medical) ,030212 general & internal medicine ,Aged, 80 and over ,Enterobacteriaceae Infections ,General Medicine ,Middle Aged ,Extended-spectrum beta-lactamase ,Klebsiella pneumoniae ,Infectious Diseases ,Beta-lactam/beta-lactamase inhibitors ,Female ,beta-Lactamase Inhibitors ,medicine.drug ,Adult ,Microbiology (medical) ,medicine.medical_specialty ,Combination therapy ,β-Lactam/β-lactamase inhibitor ,030106 microbiology ,Infectious Disease ,Biology ,beta-Lactams ,Carbapenemase ,03 medical and health sciences ,Extended-spectrum β-lactamase ,Enterobacteriaceae ,Sepsis ,Post-hoc analysis ,medicine ,Escherichia coli ,Humans ,Aged ,Retrospective Studies ,Carbapenems ,β-Lactam/β-lactamase inhibitor ,Odds ratio ,biochemical phenomena, metabolism, and nutrition ,Extended-spectrum β-lactamase ,Surgery ,Multiple drug resistance ,Observational study ,Demography - Abstract
We aimed to describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ?-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). 1,482 patients in 12 countries were included from an observational study of BSI caused by ESBL-E or CPE. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ?-lactam/?-lactamase inhibitors (BLBLI) or carbapenems, targeted use of BLBLI for ESBL-E and use of targeted combination therapy for CPE. The use of BLBLI for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.2) and Turkey (aOR 2.09, 95% CI 1.14-3.81), compared to Spain as a reference. Empirical carbapenems were more likely to be used in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89; 95% CI 1.05-3.39), and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLI for ESBL-E was more likely in sites from Italy. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. A better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts. PH is supported by an Australian Postgraduate Award from the University of Queensland. The study was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund "A way to achieve Europe" ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). BGG, JRB, APH and YC also received funds from the COMBACTE-CARE project (grant agreement 115620), Innovative Medicines Initiative (IMI), the European Union's Seventh Framework Programme (FP7/2007-2013) and in-kind contributions from EFPIA companies.
- Published
- 2017
22. Predictive value of fecal calprotectin and lactoferrin levels for negative outcomes in Clostridioides difficile infection.
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Ágreda Fernández M, Origüen J, Rodriguez-Goncer I, San Juan R, López-Medrano F, Parra P, Ruiz-Merlo T, Redondo N, Orellana MÁ, Aguado JM, and Fernández-Ruiz M
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- Humans, Leukocyte L1 Antigen Complex analysis, Prospective Studies, Feces chemistry, Biomarkers analysis, Lactoferrin metabolism, Clostridium Infections diagnosis, Clostridium Infections microbiology
- Abstract
Purpose: We investigated the role of fecal calprotectin (FC) and lactoferrin (FL) as predictive biomarkers in Clostridioides difficile infection (CDI)., Methods: We assembled a prospective cohort including all patients with a laboratory-confirmed CDI diagnosis between January and December 2017. FL and FC levels were measured at diagnosis by commercial ELISA and EIA kits. We investigated the diagnostic accuracy of FC and FL to predict CDI recurrence and severity (study outcomes) and explored optimal cut-off values in addition to those proposed by the manufacturers (200 µg/g and 7.2 µg/mL, respectively)., Results: We included 170 CDI cases (152 first episodes and 18 recurrences). The rates of recurrence (first episodes only) and severity (entire cohort) were 9.2% (14/152) and 46.5% (79/170). Both FL and FC levels were significantly higher in patients who developed study outcomes. Optimal cut-off values for FC and FL to predict CDI recurrence were 1052 µg/g and 6.0 µg/mL. The optimal cut-off value for FC yielded higher specificity (60.9%) and positive predictive value (PPV) (16.9%) than that proposed by the manufacturer. Regarding CDI severity, the optimal cut-off value for FC (439 µg/g) also provided higher specificity (43.9%) and PPV (54.1%) than that of the manufacturer, whereas the optimal cut-off value for FL (4.6 µg/mL) resulted in an improvement of PPV (57.5%)., Conclusion: By modifying the thresholds for assay positivity, the measurement of FC and FL at diagnosis is useful to predict recurrence and severity in CDI. Adding these biomarkers to current clinical scores may help to individualize CDI management., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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23. Efficacy and safety of oral fosfomycin for asymptomatic bacteriuria in kidney transplant recipients: Results from a Spanish multicenter cohort.
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Ruiz-Ruigómez M, Fernández-Ruiz M, Silva JT, Vidal E, Origüen J, Calvo-Cano A, Luna-Huerta E, Merino E, Hernández D, Jironda-Gallegos C, Escudero-Sánchez R, Gioia F, Moreno A, Roca C, Cordero E, Janeiro D, Sánchez-Sobrino B, Montero MM, Redondo D, Candel FJ, Pérez-Flores I, Armiñanzas C, González-Rico C, Fariñas MC, Rodrigo E, Loeches B, López-Oliva MO, Montejo M, Lauzurica R, Horcajada JP, Pascual J, Andrés A, Aguado JM, and López-Medrano F
- Abstract
Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR]: 1.1 - 10.5). Most episodes (96.4% [132/137]) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum β-lactamase-producing Enterobacterales [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [95%CI]: 31.9 - 48.9) for the whole cohort and 42.3% (95%CI: 31.2 - 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR]: 2.42; 95%CI: 1.11 - 5.29; P -value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 - 41.35; P -value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens., (Copyright © 2021 American Society for Microbiology.)
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- 2023
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24. Early Treatment with Sotrovimab for Covid-19.
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Origüen J, Caro-Teller JM, and López-Medrano F
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- Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Neutralizing, Humans, COVID-19 Drug Treatment
- Published
- 2022
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25. Analysis of the factors predicting clinical response to tocilizumab therapy in patients with severe COVID-19.
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San-Juan R, Fernández-Ruiz M, López-Medrano F, Carretero O, Lalueza A, Maestro de la Calle G, Pérez-Jacoiste Asín MA, Bueno H, Caro-Teller JM, Catalán M, de la Calle C, García-García R, Gómez C, Laguna-Goya R, Lizasoáin M, Martínez-López J, Origüen J, Sevillano Á, Gutiérrez E, de Miguel B, Aguilar F, Parra P, Ripoll M, Ruiz-Merlo T, Trujillo H, Pablos JL, Paz-Artal E, Lumbreras C, and Aguado JM
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- Antibodies, Monoclonal, Humanized, Humans, Retrospective Studies, SARS-CoV-2, COVID-19 Drug Treatment
- 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., Competing Interests: Conflicts of interest All the authors declare no potential conflict of interest regarding this study., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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26. Effectiveness of anakinra for tocilizumab-refractory severe COVID-19: A single-centre retrospective comparative study.
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de la Calle C, López-Medrano F, Pablos JL, Lora-Tamayo J, Maestro-de la Calle G, Sánchez-Fernández M, Fernández-Ruiz M, Pérez-Jacoiste Asín MA, Caro-Teller JM, García-García R, Catalán M, Martínez-López J, Sevillano Á, Origüen J, Ripoll M, San Juan R, Lalueza A, de Miguel B, Carretero O, Aguilar F, Gómez C, Paz-Artal E, Bueno H, Lumbreras C, and Aguado JM
- Subjects
- Aged, COVID-19 complications, Case-Control Studies, Cohort Studies, Cytokine Release Syndrome etiology, Female, Hospital Mortality, Humans, Immunomodulation drug effects, Male, Middle Aged, Retrospective Studies, Salvage Therapy, Spain epidemiology, Treatment Failure, Treatment Outcome, Antibodies, Monoclonal, Humanized therapeutic use, Cytokine Release Syndrome drug therapy, Interleukin 1 Receptor Antagonist Protein therapeutic use, SARS-CoV-2, COVID-19 Drug Treatment
- Abstract
Objectives: 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., Methods: 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., Results: 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)., Conclusions: Treatment with anakinra was not useful in improving the prognosis of patients with tocilizumab-refractory severe COVID-19., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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27. Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: A single-center retrospective study.
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López-Medrano F, Pérez-Jacoiste Asín MA, Fernández-Ruiz M, Carretero O, Lalueza A, Maestro de la Calle G, Caro JM, de la Calle C, Catalán M, García-García R, Martínez-López J, Origüen J, Ripoll M, San Juan R, Trujillo H, Sevillano Á, Gutiérrez E, de Miguel B, Aguilar F, Gómez C, Silva JT, García-Ruiz de Morales D, Saro-Buendía M, Marrero-Sánchez Á, Chiara-Graciani G, Bueno H, Paz-Artal E, Lumbreras C, Pablos JL, and Aguado JM
- Subjects
- Aged, Aged, 80 and over, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Retrospective Studies, Antibodies, Monoclonal, Humanized administration & dosage, Methylprednisolone administration & dosage, SARS-CoV-2, COVID-19 Drug Treatment
- Abstract
Background: The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear., Methods: A retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400-600mg, one to three doses) (CS-TCZ group). The 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 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied., Results: Totals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. 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=0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21-0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21-0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49-3.41; P<0.001). The occurrence of secondary infection was similar between both groups., Conclusions: The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2021
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28. Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: A single-center cohort study.
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Fernández-Ruiz M, López-Medrano F, Pérez-Jacoiste Asín MA, Maestro de la Calle G, Bueno H, Caro-Teller JM, Catalán M, de la Calle C, García-García R, Gómez C, Laguna-Goya R, Lizasoáin M, Martínez-López J, Origüen J, Pablos JL, Ripoll M, San Juan R, Trujillo H, Lumbreras C, and Aguado JM
- Subjects
- Administration, Intravenous, Adult, Body Temperature drug effects, C-Reactive Protein metabolism, COVID-19 immunology, COVID-19 mortality, COVID-19 virology, Cytokine Release Syndrome immunology, Cytokine Release Syndrome mortality, Cytokine Release Syndrome virology, Female, Heart Rate drug effects, Humans, Interferon-beta adverse effects, L-Lactate Dehydrogenase blood, Male, Middle Aged, Receptors, Interleukin-6 antagonists & inhibitors, Receptors, Interleukin-6 genetics, Receptors, Interleukin-6 immunology, Respiratory Rate drug effects, Retrospective Studies, SARS-CoV-2 immunology, Severity of Illness Index, Survival Analysis, Antibodies, Monoclonal, Humanized therapeutic use, Antiviral Agents therapeutic use, Cytokine Release Syndrome prevention & control, Immunologic Factors therapeutic use, SARS-CoV-2 pathogenicity, COVID-19 Drug Treatment
- 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/FiO
2 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., (© 2020 Wiley Periodicals LLC.)- Published
- 2021
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29. Oral fosfomycin for the treatment of lower urinary tract infections among kidney transplant recipients-Results of a Spanish multicenter cohort.
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López-Medrano F, Silva JT, Fernández-Ruiz M, Vidal E, Origüen J, Calvo-Cano A, Luna-Huerta E, Merino E, Hernández D, Jironda-Gallegos C, Escudero R, Gioia F, Moreno A, Roca C, Cordero E, Janeiro D, Sánchez-Sobrino B, Montero MM, Redondo D, Candel FJ, Pérez-Flores I, Armiñanzas C, González-Rico C, Fariñas MC, Rodrigo E, Loeches B, López-Oliva MO, Montejo M, Lauzurica R, Horcajada JP, Pascual J, Andrés A, and Aguado JM
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- Administration, Oral, Adult, Aged, Anti-Bacterial Agents therapeutic use, Female, Follow-Up Studies, Fosfomycin therapeutic use, Gram-Negative Bacterial Infections etiology, Gram-Positive Bacterial Infections etiology, Humans, Logistic Models, Male, Middle Aged, Retrospective Studies, Spain, Treatment Outcome, Urinary Tract Infections etiology, Anti-Bacterial Agents administration & dosage, Fosfomycin administration & dosage, Gram-Negative Bacterial Infections drug therapy, Gram-Positive Bacterial Infections drug therapy, Kidney Transplantation, Postoperative Complications drug therapy, Urinary Tract Infections drug therapy
- Abstract
Oral fosfomycin may constitute an alternative for the treatment of lower urinary tract infections (UTIs) in kidney transplant recipients (KTRs), particularly in view of recent safety concerns with fluroquinolones. Specific data on the efficacy and safety of fosfomycin in KTR are scarce. We performed a retrospective study in 14 Spanish hospitals including KTRs treated with oral fosfomycin (calcium and trometamol salts) for posttransplant cystitis between January 2005 and December 2017. A total of 133 KTRs developed 143 episodes of cystitis. Most episodes (131 [91.6%]) were produced by gram-negative bacilli (GNB), and 78 (54.5%) were categorized as multidrug resistant (including extended-spectrum β-lactamase-producing Enterobacteriaceae [14%] or carbapenem-resistant GNB [3.5%]). A median daily dose of 1.5 g of fosfomycin (interquartile range [IQR]: 1.5-2) was administered for a median of 7 days (IQR: 3-10). Clinical cure (remission of UTI-attributable symptoms at the end of therapy) was achieved in 83.9% (120/143) episodes. Among those episodes with follow-up urine culture, microbiological cure at month 1 was achieved in 70.2% (59/84) episodes. Percutaneous nephrostomy was associated with a lower probability of clinical cure (adjusted odds ratio: 10.50; 95% confidence interval: 0.98-112.29; P = 0.052). In conclusion, fosfomycin is an effective orally available alternative for treating cystitis among KTRs., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2020
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30. Toxin B PCR Amplification Cycle Threshold Adds Little to Clinical Variables for Predicting Outcomes in Clostridium difficile Infection: a Retrospective Cohort Study.
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Origüen J, Orellana MÁ, Fernández-Ruiz M, Corbella L, San Juan R, Ruiz-Ruigómez M, López-Medrano F, Lizasoain M, Ruiz-Merlo T, Maestro-de la Calle G, Parra P, Villa J, Delgado R, and Aguado JM
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Immunoenzyme Techniques methods, Male, Middle Aged, Prognosis, ROC Curve, Recurrence, Retrospective Studies, Sensitivity and Specificity, Treatment Outcome, Young Adult, Bacterial Proteins genetics, Bacterial Toxins genetics, Clinical Decision Rules, Clostridium Infections diagnosis, Clostridium Infections pathology, Polymerase Chain Reaction methods
- Abstract
The objective of the present study was to evaluate the value of the PCR cycle threshold ( C
T ) for predicting the recurrence/severity of infection compared to that of toxin detection plus clinical variables. First episodes of Clostridium difficile infection (CDI) diagnosed during 2015 at our institution were included. Samples were tested for glutamate dehydrogenase (GDH) and toxin A/B by use of a single enzyme immunoassay (EIA). The Xpert C. difficile PCR assay was performed on GDH-positive samples. Medical data were reviewed by investigators blinded to diagnostic results for comparison of patients with and without recurrence or a poor outcome (severe/severe-complicated CDI episodes and all-cause death). We generated two sets of predictive models by incorporating the presence of a positive toxin EIA ("EIA-including model") or the optimal PCR CT cutoff value ("PCR-including model") into the clinical variables. Among 227 episodes of CDI included in the study, the rates of recurrence and poor outcome were 15.8% and 30.8%, respectively. The mean PCR CT was lower for episodes with recurrence (24.00 ± 3.28 versus 26.02 ± 4.54; P = 0.002) or a poor outcome (24.9 ± 4.24 versus 26.05 ± 4.47; P = 0.07). The optimal cutoff value for recurrence was 25.65 (sensitivity, 77.8% [95% confidence interval {CI}, 60.9 to 89.9]; and specificity, 46.6% [95% CI, 39.4 to 53.9]). The area under the receiver operator characteristics curve (auROC) for the "PCR-including model" was similar to that for the "EIA-including model" (0.785 versus 0.775, respectively). The optimal PCR CT value for poor outcome was 27.55 (sensitivity, 78.6% [95% CI, 67.1 to 87.5]; and specificity, 35.7% [95% CI, 28.2 to 43.7]). The auROC of the "PCR-including model" was again similar to that of the "EIA-including model" (0.804 versus 0.801). Despite the inverse correlation between PCR CT and the risk of CDI recurrence/severity, this determination does not meaningfully increase the predictive value of clinical variables plus toxin EIA., (Copyright © 2019 American Society for Microbiology.)- Published
- 2019
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31. Impact on mortality of adherence to evidence-based interventions in patients with catheter-related bloodstream infection due to methicillin-sensitive Staphylococcus aureus.
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Morales-Cartagena A, Fernández-Ruiz M, Lalueza A, Lora-Tamayo J, San Juan R, López-Medrano F, Origüen J, Chaves F, and Aguado JM
- Subjects
- Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents pharmacology, Bacteremia epidemiology, Bacteremia microbiology, Bacteremia therapy, Blood Culture, Catheter-Related Infections epidemiology, Catheter-Related Infections microbiology, Catheter-Related Infections therapy, Cohort Studies, Female, Humans, Male, Methicillin pharmacology, Middle Aged, Retrospective Studies, Spain epidemiology, Staphylococcal Infections epidemiology, Staphylococcal Infections mortality, Staphylococcal Infections therapy, Treatment Adherence and Compliance, Bacteremia mortality, Catheter-Related Infections mortality, Evidence-Based Medicine, Quality of Health Care, Staphylococcal Infections microbiology, Staphylococcus aureus isolation & purification
- Abstract
Background: Recent studies have demonstrated improved survival when the management of Staphylococcus aureus bloodstream infection (BSI) is compliant with evidence-based therapeutic interventions. Whether this effect extends to low-risk sources, such as catheter-related BSI, remains unclear., Methods: We retrospectively included 225 episodes of methicillin-sensitive S. aureus catheter-related BSI diagnosed in our centre during two non-consecutive periods: 2002-2004 (first period (101 episodes)) and 2009-2013 (second period (124 episodes)). We evaluated the adherence (percentage of compliance = (no. of interventions performed/no. of interventions recommended) × 100) to the following bundle: early catheter removal (≤72 hours), early initiation of appropriate antibiotic therapy, adequate sampling of follow-up blood cultures, transthoracic echocardiography (TTE) during hospitalization and adequate duration of therapy., Results: Patients in the second period had a higher burden of comorbidities and more severe underlying conditions. All-cause 30-day mortality was 9.3%, with a significant difference between the first and second periods (13.9% versus 5.6%; p value = .035). Bundle adherence was significantly higher in the second period, particularly for follow-up blood cultures (26.7% versus 48.4%; p value = .001), performance of TTE (45.5% versus 84.7%; p value < .001) and appropriate duration of therapy (34.7% versus 50.0%; p value = .022). Bundle adherence ≥ 55% was associated with lower 30-day mortality (hazard ratio: 0.31; 95% confidence interval: 0.13-0.76). This effect remained significant across propensity score-based models adjusted for septic shock, study period and underlying conditions., Conclusions: There was a survival benefit in adhering to a bundle of evidence-based interventions in the specific setting of catheter-related BSI due to methicillin-sensitive S. aureus.
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- 2018
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32. Comparison of Predictors and Mortality Between Bloodstream Infections Caused by ESBL-Producing Escherichia coli and ESBL-Producing Klebsiella pneumoniae.
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Scheuerman O, Schechner V, Carmeli Y, Gutiérrez-Gutiérrez B, Calbo E, Almirante B, Viale PL, Oliver A, Ruiz-Garbajosa P, Gasch O, Gozalo M, Pitout J, Akova M, Peña C, Molina J, Hernández-Torres A, Venditti M, Prim N, Origüen J, Bou G, Tacconelli E, Tumbarello M, Hamprecht A, Karaiskos I, de la Calle C, Pérez F, Schwaber MJ, Bermejo J, Lowman W, Hsueh PR, Navarro-San Francisco C, Bonomo RA, Paterson DL, Pascual A, and Rodríguez-Baño J
- Subjects
- Adult, Aged, Escherichia coli enzymology, Escherichia coli genetics, Female, Genotype, Hospital Records, Humans, Klebsiella pneumoniae enzymology, Klebsiella pneumoniae genetics, Logistic Models, Male, Middle Aged, Polymerase Chain Reaction, Prognosis, Retrospective Studies, Risk Factors, Tertiary Care Centers, beta-Lactamases metabolism, Bacteremia microbiology, Bacteremia mortality, Cross Infection microbiology, Cross Infection mortality, Escherichia coli Infections mortality, Klebsiella Infections mortality
- Abstract
OBJECTIVETo compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypesMETHODSAs part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression.RESULTSThe study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction amplification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia >14 days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4%; odds ratio, 1.64; P=.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non-CTX-M ESBLs were detected.CONCLUSIONSClinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected.CLINICAL TRIALS IDENTIFIERClinicalTrials.gov. Identifier: NCT01764490.Infect Control Hosp Epidemiol 2018;39:660-667.
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- 2018
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33. T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study.
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Muñoz P, Vena A, Machado M, Gioia F, Martínez-Jiménez MC, Gómez E, Origüen J, Orellana MÁ, López-Medrano F, Fernández-Ruiz M, Merino P, González-Romo F, Frías I, Pérez-Granda MJ, Aguado JM, Fortún J, and Bouza E
- Subjects
- Adult, Aged, Antibodies, Fungal blood, Blood Culture, Candidiasis diagnosis, Candidiasis, Invasive diagnosis, Female, Humans, Male, Middle Aged, Pilot Projects, Prospective Studies, beta-Glucans blood, Antifungal Agents therapeutic use, Candidiasis diagnostic imaging, Candidiasis drug therapy, Candidiasis, Invasive diagnostic imaging, Candidiasis, Invasive drug therapy, Magnetic Resonance Imaging methods
- Abstract
Objectives: We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy., Methods: Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome)., Results: Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA [3/14 (21.4%) versus 8/35 (22.9%), P = 1] and BDG [8/14 (57.1%) versus 17/35 (48.6%), P = 0.75] results were similar in poor- and good-outcome patients. Conversely, a positive T2MR was associated with a higher risk of poor outcome [5/14 (35.7%) versus 0/35 (0.0%) P = 0.0001]. Specificity and positive predictive value of a positive T2MR for predicting poor outcome were both 100%, with a negative predictive value of 79.6%. After testing the combinations of biomarkers/standard cultures and T2MR/standard cultures, the combination of T2MR/standard cultures showed a high capacity to discriminate patients with poor outcome from those with good clinical evolution., Conclusions: T2MR may be of significant utility to identify patients who may benefit from maintaining antifungal therapy.
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- 2018
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34. T2MR contributes to the very early diagnosis of complicated candidaemia. A prospective study.
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Muñoz P, Vena A, Machado M, Martínez-Jiménez MC, Gioia F, Gómez E, Origüen J, Orellana MÁ, López-Medrano F, Pérez-Granda MJ, Aguado JM, Fortún J, and Bouza E
- Subjects
- Adult, Aged, Aged, 80 and over, Blood Culture, Early Diagnosis, Female, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Sensitivity and Specificity, beta-Glucans blood, Antifungal Agents therapeutic use, Candidemia diagnosis, Candidemia diagnostic imaging, Candidemia drug therapy, Candidemia mortality, Magnetic Resonance Imaging methods
- Abstract
Objectives: Diagnosis of complicated candidaemia represents a challenge for clinicians since early clinical manifestations may be non-specific and difficult to identify, thus precluding an appropriate treatment., Patients and Methods: This was a multicentre prospective study for predicting complicated episodes in patients with bloodstream infection caused by Candida species, while assessing the value of follow-up blood cultures (BCs) and the persistence of positive results for T2Candida MR (T2MR) and blood β-d-glucan (BDG) tests. Immediately after the first positive BC yielding Candida species, samples were obtained on days 0, +2, +4, +7 and +14, to simultaneously perform follow-up BC, T2MR and BDG. An episode of candidaemia was defined as 'complicated' when (i) it caused septic metastasis; and/or (ii) it was the cause of the patient's death., Results: From January to June 2017, 30 patients were enrolled in the study. Of these, nine (30%) had complicated candidaemia. Values of persistently positive samples for the prediction of complicated episodes for BCs, T2MR and BDG, respectively, were as follows: sensitivity (44.4%, 100%, 100%); specificity (76.1%, 76.1%, 38.9%); positive predictive value (PPV) (44.4%, 64.2%, 40.9%) and negative predictive value (NPV) (76.1%, 100%, 100%). In multivariate analysis, having a positive T2MR within the first 5 days was associated with an almost 37-fold higher risk of developing complicated candidaemia., Conclusions: The T2MR test performed in patients with proven candidaemia may be a better marker of complicated infection than follow-up BCs or BDG. It is possible that this test may change current clinical practice, influencing the length and type of antifungal therapy in this population.
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- 2018
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35. Herpes zoster in kidney transplant recipients: protective effect of anti-cytomegalovirus prophylaxis and natural killer cell count. A single-center cohort study.
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Fernández-Ruiz M, Origüen J, Lora D, López-Medrano F, González E, Polanco N, San Juan R, Ruiz-Merlo T, Parra P, Andrés A, and Aguado JM
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- Adult, Aged, Chemoprevention methods, Cohort Studies, Cytomegalovirus drug effects, Cytomegalovirus isolation & purification, Cytomegalovirus Infections drug therapy, Female, Graft Rejection, Graft Survival, Humans, Kidney Transplantation adverse effects, Killer Cells, Natural drug effects, Male, Middle Aged, Multivariate Analysis, Prognosis, ROC Curve, Retrospective Studies, Risk Assessment, Antiviral Agents administration & dosage, Cytomegalovirus Infections prevention & control, Ganciclovir administration & dosage, Herpes Zoster prevention & control, Kidney Transplantation methods, Transplant Recipients
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Despite its impact on quality of life and potential for complications, specific risk and protective factors for herpes zoster (HZ) after kidney transplantation (KT) remain to be clarified. We included 444 patients undergoing KT between November 2008 and March 2013. Peripheral blood lymphocyte subpopulations were measured at baseline and months 1 and 6. The risk factors for early (first post-transplant year) and late HZ (years 1-5) were separately assessed. We observed 35 episodes of post-transplant HZ after a median follow-up of 48.3 months (incidence rate: 0.057 per 1000 transplant-days). Median interval from transplantation was 18.3 months. Six patients (17.1%) developed disseminated infection. Postherpetic neuralgia occurred in 10 cases (28.6%). The receipt of anti-cytomegalovirus (CMV) prophylaxis with (val)ganciclovir decreased the risk of early HZ [adjusted hazard ratio (aHR): 0.08; 95% CI: 0.01-1.13; P-value = 0.062], whereas the natural killer (NK) cell at month 6 was protective for the occurrence of late HZ [aHR (per 10-cells/μl increase): 0.94; 95% CI: 0.88-1.00; P-value = 0.054]. In conclusion, two easily ascertainable factors (whether the patient is receiving anti-CMV prophylaxis and the NK cell count at month 6) might be potentially useful to tailor preventive strategies according to individual susceptibility to post-transplant HZ., (© 2017 Steunstichting ESOT.)
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- 2018
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36. Post-transplant hypocomplementemia: A novel marker of cardiovascular risk in kidney transplant recipients?
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Maestro de la Calle G, Fernández-Ruiz M, López-Medrano F, Polanco N, González E, San Juan R, Ruiz-Merlo T, Origüen J, Paz-Artal E, Andrés A, and Aguado JM
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- Adult, Aged, Biomarkers blood, Cardiovascular Diseases blood, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Female, Humans, Incidence, Male, Middle Aged, Monitoring, Immunologic, Progression-Free Survival, Prospective Studies, Retrospective Studies, Risk Assessment, Risk Factors, Spain epidemiology, Time Factors, Cardiovascular Diseases immunology, Complement C3 deficiency, Complement C4 deficiency, Kidney Transplantation adverse effects
- Abstract
Background and Aims: Cardiovascular disease (CVD) is a leading cause of mortality after kidney transplantation (KT). The potential role of the complement system in the pathogenesis of post-transplant CVD remains unexplored., Methods: Serum complement (C3 and C4) levels were measured at baseline and post-transplant months 1 and 6 in 447 kT recipients. The study outcome was post-transplant atherothrombotic event (PAE), a composite of acute coronary syndrome, critical peripheral arterial disease, stroke and/or transient ischemic attack., Results: After a median follow-up of 4.2 years, 48 PAEs occurred in 43 patients (cumulative incidence: 9.6%; incidence rate: 2.6 events per 100 transplant-years). No differences were found in C3 and C4 levels at baseline or month 1 between patients with or without PAE. However, C3 levels at month 6 were significantly lower in patients developing PAE beyond that point (i.e., late PAE) (96.9 ± 22.3 vs. 109.6 ± 24.0 mg/dL; p = 0.013). The presence of C3 hypocomplementemia at month 6 was associated with a lower PAE-free survival (p = 0.002). After adjusting for conventional CVD risk factors and acute graft rejection, C3 hypocomplementemia at month 6 remained as an independent risk factor for late PAE in all the exploratory models (minimum hazard ratio: 3.24; p = 0.011). With respect to a model exclusively based on clinical variables, the inclusion of C3 levels at month 6 improved predictive capacity (areas under ROC curves: 0.788 and 0.812, respectively)., Conclusions: Post-transplant monitoring of serum C3 levels might be useful to identify KT recipients at increased risk of CVD., (Copyright © 2018 Elsevier B.V. All rights reserved.)
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- 2018
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37. Serum sCD30: A promising biomarker for predicting the risk of bacterial infection after kidney transplantation.
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Fernández-Ruiz M, Parra P, López-Medrano F, Ruiz-Merlo T, González E, Polanco N, Origüen J, San Juan R, Andrés A, and Aguado JM
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- Adult, Aged, Bacterial Infections epidemiology, Biomarkers blood, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Graft Rejection prevention & control, Humans, Incidence, Kidney Transplantation mortality, Male, Middle Aged, Opportunistic Infections epidemiology, Prospective Studies, Regression Analysis, Risk Factors, Survival Rate, Bacterial Infections diagnosis, Immunosuppression Therapy adverse effects, Ki-1 Antigen blood, Kidney Transplantation adverse effects, Opportunistic Infections diagnosis
- Abstract
Background: The transmembrane glycoprotein CD30 contributes to regulate the balance between Th
1 and Th2 responses. Previous studies have reported conflicting results on the utility of its soluble form (sCD30) to predict post-transplant infection., Methods: Serum sCD30 was measured by a commercial ELISA assay at baseline and post-transplant months 1, 3, and 6 in 100 kidney transplant (KT) recipients (279 monitoring points). The impact of sCD30 levels on the incidence of overall, bacterial and opportunistic infection during the first 12 months after transplantation was assessed by Cox regression., Results: There were no differences in serum sCD30 according to the occurrence of overall or opportunistic infection. However, sCD30 levels were higher in patients with bacterial infection compared to those without at baseline (P=.038) and months 1 (P<.0001), 3 (P=.043), and 6 after transplantation (P=.006). Patients with baseline sCD30 levels ≥13.5 ng/mL had lower 12-month bacterial infection-free survival (35.0% vs 80.0%; P<.0001). After adjusting for potential confounders, baseline sCD30 levels ≥13.5 ng/mL remained as an independent risk factor for bacterial infection (adjusted hazard ratio [aHR]: 4.65; 95% confidence interval [CI]: 2.05-10.53; <.001). Analogously, sCD30 levels ≥6.0 ng/mL at month 1 acted as a risk factor for subsequent bacterial infection (aHR: 5.29; 95% CI: 1.11-25.14; P=.036)., Conclusion: Higher serum sCD30 levels were associated with an increased risk of bacterial infection after KT. We hypothesize that this biomarker reflects a Th2 -polarized T-cell response, which exerts a detrimental effect on the immunity against bacterial pathogens., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)- Published
- 2017
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38. Development and validation of the INCREMENT-ESBL predictive score for mortality in patients with bloodstream infections due to extended-spectrum-β-lactamase-producing Enterobacteriaceae.
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Palacios-Baena ZR, Gutiérrez-Gutiérrez B, De Cueto M, Viale P, Venditti M, Hernández-Torres A, Oliver A, Martínez-Martínez L, Calbo E, Pintado V, Gasch O, Almirante B, Antonio Lepe J, Pitout J, Akova M, Peña-Miralles C, Schwaber MJ, Tumbarello M, Tacconelli E, Origüen J, Prim N, Bou G, Giamarellou H, Bermejo J, Hamprecht A, Pérez F, Almela M, Lowman W, Hsueh PR, Navarro-San Francisco C, Torre-Cisneros J, Carmeli Y, Bonomo RA, Paterson DL, Pascual Á, and Rodríguez-Baño J
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- Aged, Anti-Bacterial Agents therapeutic use, Bacteremia drug therapy, Bacteremia microbiology, Enterobacteriaceae Infections drug therapy, Female, Humans, Klebsiella enzymology, Klebsiella isolation & purification, Klebsiella Infections drug therapy, Klebsiella Infections microbiology, Klebsiella Infections mortality, Logistic Models, Male, Middle Aged, Predictive Value of Tests, Prognosis, Retrospective Studies, Sepsis drug therapy, Bacteremia mortality, Enterobacteriaceae enzymology, Enterobacteriaceae Infections microbiology, Enterobacteriaceae Infections mortality, beta-Lactamases biosynthesis
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Background: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality., Methods: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC., Results: The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18-5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21-3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02-6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24-6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69-5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72-8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58-4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of < 11 and ≥11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC., Conclusions: We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
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39. A Multinational, Preregistered Cohort Study of β-Lactam/β-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae.
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Gutiérrez-Gutiérrez B, Pérez-Galera S, Salamanca E, de Cueto M, Calbo E, Almirante B, Viale P, Oliver A, Pintado V, Gasch O, Martínez-Martínez L, Pitout J, Akova M, Peña C, Molina J, Hernández A, Venditti M, Prim N, Origüen J, Bou G, Tacconelli E, Tumbarello M, Hamprecht A, Giamarellou H, Almela M, Pérez F, Schwaber MJ, Bermejo J, Lowman W, Hsueh PR, Mora-Rillo M, Natera C, Souli M, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, and Rodríguez-Baño J
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- Aged, Bacteremia microbiology, Bacteremia mortality, Carbapenems therapeutic use, Enterobacteriaceae drug effects, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Retrospective Studies, Anti-Bacterial Agents therapeutic use, Bacteremia drug therapy, Enterobacteriaceae enzymology, Enterobacteriaceae pathogenicity, beta-Lactamase Inhibitors therapeutic use, beta-Lactamases metabolism, beta-Lactams metabolism
- Abstract
The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
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- 2016
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40. Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study.
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Gutiérrez-Gutiérrez B, Bonomo RA, Carmeli Y, Paterson DL, Almirante B, Martínez-Martínez L, Oliver A, Calbo E, Peña C, Akova M, Pitout J, Origüen J, Pintado V, García-Vázquez E, Gasch O, Hamprecht A, Prim N, Tumbarello M, Bou G, Viale P, Tacconelli E, Almela M, Pérez F, Giamarellou H, Cisneros JM, Schwaber MJ, Venditti M, Lowman W, Bermejo J, Hsueh PR, Mora-Rillo M, Gracia-Ahulfinger I, Pascual A, and Rodríguez-Baño J
- Subjects
- Aged, Enterobacteriaceae isolation & purification, Enterobacteriaceae Infections microbiology, Ertapenem, Female, Humans, Male, Middle Aged, Retrospective Studies, Sepsis microbiology, Survival Analysis, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Carbapenems therapeutic use, Enterobacteriaceae enzymology, Enterobacteriaceae Infections drug therapy, Sepsis drug therapy, beta-Lactamases metabolism, beta-Lactams therapeutic use
- Abstract
Objectives: Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E., Methods: A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality., Results: The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P = 0.06) in the ETC and 89.8% and 82.6% (P = 0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P = 0.01) in the ETC and 9.3% and 17.1% (P = 0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24-20.08; P = 0.58) and 1.04 (0.44-2.50; P = 0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43-3.29; P = 0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43-2.03; P = 0.86) and for the propensity-matched cohorts it was 1.05 (0.46-2.44; P = 0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems., Conclusions: Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
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- 2016
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41. Executive summary. Management of urinary tract infection in solid organ transplant recipients: Consensus statement of the Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI).
- Author
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Vidal E, Cervera C, Cordero E, Armiñanzas C, Carratalá J, Cisneros JM, Fariñas MC, López-Medrano F, Moreno A, Muñoz P, Origüen J, Sabé N, Valerio M, and Torre-Cisneros J
- Subjects
- Anti-Infective Agents administration & dosage, Anti-Infective Agents therapeutic use, Drug Interactions, Female, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Immunosuppressive Agents therapeutic use, Male, Organ Transplantation, Postoperative Complications etiology, Postoperative Complications microbiology, Prostatitis drug therapy, Prostatitis etiology, Recurrence, Risk Factors, Urinary Tract Infections epidemiology, Urinary Tract Infections etiology, Urinary Tract Infections microbiology, Postoperative Complications drug therapy, Transplant Recipients, Urinary Tract Infections drug therapy
- Abstract
Urinary tract infections (UTI) are one of the most common infections in solid organ transplant (SOT) recipients. A systematic review was performed to assess the management of UTI in SOT recipients. Recommendations are provided on the management of asymptomatic bacteriuria, and prophylaxis and treatment of UTI in SOT recipients. The diagnostic-therapeutic management of recurrent UTI and the role of infection in kidney graft rejection or dysfunction are reviewed. Finally, recommendations on antimicrobials and immunosuppressant interactions are also included., (Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)
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- 2015
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42. Management of urinary tract infection in solid organ transplant recipients: Consensus statement of the Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI).
- Author
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Vidal E, Cervera C, Cordero E, Armiñanzas C, Carratalá J, Cisneros JM, Fariñas MC, López-Medrano F, Moreno A, Muñoz P, Origüen J, Sabé N, Valerio M, and Torre-Cisneros J
- Subjects
- Anti-Infective Agents administration & dosage, Anti-Infective Agents therapeutic use, Antibiotic Prophylaxis, Asymptomatic Diseases, Bacteriuria drug therapy, Drug Interactions, Female, Graft Rejection, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Immunosuppressive Agents therapeutic use, Male, Organ Transplantation, Postoperative Complications etiology, Postoperative Complications microbiology, Prostatitis drug therapy, Prostatitis etiology, Recurrence, Risk Factors, Urinary Tract Infections epidemiology, Urinary Tract Infections etiology, Urinary Tract Infections microbiology, Postoperative Complications drug therapy, Transplant Recipients, Urinary Tract Infections drug therapy
- Abstract
Background: Urinary tract infections (UTIs) are one of the most common infections in solid organ transplant (SOT) recipients., Methods: Experienced SOT researchers and clinicians have developed and implemented this consensus document in support of the optimal management of these patients. A systematic review was conducted, and evidence levels based on the available literature are given for each recommendation. This article was written in accordance with international recommendations on consensus statements and the recommendations of the Appraisal of Guidelines for Research and Evaluation II (AGREE II)., Results: Recommendations are provided on the management of asymptomatic bacteriuria, and prophylaxis and treatment of UTI in SOT recipients. The diagnostic-therapeutic management of recurrent UTI and the role of infection in kidney graft rejection or dysfunction are reviewed. Finally, recommendations on antimicrobials and immunosuppressant interactions are also included., Conclusions: The latest scientific information on UTI in SOT is incorporated in this consensus document., (Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)
- Published
- 2015
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43. Potential role of post-transplant hypogammaglobulinemia in the risk of Clostridium difficile infection after kidney transplantation: a case-control study.
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Origüen J, Fernández-Ruiz M, Lumbreras C, Orellana MÁ, López-Medrano F, Ruiz-Merlo T, San Juan R, García-Reyne A, González E, Polanco N, Paz-Artal E, Andrés A, and Aguado JM
- Subjects
- Adult, Agammaglobulinemia etiology, Agammaglobulinemia prevention & control, Aged, Case-Control Studies, Clostridium Infections epidemiology, Clostridium Infections mortality, Female, Humans, Incidence, Male, Middle Aged, Risk Factors, Survival Rate, Agammaglobulinemia complications, Clostridioides difficile, Clostridium Infections etiology, Kidney Transplantation, Postoperative Complications
- Abstract
Purpose: To identify reversible risk factors for Clostridium difficile infection (CDI) after kidney transplantation (KT) that could lead to a reduction in its incidence and associated complications., Methods: We performed a single-center case-control study in which 41 patients undergoing KT between February 2009 and July 2013 who developed a first episode of post-transplant CDI were included as cases. Patients transplanted at the same calendar day (± 2 weeks) as each case with no evidence of CDI and comparable risk exposure period were chosen as controls (2:1 ratio). Serum immunoglobulin and complement levels were systematically measured at baseline and months 1 and 6 after transplantation., Results: Multivariate regression analysis identified age-adjusted Charlson comorbidity index (odds ratio [OR] per unitary increment 1.31; P value = 0.043), delayed graft function (OR 2.76; P value = 0.039), prior cytomegalovirus (CMV) disease (OR 6.85; P value = 0.011) and prior acute graft rejection (OR 5.92; P value = 0.008) as risk factors for post-transplant CDI. Cases with their first episode of CDI occurring beyond the first month were more likely to have IgG hypogammaglobulinemia (HGG) at month 1 (P value = 0.002), whereas cases with CDI beyond the sixth month were more likely to have HGG of any class at month 6 (P value = 0.003). Poor outcome (graft loss and/or all-cause mortality) was more common among cases (adjusted hazard ratio 5.69; P value = 0.001)., Conclusion: The occurrence of CDI exerts a detrimental effect on graft and patient outcome. Post-transplant HGG was a potentially modifiable risk factor for CDI in KT recipients.
- Published
- 2015
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44. Clinical significance of Candida colonization of intravascular catheters in the absence of documented candidemia.
- Author
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López-Medrano F, Fernández-Ruiz M, Origüen J, Belarte-Tornero LC, Carazo-Medina R, Panizo-Mota F, Chaves F, Sanz-Sanz F, San Juan R, and Aguado JM
- Subjects
- Adult, Aged, Aged, 80 and over, Analysis of Variance, Candidemia etiology, Female, Humans, Logistic Models, Male, Middle Aged, Retrospective Studies, Risk Factors, Candida isolation & purification, Candidemia microbiology, Catheterization, Central Venous adverse effects, Catheters, Indwelling microbiology
- Abstract
In order to assess the significance of Candida colonization of intravascular catheters (IVC) in patients without documented candidemia, we retrospectively reviewed all Candida-positive IVC tip cultures over a 4-year period. Cases were defined as those with a culture yielding ≥15 colony-forming units of Candida spp. that either did not have blood cultures (BC) taken or had concomitant BC negative for Candida. Patients were followed up until death or 8 months after discharge. Risk factors for poor outcome following IVC removal (death, candidemia, or Candida-related complication) were analyzed. We analyzed a total of 40 patients. Overall mortality was 40.0%, with no death directly attributed to Candida infection. Twenty-two patients received antifungal therapy at the time of IVC removal. Only 1 patient developed a metastatic complication (chorioretinitis) attributable to transient candidemia (2.5% of the global cohort and 3.7% among those with concomitant BC). There were no cases of subsequent candidemia. In the multivariate analysis, the use of antifungal therapy did not show any impact on the risk of poor outcome. The risk of invasive disease in patients with isolated IVC colonization by Candida seems to be low. Nevertheless, the initiation of systemic antifungal therapy should be carefully considered in such context., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
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