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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

Author

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

Published
2017
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9. The Impact of Carbapenem Resistance on Mortality in Patients With Klebsiella Pneumoniae Bloodstream Infection: An Individual Patient Data Meta-Analysis of 1952 Patients

Author

Maraolo, A.E. Corcione, S. Grossi, A. Signori, A. Alicino, C. Hussein, K. Trecarichi, E.M. Viale, P. Timsit, J.-F. Veeraraghavan, B. Villegas, M.V. Rahav, G. Daikos, G.L. Vardakas, K.Z. Roilides, E. Uhlemann, A.-C. Ghafur, A.K. Mornese Pinna, S. Bassetti, M. Kohler, P.P. Giacobbe, D.R.

Abstract

Introduction: Available evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined. Methods: We updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256). Results: IPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infected patients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56–3.04; I2 = 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24–2.47; I2 = 0) and of active initial therapy (aOR 2.66; 95% CI 1.70–4.16; I2 = 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36–3.59; I2 = 58%). Conclusion: Resistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniae even adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials. © 2021, The Author(s).

Published
2021

10. Risk factors for bloodstream infections due to colistin-resistant KPC-producing Klebsiella pneumoniae: results from a multicenter case–control–control study

Author

Giacobbe, D.R., Del Bono, V., Trecarichi, E.M., De Rosa, F.G., Giannella, M., Bassetti, M., Bartoloni, A., Losito, A.R., Corcione, S., Bartoletti, M., Mantengoli, E., Saffioti, C., Pagani, N., Tedeschi, S., Spanu, T., Rossolini, G.M., Marchese, A., Ambretti, S., Cauda, R., Viale, P., Viscoli, C., and Tumbarello, M.

Published
2015
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11. Geographical variation in therapy for bloodstream infections due to multidrug-resistant Enterobacteriaceae: a post-hoc analysis of the INCREMENT study

Author

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

Published
2017

12. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study

Author

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

Published
2017

13. Empiric Therapy with Carbapenem-Sparing Regimens for Bloodstream Infections due to Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: Results from the INCREMENT Cohort

Author

Palacios-Baena, Z.R. Gutiérrez-Gutiérrez, B. Calbo, E. Almirante, B. Viale, P. Oliver, A. Pintado, V. Gasch, O. Martínez-Martínez, L. Pitout, J. Akova, M. Peña, C. Molina Gil-Bermejo, J. Hernández, A. Venditti, M. Prim, N. Bou, G. Tacconelli, E. Tumbarello, M. Hamprecht, A. Giamarellou, H. Almela, M. Pérez, F. Schwaber, M.J. Bermejo, J. Lowman, W. Hsueh, P.-R. Paño-Pardo, J.R. Torre-Cisneros, J. Souli, M. Bonomo, R.A. Carmeli, Y. Paterson, D.L. Pascual, Á. Rodríguez-Baño, J. Gálvez, J. Falcone, M. Russo, A. Daikos, G. Trecarichi, E.M. Losito, A.R. Gómez, J. Iosifidis, E. Roilides, E. Karaiskos, I. Doi, Y. Tuon, F.F. Navarro, F. Mirelis, B. Martínez, J.A. De La Calle, C. Morata, L. San Juan, R. Fernández-Ruiz, M. Larrosa, N. Puig, M. Molina, J. González, V. Rucci, V. Ruiz De Gopegui, E. Marinescu, C.I. Fariñas, M.C. Cano, M.E. Gozalo, M. Mora-Rillo, M. Gómez-Zorrilla, S. Tubau, F. Pournaras, S. Tsakris, A. Zarkotou, O. Azap, Ö.K. Antoniadou, A. Poulakou, G. Virmani, D. Cano, Á. Machuca, I. Helvaci, Ö. Sahin, A.O. Ruiz-Garbajosa, P. Bartoletti, M. Giannella, M. Peter, S. Badia, C. Xercavins, M. Fontanals, D. Jové, E.

Subjects
bacterial infections and mycoses
Abstract

Background. There is little information about the efficacy of active alternative drugs to carbapenems except ?-lactam/?-lactamase inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum ?-lactamase-producing Enterobacteriaceae (ESBL-E). The objective of this study was to assess the outcomes of patients with BSI due to ESBL-E who received empiric therapy with such drugs (other active drugs [OADs]) or carbapenems. Methods. A multinational retrospective cohort study of patients with BSI due to ESBL-E who received empiric treatment with OADs or carbapenems was performed. Cox regression including a propensity score for receiving OADs was performed to analyze 30-day all-cause mortality as main outcome. Clinical failure and length of stay were also analyzed. Results. Overall, 335 patients were included; 249 received empiric carbapenems and 86 OADs. The most frequent OADs were aminoglycosides (43 patients) and fluoroquinolones (20 patients). Empiric therapy with OADs was not associated with mortality (hazard ratio [HR], 0.75; 95% confidence interval [CI], .38-1.48) in the Cox regression analysis. Propensity score-matched pairs, subgroups, and sensitivity analyses did not show different trends; specifically, the adjusted HR for aminoglycosides was 1.05 (95% CI, .51-2.16). OADs were neither associated with 14-day clinical failure (adjusted odds ratio, 0.62; 95% CI, .29-1.36) nor length of hospital stay. Conclusions. We were unable to show that empiric treatment with OAD was associated with a worse outcome compared with carbapenems. This information allows more options to be considered for empiric therapy, at least for some patients, depending on local susceptibility patterns of ESBL-E. © The Author 2017.

Published
2017

14. Geographical variation in therapy for bloodstream infections due to multidrug-resistant Enterobacteriaceae: a post-hoc analysis of the INCREMENT study

Author

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

Published
2017
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15. Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: A multinational pre-registered cohort study

Author

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

Subjects
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.

Published
2016

16. A Predictive Model of Mortality in Patients With Bloodstream Infections due to Carbapenemase-Producing Enterobacteriaceae

Author

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

Published
2016

17. Enzyme-Linked Immunospot Assay as a Complementary Method to Assess and Monitor Cytomegalovirus Infection in Kidney Transplant Recipients on Pre-emptive Antiviral Therapy: A Single-Center Experience

Author

Favi, E., primary, Santangelo, R., additional, Iesari, S., additional, Morandi, M., additional, Marcovecchio, G.E., additional, Trecarichi, E.M., additional, Salerno, M.P., additional, Ferraresso, M., additional, Citterio, F., additional, and Romagnoli, J., additional

Published
2017
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18. A Predictive Model of Mortality in Patients With Bloodstream Infections due to Carbapenemase-Producing Enterobacteriaceae

Author

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, Pintado, Vicente, additional, Doi, Yohei, additional, Tuon, Felipe Francisco, additional, Karaiskos, Ilias, additional, Machuca, Isabel, 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, 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, Iosifidis, E., additional, Prim, N., additional, Navarro, F., additional, Mirelis, B., additional, Origüen, J., additional, San Juan, R., 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, Ruiz de Gopegui, E., additional, Marinescu, C.I., additional, Martínez-Martínez, L., additional, Fariñas, M.C., additional, Cano, M.E., additional, Gozalo, M., additional, Mora-Rillo, M., additional, Navarro-San Francisco, C., additional, Peña, C., additional, Gómez-Zorrilla, S., additional, Tubau, F., additional, Tsakris, A., additional, Zarkotou, O., additional, Azap, Ö.K., additional, Pitout, J., additional, Virmani, D., additional, Torre-Cisneros, J., additional, Natera, C., additional, Helvaci, Ö., additional, Sahin, A.O., additional, Cantón, R., additional, Ruiz, P., additional, Bartoletti, M., additional, Giannella, M., additional, Taconelli, E., additional, Riemenschneider, F., additional, Calbo, E., additional, Badia, C., additional, Xercavins, M., additional, Gasch, E., additional, Fontanals, D., additional, and Jové, E., additional

Published
2016
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19. Combined lymphocyte/monocyte count, D-dimer and iron status predict COVID-19 course and outcome in a long-term care facility

Author

Maria Mazzitelli, Francesco Costanzo, Giuseppe Viglietto, Daniela Foti, Carlo Torti, Salvatore Rotundo, Daniele Torella, Enrico Maria Trecarichi, Cirino Botta, Flavia Biamonte, Biamonte F., Botta C., Mazzitelli M., Rotundo S., Trecarichi E.M., Foti D., Torti C., Viglietto G., Torella D., and Costanzo F.

Subjects
Male, medicine.medical_specialty, Lymphocyte, Iron, lcsh:Medicine, Disease, Monocyte, General Biochemistry, Genetics and Molecular Biology, Monocytes, Fibrin Fibrinogen Degradation Products, Leukocyte Count, Long-term care facilitie, Internal medicine, D-dimer, medicine, Humans, Lymphocytes, Aged, Retrospective Studies, Aged, 80 and over, biology, business.industry, Platelet Count, Long-term care facilities, Clinical outcome, SARS-CoV-2, Research, lcsh:R, COVID-19, Retrospective cohort study, General Medicine, Biomarker, Middle Aged, medicine.disease, Prognosis, Long-Term Care, Ferritin, Pneumonia, medicine.anatomical_structure, Treatment Outcome, biology.protein, Female, Hemoglobin, business, Biomarkers
Abstract

Background The Sars-CoV-2 can cause severe pneumonia with multiorgan disease; thus, the identification of clinical and laboratory predictors of the progression towards severe and fatal forms of this illness is needed. Here, we retrospectively evaluated and integrated laboratory parameters of 45 elderly subjects from a long-term care facility with Sars-CoV-2 outbreak and spread, to identify potential common patterns of systemic response able to better stratify patients’ clinical course and outcome. Methods Baseline white blood cells, granulocytes’, lymphocytes’, and platelets’ counts, hemoglobin, total iron, ferritin, D-dimer, and interleukin-6 concentration were used to generate a principal component analysis. Statistical analysis was performed by using R statistical package version 4.0. Results We identified 3 laboratory patterns of response, renamed as low-risk, intermediate-risk, and high-risk, strongly associated with patients’ survival (p Conclusions Our data suggest that a combination of few laboratory parameters, i.e. iron status, D-dimer and lymphocyte/monocyte count at admission and during the hospital stay, can predict clinical progression in COVID-19.

Published
2021

20. Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Author

Maria Giovanna Quaranta, Luigina Ferrigno, Xhimi Tata, Franca D'Angelo, Marco Massari, Carmine Coppola, Elisa Biliotti, Alessia Giorgini, Diletta Laccabue, Alessia Ciancio, Pier Luigi Blanc, Marzia Margotti, Donatella Ieluzzi, Maurizia Rossana Brunetto, Francesco Barbaro, Francesco Paolo Russo, Ilaria Beretta, Giulia Morsica, Gabriella Verucchi, Annalisa Saracino, Massimo Galli, Loeta A. Kondili, Cesare Mazzaro, Manuela Bertola, Ornella Schioppa, Antonio Benedetti, Laura Schiadà, Monica Cucco, Andrea Giacometti, Laura Brescini, Sefora Castelletti, Alessandro Fiorentini, Gioacchino Angarano, Michele Milella, Alfredo Di Leo, Maria Rendina, Fulvio Salvatore D'abramo, Chiara Lillo, Andrea Iannone, Mariano Piazzolla, Lorenzo Badia, Fabio Piscaglia, Francesca Benevento, Ilaria Serio, Francesco Castelli, Serena Zaltron, Angiola Spinetti, Silvia Odolini, Raffaele Bruno, Mario Mondelli, Luchino Chessa, Martina Loi, Carlo Torti, Chiara Costa, Maria Mazzitelli, Vincenzo Pisani, Vincenzo Scaglione, Enrico Maria Trecarichi, Anna Linda Zignego, Monica Monti, Francesco Madia, Letizia Attala, Piera Pierotti, Elena Salomoni, Elisa Mariabelli, Teresa Antonia Santantonio, Serena Rita Bruno, Ester Marina Cela, Matteo Bassetti, Giovanni Mazzarello, Anna Ida Alessandrini, Antonio Di Biagio, Laura Ambra Nicolini, Giovanni Raimondo, Roberto Filomia, Alessio Aghemo, Rossella Meli, Adriano Lazzarin, Stefania Salpietro, Anna Ludovica Fracanzani, Erika Fatta, Rosa Lombardi, Pietro Lampertico, Marta Borghi, Roberta D'ambrosio, Elisabetta Degasperi, Massimo Puoti, Chiara Baiguera, Federico D'amico, Maria Vinci, Maria Grazia Rumi, Massimo Zuin, Paola Zermiani, Pietro Andreone, Paolo Caraceni, Valeria Guarneri, Erica Villa, Veronica Bernabucci, Laura Bristot, Maria Luisa Paradiso, Guglielmo Migliorino, Alessandra Gambaro, Giuseppe Lapadula, Anna Spolti, Alessandro Soria, Pietro Invernizzi, Antonio Ciaccio, Martina LucÀ, Federica Malinverno, Laura Ratti, Daniela Caterina Amoruso, Federica Pisano, Ferdinando Scarano, Laura Staiano, Filomena Morisco, Valentina Cossiga, Ivan Gentile, Antonio Riccardo Buonomo, Maria Foggia, Emanuela Zappulo, Alessandro Federico, Marcello Dallio, Nicola Coppola, Caterina Sagnelli, Salvatore Martini, Caterina Monari, Gerardo Nardone, Costantino Sgamato, Liliana Chemello, Luisa Cavalletto, Daniela Sterrantino, Alberto Zanetto, Paola Zanaga, Giuseppina Brancaccio, Antonio Craxì, Salvatore Petta, Vincenza Calvaruso, Luciano Crapanzano, Salvatore Madonia, Marco Cannizzaro, Erica Maria Bruno, Anna Licata, Simona Amodeo, Adele Rosaria Capitano, Carlo Ferrari, Elisa Negri, Alessandra Orlandini, Marco Pesci, Roberto Gulminetti, Layla Pagnucco, Giustino Parruti, Paola Di Stefano, Barbara Coco, Romina Corsini, Elisa Garlassi, Massimo Andreoni, Elisabetta Teti, Carlotta Cerva, Lorenzo Baiocchi, Giuseppe Grassi, Antonio Gasbarrini, Maurizio Pompili, Martina De Siena, Gloria Taliani, Martina Spaziante, Marcello Persico, Mario Masarone, Andrea Aglitti, Gemma Calvanese, Marco Anselmo, Pasqualina De Leo, Monica Marturano, Giorgio Maria Saracco, Quaranta M.G., Ferrigno L., Tata X., D'Angelo F., Massari M., Coppola C., Biliotti E., Giorgini A., Laccabue D., Ciancio A., Blanc P.L., Margotti M., Ieluzzi D., Brunetto M.R., Barbaro F., Russo F.P., Beretta I., Morsica G., Verucchi G., Saracino A., Galli M., Kondili L.A., Mazzaro C., Bertola M., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Fiorentini A., Angarano G., Milella M., Leo A.D., Rendina M., Salvatore D'ABRAMO F., Lillo C., Iannone A., Piazzolla M., Badia L., Piscaglia F., Benevento F., Serio I., Castelli F., Zaltron S., Spinetti A., Odolini S., Bruno R., Mondelli M., Chessa L., Loi M., Torti C., Costa C., Mazzitelli M., Pisani V., Scaglione V., Trecarichi E.M., Zignego A.L., Monti M., Madia F., Attala L., Pierotti P., Salomoni E., Mariabelli E., Santantonio T.A., Bruno S.R., Cela E.M., Bassetti M., Mazzarello G., Alessandrini A.I., Biagio A.D., Nicolini L.A., Raimondo G., Filomia R., Aghemo A., Meli R., Lazzarin A., Salpietro S., Fracanzani A.L., Fatta E., Lombardi R., Lampertico P., Borghi M., D'ambrosio R., Degasperi E., Puoti M., Baiguera C., D'AMICO F., Vinci M., Rumi M.G., Zuin M., Zermiani P., Andreone P., Caraceni P., Guarneri V., Villa E., Bernabucci V., Bristot L., Paradiso M.L., Migliorino G., Gambaro A., Lapadula G., Spolti A., Soria A., Invernizzi P., Ciaccio A., LucA M., Malinverno F., Ratti L., Amoruso D.C., Pisano F., Scarano F., Staiano L., Morisco F., Cossiga V., Gentile I., Buonomo A.R., Foggia M., Zappulo E., Federico A., Dallio M., Coppola N., Sagnelli C., Martini S., Monari C., Nardone G., Sgamato C., Chemello L., Cavalletto L., Sterrantino D., Zanetto A., Zanaga P., Brancaccio G., Craxi A., Petta S., Calvaruso V., Crapanzano L., Madonia S., Cannizzaro M., Bruno E.M., Licata A., Amodeo S., Capitano A.R., Ferrari C., Negri E., Orlandini A., Pesci M., Gulminetti R., Pagnucco L., Parruti G., Stefano P.D., Coco B., Corsini R., Garlassi E., Andreoni M., Teti E., Cerva C., Baiocchi L., Grassi G., Gasbarrini A., Pompili M., Siena M.D., Taliani G., Spaziante M., Persico M., Masarone M., Aglitti A., Calvanese G., Anselmo M., Leo P.D., Marturano M., Saracco G.M., Quaranta, M, Ferrigno, L, Tata, X, D'Angelo, F, Massari, M, Coppola, C, Biliotti, E, Giorgini, A, Laccabue, D, Ciancio, A, Blanc, P, Margotti, M, Ieluzzi, D, Brunetto, M, Barbaro, F, Russo, F, Beretta, I, Morsica, G, Verucchi, G, Saracino, A, Galli, M, Kondili, L, Mazzaro, C, Bertola, M, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Fiorentini, A, Angarano, G, Milella, M, Leo, A, Rendina, M, Salvatore D'ABRAMO, F, Lillo, C, Iannone, A, Piazzolla, M, Badia, L, Piscaglia, F, Benevento, F, Serio, I, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Bruno, R, Mondelli, M, Chessa, L, Loi, M, Torti, C, Costa, C, Mazzitelli, M, Pisani, V, Scaglione, V, Trecarichi, E, Zignego, A, Monti, M, Madia, F, Attala, L, Pierotti, P, Salomoni, E, Mariabelli, E, Santantonio, T, Bruno, S, Cela, E, Bassetti, M, Mazzarello, G, Alessandrini, A, Biagio, A, Nicolini, L, Raimondo, G, Filomia, R, Aghemo, A, Meli, R, Lazzarin, A, Salpietro, S, Fracanzani, A, Fatta, E, Lombardi, R, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Puoti, M, Baiguera, C, D'Amico, F, Vinci, M, Rumi, M, Zuin, M, Zermiani, P, Andreone, P, Caraceni, P, Guarneri, V, Villa, E, Bernabucci, V, Bristot, L, Paradiso, M, Migliorino, G, Gambaro, A, Lapadula, G, Spolti, A, Soria, A, Invernizzi, P, Ciaccio, A, Luca, M, Malinverno, F, Ratti, L, Amoruso, D, Pisano, F, Scarano, F, Staiano, L, Morisco, F, Cossiga, V, Gentile, I, Buonomo, A, Foggia, M, Zappulo, E, Federico, A, Dallio, M, Coppola, N, Sagnelli, C, Martini, S, Monari, C, Nardone, G, Sgamato, C, Chemello, L, Cavalletto, L, Sterrantino, D, Zanetto, A, Zanaga, P, Brancaccio, G, Craxi, A, Petta, S, Calvaruso, V, Crapanzano, L, Madonia, S, Cannizzaro, M, Bruno, E, Licata, A, Amodeo, S, Capitano, A, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Gulminetti, R, Pagnucco, L, Parruti, G, Stefano, P, Coco, B, Corsini, R, Garlassi, E, Andreoni, M, Teti, E, Cerva, C, Baiocchi, L, Grassi, G, Gasbarrini, A, Pompili, M, Siena, M, Taliani, G, Spaziante, M, Persico, M, Masarone, M, Aglitti, A, Calvanese, G, Anselmo, M, Leo, P, Marturano, M, Saracco, G, Quaranta, M. G., Ferrigno, L., Tata, X., D'Angelo, F., Massari, M., Coppola, C., Biliotti, E., Giorgini, A., Laccabue, D., Ciancio, A., Blanc, P. L., Margotti, M., Ieluzzi, D., Brunetto, M. R., Barbaro, F., Russo, F. P., Beretta, I., Morsica, G., Verucchi, G., Saracino, A., Galli, M., Kondili, L. A., Mazzaro, C., Bertola, M., Benedetti, A., Schiada, L., Cucco, M., Giacometti, A., Brescini, L., Castelletti, S., Fiorentini, A., Angarano, G., Milella, M., Leo, A. D., Rendina, M., Salvatore D'ABRAMO, F., Lillo, C., Iannone, A., Piazzolla, M., Badia, L., Piscaglia, F., Benevento, F., Serio, I., Castelli, F., Zaltron, S., Spinetti, A., Odolini, S., Bruno, R., Mondelli, M., Chessa, L., Loi, M., Torti, C., Costa, C., Mazzitelli, M., Pisani, V., Scaglione, V., Trecarichi, E. M., Zignego, A. L., Monti, M., Madia, F., Attala, L., Pierotti, P., Salomoni, E., Mariabelli, E., Santantonio, T. A., Bruno, S. R., Cela, E. M., Bassetti, M., Mazzarello, G., Alessandrini, A. I., Biagio, A. D., Nicolini, L. A., Raimondo, G., Filomia, R., Aghemo, A., Meli, R., Lazzarin, A., Salpietro, S., Fracanzani, A. L., Fatta, E., Lombardi, R., Lampertico, P., Borghi, M., D'Ambrosio, R., Degasperi, E., Puoti, M., Baiguera, C., D'Amico, F., Vinci, M., Rumi, M. G., Zuin, M., Zermiani, P., Andreone, P., Caraceni, P., Guarneri, V., Villa, E., Bernabucci, V., Bristot, L., Paradiso, M. L., Migliorino, G., Gambaro, A., Lapadula, G., Spolti, A., Soria, A., Invernizzi, P., Ciaccio, A., Luca, M., Malinverno, F., Ratti, L., Amoruso, D. C., Pisano, F., Scarano, F., Staiano, L., Morisco, F., Cossiga, V., Gentile, I., Buonomo, A. R., Foggia, M., Zappulo, E., Federico, A., Dallio, M., Coppola, N., Sagnelli, C., Martini, S., Monari, C., Nardone, G., Sgamato, C., Chemello, L., Cavalletto, L., Sterrantino, D., Zanetto, A., Zanaga, P., Brancaccio, G., Craxi, A., Petta, S., Calvaruso, V., Crapanzano, L., Madonia, S., Cannizzaro, M., Bruno, E. M., Licata, A., Amodeo, S., Capitano, A. R., Ferrari, C., Negri, E., Orlandini, A., Pesci, M., Gulminetti, R., Pagnucco, L., Parruti, G., Stefano, P. D., Coco, B., Corsini, R., Garlassi, E., Andreoni, M., Teti, E., Cerva, C., Baiocchi, L., Grassi, G., Gasbarrini, A., Pompili, M., Siena, M. D., Taliani, G., Spaziante, M., Persico, M., Masarone, M., Aglitti, A., Calvanese, G., Anselmo, M., Leo, P. D., Marturano, M., and Saracco, G. M.

Subjects
Male, HCV genotypes, Ethnic group, Linked-to-care patient, Comorbidity, Hepacivirus, Logistic regression, medicine.disease_cause, Comorbidities, Direct acting antivirals, HCV Cohort, Linked-to-care patients, Aged, Antiviral Agents, Coinfection, Female, Hepatitis C, Chronic, Humans, Italy, Middle Aged, Transients and Migrants, 0302 clinical medicine, Medicine, Chronic, Gastroenterology, virus diseases, Hepatitis C, Life evaluation, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Comorbiditie, Human, Hepatitis C virus, Settore MED/12 - GASTROENTEROLOGIA, 03 medical and health sciences, Disease severity, Antiviral Agent, Hepaciviru, Hepatology, business.industry, Settore MED/09 - MEDICINA INTERNA, medicine.disease, digestive system diseases, Direct acting antiviral, business, Demography
Abstract

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.

Published
2021

21. Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering

Author

Anna Sabena, Gabriele Giuliano, Raffaele Bruno, Francesco Cacciatore, Carlo Torti, Silvia Marongiu, Gloria Maccagni, Claudia Marotta, Giovanni Larizza, Francesco Petri, Massimo Mapelli, Giulio Maresca, Giulia Righetti, Alessandra Vergori, Ilaria Rossi, Damiano D'Ardes, Nicola Schiano Moriello, Ivan Gentile, Enrica Tamburrini, Luca Aiello, Piergiuseppe Agostoni, Antonio Cascio, Jovana Milic, Carlo Andrea Pivato, Agostino Virdis, Stefano Maitan, Francesco Cannata, Simona Costanzo, Carlo Signorelli, Franco Mastroianni, Federica Magni, Crizia Colombo, Giulio G. Stefanini, Lucia Caiano, Francesca Crosta, Lorenzo Marra, Giuseppe Patti, Katleen de Gaetano Donati, Valerio Langella, Annalisa Crisetti, Filippo Aucella, Antonella Cingolani, Francesco Salinaro, Augusto Di Castelnuovo, Giacomo Castiglione, Alessandro Gialluisi, Anna Odone, Cristina Mussini, Samir Al Moghazi, Lorenzo Blandi, Maria Musso, Marialaura Bonaccio, Raffaele De Caterina, Marco Olivieri, Roberto Cauda, Emanuela Pasi, Arturo Ciccullo, Stefano Perlini, Claudia Colomba, Antonella Palimodde, Gianpiero D'Offizi, Marco G. Mennuni, Walter Ageno, Raffaele Pesavento, Rosa Manuele, Roberta Mussinelli, Vincenzo Sangiovanni, Paolo Bonfanti, Andrea Antinori, Francesco Gianfagna, Andrea Rognoni, Laura Scorzolini, Riccardo Maragna, Rossella Marcucci, Filippo Minutolo, Armando Leone, Giustino Parruti, Licia Iacoviello, Lorenzo Menicanti, Sandro Mancarella, Rosa Arboretti, Greta Barbieri, Carlo Gaudiosi, Marco Rossato, Claudia Ravaglia, Andrea Vianello, Marianna Rossi, Emauele Graziani, Martina Barchitta, Giovanni Guaraldi, Enrico Maria Trecarichi, Gian Battista Danzi, Francesco Cipollone, Carlo Sanrocco, Marco Vinceti, Francesca Santilli, Marianna Meschiari, Gabriella Guarnieri, Antonella Agodi, Roberto Vettor, Raffaella Sgariglia, Ilaria My, Francesco Di Gennaro, Alessandro Mengozzi, Giuseppe Di Tano, Laura Carrozzi, Michele Spinicci, Venerino Poletti, Paola Simeone, Nausicaa Berselli, Francesco Maria Fusco, Di Castelnuovo A., Gialluisi A., Antinori A., Berselli N., Blandi L., Bonaccio M., Bruno R., Cauda R., Costanzo S., Guaraldi G., Menicanti L., Mennuni M., My I., Parruti G., Patti G., Perlini S., Santilli F., Signorelli C., Stefanini G., Vergori A., Ageno W., Agodi A., Agostoni P., Aiello L., Moghazi S.A., Arboretti R., Aucella F., Barbieri G., Barchitta M., Bonfanti P., Cacciatore F., Caiano L., Cannata F., Carrozzi L., Cascio A., Castiglione G., Cicullo A., Cingolani A., Cipollone F., Colomba C., Colombo C., Crisetti A., Crosta F., Danzi G.B., D'Ardes D., de Gaetano Donati K., Di Gennaro F., Di Tano G., D'Offizi G., Fusco F.M., Gaudiosi C., Gentile I., Gianfagna F., Giuliano G., Graziani E., Guarnieri G., Langella V., Larizza G., Leone A., Maccagni G., Magni F., Maitan S., Mancarella S., Manuele R., Mapelli M., Maragna R., Marcucci R., Maresca G., Marongiu S., Marotta C., Marra L., Mastroianni F., Mengozzi A., Meschiari M., Milic J., Minutolo F., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Palimodde A., Pasi E., Pesavento R., Petri F., Pivato C.A., Poletti V., Ravaglia C., Righetti G., Rognoni A., Rossato M., Rossi I., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Moriello N.S., Scorzolini L., Sgariglia R., Simeone P.G., Spinicci M., Tamburrini E., Torti C., Trecarichi E.M., Vettor R., Vianello A., Vinceti M., Virdis A., de Caterina R., Iacoviello L., Di Castelnuovo, A, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Costanzo, S, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Castiglione, G, Cicullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gaudiosi, C, Gentile, I, Gianfagna1, F, Giuliano, G, Graziani, E, Guarnieri, G, Langella, V, Larizza, G, Leone, A, Maccagni, G, Magni, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Meschiari, M, Milic, J, Minutolo, F, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pivato, C, Poletti, V, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Schiano Moriello, N, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Tamburrini, E, Torti, C, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virdis, A, De Caterina, R, Iacoviello, L, Di Castelnuovo, A., Gialluisi, A., Antinori, A., Berselli, N., Blandi, L., Bonaccio, M., Bruno, R., Cauda, R., Costanzo, S., Guaraldi, G., Menicanti, L., Mennuni, M., My, I., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G., Vergori, A., Ageno, W., Agodi, A., Agostoni, P., Aiello, L., Moghazi, S. A., Arboretti, R., Aucella, F., Barbieri, G., Barchitta, M., Bonfanti, P., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Castiglione, G., Cicullo, A., Cingolani, A., Cipollone, F., Colomba, C., Colombo, C., Crisetti, A., Crosta, F., Danzi, G. B., D’Ardes, D., de Gaetano Donati, K., Di Gennaro, F., Di Tano, G., D’Offizi, G., Fusco, F. M., Gaudiosi, C., Gentile, I., Gianfagna, F., Giuliano, G., Graziani, E., Guarnieri, G., Langella, V., Larizza, G., Leone, A., Maccagni, G., Magni, F., Maitan, S., Mancarella, S., Manuele, R., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marongiu, S., Marotta, C., Marra, L., Mastroianni, F., Mengozzi, A., Meschiari, M., Milic, J., Minutolo, F., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Palimodde, A., Pasi, E., Pesavento, R., Petri, F., Pivato, C. A., Poletti, V., Ravaglia, C., Righetti, G., Rognoni, A., Rossato, M., Rossi, I., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Moriello, N. S., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinicci, M., Tamburrini, E., Torti, C., Trecarichi, E. M., Vettor, R., Vianello, A., Vinceti, M., Virdis, A., de Caterina, R., and Iacoviello, L.

Subjects
Male, Medicine (General), Antimalarial, 030204 cardiovascular system & hematology, Severity of Illness Index, Hospital Mortality, 0302 clinical medicine, Retrospective Studie, 80 and over, Cluster Analysis, 030212 general & internal medicine, Aged, Aged, 80 and over, Antimalarials, COVID-19, Female, Humans, Hydroxychloroquine, Italy, Middle Aged, Retrospective Studies, SARS-CoV-2, Treatment Outcome, Biotechnology, medicine.drug, Research Article, medicine.medical_specialty, Article Subject, Biomedical Engineering, Renal function, Health Informatics, 03 medical and health sciences, R5-920, Internal medicine, Diabetes mellitus, Severity of illness, medicine, Medical technology, R855-855.5, Cluster Analysi, business.industry, Cancer, Retrospective cohort study, medicine.disease, Obesity, COVID-19 Drug Treatment, Surgery, Observational study, business
Abstract

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001 ). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Published
2021
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22. Lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: Findings from the multicenter italian corist study

Author

Augusto Di Castelnuovo, Simona Costanzo, Andrea Antinori, Nausicaa Berselli, Lorenzo Blandi, Marialaura Bonaccio, Raffaele Bruno, Roberto Cauda, Alessandro Gialluisi, Giovanni Guaraldi, Lorenzo Menicanti, Marco Mennuni, Ilaria My, Agostino Parruti, Giuseppe Patti, Stefano Perlini, Francesca Santilli, Carlo Signorelli, Giulio G. Stefanini, Alessandra Vergori, Walter Ageno, Luca Aiello, Piergiuseppe Agostoni, Samir Al Moghazi, Rosa Arboretti, Filippo Aucella, Greta Barbieri, Martina Barchitta, Alessandro Bartoloni, Carolina Bologna, Paolo Bonfanti, Lucia Caiano, Laura Carrozzi, Antonio Cascio, Giacomo Castiglione, Mauro Chiarito, Arturo Ciccullo, Antonella Cingolani, Francesco Cipollone, Claudia Colomba, Crizia Colombo, Francesco Crosta, Giovanni Dalena, Chiara Dal Pra, Gian Battista Danzi, Damiano D'Ardes, Katleen de Gaetano Donati, Francesco Di Gennaro, Giuseppe Di Tano, Gianpiero D'Offizi, Tommaso Filippini, Francesco Maria Fusco, Carlo Gaudiosi, Ivan Gentile, Giancarlo Gini, Elvira Grandone, Gabriella Guarnieri, Gennaro L. F. Lamanna, Giovanni Larizza, Armando Leone, Veronica Lio, Angela Raffaella Losito, Gloria Maccagni, Stefano Maitan, Sandro Mancarella, Rosa Manuele, Massimo Mapelli, Riccardo Maragna, Lorenzo Marra, Giulio Maresca, Claudia Marotta, Franco Mastroianni, Maria Mazzitelli, Alessandro Mengozzi, Francesco Menichetti, Jovana Milic, Filippo Minutolo, Beatrice Molena, R. Mussinelli, Cristina Mussini, Maria Musso, Anna Odone, Marco Olivieri, Emanuela Pasi, Annalisa Perroni, Francesco Petri, Biagio Pinchera, Carlo A. Pivato, Venerino Poletti, Claudia Ravaglia, Marco Rossato, Marianna Rossi, Anna Sabena, Francesco Salinaro, Vincenzo Sangiovanni, Carlo Sanrocco, Laura Scorzolini, Raffaella Sgariglia, Paola Giustina Simeone, Michele Spinicci, Enrico Maria Trecarichi, Giovanni Veronesi, Roberto Vettor, Andrea Vianello, Marco Vinceti, Elena Visconti, Laura Vocciante, Raffaele De Caterina, Licia Iacoviello, The COVID-19 RISK and Treatments (CORIST) Collaboration, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Agostino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Ageno, Walter, Aiello, Luca, Agostoni, Piergiuseppe, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Chiarito, Mauro, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesco, Dalena, Giovanni, Dal Pra, Chiara, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Filippini, Tommaso, Maria Fusco, Francesco, Gaudiosi, Carlo, Gentile, Ivan, Gini, Giancarlo, Grandone, Elvira, Guarnieri, Gabriella, Lamanna, Gennaro L F, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Losito, Angela Raffaella, Maccagni, Gloria, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marra, Lorenzo, Maresca, Giulio, Marotta, Claudia, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussinelli, R, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Perroni, Annalisa, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Trecarichi, Enrico Maria, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Visconti, Elena, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Aiello, L, Agostoni, P, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bologna, C, Bonfanti, P, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Chiarito, M, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Dalena, G, Dal Pra, C, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Filippini, T, Maria Fusco, F, Gaudiosi, C, Gentile, I, Gini, G, Grandone, E, Guarnieri, G, Lamanna, G, Larizza, G, Leone, A, Lio, V, Losito, A, Maccagni, G, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Milic, J, Minutolo, F, Molena, B, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Perroni, A, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Visconti, E, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, A., Costanzo, S., Antinori, A., Berselli, N., Blandi, L., Bonaccio, M., Bruno, R., Cauda, R., Gialluisi, A., Guaraldi, G., Menicanti, L., Mennuni, M., My, I., Parruti, A., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Ageno, W., Aiello, L., Agostoni, P., Moghazi, S. A., Arboretti, R., Aucella, F., Barbieri, G., Barchitta, M., Bartoloni, A., Bologna, C., Bonfanti, P., Caiano, L., Carrozzi, L., Cascio, A., Castiglione, G., Chiarito, M., Ciccullo, A., Cingolani, A., Cipollone, F., Colomba, C., Colombo, C., Crosta, F., Dalena, G., Dal Pra, C., Danzi, G. B., D'Ardes, D., Donati, K. G., Di Gennaro, F., Di Tano, G., D'Offizi, G., Filippini, T., Fusco, F. M., Gaudiosi, C., Gentile, I., Gini, G., Grandone, E., Guarnieri, G., Lamanna, G. L. F., Larizza, G., Leone, A., Lio, V., Losito, A. R., Maccagni, G., Maitan, S., Mancarella, S., Manuele, R., Mapelli, M., Maragna, R., Marra, L., Maresca, G., Marotta, C., Mastroianni, F., Mazzitelli, M., Mengozzi, A., Menichetti, F., Milic, J., Minutolo, F., Molena, B., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Perroni, A., Petri, F., Pinchera, B., Pivato, C. A., Poletti, V., Ravaglia, C., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinicci, M., Trecarichi, E. M., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., Visconti, E., Vocciante, L., Caterina, R. D., Iacoviello, L., Di Castelnuovo A., Costanzo S., Antinori A., Berselli N., Blandi L., Bonaccio M., Bruno R., Cauda R., Gialluisi A., Guaraldi G., Menicanti L., Mennuni M., My I., Parruti A., Patti G., Perlini S., Santilli F., Signorelli C., Stefanini G.G., Vergori A., Ageno W., Aiello L., Agostoni P., Moghazi S.A., Arboretti R., Aucella F., Barbieri G., Barchitta M., Bartoloni A., Bologna C., Bonfanti P., Caiano L., Carrozzi L., Cascio A., Castiglione G., Chiarito M., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Colombo C., Crosta F., Dalena G., Dal Pra C., Danzi G.B., D'ardes D., Donati K.G., Di Gennaro F., Di Tano G., D'offizi G., Filippini T., Fusco F.M., Gaudiosi C., Gentile I., Gini G., Grandone E., Guarnieri G., Lamanna G.L.F., Larizza G., Leone A., Lio V., Losito A.R., Maccagni G., Maitan S., Mancarella S., Manuele R., Mapelli M., Maragna R., Marra L., Maresca G., Marotta C., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Milic J., Minutolo F., Molena B., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Pasi E., Perroni A., Petri F., Pinchera B., Pivato C.A., Poletti V., Ravaglia C., Rossato M., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P.G., Spinicci M., Trecarichi E.M., Veronesi G., Vettor R., Vianello A., Vinceti M., Visconti E., Vocciante L., Caterina R.D., and Iacoviello L.

Subjects
Medicine (General), medicine.medical_specialty, Lopinavir/ritonavir, Lopinavir, R5-920, Internal medicine, medicine, Darunavir, Original Research, COVID-19, In-hospital mortality, SARS-CoV-2, darunavir, in-hospital mortality, lopinavir, business.industry, Cobicistat, Mortality rate, General Medicine, medicine.disease, Propensity score matching, Medicine, Ritonavir, business, medicine.drug, Kidney disease
Abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores.Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs.Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Published
2021

23. Ceftazidime-avibactam use for klebsiella pneumoniae carbapenemase-producing k. pneumoniae infections: A retrospective observational multicenter study

Author

Mirko Compagno, Giampaolo Corti, Maddalena Peghin, Francesca Raffaelli, Annalisa Saracino, Cristina Mussini, Spinello Antinori, Maddalena Giannella, Roberto Cauda, Marianna Rossi, Gennaro De Pascale, Elena Guffanti, Enrico Maria Trecarichi, Giancarlo Ceccarelli, Teresa Spanu, Elisabetta Mantengoli, Antonio Cascio, Mario Venditti, Loredana Sarmati, Carlo Tascini, Silvia Corcione, Daniele Roberto Giacobbe, Massimo Fantoni, Linda Bussini, Paolo Bonfanti, Alessandra Mularoni, Marianna Meschiari, Nour Shbaklo, Giusy Tiseo, Mario Tumbarello, Roberto Luzzati, Angela Raffaella Losito, Alessandra Oliva, Pierluigi Viale, Alessandro Russo, Francesco Giuseppe De Rosa, Gaetano Brindicci, Ivan Gentile, Alberto Corona, Andrea De Gasperi, Paolo Grossi, Marco Falcone, Alessandro Capone, Cristina Rovelli, Matteo Bassetti, Tumbarello M., Raffaelli F., Giannella M., Mantengoli E., Mularoni A., Venditti M., De Rosa F.G., Sarmati L., Bassetti M., Brindicci G., Rossi M., Luzzati R., Grossi P.A., Corona A., Capone A., Falcone M., Mussini C., Trecarichi E.M., Cascio A., Guffanti E., Russo A., De Pascale G., Tascini C., Gentile I., Losito A.R., Bussini L., Corti G., Ceccarelli G., Corcione S., Compagno M., Giacobbe D.R., Saracino A., Fantoni M., Antinori S., Peghin M., Bonfanti P., Oliva A., De Gasperi A., Tiseo G., Rovelli C., Meschiari M., Shbaklo N., Spanu T., Cauda R., Viale P., Tumbarello, Mario, Raffaelli, Francesca, Giannella, Maddalena, Mantengoli, Elisabetta, Mularoni, Alessandra, Venditti, Mario, De Rosa, Francesco Giuseppe, Sarmati, Loredana, Bassetti, Matteo, Brindicci, Gaetano, Rossi, Marianna, Luzzati, Roberto, Grossi, Paolo Antonio, Corona, Alberto, Capone, Alessandro, Falcone, Marco, Mussini, Cristina, Trecarichi, Enrico Maria, Cascio, Antonio, Guffanti, Elena, Russo, Alessandro, De Pascale, Gennaro, Tascini, Carlo, Gentile, Ivan, Losito, Angela Raffaella, Bussini, Linda, Conti, Giampaolo, Ceccarelli, Giancarlo, Corcione, Silvia, Compagno, Mirko, Giacobbe, Daniele Roberto, Saracino, Annalisa, Fantoni, Massimo, Antinori, Spinello, Peghin, Maddalena, Bonfanti, Paolo, Oliva, Alessandra, De Gasperi, Andrea, Tiseo, Giusy, Rovelli, Cristina, Meschiari, Marianna, Shbaklo, Nour, Spanu, Teresa, Cauda, Roberto, and Viale, Pierluigi

Subjects
Microbiology (medical), Adult, medicine.medical_specialty, Azabicyclo Compound, carbapenemases, Bacterial Protein, Microbial Sensitivity Tests, Neutropenia, Ceftazidime, beta-Lactamases, beta-Lactamase, Carbapenemase, carbapenemase, Bacterial Proteins, Retrospective Studie, Lower respiratory tract infection, Internal medicine, Drug Combination, Anti-Bacterial Agent, medicine, Humans, KPC-producing Klebsiella pneumoniae, Retrospective Studies, Septic shock, business.industry, Ceftazidime-avibactam, Microbial Sensitivity Test, ceftazidime-avibactam, Mortality rate, Carbapenemases, Anti-Bacterial Agents, Azabicyclo Compounds, Drug Combinations, Klebsiella Infections, Klebsiella pneumoniae, medicine.disease, Ceftazidime/avibactam, Settore MED/17, Infectious Diseases, Cohort, Propensity score matching, Observational study, business, medicine.drug, Human, Klebsiella Infection
Abstract

Background A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. Methods We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. Results The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P = .79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P = .002), neutropenia (P < .001), or an INCREMENT score ≥8 (P = .01); with lower respiratory tract infection (LRTI) (P = .04); and with CAZ-AVI dose adjustment for renal function (P = .01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P = .006). All associations remained significant after propensity score adjustment. Conclusions CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug’s seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.

Published
2021

24. Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

Author

Venerino Poletti, Damiano D'Ardes, Paola Simeone, Cristina Mussini, Giustino Parruti, Sandro Maccarella, Licia Iacoviello, Giulio G. Stefanini, Roberta Mussinelli, Vincenzo Sangiovanni, Paolo Bonfanti, Roberto Vettor, Andrea Vianello, Arturo Montineri, Roberto Cauda, Elvira Grandone, Maria Mazzitelli, Claudia Ravaglia, Marialaura Bonaccio, Giulio Maresca, Francesco Di Gennaro, Alessandro Mengozzi, Anna Sabena, Gian Battista Danzi, Giuseppe Di Tano, Emanuela Pasi, Ilaria Rossi, Lucia Caiano, Laura Carrozzi, Francesco Landi, Francesca Crosta, Tommaso Filippini, Francesco Menichetti, Piergiuseppe Agostoni, Andrea Madaro, Antonio Cascio, Carlo Signorelli, Michele Spinicci, Carlo Sanrocco, Enrico Guido Spinoni, Maria Musso, Alessandra Vergori, Lorenzo Marra, Giuseppe Patti, Laura Vocciante, Marco Olivieri, Francesca Santilli, Stefano Perlini, Claudia Colomba, Francesco Salinaro, Marianna Meschiari, Gabriella Guarnieri, Giampiero D'Offizi, Riccardo Maragna, Paola Del Giacomo, Giancarlo Gini, Katleen de Gaetano Donati, Andrea Antinori, Filippo Aucella, Raffaele De Caterina, Lorenzo Menicanti, Gloria Maccagni, Amedeo Venezia, Chiara Dal Pra, Carlo Andrea Pivato, Walter Ageno, Antonella Agodi, Francesco Cannata, Francesco Petri, Luca Aiello, Biagio Pinchera, Marinella Astuto, Raffaella Sgariglia, Giovanni Guaraldi, Marco Vinceti, Laura Scorzolini, Samir Al Moghazi, Armando Leone, Giovanni Veronesi, Arturo Ciccullo, Leonardo Grisafi, Francesco Cipollone, Massimo Mapelli, Greta Barbieri, Silvia Lamonica, Raffaele Bruno, Filippo Minutolo, Antonella Cingolani, Alessandro Gialluisi, Marco Rossato, Andrea Rognoni, Marianna Rossi, Claudia Marotta, Franco Mastroianni, Ilaria My, Enrico Maria Trecarichi, Anna Odone, Alessandro Bartoloni, Simona Costanzo, Francesco Cacciatore, Ivan Gentile, Massimo Rinaldi, Nausicaa Berselli, Francesco Maria Fusco, Augusto Di Castelnuovo, Lorenzo Blandi, Castelnuovo A.D., Costanzo S., Antinori A., Berselli N., Blandi L., Bruno R., Cauda R., Guaraldi G., Menicanti L., My I., Parruti G., Patti G., Perlini S., Santilli F., Signorelli C., Spinoni E., Stefanini G.G., Vergori A., Ageno W., Agodi A., Aiello L., Agostoni P., Moghazi S.A., Astuto M., Aucella F., Barbieri G., Bartoloni A., Bonaccio M., Bonfanti P., Cacciatore F., Caiano L., Cannata F., Carrozzi L., Cascio A., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Crosta F., Pra C.D., Danzi G.B., D'Ardes D., Donati K.D.G., Giacomo P.D., Gennaro F.D., Di Tano G., D'Offizi G., Filippini T., Fusco F.M., Gentile I., Gialluisi A., Gini G., Grandone E., Grisafi L., Guarnieri G., Lamonica S., Landi F., Leone A., Maccagni G., Maccarella S., Madaro A., Mapelli M., Maragna R., Marra L., Maresca G., Marotta C., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Meschiari M., Minutolo F., Montineri A., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Pasi E., Petri F., Pinchera B., Pivato C.A., Poletti V., Ravaglia C., Rinaldi M., Rognoni A., Rossato M., Rossi I., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P.G., Spinicci M., Trecarichi E.M., Venezia A., Veronesi G., Vettor R., Vianello A., Vinceti M., Vocciante L., De Caterina R., Iacoviello L., Castelnuovo, A. D., Costanzo, S., Antinori, A., Berselli, N., Blandi, L., Bruno, R., Cauda, R., Guaraldi, G., Menicanti, L., My, I., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Spinoni, E., Stefanini, G. G., Vergori, A., Ageno, W., Agodi, A., Aiello, L., Agostoni, P., Moghazi, S. A., Astuto, M., Aucella, F., Barbieri, G., Bartoloni, A., Bonaccio, M., Bonfanti, P., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Ciccullo, A., Cingolani, A., Cipollone, F., Colomba, C., Crosta, F., Pra, C. D., Danzi, G. B., D'Ardes, D., Donati, K. D. G., Giacomo, P. D., Gennaro, F. D., Di Tano, G., D'Offizi, G., Filippini, T., Fusco, F. M., Gentile, I., Gialluisi, A., Gini, G., Grandone, E., Grisafi, L., Guarnieri, G., Lamonica, S., Landi, F., Leone, A., Maccagni, G., Maccarella, S., Madaro, A., Mapelli, M., Maragna, R., Marra, L., Maresca, G., Marotta, C., Mastroianni, F., Mazzitelli, M., Mengozzi, A., Menichetti, F., Meschiari, M., Minutolo, F., Montineri, A., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Petri, F., Pinchera, B., Pivato, C. A., Poletti, V., Ravaglia, C., Rinaldi, M., Rognoni, A., Rossato, M., Rossi, I., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinicci, M., Trecarichi, E. M., Venezia, A., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., Vocciante, L., De Caterina, R., Iacoviello, L., Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bruno, R, Cauda, R, Guaraldi, G, Menicanti, L, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Spinoni, E, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Aiello, L, Agostoni, P, Moghazi, S, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonaccio, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Crosta, F, Pra, C, Danzi, G, D'Ardes, D, Donati, K, Giacomo, P, Gennaro, F, Tano, G, D'Offizi, G, Filippini, T, Fusco, F, Gentile, I, Gialluisi, A, Gini, G, Grandone, E, Grisafi, L, Guarnieri, G, Lamonica, S, Landi, F, Leone, A, Maccagni, G, Maccarella, S, Madaro, A, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Minutolo, F, Montineri, A, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rinaldi, M, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Venezia, A, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Vocciante, L, De Caterina, R, and Iacoviello, L

Subjects
Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, Lower risk, law.invention, COVID-19, Disease severity, Hydroxychloroquine, Inflammation, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Humans, Italy, Middle Aged, Retrospective Studies, Treatment Outcome, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Retrospective Studie, law, Internal medicine, 80 and over, Internal Medicine, medicine, 030212 general & internal medicine, Risk factor, business.industry, Mortality rate, Retrospective cohort study, COVID-19 Drug Treatment, Propensity score matching, Commentary, Observational study, business, Human, medicine.drug
Abstract

Background Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

Published
2020

25. Use of colistin in adult patients: a cross-sectional study

Author

Giacobbe, Daniele Roberto, Saffioti, Carolina, Losito, Angela Raffaella, Rinaldi, Matteo, Aurilio, Caterina, Bolla, Cesare, Boni, Silvia, Borgia, Guglielmo, Carannante, Novella, Cassola, Giovanni, Ceccarelli, Giancarlo, Corcione, Silvia, Gasperina, Daniela Dalla, De Rosa, Francesco Giuseppe, Dentone, Chiara, Di Bella, Stefano, Di Lauria, Nicoletta, Feasi, Marcello, Fiore, Marco, Fossati, Sara, Franceschini, Erica, Gori, Andrea, Granata, Guido, Grignolo, Sara, Grossi, Paolo Antonio, Guadagnino, Giuliana, Lagi, Filippo, Maraolo, Alberto Enrico, Marinò, Valeria, Mazzitelli, Maria, Mularoni, Alessandra, Oliva, Alessandra, Pace, Maria Caterina, Parisini, Andrea, Patti, Francesca, Petrosillo, Nicola, Pota, Vincenzo, Raffaelli, Francesca, Rossi, Marianna, Santoro, Antonella, Tascini, Carlo, Torti, Carlo, Trecarichi, Enrico Maria, Venditti, Mario, Viale, Pierluigi, Signori, Alessio, Del Bono, Valerio, Giannella, Maddalena, Mikulska, Malgorzata, Tumbarello, Mario, Viscoli, Claudio, Passavanti, Maria Beatrice, Rogati, C, Sansone, Pasquale, Sarteschi, G, Roberto Giacobbe, Daniele, Saffioti1, Carolina, Raffaella Losito, Angela, Rinaldi, Matteo, Aurilio, Caterina, Bolla, Cesare, Boni, Silvia, Borgia, Guglielmo, Carannante, Novella, Cassola, Giovanni, Ceccarelli, Giancarlo, Corcione, Silvia, Dalla Gasperina, Daniela, Giuseppe De Rosa, Francesco, Dentone, Chiara, DI BELLA, Stefano, Di Lauria, Nicoletta, Feasi, Marcello, Fiore, Marco, Fossati, Sara, Franceschini, Erica, Gori, Andrea, Granata, Guido, Grignolo, Sara, Antonio Grossi, Paolo, Guadagnino, Giuliana, Lagi, Filippo, Enrico Maraolo, Alberto, Marinò, Valeria, Mazzitelli, Maria, Mularoni, Alessandra, Oliva, Alessandra, Caterina Pace, Maria, Parisini, Andrea, Patti, Francesca, Petrosillo, Nicola, Pota, Vincenzo, Raffaelli, Francesca, Rossi, Marianna, Santoro, Antonella, Tascini, Carlo, Torti, Carlo, Maria Trecarichi, Enrico, Venditti, Mario, Viale, Pierluigi, Signori, Alessio, Bassetti, Matteo, Del Bono, Valerio, Giannella, Maddalena, Mikulska, Malgorzata, Tumbarello, Mario, Viscoli, Claudio, Giacobbe, Daniele Roberto, Saffioti, Carolina, Losito, Angela Raffaella, Gasperina, Daniela Dalla, De Rosa, Francesco Giuseppe, Di Bella, Stefano, Grossi, Paolo Antonio, Maraolo, Alberto Enrico, Pace, Maria Caterina, Trecarichi, Enrico Maria, Passavanti, Maria Beatrice, Rogati, C, Sansone, Pasquale, Sarteschi, G, Giacobbe D.R., Saffioti C., Losito A.R., Rinaldi M., Aurilio C., Bolla C., Boni S., Borgia G., Carannante N., Cassola G., Ceccarelli G., Corcione S., Dalla Gasperina D., De Rosa F.G., Dentone C., Di Bella S., Di Lauria N., Feasi M., Fiore M., Fossati S., Franceschini E., Gori A., Granata G., Grignolo S., Grossi P.A., Guadagnino G., Lagi F., Maraolo A.E., Marino V., Mazzitelli M., Mularoni A., Oliva A., Pace M.C., Parisini A., Patti F., Petrosillo N., Pota V., Raffaelli F., Rossi M., Santoro A., Tascini C., Torti C., Trecarichi E.M., Venditti M., Viale P., Signori A., Bassetti M., Del Bono V., Giannella M., Mikulska M., Tumbarello M., and Viscoli C.

Subjects
0301 basic medicine, Male, Endemic Diseases, Drug Resistance, Carbapenem-resistant enterobacteriaceae, Pseudomona, 0302 clinical medicine, Interquartile range, Levofloxacin, Drug Resistance, Multiple, Bacterial, Klebsiella, polycyclic compounds, Acinetobacter, Antimicrobial resistance, Colistimethate, Colistin, Pseudomonas, Administration, Intravenous, Aged, Anti-Bacterial Agents, Cross-Sectional Studies, Drug Prescriptions, Drug Therapy, Combination, Female, Gram-Negative Bacterial Infections, Humans, Italy, Middle Aged, Respiratory Tract Infections, Sepsis, Immunology and Allergy, 030212 general & internal medicine, colistin, colistimethate, Bacterial, QR1-502, Administration, Combination, lipids (amino acids, peptides, and proteins), antimicrobial resistance, Intravenous, Multiple, medicine.drug, Microbiology (medical), medicine.medical_specialty, Cefepime, 030106 microbiology, Immunology, Microbiology, Loading dose, 03 medical and health sciences, Drug Therapy, Internal medicine, Lower respiratory tract infection, medicine, business.industry, biochemical phenomena, metabolism, and nutrition, medicine.disease, business
Abstract

Objectives The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). Methods Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. Results A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52–73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24–8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69–13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17–0.88; P = 0.024) was associated with use of colistin monotherapy. Conclusion Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

Published
2020

26. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study

Author

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.

Subjects
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 (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

Published
2017

27. Geographical variation in therapy for bloodstream infections due to multidrug-resistant enterobacteriaceae: a post hoc analysis of the INCREMENT study

Author

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.

Subjects
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

28. 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

Author

Belén Gutiérrez Gutiérrez, Salvador Pérez Galera, Elena Salamanca, Marina de Cueto, Esther Calbo, Benito Almirante, VIALE, PIERLUIGI, Antonio Oliver, Vicente Pintado, Oriol Gasch, Luis Martínez Martínez, Johann Pitout, Murat Akova, Carmen Peña, José Molina, Alicia Hernández, Mario Venditti, Nuria Prim, Julia Origüen, German Bou, Evelina Tacconelli, Mario Tumbarello, Axel Hamprecht, Helen Giamarellou, Manel Almela, Federico Pérez, Mitchell J. Schwaber, Joaquín Bermejo, Warren Lowman, Po Ren Hsueh, Marta Mora Rillo, Clara Natera, Maria Souli, Robert A. Bonomo, Yehuda Carmeli, David L. Paterson, Alvaro Pascual, Jesús Rodríguez Baño, the REIPI/ESGBIS/INCREMENT Group [, Gálvez, J., Del Toro, M. D., Retamar, P., Falcone, M., Russo, A., Daikos, G., Karaiskos, I., Trecarichi, E. M., Losito, A. R., Paterson, D. L., García Vázquez, E., Gómez, J., Roilides, E., Iosifidis, E., Doi, Y., Tuon, F. F., Navarro, F., Mirelis, B., San Juan, R., Fernández Ruiz, M., Larrosa, N., Puig, M., Cisneros, J. M., González, V., Rucci, Victoria, 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., Antoniadou, A., Poulakou, G., Virmani, D., Torre Cisneros, J., Pérez Nadales, E., Gracia Ahulfinger, I., Helvaci, Ö., Sahin, A. O., Cantón, R., Ruiz, P., BARTOLETTI, MICHELE, GIANNELLA, MADDALENA, Riemenschneider, F., Badia, C., Xercavins, Mariona, Fontanals, D., Jové, E., Belén Gutiérrez-Gutiérrez, Salvador Pérez-Galera, Elena Salamanca, Marina de Cueto, Esther Calbo, Benito Almirante, Pierluigi Viale, Antonio Oliver, Vicente Pintado, Oriol Gasch, Luis Martínez-Martínez, Johann Pitout, Murat Akova, Carmen Peña, José Molina, Alicia Hernández, Mario Venditti, Nuria Prim, Julia Origüen, German Bou, Evelina Tacconelli, Mario Tumbarello, Axel Hamprecht, Helen Giamarellou, Manel Almela, Federico Pérez, Mitchell J. Schwaber, Joaquín Bermejo, Warren Lowman, Po-Ren Hsueh, Marta Mora-Rillo, Clara Natera, Maria Souli, Robert A. Bonomo, Yehuda Carmeli, David L. Paterson, Alvaro Pascual, Jesús Rodríguez-Baño, the REIPI/ESGBIS/INCREMENT Group [, Gálvez, J., Del Toro, M.D., Retamar, P., Falcone, M., Russo, A., Daikos, G., Karaiskos, I., Trecarichi, E.M., Losito, A.R., Paterson, D.L., García-Vázquez, E., Gómez, J., Roilides, E., Iosifidis, E., Doi, Y., Tuon, F.F., Navarro, F., Mirelis, B., San Juan, R., Fernández-Ruiz, M., Larrosa, N., Puig, M., Cisneros, J.M., González, V., Rucci, Victoria, 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., Antoniadou, A., Poulakou, G., Virmani, D., Torre-Cisneros, J., Pérez-Nadales, E., Gracia-Ahulfinger, I., Helvaci, Ö., Sahin, A.O., Cantón, R., Ruiz, P., Bartoletti, M., Giannella, M., Riemenschneider, F., Badia, C., Xercavins, Mariona, Fontanals, D., Jové, E., ], Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Red Española de Investigación en Patología Infecciosa, European Federation of Pharmaceutical Industries and Associations, Cuyahoga County Veterans Service Commission, Geriatric Research Education and Clinical Center (US), National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Peña, Carmen [0000-0002-6673-2883], Peña, Carmen, İç Hastalıkları, Universidad de Sevilla. Departamento de Microbiología, Universidad de Sevilla. Departamento de Medicina, and European Union (UE). FP7

Subjects
0301 basic medicine, Male, Carbapenem, medicine.medical_specialty, Pediatrics, 030106 microbiology, Infectious Disease, Bacteremia, Kaplan-Meier Estimate, Clinical Therapeutics, Settore MED/17 - MALATTIE INFETTIVE, beta-Lactams, Microbiology, beta-Lactamases, 03 medical and health sciences, 0302 clinical medicine, Aged, Anti-Bacterial Agents, Carbapenems, Enterobacteriaceae, Female, Humans, Middle Aged, Multivariate Analysis, Odds Ratio, Retrospective Studies, beta-Lactamase Inhibitors, Internal medicine, medicine, Pharmacology (medical), 030212 general & internal medicine, Pharmacology & Pharmacy, Beta-Lactamase Inhibitors, Pharmacology, business.industry, Mortality rate, Retrospective cohort study, Odds ratio, bacterial infections and mycoses, Confidence interval, 3. Good health, Infectious Diseases, Cohort, business, medicine.drug, Cohort study
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.), The work was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, cofinanced by European Development Regional Fund titled A Way To Achieve Europe ERDF, the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), and FIS (PI10/02021). Participants in the study received support for research from the Innovative Medicines Initiative Joint Undertaking under the Combatting Bacterial Resistance in Europe—Molecule against Gram Negative Infections (COMBACTE-MAGNET) agreement 115737 resources, which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contributions (A. Pascua and J. Rodríguez-Baño), the Cleveland Department of Veterans Affairs, the Veterans Affairs Merit Review Program, the Geriatric Research Education and Clinical Center VISN 10 (VISN 10 GRECC), and NIAID, NIH, under award numbers R01AI072219 and R01AI063517 (R. A. Bonomo).

Published
2016

29. Infections caused by KPC-producing Klebsiella pneumoniae: Differences in therapy and mortality in a multicentre study

Author

Tumbarello, Mario, Trecarichi, Enrico Maria, De Rosa, Francesco Giuseppe, Giannella, Maddalena, Giacobbe, Daniele Roberto, Bassetti, Matteo, Losito, Angela Raffaella, Bartoletti, Michele, Del Bono, Valerio, Corcione, Silvia, Maiuro, Giuseppe, Tedeschi, Sara, Celani, Luigi, Cardellino, Chiara Simona, Spanu, Teresa, Marchese, Anna, Ambretti, Simone, Cauda, Roberto, Viscoli, Claudio, Viale, Pierluigi, ISGRI-SITI, Tumbarello, M., Trecarichi, E.M., De Rosa, F.G., Giannella, M., Giacobbe, D., Bassetti, M., Losito, A., Bartoletti, M., Del Bono, V., Corcione, S., Maiuro, G., Tedeschi, S., Celani, L., Cardellino, C., Spanu, T., Marchese, A., Ambretti, S., Cauda, R., Viscoli, C., and Viale, P.

Subjects
Male, Klebsiella pneumoniae, combination therapy, carbapenemase, Risk Factors, 80 and over, Pharmacology (medical), Young adult, biology, Medicine (all), Middle Aged, Carbapenemases, Hospitals, Carbapenem resistance, Colistin resistance, Combination therapy, Inadequate empirical therapy, Meropenem MICs, Treatment, Adolescent, Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents, Bacterial Proteins, Female, Hospitals, Teaching, Humans, Italy, Klebsiella Infections, Microbial Sensitivity Tests, Retrospective Studies, Survival Analysis, Treatment Outcome, Young Adult, beta-Lactamases, Pharmacology, Infectious Diseases, colistin resistance, Cohort, medicine.drug, Microbiology (medical), medicine.medical_specialty, carbapenem resistance, Settore MED/17 - MALATTIE INFETTIVE, Meropenem, Internal medicine, medicine, Survival analysis, inadequate empirical therapy, Septic shock, business.industry, Teaching, Retrospective cohort study, medicine.disease, biology.organism_classification, Surgery, business
Abstract

Objectives Infections caused by Klebsiella pneumoniae (Kp) carbapenemase (KPC)-producing strains of Kp have become a significant threat in recent years. To assess their outcomes and identify risk factors for 14 day mortality, we conducted a 4 year (2010–13) retrospective cohort study in five large Italian teaching hospitals. Methods The cohort included 661 adults with bloodstream infections (BSIs; n = 447) or non-bacteraemic infections (lower respiratory tract, intra-abdominal structure, urinary tract or other sites) caused by a KPC-Kp isolate. All had received ≥48 h of therapy (empirical and/or non-empirical) with at least one drug to which the isolate was susceptible. Results Most deaths occurred within 2 weeks of infection onset (14 day mortality: 225/661, 34.1%). Logistic regression analysis identified BSI (OR, 2.09; 95% CI, 1.34–3.29), presentation with septic shock (OR, 2.45; 95% CI, 1.47–4.08), inadequate empirical antimicrobial therapy (OR, 1.48; 95% CI, 1.01–2.18), chronic renal failure (OR, 2.27; 95% CI, 1.44–3.58), high APACHE III score (OR, 1.05; 95% CI, 1.04–1.07) and colistin-resistant isolates (OR, 2.18; 95% CI, 1.37–3.46) as independent predictors of 14 day mortality. Combination therapy with at least two drugs displaying in vitro activity against the isolate was associated with lower mortality (OR, 0.52; 95% CI, 0.35–0.77), in particular in patients with BSIs, lung infections or high APACHE III scores and/or septic shock at infection onset. Combinations that included meropenem were associated with significantly higher survival rates when the KPC-Kp isolate had a meropenem MIC of ≤8 mg/L. Conclusions KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.

Published
2015

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