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1. Outcomes of octogenarians and nonagenarians with Pseudomonas aeruginosa bacteremia: a multicenter retrospective study

Author

Atamna, Alaa, Margalit, Ili, Ayada, Gida, Babich, Tanya, Naucler, Pontus, Valik, John Karlsson, Giske, Christian G., Benito, Natividad, Cardona, Rubén, Rivera, Alba, Pulcini, Celine, Fattah, Manal Abdel, Haquin, Justine, Macgowan, Alasdair, Chazan, Bibiana, Yanovskay, Anna, Ami, Ronen Ben, Landes, Michal, Nesher, Lior, Zaidman-Shimshovitz, Adi, McCarthy, Kate, Paterson, David L., Tacconelli, Evelina, Buhl, Michael, Mauer, Susanna, Rodríguez-Baño, Jesús, Cueto, Marina de, Oliver, Antonio, Ruiz-de-Gopegui, Enrique, Cano, Ángela, Machuca, Isabel, Gozalo-Margüello, Mónica, Martínez-Martínez, Luis, González-Barbera, Eva M., Gómez-Alfaro, Iris, Salavert, Miguel, Beovic, Bojana, Saje, Andreja, Mueller-Premru, Manica, Pagani, Leonardo, Vitrat, Virginie, Kofteridis, Diamantis, Zacharioudaki, Maria, Maraki, Sofia, Weissman, Yulia, Paul, Mical, Dickstei, Yaakov, Yahav, Dafna, ESCMID study group for infections in elderly (ESGIE), Atamna, Alaa, Margalit, Ili, Ayada, Gida, Babich, Tanya, Naucler, Pontus, Valik, John Karlsson, Giske, Christian G., Benito, Natividad, Cardona, Rubén, Rivera, Alba, Pulcini, Celine, Fattah, Manal Abdel, Haquin, Justine, Macgowan, Alasdair, Chazan, Bibiana, Yanovskay, Anna, Ami, Ronen Ben, Landes, Michal, Nesher, Lior, Zaidman-Shimshovitz, Adi, McCarthy, Kate, Paterson, David L., Tacconelli, Evelina, Buhl, Michael, Mauer, Susanna, Rodríguez-Baño, Jesús, Cueto, Marina de, Oliver, Antonio, Ruiz-de-Gopegui, Enrique, Cano, Ángela, Machuca, Isabel, Gozalo-Margüello, Mónica, Martínez-Martínez, Luis, González-Barbera, Eva M., Gómez-Alfaro, Iris, Salavert, Miguel, Beovic, Bojana, Saje, Andreja, Mueller-Premru, Manica, Pagani, Leonardo, Vitrat, Virginie, Kofteridis, Diamantis, Zacharioudaki, Maria, Maraki, Sofia, Weissman, Yulia, Paul, Mical, Dickstei, Yaakov, Yahav, Dafna, and ESCMID study group for infections in elderly (ESGIE)

Abstract

[Background] P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years)., [Methods] We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults., [Results] Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65–79 years (n = 894) and 25% among patients < 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23–1.51, p < 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24–8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33–3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality., [Conclusions] In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.

Published
2023

2. Duration of Treatment for Pseudomonas aeruginosa Bacteremia: a Retrospective Study

Author

Yahav, Dafna [0000-0003-3181-9791], Babich, Tanya, Naucler, Pontus, Valik, John Karlsson, Giske, Christian G., Benito, Natividad, Cardona, Rubén, Rivera, Alba, Pulcini, Céline, Fattah, Manal Abdel, Haquin, Justine, Macgowan, Alasdair, Grier, Sally, Chazan, Bibiana, Yanovskay, Anna, Ami, Ronen Ben, Landes, Michal, Nesher, Lior, Zaidman-Shimshovitz, Adi, McCarthy, Kate, Paterson, David L., Tacconelli, Evelina, Buhl, Michael, Mauer, Susanna, Rodríguez-Baño, Jesús, Cueto, Marina de, Oliver, Antonio, Ruiz de Gopegui Bordes, Enrique, Cano, Ángela, Machuca, Isabel, Gozalo-Margüello, Mónica, Martínez-Martínez, Luis, González-Barbera, Eva M., Gómez Alfaro, Iris, Salavert, Miguel, Beovic, Bojana, Saje, Andreja, Mueller-Premru, Manica, Pagani, Leonardo, Vitrat, Virginie, Kofteridis, Diamantis, Zacharioudaki, Maria, Maraki, Sofia, Weissman, Yulia, Paul, Mical, Dickstein, Yaakov, Leibovici, Leonard, Yahav, Dafna, Yahav, Dafna [0000-0003-3181-9791], Babich, Tanya, Naucler, Pontus, Valik, John Karlsson, Giske, Christian G., Benito, Natividad, Cardona, Rubén, Rivera, Alba, Pulcini, Céline, Fattah, Manal Abdel, Haquin, Justine, Macgowan, Alasdair, Grier, Sally, Chazan, Bibiana, Yanovskay, Anna, Ami, Ronen Ben, Landes, Michal, Nesher, Lior, Zaidman-Shimshovitz, Adi, McCarthy, Kate, Paterson, David L., Tacconelli, Evelina, Buhl, Michael, Mauer, Susanna, Rodríguez-Baño, Jesús, Cueto, Marina de, Oliver, Antonio, Ruiz de Gopegui Bordes, Enrique, Cano, Ángela, Machuca, Isabel, Gozalo-Margüello, Mónica, Martínez-Martínez, Luis, González-Barbera, Eva M., Gómez Alfaro, Iris, Salavert, Miguel, Beovic, Bojana, Saje, Andreja, Mueller-Premru, Manica, Pagani, Leonardo, Vitrat, Virginie, Kofteridis, Diamantis, Zacharioudaki, Maria, Maraki, Sofia, Weissman, Yulia, Paul, Mical, Dickstein, Yaakov, Leibovici, Leonard, and Yahav, Dafna

Abstract

[Introduction] There is no consensus regarding optimal duration of antibiotic therapy for Pseudomonas aeruginosa bacteremia. We aimed to evaluate the impact of short antibiotic course., [Methods] We present a retrospective multicenter study including patients with P. aeruginosa bacteremia during 2009–2015. We evaluated outcomes of patients treated with short (6–10 days) versus long (11–15 days) antibiotic courses. The primary outcome was a composite of 30-day mortality or bacteremia recurrence and/or persistence. Univariate and inverse probability treatment-weighted (IPTW) adjusted multivariate analysis for the primary outcome was performed. To avoid immortal time bias, the landmark method was used., [Results] We included 657 patients; 273 received a short antibiotic course and 384 a long course. There was no significant difference in baseline characteristics of patients. The composite primary outcome occurred in 61/384 patients in the long-treatment group (16%) versus 32/273 in the short-treatment group (12%) (p = 0.131). Mortality accounted for 41/384 (11%) versus 25/273 (9%) of cases, respectively. Length of hospital stay was significantly shorter in the short group [median 13 days, interquartile range (IQR) 9–21 days, versus median 15 days, IQR 11–26 days, p = 0.002]. Ten patients in the long group discontinued antibiotic therapy owing to adverse events, compared with none in the short group. On univariate and multivariate analyses, duration of therapy was not associated with the primary outcome., [Conclusions] In this retrospective study, 6–10 days of antibiotic course for P. aeruginosa bacteremia were as effective as longer courses in terms of survival and recurrence. Shorter therapy was associated with reduced length of stay and less drug discontinuation.

Published
2022

3. Adoptive transfer of ex vivo expanded SARS‐CoV‐2‐specific cytotoxic lymphocytes: A viable strategy for COVID‐19 immunosuppressed patients?

Author

Generalitat Valenciana, Consejo Superior de Investigaciones Científicas (España), Aguilar-Gallardo, Cristóbal [0000-0002-1594-3648], Piñana, José Luis [0000-0001-8533-2562], Guerreiro, Manuel, Aguilar-Gallardo, Cristóbal, Montoro, Juan, Francés-Gómez, Clara, Latorre, Victor, Luna, Irene, Planelles, Dolores, Carrasco, María Paz, Gómez, María Dolores, González-Barbera, Eva M., Aguado, Cristina, Sempere, Amparo, Solves, Pilar, Gómez-Seguí, Inés, Balaguer-Rosello, Aitana, Louro, Alberto, Perla, Aurora, Larrea, Luis, Sanz, Jaime, Arbona, Cristina, Rubia, Javier de la, Geller, Ron, Sanz, Miguel Ángel, Sanz, Guillermo, Piñana, José Luis, Generalitat Valenciana, Consejo Superior de Investigaciones Científicas (España), Aguilar-Gallardo, Cristóbal [0000-0002-1594-3648], Piñana, José Luis [0000-0001-8533-2562], Guerreiro, Manuel, Aguilar-Gallardo, Cristóbal, Montoro, Juan, Francés-Gómez, Clara, Latorre, Victor, Luna, Irene, Planelles, Dolores, Carrasco, María Paz, Gómez, María Dolores, González-Barbera, Eva M., Aguado, Cristina, Sempere, Amparo, Solves, Pilar, Gómez-Seguí, Inés, Balaguer-Rosello, Aitana, Louro, Alberto, Perla, Aurora, Larrea, Luis, Sanz, Jaime, Arbona, Cristina, Rubia, Javier de la, Geller, Ron, Sanz, Miguel Ángel, Sanz, Guillermo, and Piñana, José Luis

Abstract

Cellular and humoral response to acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections is on focus of research. We evaluate herein the feasibility of expanding virus‐specific T cells (VST) against SARS‐CoV‐2 ex vivo through a standard protocol proven effective for other viruses. The experiment was performed in three different donors' scenarios: (a) SARS‐CoV‐2 asymptomatic infection/negative serology, (b) SARS‐CoV‐2 symptomatic infection/positive serology, and (c) no history of SARS‐CoV‐2 infection/negative serology. We were able to obtain an expanded VST product from donors 1 and 2 (1.6x and 1.8x increase of baseline VST count, respectively) consisting in CD3 + cells (80.3% and 62.7%, respectively) with CD4 + dominance (60% in both donors). Higher numbers of VST were obtained from the donor 2 as compared to donor 1. T‐cell clonality test showed oligoclonal reproducible peaks on a polyclonal background for both donors. In contrast, VST could be neither expanded nor primed in a donor without evidence of prior infection. This proof‐of‐concept study supports the feasibility of expanding ex vivo SARS‐CoV‐2‐specific VST from blood of convalescent donors. The results raise the question of whether the selection of seropositive donors may be a strategy to obtain cell lines enriched in their SARS‐CoV‐2‐specificity for future adoptive transfer to immunosuppressed patients.

Published
2021

4. Risk factors for mortality among patients with Pseudomonas aeruginosa bacteraemia: a retrospective multicentre study

Author

Babich, Tanya, Naucler, Pontus, Valik, John Karlsson, Giske, Christian G., Benito, Natividad, Cardona, Rubén, Rivera, Alba, Pulcini, Céline, Abdel Fattah, Manal, Haquin, Justine, Macgowan, Alasdair, Grier, Sally, Chazan, Bibiana, Yanovskay, Anna, Ben Ami, Ronen, Landes, Michal, Nesher, Lior, Zaidman-Shimshovitz, Adi, McCarthy, Kate, Paterson, David L., Tacconelli, Evelina, Buhl, Michael, Mauer, Susanna, Rodríguez-Baño, Jesús, Morales, Isabel, Oliver, Antonio, Ruiz de Gopegui Bordes, Enrique, Cano, Ángela, Machuca, Isabel, Gozalo-Margüello, Mónica, Martínez-Martínez, Luis, González-Barbera, Eva M., Gómez Alfaro, Iris, Salavert, Miguel, Beovic, Bojana, Saje, Andreja, Mueller-Premru, Manica, Pagani, Leonardo, Vitrat, Virginie, Kofteridis, Diamantis, Zacharioudaki, Maria, Maraki, Sofia, Weissman, Yulia, Paul, Mical, Dickstein, Yaakov, Leibovici, Leonard, Yahav, Dafna, Babich, Tanya, Naucler, Pontus, Valik, John Karlsson, Giske, Christian G., Benito, Natividad, Cardona, Rubén, Rivera, Alba, Pulcini, Céline, Abdel Fattah, Manal, Haquin, Justine, Macgowan, Alasdair, Grier, Sally, Chazan, Bibiana, Yanovskay, Anna, Ben Ami, Ronen, Landes, Michal, Nesher, Lior, Zaidman-Shimshovitz, Adi, McCarthy, Kate, Paterson, David L., Tacconelli, Evelina, Buhl, Michael, Mauer, Susanna, Rodríguez-Baño, Jesús, Morales, Isabel, Oliver, Antonio, Ruiz de Gopegui Bordes, Enrique, Cano, Ángela, Machuca, Isabel, Gozalo-Margüello, Mónica, Martínez-Martínez, Luis, González-Barbera, Eva M., Gómez Alfaro, Iris, Salavert, Miguel, Beovic, Bojana, Saje, Andreja, Mueller-Premru, Manica, Pagani, Leonardo, Vitrat, Virginie, Kofteridis, Diamantis, Zacharioudaki, Maria, Maraki, Sofia, Weissman, Yulia, Paul, Mical, Dickstein, Yaakov, Leibovici, Leonard, and Yahav, Dafna

Abstract

This study aimed to evaluate risk factors for 30-day mortality among hospitalised patients with Pseudomonas aeruginosa bacteraemia, a highly fatal condition. A retrospective study was conducted between 1 January 2009 and 31 October 2015 in 25 centres (9 countries) including 2396 patients. Univariable and multivariable analyses of risk factors were conducted for the entire cohort and for patients surviving ≥48 h. A propensity score for predictors of appropriate empirical therapy was introduced into the analysis. Of the 2396 patients, 636 (26.5%) died within 30 days. Significant predictors (odds ratio and 95% confidence interval) of mortality in the multivariable analysis included patient-related factors: age (1.02, 1.01–1.03); female sex (1.34, 1.03–1.77); bedridden functional capacity (1.99, 1.24–3.21); recent hospitalisation (1.43, 1.07–1.92); concomitant corticosteroids (1.33, 1.02–1.73); and Charlson comorbidity index (1.05, 1.01–1.93). Infection-related factors were multidrug-resistant Pseudomonas (1.52, 1.15–2.1), non-urinary source (2.44, 1.54–3.85) and Sequential Organ Failure Assessment (SOFA) score (1.27, 1.18–1.36). Inappropriate empirical therapy was not associated with increased mortality (0.81, 0.49–1.33). Among 2135 patients surviving ≥48 h, hospital-acquired infection (1.59, 1.21–2.09), baseline endotracheal tube (1.63, 1.13–2.36) and ICU admission (1.53, 1.02–2.28) were additional risk factors. Risk factors for mortality among patients with P. aeruginosa were mostly irreversible. Early appropriate empirical therapy was not associated with reduced mortality. Further research should be conducted to explore subgroups that may not benefit from broad-spectrum antipseudomonal empirical therapy. Efforts should focus on prevention of infection, mainly hospital-acquired infection and multidrug-resistant pseudomonal infection.

Published
2020

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