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Mortality attributable to different Klebsiella susceptibility patterns and to the coverage of empirical antibiotic therapy: a cohort study on patients admitted to the ICU with infection

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Abstract

Purpose

To evaluate the prognostic importance of different Klebsiella spp. sensitivity patterns: multi-susceptible Klebsiella (MS-K), extended-spectrum cephalosporin-resistant, but carbapenem-susceptible Klebsiella (ESCR-CS-K), and carbapenem-resistant Klebsiella (CR-K).

Methods

We developed a prognostic model to predict hospital mortality in patients with infection on admission to the intensive care units (ICUs), and assessed its calibration in the subgroups of interest: patients with infections due to MS-K, ESCR-CS-K, CR-K. We assessed the calibration of the model also in ESCR-CS-K treated empirically with carbapenems and with piperacillin-tazobactam.

Results

A total of 13,292 adults with an ongoing infection were admitted to 137 Italian ICUs in 2012–2013. Of 801 Klebsiella spp. infected patients, 451 had MS-K, 116 ESCR-CS-K, and 234 CR-K. The prognostic model calibrated well for the MS-K and ESCR-CS-K subgroups. In the CR-K subgroup there were more deaths than predicted (standardized mortality ratio 1.20; 95% CI 1.08–1.31), indicating a negative prognostic role of the infection, mainly in the medium and high risk-of-death patients. When infection was caused by ESCR-CS-K, treatment with piperacillin-tazobactam increased adjusted mortality among the most severe patients (similarly to CR-K), while treatment with carbapenems did not (similarly to MS-K).

Conclusions

In low risk-of-death patients admitted to the ICU with a Klebsiella spp. infection, the appropriateness of empirical antibiotic therapy seemed uninfluential to eventual mortality, while it appeared to be crucial in high-risk ones. The use of piperacillin-tazobactam may be inappropriate in severe patients with ESCR-CS-K infection. CR-K is associated to a significant 20% increase of adjusted mortality, only for patients at higher risk of death.

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Acknowledgements

The authors substantially contributed to the conception and design (all authors), analysis (GB, GN, GC, CR) and interpretation (all authors) of data, drafting the article (GB, GN, GMR, DP) or critically revising it (all authors). All authors approved the final version of the manuscript. None of the authors has any conflict of interest in relation to this work. The authors thank Judith Baggott for editing the manuscript.

GiViTI Steering Committee (in alphabetic order, with their location in brackets)

Guido Bertolini (Ranica, BG), Andrea Bottazzi (Pavia), Arturo Chieregato (Milano), Roberto Fumagalli (Milano), Sergio Livigni (Torino), Giuseppe Nardi (Rmini), Giancarlo Negro (Casarano, LE), Carlo Olivieri (Novara), Daniele Poole (Belluno, BL), Danilo Radrizzani (Legnano, MI), Clara Ripamonti (Lecco), Mario Tavola (Lecco), Bruno Viaggi (Firenze).

Funding

The study did not receive any specific funding.

Author information

Authors and Affiliations

  1. GiViTI Coordinating Center, Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24020, Bergamo, Ranica, Italy

    Guido Bertolini, Giovanni Nattino, Greta Carrara, Carlotta Rossi, Daniele Crespi & Matteo Mondini

  2. Prima Divisione di Malattie Infettive, Ospedale Cotugno, Azienda Ospedaliera dei Colli, Napoli, Italy

    Carlo Tascini

  3. Servizio Anestesia e Rianimazione, Ospedale Civile San Martino, Belluno, Italy

    Daniele Poole

  4. Anestesia e Rianimazione CTO, Azienda Ospedaliera Universitaria Careggi, Florence, Italy

    Bruno Viaggi

  5. IRCCS Istituto Nazionale dei Tumori, Milano, Italy

    Martin Langer

  6. Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Florence, Italy

    Gian Maria Rossolini

  7. SOD Microbiologia e Virologia, Azienda Ospedaliera Universitaria Careggi, Florence, Italy

    Gian Maria Rossolini

  8. Rianimazione/Pronto Soccorso, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy

    Paolo Malacarne

Authors
  1. Guido Bertolini
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  2. Giovanni Nattino
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  9. Matteo Mondini
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  10. Martin Langer
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  11. Gian Maria Rossolini
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  12. Paolo Malacarne
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Consortia

GiViTI Steering Committee

  • Andrea Bottazzi
  • , Arturo Chieregato
  • , Roberto Fumagalli
  • , Sergio Livigni
  • , Giuseppe Nardi
  • , Giancarlo Negro
  • , Carlo Olivieri
  • , Danilo Radrizzani
  • , Clara Ripamonti
  • , Mario Tavola
  •  & Bruno Viaggi

Corresponding author

Correspondence to Greta Carrara.

Ethics declarations

Conflicts of interest

Guido Bertolini, Giovanni Nattino, Greta Carrara and Carlotta Rossi had full access to all study data and take responsibility for its integrity and the accuracy of data analysis. The authors declare that they have no conflict of interest.

Additional information

The members of the GiViTI Steering Committee are listed in the Acknowledgements.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 4448 kb)

Appendix

Appendix

List of participating clinicians (in alphabetic order, with their location in brackets):

Marco Abastanotti (Manerbio, BS), Pasquale Abbruzzese (Lacco Ameno, NA), Annamaria Acquarolo (Brescia, BS), Adele Adorni (Como, CO), Arnaldo Alberti (Porto Viro, RO), Maria Babini (Lugo, RA), Virginia Balestrero (Novi Ligure, AL), Bruno Balicco (Osio Sotto, BG), Alberto Baratta (Massa, MS), Massimo Barattini (Firenze, FI), Alessandro Bardini (Carrara, MS), Teresa Bartoli (Bagno a Ripoli, FI), Eduardo Beck (Desio, MB), Clara Belluomo Anello (Napoli, NA), Mara Olga Bernasconi (Rovigo, RO), Sara Bertacchini (Ferrara, FE), Alessandra Besozzi (Busto Arsizio, VA), Daniela Bettocchi (Prato, PO), Andrea Bianchin (Montebelluna, TV), Paola Bignone (Mondovì, CN), Daniela Luciana Boccalatte-rosa (Lucca, LU), Anna Bocchi (Trecenta, RO), Giuseppina Bonaccorso (Padova, PD), Maurizio Bonazzi (Cinisello Balsamo, MI), Manuela Bonizzoli (Firenze, FI), Nicola Bottino (Milano, MI), Cesare Breschi (Pesaro, PU), Giuseppe Calicchio (Salerno, SA), Manuela Carli (Pistoia, PT), Santo Caroleo (Catanzaro, CZ), Edith Casadei (Siena, SI), Maria Grazia Casadio (Orbetello, GR), Giuseppe Castellano (San Bonifacio, VR), Marina Ceradelli (La Spezia, SP), Andrea Ciani (Pescia, PT), Rita Ciceri (Lecco, LC), Marco Guido Alberto Cigada (Milano, MI), Stefano Clementi (Sesto San Giovanni, MI), Maddalena Coaloa (Savigliano, CN), Silvano Cominotti (Varese, VA), Marcella Converso (Torino, TO), Luciano Crema (Cremona, CR), Marino Dal Ferro (Oderzo, TV), Roberto Alberto De Blasi (Roma, RM), Anna Lisa De Marco (Rossano, CS), Elena De Marzi (Monselice, PD), Maria Luisa De Prisco (Oliveto Citra, SA), Ernesto Della Mora (Arzignano, VI), Andrea Della Selva (Alba, CN), Assunta Di Cocco (Lanciano, CH), Pierfrancesco Di Masi (Castellana Grotte, BA), Notburga Egger (Fano, PU), Francesca Facondini (Rimini, RN), Stefano Falini (Grosseto, GR), Raquel Fernandez Olmos (Ome, BS), Marcus Ferretti (Genova, GE), Gilberto Fiore (Torino, TO), Elsa Galeotti (Feltre, BL), Nicola Galleschi (Empoli, FI), Emiliano Gamberini (Cesena, FC), Alberto Garelli (Ravenna, RA), Maurizio Genovesi (Lido di Camaiore, LU), Teresa Gentile (Roma, RM), Stefano Giacomello (Negrar, VR), Massimo Gianni (Aosta, AO), Aimone Giugni (Bologna, BO), Adonella Gorietti (Perugia, PG), Maurizio Greco (Ariano Irpino, AV), Andreina Grioni (Cernusco sul Naviglio, MI), Clementina Guagliardi (Gallarate, VA), Ugo Lefons (Poggibonsi, SI), Rita Lembo (Verbania, VB), Susana Monica Madeira (Bibbiena, AR), Mariafederica Magatti (Como, CO), Roberta Bertolini (Pisa, PI), Filippo Mamprin (Seriate, BG), Valerio Mangani (Firenze, FI), Giovanni Mannolini (Pontremoli, MS), Roberto Mannoni (Acqui Terme, AL), Demostene Marifoglou (Castel San Giovanni, PC), Giovanni Marino (Vizzolo Predabissi, MI), Antonella Marzullo (Torino, TO), Alessandro Mastroianni (Chieri, TO), Antonio Mazzoccone (Firenze, FI), Teresa Sabina Mediani (Pavia, PV), Marianna Messina (Olbia, OT), Francesco Minnucci (Macerata, MC), Milena Mucci (Milano, MI), Anna Maria Munafò (Catania, CT), Luisa Muraro (Padova, PD), Giovanni Negri (Magenta, MI), Giancarlo Negro (Casarano, LE), Lorenzo Odetto (Orbassano, TO), Carlo Olivieri (Novara, NO), Daria Osti (Ferrara, FE), Lamberto Padovan (Este, PD), Maria Passafiume (Palermo, PA), Simonetta Pastorini (Camposampiero, PD), Maurizio Pegoraro (Castelfranco Veneto, TV), Paolo Perino Bert (Torino, TO), Alice Pero (Vercelli, VC), Mario Peta (Treviso, TV), Giuseppe Pezzi (Faenza, RA), Angelo Pezzi (Milano, MI), Silvia Pifferi (Pavia, PV), Moira Bernard (Belluno, BL), Vincenzo Pota (Castel Volturno, CE), Ioannis Psimadas (Mirano, VE), Marco Pulici (Milano, MI), Stefania Raffa (Domodossola, VB), Roberto Randellini (Montepulciano, SI), Cristina Ratto (Tortona, AL), Laura Remorini (Borgo San Lorenzo, FI), Ermino Righini (Lagosanto, FE), Eugenia Roberto (Pontedera, PI), Francesco Massimo Romito (Matera, MT), Antonio Rosano (Brescia, BS), Simona Rossi (Rho, MI), Maurizio Rossi (Menaggio, CO), Valeria Roticiani (Montevarchi, AR), Maria Rosa Salcuni (Ivrea, TO), Giovanni Salvi (Imperia, IM), Silvia Scarrone (Alessandria, AL), Marina Schiavuzzi (Brescia, BS), Maria Angela Scolari (Casalmaggiore, CR), Pieraurelio Segalini (Piacenza, PC), Daniela Silegno (Torino, TO), Ermanno Spagarino (Biella, BI), Maria José Sucre (Castellammare di Stabia, NA), Mario Tavola (Genova, GE), Marina Terzitta (Forlì, FC), Livio Todesco (Cittadella, PD), Mauro Torta (Torino, TO), Maria Giovanna Vespignani (Imola, BO), Marco Zanello (Bologna, BO), Vittorio Zanni (Bentivoglio, BO), Michela Zardin (Mantova, MN).

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GiViTI Steering Committee., Bertolini, G., Nattino, G. et al. Mortality attributable to different Klebsiella susceptibility patterns and to the coverage of empirical antibiotic therapy: a cohort study on patients admitted to the ICU with infection. Intensive Care Med 44, 1709–1719 (2018). https://doi.org/10.1007/s00134-018-5360-0

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