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
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).
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.
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).
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.
KeywordsKlebsiella infections Attributable mortality Intensive care units Drug resistance Multicenter study
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).
The study did not receive any specific funding.
Compliance with ethical standards
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.
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