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Rapid diagnostics and ceftazidime/avibactam for KPC-producing Klebsiella pneumoniae bloodstream infections: impact on mortality and role of combination therapy

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Abstract

This study was aimed at investigating risk factors for mortality in patients suffering from KPC-producing Klebsiella pneumoniae (KPC-Kp) bloodstream infections (BSIs), evaluating the impact of rapid diagnostics and ceftazidime/avibactam use. This observational retrospective study (January 2017–May 2021) included all patients with a KPC-Kp BSI. Uni-multivariable analyses were carried out to evaluate the effect of clinical variables on both in-hospital death (IHD) and 30-day all-cause mortality, and the role of the combination of ceftazidime/avibactam plus polymyxin. One hundred and ninety-six patients met the study’s inclusion criteria. Older age, having undergone renal replacement therapy during the 30 days preceding the KPC-Kp BSI onset, having an INCREMENT-CPE score ≥ 8, and having suffered from a superimposed and/or following KPC-Kp BSI treatment candidemia were found to be the main factors associated with both mortality rates. Among protective factors, the centrality of ceftazidime/avibactam in monotherapy (IHD: OR: 0.34; CI 95%: 0.11–1.00—30-day all-cause mortality: OR: 0.18; CI 95%: 0.04–0.77) or combination (IHD: OR: 0.51; CI 95%: 0.22–1.19—30-day all-cause mortality: OR: 0.62; CI 95%: 0.21–1.84) emerged and became even more evident once the effect of ceftazidime/avibactam plus polymyxin was removed. Rapid diagnostics may be useful to adopt more effective strategies for the treatment of KPC-Kp BSI patients and implement infection control measures, even if not associated with higher patient survival. Ceftazidime/avibactam, even when used alone, represents an important option against KPC-Kp, while combined use with polymyxin might not have altered its efficacy. Patient comorbidities, severity of BSI, and complications such as candidemia were confirmed to have a significant burden on survival.

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Authors and Affiliations

  1. Microbiology and Virology Unit, University Hospital Città della Salute e della Scienza di Torino, Corso Bramante 88/90, 10126, Turin, Italy

    Matteo Boattini, Gabriele Bianco, Sara Comini, Marco Iannaccone, Rossana Cavallo & Cristina Costa

  2. Department of Public Health and Paediatrics, University of Torino, Turin, Italy

    Matteo Boattini, Lorena Charrier, Sara Comini, Rossana Cavallo & Cristina Costa

  3. Department of Internal Medicine 4, Hospital de Santa Marta, Central Lisbon Hospital Centre, Lisbon, Portugal

    André Almeida

  4. NOVA Medical School, Universidade Nova de Lisboa, Campo dos Mártires da Pátria 130, 1169-056, Lisbon, Portugal

    André Almeida

  5. Department of Medical Sciences, Infectious Diseases, University of Turin, 10126, Turin, Italy

    Francesco Giuseppe De Rosa

  6. Unit of Infectious Diseases, Cardinal Massaia, 14100, Asti, Italy

    Francesco Giuseppe De Rosa

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  1. Matteo Boattini
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  8. Francesco Giuseppe De Rosa
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  9. Cristina Costa
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Contributions

Boattini M, Bianco G, Almeida A, De Rosa FG, Costa C, and Cavallo R designed the study; Boattini M, Bianco G, Comini S, and Iannaccone M acquired data; Boattini M, Bianco G, and Charrier L analyzed and interpreted data; Boattini M wrote the paper; all authors revised the article critically and approved the final version.

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Correspondence to Matteo Boattini.

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This study was conducted in accordance with the Declaration of Helsinki. Formal ethical approval was obtained by our Center’s institutional review board (Protocol No. 0029345).

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Boattini, M., Bianco, G., Charrier, L. et al. Rapid diagnostics and ceftazidime/avibactam for KPC-producing Klebsiella pneumoniae bloodstream infections: impact on mortality and role of combination therapy. Eur J Clin Microbiol Infect Dis 42, 431–439 (2023). https://doi.org/10.1007/s10096-023-04577-x

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