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Observational Study
. 2017 Jul 5;21(1):173.
doi: 10.1186/s13054-017-1769-z.

Double carbapenem as a rescue strategy for the treatment of severe carbapenemase-producing Klebsiella pneumoniae infections: a two-center, matched case-control study

Gennaro De Pascale  1   2 , Gennaro Martucci  3 , Luca Montini  4 , Giovanna Panarello  3 , Salvatore Lucio Cutuli  4 , Daniele Di Carlo  5 , Valentina Di Gravio  4 , Roberta Di Stefano  6 , Guido Capitanio  3 , Maria Sole Vallecoccia  4 , Piera Polidori  6 , Teresa Spanu  7 , Antonio Arcadipane  3 , Massimo Antonelli  4
Affiliations
Observational Study

Double carbapenem as a rescue strategy for the treatment of severe carbapenemase-producing Klebsiella pneumoniae infections: a two-center, matched case-control study

Gennaro De Pascale et al. Crit Care. .

Abstract

Background: Recent reports have suggested the efficacy of a double carbapenem (DC) combination, including ertapenem, for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infections. We aimed to evaluate the clinical impact of such a regimen in critically ill patients.

Methods: This case-control (1:2), observational, two-center study involved critically ill adults with a microbiologically documented CR-Kp invasive infection treated with the DC regimen matched with those receiving a standard treatment (ST) (i.e., colistin, tigecycline, or gentamicin).

Results: The primary end point was 28-day mortality. Secondary outcomes were clinical cure, microbiological eradication, duration of mechanical ventilation and of vasopressors, and 90-day mortality. Forty-eight patients treated with DC were matched with 96 controls. Occurrence of septic shock at infection and high procalcitonin levels were significantly more frequent in patients receiving DC treatment (p < 0.01). The 28-day mortality was significantly higher in patients receiving ST compared with the DC group (47.9% vs 29.2%, p = 0.04). Similarly, clinical cure and microbiological eradication were significantly higher when DC was used in patients infected with CR-Kp strains resistant to colistin (13/20 (65%) vs 10/32 (31.3%), p = 0.03 and 11/19 (57.9%) vs 7/27 (25.9%), p = 0.04, respectively). In the logistic regression and multivariate Cox-regression models, the DC regimen was associated with a reduction in 28-day mortality (OR 0.33, 95% CI 0.13-0.87 and OR 0.43, 95% CI 0.23-0.79, respectively).

Conclusions: Improved 28-day mortality was associated with the DC regimen compared with ST for severe CR-Kp infections. A randomized trial is needed to confirm these observational results.

Trial registration: ClinicalTrials.gov NCT03094494 . Registered 28 March 2017.

Keywords: Critically ill patients; Double carbapenem; Ertapenem; Infections; Klebsiella pneumoniae; Meropenem; Multidrug-resistant bacteria.

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the local ethics committees (approval numbers: Comitato Etico UCSC 14669/15; Comitato Etico Palermo 2 n° 359/2015). Because of its observational, noninterventional design, informed consent was waived.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
a Clinical cure rate according to antibiotic resistance. *p = 0.03, **p = 0.05. b Microbiological eradication rate according to antibiotic resistance. *p = 0.04. R resistance, DC double carbapenem, ST standard treatment, Coli colistin, Genta gentamicin, Tige tigecycline
Fig. 2
Fig. 2
Kaplan–Meier curves showing the impact of DC therapy (black line) versus ST (gray line) on a 28-day mortality and b 90-day mortality. DC double carbapenem, ST standard treatment
See this image and copyright information in PMC

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References

    1. Tumbarello M, Trecarichi EM, Tumietto F, Del Bono V, De Rosa FG, Bassetti M, Losito AR, Tedeschi S, Saffioti C, Corcione S, et al. Predictive models for identification of hospitalized patients harboring KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2014;58(6):3514–20. doi: 10.1128/AAC.02373-13. - DOI - PMC - PubMed
    1. Baraniak A, Izdebski R, Fiett J, Herda M, Derde LP, Bonten MJ, Adler A, Carmeli Y, Goossens H, Hryniewicz W, et al. KPC-Like Carbapenemase-producing enterobacteriaceae colonizing patients in Europe and Israel. Antimicrob Agents Chemother. 2015;60(3):1912–7. doi: 10.1128/AAC.02756-15. - DOI - PMC - PubMed
    1. Albiger B, Glasner C, Struelens MJ, Grundmann H, Monnet DL. Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. Euro Surveill. 2015;20(45):1-18. doi:10.2807/1560-7917.ES.2015.20.45.30062 - PubMed
    1. Dautzenberg MJ, Wekesa AN, Gniadkowski M, Antoniadou A, Giamarellou H, Petrikkos GL, Skiada A, Brun-Buisson C, Bonten MJ, Derde LP. The association between colonization with carbapenemase-producing enterobacteriaceae and overall ICU mortality: an observational cohort study. Crit Care Med. 2015;43(6):1170–7. doi: 10.1097/CCM.0000000000001028. - DOI - PMC - PubMed
    1. Gutierrez-Gutierrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Pano-Pardo JR, Venditti M, Tumbarello M, Daikos G, Pintado V, et al. A predictive model of mortality in patients with bloodstream infections due to carbapenemase-producing enterobacteriaceae. Mayo Clin Proc. 2016;91(10):1362–71. doi: 10.1016/j.mayocp.2016.06.024. - DOI - PubMed

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