Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection

Maddalena Giannella, Enrico Maria Trecarichi, Daniele Roberto Giacobbe, Francesco Giuseppe De Rosa, Matteo Bassetti, Alessandro Bartoloni, Michele Bartoletti, Angela Raffaella Losito, Valerio Del Bono, Silvia Corcione, Sara Tedeschi, Francesca Raffaelli, Carolina Saffioti, Teresa Spanu, Gian Maria Rossolini, Anna Marchese, Simone Ambretti, Roberto Cauda, Claudio Viscoli, Russell Edward LewisPierluigi Viale, Mario Tumbarello

Risultato della ricerca: Contributo in rivistaArticolo in rivista

34 Citazioni (Scopus)

Abstract

Objectives: To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI). Methods: Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model. Results: 595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC ≥16 mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20–1.43, P < 0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19–4.50, P < 0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02–2.24, P = 0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25–0.78, P = 0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47–1.00, P = 0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43–0.95, P = 0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC ≥16 mg/L. Conclusions: In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance.
Lingua originaleEnglish
pagine (da-a)244-248
Numero di pagine5
RivistaInternational Journal of Antimicrobial Agents
Volume51
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • Bloodstream infection
  • CR-KP
  • Carbapenem
  • Combination therapy
  • Infectious Diseases
  • Microbiology (medical)
  • Pharmacology (medical)

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