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

Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva (ISGRI-SITA)

Research output: Contribution to journalArticle

15 Citations (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.

Original languageEnglish
Pages (from-to)244-248
Number of pages5
JournalInternational Journal of Antimicrobial Agents
Volume51
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Fingerprint

Carbapenems
Klebsiella pneumoniae
Mortality
Infection
Therapeutics
Propensity Score
Colistin
Septic Shock

Keywords

  • Bloodstream infection
  • Carbapenem
  • Combination therapy
  • CR-KP

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection. / Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva (ISGRI-SITA).

In: International Journal of Antimicrobial Agents, Vol. 51, No. 2, 01.02.2018, p. 244-248.

Research output: Contribution to journalArticle

Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva (ISGRI-SITA). / Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection. In: International Journal of Antimicrobial Agents. 2018 ; Vol. 51, No. 2. pp. 244-248.
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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.",
keywords = "Bloodstream infection, Carbapenem, Combination therapy, CR-KP",
author = "{Italian Study Group on Resistant Infections of the Societ{\`a} Italiana Terapia Antinfettiva (ISGRI-SITA)} and Maddalena Giannella and Trecarichi, {Enrico Maria} and Giacobbe, {Daniele Roberto} and {De Rosa}, {Francesco Giuseppe} and Matteo Bassetti and Alessandro Bartoloni and Michele Bartoletti and Losito, {Angela Raffaella} and {del Bono}, Valerio and Silvia Corcione and Sara Tedeschi and Francesca Raffaelli and Carolina Saffioti and Teresa Spanu and Rossolini, {Gian Maria} and Anna Marchese and Simone Ambretti and Roberto Cauda and Claudio Viscoli and Lewis, {Russell Edward} and Pierluigi Viale and Mario Tumbarello",
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T1 - Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection

AU - Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva (ISGRI-SITA)

AU - Giannella, Maddalena

AU - Trecarichi, Enrico Maria

AU - Giacobbe, Daniele Roberto

AU - De Rosa, Francesco Giuseppe

AU - Bassetti, Matteo

AU - Bartoloni, Alessandro

AU - Bartoletti, Michele

AU - Losito, Angela Raffaella

AU - del Bono, Valerio

AU - Corcione, Silvia

AU - Tedeschi, Sara

AU - Raffaelli, Francesca

AU - Saffioti, Carolina

AU - Spanu, Teresa

AU - Rossolini, Gian Maria

AU - Marchese, Anna

AU - Ambretti, Simone

AU - Cauda, Roberto

AU - Viscoli, Claudio

AU - Lewis, Russell Edward

AU - Viale, Pierluigi

AU - Tumbarello, Mario

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - Bloodstream infection

KW - Carbapenem

KW - Combination therapy

KW - CR-KP

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