Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae

Mario Tumbarello, Enrico Maria Trecarichi, Alberto Corona, Francesco Giuseppe De Rosa, Matteo Bassetti, Cristina Mussini, Francesco Menichetti, Claudio Viscoli, Caterina Campoli, Mario Venditti, Andrea De Gasperi, Alessandra Mularoni, Carlo Tascini, Giustino Parruti, Carlo Pallotto, Simona Sica, Ercole Concia, Rosario Cultrera, Gennaro De Pascale, Alessandro Capone & 13 others Spinello Antinori, Silvia Corcione, Elda Righi, Angela Raffaella Losito, Margherita Digaetano, Francesco Amadori, Daniele Roberto Giacobbe, Giancarlo Ceccarelli, Ernestina Mazza, Francesca Raffaelli, Teresa Spanu, Roberto Cauda, Pierluigi Viale

Research output: Contribution to journalArticle

Abstract

Background: Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary-tract infections, as well as hospital-acquired pneumonia, and for Gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against KPC-enzyme producers, but clinical-trial data on its efficacy in this setting are lacking.Methods: We retrospectively reviewed 138 cases of infections caused by Klebsiella pneumoniae carbapenemase-producing (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic.Results: The 138 patients started CAZ-AVI salvage therapy after a first line treatment (median: 7 days) with other antimicrobials. CAZ-AVI was administered with at least one other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs. 55.7%, p=0.005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index >3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival.Conclusions: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.
Original languageEnglish
Pages (from-to)355
Number of pages364
JournalClinical Infectious Diseases
Volume68
Issue number3
DOIs
Publication statusAccepted/In press - Jun 6 2018

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Salvage Therapy
Klebsiella pneumoniae
Infection
Bacteremia
Compassionate Use Trials
Survival
Mortality
ceftazidime drug combination avibactam
Therapeutics
Septic Shock
Neutropenia
Artificial Respiration
Urinary Tract Infections
Pharmaceutical Preparations
Italy
Comorbidity
Pneumonia
Multivariate Analysis
Clinical Trials
Anti-Bacterial Agents

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Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae. / Tumbarello, Mario; Trecarichi, Enrico Maria; Corona, Alberto; De Rosa, Francesco Giuseppe; Bassetti, Matteo; Mussini, Cristina; Menichetti, Francesco; Viscoli, Claudio; Campoli, Caterina; Venditti, Mario; De Gasperi, Andrea; Mularoni, Alessandra; Tascini, Carlo; Parruti, Giustino; Pallotto, Carlo; Sica, Simona; Concia, Ercole; Cultrera, Rosario; De Pascale, Gennaro; Capone, Alessandro; Antinori, Spinello; Corcione, Silvia; Righi, Elda; Losito, Angela Raffaella; Digaetano, Margherita; Amadori, Francesco; Giacobbe, Daniele Roberto; Ceccarelli, Giancarlo; Mazza, Ernestina; Raffaelli, Francesca; Spanu, Teresa; Cauda, Roberto; Viale, Pierluigi.

In: Clinical Infectious Diseases, Vol. 68, No. 3, 06.06.2018, p. 355.

Research output: Contribution to journalArticle

Tumbarello, M, Trecarichi, EM, Corona, A, De Rosa, FG, Bassetti, M, Mussini, C, Menichetti, F, Viscoli, C, Campoli, C, Venditti, M, De Gasperi, A, Mularoni, A, Tascini, C, Parruti, G, Pallotto, C, Sica, S, Concia, E, Cultrera, R, De Pascale, G, Capone, A, Antinori, S, Corcione, S, Righi, E, Losito, AR, Digaetano, M, Amadori, F, Giacobbe, DR, Ceccarelli, G, Mazza, E, Raffaelli, F, Spanu, T, Cauda, R & Viale, P 2018, 'Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae', Clinical Infectious Diseases, vol. 68, no. 3, pp. 355. https://doi.org/10.1093/cid/ciy492
Tumbarello, Mario ; Trecarichi, Enrico Maria ; Corona, Alberto ; De Rosa, Francesco Giuseppe ; Bassetti, Matteo ; Mussini, Cristina ; Menichetti, Francesco ; Viscoli, Claudio ; Campoli, Caterina ; Venditti, Mario ; De Gasperi, Andrea ; Mularoni, Alessandra ; Tascini, Carlo ; Parruti, Giustino ; Pallotto, Carlo ; Sica, Simona ; Concia, Ercole ; Cultrera, Rosario ; De Pascale, Gennaro ; Capone, Alessandro ; Antinori, Spinello ; Corcione, Silvia ; Righi, Elda ; Losito, Angela Raffaella ; Digaetano, Margherita ; Amadori, Francesco ; Giacobbe, Daniele Roberto ; Ceccarelli, Giancarlo ; Mazza, Ernestina ; Raffaelli, Francesca ; Spanu, Teresa ; Cauda, Roberto ; Viale, Pierluigi. / Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae. In: Clinical Infectious Diseases. 2018 ; Vol. 68, No. 3. pp. 355.
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title = "Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae",
abstract = "Background: Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary-tract infections, as well as hospital-acquired pneumonia, and for Gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against KPC-enzyme producers, but clinical-trial data on its efficacy in this setting are lacking.Methods: We retrospectively reviewed 138 cases of infections caused by Klebsiella pneumoniae carbapenemase-producing (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic.Results: The 138 patients started CAZ-AVI salvage therapy after a first line treatment (median: 7 days) with other antimicrobials. CAZ-AVI was administered with at least one other active antibiotic in 109 (78.9{\%}) cases. Thirty days after infection onset, 47 (34.1{\%}) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5{\%} vs. 55.7{\%}, p=0.005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index >3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival.Conclusions: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.",
author = "Mario Tumbarello and Trecarichi, {Enrico Maria} and Alberto Corona and {De Rosa}, {Francesco Giuseppe} and Matteo Bassetti and Cristina Mussini and Francesco Menichetti and Claudio Viscoli and Caterina Campoli and Mario Venditti and {De Gasperi}, Andrea and Alessandra Mularoni and Carlo Tascini and Giustino Parruti and Carlo Pallotto and Simona Sica and Ercole Concia and Rosario Cultrera and {De Pascale}, Gennaro and Alessandro Capone and Spinello Antinori and Silvia Corcione and Elda Righi and Losito, {Angela Raffaella} and Margherita Digaetano and Francesco Amadori and Giacobbe, {Daniele Roberto} and Giancarlo Ceccarelli and Ernestina Mazza and Francesca Raffaelli and Teresa Spanu and Roberto Cauda and Pierluigi Viale",
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language = "English",
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TY - JOUR

T1 - Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae

AU - Tumbarello, Mario

AU - Trecarichi, Enrico Maria

AU - Corona, Alberto

AU - De Rosa, Francesco Giuseppe

AU - Bassetti, Matteo

AU - Mussini, Cristina

AU - Menichetti, Francesco

AU - Viscoli, Claudio

AU - Campoli, Caterina

AU - Venditti, Mario

AU - De Gasperi, Andrea

AU - Mularoni, Alessandra

AU - Tascini, Carlo

AU - Parruti, Giustino

AU - Pallotto, Carlo

AU - Sica, Simona

AU - Concia, Ercole

AU - Cultrera, Rosario

AU - De Pascale, Gennaro

AU - Capone, Alessandro

AU - Antinori, Spinello

AU - Corcione, Silvia

AU - Righi, Elda

AU - Losito, Angela Raffaella

AU - Digaetano, Margherita

AU - Amadori, Francesco

AU - Giacobbe, Daniele Roberto

AU - Ceccarelli, Giancarlo

AU - Mazza, Ernestina

AU - Raffaelli, Francesca

AU - Spanu, Teresa

AU - Cauda, Roberto

AU - Viale, Pierluigi

PY - 2018/6/6

Y1 - 2018/6/6

N2 - Background: Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary-tract infections, as well as hospital-acquired pneumonia, and for Gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against KPC-enzyme producers, but clinical-trial data on its efficacy in this setting are lacking.Methods: We retrospectively reviewed 138 cases of infections caused by Klebsiella pneumoniae carbapenemase-producing (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic.Results: The 138 patients started CAZ-AVI salvage therapy after a first line treatment (median: 7 days) with other antimicrobials. CAZ-AVI was administered with at least one other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs. 55.7%, p=0.005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index >3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival.Conclusions: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.

AB - Background: Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary-tract infections, as well as hospital-acquired pneumonia, and for Gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against KPC-enzyme producers, but clinical-trial data on its efficacy in this setting are lacking.Methods: We retrospectively reviewed 138 cases of infections caused by Klebsiella pneumoniae carbapenemase-producing (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic.Results: The 138 patients started CAZ-AVI salvage therapy after a first line treatment (median: 7 days) with other antimicrobials. CAZ-AVI was administered with at least one other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs. 55.7%, p=0.005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index >3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival.Conclusions: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.

U2 - 10.1093/cid/ciy492

DO - 10.1093/cid/ciy492

M3 - Article

VL - 68

SP - 355

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 3

ER -