Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae

M. Tumbarello, E.M. Trecarichi, A. Corona, F.G. De Rosa, M. Bassetti, C. Mussini, F. Menichetti, C. Viscoli, C. Campoli, M. Venditti, A. De Gasperi, A. Mularoni, C. Tascini, G. Parruti, C. Pallotto, S. Sica, E. Concia, R. Cultrera, G. De Pascale, A. CaponeS. Antinori, S. Corcione, E. Righi, A.R. Losito, M. Digaetano, F. Amadori, D.R. Giacobbe, G. Ceccarelli, E. Mazza, F. Raffaelli, T. Spanu, R. Cauda, P. 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 Klebsiella pneumoniae carbapenemase (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 KPC-producing K. pneumoniae (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 1 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 55.8%, P = .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)355-364
Number of pages10
JournalClinical Infectious Diseases
Volume68
Issue number3
DOIs
Publication statusPublished - 2019

Fingerprint

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

Cite this

Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. / Tumbarello, M.; Trecarichi, E.M.; Corona, A.; De Rosa, F.G.; 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, A.R.; Digaetano, M.; Amadori, F.; Giacobbe, D.R.; Ceccarelli, G.; Mazza, E.; Raffaelli, F.; Spanu, T.; Cauda, R.; Viale, P.

In: Clinical Infectious Diseases, Vol. 68, No. 3, 2019, p. 355-364.

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 2019, 'Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae', Clinical Infectious Diseases, vol. 68, no. 3, pp. 355-364. https://doi.org/10.1093/cid/ciy492
Tumbarello, M. ; Trecarichi, E.M. ; Corona, A. ; De Rosa, F.G. ; 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, A.R. ; Digaetano, M. ; Amadori, F. ; Giacobbe, D.R. ; Ceccarelli, G. ; Mazza, E. ; Raffaelli, F. ; Spanu, T. ; Cauda, R. ; Viale, P. / Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. In: Clinical Infectious Diseases. 2019 ; Vol. 68, No. 3. pp. 355-364.
@article{54c79fba1eff4f0da31da0d1378d28f8,
title = "Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. 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 Klebsiella pneumoniae carbapenemase (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 KPC-producing K. pneumoniae (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 1 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 55.8{\%}, P = .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 = "M. Tumbarello and E.M. Trecarichi and A. Corona and {De Rosa}, F.G. and M. Bassetti and C. Mussini and F. Menichetti and C. Viscoli and C. Campoli and M. Venditti and {De Gasperi}, A. and A. Mularoni and C. Tascini and G. Parruti and C. Pallotto and S. Sica and E. Concia and R. Cultrera and {De Pascale}, G. and A. Capone and S. Antinori and S. Corcione and E. Righi and A.R. Losito and M. Digaetano and F. Amadori and D.R. Giacobbe and G. Ceccarelli and E. Mazza and F. Raffaelli and T. Spanu and R. Cauda and P. Viale",
note = "cited By 9",
year = "2019",
doi = "10.1093/cid/ciy492",
language = "English",
volume = "68",
pages = "355--364",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "NLM (Medline)",
number = "3",

}

TY - JOUR

T1 - Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae

AU - Tumbarello, M.

AU - Trecarichi, E.M.

AU - Corona, A.

AU - De Rosa, F.G.

AU - Bassetti, M.

AU - Mussini, C.

AU - Menichetti, F.

AU - Viscoli, C.

AU - Campoli, C.

AU - Venditti, M.

AU - De Gasperi, A.

AU - Mularoni, A.

AU - Tascini, C.

AU - Parruti, G.

AU - Pallotto, C.

AU - Sica, S.

AU - Concia, E.

AU - Cultrera, R.

AU - De Pascale, G.

AU - Capone, A.

AU - Antinori, S.

AU - Corcione, S.

AU - Righi, E.

AU - Losito, A.R.

AU - Digaetano, M.

AU - Amadori, F.

AU - Giacobbe, D.R.

AU - Ceccarelli, G.

AU - Mazza, E.

AU - Raffaelli, F.

AU - Spanu, T.

AU - Cauda, R.

AU - Viale, P.

N1 - cited By 9

PY - 2019

Y1 - 2019

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 Klebsiella pneumoniae carbapenemase (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 KPC-producing K. pneumoniae (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 1 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 55.8%, P = .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 Klebsiella pneumoniae carbapenemase (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 KPC-producing K. pneumoniae (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 1 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 55.8%, P = .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

EP - 364

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 3

ER -