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 -