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.
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 KPC-producing Klebsiella pneumoniae, <<CLINICAL INFECTIOUS DISEASES>>, 2019; (68): 355-384. [doi:10.1093/cid/ciy492] [http://hdl.handle.net/10807/124519]
Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae
Tumbarello, Mario;Trecarichi, Enrico Maria;Sica, Simona;De Pascale, Gennaro;Losito, Angela Raffaella;Raffaelli, Francesca;Spanu, Teresa;Cauda, Roberto;
2019
Abstract
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.
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