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

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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

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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., ... Viale, P. (2019). Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clinical Infectious Diseases, 68(3), 355-364. https://doi.org/10.1093/cid/ciy492