Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study. (22nd February 2021)

• Record Type: Journal Article
• Authors: Tumbarello, Mario; Raffaelli, Francesca; Giannella, Maddalena; Mantengoli, Elisabetta; Mularoni, Alessandra; Venditti, Mario; De Rosa, Francesco Giuseppe; Sarmati, Loredana; Bassetti, Matteo; Brindicci, Gaetano; Rossi, Marianna; Luzzati, Roberto; Grossi, Paolo Antonio; Corona, Alberto; Capone, Alessandro; Falcone, Marco; Mussini, Cristina; Trecarichi, Enrico Maria; Cascio, Antonio; Guffanti, Elena; Russo, Alessandro; De Pascale, Gennaro; Tascini, Carlo; Gentile, Ivan; Losito, Angela Raffaella; Bussini, Linda; Corti, Giampaolo; Ceccarelli, Giancarlo; Corcione, Silvia; Compagno, Mirko; Giacobbe, Daniele Roberto; Saracino, Annalisa; Fantoni, Massimo; Antinori, Spinello; Peghin, Maddalena; Bonfanti, Paolo; Oliva, Alessandra; De Gasperi, Andrea; Tiseo, Giusy; Rovelli, Cristina; Meschiari, Marianna; Shbaklo, Nour; Spanu, Teresa; Cauda, Roberto; Viale, Pierluigi;
• Is Part Of: Clinical infectious diseases. Volume 73:Number 9(2021)
• Page Start: 1664
• Page End: 1676
• Publication Date: 2021-02-22
• Subjects: ceftazidime-avibactam -- carbapenemases -- KPC-producing Klebsiella pneumoniae; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciab176
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. Methods: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. Results: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P = .79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock ( P = .002), neutropenia ( P < .001), or an INCREMENT score ≥8 ( P = .01); with lower respiratory tract infection (LRTI) ( P = .04); and with CAZ-AVI dose adjustment for renal function ( P = .01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion ( P = .006). All associations remained significant after propensity score adjustment. Conclusions: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours. Abstract : We retrospectively analyzed observational data on the use and outcomes of ceftazidime-avibactam (CAZ-AVI) therapy for infections causedby Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-Kp) in 22 hospitals in Italy. CAZ-AVI appears to be an important drug for treatment of serious KPC-Kp infections, even when used alone.