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.

Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study

Grossi, Paolo Antonio;Peghin, Maddalena;Rovelli, Cristina;
2021

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.
KPC-producing Klebsiella pneumoniae; carbapenemases; ceftazidime-avibactam; Adult; Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; Ceftazidime; Drug Combinations; Humans; Microbial Sensitivity Tests; Retrospective Studies; beta-Lactamases; Klebsiella Infections; Klebsiella pneumoniae
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
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2140751
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