BACKGROUND: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae (CRE).METHODS: We retrospectively analyzed observational data on the use and outcomes of CAZ-AVI therapy for infections caused by KPC-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 vs. CAZ-AVI monotherapy.RESULTS: The cohort comprised 577 adults with bloodstream infections (BSIs) (n=391) or non-bacteremic infections (nBSIs) involving mainly the urinary tract, lower respiratory tract, intra-abdominal structures. All received treatment with CAZ-AVI alone (n=165) or with one or more other active antimicrobials (n=412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no statistically significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs. 25.0%, P=0.79). In multivariate analysis, mortality was positively associated with the presence at infection onset of septic shock (P=0.002), neutropenia (P <0.001), or an INCREMENT score >8 (P=0.01); with LRTI (P=0.04); and with CAZ-AVI dose adjustment for renal function (P=0.01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P=0.006). 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 the potential survival benefits of prolonging CAZ-AVI infusions to 3 hours or more.

Ceftazidime-avibactam use for KPC-Kp infections: a retrospective observational multicenter study / 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; Conti, 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. - In: CLINICAL INFECTIOUS DISEASES. - ISSN 1058-4838. - 73:9(2021), pp. 1664-1676. [10.1093/cid/ciab176]

Ceftazidime-avibactam use for KPC-Kp infections: a retrospective observational multicenter study

Mussini, Cristina;Meschiari, Marianna;
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 (CRE).METHODS: We retrospectively analyzed observational data on the use and outcomes of CAZ-AVI therapy for infections caused by KPC-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 vs. CAZ-AVI monotherapy.RESULTS: The cohort comprised 577 adults with bloodstream infections (BSIs) (n=391) or non-bacteremic infections (nBSIs) involving mainly the urinary tract, lower respiratory tract, intra-abdominal structures. All received treatment with CAZ-AVI alone (n=165) or with one or more other active antimicrobials (n=412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no statistically significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs. 25.0%, P=0.79). In multivariate analysis, mortality was positively associated with the presence at infection onset of septic shock (P=0.002), neutropenia (P <0.001), or an INCREMENT score >8 (P=0.01); with LRTI (P=0.04); and with CAZ-AVI dose adjustment for renal function (P=0.01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P=0.006). 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 the potential survival benefits of prolonging CAZ-AVI infusions to 3 hours or more.
2021
73
9
1664
1676
Ceftazidime-avibactam use for KPC-Kp infections: a retrospective observational multicenter study / 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; Conti, 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. - In: CLINICAL INFECTIOUS DISEASES. - ISSN 1058-4838. - 73:9(2021), pp. 1664-1676. [10.1093/cid/ciab176]
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; Conti, 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/11380/1239792
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