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.

Tumbarello, M., Raffaelli, F., Giannella, M., Mantengoli, E., Mularoni, A., Venditti, M., De Rosa, F., Sarmati, L., Bassetti, M., Brindicci, G., Rossi, M., Luzzati, R., Grossi, P., Corona, A., Capone, A., Falcone, M., Mussini, C., Trecarichi, E. M., Cascio, A., Guffanti, E., Russo, A., De Pascale, G., Tascini, C., Gentile, I., Losito, A. R., Bussini, L., Corti, G., Ceccarelli, G. M., Corcione, S., Compagno, M., Giacobbe, D., Saracino, A., Fantoni, M., Antinori, S., Peghin, M., Bonfanti, P., Oliva, A., De Gasperi, A., Tiseo, G., Rovelli, C., Meschiari, M., Shbaklo, N., Spanu Pennestri, T., Cauda, R., Viale, P., Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study, <<CLINICAL INFECTIOUS DISEASES>>, 2021; 73 (9): 1664-1676. [doi:10.1093/cid/ciab176] [https://hdl.handle.net/10807/304377]

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

Tumbarello, Mario;Raffaelli, Francesca;Venditti, Mario;Trecarichi, Enrico Maria;De Pascale, Gennaro;Tascini, Carlo;Losito, Angela Raffaella;Ceccarelli, Giovanni Maria;Fantoni, Massimo;Oliva, Antonio;Meschiari, Marianna;Spanu Pennestri, Teresa;Cauda, Roberto;
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.
2021
Inglese
Tumbarello, M., Raffaelli, F., Giannella, M., Mantengoli, E., Mularoni, A., Venditti, M., De Rosa, F., Sarmati, L., Bassetti, M., Brindicci, G., Rossi, M., Luzzati, R., Grossi, P., Corona, A., Capone, A., Falcone, M., Mussini, C., Trecarichi, E. M., Cascio, A., Guffanti, E., Russo, A., De Pascale, G., Tascini, C., Gentile, I., Losito, A. R., Bussini, L., Corti, G., Ceccarelli, G. M., Corcione, S., Compagno, M., Giacobbe, D., Saracino, A., Fantoni, M., Antinori, S., Peghin, M., Bonfanti, P., Oliva, A., De Gasperi, A., Tiseo, G., Rovelli, C., Meschiari, M., Shbaklo, N., Spanu Pennestri, T., Cauda, R., Viale, P., Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study, <<CLINICAL INFECTIOUS DISEASES>>, 2021; 73 (9): 1664-1676. [doi:10.1093/cid/ciab176] [https://hdl.handle.net/10807/304377]
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