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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.