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 / Tumbarello, M.; Raffaelli, F.; Giannella, M.; Mantengoli, E.; Mularoni, A.; Venditti, M.; De Rosa, F. G.; Sarmati, L.; Bassetti, M.; Brindicci, G.; Rossi, M.; Luzzati, R.; Grossi, P. A.; 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.; Corcione, S.; Compagno, M.; Giacobbe, D. R.; Saracino, A.; Fantoni, M.; Antinori, S.; Peghin, M.; Bonfanti, P.; Oliva, A.; De Gasperi, A.; Tiseo, G.; Rovelli, C.; Meschiari, M.; Shbaklo, N.; Spanu, T.; Cauda, R.; Viale, P.. - In: CLINICAL INFECTIOUS DISEASES. - ISSN 1058-4838. - 73:9(2021), pp. 1664-1676. [10.1093/cid/ciab176]
Ceftazidime-avibactam use for klebsiella pneumoniae carbapenemase-producing k. pneumoniae infections: A retrospective observational multicenter study
Gentile I.;
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.
