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.;Giannella M.;Bassetti M.;Capone A.;Mussini C.;Cascio A.;Bussini L.;Meschiari M.;Viale P.
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.
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.
File in questo prodotto:
Eventuali allegati, non sono esposti

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

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/862270
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 18
  • Scopus 27
  • ???jsp.display-item.citation.isi??? 14
social impact