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Observational Study
. 2021 Nov 2;73(9):1664-1676.
doi: 10.1093/cid/ciab176.

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

Mario Tumbarello  1   2   3 , Francesca Raffaelli  1 , Maddalena Giannella  4 , Elisabetta Mantengoli  5 , Alessandra Mularoni  6 , Mario Venditti  7 , Francesco Giuseppe De Rosa  8 , Loredana Sarmati  9 , Matteo Bassetti  10   11 , Gaetano Brindicci  12 , Marianna Rossi  13 , Roberto Luzzati  14 , Paolo Antonio Grossi  15 , Alberto Corona  16 , Alessandro Capone  17 , Marco Falcone  18 , Cristina Mussini  19 , Enrico Maria Trecarichi  20 , Antonio Cascio  21 , Elena Guffanti  22 , Alessandro Russo  23 , Gennaro De Pascale  24 , Carlo Tascini  25 , Ivan Gentile  26 , Angela Raffaella Losito  1 , Linda Bussini  4 , Giampaolo Corti  5   27 , Giancarlo Ceccarelli  7 , Silvia Corcione  8   28 , Mirko Compagno  29 , Daniele Roberto Giacobbe  10   11 , Annalisa Saracino  12 , Massimo Fantoni  1   2 , Spinello Antinori  30 , Maddalena Peghin  31 , Paolo Bonfanti  13   32 , Alessandra Oliva  7 , Andrea De Gasperi  22 , Giusy Tiseo  18 , Cristina Rovelli  15 , Marianna Meschiari  33 , Nour Shbaklo  8 , Teresa Spanu  1   34 , Roberto Cauda  1   2 , Pierluigi Viale  4
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Free article
Observational Study

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

Mario Tumbarello et al. Clin Infect Dis. .
Free article

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.

Keywords: KPC-producing Klebsiella pneumoniae; carbapenemases; ceftazidime-avibactam.

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