Pharmacoepidemiology of Ceftazidime-Avibactam Use: A Retrospective Cohort Analysis of 210 US Hospitals

Jeffrey R. Strich*, Emily Ricotta, Sarah Warner, Yi Ling Lai, Cumhur Y. Demirkale, Samuel F. Hohmann, Chanu Rhee, Michael Klompas, Tara Palmore, John H. Powers, John P. Dekker, Jennifer Adjemian, Roland Matsouaka, Christopher W. Woods, Robert L. Danner, Sameer S. Kadri

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background: Ceftazidime-avibactam has in vitro activity against some carbapenem-resistant gram-negative infections (GNIs), and therefore may be a useful alternative to more toxic antibiotics such as colistin. Understanding ceftazidime-avibactam uptake and usage patterns would inform hospitalformularies, stewardship, and antibiotic development. Methods: A retrospective cohort study assessed inpatient encounters in the Vizient database. Ceftazidime-avibactam and colistin administrations were categorized into presumed empiric (3 consecutive days of therapy or less with qualifying exclusions) versus targeted therapy (≥4 consecutive days of therapy) for presumed carbapenem-resistant GNIs. Quarterly percentage change (QPC) using modified Poisson regression and relative change in frequency of targeted ceftazidime-avibactam to colistin encounters was calculated. Factors associated with preferentially receiving targeted ceftazidime-avibactam versus colistin were identified using generalized estimating equations. Results: Between 2015 quarter (q) 1 and 2017q4, ceftazidime-avibactam was administered 21 215 times across 1901 encounters. Inpatient prescriptions for ceftazidime-avibactam increased from 0.44/10 000 hospitalizations in 2015q1 to 7.7/10 000 in 2017q4 (QPC, +11%; 95% CI, 10-13%; P <. 01), while conversely colistin prescriptions decreased quarterly by 5% (95% CI, 4-6%; P <. 01). Ceftazidime-avibactam therapy was categorized as empiric 25% of the time, targeted 65% of the time, and indeterminate 10% of the time. Patients with chronic kidney disease were twice as likely to receive targeted ceftazidime-avibactam versus colistin (RR, 2.02; 95% CI, 1.82-2.25), whereas those on dialysis were less likely to receive ceftazidime-avibactam than colistin (RR, 0.71; 95% CI,. 61-.83). Conclusions: Since approval in 2015, ceftazidime-avibactam use has grown for presumed carbapenem-resistant GNIs, while colistin has correspondingly declined. Renal function drove the choice between ceftazidime-avibactam and colistin as targeted therapy.

Original languageEnglish
Pages (from-to)611-621
Number of pages11
JournalClinical Infectious Diseases
Volume72
Issue number4
DOIs
StatePublished - 15 Feb 2021
Externally publishedYes

Keywords

  • carbapenem resistance
  • ceftazidime-avibactam
  • novel beta-lactamase inhibitors
  • ram-negative resistance

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