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

• Published in: Clinical infectious diseases 2021-02, Vol.72 (4), p.611-621
• Main Authors: Strich, Jeffrey R, Ricotta, Emily, Warner, Sarah, Lai, Yi Ling, Demirkale, Cumhur Y, Hohmann, Samuel F, Rhee, Chanu, Klompas, Michael, Palmore, Tara, Powers, John H, Dekker, John P, Adjemian, Jennifer, Matsouaka, Roland, Woods, Christopher W, Danner, Robert L, Kadri, Sameer S
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Azabicyclo Compounds - pharmacology; Azabicyclo Compounds - therapeutic use; beta-Lactamases; Ceftazidime - pharmacology; Ceftazidime - therapeutic use; Drug Combinations; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Major and Commentaries; Microbial Sensitivity Tests; Pharmacoepidemiology; Retrospective Studies
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciaa061

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 hospital formularies, 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. Since US Food and Drug Administration approval in 2015, ceftazidime-avibactam utilization has increased almost 20-fold over 3 years, corresponding to a concomitant decrease in colistin utilization. Renal function appears to be the strongest predictor that a patient will receive targeted ceftazidime-avibactam versus colistin.