Ceftolozane/Tazobactam vs Polymyxin or Aminoglycoside-based Regimens for the Treatment of Drug-resistant Pseudomonas aeruginosa

Author:

Pogue Jason M1,Kaye Keith S2,Veve Michael P3,Patel Twisha S4,Gerlach Anthony T5,Davis Susan L6,Puzniak Laura A7,File Tom M8,Olson Shannon9,Dhar Sorabh10,Bonomo Robert A11,Perez Federico11

Affiliation:

1. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan

2. Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan

3. Department of Clinical Pharmacy and Translational Science, University of Tennessee College of Pharmacy, Nashville, Tennessee

4. Department of Pharmacy Services, Michigan Medicine, Ann Arbor, Michigan

5. Department of Pharmacy Services, the Ohio State University Wexner Medical Center, Columbus, Ohio

6. Department of Pharmacy, Henry Ford Hospital, Ann Arbor, Michigan; College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan

7. Merck & Co, Inc, Kenilworth, New Jersey

8. Division of Infectious Diseases Summa Health, Northeast Ohio Medical University, Rootstown, Ohio

9. Department of Pharmacy, Sinai Grace Hospital; Detroit Medical Center, Detroit, Michigan

10. Department of Internal Medicine, Detroit Medical Center, Wayne State University School of Medicine, Michigan

11. Division of Infectious Diseases and HIV Medicine, Louis Stokes Cleveland VA Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio

Abstract

Abstract Background Ceftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination that often retains activity against resistant Pseudomonas aeruginosa. The comparative safety and efficacy vs polymyxins or aminoglycosides in this setting remains unknown. Methods A retrospective, multicenter, observational cohort study was performed. Patients who received ceftolozane/tazobactam were compared with those treated with either polymyxin or aminoglycoside-based regimens for infections due to drug-resistant P. aeruginosa. Multivariate logistic regression was performed controlling for factors associated with treatment to assess the independent impact of ceftolozane/tazobactam on clinical cure, acute kidney injury (AKI), and in-hospital mortality. Results A total of 200 patients were included (100 in each treatment arm). The cohort represented an ill population with 69% in the intensive care unit, 63% mechanically ventilated, and 42% in severe sepsis or septic shock at infection onset. The most common infection type was ventilator-associated pneumonia (52%); 7% of patients were bacteremic. Combination therapy was more commonly used in polymyxin/aminoglycoside patients than those who received ceftolozane/tazobactam (72% vs 15%, P < .001). After adjusting for differences between groups, receipt of ceftolozane/tazobactam was independently associated with clinical cure (adjusted odds ratio [aOR], 2.63; 95% confidence interval [CI], 1.31–5.30) and protective against AKI (aOR, 0.08; 95% CI, 0.03–0.22). There was no difference in in-hospital mortality. The number needed to treat for a clinical cure with ceftolozane/tazobactam was 5, and the number needed to harm with AKI with a polymyxin/aminoglycoside was 4. Conclusions These data support the preferential use of ceftolozane/tazobactam over polymyxins or aminoglycosides for drug-resistant P. aeruginosa infections.

Funder

Merck Sharp and Dohme

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

Reference19 articles.

1. Prevalence of multidrug-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae among specimens from hospitalized patients with pneumonia and bloodstream infections in the United States from 2000 to 2009;Zilberberg;J Hosp Med,2013

2. Antimicrobial susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa isolates from United States medical centers stratified by infection type: results from the International Network for Optimal Resistance Monitoring (INFORM) surveillance program, 2015–2016;Sader;Diagn Microbiol Infect Dis,2018

3. Multicenter evaluation of ceftazidime-avibactam and ceftolozane-tazobactam inhibitory activity against meropenem-nonsusceptible Pseudomonas aeruginosa from blood, respiratory tract, and wounds;Grupper;Antimicrob Agents Chemother,2017

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