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Clin Infect Dis. 2019 Sep 23. pii: ciz816. doi: 10.1093/cid/ciz816. [Epub ahead of print]

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

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Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan.
Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan.
Department of Clinical Pharmacy and Translational Science, University of Tennessee College of Pharmacy, Nashville, Tennessee.
Department of Pharmacy Services, Michigan Medicine, Ann Arbor, Michigan.
Department of Pharmacy Services, the Ohio State University Wexner Medical Center, Columbus, Ohio.
Department of Pharmacy, Henry Ford Hospital, Ann Arbor, Michigan; College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan.
Merck & Co, Inc, Kenilworth, New Jersey.
Division of Infectious Diseases Summa Health, Northeast Ohio Medical University, Rootstown, Ohio.
Department of Pharmacy, Sinai Grace Hospital; Detroit Medical Center, Detroit, Michigan.
Department of Internal Medicine, Detroit Medical Center, Wayne State University School of Medicine, Michigan.
Division of Infectious Diseases and HIV Medicine, Louis Stokes Cleveland VA Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.



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.


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.


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.


These data support the preferential use of ceftolozane/tazobactam over polymyxins or aminoglycosides for drug-resistant P. aeruginosa infections.


Pseudomonas ; aminoglycoside; ceftolozane; multidrug resistant; polymyxin


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