Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections: Clinical Effectiveness and Evolution of Resistance

Ghady Haidar, Nathan J. Philips, Ryan K. Shields, Daniel Snyder, Shaoji Cheng, Brian A. Potoski, Yohei Doi, Binghua Hao, Ellen G. Press, Vaughn S. Cooper, Cornelius J. Clancy, M. Hong Nguyen

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85 Citations (Scopus)

Abstract

Background. Data on the use of ceftolozane-tazobactam and emergence of ceftolozane-tazobactam resistance during multidrug resistant (MDR)-Pseudomonas aeruginosa infections are limited. Methods. We performed a retrospective study of 21 patients treated with ceftolozane-tazobactam for MDR-P. aeruginosa infections. Whole genome sequencing and quantitative real-time polymerase chain reaction were performed on longitudinal isolates. Results. Median age was 58 years; 9 patients (43%) were transplant recipients. Median simplified acute physiology score-II (SAPS-II) was 26. Eighteen (86%) patients were treated for respiratory tract infections; others were treated for bloodstream, complicated intraabdominal infections, or complicated urinary tract infections. Ceftolozane-tazobactam was discontinued in 1 patient (rash). Thirty-day all-cause and attributable mortality rates were 10% (2/21) and 5% (1/21), respectively; corresponding 90-day mortality rates were 48% (10/21) and 19% (4/21). The ceftolozane-tazobactam failure rate was 29% (6/21). SAPS-II score was the sole predictor of failure. Ceftolozane-tazobactam resistance emerged in 3 (14%) patients. Resistance was associated with de novo mutations, rather than acquisition of resistant nosocomial isolates. ampC overexpression and mutations were identified as potential resistance determinants. Conclusions. In this small study, ceftolozane-tazobactam was successful in treating 71% of patients with MDR-P. aeruginosa infections, most of whom had pneumonia. The emergence of ceftolozane-tazobactam resistance in 3 patients is worrisome and may be mediated in part by AmpC-related mechanisms. More research on treatment responses and resistance during various types of MDR-P. aeruginosa infections is needed to define ceftolozane-tazobactam's place in the armamentarium.

Original languageEnglish
Pages (from-to)110-120
Number of pages11
JournalClinical Infectious Diseases
Volume65
Issue number1
DOIs
Publication statusPublished - 01-07-2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

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  • Cite this

    Haidar, G., Philips, N. J., Shields, R. K., Snyder, D., Cheng, S., Potoski, B. A., Doi, Y., Hao, B., Press, E. G., Cooper, V. S., Clancy, C. J., & Nguyen, M. H. (2017). Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections: Clinical Effectiveness and Evolution of Resistance. Clinical Infectious Diseases, 65(1), 110-120. https://doi.org/10.1093/cid/cix182