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      Activity of Ceftolozane-Tazobactam Against Global Pseudomonas Aeruginosa and Non-Susceptible Phenotypes: SMART 2016

      abstract
      , MD, MPH 1 , , PhD, MPH 1 , , BS 1 , , MS 2 , , PhD 2 , , PhD 1
      Open Forum Infectious Diseases
      Oxford University Press

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          Abstract

          Background

          Pseudomonas aeruginosa (PA), one of the species of the ESKAPE pathogens that are known to “escape” the effects of many antimicrobials, is often difficult to treat. Ceftolozane-tazobactam (C/T) is an anti-pseudomonal cephalosporin/β-lactamase inhibitor recently approved by FDA and EMEA. We examined its activity against global clinical isolates of PA, including isolates non-susceptible (NS, intermediate or resistant) to other agents.

          Methods

          In 2016, 158 hospitals in 51 countries collected 5533 PA from intra-abdominal (IAI), urinary (UTI), and respiratory tract infections (RTI). MICs were determined using CLSI broth microdilution and interpreted with both CLSI and EUCAST breakpoints, as the susceptible breakpoints for C/T, cefepime (FEP), meropenem (MEM), and piperacillin-tazobactam (P/T) are the same using both criteria.

          Results

          Overall regional susceptibility of PA to C/T, prevalence of FEP-NS, MEM- NS, and P/T- NS phenotypes, and susceptibility of these phenotypes to C/T are shown below:

          Africa Asia* Europe Latin America Middle East North America South Pacific
          All PA (n) 405 795 1628 759 379 1137 430
          C/T susceptibility (%) 87.9 89.1 90.3 85.0 89.7 94.6 97.7
          PA, FEP-NS [n(% of region total)] 111 (27.4) 194 (24.4) 438 (26.9) 203 (26.7) 88 (23.2) 299 (26.3) 57 (13.3)
          C/T susceptibility (%) 56.8 55.7 66.0 45.3 59.1 80.6 84.2
          PA, MEM- NS [n(% of region total)] 138 (34.1) 203 (25.5) 525 (32.2) 258 (34.0) 135 (35.6) 247 (21.7) 55 (12.8)
          C/T susceptibility (%) 68.8 62.1 72.2 58.1 72.6 82.2 85.5
          PA, P/T- NS [n(% of region total)] 124 (30.6) 246 (30.9) 557 (34.2) 254 (33.5) 125 (33.0) 334 (29.4) 68 (15.8)
          C/T susceptibility (%) 66.1 69.1 73.3 57.9 69.6 82.6 86.8

          * Does not include China or India

          Differences in C/T susceptibility across isolates from IAI (91.4%), RTI (90.5%), and UTI (89.3%) were small.

          Conclusion

          Overall susceptibility to C/T ranged from 85% in Latin America to 98% in South Pacific. FEP-NS, MEM-NS, and P/T-NS isolates were least prevalent in South Pacific. C/T was active against these phenotypes in >80% of isolates in North America and South Pacific and against 62–73% of MEM-NS and P/T-NS isolates in all other regions except Latin America. Monitoring of C/T susceptibility to PA is warranted in light of increasing resistance to first line agents.

          Disclosures

          M. Hackel, IHMA: Employee, Salary; R. Badal, IHMA, Inc: Employee, Salary; K. Young, Merck: Employee and Shareholder, Dividends and Salary M. Motyl, Merck & Co., Inc.,: Employee, Salary

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          Author and article information

          Journal
          Open Forum Infect Dis
          Open Forum Infect Dis
          ofid
          Open Forum Infectious Diseases
          Oxford University Press (US )
          2328-8957
          Fall 2017
          04 October 2017
          04 October 2017
          : 4
          : Suppl 1 , ID Week 2017 Abstracts
          : S380
          Affiliations
          [1 ] International Health Management Associates, Inc. , Schaumburg, Illinois
          [2 ] Merck & Co., Inc. , Kenilworth, New Jersey
          Author notes

          Session: 147. Expanded Spectrum – New Antimicrobial Susceptibility Testing

          Friday, October 6, 2017: 12:30 PM

          Article
          ofx163.940
          10.1093/ofid/ofx163.940
          5631510
          8af73443-c1f7-4325-9fcd-4c96db53b6fc
          © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

          This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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