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Journal of Medical Microbiology logo Journal of Medical Microbiology

Volume 69, Issue 2

activity of imipenem-relebactam against resistant phenotypes of and isolated from intraabdominal and urinary tract infection samples – SMART Surveillance Europe 2015–2017 No Access

Abstract

Infections attributable to carbapenem-resistant Gram-negative bacilli are increasing globally. New antimicrobial agents are urgently needed to treat patients with these infections.

To describe susceptibility to the novel carbapenem-β-lactamase inhibitor combination imipenem-relebactam and comparators of clinical isolates of non-Proteeae (NPE) and from intraabdominal infections (IAIs) and urinary tract infections (UTIs).

Broth microdilution MICs were determined for isolates collected in 22 European countries in 2015–2017 and interpreted using EUCAST breakpoints; imipenem-relebactam MICs were interpreted using imipenem breakpoints.

For NPE, 98.4 % of isolates from IAIs (=10,465) and 98.5 % of UTI isolates (=7,446) were susceptible to imipenem-relebactam, as were 42.4 % of imipenem-nonsusceptible (=474), 98.6 % of carbapenemase (KPC)-positive (=138), and 93.9 % of multidrug-resistant (MDR) isolates (=4,424) from IAIs and UTIs combined. Molecular analysis demonstrated that two-thirds of imipenem-nonsusceptible isolates rendered susceptible by relebactam carried KPCs; 96 % (261/271) of imipenem-nonsusceptible isolates of NPE that remained nonsusceptible in the presence of relebactam carried metallo-β-lactamase (MBL)-type and/or OXA-48-like carbapenemases. Among , 94.4 % of IAI (=1,245) and 93.0 % of UTI isolates (=714) were susceptible to imipenem-relebactam, as were 74.4 % of imipenem-nonsusceptible (=469) and 79.8 % of MDR isolates (=595) from IAIs and UTIs combined. Among the 120 isolates of that remained nonsusceptible to imipenem upon addition of relebactam, 72 % carried MBLs. The distribution of NPE and carrying carbapenemases varied substantially across Europe, as did resistance to imipenem and imipenem-relebactam.

Continued surveillance of antimicrobial resistance and resistance mechanisms, including the study of imipenem-relebactam as it approaches regulatory approval, appears warranted.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Europe , Gram-negative bacilli , imipenem-relebactam , intraabdominal infections , SMART and urinary tract infections
Funding
This study was supported by the:
  • Merck
    • Principle Award Recipient: Not Applicable
© 2020 Not applicable
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2020-01-24
2025-01-23
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References

  1. Logan LK, Weinstein RA. The epidemiology of carbapenem-resistant Enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis 2017; 215:S28–S36 [View Article]
     [Google Scholar]
  2. van Duin D, Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae . Virulence 2017; 8:460–469 [View Article]
     [Google Scholar]
  3. Lob SH, Biedenbach DJ, Badal RE, Kazmierczak KM, Sahm DF. Antimicrobial resistance and resistance mechanisms of Enterobacteriaceae in ICU and non-ICU wards in Europe and North America: smart 2011-2013. J Glob Antimicrob Resist 2015; 3:190–197 [View Article]
     [Google Scholar]
  4. Lob SH, Hoban DJ, Young K, Motyl MR, Sahm DF. Activity of imipenem/relebactam against Gram-negative bacilli from global ICU and non-ICU wards: smart 2015-2016. J Glob Antimicrob Resist 2018; 15:12–19 [View Article]
     [Google Scholar]
  5. Karlowsky JA, Lob SH, Kazmierczak KM, Hawser SP, Magnet S et al. In vitro activity of imipenem/relebactam against Gram-negative ESKAPE pathogens isolated in 17 European countries: 2015 SMART surveillance programme. J Antimicrob Chemother 2018; 73:1872–1879 [View Article]
     [Google Scholar]
  6. Lapuebla A, Abdallah M, Olafisoye O, Cortes C, Urban C et al. Activity of imipenem with Relebactam against Gram-negative pathogens from New York City. Antimicrob Agents Chemother 2015; 59:5029–5031 [View Article]
     [Google Scholar]
  7. Livermore DM, Warner M, Mushtaq S. Activity of MK-7655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa . J Antimicrob Chemother 2013; 68:2286–2290 [View Article]
     [Google Scholar]
  8. Karlowsky JA, Lob SH, Young K, Motyl MR, Sahm DF. Activity of imipenem/relebactam against Pseudomonas aeruginosa with antimicrobial-resistant phenotypes from seven global regions: smart 2015-2016. J Glob Antimicrob Resist 2018; 15:140–147 [View Article]
     [Google Scholar]
  9. Haidar G, Clancy CJ, Chen L, Samanta P, Shields RK et al. Identifying spectra of activity and therapeutic niches for ceftazidime-avibactam and imipenem-relebactam against carbapenem-resistant Enterobacteriaceae . Antimicrob Agents Chemother 2017; 61:e00642–17 [View Article]
     [Google Scholar]
  10. Papp-Wallace KM, Barnes MD, Alsop J, Taracila MA, Bethel CR et al. Relebactam is a potent inhibitor of the KPC-2 β-lactamase and restores imipenem susceptibility in KPC-producing Enterobacteriaceae . Antimicrob Agents Chemother 2018; 62:e00174–18 [View Article]
     [Google Scholar]
  11. Livermore DM, Jamrozy D, Mushtaq S, Nichols WW, Young K et al. Ampc β-lactamase induction by avibactam and relebactam. J Antimicrob Chemother 2017; 72:3342–3348 [View Article]
     [Google Scholar]
  12. ClinicalTrials.gov National Institutes of Health. U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/results?term=imipenem-relebactam&Search=Search January 20, 2019
  13. Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing, 28th ed. West Valley Road: Wayne, PA; 2018
     [Google Scholar]
  14. Neuwirth C, Siébor E, Duez JM, Péchinot A, Kazmierczak A. Imipenem resistance in clinical isolates of Proteus mirabilis associated with alterations in penicillin-binding proteins. J Antimicrob Chemother 1995; 36:335–342 [View Article]
     [Google Scholar]
  15. Clinical and Laboratory Standards Institute Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, 11th ed. Wayne, PA: CLSI, 940 West Valley Road; 2018
     [Google Scholar]
  16. Matuschek E, Åhman J, Webster C, Kahlmeter G. Antimicrobial susceptibility testing of colistin - evaluation of seven commercial MIC products against standard broth microdilution for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. Clin Microbiol Infect 2018; 24:865–870 [View Article]
     [Google Scholar]
  17. European Committee on Antimicrobial Susceptibility Testing Breakpoint tables for interpretation of MICs and zone diameters, version 8.1, 2018 (valid from 15 May 2018)..
  18. Nichols WW, de Jonge BLM, Kazmierczak KM, Karlowsky JA, Sahm DF. In vitro susceptibility of global surveillance isolates of Pseudomonas aeruginosa to ceftazidime-avibactam (INFORM 2012 to 2014). Antimicrob Agents Chemother 2016; 60:4743–4749 [View Article]
     [Google Scholar]
  19. Livermore DM. Interplay of impermeability and chromosomal beta-lactamase activity in imipenem-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 1992; 36:2046–2048 [View Article]
     [Google Scholar]
  20. Young K, Painter RE, Raghoobar SL, Hairston NN, Racine F et al. In vitro studies evaluating the activity of imipenem in combination with relebactam against Pseudomonas aeruginosa . BMC Microbiol 2019; 19:150 [View Article]
     [Google Scholar]
  21. Sader HS, Castanheira M, Duncan LR, Flamm RK. 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. Diagn Microbiol Infect Dis 2018; 92:69–74 [View Article]
     [Google Scholar]
  22. Kazmierczak KM, Biedenbach DJ, Hackel M, Rabine S, De Jonge BLM et al. Global dissemination of bla KPC into bacterial species beyond Klebsiella pneumoniae and in vitro susceptibility to ceftazidime-avibactam and aztreonam-avibactam. Antimicrob Agents Chemother 2016; 60:4490–4500 [View Article]
     [Google Scholar]
  23. Kazmierczak KM, Rabine S, Hackel M, McLaughlin RE, Biedenbach DJ et al. Multiyear, multinational survey of the incidence and global distribution of metallo-β-lactamase-producing Enterobacteriaceae and Pseudomonas aeruginosa . Antimicrob Agents Chemother 2016; 60:1067–1078 [View Article]
     [Google Scholar]
  24. Flamm RK, Sader HS, Farrell DJ, Jones RN. Ceftazidime-avibactam and comparator agents tested against urinary tract isolates from a global surveillance program (2011). Diagn Microbiol Infect Dis 2014; 80:233–238 [View Article]
     [Google Scholar]
  25. Pfaller MA, Bassetti M, Duncan LR, Castanheira M. Ceftolozane/tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing urinary tract and intraabdominal infections in Europe: report from an antimicrobial surveillance programme (2012-15). J Antimicrob Chemother 2017; 72:1386–1395 [View Article]
     [Google Scholar]
  26. U.S. Food and Drug administration RecarbrioTM. Highlights of prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212819s000lbl.pdf August 30, 2019
/content/journal/jmm/10.1099/jmm.0.001142
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In vitro activity of imipenem-relebactam against resistant phenotypes of Enterobacteriaceae and Pseudomonas aeruginosa isolated from intraabdominal and urinary tract infection samples – SMART Surveillance Europe 2015–2017
J. Med. Microbiol. 69, 207 (2020); https://doi.org/10.1099/jmm.0.001142
/content/journal/jmm/10.1099/jmm.0.001142
/content/journal/jmm/10.1099/jmm.0.001142
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