1887

Abstract

Piperacillin/tazobactam and carbapenems are important agents for the treatment of serious Gram-negative infections in hospitalized patients. Resistance to both agents is a significant concern in clinical isolates of and ; new agents with improved activity are needed.

Publication of current, region-specific data describing the activity of newer agents such as imipenem/relebactam (IMR) against piperacillin/tazobactam-resistant and carbapenem-resistant and are needed to support their clinical use.

To describe the activity of IMR against non- (NME) and isolated from bloodstream, intra-abdominal and urinary tract infection samples by hospital laboratories in Western Europe with a focus on the activity of IMR against piperacillin/tazobactam-resistant and meropenem-resistant isolates.

From 2018 to 2020, 29 hospital laboratories in six countries in Western Europe participated in the SMART global surveillance programme and contributed 9487 NME and 1004 . isolates. MICs were determined by CLSI broth microdilution testing and interpreted by EUCAST (2021) breakpoints. β-Lactamase genes were identified in selected isolate subsets (2018–2020) and sequenced in molecularly characterized (2020).

IMR (99.4 % susceptible), amikacin (98.0 %), meropenem (97.7 %) and imipenem (97.6 %) were the most active agents against NME; 83.1 % of NME were piperacillin/tazobactam-susceptible. Relebactam increased imipenem susceptibility of NME from Italy by 8.3 %, from Portugal by 2.9 %, and from France, Germany, Spain and the UK by <1 %. In total, 96.4 % of piperacillin/tazobactam-resistant (=1601) and 73.7 % of meropenem-resistant (=152) NME were IMR-susceptible. Also, 0.4 % of NME were MBL-positive, 0.9 % OXA-48-like-positive (MBL-negative) and 1.5 % KPC-positive (MBL-negative). Amikacin (95.4 % susceptible) and IMR (94.1 %) were the most active agents against ; 81.7 % of isolates were imipenem-susceptible and 79.6 % were piperacillin/tazobactam-susceptible. Relebactam increased susceptibility to imipenem by 12.5 % overall (range by country, 4.3–17.5 %); and by 30.7 % in piperacillin/tazobactam-resistant and 24.3 % in meropenem-resistant . In total, 1.6 % of isolates were MBL-positive. Seven of eight molecularly characterized IMR-resistant isolates from 2020 were -deficient.

IMR may be a potential treatment option for bloodstream, intra-abdominal and urinary tract infections caused by NME and in Western Europe, including infections caused by piperacillin/tazobactam-resistant and meropenem-resistant isolates.

Funding
This study was supported by the:
  • Merck
    • Principle Award Recipient: NotApplicable
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/content/journal/jmm/10.1099/jmm.0.001645
2023-02-10
2024-05-01
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References

  1. Bush K, Bradford PA. Epidemiology of β-lactamase-producing pathogens. Clin Microbiol Rev 2020; 33:e00047-19 [View Article]
    [Google Scholar]
  2. Castanheira M, Deshpande LM, Mendes RE, Canton R, Sader HS et al. Variations in the occurrence of resistance phenotypes and carbapenemase genes among Enterobacteriaceae isolates in 20 Years of the SENTRY antimicrobial surveillance program. Open Forum Infect Dis 2019; 6:S23–S33 [View Article]
    [Google Scholar]
  3. de Jonge BLM, Karlowsky JA, Kazmierczak KM, Biedenbach DJ, Sahm DF et al. In Vitro susceptibility to ceftazidime-avibactam of carbapenem-nonsusceptible Enterobacteriaceae isolates collected during the INFORM global surveillance study (2012 to 2014). Antimicrob Agents Chemother 2016; 60:3163–3169 [View Article]
    [Google Scholar]
  4. Spiliopoulou I, Kazmierczak K, Stone GG. In vitro activity of ceftazidime/avibactam against isolates of carbapenem-non-susceptible Enterobacteriaceae collected during the INFORM global surveillance programme (2015-17). J Antimicrob Chemother 2020; 75:384–391 [View Article] [PubMed]
    [Google Scholar]
  5. 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]
  6. 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]
  7. 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] [PubMed]
    [Google Scholar]
  8. World Health Organization Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics; 2017 https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed
  9. Centers for Disease Control and Prevention Antibiotic resistance threats in the United States; 2019 www.cdc.gov/DrugResistance/Biggest-Threats.html
  10. Merck Sharp & Dohme LLC, Rahway, NJ, USA RECARBRIO (imipenem, cilastatin, and383 relebactam) for injection, for intravenous use, package insert; 2021 https://www.merck.com/product/usa/pi_circulars/r/recarbrio/recarbrio_pi.pdf
  11. CLSI Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—Eleventh Editionn: M07 2018
    [Google Scholar]
  12. CLSI Performance standards for antimicrobial susceptibility testing—thirty-first edition: M100; 2021
  13. EUCAST The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters; 2021 https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_11.0_Breakpoint_Tables.pdf
  14. Estabrook M, Kazmierczak KM, Wise M, Arhin FF, Stone GG et al. Molecular characterization of clinical isolates of Enterobacterales with elevated MIC values for aztreonam-avibactam from the INFORM global surveillance study, 2012-2017. J Glob Antimicrob Resist 2021; 24:316–320 [View Article]
    [Google Scholar]
  15. Bortolaia V, Kaas RS, Ruppe E, Roberts MC, Schwarz S et al. ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother 2020; 75:3491–3500 [View Article] [PubMed]
    [Google Scholar]
  16. 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]
  17. 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]
  18. Kazmierczak KM, Karlowsky JA, de Jonge BLM, Stone GG, Sahm DF. Epidemiology of carbapenem resistance determinants identified in meropenem-nonsusceptible Enterobacterales collected as part of a global surveillance program, 2012 to 2017. Antimicrob Agents Chemother 2021; 65:e0200020 [View Article]
    [Google Scholar]
  19. Kazmierczak KM, de Jonge BLM, Stone GG, Sahm DF. Longitudinal analysis of ESBL and carbapenemase carriage among Enterobacterales and Pseudomonas aeruginosa isolates collected in Europe as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme, 2013-17. J Antimicrob Chemother 2020; 75:1165–1173 [View Article]
    [Google Scholar]
  20. Cabot G, Zamorano L, Moyà B, Juan C, Navas A et al. Evolution of Pseudomonas aeruginosa antimicrobial resistance and fitness under low and high mutation rates. Antimicrob Agents Chemother 2016; 60:1767–1778 [View Article]
    [Google Scholar]
  21. 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]
  22. Kazmierczak KM, Biedenbach DJ, Hackel M, Rabine S, de Jonge BLM et al. Global dissemination of blaKPC 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. Karlowsky JA, Lob SH, Kazmierczak KM, Badal RE, Young K et al. In Vitro activity of imipenem against carbapenemase-positive Enterobacteriaceae isolates collected by the SMART global surveillance program from 2008 to 2014. J Clin Microbiol 2017; 55:1638–1649 [View Article]
    [Google Scholar]
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