Download PDF
Dtsch Med Wochenschr 2024; 149(19): 1133-1142
DOI: 10.1055/a-2258-1412
Dossier

Multiresistente Bakterien – epidemiologische Trends und neue Behandlungsoptionen

Multi-resistant bacteria – epidemiological trends and new treatment options
Winfried V. Kern
› Further Information
Also available at
    Permissions and Reprints

Multiresistente Bakterien wie Escherichia coli und Klebsiella pneumoniae sind weltweit eine wachsende Bedrohung. Besonders besorgniserregend ist die Verbreitung von Carbapenemase-produzierenden Stämmen. Neue Antibiotika und Kombinationstherapien bieten Behandlungsmöglichkeiten, aber die Entwicklung resistenter Erreger bleibt eine große Herausforderung.

Abstract

Multi-resistant bacteria such as Escherichia coli and Klebsiella pneumoniae are a growing threat worldwide. The spread of Carbapenemase-producing strains is particularly worrying. New antibiotics and combination therapies offer treatment options, but the development of resistant pathogens remains a major challenge.

Kernaussagen

  • Bakterielle Resistenz- und Multiresistenz-Phänomene sind nicht neu. Mehrere Mechanismen sind beteiligt. Problematisch ist neben der erhöhten Prävalenz von Mikroorganismen mit natürlicher Resistenz gegenüber bestimmten Substanzklassen (zum Beispiel Stenotrophomonas maltophilia oder Enterococcus faecium) vor allem der Erwerb neuer Resistenzen.

  • Die wichtigsten epidemiologischen Entwicklungen sind der Rückgang von MRSA, der relative Anstieg der Vancomycin-Resistenz unter den Enterokokken und der Anstieg Carbapenem-resistenter gramnegativer Bakterien, vor allem bei Klebsiellen und Acinetobacter baumannii. Zugleich ist die Fluorchinolon-Resistenz bei vielen gramnegativen Bakterienspezies zurückgegangen.

  • Bei Carbapenemasen werden verschiedene Typen unterschieden. Dies hat Implikationen für die Entwicklung wirksamer Beta-Laktamase-Inhibitoren. Eine wichtige Unterscheidung ist die zwischen Metallo-Beta-Laktamasen (bisher kein Inhibitor als Arzneimittel verfügbar) und Serin-Beta-Laktamasen (mehrere Inhibitoren verfügbar).

  • In Deutschland scheinen bei Klebsiellen Carbapenemasen vom Typ OXA-48 zu dominieren; sie sind hemmbar durch Avibactam (in der Kombination mit Ceftazidim verfügbar).

  • Die derzeit wichtigsten neuen, bereits zugelassenen Substanzen mit Aktivität gegen Carbapenem-resistente gramnegative Bakterien sind Ceftazidim/Avibactam und Cefiderocol.

Schlüsselwörter

multiresistente Bakterien - Epidemiologie - Carbapenemase - Antibiotikaresistenz - Behandlungsoptionen

Keywords

multidrug-resistant bacteria - epidemiology - carbapenemase - antibiotic resistance - treatment options


Publication History

Article published online:
09 September 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 European Antimicrobial Resistance Collaborators. The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis. Lancet Public Health 2022; 7: e897-e913
    CrossrefPubMedSearch in Google Scholar
  • 2 Coque TM, Cantón R, Pérez-Cobas AE. et al. Antimicrobial resistance in the Global Health Network: known unknowns and challenges for efficient responses in the 21st century. Microorganisms 2023; 11: 1050
    CrossrefPubMedSearch in Google Scholar
  • 3 Kazmierczak KM, Karlowsky JA, de Jonge BLM. et al. 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
    CrossrefPubMedSearch in Google Scholar
  • 4 Estabrook M, Muyldermans A, Sahm D. et al. Epidemiology of resistance determinants identified in meropenem-nonsusceptible Enterobacterales collected as part of a global surveillance study, 2018 to 2019. Antimicrob Agents Chemother 2023; 67: e0140622
    CrossrefPubMedSearch in Google Scholar
  • 5 Butler MS, Gigante V, Sati H. et al. An analysis of the clinical pipeline of treatments for drug-resistant bacterial infections: despite progress, more action is needed. Antimicrob Agents Chemother 2022; 66: e0199121
    CrossrefPubMedSearch in Google Scholar
  • 6 Jacobs LMC, Consol P, Chen Y. Drug discovery in the field of β-Lactams: an academic perspective. Antibiotics 2024; 13: 59
    CrossrefPubMedSearch in Google Scholar
  • 7 Darby EM, Trampari E, Siasat P. et al. Molecular mechanisms of antibiotic resistance revisited. Nat Rev Microbiol 2023; 21: 280-295
    CrossrefPubMedSearch in Google Scholar
  • 8 Huang L, Wu C, Gao H. et al. Bacterial multidrug efflux pumps at the frontline of antimicrobial resistance: an overview. Antibiotics 2022; 11: 520
    CrossrefPubMedSearch in Google Scholar
  • 9 Pfennigwerth N, Schauer J. Bericht des Nationalen Referenzzentrums für gramnegative Krankenhauserreger – Zeitraum 1. Januar 2021 bis 31. Dezember 2021. Epid Bull 2022; 19: 3-9
    CrossrefPubMedSearch in Google Scholar
  • 10 Hu Y, Gao GF, Zhu B. The antibiotic resistome: gene flow in environments, animals and human beings. Front Med 2017; 11: 161-168
    CrossrefPubMedSearch in Google Scholar
  • 11 Coyte KZ, Schluter J, Foster KR. The ecology of the microbiome: networks, competition, and stability. Science 2015; 350: 663-666
    CrossrefPubMedSearch in Google Scholar
  • 12 Partridge SR, Kwong SM, Firth N. et al. Mobile genetic elements associated with antimicrobial resistance. Clin Microbiol Rev 2018; 31: e00088-17
    CrossrefPubMedSearch in Google Scholar
  • 13 Arendrup MC, Friberg N, Mares M. et al. How to interpret MICs of antifungal compounds according to the revised clinical breakpoints v. 10.0 European committee on antimicrobial susceptibility testing (EUCAST). Clin Microbiol Infect 2020; 26: 1464-1472
    CrossrefPubMedSearch in Google Scholar
  • 14 European Centre for Disease Prevention and Control. Antimicrobial resistance in the EU/EEA (EARS-Net) – Annual Epidemiological Report for 2022. Stockholm: ECDC; November 2023. Accessed July 31, 2024 at: https://www.ecdc.europa.eu/en/publications-data/surveillance-antimicrobial-resistance-europe-2022
    PubMed
  • 15 Kern WV. Multiresistente Bakterien: Antibiotikaverordnung und Reserveantibiotika. Dtsch Med Wochenschr 2018; 143: 643-650
    Thieme ConnectPubMedSearch in Google Scholar
  • 16 Holland TL, Cosgrove SE, Doernberg SB. et al. Ceftobiprole for treatment of complicated Staphylococcus aureus bacteremia. N Engl J Med 2023; 389: 1390-1401
    CrossrefPubMedSearch in Google Scholar
  • 17 Fischer MA, Bender JK, Kriebel N. et al. Eigenschaften, Häufigkeit und Verbreitung von Vancomycin-resistenten Enterokokken in Deutschland – Update. Epid Bull 2023; 28: 3-17
    CrossrefPubMedSearch in Google Scholar
  • 18 Cairns KA, Udy AA, Peel TN. et al. Therapeutics for vancomycin-resistant enterococcal bloodstream infections. Clin Microbiol Rev 2023; 36: e0005922
    CrossrefPubMedSearch in Google Scholar
  • 19 Misiakou MA, Hertz FB, Schønning K. et al. Emergence of linezolid-resistant Enterococcus faecium in a tertiary hospital in Copenhagen. Microb Genom 2023; 9: mgen001055
    CrossrefPubMedSearch in Google Scholar
  • 20 Scheetz MH, Knechtel SA, Malczynski M. et al. Increasing incidence of linezolid-intermediate or -resistant, vancomycin-resistant Enterococcus faecium strains parallels increasing linezolid consumption. Antimicrob Agents Chemother 2008; 52: 2256-2259
    CrossrefPubMedSearch in Google Scholar
  • 21 Wang M, Earley M, Chen L. et al. Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study. Lancet Infect Dis 2022; 22: 401-412
    CrossrefPubMedSearch in Google Scholar
  • 22 Wang M, Ge L, Chen L. et al. Clinical outcomes and bacterial characteristics of carbapenem-resistant Acinetobacter baumannii among patients from different global regions. Clin Infect Dis 2024; 78: 248-258
    CrossrefPubMedSearch in Google Scholar
  • 23 Hecht J, Eisfeld J, Baum JHJ. et al. An outbreak of carbapenem-resistant Acinetobacter baumannii in multiple federal states in Germany. Dtsch Ärztebl Int 2022; 119: 508-509
    CrossrefPubMedSearch in Google Scholar
  • 24 Bager P, Kähler J, Andersson M. et al. Comparison of morbidity and mortality after bloodstream infection with vancomycin-resistant versus -susceptible Enterococcus faecium: a nationwide cohort study in Denmark, 2010–2019. Emerg Microbes Infect 2024; 13: 2309969
    CrossrefPubMedSearch in Google Scholar
  • 25 Mackow NA, van Duin D. Reviewing novel treatment options for carbapenem-resistant Enterobacterales. Expert Rev Anti Infect Ther 2024; 22: 71-85
    CrossrefPubMedSearch in Google Scholar
  • 26 Shortridge D, Streit JM, Mendes R. et al. In vitro activity of cefiderocol against U.S. and European Gram-negative clinical isolates collected in 2020 as part of the SENTRY Antimicrobial Surveillance Program. Microbiol Spectr 2022; 10: e0271221
    CrossrefPubMedSearch in Google Scholar
  • 27 McLeod SM, O’Donnell JP, Narayanan N. et al. Sulbactam-durlobactam: a β-lactam/β-lactamase inhibitor combination targeting Acinetobacter baumannii. Future Microbiol 2024; 19: 563-576
    CrossrefPubMedSearch in Google Scholar
  • 28 Collins JA, Osheroff N. Gyrase and topoisomerase IV: recycling old targets for new antibacterials to combat fluoroquinolone resistance. ACS Infect Dis 2024; 10: 1097-1115
    CrossrefPubMedSearch in Google Scholar
  • 29 Theuretzbacher U, Baraldi E, Ciabuschi F. et al. Challenges and shortcomings of antibacterial discovery projects. Clin Microbiol Infect 2023; 29: 610-615
    CrossrefPubMedSearch in Google Scholar
  • 30 Vergalli J, Bodrenko IV, Masi M. et al. Porins and small-molecule translocation across the outer membrane of Gram-negative bacteria. Nat Rev Microbiol 2020; 18: 164-176
    CrossrefPubMedSearch in Google Scholar
  • 31 Gales AC, Stone G, Sahm DF. et al. Incidence of ESBLs and carbapenemases among Enterobacterales and carbapenemases in Pseudomonas aeruginosa isolates collected globally: results from ATLAS 2017–2019. J Antimicrob Chemother 2023; 78: 1606-1615
    CrossrefPubMedSearch in Google Scholar