Zusammenfassung
Antibiotikaresistenz (AR) ist ein natürliches Phänomen, das durch die Exposition von Bakterien gegenüber antibakteriellen Substanzen entsteht. Das intestinale Mikrobiom spielt bei der Entstehung und Weitergabe von AR eine zentrale Rolle. In seiner physiologischen Zusammensetzung verfügt das Darmmikrobiom über mehrere Mechanismen, die zu einer sogenannten Kolonisierungsresistenz gegenüber potenziell pathogenen und oft auch multiresistenten Bakterien beitragen. Eine Exposition gegenüber Breitspektrumantibiotika kann die Mechanismen stören, sodass es zu einer vereinfachten Ansiedelung der Erreger kommen kann. Besteht im Anschluss weiterhin ein antibiotischer Selektionsdruck, werden das Wachstum multiresistenter Bakterien und deren Dominanz innerhalb der Darmmikrobiota gefördert. In dieser Situation wird die Entstehung invasiver Infektionen besonders begünstigt. Antibiotic Stewardship, der Einsatz von Schmalspektrumantibiotika sowie die Gabe von Substanzen, die das intestinale Mikrobiom vor Antibiotikaexposition schützen, können diesen Prozessen vorbeugen. Mehrere Interventionen wie die Anwendung von Probiotika, oralen Antibiotika und fäkalen Mikrobiomtransfers sind potenzielle Strategien zur Dekolonisierung von Patienten mit multiresistenten Bakterien, jedoch hat sich bisher keine Intervention als dauerhaft wirksam erwiesen.
Abstract
Antimicrobial resistance (AR) is a natural phenomenon resulting from the exposure of bacteria to antibacterial substances. The intestinal microbiome plays a central role in the development and transmission of AR. In its physiological state, the intestinal microbiome has several mechanisms that contribute to what is referred to as colonization resistance against potentially pathogenic and often multiresistant bacteria. Exposure to broad-spectrum antibiotics can disrupt those mechanisms, facilitating colonization with these pathogens. The persistence of antibiotic selection pressure favors growth of multiresistant bacteria and their dominance within the intestinal microbiota. Under these circumstances, the risk of the development of invasive infections increases. Antibiotic stewardship programs, the use of narrow-spectrum antibiotics, and the administration of substances that protect the intestinal microbiome from antibiotic exposure can prevent these processes. Several interventions such as the administration of probiotics, oral antibiotics, and fecal microbiome transfers are potential strategies for decolonizing patients with multidrug resistant bacteria; to date, however, no intervention has been proven to be consistently effective.
Literatur
Murray CJ, Ikuta KS, Sharara F et al (2022) Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 399(10325):629–655. https://doi.org/10.1016/S0140-6736(21)02724-0
Lawley TD, Walker AW (2013) Intestinal colonization resistance. Immunology 138(1):1–11. https://doi.org/10.1111/J.1365-2567.2012.03616.X
Almeida A, Mitchell AL, Boland M et al (2019) A new genomic blueprint of the human gut microbiota. Nature 568(7753):499–504. https://doi.org/10.1038/S41586-019-0965-1
D’Costa VM, McGrann KM, Hughes DW, Wright GD (2006) Sampling the antibiotic resistome. Science 311(5759):374–377. https://doi.org/10.1126/SCIENCE.1120800/SUPPL_FILE/D_COSTA.SOM.PDF
Casals-Pascual C, Vergara A, Vila J (2018) Intestinal microbiota and antibiotic resistance: Perspectives and solutions. Hum Microbiome J 9:11–15. https://doi.org/10.1016/J.HUMIC.2018.05.002
Huttner B, Haustein T, Uçkay I et al (2013) Decolonization of intestinal carriage of extended-spectrum β‑lactamase-producing Enterobacteriaceae with oral colistin and neomycin: a randomized, double-blind, placebo-controlled trial. j Antimicrob Chemother 68(10):2375–2382. https://doi.org/10.1093/JAC/DKT174
Machuca I, Gutiérrez-Gutiérrez B, Pérez Cortés S et al (2016) Oral decontamination with aminoglycosides is associated with lower risk of mortality and infections in high-risk patients colonized with colistin-resistant, KPC-producing Klebsiella pneumoniae. J Antimicrob Chemother 71(11):3242–3249. https://doi.org/10.1093/JAC/DKW272
Le Guern R, Stabler S, Gosset P et al (2021) Colonization resistance against multi-drug-resistant bacteria: a narrative review. J Hosp Infect 118:48–58. https://doi.org/10.1016/J.JHIN.2021.09.001
Sorbara MT, Dubin K, Littmann ER et al (2019) Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification. J Exp Med 216(1):84–98. https://doi.org/10.1084/JEM.20181639
Osbelt L, Wende M, Almási É et al (2021) Klebsiella oxytoca causes colonization resistance against multidrug-resistant K. pneumoniae in the gut via cooperative carbohydrate competition. Cell Host Microbe 29(11):1663–1679.e7. https://doi.org/10.1016/J.CHOM.2021.09.003
Eberl C, Weiss AS, Jochum LM et al (2021) E. coli enhance colonization resistance against Salmonella Typhimurium by competing for galactitol, a context-dependent limiting carbon source. Cell Host Microbe 29(11):1680–1692.e7. https://doi.org/10.1016/J.CHOM.2021.09.004
Tamma PD, Holmes A, Ashley ED (2014) Antimicrobial stewardship: another focus for patient safety? Curr Opin Infect Dis 27(4):348–355. https://doi.org/10.1097/QCO.0000000000000077
Spellberg B (2018) The maturing antibiotic mantra: “Shorter is still better”. J Hosp Med 13(5):361–362. https://doi.org/10.12788/JHM.2904
Guery B, Menichetti F, Anttila VJ et al (2018) Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis 18(3):296–307. https://doi.org/10.1016/S1473-3099(17)30751-X
Nerandzic MM, Mullane K, Miller MA, Babakhani F, Donskey CJ (2012) Reduced acquisition and overgrowth of vancomycin-resistant enterococci and Candida species in patients treated with fidaxomicin versus vancomycin for Clostridium difficile infection. Clin Infect Dis 55(Suppl 2):S121. https://doi.org/10.1093/CID/CIS440
Kokai-Kun JF, Roberts T, Coughlin O et al (2019) Use of ribaxamase (SYN-004), a β-lactamase, to prevent Clostridium difficile infection in β‑lactam-treated patients: a double-blind, phase 2b, randomised placebo-controlled trial. Lancet Infect Dis 19(5):487–496. https://doi.org/10.1016/S1473-3099(18)30731-X
Vehreschild MJGT, Ducher A, Louie T et al (2022) An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones. J Antimicrob Chemother 77(4):1155–1165. https://doi.org/10.1093/JAC/DKAB474
Saidel-Odes L, Polachek H, Peled N et al (2012) A randomized, double-blind, placebo-controlled trial of selective digestive decontamination using oral Gentamicin and oral polymyxin E for eradication of carbapenem-resistant Klebsiella pneumoniae carriage. Infect Control Hosp Epidemiol 33(1):14–19. https://doi.org/10.1086/663206
Tacconelli E, Mazzaferri F, de Smet AM et al (2019) ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers. Clin Microbiol Infect 25(7):807–817. https://doi.org/10.1016/J.CMI.2019.01.005
Gibson GR, Hutkins R, Sanders ME et al (2017) Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol 14(8):491–502. https://doi.org/10.1038/nrgastro.2017.75
Tannock GW, Tiong IS, Priest P et al (2011) Testing probiotic strain Escherichia coli Nissle 1917 (Mutaflor) for its ability to reduce carriage of multidrug-resistant E. coli by elderly residents in long-term care facilities. J Med Microbiol 60(3):366–370. https://doi.org/10.1099/JMM.0.025874-0/CITE/REFWORKS
Doron S, Hibberd PL, Goldin B, Thorpe C, McDermott L, Snydman DR (2015) Effect of lactobacillus rhamnosus GG administration on vancomycin-resistant enterococcus colonization in adults with comorbidities. Antimicrob Agents Chemother 59(8):4593–4599. https://doi.org/10.1128/AAC.00300-15
Yoon YK, Suh JW, Kang EJ, Kim JY (2019) Efficacy and safety of fecal microbiota transplantation for decolonization of intestinal multidrug-resistant microorganism carriage: beyond Clostridioides difficile infection. Ann Med 51(7–8):379–389. https://doi.org/10.1080/07853890.2019.1662477
Huttner BD, de Lastours V, Wassenberg M et al (2019) A 5‑day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial. Clin Microbiol Infect 25(7):830–838. https://doi.org/10.1016/J.CMI.2018.12.009
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M.J. Vehreschild gibt folgende Interessenskonflikte an: Förderungen für Forschungsvorhaben – MSD Sharp&Dohme GmbH, Biontec, Biologische Heilmittel HEEL GmbH, Takeda California, Roche Molecular Systems; Beratertätigkeit – Merck/MSD, MaaT, Gilead Sciences, Ferring, Astellas Pharma, EUMEDICA, SocraTec R&D GmbH, Farmak International Holding, Immunic AG; Vorträge – Merck/MSD, Ferring, 3M, Astellas Pharma, Roche, Pfizer, Janssen, Institut Mérieux, Forum für Medizinische Fortbildung GmbH, LÄK Hessen, Akademie für Infektionsmedizin, Falk Foundation, DiaLogService, CED Service, Limbach Gruppe SE, EUMEDICA, Helios Kliniken. T.M. Appel gibt an, dass kein Interessenkonflikt besteht.
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Appel, T.M., Vehreschild, M.J. Rolle des Darmmikrobioms bei der Entstehung und Weitergabe von Antibiotikaresistenzen. Innere Medizin 63, 1043–1050 (2022). https://doi.org/10.1007/s00108-022-01400-1
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DOI: https://doi.org/10.1007/s00108-022-01400-1
Schlüsselwörter
- Horizontaler Gentransfer
- Breitspektrumantibiotika
- Schmalspektrumantibiotika
- Resistenz gegen mehrere Antibiotika
- Antibiotic Stewardship