An increase in erythromycin resistance in methicillin-susceptible from blood correlates with the use of macrolide/lincosamide/streptogramin antibiotics. EARS-Net Spain (2004-2020).

Achraf El Mammery, Eva Ramírez de Arellano, Javier E Cañada-García, Emilia Cercenado, Laura Villar-Gómara, Verónica Casquero-García, Silvia García-Cobos, José Antonio Lepe, Enrique Ruiz de Gopegui Bordes, Jorge Calvo-Montes, Nieves Larrosa Escartín, Rafael Cantón, María Pérez-Vázquez, Belén Aracil, Jesús Oteo-Iglesias
Author Information
  1. Achraf El Mammery: Laboratorio de Referencia e Investigación en Resistencia a Antibióticos e Infecciones Relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
  2. Eva Ramírez de Arellano: Laboratorio de Referencia e Investigación en Resistencia a Antibióticos e Infecciones Relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
  3. Javier E Cañada-García: Laboratorio de Referencia e Investigación en Resistencia a Antibióticos e Infecciones Relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
  4. Emilia Cercenado: Servicio de Microbiología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
  5. Laura Villar-Gómara: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), Madrid, Spain.
  6. Verónica Casquero-García: Laboratorio de Referencia e Investigación en Resistencia a Antibióticos e Infecciones Relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
  7. Silvia García-Cobos: Laboratorio de Referencia e Investigación en Resistencia a Antibióticos e Infecciones Relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
  8. José Antonio Lepe: CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto Salud Carlos III, Madrid, Spain.
  9. Enrique Ruiz de Gopegui Bordes: CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto Salud Carlos III, Madrid, Spain.
  10. Jorge Calvo-Montes: CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto Salud Carlos III, Madrid, Spain.
  11. Nieves Larrosa Escartín: CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto Salud Carlos III, Madrid, Spain.
  12. Rafael Cantón: CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto Salud Carlos III, Madrid, Spain.
  13. María Pérez-Vázquez: Laboratorio de Referencia e Investigación en Resistencia a Antibióticos e Infecciones Relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
  14. Belén Aracil: Laboratorio de Referencia e Investigación en Resistencia a Antibióticos e Infecciones Relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
  15. Jesús Oteo-Iglesias: Laboratorio de Referencia e Investigación en Resistencia a Antibióticos e Infecciones Relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.

Abstract

Objectives: To describe and analyse erythromycin resistance trends in blood isolates of (EARS-Net Spain, 2004-2020) and the association of these trends with the consumption of macrolide, lincosamide, and streptogramin B (MLS) antibiotics. To assess molecular changes that could be involved in erythromycin resistance trends by whole genome analysis of representative isolates.
Materials and methods: We collected antibiotic susceptibility data for all first-blood isolates in patients from 47 Spanish hospitals according to EARS-Net criteria. MLS antibiotic consumption was obtained from the Spanish Agency for Medicines and Medical Devices (2008-2020). We sequenced 137 representative isolates for core genome multilocus sequence typing, resistome and virulome analysis.
Results: For the 36,612 invasive isolates, methicillin resistance decreased from 26.4% in 2004 to 22.4% in 2020. erythromycin resistance in methicillin-susceptible (MSSA) increased from 13.6% in 2004 to 28.9% in 2020 ( < 0.001); however, it decreased from 68.7 to 61.8% ( < 0.0001) in methicillin-resistant (MRSA). Total consumption of MLS antibiotics increased from 2.72 defined daily doses per 1,000 inhabitants per day (DID) in 2014 to 3.24 DID in 2016. By WGS, the macrolide resistance genes detected were (59.8%), (46%), and (45.2%). The genes were more prevalent in MSSA (44/57, 77.2%) than in MRSA (38/80, 47.5%). Most of the genes identified in MSSA after 2013 differed from the predominant gene (17/22, 77.3%), largely because was significantly associated with MSSA after 2013 (11/29, 37.9%). All 13 isolates in this study, except one, belonged to ST398 and came from 10 hospitals and six Spanish provinces.
Conclusion: The significant increase in erythromycin resistance in blood MSSA correlated with the consumption of the MLS antibiotics in Spain. These preliminary data seem support the hypothesis that the human ST398 MSSA clade with -mediated resistance to erythromycin may be involved in this trend.

Keywords

References

  1. Euro Surveill. 2021 Nov;26(46): [PMID: 34794536]
  2. Euro Surveill. 2011 Mar 17;16(11): [PMID: 21435327]
  3. Clin Microbiol Infect. 2016 May;22(5):451-5 [PMID: 26851655]
  4. Front Microbiol. 2023 Mar 08;14:1035547 [PMID: 36970692]
  5. Eur J Clin Microbiol Infect Dis. 2018 May;37(5):911-916 [PMID: 29450768]
  6. Microorganisms. 2023 Jan 03;11(1): [PMID: 36677414]
  7. Microorganisms. 2020 Nov 05;8(11): [PMID: 33167581]
  8. Emerg Infect Dis. 2012 Sep;18(9):1515-8 [PMID: 22932671]
  9. J Antimicrob Chemother. 2021 Jul 26;76(12 Suppl 2):ii30-ii36 [PMID: 34312653]
  10. Plasmid. 2018 Sep;99:2-10 [PMID: 29807043]
  11. Antibiotics (Basel). 2021 Nov 17;10(11): [PMID: 34827344]
  12. Pediatr Infect Dis J. 2007 Jan;26(1):8-12 [PMID: 17195698]
  13. J Antimicrob Chemother. 2009 Jan;63(1):42-6 [PMID: 18952616]
  14. mBio. 2012 Feb 28;3(2): [PMID: 22375071]
  15. J Antimicrob Chemother. 2009 Jan;63(1):21-31 [PMID: 18948410]
  16. Microb Genom. 2017 Sep 4;3(10):e000131 [PMID: 29177089]
  17. Bioinformatics. 2014 Jul 15;30(14):2068-9 [PMID: 24642063]
  18. Antibiotics (Basel). 2022 Oct 08;11(10): [PMID: 36290036]
  19. J Hosp Infect. 2006 Feb;62(2):181-6 [PMID: 16290317]
  20. J Med Microbiol. 2019 Feb;68(2):148-160 [PMID: 30540247]
  21. mBio. 2012 Feb 21;3(1): [PMID: 22354957]
  22. PLoS Comput Biol. 2017 Jun 8;13(6):e1005595 [PMID: 28594827]
  23. BMC Microbiol. 2017 Mar 28;17(1):75 [PMID: 28351345]
  24. Cold Spring Harb Perspect Med. 2016 Oct 3;6(10): [PMID: 27527699]
  25. Curr Top Med Chem. 2021;21(27):2455-2473 [PMID: 33272187]
  26. J Antimicrob Chemother. 2011 Mar;66(3):664-9 [PMID: 21172788]
  27. Lancet Infect Dis. 2018 Mar;18(3):318-327 [PMID: 29276051]
  28. FEMS Microbiol Lett. 2003 Mar 28;220(2):287-93 [PMID: 12670694]
  29. J Antimicrob Chemother. 2019 Dec 1;74(12):3489-3496 [PMID: 31504589]
  30. Biology (Basel). 2021 Jul 06;10(7): [PMID: 34356479]

Word Cloud

Created with Highcharts 10.0.0resistanceisolatesMSSAerythromycinconsumptionEARS-NetMLSantibioticsantibiotictrendsbloodSpainSpanishgenesST3982004-2020macrolideinvolvedgenomeanalysisrepresentativedata47hospitalsdecreased4%20042020methicillin-susceptibleincreased139%< 08%MRSAperDID2%772013increaseObjectives:describeanalyseassociationlincosamidestreptograminBassessmolecularchangeswholeMaterialsmethods:collectedsusceptibilityfirst-bloodpatientsaccordingcriteriaobtainedAgencyMedicinesMedicalDevices2008-2020sequenced137coremultilocussequencetypingresistomevirulomeResults:36612invasivemethicillin2622Erythromycin6%28001however687610001methicillin-resistantTotal272defineddailydoses1000inhabitantsday20143242016WGSdetected5946%45prevalent44/5738/805%identifieddifferedpredominantgene17/223%largelysignificantlyassociated11/2937studyexceptonebelongedcame10sixprovincesConclusion:significantcorrelatedpreliminaryseemsupporthypothesishumanclade-mediatedmaytrendcorrelatesusemacrolide/lincosamide/streptograminStaphylococcusaureusermTmacrolides

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