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The role of vaccines in combatting antimicrobial resistance. ​

Literature Information ​

DOI10.1038/s41579-020-00506-3
PMID33542518
JournalNature reviews. Microbiology
Impact Factor103.3
JCR QuartileQ1
Publication Year2021
Times Cited190
KeywordsVaccines, Antimicrobial Resistance, Bacterial Infections, Prevention Strategies
Literature TypeJournal Article, Review
ISSN1740-1526
Pages287-302
Issue19(5)
AuthorsFrancesca Micoli, Fabio Bagnoli, Rino Rappuoli, Davide Serruto

TL;DR ​

This review highlights the critical role of vaccines in combating antimicrobial resistance (AMR), a growing global threat due to the rise of drug-resistant pathogens that cause significant morbidity and mortality. By reducing infectious disease cases and consequently lowering antibiotic use, vaccines could be pivotal in preventing the spread of AMR, while the paper also addresses current vaccine development efforts and the challenges faced in creating effective solutions against resistant bacterial infections.

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Vaccines · Antimicrobial Resistance · Bacterial Infections · Prevention Strategies

Abstract ​

The use of antibiotics has enabled the successful treatment of bacterial infections, saving the lives and improving the health of many patients worldwide. However, the emergence and spread of antimicrobial resistance (AMR) has been highlighted as a global threat by different health organizations, and pathogens resistant to antimicrobials cause substantial morbidity and death. As resistance to multiple drugs increases, novel and effective therapies as well as prevention strategies are needed. In this Review, we discuss evidence that vaccines can have a major role in fighting AMR. Vaccines are used prophylactically, decreasing the number of infectious disease cases, and thus antibiotic use and the emergence and spread of AMR. We also describe the current state of development of vaccines against resistant bacterial pathogens that cause a substantial disease burden both in high-income countries and in low- and medium-income countries, discuss possible obstacles that hinder progress in vaccine development and speculate on the impact of next-generation vaccines against bacterial infectious diseases on AMR.

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Primary Questions Addressed ​

  1. What specific types of vaccines have shown the most promise in reducing the incidence of antimicrobial resistance?
  2. How do the mechanisms of action for vaccines differ from those of traditional antibiotics in combating resistant infections?
  3. What are the challenges faced in the global distribution and administration of vaccines aimed at preventing AMR in low-income countries?
  4. In what ways can public health policies be adjusted to promote vaccine use as a strategy against antimicrobial resistance?
  5. How does the development of next-generation vaccines compare to the traditional vaccine approaches in terms of efficacy against resistant bacterial pathogens?

Key Findings ​

Research Background and Objectives ​

The increasing prevalence of antimicrobial resistance (AMR) poses a significant threat to global health, making it crucial to explore alternative strategies to combat infections. This study focuses on the role of vaccines in addressing AMR, particularly against bacterial pathogens that have developed resistance to conventional antibiotics.

Main Methods/Materials/Experimental Design ​

The research employs a comprehensive review of existing literature on the mechanisms of AMR, the pathogens involved, and the potential for vaccine development. The study categorizes AMR pathogens and their characteristics, assesses the current state of vaccine research, and identifies gaps in existing approaches.

Mermaid diagram

Key Results and Findings ​

  1. Mechanisms of Resistance: The study identifies three primary mechanisms by which bacteria acquire resistance:

    • Prevention of antibiotic access to targets (e.g., efflux pumps).
    • Modification of antibiotic targets through mutations.
    • Inactivation of antibiotics via enzymatic degradation.

  2. Pathogen Overview: The review highlights several key AMR pathogens, including:

    • Clostridioides difficile: Increasing incidence linked to antibiotic therapy.
    • Escherichia coli: High rates of fluoroquinolone resistance.
    • Staphylococcus aureus: Major cause of skin and soft tissue infections, with a high prevalence of methicillin-resistant strains (MRSA).
    • Neisseria gonorrhoeae: Rapid development of resistance to multiple antibiotic classes.
    • Pseudomonas aeruginosa: Notable for its metabolic adaptability and resistance to numerous antibiotics.
    • Klebsiella pneumoniae: Emergence of carbapenem-resistant strains.
    • Salmonella species: Significant public health concern due to multi-drug resistance.
    • Shigella: High rates of resistance impacting treatment options.

  3. Vaccine Development Status: The study presents a detailed table summarizing the status of various vaccine candidates in development for AMR pathogens, indicating phases of clinical trials and types of vaccines being researched.

Main Conclusions/Significance/Innovativeness ​

The study concludes that vaccines represent a promising strategy to mitigate AMR by preventing infections and reducing the need for antibiotics. Vaccination could decrease the incidence of infections caused by resistant pathogens, thereby limiting the selective pressure that drives resistance. The authors advocate for increased investment in vaccine research and development to address the urgent challenge of AMR.

Research Limitations and Future Directions ​

  • Limitations: The study acknowledges the variability in vaccine development stages and the need for robust clinical trial data to validate vaccine efficacy.
  • Future Directions: Recommendations include:
    • Expanding research into vaccine platforms that target multiple pathogens.
    • Enhancing global collaboration to share data and resources.
    • Focusing on public health strategies that integrate vaccination with antibiotic stewardship programs to effectively combat AMR.

Overall, the research underscores the critical role of vaccines in the fight against AMR, highlighting both the challenges and opportunities in this evolving field.

References ​

  1. Action and resistance mechanisms of antibiotics: A guide for clinicians. - Garima Kapoor;Saurabh Saigal;Ashok Elongavan - Journal of anaesthesiology, clinical pharmacology (2017)
  2. Correlation between antimicrobial consumption and antimicrobial resistance of Pseudomonas aeruginosa in a hospital setting: a 10-year study. - S Mladenovic-Antic;B Kocic;R Velickovic-Radovanovic;M Dinic;J Petrovic;G Randjelovic;R Mitic - Journal of clinical pharmacy and therapeutics (2016)
  3. Measuring and mapping the global burden of antimicrobial resistance. - Simon I Hay;Puja C Rao;Christiane Dolecek;Nicholas P J Day;Andy Stergachis;Alan D Lopez;Christopher J L Murray - BMC medicine (2018)
  4. Antibiotic resistance: a rundown of a global crisis. - Bilal Aslam;Wei Wang;Muhammad Imran Arshad;Mohsin Khurshid;Saima Muzammil;Muhammad Hidayat Rasool;Muhammad Atif Nisar;Ruman Farooq Alvi;Muhammad Aamir Aslam;Muhammad Usman Qamar;Muhammad Khalid Farooq Salamat;Zulqarnain Baloch - Infection and drug resistance (2018)
  5. Vaccines: An achievement of civilization, a human right, our health insurance for the future. - Rino Rappuoli;Angela Santoni;Alberto Mantovani - The Journal of experimental medicine (2019)
  6. Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance. - David A Kennedy;Andrew F Read - Proceedings of the National Academy of Sciences of the United States of America (2018)
  7. Technologies to address antimicrobial resistance. - Stephen J Baker;David J Payne;Rino Rappuoli;Ennio De Gregorio - Proceedings of the National Academy of Sciences of the United States of America (2018)
  8. Impact of existing vaccines in reducing antibiotic resistance: Primary and secondary effects. - Keith P Klugman;Steven Black - Proceedings of the National Academy of Sciences of the United States of America (2018)
  9. The role of vaccines in preventing bacterial antimicrobial resistance. - Kathrin U Jansen;Charles Knirsch;Annaliesa S Anderson - Nature medicine (2018)
  10. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. - Alessandro Cassini;Liselotte Diaz Högberg;Diamantis Plachouras;Annalisa Quattrocchi;Ana Hoxha;Gunnar Skov Simonsen;Mélanie Colomb-Cotinat;Mirjam E Kretzschmar;Brecht Devleesschauwer;Michele Cecchini;Driss Ait Ouakrim;Tiago Cravo Oliveira;Marc J Struelens;Carl Suetens;Dominique L Monnet; - The Lancet. Infectious diseases (2019)

Literatures Citing This Work ​

  1. Prophylaxis and Treatment against Klebsiella pneumoniae: Current Insights on This Emerging Anti-Microbial Resistant Global Threat. - Vanessa Arato;Maria Michelina Raso;Gianmarco Gasperini;Francesco Berlanda Scorza;Francesca Micoli - International journal of molecular sciences (2021)
  2. Fighting Antibiotic Resistance in Hospital-Acquired Infections: Current State and Emerging Technologies in Disease Prevention, Diagnostics and Therapy. - Ekaterina Avershina;Valeria Shapovalova;German Shipulin - Frontiers in microbiology (2021)
  3. Bacterial Outer Membrane Vesicles as a Versatile Tool in Vaccine Research and the Fight against Antimicrobial Resistance. - Zhuang Zhu;Fabio Antenucci;Kasper Rømer Villumsen;Anders Miki Bojesen - mBio (2021)
  4. Antimicrobial Peptides: A Potent Alternative to Antibiotics. - Mariam Rima;Mohamad Rima;Ziad Fajloun;Jean-Marc Sabatier;Burkhard Bechinger;Thierry Naas - Antibiotics (Basel, Switzerland) (2021)
  5. Nanovaccines against Animal Pathogens: The Latest Findings. - Carmen Teresa Celis-Giraldo;Julio López-Abán;Antonio Muro;Manuel Alfonso Patarroyo;Raúl Manzano-Román - Vaccines (2021)
  6. Survey among Italian experts on existing vaccines' role in limiting antibiotic resistance. - Federico Marchetti;Rosa Prato;Pierluigi Viale - Human vaccines & immunotherapeutics (2021)
  7. Multivalent poultry vaccine development using Protein Glycan Coupling Technology. - Marta Mauri;Thippeswamy H Sannasiddappa;Prerna Vohra;Ricardo Corona-Torres;Alexander A Smith;Cosmin Chintoan-Uta;Abi Bremner;Vanessa S Terra;Sherif Abouelhadid;Mark P Stevens;Andrew J Grant;Jon Cuccui;Brendan W Wren; - Microbial cell factories (2021)
  8. Towards A Novel Multi-Epitopes Chimeric Vaccine for Simulating Strong Immune Responses and Protection against Morganella morganii. - Asad Ullah;Sajjad Ahmad;Saba Ismail;Zobia Afsheen;Muhammad Khurram;Muhammad Tahir Ul Qamar;Naif AlSuhaymi;Mahdi H Alsugoor;Khaled S Allemailem - International journal of environmental research and public health (2021)
  9. Manifesto on the Value of Adult Immunization: "We Know, We Intend, We Advocate". - Raffaele Antonelli-Incalzi;Francesco Blasi;Michele Conversano;Giovanni Gabutti;Sandro Giuffrida;Stefania Maggi;Cinzia Marano;Alessandro Rossi;Marta Vicentini - Vaccines (2021)
  10. The role of vaccines in combating antimicrobial resistance (AMR) bacteria. - Saad Alghamdi - Saudi journal of biological sciences (2021)

... (180 more literatures)

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