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Why I Believe a Vaccine Against ExPEC is a Possible Antimicrobial Stewardship Tool to Reduce Resistance

Lilian Abbo Headshot
Lilian Abbo, MD, FIDSA

Associate Chief Medical Officer in Infectious Diseases
Jackson Health System
Professor of Infectious Diseases
Department of Medicine & Miami Transplant Institute
University of Miami Miller School of Medicine
Miami, Florida

Lilian Abbo, MD, FIDSA: consultant/advisor/speaker: Ferring.

View ClinicalThoughts from this Author

Released: October 6, 2022

Key Takeaways

  • Vaccine resistance occurs less commonly than antimicrobial resistance, and thus a vaccine against ExPEC could be an important part of antimicrobial stewardship and fighting the development of antimicrobial resistance.
  • Vaccines targeting ExPEC are an active area of research and are being evaluated in phase I, II, and III clinical trials.

Extraintestinal pathogenic Escherichia coli (ExPEC), especially strains that are multidrug resistant, can cause invasive infections and are associated with significant morbidity and mortality. In this commentary, I will discuss progress in the development of vaccines for ExPEC, as well as the potential impact these vaccines will have on antimicrobial stewardship.

Ongoing Clinical Trials
Vaccines for ExPEC are an active area of research and development, with several candidates under evaluation in phase I, II, and III clinical trials for prophylaxis and/or therapeutic use. We currently do not have clinical outcome data from the trials.

At present, the most promising vaccine targets are O polysaccharides, outer membrane vesicles, and adhesin proteins (eg, FimH). Some of the vaccines being studied are oral, and some are parenteral; some for prophylaxis, some for treatment, or both.

Each clinical trial is studying a different patient population, with some enrolling people older than 60 years of age who have a history of recurrent urinary tract infections and others enrolling younger people. The prophylactic trials are measuring differences in the rate of colonization with ExPEC, whereas trials evaluating therapeutics are evaluating the extent of ExPEC eradication. The immunogenicity of the vaccines also is being measured because they need to trigger an antibody response but not cause harm. We want to minimize adverse events so that the vaccines can be as safe and tolerable as possible.

Role of Vaccination in Antimicrobial Stewardship
Antimicrobial stewardship is the critical process of selecting the correct drug for each patient and giving it at the right time for the right duration. Good stewardship remains critical in preventing multidrug-resistant organisms, including ExPEC, and making sure we stop the chain of transmission between household members, patients in hospitals, and members of our community.

Our experience with diseases such as Streptococcus pneumoniae, Haemophilus influenzae, and even influenza show that vaccines have the power to decrease the number of infections and antibiotics prescribed (whether appropriately or inappropriately). Using fewer antibiotics means the development of antimicrobial resistance is less common. Preventive measures such as vaccination are strong antimicrobial stewardship tools that need more development so the attention is not focused only on the development of new antibiotics.

Challenges in Vaccine Development
If ExPEC vaccines would be so helpful, why has one not been developed yet? Part of the answer lies in the various vaccine targets (eg, ExPEC virulence factors) to choose from and the need to identify those only expressed by pathogenic strains and not commensal strains. These vaccines also need to generate a robust immune response in mucosal tissue to provide protection against common infections caused by ExPEC, such as urinary tract infections and pyelonephritis.

Another challenge is that these vaccines will not likely be the type given to people shortly after they are born or when they are children. Development needs to focus on a target niche of patients who will benefit the most, which is difficult when so much time and money are invested in researching and developing these drugs. But we need to determine the most appropriate use of the vaccines and steward their use so that the right people will be able to receive and benefit from them.

The final challenge in designing and developing these vaccines is the possibility that ExPEC strains could outsmart them by mutating and developing new serotypes that are resistant to the vaccine-induced immunity, as has been seen with COVID-19. We must ensure that vaccines will remain effective even with selective pressure.

Fortunately, vaccine resistance is less likely than antibiotic resistance because more mutations are required. This means vaccines should remain an important part of antimicrobial stewardship and fighting the development of antimicrobial resistance.

Your Thoughts?
Do you think ExPEC vaccines could be an important tool to combat antimicrobial resistance? Join the discussion by posting a comment.

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