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Activity Title: Collaborating with the Innate Immune System to Treat Multidrug-Resistant Superbugs

Release Date: November 23, 2020

Estimated Time to Complete Activity: 70 minutes

Statement of Need:

Before the patient has even seen a doctor, their infection is already being treated by multiple antimicrobials - namely the cellular and molecular components of the innate immune system. Conventional screening paradigms in antibiotic discovery are based on MIC/MBC testing in conventional bacteriologic media, and similar tests on patient isolates are used to guide physician management. Antibiotics can synergize with endogenous antimicrobial peptides to effect bacterial killing. These studies will reveal how standard MIC testing can be misleading, overlooking potent antibiotic activities that are recognized only the context of the normal innate immune system.  In this new discovery and treatment framework, drugs used in medicine for other indications (e.g. cholesterol-lowering or antiplatelet drugs), or antibiotics otherwise deemed ineffective, can be "repositioned" for treatment of multi-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) or carbapenemase-resistant strains of Gram-negative pathogens including Acinetobacter baumanniiKlebsiella pneumoniae and Pseudomonas aeruginosa

Faculty:
Professor Victor Nizet
Vice Chair for Basic Research in the Department of Pediatrics and Chief of the Division of Host-Microbe Systems & Therapeutics at the University of California, San Diego (UCSD), School of Medicine as well as Professor at UCSD Skaggs School of Pharmacy & Pharmaceutical Sciences.

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Contact Information

If you have questions about this CME activity, please contact The International Society for Infectious Diseases at info@isid.org.

For technical support issues, please contact Multilearning at support@multilearning.com

Upon completion of this module, participants should be able to:

  • Explain how standard MIC testing can be misleading, overlooking potent antibiotic activities that are recognized only the context of the normal innate immune system
  • Discuss how in this new screening paradigms and treatment framework, drugs used in medicine for other indications (e.g. cholesterol-lowering or antiplatelet drugs), or antibiotics otherwise deemed ineffective, can be "repositioned" for treatment of multi-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) or carbapenemase-resistant strains of Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. 

The target audience for this module is physicians, nurses, public health officials, researchers, immunization officers, and other health professionals.

Berti A, Rose W, Nizet V, Sakoulas G. Antibiotics and Innate Immunity: A Cooperative Effort Toward the Successful Treatment of Infections. Open Forum Infect Dis. 2020 Jul 20;7(8):ofaa302. doi: 10.1093/ofid/ofaa302. PMID: 32818143; PMCID: PMC7423293.

https://pubmed.ncbi.nlm.nih.gov/32818143/

 

Turvey SE, Broide DH. Innate immunity. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S24-32. doi: 10.1016/j.jaci.2009.07.016. Epub 2009 Nov 24. PMID: 19932920; PMCID: PMC2832725.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832725/

 

Ulloa E, Uchiyama S, Gillespie R, Nizet V, Sakoulas G. Ticagrelor Increases Platelet-Mediated Staphylococcus aureus Killing Resulting in Clearance of Bacteremia. J Infect Dis. 2021 May 9:jiab146. doi: 10.1093/infdis/jiab146. 

https://pubmed.ncbi.nlm.nih.gov/33966075/

 

Munguia J, Nizet V. Pharmacological Targeting of the Host-Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs. Trends Pharmacol Sci. 2017 May;38(5):473-488. doi: 10.1016/j.tips.2017.02.003. Epub 2017 Mar 8 https://pubmed.ncbi.nlm.nih.gov/28283200/

 

 

Sun J, Uchiyama S, Olson J, et al. Repurposed drugs block toxin-driven platelet clearance by the hepatic Ashwell-Morell receptor to clear Staphylococcus aureus bacteremia. Sci Transl Med. 2021 Mar 24;13(586):eabd6737. doi: 10.1126/scitranslmed.abd6737. https://pubmed.ncbi.nlm.nih.gov/33762439/

 
 

Disclosure Policy

In accordance with the EACCME Standards for Commercial Support, the International Society for Infectious Diseases (ISID) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any commercial interest. ISID  resolves all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all our educational programs. Furthermore, ISID seeks to verify that all scientific research referred to, reported, or used in a CME/CE activity conforms to the generally accepted standards of experimental design, data collection, and analysis. ISID is committed to providing learners with high-quality CME/CE activities that promote improvements in health care and not those of a commercial interest.

Activity Staff Disclosures:

The planners, reviewers, editors, staff, or other members at the International Society for Infectious Diseases who control content have no relevant financial relationships to disclose. 

ISID Knowledge Exchange and E-Learning Platform Organizing Committee members are listed here along with Committee members’ disclosure forms. 

Faculty Disclosure:

ProfessorVictor Nizet 
Grants/Research Support: CARB-X grants with Cellics Therapeutics and VaxCyte, Inc.
Stock Shareholder: Stock Options: Clarmetyx SAB and Cellics SAB

Moderator Disclosures:

Professor Marc Mendelson and Dr. Constance Georgina Khaendi Walyaro  have no actual or potential conflict of interest in relation to this program/presentation.

Disclosure of Unlabeled Use

The International Society for Infectious Diseases  requires CME faculty (speakers) to disclose when products or procedures being discussed are off label, unlabeled, experimental, and/or investigational, and any limitations on the information that is presented, such as data that are preliminary, or that represent ongoing research, interim analyses, and/or unsupported opinion. Faculty in this activity may discuss information about pharmaceutical agents that is outside of US Food and Drug Administration approved labeling. This information is intended solely for continuing medical education and is not intended to promote off-label use of these medications. ISID does not recommend the use of any agent outside of the labeled indications. If you have questions, contact the Medical Affairs Department of the manufacturer for the most recent prescribing information.

Disclaimer

The International Society for Infectious Diseases presents this information for educational purposes only. The content is provided solely by faculty who have been selected because of recognized expertise in their field. Participants have the professional responsibility to ensure that products are prescribed and used appropriately on the basis of their own clinical judgment and accepted standards of care. The International Society for Infectious Diseases, and the former commercial supporter assume no liability for the information herein.

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Collaborating with the Innate Immune System to Treat Multidrug-Resistant Superbugs

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