Vaccination as a potential strategy to combat Antimicrobial Resistance in the elderly Wilbur Chen, MD, MS 22-23 March 2017 WHO meeting on Immunization of the Elderly
The Problem Increasing consumption of antimicrobials Widespread agricultural use of antimicrobials Rising incidence of antimicrobial resistance Limited pipeline of new antimicrobials 2
Global strategies to combat Antimicrobial Resistance gaining momentum Sep 2011: WHO-Europe European strategic action plan on antibiotic resistance Nov 2011: European Commission Action plan against the rising threats from Antimicrobial Resistance July 2014: UK-Wellcome Trust Review on Antimicrobial Resistance Sep 2014: U.S. Presidential Exec Order Combating Antibiotic-Resistant Bacteria Mar 2015: PACCARB May 2015, 68 th World Health Assembly WHO s Global Action Plan on Antimicrobial Resistance Global Antibiotic Awareness Week November 14-20, 2016 November 13-19, 2017 3
Mechanisms by which vaccines could reduce antibiotic use or antimicrobial resistance Direct and Indirect (herd immunity) reduction of infection or colonization of the vaccine organism(s) Need for antibiotics eliminated Reduction of events for appropriate or inappropriate use of a antibiotic Reduction of opportunities for resistance to emerge 4
Example Organisms with significant drug-resistance Diphtheria Tetanus Hib Pneumococcus Meningococcus Gonococcus Candida sp. M. tuberculosis Malaria HIV Enterococcus faecium Staphylococcus aureus Klebsiella pneumoniae Acinetobacter baumannii Pseudomonas aeruginosa Enterobacter sp. E. coli Clostridium difficile Typhoidal & NT Salmonella Shigella sp. 5
WHO Priority Pathogens (in need of R&D for new antibiotic treatments) Priority 1: Critical Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant, ESBL-producing Priority 2: High Enterococcus faecium, vancomycin-resistant Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant Helicobacter pylori, clarithromycin-resistant Campylobacter sp., fluoroquinolone-resistant Salmonellae, fluoroquinolone-resistant Neisseria gonorrheae, cephalosporin- and fluoroquinolone-resistant Priority 3: Medium Streptococcus pneumoniae, penicillin-non-susceptible Haemophilus influenzae, ampicillin-resistant Shigella sp., fluoroquinolone-resistant 6 WHO, 27 February 2017
Question What can vaccines do for AMR? 7
Current vaccines in routine use for older adults Pneumococcus Influenza Zoster Tetanus, diphtheria, pertussis 8
Direct Reduction Rates of Vaccine-type Pneumococcal Disease CAPiTA RCT of PCV13 vs placebo in age 65+ yo VE = 45.6% VE = 45.0% VE = 75.0% 9 Bonten et al. NEJM 2015; 372: 1114-25
Indirect Reduction Rates of Invasive Disease Active Bacterial Core (ABC) surveillance: Effect of herd immunity, from pediatric vaccination w/pcv7 49% decrease in rates of penicillin-nonsusceptible invasive pneumococcal disease in older adults 10 Kyaw et al. NEJM 2006; 354: 1455-63
Direct & Indirect Reduction Rates of Invasive Disease 11 CDC ABC Surveillance website
Reduce Antibiotic Prescriptions (1) 7-v PCV vs. MenC (Wyeth) Children in N. Calif (Kaiser-Permanente) Primary Measure - Visits for otitis media, VE =7.8% Co-primary Measure - Tympanostomy tube procedures, VE =25% Secondary Measure Reduced antibiotic prescriptions, VE =5.7% 12 Fireman et al. PIDJ 2003; 22: 10-16
Reduce Antibiotic Prescriptions (2) 10-v PCV (GSK): Children (<19m) in Finland VE 8% in outpatient prescriptions of antimicrobials 13 Palmu et al. Lancet ID 2014; 14: 205-12
Limit Duration on Antibiotics (1) 9-v PCV vs. MenC Toddlers (12-35 m) in Israel Co-primary measure: 17% reduction in Antibiotic use, days 14 Dagan et al. PIDJ 2001; 20: 951-8
Limit Duration on Antibiotics (2) Modeling Estimated proportion of pneumonia-attributable deaths potential averted through universal provision of antibiotics Estimated burden of neonatal deaths attributable to resistance Antibiotic days reduced by 47 % (11.4 million days) through universal pneumococcal vaccination 15 Laxminarayan et al. Lancet 2016; 387: 168-75
Influenza and AMR Antibiotics prescribed inappropriately in 38% influenza cases (ambulatory care setting) 1 Antibiotics prescribed inappropriately in 79% influenza cases (managed care setting) 2 Antibiotic prescriptions assoc w/ influenza decreased 64%, after implementation of universal influenza immunization program (ecological study) 3 16 1. Ciesla et al. Respir Med 2004; 98: 1093-101 2. Misurski et al. Am J Managed Care 2011; 17: 601-8 3. Kwong et al. Clin Infect Dis 2009; 49: 750-6
Other Respiratory Viruses and AMR Majority of hospitalized adults are continued on antibiotics, despite a viral RTI diagnosis and normal chest imaging 1 17 1. Shiley et al. ICHE 2011; 31: 1177-83.
Weaknesses & Knowledge Gaps No studies on LMIC populations Existing studies (which are few) provide predominantly indirect evidence or effects on AMR No studies directly measure the effect of routine vaccination on antimicrobial consumption or prescriptions in the elderly population Need studies to address these knowledge gaps 18
Desired Vaccines for the Elderly Staph aureus to directly combat AMR Clostridium difficile RSV Gram-negative org. associated with UTIs, sepsis, etc. others 19
SUMMARY What can vaccines do for AMR? Use of existing vaccines may directly and indirectly reduce disease from targeted organisms Fewer illnesses can decrease the opportunity for appropriate and inappropriate use of antimicrobials New/future vaccines to target AMR organisms Minimize opportunities for resistance to emerge 20