Vaccination to reduce antimicrobial resistance
Authors: Amy Sarah Ginsburg, Keith P Klugman
Journal: The Lancet Global Health (2017)

Pneumonia remains the leading infectious cause of death in children worldwide, and how best to reduce this burden is worth consideration on World Pneumonia Day on November 12. Antibiotics are effective in treating bacterial pneumonia and access to appropriate antibiotics can be lifesaving. Universal provision of antibiotics to children younger than 5 years could prevent an estimated mean of 445 000 deaths per year due to community-acquired pneumonia—a 75·4% reduction across 101 countries.1Laxminarayan R Matsoso P Pant S et al.Access to effective antimicrobials: a worldwide challenge.Lancet. 2016; 387: 168-175Summary Full Text Full Text PDF PubMed Scopus (653) Google Scholar Antibiotics need to be available and accessible to effectively treat pneumonia; however, inappropriate use of antibiotics can lead to the emergence and progression of antibiotic resistance, a serious public health threat. Barriers to rational use of antibiotics for pneumonia include a scarcity of point-of-care diagnostics appropriate for use in low-resource settings to identify pneumonia in children and to determine causative pathogens. Consequently, health-care providers, particularly those in low-resource settings, are guided to overtreat respiratory symptoms and signs that are not actually pneumonia with antibiotics. At the same time, many children still have little access to treatment and pneumonia mortality is high. Consequences of inappropriate treatment with antibiotics are profound. Overuse of antibiotics is well known to lead to the development of antibiotic resistance to multiple antibiotic classes.2Low DE Pichichero ME Schaad UB Optimizing antibacterial therapy for community-acquired respiratory tract infections in children in an era of bacterial resistance.Clin Pediatr. 2004; 43: 135-151Crossref PubMed Scopus (35) Google Scholar Amoxicillin is the recommended first-line treatment for pneumonia because of widespread resistance to co-trimoxazole. Pneumococcal resistance to amoxicillin is low in African countries; however, prevalence of bacterial resistance to other antibiotics used to treat pneumonia is on the rise.3Ginsburg AS Tinkham L Riley K Kay NA Klugman KP Gill CJ Antibiotic non-susceptibility among Streptococcus pneumoniae and Haemophilus influenzae isolates identified in African cohorts: a meta-analysis of three decades of published studies.Int J Antimicrob Agents. 2013; 42: 482-491Crossref PubMed Scopus (24) Google Scholar Many common pathogens causing childhood respiratory infection, diarrhoea, and sepsis are resistant to virtually all first-generation antibiotics as a result of decades of extensive use.4Neu HC The crisis in antibiotic resistance.Science. 1992; 257: 1064-1073Crossref PubMed Scopus (2344) Google Scholar For example, 89–96% of Streptococcus pneumoniae is now resistant to co-trimoxazole in patients receiving treatment in hospitals in Malawi.5Cornick JE Harris SR Parry CM et al.Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi.J Antimicrob Chemother. 2014; 69: 368-374Crossref PubMed Scopus (14) Google Scholar Malawian surveillance studies6Makoka MH Miller WC Hoffman IF et al.Bacterial infections in Lilongwe, Malawi: aetiologyand antibiotic resistance.BMC Infect Dis. 2012; 12: 67Crossref PubMed Scopus (34) Google Scholar, 7Cornick JE Harris SR Parry CM et al.Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi.J Antimicrob Chemother. 2014; 69: 368-464Crossref PubMed Scopus (19) Google Scholar have identified multiple other antibiotics with appreciable antimicrobial resistance prevalence. As the use of oral amoxicillin increases, good antibiotic stewardship is increasingly important for amoxicillin to remain a long-term solution for treating childhood pneumonia. An additional and urgent consideration is the emergence of extended-spectrum β-lactamase and carbapenemase-producing Gram-negative pathogens as a major threat to the treatment of neonatal sepsis.1Laxminarayan R Matsoso P Pant S et al.Access to effective antimicrobials: a worldwide challenge.Lancet. 2016; 387: 168-175Summary Full Text Full Text PDF PubMed Scopus (653) Google Scholar Reducing the development of antimicrobial resistance is a key factor for consideration in the prevention and treatment of childhood pneumonia. Diminishing the need for antibiotics by decreasing the incidence and burden of pneumonia is a first step. Prevention measures, such as nutrition, safe water, hygiene and sanitation, and reduction of household air pollution, all play a role; however, vaccination to reduce antimicrobial use and resistance might be an easier alternative in most countries. Antibiotic-resistant bacteria confound management choices, produce treatment failures, and increase health-care costs. Decreasing antimicrobial resistance through a strategy of expanded vaccination has shown promising results. For example, in northern California, introduction of a pneumococcal conjugate vaccine prevented 35 antibiotic prescriptions per 100 vaccinated children, suggesting that 1·4 million antibiotic prescriptions per year are preventable with pneumococcal conjugate vaccine in the USA.8Fireman B Black SB Shinefield HR Lee J Lewis E Ray P Impact of the pneumococcal conjugate vaccine on otitis media.Pediatr Infect Dis J. 2003; 22: 10-16Crossref PubMed Scopus (380) Google Scholar Vaccination strategies targeting S pneumoniae and Haemophilus influenzae type b have reduced the overall prevalence of invasive bacterial diseases (ie, pneumonia, meningitis, and sepsis) most associated with mortality. Clear direct benefits of the pneumococcal conjugate vaccine include the reduction of invasive pneumococcal disease among vaccinated young children; indirect benefits include reduction of disease in older children and adults. Most antibiotic-resistant pneumococci are of serotypes included in the pneumococcal conjugate vaccine; therefore declines in overall incidence of invasive pneumococcal disease include that due to multiple antibiotic-resistant strains.9Kyaw MH Lynfield R Schaffner W et al.Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae.N Engl J Med. 2006; 354: 1455-1463Crossref PubMed Scopus (713) Google Scholar, 10von Gottberg A de Gouveia L Tempia S et al.Effects of vaccination on invasive pneumococcal disease in South Africa.N Engl J Med. 2014; 371: 1889-1899Crossref PubMed Scopus (258) Google Scholar In the USA, after the introduction of pneumococcal conjugate vaccine into the routine childhood immunisation programme, incidence of penicillin non-susceptible invasive pneumococcal disease decreased by 81% in children younger than 2 years.9Kyaw MH Lynfield R Schaffner W et al.Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae.N Engl J Med. 2006; 354: 1455-1463Crossref PubMed Scopus (713) Google Scholar Interruption of the transmission of antibiotic-resistant vaccine type strains also led to reductions in incidence in older children and adults. With all age groups considered together, the estimated number of cases of invasive pneumococcal disease caused by strains with reduced susceptibility to penicillin or multiple antibiotics decreased by half after introduction of the pneumococcal conjugate vaccine. Within 4 years after introduction of the pneumococcal conjugate vaccine in children younger than 2 years in South Africa, reductions of greater than 80% were recorded in incidence of invasive pneumococcal disease caused by penicillin, ceftriaxone, and multidrug non-susceptible serotypes.10von Gottberg A de Gouveia L Tempia S et al.Effects of vaccination on invasive pneumococcal disease in South Africa.N Engl J Med. 2014; 371: 1889-1899Crossref PubMed Scopus (258) Google Scholar Similarly, prevalence of invasive disease due to H influenzae type b has all but vanished after introduction of the H influenzae type b conjugate vaccine.11Adegbola RA Secka O Lahai G et al.Elimination of Haemophilus influenzae type b (Hib) disease from The Gambia after the introduction of routine immunisation with a Hib conjugate vaccine: a prospective study.Lancet. 2005; 366: 144-150Summary Full Text Full Text PDF PubMed Scopus (240) Google Scholar Pneumococcal and H influenzae type b conjugate vaccines have reduced the burden of antibiotic-resistant bacterial disease globally. However, the continued use of antibiotics induces selection of replacement antibiotic non-susceptible strains among the remaining non-vaccine serotypes.8Fireman B Black SB Shinefield HR Lee J Lewis E Ray P Impact of the pneumococcal conjugate vaccine on otitis media.Pediatr Infect Dis J. 2003; 22: 10-16Crossref PubMed Scopus (380) Google Scholar This replacement disease has the potential to erode some of the gains vaccination has shown against resistant infections. Viral vaccines, such as influenza and measles vaccines, might also reduce antibiotic use.12Marchisio P Esposito S Bianchini S et al.Efficacy of injectable trivalent virosomal-adjuvanted inactivated influenza vaccine in preventing acute otitis media in children with recurrent complicated or noncomplicated acute otitis media.Pediatr Infect Dis J. 2009; 28: 855-859Crossref PubMed Scopus (38) Google Scholar, 13Hansen NS Byberg S Hervig Jacobsen L et al.Effect of early measles vaccine on pneumococcal colonization: a randomized trial from Guinea-Bissau.PLoS One. 2017; 12: e0177547Crossref PubMed Scopus (4) Google Scholar There is an urgent need to search for vaccines or monoclonal antibodies to protect neonates from antibiotic-resistant Gram-negative infections. Widespread vaccination against both bacterial and viral respiratory pathogens should be the first line of defence against antimicrobial-resistant respiratory pathogens, and novel vaccines are required. We declare no competing interests. Vaccination to reduce antimicrobial resistanceWith the pipeline of new antibiotics running dry, vaccines are being proposed as a key part of the toolkit used to fight antimicrobial resistance.1 Amy Ginsburg and Keith Klugman (November 2017, e1176–77)2 suggest that a reduction in resistant pathogens might be easier to achieve in many countries via vaccines than through other interventions, such as improved hygiene and sanitation. However, vaccines are rarely designed to target resistant pathogens directly, with the notable exception of pneumococcal conjugate vaccines (PCVs) that protect against serotypes of Streptococcus pneumoniae displaying high resistance frequency. Full-Text PDF Open Access