You are viewing a javascript disabled version of the site. Please enable Javascript for this site to function properly.
Go to headerGo to navigationGo to searchGo to contentsGo to footer
In content section. Select this link to jump to navigation

The global response to the threat of antimicrobial resistance and the important role of vaccines

Abstract

Antimicrobial resistance (AMR) has emerged as a significant threat to global health security and threatens the achievements of modern medicine. Research and successful development of new antibiotics, especially those with novel mechanisms of action vital to combat resistance, has slowed dramatically since the 1980s. Surveillance for AMR is highly variable globally with significant limitations in many countries impeding the ability to fully characterize the problem. Global efforts to control tuberculosis, malaria and HIV are facing increasing difficulties from the emergence of resistance. Similarly, bacteria causing some of the most common infections in communities or in hospitals such as Escherichia coli and Klebsiella pneumoniae have shown high levels of resistance to third generation cephalosporins requiring treatment with expensive carbapenems as last-resort. Additionally, Streptococcus pneumoniae has shown reduced susceptibility to penicillin in many regions, exceeding 50% in some settings. The cost in lives from AMR over the next 40 years could go as high as 10 million per year with the cost to economic development as high as $3 trillion per year if current trends continue. In addition to ensuring appropriate use of antibiotics and development of novel classes with new or enhanced mechanisms of action, many plans for the global response call for new vaccines as integral to the fight against AMR. Vaccines and antibiotics should be used together to produce synergistic gains in public health, and ultimately, vaccines will extend the clinical utility of antibiotics. The decrease in cases of invasive pneumococcal disease and decrease in prescriptions for antibiotics in some settings resulting from the introduction of broad access to, and utilization of conjugate vaccines for Streptococcus pneumoniae exemplifies the synergy that can be achieved in the fight against AMR.

References

[1] 

United Nations General Assembly - Seventieth session, Agenda item 125. A/RES/70/183 Global health and foreign policy: strengthening the management of international health crises http://www.un.org/en/ga/search/view_doc.asp?symbol=A/RES/70/183.

[2] 

SIXTY-SEVENTH WORLD HEALTH ASSEMBLY WHA67.25; Agenda item 16.5 24 May 2014, Antimicrobial resistance. http://apps.who.int/gb/ebwha/pdf_files/WHA67/A67_R25-en.pdf.

[3] 

World Health Organization, document WHA64/2011/REC/1. United Nations. Millennium Development Goals indicators. United Nations; 2008 http://mdgs.un.org/unsd/mdg/Host.aspx?Content= indicators/officiallist.htm.

[4] 

Bate R., , Jensen P., , Hess K., , Mooney L., and Milligan J., Substandard and falsified anti-tuberculosis drugs: A preliminary field analysis, Int J Tuberc Lung Dis. 17(3) (2013), 308-311. doi: 10.5588/ ijtld.12.0355.

[5] 

Roberts R.R. et al., Hospital and Societal Costs of Antimicrobial-Resistant Infections in a Chicago Teaching Hospital: Implications for Antibiotic Stewardship, CID 49 (2009), 1175-1184.

[6] 

WHO AMR Report, 2014 - World Health Organization (2014a) Antimicrobial resistance: global report on surveillance 2014. Available from http://www.who.int/drugresistance/documents/surveillancereport/en/.

[7] 

The Pew Charitable Trusts, Infectious Diseases Society of America, Pharmaceutical Research and Manufacturers of America, ``Reviving the Pipeline of Life-Saving Antibiotics: Exploring Solutions to Spur Innovation,'' conference proceedings, Sept. 22, 2011, Washington, http://www.idsociety.org/uploadedFiles/IDSA/Policy_and_Advocacy/Current_Topics_and_Issues/Advancing_Product_Research_and_Development/Bad_Bugs_No_Drugs/Press_Releases/Conference%20Proceedings_FINAL_4.11.12.pdf.

[8] 

Shlaes D.M., , Sahm D., , Opiela C., and Spellberg B., The FDA reboot of antibiotic development, Antimicrob Agents Chemother 57(10) (2013), 4605-4507. doi: 10.1128/AAC.01277-13. Epub 2013 Jul 29.

[9] 

Silver, ``Challenges of Antibacterial Discovery,'' 71-109; Tommasi et al., ``SKAPEing the Labyrinth of Antibacterial Discovery,'' 529-542.

[10] 

Despite Growing Crisis, Few New Antibiotics Are in Pipeline. Clin Infect Dis. Published online April 18, 2013. http://cid.oxfordjournals.org.proxy1.athensams.net/content/early/2013/04/16/cid.cit152.full.

[11] 

WHO AMR Report, 2014 - World Health Organization (2014a) Antimicrobial resistance: global report on surveillance 2014. http://www.who.int/drugresistance/documents/surveillancereport/en/.

[12] 

World Health Organization. Global Tuberculosis Report 2015. WHO/HTM/TB/2015.22.

[13] 

Udwadia Z.F., , Amale R.A., , Ajbani K.K., and Rodrigues C., Totally drug-resistant tuberculosis in India, Clin Infect Dis. 54(4) (2012), 579-581. doi: 10.1093/cid/cir889. Epub 2011 Dec 21.

[14] 

World Health Organization. World Malaria Report 2015 http://www.who.int/malaria/publications/world_malaria_report_2015/en.

[15] 

WHO HIV drug resistance report. Geneva, World Health Organization (WHO), 2012. (http:// apps.who.int/iris/bitstream/10665/75183/1/9789241503938_eng.pdf).

[16] 

Wittkop L., , Gunthard H.F., , de Wolf F., , Dunn D., , Cozzi-Lepri A., , de Luca A. et al., Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study, Lancet Infect Dis. 11(5) (2011), 363-371. doi: 10.1016/S1473-3099(11)70032-9.

[17] 

Hamers R.L., , Schuurman R., , Sigaloff K.C., , Wallis C.L., , Kityo C., , Siwale M. et al., PharmAccess African Studies to Evaluate Resistance (PASER) Investigators. Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: A multicentre cohort study, Lancet Infect Dis. 12(4) (2012), 307-317. doi: 10.1016/S1473-3099(11)70255-9.

[18] 

WHO AMR Report, 2014 - World Health Organization (2014a) Antimicrobial resistance: global report on surveillance 2014. http://www.who.int/drugresistance/documents/surveillancereport/en/.

[19] 

WHO AMR Report, 2014 - World Health Organization (2014a) Antimicrobial resistance: global report on surveillance 2014. http://www.who.int/drugresistance/documents/surveillancereport/en/.

[20] 

WHO AMR Report, 2014 - World Health Organization (2014a) Antimicrobial resistance: global report on surveillance 2014. http://www.who.int/drugresistance/documents/surveillancereport/en/.

[21] 

Tackling antibiotic resistance from a food safety perspective in Europe. http://www.euro.who.int/ __data/assets/pdf_file/0005/136454/e94889.pdf.

[22] 

European Commission. EU research on antimicrobial resistance: EU projects 2007-2010. Brussels: UC; 2011. Available from: http://ec.europa.eu/research/health/infectious-diseases/antimicrobial-drug-resistance/pdf/eu-research-on-antimicrobial-resistance_en.pdf.

[23] 

Pumart P., , Phodha T., , Thamlikitkul V., , Riewpaiboon A., , Prakongsai P., and Limwattananon S., Health and economic impacts of antimicrobial resistance in Thailand, J Health Systems Res 6 (2012), 352-360.

[24] 

Centers for Disease Control and Prevention. Antibiotic Resistance Threats, 2013.

[25] 

Roberts R.R., , Hota B., , Ahmad I. et al., Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship, Clin Infect Dis. 49(8) (2009), 1175-1184.

[26] 

http://www.tufts.edu/med/apua/consumers/personal_home_5_1451036133.pdf (accessed 8-5-2013).

[27] 

Taylor J., , Hafner M., , Yerushalmi E., , Smith R., , Bellasio J., , Vardavas R., , Bienkowska-Gibbs T., and Rubin J., Estimating the economic costs of antimicrobial resistance, Model and Results, 2014. www.rand.org/t/rr911.

[28] 

Roberts R.R. et al. Hospital and Societal Costs of Antimicrobial-Resistant Infections in a Chicago Teaching Hospital: Implications for Antibiotic Stewardship, Clinical Infectious Diseases 49 (2009), 1175-1184.

[29] 

Tackling drug-resistant infections globally: Final report and recommendations the review on antimicrobial resistance chaired by Jim O'Neill.

[30] 

Centers for Disease Control and Prevention: Antibiotic Resistance Threats in the United States, 2013. http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf.

[31] 

Liu Y.-Y., , Wang Y., , Walsh T.R. et al., Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study, The Lancet Infectious Disease 16(2) (2016), 161-168.

[32] 

Centers for Disease Control and Prevention. Antibiotic Resistance Threats, 2013.

[33] 

Earnshaw S., , Monnet D.L., , Duncan B., , O'Toole J., , Ekdahl K., and Goossens H., European Antibiotic Awareness Day Technical Advisory Committee, European Antibiotic Awareness Day Collaborative Group European antibiotic awareness day 2008: The first Europe-wide public information campaign on prudent antibiotic use; methods and survey activities in participating countries, Eurosurveillance 14 (2009), 418-425.

[34] 

Ghazaryan V.A., , Pyshnik G., , Spasojevic T. et al., Antibiotic use in Eastern Europe: A cross-national database study in coordination with the WHO Regional Office for Europe, Lancet Infect Dis. 14 (2014), 381-387.

[35] 

Broughton E.I., , Chitashvili T., , Hill K., , Cherkezishvili E., and Shengelia N., Commentary: Antibiotic use worldwide, Lancet Infect Dis. 14 (2014), 1179.

[36] 

Sumpradit N., , Chongtrakul P., , Anuwong K., , Pumtong S., , Kongsomboon K. et al., Antibiotics Smart Use: A workable model for promoting the rational use of medicines in Thailand, Bulletin of the World Health Organization 90 (2012), 905-913. doi: 10.2471/BLT.12.105445.

[37] 

Bhavnani D., , Phatinawin L., , Chantra S., , Olsen S.J., and Simmerman J.M., The influence of rapid influenza diagnostic testing on antibiotic prescribing patterns in rural Thailand, Int J Infect Dis. 11 (2007), 355-359. doi: 10.1016/j.ijid.2006.09.009. PMID: 17324602.

[38] 

Suttajit S., , Wagner A.K., , Tantipidoke R., and Ross-Degnan D., , Patterns Sitthi-amorn C., Appropriateness, and predictors of antimicrobial prescribing for adults with upper respiratory infections in urban slum communities of Bangkok, Southeast Asian J Trop Med Public Health 36 (2005), 489-497. PMID: 15916061.

[39] 

Sumpradit N., , Chongtrakul P., , Anuwong K., , Pumtong S., , Kongsomboon K. et al., Antibiotics Smart Use: A workable model for promoting the rational use of medicines in Thailand, Bulletin of the World Health Organization 90 (2012), 905-913. doi: 10.2471/BLT.12.105445.

[40] 

Treebupachatsakul P., , Tiengrim S., and Thamlikitkul V., Upper respiratory tract Infection in Thai adults: prevalence and prediction of bacterial causes, and effectiveness of using clinical practice guidelines, J Med Assoc Thai 89 (2006), 1178-1186. PMID: 17048427.

[41] 

Sumpradit N., , Chongtrakul P., , Anuwong K., , Pumtong S., , Kongsomboon K. et al., Antibiotics Smart Use: A workable model for promoting the rational use of medicines in Thailand, Bulletin of the World Health Organization 90 (2012), 905-913. doi: 10.2471/BLT.12.105445.

[42] 

Suttajit S., , Wagner A.K., , Tantipidoke R., , Ross-Degnan D., and Patterns S.A.C., Appropriateness, and predictors of antimicrobial prescribing for adults with upper respiratory infections in urban slum communities of Bangkok, Southeast Asian J Trop Med Public Health 36 (2005), 489-497. PMID: 15916061.

[43] 

Panpanich R., , Siviroj P., , Chansung K., , Sanchaisuriya P., , Laohasiriwong L., , Tasaniyom S. et al., Antibiotics prescription rates for upper respiratory tract infections in Thai National Health Insurance System, J Health Sci 12 (2003), 522-529.

[44] 

Thamlikitkul V., Antibiotic dispensing by drug store personnel in Bangkok, Thailand, J Antimicrob Chemother 21 (1998), 125-131. doi: 10.1093/jac/21.1.125. PMID: 3356619.

[45] 

Apisarnthanarak A., and Mundy L.M., Comparison of methods of measuring pharmacy sales of antibiotics without prescriptions in Pratumthani, Infect Control Hosp Epidemiol 30 (2009), 1130-1132.

[46] 

Sumpradit N., , Chongtrakul P., , Anuwong K., , Pumtong S., , Kongsomboon K. et al., Antibiotics Smart Use: A workable model for promoting the rational use of medicines in Thailand, Bulletin of the World Health Organization 90 (2012), 905-913. doi: 10.2471/BLT.12.105445.

[47] 

Treebupachatsakul P., , Tiengrim S., and Thamlikitkul V., Upper respiratory tract Infection in Thai adults: prevalence and prediction of bacterial causes, and effectiveness of using clinical practice guidelines, J Med Assoc Thai 89 (2006), 1178-1186. PMID: 17048427.

[48] 

Tackling drug-resistant infections globally: Final report and recommendations the review on antimicrobial resistance chaired by Jim O'Neill.

[49] 

Centers for Disease Control and Prevention. Antibiotic Resistance Threats, 2013.

[50] 

ibid.

[51] 

Gupta R., , Cegielski J.P., , Espinal M.A., , Henkens M., and Kim J.Y., , Lambregts-van Weezenbeek C.S.B., , Lee J.W., , Raviglione M.C., , Suarez P.G., and Varaine F.. Increasing transparency in partnerships for health - introducing the Green Light Committee, Tropical Medicine and International Health 7(11) (2002), 970-976.

[52] 

Cegielski J.P., , Kurbatova E., , van der Walt M., , Brand J., , Ershova J. et al., Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance, Clinical Infectious Diseases 62(4) (2016), 418-430.

[53] 

Mölstad S., , Cars O., and Strama S.J., A Swedish working model for containment of antibiotic resistance, Eurosurveillance 13 (2008), 22-25. PMID: 19021951.

[54] 

Gonzales R., , Corbett K.K., , Wong S., , Glazner J.E., , Deas E., , Leeman-Castillo B. et al., "Get Smart Colorado": impact of a mass media campaign to improve community antibiotic use, Med Care 46 (2008), 597-605. doi: 10.1097/MLR.0b013e3181653d2e. PMID: 18520314.

[55] 

Huttner B., , Goossens H., , Verheij T., and Harbarth S., Characteristics and outcomes of public campaigns aimed at improving the use of antibiotics in outpatients in high-income countries, Lancet 10 (2010), 17-31. doi: 10.1016/S1473-3099(09)70305-6.

[56] 

Sabuncu E., , David J., , Bernède-Bauduin C., , Pépin S., , Leroy M., , Boëlle P.Y. et al., Significant reduction of antibiotic use in the community after a nationwide campaign in France, 2002-2007, PLoS Med 6 (2009), e1000084. doi: 10.1371/journal.pmed.1000084. PMID: 19492093.

[57] 

Sumpradit N., , Chongtrakul P., , Anuwong K., , Pumtong S., , Kongsomboon K. et al., Antibiotics Smart Use: A workable model for promoting the rational use of medicines in Thailand, Bulletin of the World Health Organization 90 (2012), 905-913. doi: 10.2471/BLT.12.105445.

[58] 

https://www.gov.uk/government/news/prime-minister-warns-of-global-threat-of-antibiotic-resistance.

[59] 

http://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf.

[60] 

http://www.whitehouse.gov/the-press-office/2014/09/18/fact-sheet-obama-administration-takes-actions-combat-antibiotic-resistan.

[61] 

http://www.phe.gov/about/BARDA/Pages/default.aspx.

[62] 

http://www.who.int/phi/implementation/1_infobrief_innovative_medicines_initiative_ND4BB_models_of_collaboration.pdf.

[63] 

http://amr-review.org/industry-declaration.

[64] 

http://amr-review.org/industry-declaration.

[65] 

p://www.bmg.bund.de/fileadmin/dateien/Downloads/G/G7-Ges.Minister_2015/G7_Health_Ministers_Declaration_AMR_and_EBOLA.pdf.

[66] 

http://www.mofa.go.jp/files/000160273.pdf.

[67] 

http://apps.who.int/gb/ebwha/pdf_files/WHA68/A68_R7-en.pdf.

[68] 

Palmu A.A. et al., Lancet Infect. Dis. 14 (2014), 205-212.

[69] 

Hoffman S.J. et al., Strategies for achieving global collective action on antimicrobial resistance, Bull World Health Organ 93 (2015), 867-876. doi: 10.2471/BLT.15.153171.

[70] 

Wilby K.J., and Werry D., A review of the effect of immunization programs on antimicrobial utilization, Vaccine 30(46) (2012), 650914.

[71] 

http://www.niaid.nih.gov/topics/pneumococal/pages/pneumococcaldisease.aspx.

[72] 

Lexau C.A. et al., Changing Epidemiology of Invasive Pneumococcal Disease among Older Adults in the Era of Pediatric Pneumococcal Conjugate Vaccine, JAMA 294(16) (2005), 2043-2051. doi: 10.1001/jama.294.16.2043.

[73] 

Advisory Committee on Immunization Practices, Preventing pneumococcal disease among infants and young children. Recommendations of the advisory committee on immunization practices (ACIP), MMWR Recomm Rep 49(RR-9) (2000), 1-35.

[74] 

Poehling K.A., , Talbot T.R., , Griffin M.R., , Craig A.S., , Whitney C.G., , Zell E., , Lexau C.A., , Thomas A.R., , Harrison L.H., , Reingold A.L. et al., Invasive pneumococcal disease among infants before and after introduction of pneumococcal conjugate vaccine, JAMA 295(14) (2006), 1668-1674; PMID: 16609088; http://dx.doi.org/10.1001/jama.295.14.1668.

[75] 

Nuorti J.P., and Whitney C.G., Centers for Disease Control and Prevention (CDC). Prevention of pneumococcal disease among infants and children - use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine - recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR Recomm Rep 59(RR-11) (2010), 1-18; PMID: 21150868.

[76] 

Zhou F. et al., Pediatrics 121 (2008), 253-260.

[77] 

www.thelancet.com/infection Vol 8 December 2008.

[78] 

Whitney C. et al., Seminars in Pediatric Infectious Diseases 15(2) (2004), 86-93.

[79] 

Lancet Infectious Diseases 1 (2001), 85-91.

[80] 

N Engl J Med 354 (2006), 1455.

[81] 

Hampton L.M. et al., J. Infect. Dis. 205 (2012), 401-411.

[82] 

Nature 512 (2014), 14-15.

[83] 

Tomczyk S. et al., Prevention of Antibiotic-Nonsusceptible Invasive Pneumococcal Disease With the 13-Valent Pneumococcal Conjugate Vaccine, Clinical Infectious Diseases 62(9) (2016), 1119-1125.

[84] 

World Health Organization. 2005. Haemophilus influenzae type B (HiB). WHO fact sheet no. 294, December 2005. http://www/who.int/mediacentre/factsheets/fs294/en/index.html.

[85] 

Tristram S., , Jacobs M.R., and Appelbaum P.C., Antimicrobial Resistance in Haemophilus influenzae. CLINICAL MICROBIOLOGY REVIEWS, Apr. 2007, pp. 368-389.

[86] 

WHO Global Immunization Data available at: http://www.who.int/immunization/monitoring_surveillance/Global_Immunization_Data.pdf?ua=1.

[87] 

Giufrèa M. et al., Ten years of Hib vaccination in Italy: Prevalence of non-encapsulated Haemophilus influenzae among invasive isolates and the possible impact on antibiotic resistance, Vaccine 29 (2011), 3857-3862.

[88] 

García-Cobos S., , Campos J., , Cercenado E., , Romän F., , Läzaro E., , Pérez-Vázquez M. et al., Antibiotic resistance in Haemophilus influenzae decreased, except for beta-lactamase-negative amoxicillin-resistant isolates, in parallel with community antibiotic consumption in Spain from 1997 to 2007, Antimicrob Agents Chemother 52(8) (2008), 2760-2766.

[89] 

ibid.

[90] 

Heilmann K.P., , Rice C.L., , Miller A.L., , Miller N.J., , Beekmann S.E., , Pfaller M.A. et al., Decreasing prevalence of beta-lactamase production among respiratory tract isolates of Haemophilus influenzae in the United States, Antimicrob Agents Chemother 49 (2005), 2561-2564.

[91] 

Jansen W.T., , Verel A., , Beitsma M., , Verhoef J., and Milatovic D., Longitudinal European surveillance study of antibiotic resistance of Haemophilus influenzae, J Antimicrob Chemother 58 (2006), 873-877.

[92] 

Kwong J.C. et al., The Effect of Universal Influenza Immunization on Antibiotic Prescriptions: An Ecological Study, Clinical Infectious Diseases 49 (2009), 750-756.

[93] 

European Commission (2011). Action Plan against the risising threats from antimicrobial resistance COM (2011) 748. Available at: http://ec.europa.eu/dgs/health_consumer/docs/communication_amr_2011_748_en.pdf and ECDC (2011). Report from the Transatlantic Taskforce on Antimicrobial Resistance. Recommendations for future collaboration between the US and EU. Available at: http://ecdc.europa.eu/en/activities/diseaseprogrammes/tatfar/documents/210911_tatfar_report.pdf.

[94] 

OMS, Guide pratique sur la prévention des infections nosocomiales, Chapitre X. 2008. WHO/CDS/ CSR/EPH/2002.12.

[95] 

WHO AMR Report, 2014 - World Health Organization (2014a) Antimicrobial resistance: global report on surveillance 2014. http://www.who.int/drugresistance/documents/surveillancereport/en/.

[96] 

AMR_report_Web_slide_set. WHO AMR Report, 2014 - World Health Organization (2014a) Antimicrobial resistance: global report on surveillance 2014.

[97] 

Commission. EU research on antimicrobial resistance: EU projects 2007-2010. Brussels: UC; 2011. Available from: http://ec.europa.eu/research/health/infectious-diseases/antimicrobial-drug-resistance/pdf/eu-research-on-antimicrobial-resistance_en.pdf [accessed 13 September 2012].

[98] 

Thamlikitkul V., , Riewpaiboon A., , Prakongsai P., and Limwattananon S., Health and economic impacts of antimicrobial resistance in Thailand, J Health Systems Res 6 (2012), 352-360.

[99] 

Centers for Disease Control and Prevention. Antibiotic Resistance Threats, 2013.