Zoonoses and Public Health
ORIGINAL ARTICLE
A Collaborative Initiative For the Containment of Antimicrobial Resistance in Mexico Mussaret B. Zaidi1,2, Anahi Dreser3 and Inda Marcela Figueroa4 1 2 3 4
Microbiology Research Laboratory, Hospital General O’Horan, Merida, Mexico Infectious Diseases Research Unit, Hospital Regional de Alta Especialidad de la Peninsula de Yucatan, Merida, Mexico Center for Health Systems Research, National Institute of Public Health, Cuernavaca, Mexico School of Veterinary Medicine, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Impacts
• In 2010, an unprecedented collaboration in Mexico between infectious •
•
disease specialists, public health experts, veterinarians and a wide array of stakeholders culminated in a consensus document that called for seven priority actions to improve antimicrobial use and mitigate resistance. Although the initiative failed to achieve a comprehensive national antibiotic policy, it effectuated the enforcement of regulations requiring medical prescriptions for the sale of antibiotics, the development of national guidelines for good animal husbandry practices and a ban on five antimicrobial compounds for use in food-animals. Establishing a national policy for containment of antimicrobial resistance is a major challenge for Mexico. Using a systemic approach, novel strategies should include a massive public education campaign and consensus meetings with stakeholders.
Keywords: Antimicrobial resistance; Containment strategies; Public policies; Regulation; Stewardship Correspondence: n, Dr. Mussaret B. Zaidi, Depto. De Investigacio Hospital General O’Horan, Av. Itzaes x Jacinto Canek, C.P. 97000, M erida, Yucat an, Mexico. Tel.: +52-999-9233869; Fax: +52-9999238673; E-mail: [email protected] Contents of this article were presented in an international expert meeting, ‘Reducing antimicrobial usage in agriculture and aquaculture: beyond regulatory policy’, held in Utrecht, The Netherlands, 1–3 July 2013. The Workshop was sponsored by the OECD Co-operative Research Programme on Biological Resource Management for Sustainable Agricultural Systems, the Netherlands Organization for Health Research and Development (ZonMW), and the Dutch Ministry of Economic Affairs. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its member countries.
© 2014 Blackwell Verlag GmbH, 2014, 61 (Suppl. 2), 1–6
Summary Antimicrobial resistance exacts worldwide an increasingly significant clinical and economic toll. Despite the international calls for urgent action, antimicrobial use and resistance have been low on the Mexican government’s policy agenda. In early 2010, a multidisciplinary group of experts launched a national initiative for containment of antimicrobial resistance that was endorsed by major medical, veterinary and public health institutions. The initiative called for seven priority actions including the creation of an ad hoc intersectoral advisory group, a requirement that human and veterinary antibiotics be dispensed only with prescription, and the establishment of effective surveillance systems. A consensus document was disseminated among key decision-makers at the ministries of Health and Agriculture and the legislature. The Ministry of Health (MoH) enacted a decree effective as of August 2010, which enforced the regulations that required medical prescriptions for the sale of human antibiotics. While the information disseminated by the MoH did focus on the dangers of self-medication, it failed to highlight the inherent perils of antibiotic resistance or the consequences of antibiotic use in food-animals. Following the decree, there was a surge of medical offices controlled by retail pharmacies. In the veterinary sector, voluntary guidelines were developed for good husbandry practices, including antibiotic use in food animals; five antimicrobials for use in food-animals were banned. No intersectoral advisory group or surveillance systems were established. This study describes a bottom-top approach in Mexico for the development of a national strategy to improve antibiotic use and contain antimicrobial resistance. Its experiences suggest that, in countries such as Mexico that lack strong regulatory systems and surveillance capacities, a more systemic approach is warranted. Future
1
Initiative for Improving Antibiotic use in Mexico
Received for publication October 8, 2013 doi: 10.1111/zph.12166
efforts should begin with early involvement of key stakeholders and informing policy makers, professionals and the population at large about the critical importance of antibiotic resistance.
Introduction The misuse and overuse of antibiotics in medicine and food-animal production has led to a global epidemic of antimicrobial resistance (WHO, 2012). Numerous studies show that antimicrobial resistance is associated with excess mortality, length of hospitalization and costs. In the USA, the total cost of antimicrobial resistance is estimated at $30 billion dollars annually (Maragakis et al., 2008), with 23 000 excess deaths (CDC, 2013). In Europe, MRSA and third-generation cephalosporin-resistant Escherichia coli bloodstream infections alone cause 8000 excess deaths and 62 million Euros in excess cost (de Kraker et al., 2011). Insofar as our inaction today portends disastrous consequences (Smith and Coast, 2013) that could bring about ‘the end of modern medicine as we know it’ (Chan, 2012), international organizations have called on governments for political will at the highest level to implement urgent interventions in the human and animal health sectors (WHO, 2012). Mexico has high rates of antibiotic resistance in community and hospital-acquired infections (Zaidi et al., 2008; Casta~ neda et al., 2009; Morfin-Otero et al., 2012); these are, moreover, associated with a significantly greater burden of disease (Zaidi et al., 2002, 2007). Over the last decade, antibiotic usage in the human health sector has been one of the highest in Latin America (Wirtz et al., 2010). Inappropriate medical prescription, and until recently, as a consequence of lacklustre enforcement, widespread selfmedication with antibiotics have been implicated in antibiotic misuse and overuse (Dreser et al., 2008, Homedes and Ugalde 2012). Major shortcomings in the veterinary sector include insufficient laboratory infrastructure for susceptibility testing and quality control, as well as easy access to veterinary antibiotics without prescription for food and companion animals. The few antimicrobial susceptibility studies conducted on veterinary and zoonotic foodborne pathogens all show that antimicrobial resistance is a significant problem (Zaidi et al., 2008, 2012; Orozco and Hernandez-Castro, 2009). In south-east Mexico, severe and fatal multidrug-resistant, extended-spectrum cephalosporin-resistant Salmonella Typhimurium infections in infants have been traced to swine and contaminated pork meat (Zaidi et al., 2007). Despite the evidence underscoring the need for urgent action, the problem of antibiotic resistance has been low on the Mexican government’s policy agenda. Possible reasons are the absence of clear indicators that measure the severity 2
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of the problem, the priority given to assuring the supply and access to medicines, anticipation of opposition by powerful stakeholders and insufficient understanding of policy alternatives (Dreser et al., 2012). On the other hand, medical associations, notably, the Mexican Association for Infectious Diseases and Clinical Microbiology, AMIMC) have a strong tradition of promoting antimicrobial stewardship among their members. Activities have included the following: (i) promoting the use of guidelines, (ii) establishment of hospital networks for antimicrobial resistance surveillance and (iii) training programs for quality control in clinical microbiology laboratories. Veterinary associations, in contrast, have just recently established training programs on antimicrobial resistance. Addressing the need for an effective antibiotic policy in Mexico, a group of concerned physicians, veterinarians and public health experts launched a national initiative (hereby referred to as the IIAU, ‘Initiative for Improving Antimicrobial Use’, Dreser et al., 2010), in early 2010, in which all the authors of this study participated as group leaders and coordinators. This study describes the process and outcomes involved in the development of this endeavour. We consider the challenges encountered by this initiative as well as its potentialities and draw lessons for Mexico and other countries seeking to establish national strategies for improved antimicrobial use and containment of resistance. Development of the IIAU The first meeting was held in October 2009 at the AMIMC Annual Meeting in Guadalajara. As the first formal collaborative effort between public health experts, physicians, microbiologists and veterinarians, it included participants from different academic institutions and hospitals throughout the country, as well as representatives from the Alliance for the Prudent Use of Antibiotics (APUA), the World Organization for Animal Health (OIE) and industry representatives. A contextual circumstance that facilitated AMIMC sponsorship and active collaboration of its members in the IIAU was the recent public debate regarding the perils of selfmedication with antibiotics for respiratory infections occasioned by the 2009 H1N1 influenza epidemic. This public debate opened a window of opportunity to place antibiotics at the top of the policy agenda (Dreser et al., 2012). Among veterinarians, diffusion of WHO, OIE and Codex Alimentarius recommendations (WHO, 2001; CODEX, 2005) helped develop awareness of the adverse impact of © 2014 Blackwell Verlag GmbH, 2014, 61 (Suppl. 2), 1–6
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antimicrobial use in food-producing animals and the need for changing standard practices. At the first meeting, emphasis was placed on prioritizing measures essential to a reduction in antibiotic usage and the containment of antimicrobial resistance in both human and veterinary health sectors. During the second meeting, hosted by the School of Veterinary Medicine at the National Autonomous University, a broader range of veterinarians with expertise in different food-animals was included. Group discussions focused in more detail on regulatory measures aimed at improving the licensing and dispensing of antibiotics. Other important topics of discussion were as follows: (i) the need to develop training programs for professionals and education campaigns for the general public, (ii) the establishment of surveillance systems for antimicrobial usage and resistance and (iii) a plan to develop and disseminate the IIAU among key decisionmakers. Over the next few months, the group worked on a consensus document that was ultimately endorsed by major medical and veterinary associations and institutions. The proposal, drafted as a policy brief, called for seven priority actions to improve human and veterinary antimicrobial use and mitigate resistance (Table 1). During the first trimester of 2010, the proposal was sent, in both printed and electronic forms, to head offices at the Ministries of Health and Agriculture. It was also submitted to the health and agriculture commissions of the legislature, as well to various interest groups including professional, pharmaceutical industry and pharmacy associations. Each one of us met with different policy makers for discussion and participated in press interviews. Press releases were run in major newspapers (Davila, 2010). Outcomes of the IIAU Human sector In May 2010, the Ministry of Health (MoH) enacted a decree, effective as of August of that year, which enforced the regulations for the sale of human antibiotics by medical
Initiative for Improving Antibiotic use in Mexico
prescriptions (Diario Oficial de la Federaci on, 2010). An additional requirement was that pharmacies retain and register all prescription data. Although the text of the decree incorporated many sections of the IIAU document, and indeed, called for actions directed towards counteracting self-medication with antibiotics, it simultaneously neglected other priority actions enumerated in the initiative. Likewise, while the information disseminated through mass media by the Federal Commission for the Protection against Sanitary Risks (COFEPRIS, MoH) did underscore the dangers of self-medication, it did not elaborate sufficiently on antibiotic resistance nor did it address the possible human health impact of antibiotic use in food animals. After the change in federal administration in December 2012, antibiotic prescriptions were stamped but not retained. To our knowledge, the data from retained prescriptions have not been used for antibiotic usage analysis. One unanticipated consequence of the decree was a significant increase in the number of retail pharmacies that hired general practitioners to provide cheap – or even free – medical consultations and prescriptions. Veterinary sector The IIAU initially resulted in a series of voluntary guidelines and more recently, in regulatory interventions. In 2010, the National Technical Advisory Council for Animal Health (CONASA) developed a series of documents promoting good husbandry practices, including antibiotic usage, for different food-animals (CONASA, 2010). A year later, it established a multidisciplinary ad hoc group to assess the burden of antimicrobial resistance in veterinary medicine and recommend practices for the use of anti-microbials in animals. Among the salient recommendations were the implementation of equal standards for exported and domestic animal-derived food products and strict adherence to the purchase of veterinary antibiotics exclusively through licensed professionals. In 2012, the group revised the list of antimicrobials licensed for veterinary use, placing a ban on nitrofurans, nitroimidazoles,
Table 1. Priority actions proposed in the Initiative for Improving Antimicrobial Use, Mexico, 2010 Priority action
Type of intervention
1.- Creation of a multidisciplinary advisory group for antimicrobial regulation and licensure 2a.- Enforcement of national regulations requiring human and veterinary antibiotics to be dispensed only with prescription 2b- Stricter control of the critically important antibiotics 3.- Establishment of national guidelines for the use of antibiotics for growth promotion and metaphylaxis in animals 4.- Review of licensure requirements in order to safeguard antimicrobials for human use 5.- Creation of legal mechanisms to guarantee the quality, safety and efficacy of human and veterinary antibiotics 6.- Implementation of national surveillance systems for antibiotic usage and antimicrobial resistance 7a.- Development of educational programs for pharmacists, physicians and veterinarians 7b.- Development of public education campaigns through mass media
Managerial
© 2014 Blackwell Verlag GmbH, 2014, 61 (Suppl. 2), 1–6
Regulatory Managerial Regulatory Regulatory Managerial Educational
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olaquindox, carbadox and chloramphenicol in food-animals (Diario Oficial de la Federaci on, 2012). The group is currently discussing the removal of dosage labels on the packages of veterinary anti-microbials with the intent of encouraging professional consultation prior to the administration of veterinary antibiotics. The regulation of antibiotics used for growth promotion and metaphylaxis is also under consideration (Inda Marcela Figueroa, IMF, personal communication). Despite these encouraging developments, the government has failed to implement IIAU recommendations essential for the successful containment of anti-microbial resistance, namely tighter regulations for assuring antibiotic quality and the establishment of surveillance systems for antimicrobial usage and antimicrobial resistance. In addition, comprehensive training programs for physicians, veterinarians and producers have yet to be established. Discussion and conclusions This study describes a bottom-top approach in Mexico for developing a national strategy to improve antimicrobial use and contain antimicrobial resistance. While the initiative was not entirely successful in achieving all of its ambitious goals, its experiences to date point to new, promising areas for action and remediation. Positive aspects of this initiative were the unprecedented collaboration between infectious disease specialists, public health experts and veterinarians, and the inclusion of a wide array of stakeholders that culminated in a consensus document. Consistent with a ‘One Health’ approach (Parmley et al., 2012), the initiative allowed for communication and scientific exchange between academic institutions, policy makers and industry. Significantly, it led to specific regulatory, managerial and educational interventions by the Ministries of Health and Agriculture. The initiative failed, however, to achieve a comprehensive, successfully implemented national antibiotic policy. There were major shortcomings in the policy process. The Ministries of Health and Agriculture did not establish an advisory group (Priority Action 1) drawn from relevant sectors and disciplines to address, in all its complexity, the containment of antimicrobial resistance. An informed debate in the legislature, which never took place, might well have led to other policy alternatives. Greater restrictions to antibiotic access generated opposition by interest groups and the general public. The conflict was ostensibly resolved by establishing pharmacy-controlled medical offices. Prescribing and dispensing in the same establishment represents a clear conflict of interest that leads to overprescription (Perez-Cuevas et al., 2012; Wegener, 2012). The emergence of such establishments likely explains the modest impact of the decree on overall antibiotic sales 4
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(Santa-Ana-Tellez et al., 2013). Instead, an intense public education campaign detailing the health risks of antibiotic resistance, conducted prior to the decree (as the IIAU recommended), would have been more effective in ameliorating opposition to the new measures. Surveillance systems for antimicrobial usage and resistance, which are critical for measuring the true impact of interventions, were never established. In the absence of real indicators, an accurate evaluation of the measures taken by the Mexican government is nearly impossible. The failure to analyse the valuable information contained in retained prescriptions, for example, forfeited a clear opportunity. Flaws were also present in the advocacy process. The multidisciplinary group focused most of their efforts on drafting the consensus document and its dissemination. Far less time was devoted to dialogue with decision-makers and key stakeholders or to the establishment of an effective deliberative process. At this juncture, a prudent course would likely involve alternative interventions to initiate and monitor change in key sectors. Many European countries have successfully introduced a series of regulatory measures that have led to the prohibition of growth promoters, a decrease in the overall use of antimicrobial usage and the establishment of rigorous monitoring systems for antimicrobial usage and resistance (WHO, 2003). Our experience suggests that countries such as Mexico that lack strong regulatory systems and surveillance capacities should employ a systemic approach (Midgley, 2006). Placing antimicrobial resistance once again on the public and political agendas should be the first step in the advancement of the seven priority actions of the IIAU. Early involvement of relevant stakeholders and actors will be critical. Strategies that could be used to achieve a national strategy to contain antimicrobial resistance are as follows: (i) raising awareness among policy makers and medical and veterinary professionals through varied communication channels, (ii) delivering a massive public education campaign with media involvement (Sanchez and Sivaraman, 2010), and (iii) facilitating consensus meetings with government authorities, scientists, clinicians, industry and producers (Lomas et al., 2005). The participation of experts in advocacy and social communication skills will be essential to strengthen this process. Finding novel pathways to containing antimicrobial resistance worldwide will require tenacity, collaboration and political will. The stakes for Mexico, and the world, could not be greater. Conflict of interest The authors have no conflicts of interest to declare. © 2014 Blackwell Verlag GmbH, 2014, 61 (Suppl. 2), 1–6
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References CAC (Codex Alimentarius Commission), 2005. Code of practice to minimize and contain antimicrobial resistance, (Codex Alimentarius Commission); CAC/RCP 61-2005. http://www. codexalimentarius.org/standards/list-of-standards/en Casta~ neda, E., C.I. Agudelo, M. Regueira, A. Corso, de Cunto-Brandileone M.C., A.P. Brandao, A. Maldonado, J.C. Hormazabal, I.T. Martinez, R. Llanes, J. Sanchez, J.M. Feris, G. Echaniz-Aviles, M.N. Carnalla-Barajas, M.G. Terrazas, I.H. Monroy, G. Chamorro, N. Weiler, T. Camou, G.G. Gabarrot, E. Spadola, D. Payares, J.M. Gabastou, J.L. Di Fabio, de la Hoz F., and SIREVA II Group, 2009: Laboratory-based surveillance of Streptococcus pneumoniae invasive disease in children in 10 Latin American countries: a SIREVA II Project, 2000-2005. Ped. Infect. Dis. J. 28: e265– e270. Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013: US Department of Health and Human Services, Atlanta, Georgia, Available at: http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ ar-threats-2013-508.pdf. Chan, M, 2012: Antimicrobial resistance in the European Union and the world, Copenhagen, March 14, 2012. http://www. who.int/dg/speeches/2012/amr_20120314/en/ Consejo Nacional de Sanidad Animal, 2010: Buenas practicas pecuarias. http://www.conasamexico.org.mx/conasa/ 20100825_buenas-practicas-pecuarias Davila, R. 2010: Regulaci on y promoci on para el uso adecuado de antibi oticos en Mexico. Journalmex, http://journalmex. wordpress.com/2010/03/30/regulacion-y-promocion-para-el-uso-adecuado-de-antibioticos-en-mexico/ Diario Oficial de la Federaci on, 2010: ACUERDO por el que se determinan los lineamientos a los que estara sujeta la venta y dispensaci on de antibi oticos. Secretarıa de Salud, 27 de mayo de 2010. Diario Oficial de la Federaci on, 2012: ACUERDO por el que modifica el diverso por el que se establece la clasificaci on y prescripci on de los productos farmaceuticos veterinarios por el nivel de riesgo de sus ingredientes activos. Secretarıa de Agricultura, Ganaderıa, Desarrollo Rural, Pesca y Alimentacion. 5 de marzo de 2012. Dreser, A., V.J. Wirtz, K.K. Corbett, and G. Echaniz, 2008: Antibiotic use in Mexico: review of problems and policies. Salud Publica Mex. 50(Suppl 4), S480–S487. Dreser, A., M.B. Zaidi, and M.A. Peredo, 2010 (coordinadores): Regulaci on y promoci on del uso adecuado de antibi oticos en Mexico: Propuesta de lineamientos para la acci on. http:// www.insp.mx/images/stories/Lineas/medicamentos/doc/acciones_antibioticos.pdf Dreser, A., E. Vazquez-Velez, S. Trevi~ no, and V.J. Wirtz, 2012: Regulation of antibiotic sales in Mexico: an analysis of printed media coverage and stakeholder participation. BMC Public Health 12, 1051.
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Homedes, N., and A. Ugalde, 2012: Mexican pharmacies and antibiotic consumption at the US-Mexico border. South Med Rev. 5, 9–19. de Kraker, M.E.A., P.G. Davey, H. Grundmann, and the BURDEN study group, 2011: Mortality and hospital stay associated with resistant Staphylococcus aureus and Escherichia coli bacteremia: estimating the burden of antibiotic resistance in Europe. PLoS Med. 8, e1001104. Lomas, J., T. Culyer, C. McCutcheon, L. McAuley, and S. Law, 2005: Conceptualizing and combining evidence for health system guidance. Final report to Canadian Health Services Research Foundation, Ottawa. Available at: http://www.cfhi-fcass.ca/migrated/pdf/insightAction/evidence_e.pdf (accessed on 16 January 2014). Maragakis, L.L., E.N. Perencevich, and S.E. Cosgrove, 2008: Clinical and economic burden of antibiotic resistance. Expert Rev. Anti. Infect. Ther. 6, 751–763. Midgley, G., 2006: Systemic intervention for public health. Am J. Pub. Health 96, 466–472. Morfin-Otero, R., J.C. Tinoco-Favila, H.S. Sader, L. SalcidoGutierrez, H.R. Perez-Gomez, E. Gonzalez-Diaz, L. Petersen, and E. Rodriguez-Noriega, 2012: Resistance trends in gramnegative bacteria:surveillance results from two Mexican hospitals, 2005–2010. BMC Res. Notes 5, 277. Orozco, T.V., and R. Hernandez-Castro, 2009: Detecci on de beta-lactamasas de espectro extendido tipo TEM,SHV, y CTX-M en cepas de Pasteurella multocida. BSc Thesis, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autonoma de Mexico, Mexico City. Parmley, J., Z. Leung, D. Leger, R. Finley, R Irwin, K. Pintar, F. Pollari, R. Reid-Smith, D. Waltner-Toews, M. Karmali, and R. Engelhardt, 2012: A4. One health and food safety- The Canadian experience: a holistic approach toward enteric bacterial pathogens and antimicrobial resistance surveillance. In: Institute of Medicine (US). Improving Food Safety through a One Health Approach: Workshop Summary. National Academies Press, Washington, DC, USA. Perez-Cuevas, R., S.V. Doubova, V.J. Wirtz, A. Dreser, E. Servan Mori, and M. Hernandez Avila, 2012: Consultorios medicos en farmacias privadas: efectos inesperados en el uso de servicios de salud y el acceso a medicamentos. Encuesta Nacional de Salud y Nutrici on ENSANUT 2012, INSP. Sanchez, M., and S. Sivaraman, 2010: News media reporting of antimicrobial resistance in Latin America and India. In: Sosa, A., D.K. Byarugaba, C.F. Amabile-Cuevas, P.R. Hsueh, S. Kariuki, and I.N. Okeke (eds.), Antimicrobial Resistance in Developing Countries, pp. 525–537. Springer, New York. Santa-Ana-Tellez, Y., A.K. Mantel-Teeuwisse, A. Dreser, H.G.M. Leufkens, and V.J. Wirtz, 2013: Impact of over-the-counter restrictions on antibiotic consumption in Brazil and Mexico. PLoS ONE 8, e75550. Smith, R., and J. Coast, 2013: The true cost of antimicrobial resistance. BMJ 346, 1493.
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Wegener, H.C., 2012: A15. Antibiotic resistance-linking human and animal health. In: Institute of Medicine (US). Improving Food Safety through a One Health Approach: Workshop Summary. National Academies Press, Washington, DC, USA. WHO, 2001: WHO global principles for the containment of antimicrobial resistance in animals intended for food. World Health Organization, Geneva, Switzerland. WHO/CDS/CSR/ APH/2000.4 WHO, 2003: Impacts of antimicrobial growth promoter termination in Denmark. The WHO international review panel’s evaluation of the termination of the use of antimicrobial growth promoters in Denmark. World Health Organization, Geneva, Switzerland. WHO/CDS/CPE/ZFK/2003.1 WHO, 2012: The Evolving Threat of Antimicrobial Resistanceoptions For Action. World Health Organization, Geneva, Switzerland. Wirtz, V.J., A. Dreser, and R. Gonzales, 2010: Trends in antibiotic utilization in eight Latin American countries, 1997–2007. Rev. Panam. Salud Publica 27, 219–225.
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Zaidi, M., J. Sifuentes-Osornio, A.L. Rol on, G. Vazquez, R. Rosado, M. Sanchez, J.J. Calva, and S. Ponce de Le on-Rosales, 2002: Inadequate therapy and antibiotic resistance. Risk factors for mortality in the intensive care unit. Arch. Med. Res. 33, 290–294. Zaidi, M.B., V. Leon, C. Canche, C. Perez, S. Zhao, S.K. Hubert, J. Abbott, K. Blickenstaff, and P.F. McDermott, 2007: Rapid and widespread dissemination of multidrug-resistant blaCMY-2 Salmonella Typhimurium in Mexico. J. Antimicrob. Chemother. 60, 398–401. Zaidi, M.B., J.J. Calva, M.T. Estrada-Garcia, V. Leon, G. Vazquez, G. Figueroa, E. Lopez, J. Contreras, J. Abbott, S. Zhao, P.F. McDermott, and L. Tollefson, 2008: Integrated food chain surveillance system for Salmonella spp. in Mexico. Emerg. Infect. Dis. 14, 429–435. Zaidi, M.B., P.F. McDermott, F.D. Campos, R. Chim, M. Leon, G. Vazquez, G. Figueroa, E. Lopez, J. Contreras, and T. Estrada-Garcia, 2012: Antimicrobial-resistant Campylobacter in the food chain in Mexico. Foodborne Pathog. Dis. 9, 841–847.
© 2014 Blackwell Verlag GmbH, 2014, 61 (Suppl. 2), 1–6
ORIGINAL ARTICLE
A Collaborative Initiative For the Containment of Antimicrobial Resistance in Mexico Mussaret B. Zaidi1,2, Anahi Dreser3 and Inda Marcela Figueroa4 1 2 3 4
Microbiology Research Laboratory, Hospital General O’Horan, Merida, Mexico Infectious Diseases Research Unit, Hospital Regional de Alta Especialidad de la Peninsula de Yucatan, Merida, Mexico Center for Health Systems Research, National Institute of Public Health, Cuernavaca, Mexico School of Veterinary Medicine, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Impacts
• In 2010, an unprecedented collaboration in Mexico between infectious •
•
disease specialists, public health experts, veterinarians and a wide array of stakeholders culminated in a consensus document that called for seven priority actions to improve antimicrobial use and mitigate resistance. Although the initiative failed to achieve a comprehensive national antibiotic policy, it effectuated the enforcement of regulations requiring medical prescriptions for the sale of antibiotics, the development of national guidelines for good animal husbandry practices and a ban on five antimicrobial compounds for use in food-animals. Establishing a national policy for containment of antimicrobial resistance is a major challenge for Mexico. Using a systemic approach, novel strategies should include a massive public education campaign and consensus meetings with stakeholders.
Keywords: Antimicrobial resistance; Containment strategies; Public policies; Regulation; Stewardship Correspondence: n, Dr. Mussaret B. Zaidi, Depto. De Investigacio Hospital General O’Horan, Av. Itzaes x Jacinto Canek, C.P. 97000, M erida, Yucat an, Mexico. Tel.: +52-999-9233869; Fax: +52-9999238673; E-mail: [email protected] Contents of this article were presented in an international expert meeting, ‘Reducing antimicrobial usage in agriculture and aquaculture: beyond regulatory policy’, held in Utrecht, The Netherlands, 1–3 July 2013. The Workshop was sponsored by the OECD Co-operative Research Programme on Biological Resource Management for Sustainable Agricultural Systems, the Netherlands Organization for Health Research and Development (ZonMW), and the Dutch Ministry of Economic Affairs. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its member countries.
© 2014 Blackwell Verlag GmbH, 2014, 61 (Suppl. 2), 1–6
Summary Antimicrobial resistance exacts worldwide an increasingly significant clinical and economic toll. Despite the international calls for urgent action, antimicrobial use and resistance have been low on the Mexican government’s policy agenda. In early 2010, a multidisciplinary group of experts launched a national initiative for containment of antimicrobial resistance that was endorsed by major medical, veterinary and public health institutions. The initiative called for seven priority actions including the creation of an ad hoc intersectoral advisory group, a requirement that human and veterinary antibiotics be dispensed only with prescription, and the establishment of effective surveillance systems. A consensus document was disseminated among key decision-makers at the ministries of Health and Agriculture and the legislature. The Ministry of Health (MoH) enacted a decree effective as of August 2010, which enforced the regulations that required medical prescriptions for the sale of human antibiotics. While the information disseminated by the MoH did focus on the dangers of self-medication, it failed to highlight the inherent perils of antibiotic resistance or the consequences of antibiotic use in food-animals. Following the decree, there was a surge of medical offices controlled by retail pharmacies. In the veterinary sector, voluntary guidelines were developed for good husbandry practices, including antibiotic use in food animals; five antimicrobials for use in food-animals were banned. No intersectoral advisory group or surveillance systems were established. This study describes a bottom-top approach in Mexico for the development of a national strategy to improve antibiotic use and contain antimicrobial resistance. Its experiences suggest that, in countries such as Mexico that lack strong regulatory systems and surveillance capacities, a more systemic approach is warranted. Future
1
Initiative for Improving Antibiotic use in Mexico
Received for publication October 8, 2013 doi: 10.1111/zph.12166
efforts should begin with early involvement of key stakeholders and informing policy makers, professionals and the population at large about the critical importance of antibiotic resistance.
Introduction The misuse and overuse of antibiotics in medicine and food-animal production has led to a global epidemic of antimicrobial resistance (WHO, 2012). Numerous studies show that antimicrobial resistance is associated with excess mortality, length of hospitalization and costs. In the USA, the total cost of antimicrobial resistance is estimated at $30 billion dollars annually (Maragakis et al., 2008), with 23 000 excess deaths (CDC, 2013). In Europe, MRSA and third-generation cephalosporin-resistant Escherichia coli bloodstream infections alone cause 8000 excess deaths and 62 million Euros in excess cost (de Kraker et al., 2011). Insofar as our inaction today portends disastrous consequences (Smith and Coast, 2013) that could bring about ‘the end of modern medicine as we know it’ (Chan, 2012), international organizations have called on governments for political will at the highest level to implement urgent interventions in the human and animal health sectors (WHO, 2012). Mexico has high rates of antibiotic resistance in community and hospital-acquired infections (Zaidi et al., 2008; Casta~ neda et al., 2009; Morfin-Otero et al., 2012); these are, moreover, associated with a significantly greater burden of disease (Zaidi et al., 2002, 2007). Over the last decade, antibiotic usage in the human health sector has been one of the highest in Latin America (Wirtz et al., 2010). Inappropriate medical prescription, and until recently, as a consequence of lacklustre enforcement, widespread selfmedication with antibiotics have been implicated in antibiotic misuse and overuse (Dreser et al., 2008, Homedes and Ugalde 2012). Major shortcomings in the veterinary sector include insufficient laboratory infrastructure for susceptibility testing and quality control, as well as easy access to veterinary antibiotics without prescription for food and companion animals. The few antimicrobial susceptibility studies conducted on veterinary and zoonotic foodborne pathogens all show that antimicrobial resistance is a significant problem (Zaidi et al., 2008, 2012; Orozco and Hernandez-Castro, 2009). In south-east Mexico, severe and fatal multidrug-resistant, extended-spectrum cephalosporin-resistant Salmonella Typhimurium infections in infants have been traced to swine and contaminated pork meat (Zaidi et al., 2007). Despite the evidence underscoring the need for urgent action, the problem of antibiotic resistance has been low on the Mexican government’s policy agenda. Possible reasons are the absence of clear indicators that measure the severity 2
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of the problem, the priority given to assuring the supply and access to medicines, anticipation of opposition by powerful stakeholders and insufficient understanding of policy alternatives (Dreser et al., 2012). On the other hand, medical associations, notably, the Mexican Association for Infectious Diseases and Clinical Microbiology, AMIMC) have a strong tradition of promoting antimicrobial stewardship among their members. Activities have included the following: (i) promoting the use of guidelines, (ii) establishment of hospital networks for antimicrobial resistance surveillance and (iii) training programs for quality control in clinical microbiology laboratories. Veterinary associations, in contrast, have just recently established training programs on antimicrobial resistance. Addressing the need for an effective antibiotic policy in Mexico, a group of concerned physicians, veterinarians and public health experts launched a national initiative (hereby referred to as the IIAU, ‘Initiative for Improving Antimicrobial Use’, Dreser et al., 2010), in early 2010, in which all the authors of this study participated as group leaders and coordinators. This study describes the process and outcomes involved in the development of this endeavour. We consider the challenges encountered by this initiative as well as its potentialities and draw lessons for Mexico and other countries seeking to establish national strategies for improved antimicrobial use and containment of resistance. Development of the IIAU The first meeting was held in October 2009 at the AMIMC Annual Meeting in Guadalajara. As the first formal collaborative effort between public health experts, physicians, microbiologists and veterinarians, it included participants from different academic institutions and hospitals throughout the country, as well as representatives from the Alliance for the Prudent Use of Antibiotics (APUA), the World Organization for Animal Health (OIE) and industry representatives. A contextual circumstance that facilitated AMIMC sponsorship and active collaboration of its members in the IIAU was the recent public debate regarding the perils of selfmedication with antibiotics for respiratory infections occasioned by the 2009 H1N1 influenza epidemic. This public debate opened a window of opportunity to place antibiotics at the top of the policy agenda (Dreser et al., 2012). Among veterinarians, diffusion of WHO, OIE and Codex Alimentarius recommendations (WHO, 2001; CODEX, 2005) helped develop awareness of the adverse impact of © 2014 Blackwell Verlag GmbH, 2014, 61 (Suppl. 2), 1–6
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antimicrobial use in food-producing animals and the need for changing standard practices. At the first meeting, emphasis was placed on prioritizing measures essential to a reduction in antibiotic usage and the containment of antimicrobial resistance in both human and veterinary health sectors. During the second meeting, hosted by the School of Veterinary Medicine at the National Autonomous University, a broader range of veterinarians with expertise in different food-animals was included. Group discussions focused in more detail on regulatory measures aimed at improving the licensing and dispensing of antibiotics. Other important topics of discussion were as follows: (i) the need to develop training programs for professionals and education campaigns for the general public, (ii) the establishment of surveillance systems for antimicrobial usage and resistance and (iii) a plan to develop and disseminate the IIAU among key decisionmakers. Over the next few months, the group worked on a consensus document that was ultimately endorsed by major medical and veterinary associations and institutions. The proposal, drafted as a policy brief, called for seven priority actions to improve human and veterinary antimicrobial use and mitigate resistance (Table 1). During the first trimester of 2010, the proposal was sent, in both printed and electronic forms, to head offices at the Ministries of Health and Agriculture. It was also submitted to the health and agriculture commissions of the legislature, as well to various interest groups including professional, pharmaceutical industry and pharmacy associations. Each one of us met with different policy makers for discussion and participated in press interviews. Press releases were run in major newspapers (Davila, 2010). Outcomes of the IIAU Human sector In May 2010, the Ministry of Health (MoH) enacted a decree, effective as of August of that year, which enforced the regulations for the sale of human antibiotics by medical
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prescriptions (Diario Oficial de la Federaci on, 2010). An additional requirement was that pharmacies retain and register all prescription data. Although the text of the decree incorporated many sections of the IIAU document, and indeed, called for actions directed towards counteracting self-medication with antibiotics, it simultaneously neglected other priority actions enumerated in the initiative. Likewise, while the information disseminated through mass media by the Federal Commission for the Protection against Sanitary Risks (COFEPRIS, MoH) did underscore the dangers of self-medication, it did not elaborate sufficiently on antibiotic resistance nor did it address the possible human health impact of antibiotic use in food animals. After the change in federal administration in December 2012, antibiotic prescriptions were stamped but not retained. To our knowledge, the data from retained prescriptions have not been used for antibiotic usage analysis. One unanticipated consequence of the decree was a significant increase in the number of retail pharmacies that hired general practitioners to provide cheap – or even free – medical consultations and prescriptions. Veterinary sector The IIAU initially resulted in a series of voluntary guidelines and more recently, in regulatory interventions. In 2010, the National Technical Advisory Council for Animal Health (CONASA) developed a series of documents promoting good husbandry practices, including antibiotic usage, for different food-animals (CONASA, 2010). A year later, it established a multidisciplinary ad hoc group to assess the burden of antimicrobial resistance in veterinary medicine and recommend practices for the use of anti-microbials in animals. Among the salient recommendations were the implementation of equal standards for exported and domestic animal-derived food products and strict adherence to the purchase of veterinary antibiotics exclusively through licensed professionals. In 2012, the group revised the list of antimicrobials licensed for veterinary use, placing a ban on nitrofurans, nitroimidazoles,
Table 1. Priority actions proposed in the Initiative for Improving Antimicrobial Use, Mexico, 2010 Priority action
Type of intervention
1.- Creation of a multidisciplinary advisory group for antimicrobial regulation and licensure 2a.- Enforcement of national regulations requiring human and veterinary antibiotics to be dispensed only with prescription 2b- Stricter control of the critically important antibiotics 3.- Establishment of national guidelines for the use of antibiotics for growth promotion and metaphylaxis in animals 4.- Review of licensure requirements in order to safeguard antimicrobials for human use 5.- Creation of legal mechanisms to guarantee the quality, safety and efficacy of human and veterinary antibiotics 6.- Implementation of national surveillance systems for antibiotic usage and antimicrobial resistance 7a.- Development of educational programs for pharmacists, physicians and veterinarians 7b.- Development of public education campaigns through mass media
Managerial
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Regulatory Managerial Regulatory Regulatory Managerial Educational
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olaquindox, carbadox and chloramphenicol in food-animals (Diario Oficial de la Federaci on, 2012). The group is currently discussing the removal of dosage labels on the packages of veterinary anti-microbials with the intent of encouraging professional consultation prior to the administration of veterinary antibiotics. The regulation of antibiotics used for growth promotion and metaphylaxis is also under consideration (Inda Marcela Figueroa, IMF, personal communication). Despite these encouraging developments, the government has failed to implement IIAU recommendations essential for the successful containment of anti-microbial resistance, namely tighter regulations for assuring antibiotic quality and the establishment of surveillance systems for antimicrobial usage and antimicrobial resistance. In addition, comprehensive training programs for physicians, veterinarians and producers have yet to be established. Discussion and conclusions This study describes a bottom-top approach in Mexico for developing a national strategy to improve antimicrobial use and contain antimicrobial resistance. While the initiative was not entirely successful in achieving all of its ambitious goals, its experiences to date point to new, promising areas for action and remediation. Positive aspects of this initiative were the unprecedented collaboration between infectious disease specialists, public health experts and veterinarians, and the inclusion of a wide array of stakeholders that culminated in a consensus document. Consistent with a ‘One Health’ approach (Parmley et al., 2012), the initiative allowed for communication and scientific exchange between academic institutions, policy makers and industry. Significantly, it led to specific regulatory, managerial and educational interventions by the Ministries of Health and Agriculture. The initiative failed, however, to achieve a comprehensive, successfully implemented national antibiotic policy. There were major shortcomings in the policy process. The Ministries of Health and Agriculture did not establish an advisory group (Priority Action 1) drawn from relevant sectors and disciplines to address, in all its complexity, the containment of antimicrobial resistance. An informed debate in the legislature, which never took place, might well have led to other policy alternatives. Greater restrictions to antibiotic access generated opposition by interest groups and the general public. The conflict was ostensibly resolved by establishing pharmacy-controlled medical offices. Prescribing and dispensing in the same establishment represents a clear conflict of interest that leads to overprescription (Perez-Cuevas et al., 2012; Wegener, 2012). The emergence of such establishments likely explains the modest impact of the decree on overall antibiotic sales 4
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(Santa-Ana-Tellez et al., 2013). Instead, an intense public education campaign detailing the health risks of antibiotic resistance, conducted prior to the decree (as the IIAU recommended), would have been more effective in ameliorating opposition to the new measures. Surveillance systems for antimicrobial usage and resistance, which are critical for measuring the true impact of interventions, were never established. In the absence of real indicators, an accurate evaluation of the measures taken by the Mexican government is nearly impossible. The failure to analyse the valuable information contained in retained prescriptions, for example, forfeited a clear opportunity. Flaws were also present in the advocacy process. The multidisciplinary group focused most of their efforts on drafting the consensus document and its dissemination. Far less time was devoted to dialogue with decision-makers and key stakeholders or to the establishment of an effective deliberative process. At this juncture, a prudent course would likely involve alternative interventions to initiate and monitor change in key sectors. Many European countries have successfully introduced a series of regulatory measures that have led to the prohibition of growth promoters, a decrease in the overall use of antimicrobial usage and the establishment of rigorous monitoring systems for antimicrobial usage and resistance (WHO, 2003). Our experience suggests that countries such as Mexico that lack strong regulatory systems and surveillance capacities should employ a systemic approach (Midgley, 2006). Placing antimicrobial resistance once again on the public and political agendas should be the first step in the advancement of the seven priority actions of the IIAU. Early involvement of relevant stakeholders and actors will be critical. Strategies that could be used to achieve a national strategy to contain antimicrobial resistance are as follows: (i) raising awareness among policy makers and medical and veterinary professionals through varied communication channels, (ii) delivering a massive public education campaign with media involvement (Sanchez and Sivaraman, 2010), and (iii) facilitating consensus meetings with government authorities, scientists, clinicians, industry and producers (Lomas et al., 2005). The participation of experts in advocacy and social communication skills will be essential to strengthen this process. Finding novel pathways to containing antimicrobial resistance worldwide will require tenacity, collaboration and political will. The stakes for Mexico, and the world, could not be greater. Conflict of interest The authors have no conflicts of interest to declare. © 2014 Blackwell Verlag GmbH, 2014, 61 (Suppl. 2), 1–6
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