Review
Antimicrobial resistance in developing countries. Part II: strategies for containment

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Summary

The growing threat from resistant organisms calls for concerted action to prevent the emergence of new resistant strains and the spread of existing ones. Developing countries have experienced unfavourable trends in resistance—as detailed in part I, published last month—and implementation of many of the containment strategies recommended by WHO is complicated by universal, as well as developing country-specific, factors. The control of selective pressure for resistance could potentially be addressed through educational and other interventions for orthodox and unorthodox prescribers, distributors, and consumers of antimicrobials. At national levels, the implementation of drug use strategies—eg, combination therapy or cycling—may prove useful to lengthen the lifespan of existing and future agents. Programmes such as the Integrated Management of Childhood Illnesses (IMCI) and directly observed short-course therapy (DOTS) for tuberculosis are prescriber-focused and patient-focused, respectively, and have both been shown to positively influence factors that contribute to the selective pressure that affects resistance. The institution of interventions to prevent the transmission of infectious diseases could also lead to beneficial effects on the prevalence of resistance, as has vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae. There has been an upsurge in the number of organisations and programmes that directly address issues of resistance, and collaboration could be one way to stem the dire trend. Additional factors such as unregulated drug availability, inadequate antimicrobial drug quality assurance, inadequate surveillance, and cultures of antimicrobial abuse must be addressed to permit a holistic strategy for resistance control.

Introduction

Antimicrobial resistance contributes to health and economic losses worldwide.1, 2 In developing countries, a high infectious disease burden commonly co-exists with rapid emergence and spread of microbial resistance. As indicated in part I of this review—published last month—the prevalence of resistance in seminal developing country pathogens is high and rising.3 Addressing the serious threat from resistant bacteria will require strategies for preventing the emergence of resistance, as well as containing resistant organisms that have already emerged.4 Most of the studies evaluating such strategies have been conducted within hospitals and other closed environments, predominantly in western Europe and North America, within well-functioning health-care systems. The structure and effectiveness of developing country health-care systems varies tremendously and therefore a one-size-fits-all model is neither useful nor desirable. Implicit from this variation is the need for area-specific surveillance to inform policy. Almost all developing countries have been insufficiently studied, but there are some areas, notably francophone Africa, the Pacific, and newly independent Soviet states, from which few or no data are available.5 Seemingly rational interventions do not always affect the prevalence of resistant microbes or alter practices that contribute to the emergence and spread of resistant organisms. Because there is no guarantee that untested interventions will be effective, particularly over the long term,6, 7, 8 pilot programmes to evaluate interventions should precede large-scale implementation.

Section snippets

Risk factors for resistance emergence and spread, particularly in developing countries

A summary of risk factors for resistance particularly pertinent to, but not limited to, developing countries is outlined in panel 1. Antimicrobial use produces selective pressure for resistance, and there is evidence to suggest that the number of patients consuming antimicrobials in developing countries is rising.9 Much of this increase is due to rising incomes and improved access to health care—both positive developments—and to changing disease patterns, such as opportunistic infections in

Interfering with the spread of resistant microorganisms in the community

A reduction in resistant S pneumoniae infections was seen in the USA following the introduction of a multivalent vaccine that protected against the serovars with which resistance is commonly associated.36 By contrast, Arason and colleagues8 found that, in Iceland, a fall in antibiotic use was unable to produce a sustainable effect on resistance. The use of pneumococcal vaccines could potentially achieve similar results in developing countries where only a few serotypes account for most

Educational interventions

The implementation of educational interventions is typically affordable for developing countries because the principal requirement is locally sourced manpower rather than expensive, typically imported, material inputs.18 Educational interventions that fail to change the prescribing behaviour of a sufficiently large proportion of prescribers can be reinforced through multiple interventions.47, 48 Integrating pharmacotherapy modules into standard medical and allied health curricula has been shown

Support and partnerships for antimicrobial resistance interventions and research

WHO published its Global strategy for containment of antimicrobial resistance report in 2001 in response to a growing problem.16 Broadly, the report recommends reducing the infectious disease burden, improving access to and use of antimicrobials, strengthening surveillance capabilities and other aspects of health-care systems, enforcing regulations, and developing new preventive and therapeutic medications.16 For developing countries, with constrained budgets that demand prioritisation, very

Search strategy and selection criteria

References for this review were identified by searches of Medline, ISI WebofScience, and references from relevant articles; additional articles were identified through searches of the extensive files of the authors. Search terms used in combination were “antimicrobial resistance”, “antibiotic resistance”, “antimicrobial use”, “antibiotic use”, “developing countries”, “Africa”, “Asia”, “Latin America”, “South America”, and “intervention”.

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      Thus, in LMICs, the first priority will be antimicrobial stewardship and infection control rather than reducing antibiotic consumption to contain the emergence and spread of resistant bacterial pathogens. Thus, the successful experiences in antibiotic stewardship and infection control strategies (e.g., improving nonprescription antimicrobial use, educational interventions, legislation for antibiotic drug advertising, investments in improved hygiene, sanitation, vaccination, and hand hygiene) in HICs could provide models in LMICs (Apisarnthanarak and Mundy, 2008; Bavestrello et al., 2002; Bi et al., 2000; Cairncross, 2003; Chow and Szeto, 2003; Goossens et al., 2007, 2006; Guyon et al., 1994; Harbarth and Samore, 2005; Hawkey, 2008; Kumarasamy et al., 2010; Lawes et al., 2015; Laxminarayan et al., 2016; Lee et al., 2014a; Mölstad et al., 2008; Morgan et al., 2011; Okeke et al., 2005; Park et al., 2005; Poehling et al., 2004; Reyes et al., 1997; Rossolini et al., 2008; Sabuncu et al., 2009; Tängdén et al., 2010; Walsh et al., 2011; Whitney et al., 2003; Woloshin et al., 2001). However, the priorities and combinations of those interventions should still be determined at the local level of LMICs given the national infectious disease burdens, resistance patterns, and economic level.

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