Maximising access to achieve appropriate human antimicrobial use in low-income and middle-income countries

doi:10.1016/S0140-6736(15)00547-4

The Lancet

Volume 387, Issue 10014, 9–15 January 2016, Pages 188-198

https://doi.org/10.1016/S0140-6736(15)00547-4 Get rights and content

Summary

Access to quality-assured antimicrobials is regarded as part of the human right to health, yet universal access is often undermined in low-income and middle-income countries. Lack of access to the instruments necessary to make the correct diagnosis and prescribe antimicrobials appropriately, in addition to weak health systems, heightens the challenge faced by prescribers. Evidence-based interventions in community and health-care settings can increase access to appropriately prescribed antimicrobials. The key global enablers of sustainable financing, governance, and leadership will be necessary to achieve access while preventing excess antimicrobial use.

Section snippets

Introduction—balancing access and excess

Antimicrobials are life-saving drugs that, together with vaccination and improvements in the social determinants of disease, have a fundamental worldwide effect on individual and public health. Access to antimicrobials and prevention measures has been a crucial factor in the 50% reduction in maternal and child deaths since 1990.¹ However, in 2010, the number of deaths of children younger than 5 years still reached 7·6 million.² The importance of increasing access to antimicrobials, vaccination,

Guiding principles and measures

The main drivers of excess are related to high infectious disease burden as a result of improper prevention, availability of substandard drugs because of deficient regulatory and enforcement capacity, insufficient health personnel or community health workers, or inadequate training and skills among them. Little access to diagnostics and laboratory services to guide treatment compounds the problem.

Key messages

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Access to quality-assured antimicrobials is part of the human right to health, yet

Access for all in need

Access to essential medicines, of which antimicrobials are one example, is part of the right to health—ie, the enjoyment of the highest attainable standard of health, which is one of the state's obligations under human rights law.11, 12 The principle of access to essential antimicrobials for those in need is often undermined in low-income and middle-income countries (LMICs) by financial, infrastructural, and human resource limitations. Universal access to antimicrobials is not only about

Access to health services

In view of human resource shortages³² and limited access to public health facilities in LMICs, several innovative community-based strategies have been developed and tested to improve antimicrobial access for millions who live at or beyond the periphery of the health system (panel 1). In many parts of the world, private practice physicians or pharmacists (including drug shops and private medicine vendors) are the primary access points for antimicrobials. A recent Ugandan household survey⁴⁷

Access to prevention measures

Access to interventions that reduce the overall burden of infections (both incidence and transmission), and thereby prevent the need for antimicrobials in the first place, could affect antimicrobial resistance (appendix).

Many of these interventions are simple health promotion strategies, such as improving access to clean water and sanitation. In Karachi, Pakistan, washing hands with soap reduced both diarrhoea and acute respiratory infections by half, and the incidence of impetigo that would

Access to diagnostics

Overprescription of antimicrobials is typically driven by diagnostic uncertainty around undifferentiated fever (one for which a definite cause is unapparent). The reasons for lack of access to diagnostics are multifactorial and include unavailability of point-of-care tests; underuse of diagnostic services because of long laboratory turnaround times, poor performance characteristics, or affordability issues; little access to laboratory services; and inadequate maintenance and assurance of

Access to evidence-based management protocols, service provision enhancement, and education

The provision of straightforward physician-directed educational material in isolation generally has little effect on physician behaviour.⁶⁶ However, basic algorithmic guidelines can improve appropriate antimicrobial delivery, especially if they are integrated with more complex, system-wide interventions.66, 67, 68 If coupled to an expanding RDT capability, programmes such as the WHO Integrated Management of Childhood Illness (IMCI),⁶⁷ which has been introduced in more than 75 countries, and the

Access to appropriate antimicrobials of assured quality

Weak health systems and lack of regulatory authorities, which often characterise LMICs, compound problems of access. Poor drug quality increases selection pressure, and substandard and falsified drugs remain a serious problem in resource-limited settings (appendix).83, 84 Although some such drugs contain no active ingredients and hence do not drive resistance, those with suboptimal concentrations of antimicrobials will do so.

As multidrug-resistant organisms become more prevalent, access to

Access to new innovations

Much of the world's innovation capability is located in HICs and predominantly within the private sector, with drug development driven mostly by profitable market opportunities.⁹⁵ The pharmaceutical industry is incentivised to bring new products to the market through a global system of intellectual property rights regulated in the agreement on Trade-Related Aspects of Intellectual Property Rights and its national equivalents.⁹⁶ The intellectual property rights system encourages industry to take

Health systems strengthening

Limited access to and overuse of antimicrobials often coexist within one health system and cannot be tackled by targeting any one of these challenges in isolation.¹⁰⁵ For interventions and policies aiming for universal access and appropriate use to be successful, measures to strengthen health systems are needed. These measures should be designed from a systems perspective¹⁰⁶ and take into account possible barriers and facilitators on individual, household and community, health facility, health

Mechanisms to implement access and minimise excess

To implement core principles and measures driving access worldwide, sustainable financing, governance, and leadership are necessary. As a global challenge, long-term commitment, with sustained financing from all affected countries, is needed to improve universal access to and appropriate use of antimicrobials. Therefore, it will be important to move away from the present donor-driven model for LMICs, especially since coordination of resources might be necessary at international, regional, and

Conclusions and recommendations

The challenge for LMICs, and indeed many HICs, in accessing quality-assured antimicrobials, infection prevention measures, and the instruments needed to enable appropriate prescribing demands a context-adjusted approach that can be applied across a range of health-care settings. We recommend national-level research and assessments to understand the particular needs of LMICs, with respect to access to effective antimicrobials, and to have a heightened focus on access of populations to vaccines

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The emergence of antimicrobial resistance (AMR) is a growing public health threat worldwide and antibiotic consumption is being increasingly recognized as the main selective pressure driving this resistance. However, global trend in antibiotic resistance in response to antibiotic consumption is not fully understood. In this study, we collected national resistance data on specific resistant pathogens considered by the World Health Organization (WHO) as priority and antibiotic consumption data for 61 countries to assess the global trends in antibiotic resistance of those common bacterial pathogens and their association with antibiotic consumption. The low- and middle-income countries (LMICs) represented the largest hotspots of resistance, which presented relatively higher resistance rates in common bacterial pathogens but lower antibiotic consumption rates compared to high-income countries (HICs). Specifically, we developed the Normalized Antibiotic Resistance/Consumption Index (NARCI) and produced global maps of NARCI to roughly assess the appropriateness of antibiotic consumption across countries and to indicate the potentially inappropriate antibiotic consumption in LMICs compared with HICs. Additionally, we linked antibiotic consumption rates and resistance rates of target pathogens, in conjunction with NARCI and the correlation analysis between antibiotic use and resistance, to inform strategies to alleviate the threat of antibiotic resistance worldwide.
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Citation Excerpt :
However, the cost-effectiveness of using such point-of-care testing in low- and lower-middle-income countries (LLMICs) has not been well studied [14]. Given the shortcomings in LLMICs, including insufficient basic infrastructure, poor management commitment, limited policies and programmes, inadequately funded health systems, diagnostic/laboratory challenges and shortages of experienced laboratory/infectious disease personnel [14,15], point-of-care testing and digital interventions may not be sustainable. It has been noted that the content, delivery and function of each intervention component should be evaluated to understand how they might perform in different settings [16].
Antimicrobial stewardship (AMS) initiatives in hospitals often include the implementation of clustered intervention components to improve the surveillance and targeting of antibiotics. However, impacts of the individual components of AMS interventions are not well known, especially in low- and lower-middle-income countries (LLMICs).
A scoping review was conducted to summarize evidence from systematic reviews (SRs) on the impact of common hospital-implemented healthcare-worker-targeted components of AMS interventions that may be appropriate for LLMICs.
Major databases were searched systematically for SRs of AMS interventions that were evaluated in hospitals. For SRs to be eligible, they had to report on at least one intervention that could be categorized according to the Effective Practice and Organisation of Care taxonomy. Clinical and process outcomes were considered. Primary studies from LLMICs were consulted for additional information.
Eighteen SRs of the evaluation of intervention components met the inclusion criteria. The evidence shows that audit and feedback, and clinical practice guidelines improved several clinical and process outcomes in hospitals. An unintended consequence of interventions was an increase in the use of antibiotics. There was a cumulative total of 547 unique studies, but only 2% (N=12) were conducted in hospitals in LLMICs. Two studies in LLMICs reported that guidelines and educational meetings were effective in hospitals.
Evidence from high- and upper-middle-income countries suggests that audit and feedback, and clinical practice guidelines have the potential to improve various clinical and process outcomes in hospitals. The lack of evidence in LLMIC settings prevents firm conclusions from being drawn, and highlights the need for further research.
Antibiotic geographies and access to medicines: Tracing the role of India's pharmaceutical industry in global trade
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Access to medicines has become a major concern for countries worldwide during the COVID-19 pandemic, as pharmaceutical production and trade have been disrupted in the course of the crisis. Antibiotics are one group of medicines where worries about access have been raised. Access to the right antibiotic at the right time is important not only for curing infections of individual patients, but also for curbing antibiotic resistance globally. Reliable pharmaceutical supply is key to ensuring access to medicines. The global supply of generic medicines has over the last decades been transformed by the rise of India's pharmaceutical industry. In this paper, I trace the changing role of this industry for the global export of antibiotics, by mapping and describing changes in Indian antibiotic exports and discussing these in light of historical processes and events. The paper offers a novel approach to analyse global antibiotic trajectories by using international trade data from publicly available resources combined with a secondary literature review. I show that India's pharmaceutical industry today holds a key role as one of the world's biggest exporters of antibiotic medicines, but with an increasing dependency on China as a supplier of antibiotic ingredients. This produces both opportunities and concerns for access to antibiotics globally.
Interventions to improve dispensing of antibiotics at the community level in low and middle income countries: a systematic review
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Inappropriate antibiotic dispensing is one of the key drivers of antibiotic resistance. This review documents the effectiveness of interventions aimed at improving antibiotic dispensing practices at the community level by drug dispensers in low- and middle-income countries (LMIC).
We conducted a systematic search in PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science (11 November 2019). Studies were included if they reported data on the outcome measure: appropriate dispensing of medicine including antibiotics. The effectiveness of studies was assessed based on quantitative results reported in the studies included.
A total of 1158 articles were screened. Thirteen studies from Asia (six), Africa (five) and South America (one) and one study from both Africa and Asia were included in this review. Nine (69.2%) studies reported significant effectiveness of interventions on all or more than 50% of antibiotic-related outcomes. Cochrane Effective Practice and Organization of Care interventions frequently applied were educational meetings (9/13), distribution of educational materials (7/13), educational outreach meetings (7/13), reminders (6/13), local consensus processes (6/13), distribution of supplies (6/14) and clinical practice guidelines (4/14), Nine studies reported on stakeholder involvement.
This review shows that it is possible to improve antibiotic dispensing practices at the community level in LMIC. Stakeholders’ involvement was key in the design and implementation of interventions.
Global antibiotic consumption and usage in humans, 2000–18: a spatial modelling study
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Antimicrobial resistance (AMR) is a serious threat to global public health. WHO emphasises the need for countries to monitor antibiotic consumption to combat AMR. Many low-income and middle-income countries (LMICs) lack surveillance capacity; we aimed to use multiple data sources and statistical models to estimate global antibiotic consumption.
In this spatial modelling study, we used individual-level data from household surveys to inform a Bayesian geostatistical model of antibiotic usage in children (aged <5 years) with lower respiratory tract infections in LMICs. Antibiotic consumption data were obtained from multiple sources, including IQVIA, WHO, and the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). The estimates of the antibiotic usage model were used alongside sociodemographic and health covariates to inform a model of total antibiotic consumption in LMICs. This was combined with a single model of antibiotic consumption in high-income countries to produce estimates of antibiotic consumption covering 204 countries and 19 years.
We analysed 209 surveys done between 2000 and 2018, covering 284 045 children with lower respiratory tract infections. We identified large national and subnational variations of antibiotic usage in LMICs, with the lowest levels estimated in sub-Saharan Africa and the highest in eastern Europe and central Asia. We estimated a global antibiotic consumption rate of 14·3 (95% uncertainty interval 13·2–15·6) defined daily doses (DDD) per 1000 population per day in 2018 (40·2 [37·2–43·7] billion DDD), an increase of 46% from 9·8 (9·2–10·5) DDD per 1000 per day in 2000. We identified large spatial disparities, with antibiotic consumption rates varying from 5·0 (4·8–5·3) DDD per 1000 per day in the Philippines to 45·9 DDD per 1000 per day in Greece in 2018. Additionally, we present trends in consumption of different classes of antibiotics for selected Global Burden of Disease study regions using the IQVIA, WHO, and ESAC-net input data. We identified large increases in the consumption of fluoroquinolones and third-generation cephalosporins in North Africa and Middle East, and south Asia.
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Reported antibiotic use among patients in the multicenter ANDEMIA infectious diseases surveillance study in sub-saharan Africa
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SeriesMaximising access to achieve appropriate human antimicrobial use in low-income and middle-income countries

Summary

Section snippets

Introduction—balancing access and excess

Guiding principles and measures

Access for all in need

Access to health services

Access to prevention measures

Access to diagnostics

Access to evidence-based management protocols, service provision enhancement, and education

Access to appropriate antimicrobials of assured quality

Access to new innovations

Health systems strengthening

Mechanisms to implement access and minimise excess

Conclusions and recommendations

Lancet

Lancet

Lancet

Lancet

Lancet Infect Dis

Value Health

Lancet

Health Policy

Lancet

Lancet Infect Dis

Lancet

Lancet

Lancet

Lancet

Lancet

Clin Microbiol Infect

Vaccine

Lancet

Lancet Infect Dis

Lancet

Lancet Infect Dis

Lancet Infect Dis

BMJ

Lancet Infect Dis

Clin Microbiol Infect

Lancet

Curr Opin Microbiol

Accountability for maternal, newborn & child survival: the 2013 update

Transforming our world: the 2030 Agenda for Sustainable Development. Document A/70/L.1

Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial

JAMA

The impact of antibiotics on growth in children in low and middle income countries: systematic review and meta-analysis of randomised controlled trials

BMJ

Antibiotic selection pressure and macrolide resistance in nasopharyngeal Streptococcus pneumoniae: a cluster-randomized clinical trial

PLoS Med

Ban on antibiotics as growth promoters in animal feed enters into effect. IP/05/1687

Exploring the evidence base for national and regional policy interventions to combat resistance

Lancet

A win–win solution? A critical analysis of tiered pricing to improve access to medicines in developing countries

Global Health

Constitution of the World Health Organization

International covenant on economic, social and cultural rights

Public health. From financing to fevers: lessons of an antimalarial subsidy program

Science

Q&A on the Affordable Medicines Facility malaria (AMFm)

Trends in availability and prices of subsidized ACT over the first year of the AMFm: evidence from remote regions of Tanzania

Malar J

Where are we now: assessing the price, availability and affordability of essential medicines in Delhi as India plans free medicine for all

BMC Health Serv Res

Availability of antibiotics for purchase without a prescription on the internet

Ann Fam Med

The market dynamics of generic medicines in the private sector of 19 low and middle income countries between 2001 and 2011: a descriptive time series analysis

PLoS One

Impact of regulatory requirements on medicine registration in African countries—perceptions and experiences of pharmaceutical companies in South Africa

South Med Rev

Variation in antibiotic prescribing and its impact on recovery in patients with acute cough in primary care: prospective study in 13 countries

BMJ

The New York Times (New York), Jan 19, 2009

Antibiotic use and resistance in emerging economies: a situation analysis for Viet Nam

BMC Public Health

Global supply of health professionals

N Engl J Med

Pneumonia and diarrhoea: tackling the deadliest diseases for the world's poorest children

Series
Maximising access to achieve appropriate human antimicrobial use in low-income and middle-income countries