Review
Non-prescription antimicrobial use worldwide: a systematic review

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Summary

In much of the world antimicrobial drugs are sold without prescription or oversight by health-care professionals. The scale and effect of this practice is unknown. We systematically reviewed published works about non-prescription antimicrobials from 1970–2009, identifying 117 relevant articles. 35 community surveys from five continents showed that non-prescription use occurred worldwide and accounted for 19–100% of antimicrobial use outside of northern Europe and North America. Safety issues associated with non-prescription use included adverse drug reactions and masking of underlying infectious processes. Non-prescription use was common for non-bacterial disease, and antituberculosis drugs were available in many areas. Antimicrobial-resistant bacteria are common in communities with frequent non-prescription use. In a few settings, control efforts that included regulation decreased antimicrobial use and resistance. Non-prescription antimicrobial and antituberculosis use is common outside of North America and northern Europe and must be accounted for in public health efforts to reduce antimicrobial resistance.

Introduction

Antimicrobials are among the most commonly purchased drugs worldwide.1 They are essential treatments, especially in the developing world where infectious diseases are a common cause of death.2 Crucial to success of antimicrobial treatment is the use of well-tolerated drugs with activity against common pathogens. Antimicrobial resistance is shrinking the range of antimicrobial drugs and is a worldwide public health problem.3, 4, 5 Although resistance is commonly studied in Europe and North America, developing countries also face the threat of antimicrobial resistance. A substantial proportion of healthy people in developing countries are colonised with multidrug-resistant bacteria.6, 7, 8, 9, 10, 11 Common bacterial pathogens such as Escherichia coli, Salmonella spp, or Streptococcus pneumoniae are often multidrug resistant in these settings. Mycobacterium tuberculosis, including multidrug-resistant M tuberculosis, is also common in low-income to middle-income countries, and extremely drug resistant strains have emerged.12, 13 By contrast with Europe and North America, developing countries have limited access to antimicrobials, particularly to new drug classes, and drugs that are available often lack activity against these multidrug-resistant bacteria that are becoming more common.14, 15, 16

Antimicrobial resistance is a global issue.17 Resistance genes spread throughout the world, as shown by the global spread of CTX-M extended spectrum β-lactamase (ESBL), NDM-1, or Klebsiella pneumoniae carbapenemase (KPC) producing Enterobacteriaceae.18, 19, 20 Travellers might acquire resistant bacteria that can be transmitted in their home countries.20, 21, 22 Transmission between developed and developing countries is presumably two-way and is rarely identified in developing countries because of inadequate surveillance.17, 19, 20

Antimicrobials, when appropriately targeted to a susceptible pathogen, improve outcomes for patients.23 However, use and overuse at the population level is associated with the emergence of bacterial resistance.16, 24 Behaviours that promote resistance in one individual or population can have wider consequences for the global community.25 These behaviours extend beyond human antimicrobial use to areas such as antimicrobial use in livestock production.26 Although non-prescription antimicrobial use is typically studied within a single country, the effect of widespread antimicrobial overuse is likely to be felt worldwide.15

By contrast with northern Europe and North America, where outpatient antimicrobials are largely restricted to prescription-only use, non-prescription access to antimicrobials is common in the rest of the world.9, 14, 15, 16 Pharmaceutical surveillance in Spain showed that about 30% of outpatient antimicrobials purchased were not identified by reimbursement data, largely because non-prescription sales were not tracked.27 In all countries, most antimicrobial use occurs outside of hospitals.28 Interventions to preserve the effectiveness of antimicrobials have focused on hospitals or providers thereby missing non-prescription antimicrobial use.29 Previous reviews have broadly described the problem of antimicrobial resistance in developing countries. However, none have expressly addressed non-prescription antimicrobial use.14, 15, 30, 31, 32, 33, 34, 35 To quantify the global frequency and effect of non-prescription antimicrobial use, we did a systematic review of published work.

Section snippets

Search strategy and selection criteria

We searched Medline, PubMed, and Google Scholar for articles published in English or Spanish between 1970–2009 using the keywords “antibiotic(s)”, “antimicrobial(s)”, “antituberculosis”, or “antitubercular” combined with “over-the-counter (OTC)”, “nonprescription”, “community pharmacy”, “pharmacies”, “developing country”, “pharmacoepidemiology”, “rational use of medicines”, and “self-medication”, and the corresponding Medical Subject Heading (MeSH) terms for the above keywords.

Data extraction and analysis

DJM and SW

Frequency of non-prescription use

We identified 1434 potential references. 117 articles are included in this Review (figure 1). We identified 35 studies that surveyed use of antimicrobials by patients outside of hospital settings (figure 2). We identified three African surveys; two were surveys of the general population in Nigeria40 and Sudan41 and one was a survey of sex workers or soldiers who had sex with them in Nigeria.42 Both general community surveys focused on non-prescription use of antimicrobials and reported

Discussion

The causes and consequences of non-prescription antimicrobial use are varied. Poor regulation of antimicrobials results from absent policies or, more commonly, from absent enforcement of policies, as happens in southern European countries.51, 52, 53, 54, 55 Community antimicrobial resistance was common in several studies that examined communities with frequent use of non-prescription antimicrobials.6, 7, 8, 9, 10, 11 Antimicrobial use, whether it is prescription or non-prescription, exerts

Search strategy and selection criteria

These are described in detail in the Methods section.

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