Use of WATCH antibiotics prior to presentation to the hospital in rural Burkina Faso

The emergence of antimicrobial resistance (AMR) is driven by appropriate and inappropriate use of antimicrobials. Increasing microorganisms’ exposure to antibiotics results in selection pressure, while suboptimal regimen allows selective survival of resistant microorganisms [1, 2]. Globally, mortality attributable to AMR infections has been estimated to increase from 700,000 annual deaths in 2014 to 10 million in 2050 [3]. The World Health Organization's 2015 Global Action Plan on AMR urges a.o. to strengthen surveillance of AMR and antibiotic use, and to optimize the use of antibiotics [4]. A global surveillance network for monitoring concurrently AMR and antibiotic use, the Global Antimicrobial Resistance Surveillance System (GLASS), has since been set up, reporting country-wide AMR prevalence of key human pathogens and antibiotics [5]. To monitor antibiotic use, WHO proposed a classification of antibiotics for human use in three groups, "Access", "Watch" and "Reserve", according to their clinical importance, specific recommendations for their appropriate use, and resistance potential [6]. Antibiotic sales data during 2000–2015 showed that the human use of so-called Watch antibiotics, critically important antibiotics particularly at risk of AMR emergence, was declining in high-income countries, while importantly increasing in middle income countries for which data were available [7, 8].

In sub-Saharan Africa, self-medication with over-the-counter antibiotics from private pharmacies or informal drug stores, without prior prescription by a qualified health worker, is frequent and facilitates uncontrolled antibiotic use [8‐11]. To optimize antibiotic use, it is crucial to understand the epidemiology of antibiotic use, in the community as well as in the hospital. Furthermore, also in local primary health care centers, antibiotic prescriptions are not always rational [9, 12]. Peripheral health workers’ poor understanding of the correct use of antibiotics and risks of AMR, limited availability and use of diagnostic tools and difficult access to qualified referral healthcare are likely to be fuelling irrational prescribing of antibiotics [13, 14]. National level antibiotic consumption estimated from wholesale data, as in Burkina Faso, is limited to the official healthcare sector and usually aggregates in- and outpatient use [15]. To our knowledge, no studies so far have investigated community-level antibiotic use. The purpose of this study is to understand community-level antibiotic use in febrile patients prior to presentation to the hospital in a rural district of Burkina Faso.

Nearly 40% of patients presenting with acute fever to a referral hospital in rural Burkina, reported pre-hospital antibiotic use; more than half of patients who were referred by a primary health care centre, and a quarter of self-referred patients. Nearly 60% of febrile patients with pre-hospital antibiotic use for whom a microbiological diagnosis was available did not have a bacterial infection confirmed.

While empirical first- or second-choice (Access) antibiotics were most frequently used, Watch antibiotics were used by 42% of patients referred from a primary health care center. The high use of Watch antibiotics in referred patients is worrisome particular since ceftriaxone (Watch) is not on the Burkina Faso medicine list for use in primary health care centers and is recommended at this level only in case of a meningitis outbreak (which did not occur during our study period) [24]. Moreover, Watch antibiotics accounted for 28% of antibiotics used by self-referred patients, who presumably self-medicated with antibiotics obtained without prescription at private pharmacies or from informal drug sellers. Use of Watch antibiotics was not associated with severity or seasonality as there was no increased risk for patients admitted compared to those treated as outpatients nor during low-malaria transmission season compared to high-malaria transmission season.

High and increasing use of Watch antibiotics has been observed in other low- and middle-income settings [7, 25, 26]. To optimize antibiotic use, it is important to better understand the origins of and reasons why Watch antibiotics are used, both at primary health care center level and without prescription at the community-level. Our study illustrates the need to monitor antibiotic use among official and informal healthcare providers. Nationwide antibiotic use estimated from official sales data found that, in 2015, 75% of antibiotics used in Burkina Faso were Access and 24% Watch group, achieving the WHO target of at least 60% of antibiotics used to be Access antibiotics [15]. This use of Watch antibiotics is lower than the proportion of Watch antibiotics reported in the present study. In comparison, the frequency of pre-hospital antibiotic use by febrile patients admitted to the Nanoro district hospital in 2012–2013 was lower (28.2%), and the proportion of Access antibiotics used was higher (45.9% amoxicillin or ampicillin vs. 32.3% now and 35.1% trimethoprim + sulfamethoxazole vs. 10.6% now) [19], further confirming the need to halt and reverse this high prevalence of Watch antibiotic use.

Despite ampicillin being the treatment of choice for patients with severe infectious diseases at primary health care center level pending referral, it is increasingly ineffective against Enterobacterales. Indeed, most (90.5%) of non-Typhi Salmonella and 87.5% of Escherichia coli were resistant to ampicillin in Nanoro during 2012–2013 [19]. This could explain (systematic) use of ceftriaxone when—in the absence of a microbiological diagnosis—bloodstream infection is suspected. Rapid referral to the district hospital, where laboratory testing should be available as recommended in the WHO model list of essential in vitro diagnostics [27] is then indicated. Because cephalosporin use has been associated to the emergence of beta-lactamase-producing pathogens, particular caution must be taken to optimize its use [28]. Integrating point-of-care CRP or procalcitonin tests at primary health care center level, to differentiate between bacterial and non-bacterial causes of fever, could be explored [29].

Some caution interpreting these findings is needed. First, the inclusion of outpatients during the second half of the study period might have resulted in some changes in the study population and pre-hospital antibiotic use. However, we observed no difference in the prevalence of antibiotic use, when comparing the two populations from both recruitment periods. Further, data about pre-hospital antibiotic use were missing for a quarter of screened patients. Also, antibiotic use was collected via a survey capturing use during the two weeks before consultation at the hospital, potentially underestimating actual use. Whenever possible, reported antibiotic use was verified from referral forms, patient medical files (healthcare booklet), and antibiotic packaging or blisters. Dosage and duration of antibiotic used were not available and the final diagnoses at the district hospital may not correspond to those that had triggered prescription or self-medication within the two preceding weeks.

The frequent use of Watch antibiotics in primary health care centers and at community-level in rural Burkina Faso is concerning in a context of increasingly ineffective first-line antibiotics. It points to the need to set up antibiotic use monitoring and antibiotic stewardship in rural communities in low- and middle-income countries (LMIC. As no alternatives for the currently available Watch antibiotics are available nor affordable in many LMIC settings, it is imperative to act to avoid even more alarming levels of resistance in years to come.