Antibiotic prescription practices in primary care in low- and middle-income countries: A systematic review and meta-analysis

BACKGROUND: The widespread use of antibiotics plays a major role in the development and spread of antimicrobial resistance. However, important knowledge gaps still exist regarding the extent of their use in low- and middle-income countries (LMICs), particularly at the primary care level. We performed a systematic review and meta-analysis of studies conducted in primary care in LMICs to estimate the prevalence of antibiotic prescriptions as well as the proportion of such prescriptions that are inappropriate. METHODS AND FINDINGS: We searched PubMed, Embase, Global Health, and CENTRAL for articles published between 1 January 2010 and 4 April 2019 without language restrictions. We subsequently updated our search on PubMed only to capture publications up to 11 March 2020. Studies conducted in LMICs (defined as per the World Bank criteria) reporting data on medicine use in primary care were included. Three reviewers independently screened citations by title and abstract, whereas the full-text evaluation of all selected records was performed by 2 reviewers, who also conducted data extraction and quality assessment. A modified version of a tool developed by Hoy and colleagues was utilized to evaluate the risk of bias of each included study. Meta-analyses using random-effects models were performed to identify the proportion of patients receiving antibiotics. The WHO Access, Watch, and Reserve (AWaRe) framework was used to classify prescribed antibiotics. We identified 48 studies from 27 LMICs, mostly conducted in the public sector and in urban areas, and predominantly based on medical records abstraction and/or drug prescription audits. The pooled prevalence proportion of antibiotic prescribing was 52% (95% CI: 51%-53%), with a prediction interval of 44%-60%. Individual studies\u27 estimates were consistent across settings. Only 9 studies assessed rationality, and the proportion of inappropriate prescription among patients with various conditions ranged from 8% to 100%. Among 16 studies in 15 countries that reported details on prescribed antibiotics, Access-group antibiotics accounted for more than 60% of the total in 12 countries. The interpretation of pooled estimates is limited by the considerable between-study heterogeneity. Also, most of the available studies suffer from methodological issues and report insufficient details to assess appropriateness of prescription. CONCLUSIONS: Antibiotics are highly prescribed in primary care across LMICs. Although a subset of studies reported a high proportion of inappropriate use, the true extent could not be assessed due to methodological limitations. Yet, our findings highlight the need for urgent action to improve prescription practices, starting from the integration of WHO treatment recommendations and the AWaRe classification into national guidelines. TRIAL REGISTRATION: PROSPERO registration number: CRD42019123269

Over-the-counter antibiotic dispensing in South India: a standardised patient study

Background. Antimicrobial resistance is a global health emergency, and one of the contributing factors is overuse and misuse of antibiotics. India is one of the world's largest consumers of antibiotics, and inappropriate use is potentially widespread, particularly in private pharmacies. This study aimed to use standardised patients (SPs) to measure over-the-counter antibiotic dispensing in one region.Methods. Three adults from the local community in Udupi, India, were recruited and trained as SPs. Three conditions were considered: diarrhoea, upper respiratory tract infection (URI), and acute fever suggestive of malaria. For each condition, there was a paediatric case and an adult case, giving a total of six SP case presentations. Adult SPs were used as proxies for the paediatric cases. Each individual recruited as an SP visited 279 of 350 pharmacies in the district during July to October 2018, seeking care for a sick child at home with one of the conditions. Upon the completion of this interaction, the SP additionally asked for help for their own symptoms of one of the other conditions. A model using generalised estimating equations with a logit link was fit to determine if the following factors affected antibiotic dispensing: urban vs. rural pharmacy, presence of other customers, referral to another provider, questions asked by the pharmacy staff, and length of the SP-pharmacy interaction. Results. A total of 1522 SP interactions were successfully completed. The proportion of SP interactions resulting in the provision of an antibiotic was 4.31% [95% CI: 3.04%, 6.08%] for adult SPs and 2.88% [95% CI: 1.86%, 4.4%] for child SPs. In the model, three covariates showed a significant association with the outcome of antibiotic dispensing. Referral to another provider was associated with an odds ratio of 0.38 [95% CI: 0.18 – 0.79], number of questions asked was associated with an odds ratio of 1.54 [95% CI: 1.30 – 1.84], and a SP-pharmacist interaction lasting longer than three minutes was associated with an odds ratio of 3.03 [95% CI: 1.11 – 8.27] as compared to an interaction lasting less than one minute. The difference between the proportion of antibiotic dispensing for the adult and paediatric cases was non-significant (p = 0.1), but in a model examining antibiotic dispensing for paediatric diarrhoea, dispensing for adult SPs was associated with an increase in the odds of the child SPs receiving an antibiotic.Conclusion. Over-the-counter antibiotic dispensing rate was low in Udupi district and substantially lower than previously published SP studies in other regions of India. Dispensing was lowest when pharmacies referred to a doctor, and higher when pharmacies asked more questions or spent more time with clients.Introduction. La résistance aux antibiotiques est une menace pour la santé des êtres humains. L’une des causes principales est l’abus d’antibiotique, à savoir la surutilisation ou la mauvaise utilisation des antibiotiques. L’Inde en est l’un des plus grands consommateurs, et leur usage inapproprié y est répandu, particulièrement dans le secteur privé. Cette étude vise à utiliser des patients simulés (PS) pour mesurer la distribution d’antibiotiques sans prescription dans une région. Méthode. Trois adultes de la communauté locale de Udupi en Inde ont été embauchés et entrainés comme patients simulés. Trois maladies ont été utilisées : diarrhée, infection des voies respiratoires supérieures, et une fièvre aiguë qui suggère le paludisme. Il y avait un cas simulé adulte et un cas simulé pédiatrique pour chacune d’entre elles, donnant un total de six cas simulés. Chaque adulte entrainé comme PS a visité 279 des 350 pharmacies de Udupi entre juillet et octobre 2018. Le PS commençait par demander de l’aide pour un enfant chez lui avec une des maladies choisies. Ensuite, il demandait de l’aide pour ses propres symptômes d’une autre maladie. En utilisant une régression logistique ajustée avec des équations d’estimation généralisées, nous avons essayé d’identifier si les caractéristiques de la visite affectaient la distribution d’antibiotiques. Nous avons considéré comme caractéristiques de la visite : l’emplacement de la pharmacie (urbaine ou rurale), la présence d’autres clients au moment de la visite, la référence médicale, le nombre de questions posées au PS par la pharmacie, et la durée de la visite.Résultat. Un total de 1522 interactions PS-pharmacie ont été complétées avec succès. La proportion d’interactions qui ont mené à la distribution d’un antibiotique était de 4.31% [95% IC: 3.04%, 6.08%] pour les PS adultes et de 2.88% [95% IC: 1.86%, 4.4%] pour les PS enfants. Dans ce modèle, trois covariables ont montré une association significative avec la variable de distribution d’antibiotiques. Pour la variable “référence médicale”, le rapport des cotes était de 0.38 [95% IC: 0.18 – 0.79] et pour la variable “nombre de questions posées”, il était de 1.54 [95% IC: 1.30 – 1.84]. Comparativement à une interaction durant moins d’une minute, une interaction qui durait plus de trois minutes avait 3.03 [95% CI: 1.11 – 8.27] fois plus de chances de se conclure par la distribution d’un antibiotique. Il n’y avait pas une différence statistiquement significative entre les proportions d’adultes et d’enfants qui ont reçu un antibiotique (p = 0.1). Cependant, dans un modèle pour la diarrhée pédiatrique, si le PS adulte recevait un antibiotique, le PS enfant avait plus de chances de recevoir un antibiotique.Conclusion. La distribution d’antibiotiques sans prescription était faible à Udupi, particulièrement si nous comparons les résultats aux autres étudies de patients simulés qui ont pu être effectuées dans d’autres régions en Inde. La distribution était la plus faible lorsque les pharmacies dirigeaient les patients vers un médecin et plus élevée lorsque les pharmacies posaient plus de questions ou passaient plus de temps avec les patients

A bibliometric analysis of tuberculosis research, 2007-2016.

BACKGROUND:Tuberculosis (TB) research is a key component of the End TB Strategy. To track research output, we conducted a bibliometric analysis of TB research from the past decade. METHODS:The Web of Science database was searched for publications from January 2007 to December 2016 with "tuberculosis" in the title. References were analysed using the R bibliometrix package. A year-stratified 5% random subset was drawn to extract funding sources and identify research areas. FINDINGS:The annual growth rate of publications was 7.3%, and was highest (13.1%) among Brazil, Russia, India, China and South Africa (BRICS). The USA was the most productive country, with 18.4% of references, followed by India (9.7%), China (7.3%), England (6.5%), and South Africa (3.9%). In the subset analysis, the most common research area was 'fundamental research' (33.8%). Frequently acknowledged funders were US and EU-based, with China and India emerging as top funders. Collaborations appeared more frequently between high-income countries and low/medium income countries (LMICs), with fewer collaborations among LMICs. CONCLUSION:The past decade has seen a continued increase in TB publications. While USA continues to dominate research output and funding, BRICS countries have emerged as major research producers and funders. Collaborations among BRICS would enhance future TB research productivity

International collaborations in TB research.

<p>Each diagram includes the top five publishing countries for that year. Each line between countries represents an article with an author from each country. Dense regions of each plot indicate numerous collaborations between the two countries, demonstrating that collaborations have increased throughout the decade.</p

Proportion of original research articles in each research area by year.

<p>Proportion of original research articles in each research area by year.</p

Top ten publishing countries in TB research, 2007–2016.

<p>Top ten publishing countries in TB research, 2007–2016.</p

Top ten journals most commonly published in over the period 2007–2016 and 5-year impact factor.

<p>Top ten journals most commonly published in over the period 2007–2016 and 5-year impact factor.</p

Flow chart of the bibliometric and subset analysis.

<p>Flow chart of the bibliometric and subset analysis.</p