Magnitude and determinants of antibiotic dispensing without prescription in Spain: a simulated patient study

Magnitude and determinants of antibiotic dispensing without prescription in Spain: a simulated patient study Maruxa Zapata-Cachafeiro 1,2 , Marı´a Pi~ neiro-Lamas 2,3 , Marı´a C. Guinovart 4 , Paula Lo´pez-Va´zquez 1 , Juan Manuel Va´zquez-Lago 1 and Adolfo Figueiras 1–3 * 1 Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain; 2 Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiologı´a y Salud Pu´blica - CIBERESP), Santiago de Compostela, Spain; 3 Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; 4 Unitat d’atencio´ farmace´utica, Regio´ sanita`ria Camp de Tarragona, CatSalut, Tarragona, Spain *Corresponding author. Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain. Tel: !34-981-951-192; E-mail: adolfo.figueira[email protected] Received 5 July 2018; returned 23 August 2018; revised 27 September 2018; accepted 1 October 2018 Objectives: Excessive and inappropriate use of antibiotics increases antimicrobial resistance. The aim of this study was to determine the magnitude and determinants of antibiotic dispensing without prescription in Spain by the simulated patient technique. Methods: A cross-sectional study was conducted with all the pharmacies in a region of north-west Spain (n"977), between December 2016 and January 2017. Four actors visited the pharmacies simulating a respiratory infection. Four incremental levels of pressure were used to obtain an antibiotic. The education and sex of the person who was dispensing and the area where the pharmacy was located were recorded. The effect of these independent variables on the dispensing of an antibiotic without prescription (1 "yes, 0 "no) was modelled by logistic regression. Results: An antibiotic was obtained in 18.83% (95% CI "16.5%–21.41%) of the visits. The area influenced the dispensing of antibiotics without a medical prescription, with a greater likelihood of dispensing in rural (OR "1.79; 95% CI "1.20–2.68) or semi-rural (OR "1.66; 95% CI "1.13–2.44) areas than in urban areas. No association was found with the sex or the training of the person who dispensed the antibiotic. In the pharmacies in urban areas, a lower level of pressure was needed to obtain the antibiotic. Conclusions: This study shows that one-fifth of the pharmacies still dispense antibiotics without prescription, especially under patient pressure. A rural setting has been identified as a risk factor for dispensing without prescription, so it must be taken into account for future interventions. Introduction Resistance to antibiotics is a major challenge facing public health, 1 due to the morbidity, mortality and costs it generates. 2 It is not only a local problem, but also a global one because travellers contribute to the spread of antimicrobial drug resistance. 3 Currently, no one doubts that it is linked to the excessive and inappropriate use of antibiotics. The majority of consumption is outside hospitals and, except for North America and some European countries, part of this is due to self-medication. 4 Controlling access to nonprescribed antibiotics is a key element in decreasing it, and pharmacies play a fundamental role in this. Spain is one of the countries with the highest consumption of antibiotics in the EU and consumption does not cease to grow. 5 It is estimated that 30% of the dispensed antibiotics are not charged to the public reimbursement system, 6 but how much is due to other non-reimbursed resources (e.g. private medicine) and how much to the dispensing of antibiotics without a medical prescription (DAwMP), an unlawful practice, 7 is unknown. Estimating this is a challenge: the use of interviews or surveys can produce results biased by the Hawthorne effect. A robust method could be the simulated patient (SP) method, 8 where an individual visits a pharmacy simulating specific symptoms and requiring an antibiotic. DAwMP near to the real ones are obtained and it allows the quality of pharmaceutical care to be assessed. Using the SP technique, this study aimed to quantify the magnitude of DAwMP in the north-west of Spain and to determine the associated factors. V CThe Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permi[email protected] 511 J Antimicrob Chemother 2019; 74: 511–514 doi:10.1093/jac/dky440 Advance Access publication 5 November 2018 Downloaded from https://academic.oup.com/jac/article-abstract/74/2/511/5161208 by Fac de Medicine Biblioteca user on 20 April 2020 Methods Design and population A cross-sectional study was conducted in two provinces (A Coru~ na and Pontevedra) of north-western Spain. The sampling was comprehensive, including all the pharmacies in the studied geographical area (n"977). Study setting In Spain, the National Health System covers practically all the population and medical care is free. Patients contribute to drug costs depending on the treatment and their income. 9 Drugs can only be dispensed in pharmacies, and some kinds, such as antibiotics, require a medical prescription. Data collection The SP technique was used. 10 Four amateur actors (two women and two men with apparent ages between 30 and 45years) visited the pharmacies between December 2016 and January 2017; 10 pharmacies were visited per day by each SP. They were trained by an expert SP, 11 so that the representation would be uniform. The same symptoms as in previous studies were represented: 11,12 sore throat, difficulty swallowing and feeling feverish, in addition to congestion and cough. Four gradually incremental levels of pressure were used to obtain an antibiotic without prescription: (i) request for medication to relieve the symptoms; (ii) request for a stronger medication than that offered; (iii) request for an antibiotic; and (iv) specific request for amoxicillin. In a data collection notebook (case report form) we recorded the result of the demand process, reason why DAwMP did not occur, pharmaceutical care (referral to a doctor, questions about allergies and pregnancy), sex and training (pharmacist or assistant) of dispenser and area where the pharmacy was located [rural (,10000 inhabitants), semi-rural (between 10000 and 50000inhabitants) and urban (.50000 inhabitants)]. Ethics The Galician Ethics Committee approved the study (code number 2015/597). No personal data of professionals were recorded. We generated an automatic code for each pharmacy, which made it impossible for the researchers to matcheachrecordtothecorrespondingpharmacyanditsoutcomeinthe demand process. Outcomes and analysis The effects of independent variables on DAwMP (1 "yes, 0 "no) were modelled by simple logistic regression (crude analysis) and by multiple logistic regression (adjusted analysis). The variables with a Pvalue ,0.20 in the bivariate analysis were considered potentially confounding. They were confirmed as confounders if they produced a .10% change in the coefficient when they were deleted from the multivariate model. The results were expressed as ORs and 95% CIs. To analyse whether the area influenced the level of pressure required to obtain the antibiotic, we performed a sub-analysis of those pharmacies classified as DAwMP. We created a binary variable, with a value of 1 if the antibiotic was obtained at the first or second levelof pressure (the antibiotic was not openly requested) and 0 for those at the third or fourth level (the SP requested an antibiotic). Results An antibiotic was obtained in 184 pharmacies (18.83%; 95% CI "16.50%–21.41%), mostly between the third and fourth levels of pressure (Figure 1). Of the pharmacies that carried out DAwMP, 74.5% explained the frequency with which the antibiotic should be taken, 24.5% asked about allergies to medications, 35.9% recommended seeing a doctor, and 37.5% asked female SPs about the possibility of pregnancy. The most frequently dispensed antibiotic was amoxicillin (n"127, 69.0%), in 7% of cases in combination with clavulanic acid. Azithromycin (n"42, 22.8%), co-trimoxazole (n"7, 3.8%), moxifloxacin (n"4, 2.2%), cefuroxime (n"2, 1.1%), clarithromycin (n"1, 0.5%) and clindamycin (n"1, 0.5%) were obtained less frequently. The level of pressure at which each antibiotic was obtained can be found in Table S1 (available as Supplementary Population (N) 977 pharmacies Sample (n) 977 pharmacies Dispenses antibiotic without prescription 184 (18.83%) At the first level 29/977 (2.97 %) At the second level 40/948 (4.22%) At the third level 41/908 (4.52%) At the fourth level 74/867 (8.54%) Does not dispense antibiotics without prescription 793 (81.17%) • Administrative reasons: 489 (61.66%) • Public health reasons: 64 (8.07%) • Both 240 (30.26%) Figure 1. Flow of participants through the study. Zapata-Cachafeiro et al. 512 Downloaded from https://academic.oup.com/jac/article-abstract/74/2/511/5161208 by Fac de Medicine Biblioteca user on 20 April 2020 data at JAC Online). In most cases, an over-the-counter cold medicine was offeredinstead of an antibiotic. Associated factors It was found that the area influenced DAwMP (Table 1)andDAwMP wasmorelikelyinrural(OR"1.79; 95% CI "1.20–2.68) or semi-rural (OR "1.66; 95% CI "1.13–2.44) areas. There were no differences as a function of sex or the training of the person who dispensed medication. There were also no differences between the four SPs. The sub-analysis of the pharmacies that carried out DAwMP showed an increased risk of obtaining an antibiotic without an SP request in urban areas compared with rural areas (1/OR"2.29; 95% CI "1.08–4.83). No DAwMP Among the pharmacies that did not carry out DAwMP, 91.9% provided reasons related to administration; for instance, pharmacies are not allowed to sell antibiotics (Figure 1). In 30.26% of the cases, this was reinforced with reasons related to health (absence of a diagnosis, development of resistance or possible viral aetiology). Furthermore, 83.61% advised consulting a doctor. Discussion This large study with SPs shows that almost one-fifth of the pharmacies carried out DAwMP and that this depended on the area and the customer’s level of pressure. This indicates the need for interventions to reduce this practice and their prioritization in rural environments. Our percentage of visits resulting in DAwMP (18.8%) is lower than that obtained by other studies carried out with the same methodology in another part of Spain, where 47.9% was obtained. 11 It is also lower than those reported in other countries, 4 which may indicate that the recent campaigns to reduce inappropriate use of antibiotics have been effective. We believe that the comparison of studies using SPs should be done cautiously. The symptomatology and levels of pressure used may differ. SPs even frequently request the antibiotic for a family member, which can affect DAwMP. We also found that DAwMP was lower than that obtained in a survey in a nearby area (65%). 7 This may be due to various aspects: the study included dispensing for other infections (urinary tract, dental infections) and a cumulative percentage was obtained, such that a pharmacist could be classified as carrying out DAwMP even if he or she only did so occasionally (for example, for a regular customer). As in a medical consultation, the patient’s pressure is decisive in obtaining an antibiotic. 13 We also found higher DAwMP in rural areas. This may be because there are no nearby continuous medical care centres, which was also observed in a study in the same setting. 7 However, antibiotics were obtained at lower levels of pressure in urban areas, perhaps because these areas are more commercial or the professionals bear a greater workload, which could lead to a poorer quality of dispensing. 14 This study also allowed pharmaceutical care to be rated. Almost three-quarters of the pharmacies suggested consulting a doctor. Insome cases, they referred the patient directly tothe doctor without offering any product over the counter, because they considered the diagnosis doubtful. Increasing access of pharmacists to clinical guidelines on respiratory infections might be beneficial for the health system. Pharmacies would act like a screening test, decreasing the demand for consultation in primary care and/or emergency wards for common and self-limiting diseases. If educational interventions were carried out conjointly in pharmacies and the general population (to decrease erroneous knowledge on antibiotics), 15 the inappropriate use of antibiotics could be reduced. Strengths and limitations As strengths, we stress that this is the SP study with the largest sample size that we know of, 4,16 and that the sampling was exhaustive. The visits were carried out in a short period of time (minimizing the impact of interventions that may have taken place at Table 1. Influence of independent variables on DAwMP Characteristic DAwMP OR a 95% CI Pno, n(%) yes, n(%) Sex women 634 (82.2) 137 (17.8) 1 men 159 (77.2) 47 (22.8) 1.37 0.94–1.99 0.101 Area b urban 360 (85.7) 60 (14.3) 1 semi-rural 242 (78.3) 67 (21.7) 1.66 1.13-2.44 0.010 rural 191 (77.0) 57 (23.0) 1.79 1.20–2.68 0.005 Identification pharmacist 454 (81.7) 102 (18.4) 1 assistant 136 (84.5) 25 (15.5) 0.82 0.51–1.32 0.410 no identification 203 (78.1) 57 (21.9) 1.25 0.87–1.80 0.230 SP number 1 200 (80.3) 49 (19.7) 1 2 193 (83.2) 39 (16.8) 0.82 0.52–1.31 0.417 3 189 (77.8) 54 (22.2) 1.17 0.75–1.80 0.488 4 211 (83.4) 42 (16.6) 0.81 0.52–1.28 0.371 a Crude analysis. None of the independent variables has shown a confounding effect. b Area: rural (,10000 inhabitants), semi-rural (between 10000 and 50000 inhabitants) and urban (.50000 inhabitants). Antibiotic dispensing without prescription in Spain JAC 513 Downloaded from https://academic.oup.com/jac/article-abstract/74/2/511/5161208 by Fac de Medicine Biblioteca user on 20 April 2020 the same time) and there were no differences in the number of antibiotics obtained by the four actors. In addition, by using SPs rather than surveys we avoided the social desirability bias 17,18 (obtaining socially accepted answers) and this allowed appraisal of the effect of patient pressure. As limitations, it should be noted that the number of antibiotics obtained without a medical prescription can vary for regular customers and according to the type of infection the SP claims to have. Conclusions Reducing self-medication with antibiotics is essential in the fight against drug resistance. This study shows that 19% of pharmacies still carry out DAwMP at the insistence of a client and it has identified the rural area as a risk factor. Interventions aimed at reducing dispensing of non-prescribed antibiotics should be carried out, prioritizing them in rural pharmacies. Acknowledgements We would like to thank the four SPs for their work and Virginia Navascues for her assistance with the English text. Funding This study was supported by a Health Research Fund (Fondo de Investigacio´n Sanitaria) grant (PI15/00844) from the Carlos III Health Institute (Instituto de Salud Carlos III). The funder had no role in the study design, data collection and analysis, or decision to publish. Transparency declarations None to declare. Author contributions M. Z.-C., A. F., M. C. G., M. P.-L., P. L.-V. and J. M. V.-L. designed the study; the fieldwork was coordinated by M. Z.-C., M. P.-L. and A. F.; M. Z.-C. undertook database management and statistical analysis; interpretation of the statistical analysis was performed by M. Z.-C., M. P.-L. and A. F.; and the text was drafted by M. Z.-C. and A. F.; and discussed in depth with M. P.-L., M. C. G., P. L.-V. and J. M. V.-L. Supplementary data Table S1 is available as Supplementary data at JAC Online. References 1Laxminarayan R, Duse A, Wattal C et al. Antibiotic resistance—the need for global solutions. Lancet Infect Dis 2013; 13: 1057–98. 2O’Neill J. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. 2014. https://amr-review.org/sites/default/files/AMR%20 Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20 health%20and%20wealth%20of%20nations_1.pdf. 3Von Wintersdorff CJH, Penders J, Stobberingh EE et al. High rates of antimicrobial drug resistance gene acquisition after international travel, The Netherlands. Emerg Infect Dis 2014; 20: 649–57. 4Morgan DJ, Okeke IN, Laxminarayan R et al. Non-prescription antimicrobial use worldwide: a systematic review. Lancet Infect Dis 2011; 11: 692–701. 5ECDC. Summary of the Latest Data on Antibiotic Consumption in the European Union. 2017. https://ecdc.europa.eu/sites/portal/files/documents/ Final_2017_EAAD_ESAC-Net_Summary-edited%20-%20FINALwith%20er ratum.pdf. 6Campos J, Ferech M, La´zaro E et al. Surveillance of outpatient antibiotic consumption in Spain according to sales data and reimbursement data. J Antimicrob Chemother 2007; 60: 698–701. 7Zapata-Cachafeiro M, Gonza´lez-Gonza´lez C, Va´quez-Lago JM et al. Determinants of antibiotic dispensing without a medical prescription: a crosssectional study in the north of Spain. J Antimicrob Chemother 2014; 69: 3156–60. 8Watson M, Norris P, Granas A. A systematic review of the use of simulated patients and pharmacy practice research. Int J Pharm Pract 2006; 14: 83–93. 9Legido-Quigley H, Urdaneta E, Gonzalez A et al. Erosion of universal health coverage in Spain. Lancet 2013; 382: 1977. 10 Caama~ no F, Ruano A, Figueiras A et al. Data collection methods for analyzing the quality of the dispensing in pharmacies. Pharm World Sci 2002; 24: 217–23. 11 Guinovart MC, Figueras A, Llop JC et al. Obtaining antibiotics without prescription in Spain in 2014: even easier now than 6 years ago. J Antimicrob Chemother 2015; 70: 1270–1. 12 Llor C, Cots JM. The sale of antibiotics without prescription in pharmacies in Catalonia, Spain. Clin Infect Dis 2009; 48: 1345–9. 13 Lopez-Vazquez P, Vazquez-Lago JM, Figueiras A. Misprescription of antibiotics in primary care: a critical systematic review of its determinants. JEval Clin Pract 2012; 18: 473–84. 14 Caama~ no F, Tome´-OteroM,TakkoucheBet al. Influence of pharmacists’ opinions on their dispensing medicines without requirement of a doctor’s prescription. Gac Sanit Sespas 2005; 19: 9–14. 15 TNS Opinion & Social. Special Eurobarometer 445: Antimicrobial Resistance. Brussels, Belgium, 2016. https://ec.europa.eu/health/amr/sites/ amr/files/eb445_amr_generalreport_en.pdf. 16 Chang J, Ye D, Lv B et al. Sale of antibiotics without a prescription at community pharmacies in urban China: a multicentre cross-sectional survey. J Antimicrob Chemother 2017; 72: 1235–42. 17 Peabody JW, Luck J, Glassman P et al. Comparison of vignettes, standardized patients, and chart abstraction: a prospective validation study of 3 methods for measuring quality. JAMA 2000; 283: 1715–22. 18 Brenner PS, DeLamater J. Lies, damned lies, and survey self-reports? Identity as a cause of measurement bias. Soc Psychol Q 2016; 79: 333–54. Zapata-Cachafeiro et al. 514 Downloaded from https://academic.oup.com/jac/article-abstract/74/2/511/5161208 by Fac de Medicine Biblioteca user on 20 April 2020