de la Poza Abad et al. BMC Family Practice (2019) 20:45 https://doi.org/10.1186/s12875-019-0934-7 RESEARCH ARTICLE Open Access Use of delayed antibiotic prescription in primary care: a cross-sectional study Mariam de la Poza Abad1* , Gemma Mas Dalmau2, Ignasi Gich Saladich2,4, Laura Martínez García2, Carl Llor3 and Pablo Alonso-Coello2,4 Abstract Background: One of several strategies developed to reduce inappropriate antibiotic use in situations where the indication is not clear is delayed antibiotic prescription (DAP), defined as an antibiotic prescription issued for the patient to take only in case of feeling worse or not feeling better several days after the visit. We conducted a survey to identify DAP use in Spanish primary care settings. Methods: We surveyed 23 healthcare centers located in 4 autonomous regions where a randomized controlled trial (RCT) on DAP was underway. The primary variable was use of DAP. Categorical and quantitative variables were analyzed by means of the chi-squared test and non-parametric tests, respectively. Results: The survey was sent to 375 healthcare professionals, 215 of whom responded (57.3% response rate), with 46% of these respondents declaring that they had used DAP in routine practice before the RCT started (66.6% afterwards), mostly (91.5%) for respiratory tract infections (RTIs), followed by urinary infections (45.1%). Regarding DAP use for RTIs, the most frequent conditions were pharyngotonsillitis (88.7%), acute bronchitis (62.7%), mild chronic obstructive pulmonary disease exacerbations (59.9%), sinusitis (51.4%), and acute otitis media (45.1%). Most respondents considered that DAP reduced emergency visits (85.4%), scheduled visits (79%) and inappropriate antibiotic use (73.7%) and most also perceived patients to be generally satisfied with the DAP approach (75.6%). Having participated or not in the DAP RCT (74.1% versus 46.2%; p < 0.001), having previously used or not used DAP (86.8% versus 44.2%; p < 0.001), and being a physician versus being a nurse (81.8% versus 18.2%; p < 0.001) were factors that reflected significantly higher rates of DAP use. Conclusions: The majority of primary healthcare professionals in Spain do not use DAP. Those who use DAP believe that it reduces primary care visits and inappropriate antibiotic use, while maintaining patient satisfaction. Given the limited use of DAP in our setting, and given that its use is mainly limited to RTIs, DAP has considerable potential in terms of its implementation in routine practice. Keywords: Delayed antibiotic prescription, Primary care, Survey, Infectious disease Background systems and fostering a false belief that antibiotics are always Infectious diseases are among the most common reasons for beneficial— has serious consequences for patients’ health, in- visits to primary care centers. Approximately 70% are re- cluding the risk of adverse effects and antimicrobial resist- spiratory tract infections (RTIs), most frequently, rhinitis, ance [4]. In recent years, the World Health Organization pharyngitis, and acute bronchitis [1]. Most RTIs are (WHO) has prioritized the problem of antimicrobial resist- self-limiting, with recent reviews suggesting that —except in ance in its agenda [5]. the case of an underlying comorbidity— antibiotics offer lit- Several strategies have been developed to reduce inappro- tle or no clinical benefit [2, 3]. Inappropriate prescription of priate use of antibiotics. One of them is delayed antibiotic antibiotics —as well as implying a cost for national health prescription (DAP), whereby the prescription is issued for the patient to take only in the event of feeling worse or not * Correspondence: mariamdelapoza@gmail.com feeling better several days after the visit. DAP has been 1 Dr Carles Ribas Primary Care Center, C/Foc 112, 08038 Barcelona, Spain widely studied and applied in English-speaking countries [6], Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. de la Poza Abad et al. BMC Family Practice (2019) 20:45 Page 2 of 6 and is especially recommended as a potential strategy for antibiotics, namely, pharyngotonsillitis and chronic obstruct- treating acute uncomplicated RTIs [7]. DAP has also been ive pulmonary disease (COPD) exacerbation. An online tool shown to be effective in uncomplicated urinary tract infec- was used to run the survey and to collect responses, and 3 tions [8] and in acute infective conjunctivitis [9], with better reminders were sent by email at 2-week intervals following results when DAP is implemented in conjunction with ap- initial contact. propriate and structured advice for the patient [10]. In Spain there is little information about the use of DAP. Analysis Llor et al. [11] conducted an observational study that showed The data were analyzed descriptively, with absolute frequen- that DAP resulted in reduced antibiotic use. More recently, cies and proportions calculated for categorical variables, and our research group published results for a multicenter ran- means and standard deviations (or median and range when domized controlled trial (RCT) of DAP [12] that confirmed normality criteria were not fulfilled) calculated for quantita- reduced antibiotic use, similar satisfaction levels with other tive variables. Groups of categorical variables were compared antibiotic strategies, and no increase in adverse effects or using the chi-squared test, and groups of quantitative vari- re-visits [13]. Since no information on use of DAP is avail- ables using analysis of variance (ANOVA) for unpaired data able for our setting, despite its effectiveness in treating acute or non-parametric tests (Mann-Whitney). uncomplicated RTIs, we conducted a survey in primary care Differences in DAP use by disease and by healthcare healthcare centers in Spain. professional characteristics (age, occupation, and RCT participation) were analyzed by comparing proportions Methods using the chi-squared test. Responses to open questions Design were analyzed and coded according to the most frequent Multicenter cross-sectional survey. topics. Statistical significance was set to p < 0.05 and data were analyzed using SPSS version 24.0 (IBM-SPSS). Study population Healthcare staff from 23 Spanish health centers where an Results RCT on DAP was being conducted [12]. The healthcare cen- A total of 375 healthcare professionals received the ques- ters were located in the 4 Spanish Autonomous Regions of tionnaire, of whom 37.7% were participating in the RCT; Catalonia, Navarra, Madrid, and the Basque Country. In- 215 individuals replied to the questionnaire (response rate cluded were all healthcare professionals employed in those 56%). The mean age of respondents was 46.2 (10.1 SD) centers regardless of whether or not they were participating years, 72.6% (n = 156) were family physicians, and 74.4% in the RCT. (n = 160) were women. Respondent characteristics are de- The selected participants were those authorized to scribed in Table 1. prescribe treatments, namely, primary care physicians, Of the total respondents (n = 215), 46% (n = 99) had used medical residents and registered nurses. Nurses were DAP in routine practice before the DAP RCT (37.8% of phy- taken into account, given that in Spain they are autho- sicians and 15.3% of nurses; p = 0.013), and 66.6% (n = 143) rized to attend to initial emergency cases in primary care used DAP in routine practice during the DAP RCT (69.2% centers [14]. We defined respondents as all individuals of physicians and 20.3% of nurses; p < 0.001). Regarding how who returned a filled-in questionnaire. DAP was applied, 76.3% (n = 106) of patients received DAP directly, 15.1% (n = 21) collected the prescription from recep- Survey development tion, 7.2% (n = 10) were referred to their physician, and other We developed the questionnaire based on a review of the strategies were used for 1.4% (n = 2) of patients. scientific literature. Using a combination of descriptors DAP was used mainly for acute RTIs (n = 143; 91.5%), and free-text terms (Additional file 1), we conducted a followed, at a distance, by urinary infections (45.1%), dental search in MEDLINE (via PubMed, from inception until infections (36.6%), skin infections (23.9%), eye infections March 2012) to identify studies of DAP. (14.8%), digestive infections (5.6%), and other infections (7%) We piloted the questionnaire with 6 healthcare profes- (Fig. 1). Regarding DAP use for RTIs, the most frequent con- sionals (2 primary care physicians, 2 nurses and 2 epidemiol- ditions were pharyngotonsillitis (88.7%), acute bronchitis ogists) and evaluated its sensitivity. The final questionnaire (62.7%), mild COPD exacerbations (59.9%), sinusitis (51.4%), included 22 items grouped into 5 sections (Additional file 2): and acute otitis media (45.1%) (Fig. 2). Regarding prescrip- (1) sociodemographic data; (2) clinical scenarios; (3) aware- tion strategies for patients with pharyngotonsillitis, 50.2% re- ness of and participation in the DAP RCT; (4) use of DAP; ceived no antibiotic prescription, 3.3% immediate antibiotic and (5) perceptions of DAP. Referring to the clinical scenar- prescription, and 30.7% received DAP (19.1% directly and ios, with the aim of assessing use of DAP in routine practice, 11.6% at reception). As for mild COPD exacerbations, 0 and the respondents were asked about 2 cases of uncomplicated 84.7% received no and immediate antibiotic prescriptions, re- RTIs posing clinical uncertainty regarding the prescription of spectively, and 4.2% received DAP (directly in all cases). de la Poza Abad et al. BMC Family Practice (2019) 20:45 Page 3 of 6 Table 1 Descriptive characteristics of delayed antibiotic prescription (DAP) survey respondents Number Percent Profession Physician 156 72.6% Nurse 59 27.4% Participating center Catalonia 115 53.5% Madrid 72 33.5% Navarra 23 10.7% Basque Country 5 2.3% Teaching center Yes 146 67.4% No 70 32.6% a Rapid diagnostic techniques Multistix urine test strip 194 90.2% Reactive Strep-A 39 18.1% Reactive PCR 22 10.2% Other 15 7% Used DAP before RCT Yes 99 46% No 57 26.5% Used DAP during RCT Yes 143 66.6% No 16 7.4% DAP type (for DAP users) Direct (patient-led) 106 76.3% Collection from reception 21 15.1% Referral to physician 10 7.2% Other 2 1.4% a Multistix urine test strip (in diagnosis of urine infection), Rapid antigen detection test (Group A streptococcal in pharyngitis) and C-reactive protein (in assessing etiological diagnosis of acute respiratory infection) Strongly agree/agree responses from the survey partici- Professionals who had already used DAP in routine prac- pants (Fig. 3) were as follows: DAP reduces the number of tice had a consistently more favorable perspective on DAP, primary-care emergency visits (85.4%; n = 134); DAP reduces as these strongly agreed/agreed more frequently than those the number of scheduled visits (79%; n = 124); DAP is a good who had not used DAP, as follows: DAP reduces the strategy to optimize the use of available resources (85.2%; number of primary-care emergency visits (93.6% ver- n = 133); DAP reduces inappropriate antibiotic use (73.7%; sus 80%; p < 0.001); DAP is a good strategy to n = 115); patients were satisfied with DAP (75.6%; n = 118); optimize the use of available resources (95.1% versus and DAP can change patients’ perceptions about the need 78.9%; p < 0.001); DAP reduces inappropriate antibiotic for antibiotics for certain infections (68.8%; n = 108). use (86.9% versus 65.2%; p < 0.001)); patients were satisfied Fig. 1 Delayed antibiotic prescription use by infection type de la Poza Abad et al. BMC Family Practice (2019) 20:45 Page 4 of 6 Fig. 2 Delayed antibiotic prescription use by respiratory disease with DAP (91.8% versus 65.3%; p < 0.001); and DAP can experience (mean 21.8 versus 21.71 years; p = 0.929); and change patients’ perceptions about the need for antibiotics employment in a teaching center versus a non-teaching cen- for certain infections (87.1% versus 56.9%; p < 0.001). Dif- ter (69.2% versus 65%; p = 0.561). ferences were only non-significant for DAP reducing the number of scheduled visits (80.7% versus 77.9%; p = 0.131). Discussion Factors that reflected significantly higher rates of DAP Main findings use were as follows: participation versus non-participation Our study shows that an important proportion of pri- in the DAP RCT (74.1% versus 46.2%; p < 0.001), having mary healthcare professionals make no use of DAP strat- previously used versus not having previously used DAP egies for the treatment of acute uncomplicated RTIs. (86.8% versus 44.2%; p < 0.001), and being a physician ver- DAP, when used, was most frequently used for pharyn- sus being a nurse (81.8% versus 18.2%; p < 0.001). No sig- gotonsillitis and least frequently used for otitis and si- nificant differences in DAP use were observed in relation to nusitis. Professionals who became aware of DAP during the following factors: having rapid diagnostic techniques the RCT started to implement a DAP strategy in their available; age (mean 46.7 versus 46.4 years; p = 0.796); work own routine clinical practice. Fig. 3 Healthcare professional perceptions of delayed antibiotic prescription de la Poza Abad et al. BMC Family Practice (2019) 20:45 Page 5 of 6 Most of the respondents considered DAP to reduce the be highly effective [6, 13]. The absence of information on number of primary-care emergency visits (85.4%), the num- DAP use in Spain motivated us to conduct this study. ber of scheduled visits (79%), and inappropriate antibiotic use (73.7%), and most also considered that patients were Limitations and strengths broadly satisfied with DAP (75.6%). Use of DAP was not af- The main limitation of our study was the low response rate fected by the fact of having rapid diagnostic techniques avail- to the survey despite several reminders. Another limitation able, age, work experience or the fact of being employed in a was that we exclusively surveyed professionals from health- teaching versus a non-teaching center. care centers where the DAP RCT was conducted. Thus, since some non-participants in that RCT may have become Our results in the context of previous research aware of DAP through word-of-mouth, our results on DAP The level of use of DAP as documented in our study use may be overestimated. Nonetheless, this fact merely (46%) is lower than in northern European countries; a strengthens our conclusions. Norwegian study [15], for instance, reported that almost The main strengths of our study are that, as far as we 70% of family physicians considered DAP to be a feasible know, this is the first Spanish multicenter survey (23 partici- strategy for treating uncomplicated RTIs. According to pating centers) exploring use of DAP among healthcare pro- that study, sinusitis was the infection for which DAP fessionals, and evaluating predictive factors regarding DAP was most used, contrasting with our study, in which use. Another potential strength is that we also included DAP was most frequently used for pharyngotonsillitis. nurses in the survey; given that they prescribe symptomatic Although our results show lower use of DAP in Spain than treatment and participate in DAP procedures. in English-speaking countries, noteworthy is the fact its use led to more positive perceptions of DAP. This finding reso- Implications for practice and research nates with results from other countries with a lengthy DAP The current level of use of DAP by healthcare staff in Spain track record [16]. Note, however, that a qualitative study suggests that much needs to be done to make this strategy conducted in the UK showed that DAP was not considered known among primary care health professionals. Healthcare to be a feasible strategy by physicians, as these felt uncom- policymakers should also be made aware of DAP as a poten- fortable giving patients clinical responsibilities, and only used tially effective way to improve decision-making regarding an- it for uncertain diagnoses or to avoid conflict with patients tibiotics and to rationalize their prescription and use in [17]. This would indicate that it is important to determine primary care settings. It is also important to foster awareness the baseline situation of a country before designing, dissem- of DAP as a potential treatment strategy among patients. In inating, and implementing DAP strategies in routine prac- order to achieve this we should make known to the GP both tice. This was done, for instance, in Australia [18], where, in the results obtained in other countries, and the excellent re- an effort to combat high antibiotic prescription rates, sults that were obtained in our own country without forget- strategies, including DAP, were designed and implemented ting beforehand to address the barriers that we could find to reduce inappropriate antibiotic use. for Implement the DAP in the usual GP practice as well as Spain continues to have a particularly high rate of anti- the barriers that patients can offer to accept them. Further biotic prescription [19]; moreover, the latest update on anti- studies of optimal strategies for implementing DAP in pri- biotic use published by the European Center for Disease mary care, both in Spain and elsewhere. Thus qualitative re- Prevention and Control —referring to the period 2010– search is necessary, which will reveal the barriers that we can 2014— pointed to an increasing trend in the European find for its implementation by both sides, professionals and Union in general [20]. High antibiotic prescription rates not patients. As well as it will also provide us with information only represent an economic burden but are also a serious about the perspectives of the patients and how they receive public health problem, since overuse of antibiotics is the the DAP and how they use. In this way our group are con- main cause of antimicrobial resistance. The latest data for ducting a qualitative research study in parallel to assess these the European Union confirm that a growing number of items, with groups of both professionals and patients. patients are infected by resistant bacteria [21]. Patients are not generally aware of the serious implications Conclusions of antimicrobial resistance, nor are they aware that they too Most primary care professionals in Spain still do not use can contribute to the solution [22]. Although the association DAP in routine practice. Once professionals become aware between antibiotic prescription and antimicrobial resistance of and use DAP, they report that this strategy reduces pri- is well documented, studies show that reduced antibiotic mary care scheduled and emergency visits and inappropriate prescription at the primary care level can help reduce anti- antibiotic use, while maintaining patient satisfaction. These biotic resistance [23]. Evidence-based strategies are needed findings, combined with positive efficacy and safety results to reduce inappropriate antibiotic use in primary care set- from clinical studies of DAP, highlight the need to actively tings, and DAP is one such strategy that has been shown to implement this strategy in primary care. de la Poza Abad et al. BMC Family Practice (2019) 20:45 Page 6 of 6 Additional files acute rhinosinusitis: a meta-analysis of individual patient data. Lancet. 2008; 371(9616):908–144. 4. Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD. Effect of antibiotic Additional file 1: Search strategy. Search strategy in MEDLINE (via prescribing in primary care on antimicrobial resistance in individual patients: PubMed) from inception up to March 2012. (PDF 12 kb) systematic review and meta-analysis. BMJ. 2010;340:c2096. Additional file 2: Delayed antibiotic prescription (DAP) questionnaire. 5. Zumla A, Blasi F, Raviglione M. Rational use of anti-tuberculosis drugs in the This is a survey aimed at understanding perceptions and attitudes of EU: better patient care and less drug resistance. Eur Respir J. 2012;39(4):802–4. primary care professionals to antibiotic prescription for uncomplicated 6. Spurling GK, Del Mar CB, Dooley L, Foxlee R, Farley R. Delayed antibiotics for infections. (PDF 35 kb) respiratory infections. Cochrane Database Syst Rev. 2017;9:CD004417. https://doi.org/10.1002/14651858.CD004417.pub5.Review 7. National Institute for Health and Clinical Excellence. Prescribing of Abbreviations antibiotics for self-limiting respiratory tract infections in adults and children COPD: Chronic obstructive pulmonary disease; DAP: Delayed antibiotic in primary care. Clinical guideline 69. London: NICE; 2008. prescription; RCT: Randomized controlled trial; RTI: Respiratory tract infection 8. Knottnerus BJ, Geerlings SE, Moll van Charante EP, ter Riet G. Women with symptoms of uncomplicated urinary tract infection are often willing to delay Acknowledgments antibiotic treatment: a prospective cohort study. BMC Fam Pract. 2013;14:71. We would like to thank Ailish Maher and Andrea Cervera for their assistance 9. Everitt HA, Little PS, Smith PW. A randomised controlled trial of management with the English in a version of the manuscript. strategies for acute infective conjunctivitis in general practice. BMJ. 2006; 333(7563):321. Epub 2006 Jul 17. Erratum in: BMJ. 2006 Sep 2;333(7566):468. Funding 10. Little P, Moore M, Kelly J, Williamson I, Leydon G, McDermott L, et al. Delayed This article is part of the doctoral thesis of the main author, MDP, grant- antibiotic prescribing strategies for respiratory tract infections in primary care: aided by the Jordi Gol University Institute for Primary Care Research (IDIAP). pragmatic, factorial, randomised controlled trial. BMJ []. 2014;348():g1606. PAC is supported by a Miguel Servet investigator contract from the Instituto Available from: http://www.ncbi.nlm.nih.gov/pubmed/24603565%5Cn, http:// de Salud Carlos III (CPII15/0034). www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3944682 11. Llor C, Hernández S, Calviño OMA. Prescripción diferida de antibióticos en Availability of data and materials España. Med Clin. 2005;125:76. All data generated or analyzed in this study are included in this published 12. de la Poza Abad M, Mas Dalmau G, Moreno Bakedano M, González article and its additional files. González AI, Canellas Criado Y, Hernández Anadón S, Rotaeche del Campo R, Torán Monserrat P, Negrete Palma A, Pera G, Borrell Thió E, Llor C, Little P, Authors’ contributions Alonso Coello P. Delayed antibiotic prescription (DAP) working group. MPA, PAC, and GMD designed the study and were responsible for Rationale, design and organization of the delayed antibiotic prescription conducting the study. All other authors (MPA, PAC, GMD and LMG and CL) (DAP) trial: a randomized controlled trial of the efficacy and safety of critically commented on the study design. MPA and IG analyzed the data. delayed antibiotic prescribing strategies in the non-complicated acute MPA, GMD, LMG, CL, and PAC interpreted the data. MPA wrote the first draft respiratory tract infections in general practice. BMC Fam Pract. 2013;14:63. of the manuscript. All authors critically read and approved the final version. 13. de la Poza Abad M, Mas Dalmau G, Moreno Bakedano M, González González AI, Canellas Criado Y, Hernández Anadón S, et al. Prescription Ethics approval and consent to participate strategies in acute uncomplicated respiratory infections. JAMA Intern Med. Given that the questionnaire was completed by medical professionals who 2016;176(1):21. Available from: http://archinte.jamanetwork.com/article.aspx? had been previously informed, by completing the questionnaire it was https://doi.org/10.1001/jamainternmed.2015.7088. considered that their informed consent had been given. 14. Diari Oficial de la Generalitat de Catalunya. Núm. 6412- 8.7.2013. CVEDOGC- The protocol was approved by the Clinical Research Ethics Committee of the A-13178094-2013. Available from: http://www.gencat.cat/dogc. Jordi Gol University Institute for Primary Care Research (IDIAP). 15. Høye S, Frich JC, Lindbæk M. Use and feasibility of delayed prescribing for respiratory tract infections: a questionnaire survey. BMC Fam Pract 2011;12: 34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21592334%5Cn, Consent for publication http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3114766 Not applicable. 16. Ryves R, Eyles C, Moore M, McDermott L, Little P, Leydon GM. Understanding the delayed prescribing of antibiotics for respiratory tract infection in primary Competing interests care: a qualitative analysis. BMJ Open [Internet]. 2016;6(11):e011882 Available The authors declare that they have no competing interests. from: http://www.ncbi.nlm.nih.gov/pubmed/27864242. 17. Peters S, Rowbotham S, Chisholm A, Wearden A, Moschogianis S, Cordingley L, Baker D, Hyde C, Chew-Graham C. Managing self-limiting respiratory tract infections: Publisher’s Note a qualitative study of the usefulness of the delayed prescribing strategy. Br J Gen Springer Nature remains neutral with regard to jurisdictional claims in Pract. 2011;61:e579–89. https://doi.org/10.3399/bjgp11X593866. published maps and institutional affiliations. 18. Sargent L, McCullough A, Del MC, Lowe J. Is Australia ready to implement delayed prescribing in primary care? A review of the evidence. Aust Fam Author details 1 Physician. 2016;45(9):688–90. Dr Carles Ribas Primary Care Center, C/Foc 112, 08038 Barcelona, Spain. 2 19. Llor C. Antibiotic reimbursement data represent a part of the actual antibiotic Iberoamerican Cochrane Center, Biomedical Research Institute Sant Pau (IIB consumption. Aten Primaria. 2017; https://doi.org/10.1016/j.aprim.2017.09.008. Sant Pau), Barcelona, Spain. 3Via Roma Primary Care Center, Barcelona, Spain. 4 20. Euro-CDC. Summary of the latest data on antibiotic consumption in the European CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain. Union antibiotic consumption in Europe. Euro-Cdc. 2012;(November):1–8. 21. DANMAP 2015 - Use of antimicrobial agents and occurrence of Received: 14 February 2018 Accepted: 14 March 2019 antimicrobial resistance in bacteria from food animals, food and humans in Denmark. ISSN 1600-2032. Available from www.danmap.org. 22. McCullough AR, Parekh S, Rathbone J, Del Mar CB, Hoffmann TC. 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