European Journal of General Practice, 2015; Early Online: 1–6
Original Article
Eur J Gen Pract Downloaded from informahealthcare.com by University of Birmingham on 03/21/15 For personal use only.
Inappropriate antibiotic prescribing and demand for antibiotics in patients with upper respiratory tract infections is hardly different in female versus male patients as seen in primary care
Kathrine Bagger, Anni B Sternhagen Nielsen, Volkert Siersma & Lars Bjerrum Section and Research Unit of General Practice, Department of Public Health, University of Copenhagen, Denmark KEY MESSAGE: · In general practice, there seems to be no difference in unnecessary prescribing of antibiotics for men and women with upper respiratory tract infections. · Minor differences between genders could not be explained by the differences in patient demand for antibiotics.
ABSTRACT Background: Unnecessary prescribing of antibiotics is a major public health concern. General practitioners (GPs) prescribe most antibiotics, often for upper respiratory tract infections (URTIs), and have in general been shown to prescribe antibiotics more often to women. No studies have examined the influence of patient gender on unnecessary antibiotic prescribing. Objectives: To study a possible gender difference in unnecessary antibiotic prescriptions for URTIs in general practice; to assess whether a possible difference is explained by patient demand for antibiotics. Methods: Post-hoc analysis of a cross-sectional study including 15 022 patients with URTI (acute rhinitis, acute otitis media, acute sinusitis, acute pharyngotonsillitis) from Argentina, Denmark, Lithuania, Russia, Spain and Sweden (HAPPY AUDIT Project). The association between gender and unnecessary antibiotic prescriptions, unadjusted and adjusted for treatment demand, was analysed using logistic regression models. Results: A total of 25% of patients with URTI received antibiotics; in 45% of the cases, antibiotics were unnecessary. Overall, no gender difference for unnecessary prescribing of antibiotics for URTIs was found. Women with acute otitis media received an unnecessary antibiotic twice as often as men (14.4% versus 7.1%). In Danish patients with acute pharyngotonsillitis, there was a gender difference in unnecessary prescriptions for antibiotics (women 29.1% versus men 48.6%). Some 14% of patients receiving unnecessary antibiotics demonstrated a demand for antibiotics, but no gender difference was found in this group. Conclusion: This study indicated a high rate of unnecessary antibiotic prescribing for URTIs in general practice, but overall found no gender differences in receiving unnecessary antibiotic prescriptions. Keywords: General practice, antibiotics, infectious diseases, upper respiratory tract, gender
INTRODUCTION Unnecessary use of antibiotics is a major public health problem causing development of antimicrobial resistance (1). Some 50–60% of all antibiotics prescribed in general practice are for respiratory tract infections (2,3), which are among the most common reasons for patient encounter (9–28%) (4,5). Upper respiratory tract infections (URTIs) represent the majority of RTIs worldwide (6) and lead to prescribing of antibiotics in 60% of all
consultations (7). However, most URTIs are caused by virus where antibiotics have no beneficial effect (8–10). Studies from general practice have demonstrated high rates of unnecessary antibiotic prescribing for patients with URTIs: 18% of patients with acute otitis media are treated unnecessarily with antibiotics (11), 22% with acute sinusitis, and 71% with acute tonsillitis (12). In earlier studies of unnecessary antibiotic prescribing many factors linked to the general practitioner (GP)
Correspondence: K. Bagger, Section and Research Unit of General Practice, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, DK-1014 Copenhagen K; Denmark. Fax: 45 35 32 79 46. E-mail: [email protected] (Received 10 December 2013; revised 30 November 2014; accepted 14 December 2014) ISSN 1381-4788 print/ISSN 1751-1402 online © 2015 Informa Healthcare DOI: 10.3109/13814788.2014.1001361
Eur J Gen Pract Downloaded from informahealthcare.com by University of Birmingham on 03/21/15 For personal use only.
2
K. Bagger et al.
have been associated with increased rates of unnecessary antibiotic prescribing for RTIs, e.g. the GPs’ seniority, high-volume practice and single-handed practice (13,14). However, no studies have yet examined the association between patient gender and unnecessary/ inappropriate prescribing of antibiotics in general practice, although female gender in several studies has been associated with a higher likelihood of receiving a prescription for antibiotics in general (2,15–17). This has led us to the hypothesis that women with URTIs may be more likely to receive an unnecessary prescription for antibiotics compared to men. Previous studies have also shown that patient demand for unnecessary antibiotics influences the GPs’ prescribing for RTIs (18,19). Thus, it is interesting to study possible gender differences in patient demand for antibiotics. The aim of this study was to examine whether women with URTIs had a higher risk of being unnecessarily treated with antibiotics compared to men. Furthermore, we wanted to investigate whether a potential increased risk of unnecessary antibiotic prescribing among women could be explained by an increased demand for antibiotics. METHODS Study design The current study represents a post-hoc analysis— performed in 2013—of the dataset of the HAPPY AUDIT study (health alliance for prudent prescribing, yield and use of antimicrobial drugs in the treatment of respiratory tract infections) (20). Briefly, data were collected from GPs in six countries: Sweden, Denmark, Argentina, Spain, Russia and Lithuania. A total of 618 GPs participated voluntarily in the study, after receiving random invitations. All patients with RTIs were registered during a three-week period in the winter of 2007/2008. The study protocol was submitted to a legally constituted ethics committee and deemed exempt from review (The Scientific Ethics Committee for the County of Vejle and Funen, Denmark).
Data collection Registration was performed during the consultation on a registration chart developed according to the Audit Project Odense (APO) method (21). Variables recorded were: patient gender, age, duration of symptoms, patient symptoms and signs, diagnostic tests performed, assumed aetiology, diagnosis of consultation, choice of treatment and possible patient demand for antibiotics. URTIs were classified in accordance with the International Classification of Primary Care (ICPC): acute rhinitis (R74), acute otitis media (H71, H72), acute sinusitis (R75), and acute pharyngotonsillitis (R72, R74). All antibiotic prescriptions were classified as necessary or unnecessary (Table 1). Antibiotic prescriptions following recommendations for antibiotic prescribing according to international guidelines were classified as necessary prescriptions. Prescriptions in conflict with recommendations were classified as unnecessary. We used widely accepted international guidelines for treatment of URTIs: NICE, EPOS and HAPPY AUDIT (22–24). Study population Patients with URTI accounted for 21 206 (63.7%) of the 33 273 patients registered with RTI. Patients aged 16 years, patients referred to specialist or hospital, and patients of unreported gender were excluded (Figure 1). An additional 105 patients were not enrolled due to insufficient registration. Statistical analyses The data was analysed in Statistical Analysis System (SAS), version 9.2 (SAS Institute, Cary, North Carolina). Multivariable logistic regression was used, performed with SAS PROC GENMOD, using generalized estimating equations (GEE) to account for clustering at GP level. We analysed unnecessary antibiotic prescribing in men versus women and determined confounding or modification of a gender difference by patient demand for antibiotics. Results are presented as the estimated incidence with
Table 1. Criteria for classification of the appropriateness of antibiotic prescribing (necessary and unnecessary prescribing) in patients with upper respiratory tract infections (RTIs).
Acute rhinitis Acute otitis media Acute sinusitis Acute pharyngotonsillitis aFollowing
Necessary prescribinga
Unnecessary prescribingb
Never Symptoms 3 days or purulent ear secretion Symptoms 5 days or fever 38.5°C 3 Centor criteriac or 2 Centor criteria and a positive strep A testd
Always Symptoms 3 days and absence of purulent ear secretion Symptoms 5 days and fever 38.5°C 3 Centor criteriac or a negative strep A testd
international guidelines on antibiotic prescribing. prescription in conflict with international guidelines. cPresence of tonsillar exudate, tender anterior cervical lymphadenopathy or lymphadenitis, history of fever and absence of cough. dStreptococcus antigen test bAntibiotic
Gender difference in antibiotic overprescribing
3
Patients with RTI n = 33 273 n = 12 067
Patients with lower RTI
n = 97
Referred to others
n = 5 961
_ 16 years old n = 15 148
Study population n = 15 022
Figure 1. Flow chart showing the inclusion and exclusion of patients in the study population.
95% confidence interval (CI) of unnecessary prescribing for the corresponding gender. Gender differences are expressed in odds ratios (OR; with 95% CI). The statistical significance of the gender difference was tested by a likelihood ratio test for this OR. A P-value 0.05 was considered statistically significant. RESULTS Antibiotic prescribing A total of 15 022 patients met the inclusion criteria (70.8% of all patients with URTI). Antibiotics were prescribed in 25.4% of all consultations. There was no difference between male and female patients (Table 2).
The lowest antibiotic prescribing rate was found in patients with acute rhinitis (2–4%), and highest in patients with acute otitis media (74–97%) and acute sinusitis (78–93%). Unnecessary antibiotic prescriptions For both genders, 45% of antibiotic prescriptions were classified as unnecessary (Table 2). The highest proportion of unnecessary prescriptions was found in patients who were prescribed an antibiotic for acute rhinitis (100%), followed by acute pharyngotonsillitis (53.6%). For the whole group of URTIs, no gender difference was found in the proportion of unnecessary antibiotic prescriptions (OR 1.02; 95% CI: 0.90–1.15). A gender
Table 2. Number of office visits, antibiotic prescriptions and proportion of unnecessary prescriptions for antibiotics for upper respiratory tract infections (RTIs) among men and women visiting general practices participating in HAPPY AUDITa.
Total no. of office visits men/women
Men No. of antibiotic prescriptions (%)
All upper RTIs 5 946/9 076 1 495 (25.1%) Acute rhinitis 3 522/5 120 92 (2.6%) Acute otitis media 192/292 170 (88.5%) Acute sinusitis 318/649 266 (83.6%) Acute 1 914/3015 967 (50.5%) pharyngotonsillitis aHealth
No. of unnecessary prescriptions 677 92 12 64 509
% of unnecessary prescriptions (95% CI)b
Women No. of antibiotic No. of % of unnecessary prescriptions unnecessary prescriptions (%) prescriptions (95% CI)b P-valueb
45.3 (41.7; 48.9) 2 320 (25.6%) 100% 127 (2.5%) 7.1 (3.8; 12.8) 257 (88.0%) 24.1 (18.9; 30.1) 562 (86.6%) 52.6 (48.4; 56.8) 1 374 (45.6%)
1 032 127 37 123 745
44.5 (41.0; 48.0) 100% 14.4 (10.6; 19.3) 21.9 (18.1; 26.2) 54.2 (49.7; 58.7)
alliance for prudent prescribing, yield and use of antimicrobial drugs in the treatment of respiratory tract infections. presented proportions of unnecessary prescriptions, confidence intervals and P-value are adjusted for clustering at doctor level CI, confidence interval. bThe
0.77 – 0.02 0.46 0.47
43.3–65.3 52.9–72.4 – – 1.4–52.1 1.9–59.3 7.4–50.5 9.0–58.6 53.0–78.0 64.9–84.5 54 (54.5) 67 (63.2) 3 (100.0) 6 (100.0) 1 (11.1) 1 (14.3) 4 (22.2) 6 (27.3) 46 (66.7) 54 (76.1) 41.4–67.8 33.5–59.5 – – 0.9–24.7 – 28.1–48.5 25.3–68.4 42.9–77.2 32.8–63.2 144 (55.0) 56 (46.3) 11 (100.0) 7 (100.0) 1 (5.3) 0 (0) 17 (37.8) 6 (46.2) 115 (61.5) 43 (47.8) bThe
aNumber
Acute pharyngotonsillitis
Acute sinusitis
Acute otitis media
Acute rhinitis
of unnecessary prescriptions for antibiotics (% of total antibiotic prescriptions). presented proportions of unnecessary prescriptions, confidence intervals and P–value are adjusted for clustering at doctor level. cP-value 0.02. ♀, female; ♂, male; RTIs, respiratory tract infections; CI, confidence interval.
44.1–53.2 43.7–53.2 – – 10.5–21.8 4.0–16.3 19.1–31.5 17.8–33.5 52.1–62.5 50.5–61.2 612 (48.6) 426 (48.5) 92 (100.0) 63 (100.0) 26 (15.3) 9 (8.3) 59 (24.8) 33 (24.8) 435 (57.4) 321 (55.9) 37.3–57.5 28.9–50.5 – – 3.9–23.1 0.5–25.7 20.0–50.0 12.0–48.4 42.8–67.8 32.8–55.6
n (%) 95% CI n (%) 95% CI n (%) 95% CI n (%)
121 (59.0) 124 (47.3) 65 (39.2) 6 (100.0) 9 (100.0) 3 (10.0) 1 (4.2) 16 (33.3) 5 (26.3) 99 (55.6) 50 (43.9) 200 (52.2) 19.2–29.9 26.0–43.1 – – 8.5–46.9 2.0–58.1 9.4–21.9 8.5–28.3 21.1–38.5c 35.4–61.9
95% CI n (%)
1 038 (48.6) 68 (24.1) 46 (34.1) 10 (100.0) 2 (100.0) 4 (22.2) 1 (14.3) 20 (14.6) 9 (16.1) 34 (29.1) 34 (48.6) 189 (44.2) 13.7–26.0 12.0–30.3 – – 4.4–51.5 – 4.7–17.4 9.6–42.0 15.4–36.9 7.1–27.7 114 (27.3) 30 (19.1) 17 (19.5) 5 (100.0) 5 (100.0) 2 (18.2) 0 (0) 7 (9.2) 5 (21.7) 16 (24.6) 7 (14.6)
Russia Spain Argentina
47 (19.3) ♀ ♂ ♀ ♂ ♀ ♂ ♀ ♂ ♀ ♂
The strength of this study is the large number of participating GPs and patients from different countries. The registration was performed in a real life setting with usual time schedule and no prior information about the patients. It is, therefore, likely that the data reflect the actual conditions in the six countries studied and can be extrapolated to areas with similar practice settings. In addition, our classification of antibiotic prescriptions as necessary or unnecessary was based on well approved international guidelines (22–24).
Total number, ♀♂ All upper RTIs
Strengths and limitations
95% CIb
Overall, the results could not support the hypothesis that there is a gender difference in the proportion of unnecessary antibiotic prescriptions for URTI. A general gender difference was found for acute otitis media, where women had twice as many unnecessary antibiotic prescriptions than men (14.4% versus 7.1%). In Denmark, men with acute pharyngotonsillitis more often received an unnecessary antibiotic prescription. There were no differences in demand for antibiotics between men and women.
n (%)a
Main findings
Denmark
DISCUSSION
Sweden
Of all patients receiving unnecessary antibiotics, 120 (14%) demanded antibiotics. Overall, no differences between male and female demand for antibiotics were found among patients receiving unnecessary antibiotics: Rhinitis (28.5% versus 19.7%, P 0.56), acute otitis media (0% versus 2.7%), acute sinusitis (0% versus 3.3%), and acute pharyngotonsillitis (4.5% versus 6.7%, P 0.16).
Unnecessary prescription of antibiotics
Patient demand for antibiotics
Lithuania
difference was only found in antibiotic prescriptions for acute otitis media, where prescriptions for antibiotics for women were significantly more unnecessary compared to those for men (OR 2.03; 95% CI: 1.05–3.93). Table 3 (Appendix, web only) shows the distribution of unnecessary antibiotic prescriptions for male and female patients by country and type of URTI. Sweden had the lowest rates of unnecessary antibiotic prescribing. In four of the six countries, most antibiotic prescriptions for acute pharyngotonsillitis were classified as unnecessary. Only in Denmark could a gender difference in unnecessary antibiotic prescription be found (P-value 0.02). This was mostly accounted for by more unnecessary antibiotic prescriptions for acute pharyngotonsillitis in Danish men as compared to women (OR 2.16; 95% CI: 1.32–3.56).
95% CI
K. Bagger et al.
Table 3. Rate of unnecessary antibiotic prescribing (% of consultations followed by a prescription) in men and women by country and diagnosis.
Eur J Gen Pract Downloaded from informahealthcare.com by University of Birmingham on 03/21/15 For personal use only.
4
Eur J Gen Pract Downloaded from informahealthcare.com by University of Birmingham on 03/21/15 For personal use only.
A possible weakness is that GPs participated on a voluntary basis and may represent a group of doctors more interested in rational antibiotic use. Our results may, therefore, underestimate the rate of unnecessary antibiotic prescribing worldwide. Additionally, participating in an audit may have influenced the prescribing pattern: the GPs might be tempted to register a diagnosis that justified the treatment instead of vice versa, which could lead to diagnostic misclassification bias. However, such a potential bias would not be expected to influence the effect of gender on unnecessary antibiotic prescribing. Furthermore, the fact that data collection took place in 2007 and the analysis in 2013 could potentially lead to bias, but since there was no change in clinical guidelines in that period, this is not expected to influence the outcome. Interpretation The high rates of unnecessary antibiotic prescriptions for URTIs in general practice are in accordance with previous studies (7,11,12,16). Few gender differences in the rate of unnecessary antibiotic prescribing were found. The results point in different directions and do not support our prior hypothesis that women had a higher risk of receiving unnecessary antibiotic prescriptions for URTIs than men. We found no gender differences in patient demand. Previous studies have concluded that patient demand for treatment was the most important non-clinical factor for prescription of non-indicated antibiotics for RTIs, irrespective of gender (18,19). Implication for practice and future research Women received an unnecessary antibiotic prescription for acute otitis media almost twice as often as men. This finding should be taken into account when clinical practice guidelines for URTIs are being updated (25,26). Detailed insights into the decision-making process of antibiotic prescribing by the individual GP, e.g. by qualitative studies, could further elucidate where efforts could best be directed in the continuous campaign to reduce unnecessary antibiotic prescribing. Conclusion Our results could not support the hypothesis that there is a gender difference in the proportion of unnecessary antibiotic prescriptions for URTI. There were no differences in demand for antibiotics between men and women. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Gender difference in antibiotic overprescribing
5
REFERENCES 1. Bronzwaer SLAM, Cars O, Buchholz U, Mölstad S, Goettsch W, Veldhuijzen IK, et al. The relationship between antimicrobial use and antimicrobial resistance in Europe. Emerg Infect Dis. 2002; 8:278–82. 2. Straand J, Rokstad KS, Sandvik H. Prescribing systemic antibiotics in general practice. A report from the Møre & Romsdal prescription study. Scand J Prim Health Care 1998;16:121–7. 3. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing among office-based physicians in the United States. J Am Med Assoc. 1995;273:214–9. 4. Grimsmo A, Hagman E, Falkø E, Matthiessen L, Njálsson T. Patients, diagnoses and processes in general practice in the Nordic countries. An attempt to make data from computerised medical records available for comparable statistics. Scand J Prim Health Care 2001;19:76–82. 5. Månsson J, Nilsson G, Strender L-E, Björkelund C. Reasons for encounters, investigations, referrals, diagnoses and treatments in general practice in Sweden—a multicentre pilot study using electronic patient records. Eur J Gen Pract. 2011;17:87–94. 6. Bjerrum L, Munck A, Gahrn-Hansen B, Hansen MP, Jarbol DE, Cordoba G, et al. Health alliance for prudent antibiotic prescribing in patients with respiratory tract infections (HAPPY AUDIT)—impact of a non-randomised multifaceted intervention programme. BMC Fam Pract. 2011;12:52. 7. André M, Odenholt I, Schwan A, Axelsson I, Eriksson M, Hoffman M, et al. Upper respiratory tract infections in general practice: Diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests. Scand J Infect Dis. 2002;34:880–6. 8. Ahovuo-Saloranta A, Borisenko OV, Kovanen N, Varonen H, Rautakorpi UM, Williams JW, et al. Antibiotics for acute maxillary sinusitis. Cochrane Database Syst Rev. 2008;16:CD000243. 9. Arroll B. Antibiotics for upper respiratory tract infections: An overview of Cochrane reviews. Respir Med. 2005;99:255–61. 10. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2004;2:CD000023. 11. Akkerman AE, Kuyvenhoven MM, van der Wouden JC, Verheij TJM. Analysis of under- and overprescribing of antibiotics in acute otitis media in general practice. J Antimicrob Chemother. 2005;56:569–74. 12. Akkerman AE, Kuyvenhoven MM, van der Wouden JC, Verheij TJM. Determinants of antibiotic overprescribing in respiratory tract infections in general practice. J Antimicrob Chemother. 2005;56:930–6. 13. Cadieux G, Tamblyn R, Dauphinee D, Libman M. Predictors of inappropriate antibiotic prescribing among primary care physicians. CMAJ 2007;177:877–83. 14. Otters HBM, van der Wouden JC, Schellevis FG, van SuijlekomSmit LW, Koes BW. Trends in prescribing antibiotics for children in Dutch general practice. J Antimicrob Chemother. 2004;53: 361–6. 15. Sayer GP, Britt H. Sex differences in prescribed medications: Another case of discrimination in general practice. Soc Sci Med. 1997;45:1581–7. 16. Gonzales R, Steiner JF, Sande AM. Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. J Am Med Assoc. 1997; 278:901–4. 17. Statens Serum Institut. Statistik over forbruget af antibiotika [Online]. Available at http://www.ssi.dk/Sundhedsdataogit/ Dataformidling/Laegemiddelstatistikker/forbruget af antibiotika. aspx (accessed 9 November 2013). 18. Macfarlane J, Holmes W, Macfarlane R, Britten N. Influence of patients’ expectations on antibiotic management of acute lower respiratory tract illness in general practice: Questionnaire study. Br Med J. 1997;315:1211–4.
6
K. Bagger et al.
Eur J Gen Pract Downloaded from informahealthcare.com by University of Birmingham on 03/21/15 For personal use only.
19. Hummers-Pradier E, Pelz J, Himmel W, Kochen MM. Treatment of respiratory tract infections—a study in 18 general practices in Germany. Eur J Gen Pract. 1999;5:15–20. 20. Bjerrum L, Munck A, Gahrn-Hansen B, Hansen MP, Jarboel D, Llor C, et al. Health alliance for prudent prescribing, yield and use of antimicrobial drugs in the treatment of respiratory tract infections (HAPPY AUDIT). BMC Fam Pract. 2010;11:29. 21. Munck AP, Hansen DG, Lindman A, Ovhed I, Førre S, Torsteinsson JB. A Nordic collaboration on medical audit. The APO method for quality developement and continuous medical education (CME) in primary health care. Scand J Prim Health Care 1998;16:2–6. 22. NICE. Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care. NICE Clinical Guideline 69. London, UK; 2008. 23. Thomas M, Yawn BP, Price D, Lund V, Mullol J, Fokkens W. EPOS primary care guidelines: European position paper on the
primary care diagnosis and management of rhinosinusitis and nasal polyps 2007—a summary. Prim Care Respir J. 2008; 17:79–89. 24. Health alliance for prudent prescribing, yield and use of antimicrobial drugs in the treatment of respiratory tract infections, HAPPY AUDIT. HAPPY AUDIT guidelines. http://www.happyaudit. org/front_page/publications.aspx (accessed 15 November 2012). 25. Grol R. Successes and failures in the implementation of evidence-based guidelines for clinical practice. Medical Care 2001;39:46–54. 26. Shekelle P, Woolf S, Grimshaw JM, Schünemann HJ, Eccles MP. Developing clinical practice guidelines: Reviewing, reporting, and publishing guidelines; updating, guidelines; and the emerging issues of enhancing guideline implementability and accounting for comorbid conditions in guideline development. Implement Sci. 2012;7:62.
Original Article
Eur J Gen Pract Downloaded from informahealthcare.com by University of Birmingham on 03/21/15 For personal use only.
Inappropriate antibiotic prescribing and demand for antibiotics in patients with upper respiratory tract infections is hardly different in female versus male patients as seen in primary care
Kathrine Bagger, Anni B Sternhagen Nielsen, Volkert Siersma & Lars Bjerrum Section and Research Unit of General Practice, Department of Public Health, University of Copenhagen, Denmark KEY MESSAGE: · In general practice, there seems to be no difference in unnecessary prescribing of antibiotics for men and women with upper respiratory tract infections. · Minor differences between genders could not be explained by the differences in patient demand for antibiotics.
ABSTRACT Background: Unnecessary prescribing of antibiotics is a major public health concern. General practitioners (GPs) prescribe most antibiotics, often for upper respiratory tract infections (URTIs), and have in general been shown to prescribe antibiotics more often to women. No studies have examined the influence of patient gender on unnecessary antibiotic prescribing. Objectives: To study a possible gender difference in unnecessary antibiotic prescriptions for URTIs in general practice; to assess whether a possible difference is explained by patient demand for antibiotics. Methods: Post-hoc analysis of a cross-sectional study including 15 022 patients with URTI (acute rhinitis, acute otitis media, acute sinusitis, acute pharyngotonsillitis) from Argentina, Denmark, Lithuania, Russia, Spain and Sweden (HAPPY AUDIT Project). The association between gender and unnecessary antibiotic prescriptions, unadjusted and adjusted for treatment demand, was analysed using logistic regression models. Results: A total of 25% of patients with URTI received antibiotics; in 45% of the cases, antibiotics were unnecessary. Overall, no gender difference for unnecessary prescribing of antibiotics for URTIs was found. Women with acute otitis media received an unnecessary antibiotic twice as often as men (14.4% versus 7.1%). In Danish patients with acute pharyngotonsillitis, there was a gender difference in unnecessary prescriptions for antibiotics (women 29.1% versus men 48.6%). Some 14% of patients receiving unnecessary antibiotics demonstrated a demand for antibiotics, but no gender difference was found in this group. Conclusion: This study indicated a high rate of unnecessary antibiotic prescribing for URTIs in general practice, but overall found no gender differences in receiving unnecessary antibiotic prescriptions. Keywords: General practice, antibiotics, infectious diseases, upper respiratory tract, gender
INTRODUCTION Unnecessary use of antibiotics is a major public health problem causing development of antimicrobial resistance (1). Some 50–60% of all antibiotics prescribed in general practice are for respiratory tract infections (2,3), which are among the most common reasons for patient encounter (9–28%) (4,5). Upper respiratory tract infections (URTIs) represent the majority of RTIs worldwide (6) and lead to prescribing of antibiotics in 60% of all
consultations (7). However, most URTIs are caused by virus where antibiotics have no beneficial effect (8–10). Studies from general practice have demonstrated high rates of unnecessary antibiotic prescribing for patients with URTIs: 18% of patients with acute otitis media are treated unnecessarily with antibiotics (11), 22% with acute sinusitis, and 71% with acute tonsillitis (12). In earlier studies of unnecessary antibiotic prescribing many factors linked to the general practitioner (GP)
Correspondence: K. Bagger, Section and Research Unit of General Practice, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, DK-1014 Copenhagen K; Denmark. Fax: 45 35 32 79 46. E-mail: [email protected] (Received 10 December 2013; revised 30 November 2014; accepted 14 December 2014) ISSN 1381-4788 print/ISSN 1751-1402 online © 2015 Informa Healthcare DOI: 10.3109/13814788.2014.1001361
Eur J Gen Pract Downloaded from informahealthcare.com by University of Birmingham on 03/21/15 For personal use only.
2
K. Bagger et al.
have been associated with increased rates of unnecessary antibiotic prescribing for RTIs, e.g. the GPs’ seniority, high-volume practice and single-handed practice (13,14). However, no studies have yet examined the association between patient gender and unnecessary/ inappropriate prescribing of antibiotics in general practice, although female gender in several studies has been associated with a higher likelihood of receiving a prescription for antibiotics in general (2,15–17). This has led us to the hypothesis that women with URTIs may be more likely to receive an unnecessary prescription for antibiotics compared to men. Previous studies have also shown that patient demand for unnecessary antibiotics influences the GPs’ prescribing for RTIs (18,19). Thus, it is interesting to study possible gender differences in patient demand for antibiotics. The aim of this study was to examine whether women with URTIs had a higher risk of being unnecessarily treated with antibiotics compared to men. Furthermore, we wanted to investigate whether a potential increased risk of unnecessary antibiotic prescribing among women could be explained by an increased demand for antibiotics. METHODS Study design The current study represents a post-hoc analysis— performed in 2013—of the dataset of the HAPPY AUDIT study (health alliance for prudent prescribing, yield and use of antimicrobial drugs in the treatment of respiratory tract infections) (20). Briefly, data were collected from GPs in six countries: Sweden, Denmark, Argentina, Spain, Russia and Lithuania. A total of 618 GPs participated voluntarily in the study, after receiving random invitations. All patients with RTIs were registered during a three-week period in the winter of 2007/2008. The study protocol was submitted to a legally constituted ethics committee and deemed exempt from review (The Scientific Ethics Committee for the County of Vejle and Funen, Denmark).
Data collection Registration was performed during the consultation on a registration chart developed according to the Audit Project Odense (APO) method (21). Variables recorded were: patient gender, age, duration of symptoms, patient symptoms and signs, diagnostic tests performed, assumed aetiology, diagnosis of consultation, choice of treatment and possible patient demand for antibiotics. URTIs were classified in accordance with the International Classification of Primary Care (ICPC): acute rhinitis (R74), acute otitis media (H71, H72), acute sinusitis (R75), and acute pharyngotonsillitis (R72, R74). All antibiotic prescriptions were classified as necessary or unnecessary (Table 1). Antibiotic prescriptions following recommendations for antibiotic prescribing according to international guidelines were classified as necessary prescriptions. Prescriptions in conflict with recommendations were classified as unnecessary. We used widely accepted international guidelines for treatment of URTIs: NICE, EPOS and HAPPY AUDIT (22–24). Study population Patients with URTI accounted for 21 206 (63.7%) of the 33 273 patients registered with RTI. Patients aged 16 years, patients referred to specialist or hospital, and patients of unreported gender were excluded (Figure 1). An additional 105 patients were not enrolled due to insufficient registration. Statistical analyses The data was analysed in Statistical Analysis System (SAS), version 9.2 (SAS Institute, Cary, North Carolina). Multivariable logistic regression was used, performed with SAS PROC GENMOD, using generalized estimating equations (GEE) to account for clustering at GP level. We analysed unnecessary antibiotic prescribing in men versus women and determined confounding or modification of a gender difference by patient demand for antibiotics. Results are presented as the estimated incidence with
Table 1. Criteria for classification of the appropriateness of antibiotic prescribing (necessary and unnecessary prescribing) in patients with upper respiratory tract infections (RTIs).
Acute rhinitis Acute otitis media Acute sinusitis Acute pharyngotonsillitis aFollowing
Necessary prescribinga
Unnecessary prescribingb
Never Symptoms 3 days or purulent ear secretion Symptoms 5 days or fever 38.5°C 3 Centor criteriac or 2 Centor criteria and a positive strep A testd
Always Symptoms 3 days and absence of purulent ear secretion Symptoms 5 days and fever 38.5°C 3 Centor criteriac or a negative strep A testd
international guidelines on antibiotic prescribing. prescription in conflict with international guidelines. cPresence of tonsillar exudate, tender anterior cervical lymphadenopathy or lymphadenitis, history of fever and absence of cough. dStreptococcus antigen test bAntibiotic
Gender difference in antibiotic overprescribing
3
Patients with RTI n = 33 273 n = 12 067
Patients with lower RTI
n = 97
Referred to others
n = 5 961
_ 16 years old n = 15 148
Study population n = 15 022
Figure 1. Flow chart showing the inclusion and exclusion of patients in the study population.
95% confidence interval (CI) of unnecessary prescribing for the corresponding gender. Gender differences are expressed in odds ratios (OR; with 95% CI). The statistical significance of the gender difference was tested by a likelihood ratio test for this OR. A P-value 0.05 was considered statistically significant. RESULTS Antibiotic prescribing A total of 15 022 patients met the inclusion criteria (70.8% of all patients with URTI). Antibiotics were prescribed in 25.4% of all consultations. There was no difference between male and female patients (Table 2).
The lowest antibiotic prescribing rate was found in patients with acute rhinitis (2–4%), and highest in patients with acute otitis media (74–97%) and acute sinusitis (78–93%). Unnecessary antibiotic prescriptions For both genders, 45% of antibiotic prescriptions were classified as unnecessary (Table 2). The highest proportion of unnecessary prescriptions was found in patients who were prescribed an antibiotic for acute rhinitis (100%), followed by acute pharyngotonsillitis (53.6%). For the whole group of URTIs, no gender difference was found in the proportion of unnecessary antibiotic prescriptions (OR 1.02; 95% CI: 0.90–1.15). A gender
Table 2. Number of office visits, antibiotic prescriptions and proportion of unnecessary prescriptions for antibiotics for upper respiratory tract infections (RTIs) among men and women visiting general practices participating in HAPPY AUDITa.
Total no. of office visits men/women
Men No. of antibiotic prescriptions (%)
All upper RTIs 5 946/9 076 1 495 (25.1%) Acute rhinitis 3 522/5 120 92 (2.6%) Acute otitis media 192/292 170 (88.5%) Acute sinusitis 318/649 266 (83.6%) Acute 1 914/3015 967 (50.5%) pharyngotonsillitis aHealth
No. of unnecessary prescriptions 677 92 12 64 509
% of unnecessary prescriptions (95% CI)b
Women No. of antibiotic No. of % of unnecessary prescriptions unnecessary prescriptions (%) prescriptions (95% CI)b P-valueb
45.3 (41.7; 48.9) 2 320 (25.6%) 100% 127 (2.5%) 7.1 (3.8; 12.8) 257 (88.0%) 24.1 (18.9; 30.1) 562 (86.6%) 52.6 (48.4; 56.8) 1 374 (45.6%)
1 032 127 37 123 745
44.5 (41.0; 48.0) 100% 14.4 (10.6; 19.3) 21.9 (18.1; 26.2) 54.2 (49.7; 58.7)
alliance for prudent prescribing, yield and use of antimicrobial drugs in the treatment of respiratory tract infections. presented proportions of unnecessary prescriptions, confidence intervals and P-value are adjusted for clustering at doctor level CI, confidence interval. bThe
0.77 – 0.02 0.46 0.47
43.3–65.3 52.9–72.4 – – 1.4–52.1 1.9–59.3 7.4–50.5 9.0–58.6 53.0–78.0 64.9–84.5 54 (54.5) 67 (63.2) 3 (100.0) 6 (100.0) 1 (11.1) 1 (14.3) 4 (22.2) 6 (27.3) 46 (66.7) 54 (76.1) 41.4–67.8 33.5–59.5 – – 0.9–24.7 – 28.1–48.5 25.3–68.4 42.9–77.2 32.8–63.2 144 (55.0) 56 (46.3) 11 (100.0) 7 (100.0) 1 (5.3) 0 (0) 17 (37.8) 6 (46.2) 115 (61.5) 43 (47.8) bThe
aNumber
Acute pharyngotonsillitis
Acute sinusitis
Acute otitis media
Acute rhinitis
of unnecessary prescriptions for antibiotics (% of total antibiotic prescriptions). presented proportions of unnecessary prescriptions, confidence intervals and P–value are adjusted for clustering at doctor level. cP-value 0.02. ♀, female; ♂, male; RTIs, respiratory tract infections; CI, confidence interval.
44.1–53.2 43.7–53.2 – – 10.5–21.8 4.0–16.3 19.1–31.5 17.8–33.5 52.1–62.5 50.5–61.2 612 (48.6) 426 (48.5) 92 (100.0) 63 (100.0) 26 (15.3) 9 (8.3) 59 (24.8) 33 (24.8) 435 (57.4) 321 (55.9) 37.3–57.5 28.9–50.5 – – 3.9–23.1 0.5–25.7 20.0–50.0 12.0–48.4 42.8–67.8 32.8–55.6
n (%) 95% CI n (%) 95% CI n (%) 95% CI n (%)
121 (59.0) 124 (47.3) 65 (39.2) 6 (100.0) 9 (100.0) 3 (10.0) 1 (4.2) 16 (33.3) 5 (26.3) 99 (55.6) 50 (43.9) 200 (52.2) 19.2–29.9 26.0–43.1 – – 8.5–46.9 2.0–58.1 9.4–21.9 8.5–28.3 21.1–38.5c 35.4–61.9
95% CI n (%)
1 038 (48.6) 68 (24.1) 46 (34.1) 10 (100.0) 2 (100.0) 4 (22.2) 1 (14.3) 20 (14.6) 9 (16.1) 34 (29.1) 34 (48.6) 189 (44.2) 13.7–26.0 12.0–30.3 – – 4.4–51.5 – 4.7–17.4 9.6–42.0 15.4–36.9 7.1–27.7 114 (27.3) 30 (19.1) 17 (19.5) 5 (100.0) 5 (100.0) 2 (18.2) 0 (0) 7 (9.2) 5 (21.7) 16 (24.6) 7 (14.6)
Russia Spain Argentina
47 (19.3) ♀ ♂ ♀ ♂ ♀ ♂ ♀ ♂ ♀ ♂
The strength of this study is the large number of participating GPs and patients from different countries. The registration was performed in a real life setting with usual time schedule and no prior information about the patients. It is, therefore, likely that the data reflect the actual conditions in the six countries studied and can be extrapolated to areas with similar practice settings. In addition, our classification of antibiotic prescriptions as necessary or unnecessary was based on well approved international guidelines (22–24).
Total number, ♀♂ All upper RTIs
Strengths and limitations
95% CIb
Overall, the results could not support the hypothesis that there is a gender difference in the proportion of unnecessary antibiotic prescriptions for URTI. A general gender difference was found for acute otitis media, where women had twice as many unnecessary antibiotic prescriptions than men (14.4% versus 7.1%). In Denmark, men with acute pharyngotonsillitis more often received an unnecessary antibiotic prescription. There were no differences in demand for antibiotics between men and women.
n (%)a
Main findings
Denmark
DISCUSSION
Sweden
Of all patients receiving unnecessary antibiotics, 120 (14%) demanded antibiotics. Overall, no differences between male and female demand for antibiotics were found among patients receiving unnecessary antibiotics: Rhinitis (28.5% versus 19.7%, P 0.56), acute otitis media (0% versus 2.7%), acute sinusitis (0% versus 3.3%), and acute pharyngotonsillitis (4.5% versus 6.7%, P 0.16).
Unnecessary prescription of antibiotics
Patient demand for antibiotics
Lithuania
difference was only found in antibiotic prescriptions for acute otitis media, where prescriptions for antibiotics for women were significantly more unnecessary compared to those for men (OR 2.03; 95% CI: 1.05–3.93). Table 3 (Appendix, web only) shows the distribution of unnecessary antibiotic prescriptions for male and female patients by country and type of URTI. Sweden had the lowest rates of unnecessary antibiotic prescribing. In four of the six countries, most antibiotic prescriptions for acute pharyngotonsillitis were classified as unnecessary. Only in Denmark could a gender difference in unnecessary antibiotic prescription be found (P-value 0.02). This was mostly accounted for by more unnecessary antibiotic prescriptions for acute pharyngotonsillitis in Danish men as compared to women (OR 2.16; 95% CI: 1.32–3.56).
95% CI
K. Bagger et al.
Table 3. Rate of unnecessary antibiotic prescribing (% of consultations followed by a prescription) in men and women by country and diagnosis.
Eur J Gen Pract Downloaded from informahealthcare.com by University of Birmingham on 03/21/15 For personal use only.
4
Eur J Gen Pract Downloaded from informahealthcare.com by University of Birmingham on 03/21/15 For personal use only.
A possible weakness is that GPs participated on a voluntary basis and may represent a group of doctors more interested in rational antibiotic use. Our results may, therefore, underestimate the rate of unnecessary antibiotic prescribing worldwide. Additionally, participating in an audit may have influenced the prescribing pattern: the GPs might be tempted to register a diagnosis that justified the treatment instead of vice versa, which could lead to diagnostic misclassification bias. However, such a potential bias would not be expected to influence the effect of gender on unnecessary antibiotic prescribing. Furthermore, the fact that data collection took place in 2007 and the analysis in 2013 could potentially lead to bias, but since there was no change in clinical guidelines in that period, this is not expected to influence the outcome. Interpretation The high rates of unnecessary antibiotic prescriptions for URTIs in general practice are in accordance with previous studies (7,11,12,16). Few gender differences in the rate of unnecessary antibiotic prescribing were found. The results point in different directions and do not support our prior hypothesis that women had a higher risk of receiving unnecessary antibiotic prescriptions for URTIs than men. We found no gender differences in patient demand. Previous studies have concluded that patient demand for treatment was the most important non-clinical factor for prescription of non-indicated antibiotics for RTIs, irrespective of gender (18,19). Implication for practice and future research Women received an unnecessary antibiotic prescription for acute otitis media almost twice as often as men. This finding should be taken into account when clinical practice guidelines for URTIs are being updated (25,26). Detailed insights into the decision-making process of antibiotic prescribing by the individual GP, e.g. by qualitative studies, could further elucidate where efforts could best be directed in the continuous campaign to reduce unnecessary antibiotic prescribing. Conclusion Our results could not support the hypothesis that there is a gender difference in the proportion of unnecessary antibiotic prescriptions for URTI. There were no differences in demand for antibiotics between men and women. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Gender difference in antibiotic overprescribing
5
REFERENCES 1. Bronzwaer SLAM, Cars O, Buchholz U, Mölstad S, Goettsch W, Veldhuijzen IK, et al. The relationship between antimicrobial use and antimicrobial resistance in Europe. Emerg Infect Dis. 2002; 8:278–82. 2. Straand J, Rokstad KS, Sandvik H. Prescribing systemic antibiotics in general practice. A report from the Møre & Romsdal prescription study. Scand J Prim Health Care 1998;16:121–7. 3. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing among office-based physicians in the United States. J Am Med Assoc. 1995;273:214–9. 4. Grimsmo A, Hagman E, Falkø E, Matthiessen L, Njálsson T. Patients, diagnoses and processes in general practice in the Nordic countries. An attempt to make data from computerised medical records available for comparable statistics. Scand J Prim Health Care 2001;19:76–82. 5. Månsson J, Nilsson G, Strender L-E, Björkelund C. Reasons for encounters, investigations, referrals, diagnoses and treatments in general practice in Sweden—a multicentre pilot study using electronic patient records. Eur J Gen Pract. 2011;17:87–94. 6. Bjerrum L, Munck A, Gahrn-Hansen B, Hansen MP, Jarbol DE, Cordoba G, et al. Health alliance for prudent antibiotic prescribing in patients with respiratory tract infections (HAPPY AUDIT)—impact of a non-randomised multifaceted intervention programme. BMC Fam Pract. 2011;12:52. 7. André M, Odenholt I, Schwan A, Axelsson I, Eriksson M, Hoffman M, et al. Upper respiratory tract infections in general practice: Diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests. Scand J Infect Dis. 2002;34:880–6. 8. Ahovuo-Saloranta A, Borisenko OV, Kovanen N, Varonen H, Rautakorpi UM, Williams JW, et al. Antibiotics for acute maxillary sinusitis. Cochrane Database Syst Rev. 2008;16:CD000243. 9. Arroll B. Antibiotics for upper respiratory tract infections: An overview of Cochrane reviews. Respir Med. 2005;99:255–61. 10. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2004;2:CD000023. 11. Akkerman AE, Kuyvenhoven MM, van der Wouden JC, Verheij TJM. Analysis of under- and overprescribing of antibiotics in acute otitis media in general practice. J Antimicrob Chemother. 2005;56:569–74. 12. Akkerman AE, Kuyvenhoven MM, van der Wouden JC, Verheij TJM. Determinants of antibiotic overprescribing in respiratory tract infections in general practice. J Antimicrob Chemother. 2005;56:930–6. 13. Cadieux G, Tamblyn R, Dauphinee D, Libman M. Predictors of inappropriate antibiotic prescribing among primary care physicians. CMAJ 2007;177:877–83. 14. Otters HBM, van der Wouden JC, Schellevis FG, van SuijlekomSmit LW, Koes BW. Trends in prescribing antibiotics for children in Dutch general practice. J Antimicrob Chemother. 2004;53: 361–6. 15. Sayer GP, Britt H. Sex differences in prescribed medications: Another case of discrimination in general practice. Soc Sci Med. 1997;45:1581–7. 16. Gonzales R, Steiner JF, Sande AM. Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. J Am Med Assoc. 1997; 278:901–4. 17. Statens Serum Institut. Statistik over forbruget af antibiotika [Online]. Available at http://www.ssi.dk/Sundhedsdataogit/ Dataformidling/Laegemiddelstatistikker/forbruget af antibiotika. aspx (accessed 9 November 2013). 18. Macfarlane J, Holmes W, Macfarlane R, Britten N. Influence of patients’ expectations on antibiotic management of acute lower respiratory tract illness in general practice: Questionnaire study. Br Med J. 1997;315:1211–4.
6
K. Bagger et al.
Eur J Gen Pract Downloaded from informahealthcare.com by University of Birmingham on 03/21/15 For personal use only.
19. Hummers-Pradier E, Pelz J, Himmel W, Kochen MM. Treatment of respiratory tract infections—a study in 18 general practices in Germany. Eur J Gen Pract. 1999;5:15–20. 20. Bjerrum L, Munck A, Gahrn-Hansen B, Hansen MP, Jarboel D, Llor C, et al. Health alliance for prudent prescribing, yield and use of antimicrobial drugs in the treatment of respiratory tract infections (HAPPY AUDIT). BMC Fam Pract. 2010;11:29. 21. Munck AP, Hansen DG, Lindman A, Ovhed I, Førre S, Torsteinsson JB. A Nordic collaboration on medical audit. The APO method for quality developement and continuous medical education (CME) in primary health care. Scand J Prim Health Care 1998;16:2–6. 22. NICE. Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care. NICE Clinical Guideline 69. London, UK; 2008. 23. Thomas M, Yawn BP, Price D, Lund V, Mullol J, Fokkens W. EPOS primary care guidelines: European position paper on the
primary care diagnosis and management of rhinosinusitis and nasal polyps 2007—a summary. Prim Care Respir J. 2008; 17:79–89. 24. Health alliance for prudent prescribing, yield and use of antimicrobial drugs in the treatment of respiratory tract infections, HAPPY AUDIT. HAPPY AUDIT guidelines. http://www.happyaudit. org/front_page/publications.aspx (accessed 15 November 2012). 25. Grol R. Successes and failures in the implementation of evidence-based guidelines for clinical practice. Medical Care 2001;39:46–54. 26. Shekelle P, Woolf S, Grimshaw JM, Schünemann HJ, Eccles MP. Developing clinical practice guidelines: Reviewing, reporting, and publishing guidelines; updating, guidelines; and the emerging issues of enhancing guideline implementability and accounting for comorbid conditions in guideline development. Implement Sci. 2012;7:62.
