Trends in antibiotic prescribing by dental practitioners in Germany

Accepted Manuscript Trends in antibiotic prescribing by dental practitioners in Germany Frank Halling, MD, DMD, Andreas Neff, MD, DMD, PhD, Prof, Paul Heymann, MD, DMD, Thomas Ziebart, MD, DMD, PhD PII:

S1010-5182(17)30270-6

DOI:

10.1016/j.jcms.2017.08.010

Reference:

YJCMS 2755

To appear in:

Journal of Cranio-Maxillo-Facial Surgery

Received Date: 1 March 2017 Revised Date:

4 July 2017

Accepted Date: 10 August 2017

Please cite this article as: Halling F, Neff A, Heymann P, Ziebart T, Trends in antibiotic prescribing by dental practitioners in Germany, Journal of Cranio-Maxillofacial Surgery (2017), doi: 10.1016/ j.jcms.2017.08.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Trends in antibiotic prescribing by dental practitioners in Germany

Frank Hallinga,b MD, DMD a

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Gesundheitszentrum Fulda, Praxis für MKG-Chirurgie, Gerloser Weg 23a, D-36039 Fulda, Germany (Head: Dr. Dr. Frank Halling)

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Dept. of Maxillofacial Surgery, University Hospital, Baldingerstr., D-35043 Marburg, Germany (Head: Prof. Dr. Dr. Andreas Neff)

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Andreas Neffb MD, DMD, PhD b

Paul Heymannb MD, DMD b

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Dept. of Maxillofacial Surgery, University Hospital, Baldingerstr., D-35043 Marburg, Germany (Head: Prof. Dr. Dr. Andreas Neff)

Dept. of Maxillofacial Surgery, University Hospital, Baldingerstr., D-35043 Marburg, Germany (Head: Prof. Dr. Dr. Andreas Neff)

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Thomas Ziebartb MD, DMD, PhD b

Dept. of Maxillofacial Surgery, University Hospital, Baldingerstr., D-35043 Marburg, Germany (Head: Prof. Dr. Dr. Andreas Neff)

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Corresponding author: Frank Halling, Gesundheitszentrum Fulda, Praxis für MKG-Chirurgie, Gerloser Weg 23a, D-36039 Fulda, Germany. Phone: +49 661 63362, FAX: +49 661 63368, [email protected]

Declaration

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

ACCEPTED MANUSCRIPT Summary

INTRODUCTION Since their discovery in the 20th century, antibiotics have

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been saving the lives and easing the suffering of millions of people. They are the most important instrument in the treatment of infectious diseases. Antibiotics alongside

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with analgesics and local anesthetics are the most

frequently used drugs in dentistry (Dar-Odeh et al., 2008).

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Predominantly, they are needed for the treatment of

odontogenic infections (Oberoi et al., 2015), to a smaller degree also for infective prophylaxis preceding invasive dental surgery in the case of different previous conditions

2015).

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and high-risk patients (Dayer et al., 2015; Bodem et al.,

The percentage of antibiotics prescribed by dentists in

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relation to all antibiotic prescriptions in industrial countries is around 10% (Al-Haroni and Skaug, 2007;

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Pipalova et al., 2014; Marra et al., 2016). A large number of studies and surveys show a huge variation as to measuring into doses and duration of the dental antibiotic therapy. It is probable that numerous prescriptions of antibiotics in dentistry also turn out to be superfluous (Dar-Odeh et al., 2010; Palmer et al., 2000; Marra et al., 2016).

ACCEPTED MANUSCRIPT However, the number of problems concerning the consumption of antibiotics in human medicine are by no means less obvious. In ambulatory care in the United States, medical doctors prescribed antibiotics at every

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tenth ambulatory visit between 2007 and 2009. In all, 60% of the prescriptions were broad spectrum antibiotics, and

25% of these prescriptions were made to treat diseases for

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which the use of an antibiotic is not indicated (Shapiro et

al., 2014). In England, as much as 57% of all patients with

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dental problems, seeking treatment in a general medical

practice, received prescriptions of antibiotics (Cope et al., 2016b). Also, in Germany, physicians prescribe broadspectrum antibiotics far too often (Bätzing-Feigenbaum et

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al., 2016; Falkenstein et al., 2016).

Bacterial resistance in this context becomes an important issue for medicine and is now also intensely discussed in

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the dental literature (Al-Haroni and Skaug, 2007; Rams et

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al., 2013; Oberoi et al., 2015). As a main reason for an increase of resistance to antibiotics over the last years, the overprescription and inappropriate use especially of broadspectrum antibiotics is considered (Garg et al., 2014; Karki et al., 2011; Oberoi et al., 2015; Shapiro et al., 2014). The literature provides evidence of inadequate prescribing by dentists for a number of reasons, ranging from lack of

ACCEPTED MANUSCRIPT knowledge, absence of infection, and social factors (Oberoi et al., 2015; Cope et al., 2016c). In many cases, antibiotics are being prescribed for too long a period of time and with nonstandardized frequency and duration

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(Palmer and Martin, 1998). In order to solve this problem, different strategies are being discussed. First of all, trends and quantity of the medical and dental prescriptions

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should be monitored on reliable data. On the basis of these data, the use of the different antibiotics should be

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evaluated in order to reduce the consumption to a

reasonable level (Al-Haroni and Skaug, 2007). In the scientific literature, antibiotic prescriptions in dentistry are often being analyzed, either in the field of a university

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clinic (Dar-Odeh et al, 2008; Halti et al., 2015), by means of regional surveys (Epstein et al., 2000; Mainjot et al., 2009; Köhler et al., 2013) or by the evaluation of

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prescriptions (Palmer et al., 2000). Reliably structured figures concerning the actual number of prescriptions of

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antibiotics by dentists on a national or at least regional scale are hardly available. Only in a few countries or regions are these data published periodically, e.g., in England, Wales, Norway, Australia, and British Columbia, Canada. In this study, the actual dental and medical prescriptions of antibiotics in Germany are analyzed for the first time covering the period of 4 years (2012–2015).

ACCEPTED MANUSCRIPT MATERIALS AND METHODS This study is based on data issued by a scientific institute called WIdO, based in Berlin. WIdO is an independent “Research Institute for Local Health Care Systems,”

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which, among other tasks, carries out analysis of the

provision of drugs in Germany. The annually published scientific report of WIdO is the “The Drug Prescription

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Report (Arzneimittelverordnungs-Report [AVR]).” In this

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report, all medical and dental recipes at the expense of the statutory health insurances are included. The basis of this analysis were all prescriptions of resident physicians and dentists that were cashed up by public pharmacies within Germany. Since 2012, all dental prescriptions of

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antibiotics have been documented annually in a separate chapter of the report. Therefore, antibiotic drug prescriptions by dentists dating from January 1, 2012, to

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December 31, 2015, can be analyzed. This amounted to

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97% of all dental prescriptions of antibiotics in the field of the statutory health insurances, because antibiotics with less than 3,000 (2012-2014), respectively less than 10,000 prescriptions in 2015 per year, are not included (Halling, 2016). The report does not cover the prescriptions at the cost of the private health insurances in Germany. In 2015, 86.1% of the people in Germany had a statutory health insurance, 10.7% were covered by a private health insurance (VdEK, 2016). The number of resident doctors

ACCEPTED MANUSCRIPT with nearly 143,000 remained constant between 2012 and 2015, whereas the number of the registered dentists with their own practices slightly increased, from 60,500 to 62,000 (Schaufler and Telschow, 2013; Schaufler and

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Telschow, 2016).

For the analysis, we used the World Health Organization’s Anatomical Therapeutic Chemical (ATC) Classification

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standard codes for the classification of the prescriptions

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and the defined daily dose (DDD), a unit that is

independent of different drug preparations. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults and does not reflect the recommended or prescribed daily dose. The DDD

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provide a fixed unit of measurement independent of price, dosage form, or package size, enabling the researcher to assess trends in drug consumption and to perform

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comparisons between population groups. As a

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consequence, studies of the medication use that are comparable transnationally are possible (Merlo et al., 1996). Meanwhile, DDD is the sole standard dose unit in most of the pharmacoepidemiologic studies. Data management and statistical analysis The subject matter of the analysis is the total number of all prescriptions of antibiotics by resident physicians and dentists during the investigation period of 4 years (from 1

ACCEPTED MANUSCRIPT January 2012 to 31 December 2015). Furthermore, the shares of the different groups of antibiotics per year in relation to all dental antibiotic prescriptions within the period of investigation were identified. Differences in the

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portions of the different antibiotics were tested by means of the Student t-test for related samples and Wilcoxon

signed-ranks test. The Pearson test was used to measure

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the correlation between the increase respectively and the

decrease of the portions of antibiotic substances within the

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period of investigation.

In addition, the relative shares (in percent) of the different antibiotic groups on all dental and medical antibiotic prescriptions of each year of the investigation period were

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determined. The mean values within the study period of the dental and medical prescriptions were compared and tested for significance by the Student t-test for

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independent samples and the Mann-Whitney U-test.

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Statistical analysis was carried out using SPSS data analysis software (version 24.0; SPSS Inc., Chicago, IL, USA) and Microsoft Excel (Microsoft Corp., Redmond, WA, USA). Any p values of less than 0.05 (p< 0.05) were considered significant, and of less than 0.01 (p< 0.01) highly significant. A p value below 0.05 is marked using an asterisk within the graph or table. RESULTS

ACCEPTED MANUSCRIPT During the investigation period, the average of all prescriptions of antibiotics by physicians were 36.6 million, representing 91.2% and the on the part of the dentists 3.53 million representing 8.8% of all antibiotic

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drug prescriptions. Between 2012 and 2015, the dental

prescriptions of antibiotics in total decreased by 440,000

prescription, or 12.1%. On the part of the physicians, the

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reduction amounted to 1.3 million prescriptions or 3.5%

during the same period. These differences are statistically

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significant (p < 0.05) (Table 1).

In the field of the DDDs of antibiotics, the reduction

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amounted to 8.3% on the part of the dentists and merely 1.5% on the side of the physicians during the study period. In total, the reduction of the DDDs of antibiotics was only

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0.8%. Although the number of conservative and surgical treatments in dentistry grew 8% during the investigation

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period (KZBV, 2016), the amount of dental antibiotic prescriptions and DDD decreased. However, there is no statistically significant correlation between the quantity of antibiotic prescriptions or DDDs and the number of accounts for dental treatment. In the year 2012, each dentist in Germany made 60 prescriptions of antibiotics in total, in 2015 only 51.6 prescriptions representing a reduction of 14%. On the side of the physicians, the

ACCEPTED MANUSCRIPT decline was only 3.5%. This difference was statistically significant (p < 0.05) (Table 1). The proportion of antibiotic prescriptions on all dental prescriptions decreased by 48% in 2012 to 45.8% in 2015, representing

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a reduction of 4.6%. Independently of price changes, the

average costs of all antibiotic prescriptions of each dentist per year amounted to € 971 in 2012 and € 888 in 2015,

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representing a reduction of 8.5%.

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Figure 1 shows a differentiated view of the antibiotic

prescriptions by dentists: penicillins and clindamycin were the most often prescribed antibiotics in the investigation period, but between 2012 and 2015 there was a shift from clindamycin to amoxicillin as the first-place antibiotic. In

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the investigation period, the share of prescriptions of amoxicillin climbed by 10.2%. The total amount in 2015 was 45.8% of all antibiotic prescriptions. Simultaneously

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the proportion of prescriptions of clindamycin was

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reduced from 37.8% in 2012 to 31.7% in 2015 representing an absolute decrease of 6.1% (Figure 1). This contrary development was highly statistically significant (p<0.01). In total, the percentage of both antibiotics on all antibiotic prescriptions increased from 73.4% in 2012 to 77.5% in 2015.

ACCEPTED MANUSCRIPT The increase oin the prescriptions of co-amoxiclav in relation to the decline of clindamycin was also highly statistically significant (p<0.01). The averages of the medical and dental prescriptions

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between 2012 and 2015, referring to the proportions of the various antibiotic groups, are remarkably different (Figure 2). For penicillin V, amoxicillin, clindamycin, and

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tetracyclines, significant differences exist (p<0.05).

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Particularly the proportion of clindamycin in the medical group (1.9%) is 18-fold lower than in the dental group (34.9%). In 2015, more than the half (57.9%) of all DDDs of clindamycin in Germany had their origin in dental prescriptions. On the part of the physicians, the structure

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of the antibiotic prescriptions is by far more heterogenous and less focused on specific substances. This fact is represented by the high proportion of “other antibiotics” in

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the medical group (55.5%). Because of the heterogenity of

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this group, it is pointless to perform a test for significance.

DISCUSSION

Judicious use of antibiotics in conjunction with surgical therapy is the most appropriate method to manage orofacial infections (Swift et al., 2002). In general, dentists of all countries prefer only a few different antibiotics. There is consensus that antibiotics with the narrowest

ACCEPTED MANUSCRIPT antimicrobial spectrum should be used in order to prevent resistance. Moreover, they should have characteristics such as low incidence of toxicity and side effects and bactericide, if possible (Gonul et al., 2013). However,

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evidence-based information concerning the proper choice of antibiotics, dosages, dosing intervals and duration of

antibiotic therapy is limited (Dar Odeh et al., 2008). The

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Centers for Disease Control and Prevention estimate that approximately one-third of all outpatient antibiotic

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prescriptions are unnecessary (CDC, 2016). In a recent dental study, nearly two-thirds of antibiotics were

prescribed in situations in which there was no spreading infection, and more than 70% were used without the

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precaution for a surgical procedure (Cope et al., 2016c). In British emergency wards, three-fourths of all dental patients received inadequate prescriptions of antibiotics

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(Dailey and Martin, 2001).

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Our study is the first in Germany to analyze antibiotic prescribing rates by dentists over a period of 4 years. Drug prescriptions by dentists account for only 1.1% of the total prescription volume of drugs in Germany (Halling, 2016). In England, the ratio of dental prescriptions amounts even only to 0.5% of the total prescription volume (HSCIC, 2015). In the year 2015, prescriptions of antibiotics represented 45.8% of all dental prescriptions in Germany. In Wales in 2008, as much as 67.2% of all dental

ACCEPTED MANUSCRIPT prescriptions related to antibiotics (Karki et al., 2008), and in England in 2014, the percentage of antibiotics was 66.6% of the total consumption in dentistry (HSCIC, 2015).

concentrated on the knowledge, indications, and

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Previous studies concerning antibiotics in dentistry mainly

preferences of dentists (Palmer et al., 2000; Lauber et al.,

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2007). Only a few studies have examined longitudinal

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prescribing trends in dentistry (Al-Haroni and Skaug,

2007; Ford et al., 2007; Karki et al., 2011; Marra et al., 2016; Pipalova et al., 2014); the longest investigation period analyzed was 17 years (Marra et al., 2016). In England, information on the items prescribed by dentists

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are provided annually by NHS Prescription Services (HSCIC, 2015). The available studies show that the proportion of dentistry on all antibiotic prescriptions

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ranged between 8% and 11.3% (Al-Haroni and Skaug,

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2007; Karki et al., 2010; Marra et al., 2016), whereas the corresponding number in Germany in the year 2015 was 8.3% (Halling, 2016). In 2014, on average, 1.7 antibiotic prescriptions per week are ordered by each dentist in England (HSCIC 2015), which is about three times more frequent than in Norway (Al-Haroni und Skaug, 2007). In 2015, Germany ranked in a mid-field position with 1 prescription a week. Seven

ACCEPTED MANUSCRIPT years earlier, each dentist even prescribed twice as many antibiotics as in 2015 (Halling, 2010). The DDD per prescription is, at 9.76, only slightly higher than in British Columbia, Canada (9.3) and Norway (9.26) (Al-Haroni

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and Skaug, 2007; Marra et al., 2016). Looking at studies

reflecting at least a 4-year course, it is striking that only in

England (Public Health England, 2015; HSCIC, 2015) and

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Germany a reduction of the prescription frequency could

be found, whereas in the Czech Republic and in Australia

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an increase of the volume of prescriptions between 16.4% and 23.8% took place (Pipalova et al., 2014; Marra et al., 2016). In contrast to Germany, the total consumption of antibiotics in primary and secondary care in England

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increased significantly by 6.5% between 2011 and 2014 (Public Health England, 2015). There are substantial variations in the shares of the

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different antibiotics prescribed by dentists throughout the

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world (Table 2). In all comparable long-term studies, penicillin V and amoxicillin are the most frequently prescribed antibiotics in dentistry. The percentages of these antibiotics range from 47% (Pipalova et al., 2014) to 90% (Marra et al. 2016). Notable are the Norwegian data of 2007, with an exceptional proportion of 73% penicillin V (Al-Haroni and Skaug, 2007) and a high percentage of 31.4% amoxicillin and clavulanic acid in the Czech Republic (Pipalova et al., 2014). For other antibiotics, the

ACCEPTED MANUSCRIPT large percentages of clindamycin in Germany (31.7%) and in the Czech Republic (25.1%) are remarkable (Pipalova et al., 2014). This contrasts with the shares of clindamycin in England, Wales. and Norway which are less than 5%

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(Al-Haroni and Skaug 2007; HSCIC, 2015; Karki et al.,

2011). In England, the share of the second most common dental antibiotic, metronidazole is 28.3%, whereas this

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pharmaceutical agent in Germany, with a share of 0.9%, is of marginal importance. In all previously mentioned

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studies, tetracyclines and macrolides play no essential role.

Looking at the dental shares of specific antibiotics in the total consumption of antibiotics, noticeable differences

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can be seen. Although almost 80% of antibiotics are prescribed by general practices a lot of studies show a substantial increase in the proportionate and absolute

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prescribing rates by dentists (Marra et al. 2016; Ford et al.

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2016; Pipalova et al. 2014). The proportion of dental prescriptions of certain antibiotics in primary health care can be very different. Amoxicillin remains the most frequently used antibiotic in treatment of odontogenic infections all over the world (Dar-Odeh et al., 2008; Garg et al., 2014; Haliti et al., 2015; Marra et al., 2016). It is also the drug of choice for prophylaxis of infectious endocarditis and comparatively

ACCEPTED MANUSCRIPT safe for patients without a history of amoxicillin allergy (Thornhill et al., 2015). In Germany, 12.7% of all prescriptions of co-amoxiclav are made by dentists, in the Czech Republic even up to 18.7% (Pipalova et al., 2014);

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however, in Australia and British Columbia, Canada, only the figures are only 1.1% and 0.3%, respectively (Ford et

al., 2016; Marra et al., 2016). The high proportions of co-

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amoxiclav corresponds with the findings that the oral

cavity is more often inhabited by bacterial beta-lactamase-

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producing strains (Rams et al., 2013). However, in

Scotland, co-amoxiclav is classified as a second-line antibiotic without advantage in routine use and one that could contribute to the development of antimicrobial

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resistance (Dundee Dental Education Centre, 2016). In the Czech Republic, nearly two-thirds of all prescriptions of metronidazole are ordered by dentists

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(Pipalova et al., 2014); in England the percentage is 36.5%

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(HSCIC, 2015); and in Germany, it is only 8.8%. Although there is no evidence that adjunct systemic antibiotics are of additional benefit to conventional mechanical debridement in refractory periodontitis (Santos et al., 2016), in some countries, synthetic nitroimidazole drugs, mostly metronidazole, are recommended as firstline antibiotics in the treatment of advanced or refractory periodontitis (Dundee Dental Education Centre, 2016; Pipalova et al., 2016).

ACCEPTED MANUSCRIPT The specific phenomenon in contemporary dental care is the very often prescribed and misused clindamycin (Pipalova et al., 2014). Clindamycin was introduced in dentistry in the 1990s (van der Bijl, 1994). Particularly

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striking are the extremely high dental proportions at 83% and 57.9% in the Czech Republic and Germany,

respectively (Pipalova et al., 2014). Possible factors

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contributing to this trend may be the advantage of good bone penetration or the fact that clindamycin is being

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substituted for penicillins or amoxicillin in case of allergic reactions to betalactam antibiotics or potentially

influenced by commercial companies (Dar-Odeh et al., 2010; Halling, 2010; Pipalova et al., 2014; Ford et al.,

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2016). In England, Norway, and British Columbia, Canada, clindamycin is of no importance in dentistry or in general medicine (Al- Haroni and Skaug, 2007; HSCIC,

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2015; Marra et al., 2016). The insignificance of clindamycin in the United Kingdom could be explained by

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the current Scottish dental clinical guidance, in which clindamycin is qualified as second-line antibiotic for dental abscess (Dundee Dental Education Centre, 2016). A meta-analysis considering the antibiotic class and the risk of Clostridium difficile infections in the community setting

relative to no antibiotic exposure showed a 6-fold higher risk for clindamycin in comparison to penicillins (odds ratio = 16.8 vs. 2.7) (Brown et al., 2013).

ACCEPTED MANUSCRIPT Limitations of the current study are the lack of information on doses used, the frequency and duration of administration, the combinations of antibiotics, and the reasons for individual prescriptions. Additionally, no

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country-specific data are provided concerning the amount of antibiotics prescribed by specialists such as pediatric dentists or oral and maxillofacial surgeons in Germany

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and worldwide. None of the available studies based on

reliable prescription data (Table 2) supply information on

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indications for antibiotic prescriptions or data on antibiotic prescribing practices of specialized dental practitioners or maxillofacial surgeons, because they are subsumed under terms such as “dentists,” “dental practitioners,” or

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“primary care dentists.” This should be reason enough to initiate further investigations on these issues. Current studies based on questionnaires show that the

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diagnoses “acute apical or periodontal abscess,”

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“pericoronitis,” “aggressive marginal periodontitis,” and “irreversible pulpitis” are the most common indications for antibiotic prescribing (Cope et al., 2016a; Garg et al., 2014; Köhler et al., 2013; Mainjot et al., 2009). However, there is currently either no or unclear evidence for efficacy of antibiotics in the treatment of any of these conditions (Cope et al., 2014; Dar-Odeh et al., 2010). Many uncertainties exist regarding the indications for and modalities of antibiotic treatment in dentistry (Köhler et

ACCEPTED MANUSCRIPT al., 2013), but some authors argue that medical issues such as the rational pharmacotherapy of infectious diseases and pharmacotherapy at all are currently only of marginal interest in dentistry (Pipalova et al., 2014). As a

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consequence, regular continuing education for dental

practitioners in the safe and appropriate use of medicines

based on rational guidelines should be mandatory (Cope et

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al., 2016a; Ford et al., 2016; Oberoi et al., 2015; Pipalova et al., 2014). However, user-friendly manuals for

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antibiotic prescribing that can be found, for instance, in

the Scottish dental clinical guidance “Drug Prescribing for Dentistry” are rare, and yet essential to establish a system of antimicrobial stewardship (Dundee Dental Education

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Centre, 2016). Antibiotic stewardship includes the following: ongoing update of the pharmacological knowledge in dental education’ continuous assessment of

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dental practices education; persuading prescribers to prescribe antibiotics appropriately; restricting the

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prescribing of key antibiotics; measurement and feedback regarding antibiotic use; and explaining to patients the risks of antibiotics (Falkenstein et al., 2016; Marra et al., 2016; Public Health England, 2015). In dentistry, there is copious evidence that the implementation of guidance by dental professionals is variable, and understanding how to change this is limited (Clarkson et al., 2008). However, there is a lack of robust, generalizable evidence on how

ACCEPTED MANUSCRIPT best to promote the translation of guidance into practice. One possible approach is an audit and feedback intervention, which is defined as “any summary of clinical performance of healthcare over a specified period of time”

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aimed at improving health professional practice (Jamtvedt et al., 2007). First findings of a clinical audit of antibiotic prescribing in general dental practices in Wales indicate

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that this process can be a useful tool for dentists to identify guideline-incongruent antimicrobial use (Cope et al,

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2016a). In a recent controlled trial, the antibiotic

prescribing rate of dentists in Scotland who received individualized feedback was 5.7% lower than the antibiotic prescribing rate of dentists without this kind of

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feedback (Elouafkaoui et al., 2016). Apart from the duty of every dentist to use the best evidence-based practice, it is essential to educate our patients about the choices that

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we make and the reasons for making these choices. It is a quite general experience that patients in dental surgeries

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routinely expect an antibiotic for the treatment of toothache (Lewis, 2008). Therefore, the general public needs to be informed about the risks of antibiotic use and the importance of restricting antibiotics only in cases of severe infection. It is an urgent requirement for both professional and public understanding of the appropriate use of this life-saving component of treatment (Lewis, 2008).

ACCEPTED MANUSCRIPT CONCLUSION During the period of investigation, there was a shift from clindamycin to amoxicillin as the most-prescribed antibiotic in German dentistry. However, the share of

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clindamycin is still very high and amounts to around one-

third of all antibiotic prescriptions by dentists. This aspect differs considerably from the antibiotic prescriptions by

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German physicians, in which amoxicillin plays a minor

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role and clindamycin is of no importance. In most of the countries, amoxicillin is the first-line antibiotic in

dentistry. To improve standards of antibiotic treatment in dentistry, antibiotic stewardship measures such as further outcome studies, analyses of prescriptions, and strict

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guidelines are needed.

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Acknowledgements The authors wish to thank Nils Wehner, MA, for his help in the statistical analysis.

Conflict of interest None.

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Ford PJ, Saladine C, Zhang K, Hollingworth SA: Prescribing patterns of dental practitioners in Australia from 2001-2012. Part I: antimicrobials. Aust Dent J. Available at: http://doi: 10.1111/adj.12427, 2016 Garg AK, Agrawal N, Tewari RK, Kumar A, Chandra A: Antibiotic prescription pattern among Indian oral healthcare providers: a cross-sectional survey. J Antimicrob Chemother 69:526-528, 2014

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Gonul O, Aktop S, Satilmis T, Garip H, Goker K: Odontogenic Infections. In: Motamedi MHK (ed.) A Textbook of Advanced Oral and Maxillofacial Surgery. Available at: http://www.intechopen.com/books/a-textbook-of-advanced-oral-and-maxillofacialsurgery/odontogenic-infections; 2013. Accessed November 28, 2016.

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Haliti NR, Haliti FR, Koçani FK, Gashi AA, Mrasori SI, Hyseni VI, Bytyqi SI, Krasniqi LL, Murtezani AF, Krasniqi SL: Surveillance of antibiotic and analgesic use in the Oral Surgery Department of the University Dentistry Clinical Center of Kosovo. Ther Clin Risk Manag 11:1497-1503, 2015 Halling F: Zahnärztliche Antibiotikaverordnungen: Zwischen Anspruch und Wirklichkeit. Zahnärztl Mitt 100:50-55, 2010

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Halling F: Zahnärztliche Arzneiverordnungen. In: Schwabe U, Paffrath D (eds.) Arzneiverordnungs─Report 2016. Berlin: Springer,739-749, 2016 Health and Social Care Information Center: Prescribing by Dentists. England 2014. Available at: http://content.digital.nhs.uk/catalogue/PUB17425/pres_dent_eng_2014_rep.pdf; 2015. Accessed November 29, 2016. Jamtvedt G, Young JM, Kristoffersen DT, O’Brien MA, Oxman AD: Audit and feedback: effects on professional practice and health care outcomes. Cochrane Database Syst Rev. 19 (2):CD000259, 2007 Karki AJ, Holyfield G, Thomas D: Dental prescribing in Wales and associated public health issues. Br Dent J 210:E21, 2011 Köhler M, Meyer J, Linder M, Lambrecht JT, Filippi A, Kulik Kunz EM: Prescription of antibiotics in the dental practice: a survey of dentists in Switzerland. Schweiz Monatsschr Zahnmed 123:748-759, 2013

ACCEPTED MANUSCRIPT Lauber C, Lalh SS, Grace M, Smith MH, MacDougall K, West P, Compton S: Antibiotic prophylaxis practices in dentistry: a survey of dentists and physicians. J Can Dent Assoc 73:245, 2007 Lewis MA: Why we must reduce dental prescription of antibiotics: European Union Antibiotic Awareness Day. Br Dent J 205:537-538, 2008

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Mainjot A, D'Hoore W, Vanheusden A, Van Nieuwenhuysen JP: Antibiotic prescribing in dental practice in Belgium. Int Endod J 42:1112-1117, 2009 Marra F, George D, Chong M, Sutherland S, Patrick DM: Antibiotic prescribing by dentists has increased: Why? J Am Dent Assoc 147:320-327, 2016 Merlo J, Wessling A, Melander A: Comparison of dose standard units for drug utilisation studies. Eur J Clin Pharmacol 50:27-30, 1996

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Oberoi SS, Dhingra C, Sharma G, Sardana D: Antibiotics in dental practice: how justified are we. Int Dent J 65:4-10, 2015

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Palmer N, Martin M: An investigation of antibiotic prescribing by general dental practitioners: a pilot study. Prim Dent Care 5:11-14, 1998 Palmer NA, Pealing R, Ireland RS, Martin MV: A study of therapeutic antibiotic prescribing in National Health Service general dental practice in England. Br Dent J 188:554-558, 2000 Pipalova R, Vlcek J, Slezak R: The trends in antibiotic use by general dental practitioners in the Czech Republic (2006-2012). Int Dent J 64:138-143, 2014

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Public Health England: English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) report. Available at: https://www.gov.uk/government/publications/english-surveillance-programme-antimicrobialutilisation-and-resistance-espaur-report; 2015. Accessed December 29, 2016.

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Rams TE, Degener JE, van Winkelhoff AJ: Prevalence of β-lactamase-producing bacteria in human periodontitis. J Periodontal Res 48:493-499, 2014

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Santos RS, Macedo RF, Souza EA, Soares RS, Feitosa DS: The use of systemic antibiotics in the treatment of refractory periodontitis: a systematic review. Am Dent Assoc 147:577-585, 2016 Schaufler J, Telschow C: Überblick über die Arzneiverordnungen nach Arztgruppen. In: Schwabe U, Paffrath D (eds.) Arzneiverordnungsreport 2013. Berlin: Springer, 954-966, 2013 Schaufler J, Telschow C: Überblick über die Arzneiverordnungen nach Arztgruppen. In: Schwabe U, Paffrath D (eds.) Arzneiverordnungsreport 2016. Berlin: Springer, 753-762, 2016 Shapiro DJ, Hicks LA, Pavia AT, Hersh AL: Antibiotic prescribing for adults in ambulatory care in the USA, 2007-09. J Antimicrob Chemother 69:234-240, 2014 Swift JQ, Gulden WS: Antibiotic therapy─managing odontogenic infections. Dent Clin North Am 46:623-633, 2002

ACCEPTED MANUSCRIPT Thornhill MH, Dayer MJ, Prendergast B, Baddour LM, Jones S, Lockhart PB: Incidence and nature of adverse reactions to antibiotics used as endocarditis prophylaxis. Antimicrob Chemother 70:2382-2388, 2015 Van der Bijl P: Clindamycin in dentistry. J Dent Assoc S Afr 49:563-566, 1994

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Verband der Ersatzkassen: Daten zum Gesundheitswesen: Versicherte. Available at: https://www.vdek.com/presse/daten/b_versicherte.html; 2016. Accessed November 10, 2016.

ACCEPTED MANUSCRIPT

Figure 1. Proportions of the different antibiotic groups

RI PT

prescribed by German dentists in the years 2012 to 2015 (100% represents all antibiotic prescriptions by dental

SC

practitioners).

Figure 2. Means of shares (%) of the proportions of the

M AN U

different antibiotic groups prescribed by dentists and

AC C

EP

TE D

physicians between 2012 and 2015 (*p< 0.05).

ACCEPTED MANUSCRIPT

otic

Antibiotic prescriptions,

Antibiotic prescriptions

(Physicians)

(Dentists)

prescri

Prescrip

ptions

tions/

(mio.)

year

Share on all prescription s (%)

(mio.)

Annual

Prescrip

Prescriptio

tions/ye

ns/

ar

physician

(mio.)

Share

of

all

Annual

prescripti

prescriptio

ons

ns /dentist

RI PT

Antibi

(%)

40.34

36.7

91

256

3.64

2013

42.24

38.5

91.1

269

3.74

2014

39.25

35.7

91

251

3.55

2015

38.6

35.4

91.7

247

3.2

8.3

51.6

x̅

40.1

36.6

91.2

255.8

3.53

8.8

57.6

−4.2

−3.5*

0.8*

−7.8*

−14*

20122015

M AN U

∆ (%)

−3.5*

9

60

8.9

61.3

9

57.6

SC

2012

−12.1*

Table 1. Medical and dental prescriptions between 2012

AC C

EP

TE D

and 2015 (*p< 0.05)

ACCEPTED MANUSCRIPT Penicllin V Halling, 2016

Amoxicillin

Coamoxiclav

Clindamycin

Metronidazole

Macrolides

Tetracyclines

>0.1

2.7

9

45.8

4.2

31.7

0.9

73

4.7

n.d.

4.5

6.9

0.5

28.3

Al-

and. Skaug,

HSCIC,

66.1

al., 2016 Pipalova al., 2014

5.7

82

2.6

6

11.5

31.4

Karki et

67

al, 2011

1

66.3

7.1

n.d.

n.d.= no data available.

0.8

4.5

0.2

n.d.

1.6

4.8

16.5

5

2

25

5

1

6.1

13.6

n.d.

0.3

prescriptions in different studies (100% = all dental antibiotic prescriptions)

7

25.1

Table 2. Proportions and types of antibiotics in dental

EP

al., 2016

AC C

Ford et

7.8

TE D

Marra et

M AN U

2015

SC

2007

RI PT

Haroni

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT