Antibiotic Administration Along with Endodontic Therapy in the Republic of Croatia: a Pilot Study.

OBJECTIVE: To evaluate the type and the frequency of antibiotic prescribing along with endodontic therapy in Croatia. The aim is, also, to assess the attitudes of Croatian doctors towards endodontic treatment of patients at risk of developing bacterial endocarditis.
MATERIAL AND METHODS: Data were collected by a survey questionnaire.
RESULTS: 8.4% of the examined practitioners stated that they prescribe antibiotics often, and 91.6% of them stated that they prescribed them never/ very rarely/rarely. Most of them (41%) prescribe antibiotics once or twice a month, 32.5% once or twice in several months and 20.5% once or twice a week. The most commonly used antibiotic was penicillin with clavulanic acid. Also, 26.2% of examined practitioners prescribed antibiotics for gangrene pulp, 51.2% of them for localized acute apical periodontitis without swelling, 85% of them for cellulitis, 75% of them for fever and enlarged lymph nodes, 16.9% of them for tooth with fistula and 94.1% of them for prophylaxis of infectious endocarditis. According to the results of study, 54.4% of dental practitioners did not prescribe antibiotics without intervention on susceptible tooth; 76% of participants often/almost always/ always accepted endodontic treatment of patients requiring antibiotic prophylaxis to prevent infectious endocarditis, and 96.7% of participants indicated they were familiar with recent instructions for antibiotic prophylaxis.
CONCLUSION: These findings point to inappropriate use of antibiotics in the practice of 83 dental practitioners questioned regarding the frequency of administration and indications. The most commonly used antibiotic was penicillin with clavulanic acid. A high percentage of surveyed practitioners stated that they were familiar with recent instructions for antibiotic prophylaxis. They also stated that they performed endodontic procedures on patients who were at risk of bacterial endocarditis. There is a noticeable need for targeted continuing education of dental practitioners in the Republic of Croatia.

Introduction

Endodontic infections, as a part of odontogenic infections, are polymicrobial, involving a combination of gram-positive, gram-negative, facultative anaerobes and strict anaerobic bacteria (, ). For this reason, dentists often prescribe antibiotics as a support to dental treatment or as the only therapy procedure (). Inappropriate use of antibiotics and the emergence of antibiotic-resistant bacterial strains are global problems in medicine today (). According to Cope and Chestnutt () dentists’ prescriptions accounted for approximately 10% of prescriptions of antimicrobials in primary care. Within the European Union (EU), according to Eurostat data from the EU Statistical Office, there are around 1.8 million doctors of medicine () and about 345,000 doctors of dental medicine (). Therefore, the contribution of individual medical professions to the emergence of antibiotic-resistant bacterial strains must be considered (, ).

Sensitivity of oral bacteria to antibiotics has been gradually decreasing and the number of resistant strains is growing, in particular Porphyromonas species and Prevotella species (). Similar problem has also been reported for alpha hemolytic streptococci (Streptococcus viridans) and for drugs such as macrolides, penicillin and clindamycin (, ). When bacteria become resistant to antibiotics, they also gain the ability to exchange antibiotic resistance with other bacterial species (). In addition, inappropriate use of antibiotics increases the risk of potentially fatal anaphylactic reactions and antibiotic side effects (, -) as well as patient demands and expectations for antibiotic therapy ().

Due to the emergence of bacterial resistance, numerous studies have been conducted to date to evaluate the manner and cost/benefit effects of prescribing antibiotics in the therapy of oral and dental diseases (-).

The aim of this pilot study was to evaluate the type and the frequency of antibiotic prescribing by dental practitioners along with endodontic therapy in the Republic of Croatia. Besides, the aim was to assess whether Croatian doctors of dental medicine follow the guidelines on the use of antibiotic prophylaxis for the prevention of bacterial endocarditis and whether they accept endodontic treatment of patients at risk of developing bacterial endocarditis.

Materials and methods

This study is a part of the dissertation: "Assessment of procedures in the performance of endodontic therapy in dental offices in the Republic of Croatia", which was approved by The Ethics Committee of the School of Dental Medicine of the University of Zagreb (05-PA.23.3/2018). For the purpose of this dissertation, a questionnaire containing about 100 questions was designed and distributed to dental practitioners in the Republic of Croatia in printed and electronic forms. The electronic form is accessible at the following link: https://goo.gl/forms/DrT0AaM9Y2YeRUty2. Only the questions related to antibiotics were included in this study (Table 1).

Table 1

Questions about antibiotic administration

QUESTIONS ABOUT ANTIBIOTIC ADMINISTRATION
1. Do you prescribe antibiotics with endodontic therapy?          never / very rarely / rarely / often / almost always / always
2. How often do you prescribe antibiotics for endodontic etiology problems?          (once a day; two or more times a day; once or twice a week; more than twice a week; once or twice a month; once or twice in several months)
3. What antibiotics are you most likely to prescribe to your patients for endodontic etiology problems?
4. For which diseases of the endodontic etiology do you most commonly prescribe antibiotics (you can tick more answers)? (answers offered)
5. How often do you prescribe an antibiotic without any local dental intervention on the cause of the endodontic problem?          never / very rarely / rarely / often / almost always / always
6. Do you accept to perform endodontic treatment in patients who need antibiotic prophylaxis to prevent infectious endocarditis?          never / very rarely / rarely / often / almost always / always
7. Are you familiar with the recent instructions (updates) on the use of antibiotic prophylaxis in bacterial endocarditis at-risk patients?          yes/no

Ninety (90) responses have been collected. Since seven questionnaires were answered by doctors who have not performed endodontic procedures in their clinical practice, their answers were not taken into account and a total of 83 questionnaires were processed (92%).

Results

In this pilot study the results are evaluated as a percentage.

The distribution of the participating dental practitioners regarding educational groups is shown in Table 2.

Table 2

Distribution of the participating dental practitioners regarding educational groups (%)

GROUP	DENTAL PRACTITIONERS (%)(N=90)
General practitioners	75.8%
Specialists and residents in endodontics and pedodontics	10.0%
Specialists and residents in periodontology, oral surgery, oral medicine, prosthodontics and orthodontics	14.2%

The frequency of antibiotic prescriptions along with endodontic therapy is presented in Table 3. Table 4 presents the average number of antibiotics prescribed in predefined time intervals. Table 5 shows the most commonly prescribed antibiotics.

Table 3

Frequency of antibiotic prescriptions along with endodontic therapy (%)

FREQUENCY OF ANTIBIOTIC PRESCRIPTION ALONG WITH ENDODONTIC THERAPY	DENTAL PRACTITIONERS (%)(N=83)
Never	9.6
Very rarely	38.6
Rarely	43.4
Often	8.4
Almost always	0.0
Always	0.0

Table 4

Antibiotic administration along with endodontic therapy on a daily/weekly/monthly basis (%)

AVERAGE OF ANTIBIOTIC ADMINISTRATION ALONG WITH ENDODONTIC THERAPY	DENTAL PRACTITIONERS (%)(N=83)
Once a day	2.4
Two or more times a day	1.2
Once or twice a week	20.5
More than twice a week	2.4
Once or twice a month	41.0
Once or twice in several months	32.5

Table 5

Presentation of the most commonly prescribed antibiotics for treatment of patients with endodontic etiology of dental disease (multiple-choice)

TYPE OF ANTIBIOTIC	NUMBER OF DENTAL PRACTITIONERS WHO MARKED THAT THEY USE THE TYPE OF ANTIBIOTIC (N=83)
penicillin (generally)	5
penicillin (Amoxicilin)	13
penicillin in combination with clavulanic acid (Klavocin, Augmentin)	50
clindamycin (Klindamicin, Klimicin, Dalacin)	41
metronidazole (Medazol)	18

The percentage of practitioners who prescribe antibiotics for various endodontic diseases is presented in Table 6.

Table 6

Frequency of antibiotic prescribing for various diseases of endodontic etiology (%)

ENDODONTIC DISEASES	DENTAL PRACTITIONERS WHO PRESCRIBE ANTIBIOTIC (%)(N=83)
Direct pulp capping	0.0
Irreversible pulpitis	6.0
Pulp necrosis	1.2
Gangrene pulp	26.2
Localized acute apical periodontitis without swelling	51.2
Diffuse spread of inflammation (cellulitis)	85.0
Fever, enlarged lymph nodes	75.0
Tooth with fistula	16.9
Prophylaxis of infectious endocarditis	94.1
Along with one visit endodontic treatment	15.5

The description of antibiotic usage without any local dental treatment of the cause of the endodontic problem is presented in Table 7. The data regarding the answers about performing endodontic treatment for patients requiring antibiotic prophylaxis are shown in Table 8. Almost all surveyed dental practitioners (96.7%) stated that they were familiar with the recent instructions (updates) on the use of antibiotic prophylaxis in at-risk patients.

Table 7

Frequency of antibiotic prescribing without any local dental treatment of the cause of the endodontic problem (%)

FREQUENCY OF ANTIBIOTIC PRESCRIBING WITHOUT ANY LOCAL DENTAL TREATMENT	DENTAL PRACTITIONERS (%)(N=83)
Never	54.4
Very rarely	36.9
Rarely	8.7
Often	0.0
Almost always	0.0
Always	0.0

Table 8

Number (%) of dental practitioners who accept to perform endodontic therapy in patients at risk of developing infectious endocarditis

ACCEPTANCE OF ENDODONTIC DENTAL TREATMENT IN PATIENTS AT RISK OF INFECTIOUS ENDOCARDITIS	DENTAL PRACTITIONERS (%)(N=83)
Never	5.5
Very rarely	9.8
Rarely	8.7
Often	19.6
Almost always	16.3
Always	40.1

Discussion

Nowadays, we are evaluating the appropriateness of antibiotic use in all fields of dental medicine (-). Since 1970, cross-sectional studies have been conducted on the use of antibiotics in dentistry, especially in endodontic clinical practice (). Questionnaire surveys have been proven useful in such studies. The questions used in such surveys are usually about the types of antibiotic used, prescribing habits of dentists as determined by their age, gender, experience, expertise, educational degree and country area and frequency of antibiotic prescribing due to endodontic etiology (-). In these survey studies (, ) the overall response rate ranged between 30% and 45%. In our pilot study, we analyzed the first 90 survey questionnaires, which is what we have collected so far. It is too early to evaluate the response rate which is to be estimated at the end of the entire study.

In our study on the frequency of antibiotic prescribing, it can be concluded that 83 surveyed dental practitioners who perform endodontics in their clinical practice do not prescribe antibiotics frequently along with endodontic procedures (Table 3).

Regarding the question of antibiotic prescribing along with endodontic therapy on daily/weekly/monthly basis, 20.5% of dental practitioners in this survey prescribed antibiotics 1or 2 times a week and 41% of them prescribed antibiotics 1or 2 times a month (Table 4). Assuming that 17 dental practitioners prescribe antibiotics at least once a week (68 prescribed antibiotics a month), and 34 practitioners prescribe them once a month, we come to a total of 102 prescribed antibiotics a month just in the clinical practice of our first 83 surveyed dental practitioners who perform endodontic procedures in their clinical practice. We must also add 2.4% of dental practitioners who prescribe antibiotics once a day, 1.2% of them who prescribe antibiotics two or more times a day, and 2.4% of them who prescribe antibiotics more than two times a week, which is significantly increasing the number of prescribed antibiotics per month in the surveyed group of dental practitioners (ideally about 100 more antibiotics prescribed). If we compare the situation in Croatia with that in the UK, we can observe that 40% of dentists in the UK prescribed antibiotics at least three times each week, and 15% prescribed antibiotics on a daily basis (), which is evidently a much bigger consumption of antibiotics than in Croatia according to the results of our study.

From the answers in Table 6, it is clearly evident that a large number of surveyed dental practitioners prescribed antibiotics in cases of endodontic problems that did not require antibiotic support. Probably, practitioners do not take into account that antibiotics do not reduce the pain or swelling of the tissue resulting from symptomatic apical pathosis with no evident systemic response nor the pain resulting from irreversible pulpitis (, , ). From the abovementioned, the obtained results justify the processing of this study among dental practitioners in the Republic of Croatia.

The situation is not significantly different in other European countries. Mainjot et al. () analyzed the antibiotic prescribing in dental practice within Belgium, concluding that antibiotics were prescribed to 63.3% of patients with periapical abscess and to 4.3% of patients with pulpitis. Rodriguez-Núñez et al. () reported that 40% of active members of the Spanish Endodontic Society prescribed antibiotics for cases of irreversible pulpitis, while 53% of them prescribed antibiotics in cases of a necrotic pulp, acute apical periodontitis and no swelling. The majority (84%) of dental practitioners surveyed in Lithuanian study () reported antibiotic administration in cases of symptomatic apical periodontitis with periostitis and 2% of them in cases of symptomatic pulpitis. Among the members of the Spanish Oral Surgery Society (), 86% of respondents prescribed antibiotics for cases of irreversible pulpitis, and 71% of them administrated antibiotics in cases of necrotic pulp, acute apical periodontitis and no swelling. It is obvious that European dental practitioners, including the Croatian dental practitioners, prescribe antibiotics inappropriately and excessively when treating endodontic diseases.

According to the results of this study, 54.4% of dental practitioners did not prescribe antibiotics without intervention on susceptible tooth. On the other hand, 36.9% of dental practitioners rarely prescribed antibiotics without local dental treatment, while 8.7% of them rarely administrated antibiotics without any local interventions (Table 7). Mainjot et al. () reported that 54.2% of dental practitioners in Belgium administrated antibiotics with no local treatment.

According to data on commonly used antibiotics in endodontic therapy, penicillin antibiotics in combination with clavulanic acid and clindamycin were the most prevalent in this pilot study, while penicillins themselves were much less represented (Table 5). Metronidazole has most probably been used as an adjunct antibiotic in addition to penicillins in the treatment of more complex cases. According to Macan's () study, amoxicillin with clavulanic acid was the most effective antibiotic in the treatment of dental infections if the local dental intervention on the causative teeth was performed. If there had not been any improvement in the following two days, additional metronidazole would have been administered. Our results are comparable to those of Perić et al. () on the use of antibiotics in Zagreb in 2015, according to which the use of penicillin antibiotics was observed in the treatment of dental diseases in 72.5% of cases, in 57.6% of which penicillins were combined with clavulanic acid.

In other studies (, , , , ) amoxicillin was the first antibiotic of choice in the treatment of endodontic infections, while clindamycin was the first drug of choice for patients with allergy (, , , ). Besides, erythromycin was () used. According to one Turkish study, in 2000 () the antibiotic of choice was ampicillin, while a Turkish most recent study suggests that, in 2019, amoxicillin with clavulanic acid was the first antibiotic of choice ().

The results of this study showed that 76% of participants often/almost always/ always accept endodontic treatment in patients requiring antibiotic prophylaxis to prevent infectious endocarditis (Table 8), and 96.7% of participants stated that they were familiar with recent instructions for antibiotic prophylaxis.

Considering that 75.8% of those surveyed in this study were general dental practitioners, 14.2% were specialists and residents in the field of dental medicine, who had not necessarily performed endodontic treatment, and only 10% were specialists and residents in endodontics and pedodontics (Table 2), the results have shown that a high percentage of non-specialist practitioners perform endodontic procedures in bacterial endocarditis at-risk patients, even though endodontic procedures may be extremely demanding.

In this pilot study, the impacts of other variables such as age, gender, years of work, education, etc. were not evaluated due to a small number of responses received for this survey. These variables will be addressed at the end of the study.

Conclusion

The results of this pilot study show that there is inappropriate use of antibiotics in the practice of 83 dental practitioners questioned regarding frequency of administration and indications. The most commonly used antibiotic is penicillin with clavulanic acid. A high percentage of surveyed practitioners have stated that they are familiar with most recent instructions for antibiotic prophylaxis. In addition, they have stated that they perform endodontic procedures in bacterial endocarditis at-risk patients.

Although this is a pilot study with known limitations (a small number of respondents as well as small number of questions), there is a noticeable need for targeted continuing education of dental practitioners in the Republic of Croatia.