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I. Introduction
Antibiotics are commonly prescribed in dental clinics along with nonsteroidal anti-inflammatory drugs1. In dental clinics, antibiotics are often prescribed to assist with surgical procedures, treat inflammatory conditions such as acute ulcerative gingivitis, and prevent systemic infections such as bacterial endocarditis23. However, misuse of antibiotics has highlighted the issue of antibiotic resistance, to the extent that a warning was announced by the World Health Organization4. A recent study reported that infection with antibiotic-resistant bacteria may kill 10 million people every year until 20505. In addition, another study that assessed Staphylococcus aureus in saliva samples collected from 122 participants showed that 88.6% of the strain exhibited resistance to two or more antibiotics6.
Among all antibiotic prescriptions, the proportion of prescriptions from dental clinics was reported to be approximately 10%3789. Several previous studies have reported inappropriate prescription of antibiotics in dental clinics1011, and the high rate of broad-spectrum antibiotic prescription in dental clinics has been identified as a cause of antibiotic resistance12. In order to prevent antibiotic-resistance development caused by the misuse of antibiotics, broad-spectrum antibiotic use should be limited to cases of severe infection13.
In dental clinics, antibiotics are frequently prescribed to prevent local and systemic infections that may occur after invasive surgical treatment. Among various invasive procedures, the rate of antibiotic prescription is particularly high after tooth extractions1415. However, indiscriminate prescription of antibiotics to all patients after tooth extraction has been highlighted as antibiotic misuse, particularly in patients who have a very low risk of infection (e.g., simple tooth extraction in a healthy patient without systemic disease)16.
Antibiotic prescription patterns in dental clinics have been described for various countries. A previous study that analyzed antibiotic prescription in Korean dental clinics reported that antibiotics prescribed after tooth extractions account for the greatest proportion of antibiotic use following dental procedures17. A nationwide study that analyzed antibiotic prescriptions from dentists in Germany over a 4-year period reported that, although the most frequently prescribed antibiotic was amoxicillin, the rate of prescribing clindamycin (a broad-spectrum antibiotic) increased over the study period, and the rate of prescribing clindamycin in the most recent year was markedly higher than the rate prescribed in medical clinics12. A retrospective cross-sectional study in the United States analyzed the medical records of antibiotic prescription in 2015. Similar to the German study, amoxicillin was the most frequently prescribed antibiotic, but broad-spectrum antibiotics such as amoxicillin clavulanate or clindamycin were frequently used and the prescription duration was longer than that in medical clinics9.
Studies assessing the status of antibiotic prescription in dental clinics are essential to resolve the issue of antibiotic misuse. In Korea, enrollment in the National Health Insurance Service (NHIS) is enforced by law, and ≥98% of the citizens are enrolled in this service. The National Health Insurance Service–National Sample Cohort (NHIS–NSC) is a dataset comprised of data representing 2% of the entire Korean population and involves stratified sampling based on sex, age, health insurance cost, and region. In addition, this vast database includes information on not only the use of medical services, but also on sociodemographic factors and family relationships of the population. Furthermore, detailed information regarding medications prescribed at medical and dental clinics is included, making this database an optimal source for the analysis of antibiotic prescriptions in dental clinics. To the best of our knowledge, no previous study has assessed antibiotic prescription after tooth extraction using the Korean NHIS–NSC database. Thus, this study aimed to utilize the NHIS–NSC database to understand the nationwide patterns of antibiotic prescription after tooth extraction and to identify factors affecting the prescription of broad-spectrum antibiotics in Korea.
II. Materials and Methods
1. Study participants
Among the NHIS–NSC participants, adults ≥19 years of age who underwent tooth extraction in dental institutions in Korea between 2011 and 2015 were included in this study. Of the 528,483 cases of tooth extraction that met the inclusion criteria, cases with missing values for variables were excluded. A total of 503,725 cases were included in this study. (Table 1)
2. Variables
Explanatory variables in this study included patient sex, age, household income, systemic disease (diabetes mellitus and hypertension), type of dental institution, region of dental institution, year of prescription, and type of tooth extraction procedure. The patients were divided into the following age groups: 19–30, 31–40, 41–50, 51–60, 61–70, and ≥71 years, and the household income was classified into quintiles based on the health insurance premium. Systemic disease in patients was assessed using medical records containing the codes for diabetes (E10–E14) and hypertension (I10–I15) based on the International Classification of Disease, 10th revision (ICD–10) between 2011 and 201518. The types of dental institutions were divided into dental hospitals or dental clinics, and the region of the dental institution was divided into rural or urban areas. The type of tooth extraction was classified according to NHIS treatment codes: U4412 (incisor extraction), U4413 (molar extraction), U4414 (complicated extraction: although not impacted, simple extraction is not possible due to dental root hypertrophy, root dilacerations, or osseointegration), U4415 (simply impacted tooth), U4416 (complexly impacted tooth: cases involving tooth splitting), and U4417 (completely impacted tooth: cases involving simultaneous tooth splitting and ostectomy of impacted tooth with ≥2/3 of crown impacted into alveolar bone). If more than two types of tooth extractions were performed in a single day, the more invasive technique was included.
3. Types of antibiotics
Types (groups) of antibiotics were classified as follows based on the Anatomical Therapeutic Chemical (ATC) classification system19 and with reference to a previous study20: penicillins, first-generation cephalosporins, tetracyclines, penicillins with beta-lactamase inhibitors, metronidazole, second- to fourth-generation cephalosporins, macrolides, quinolones, lincomycin-derivatives, and others. Among these, penicillins with beta-lactamase inhibitors, metronidazole, second- to fourth-generation cephalosporins, macrolides, quinolones, and lincomycin-derivatives were defined as broad-spectrum antibiotics132122. If two or more antibiotics were prescribed at a single visit, the case was classified as broad-spectrum antibiotic prescription.
4. Data analysis
Chi-squared tests were performed to compare the types of antibiotics prescribed for different types of tooth extraction procedures and to compare the rates of antibiotic prescription and broad-spectrum antibiotic prescription. Furthermore, to identify the factors affecting the prescription of broad-spectrum antibiotics, a multivariate logistic regression analysis was performed. All statistical analyses were performed using SAS Statistics (ver. 9.2; SAS Institute, Cary, NC, USA), and P-values of <0.05 were considered significant.
5. Ethics approval
This study was performed after receiving ethics approval from the Public Institutional Review Board Committee (P01-201901-21-004), and all experimental procedures were conducted in compliance with the Declaration of Helsinki. Data from the NHIS–NSC are reconstituted data that do not include personal identification, and thus the need for obtaining informed consent from subjects was waived by the institutional review board committee.
III. Results
This study included 503,725 tooth extraction cases, of which 443,473 were given prescriptions. Among them, 412,308 cases had prescriptions that included antibiotics in 252,549 unique patients.(Table 1)
1. Types of antibiotics prescribed for different tooth extraction procedures
Overall, the most common type of antibiotic prescribed after tooth extraction was penicillin (45.25%) (Table 2), followed by penicillin with beta-lactamase inhibitors (18.76%), metronidazole (12.29%), second- to fourth-generation cephalosporins (11.52%), and first-generation cephalosporins (8.61%). Penicillin accounted for a markedly high proportion of the antibiotics prescribed after incisor extraction and molar extraction, at 46.47% and 47.21%, respectively. On the other hand, the proportion of penicillin prescribed after extraction of completely impacted teeth was merely 29.55%, while penicillin with beta-lactamase inhibitors accounted for 29.36% and second- to fourth-generation cephalosporins accounted for 19.13% of these cases. These outcomes suggest that dentists prescribe broad-spectrum antibiotics more often after invasive tooth extraction procedures.
2. Antibiotic prescription rates following tooth extraction
The rate of antibiotic prescription after tooth extraction in Korean adult patients during the 5-year study period (2011–2015) was 81.85%.(Table 3) The rate of such prescriptions was significantly higher in male patients (82.15%) than in female patients (81.49%) (P<0.001). Based on age, the rate in the 19- to 30-year-old group (83.39%) was significantly higher than in any other age group (P<0.001). Based on household income, the rate of antibiotic prescription was highest in the ‘medium-low income’ group (P<0.001) and healthy individuals were more frequently prescribed antibiotics than individuals with diabetes and hypertension (P<0.001). The rate of antibiotic prescription was highest in 2015 (83.00%) while the lowest rate was in 2011 (80.11%) (P<0.001). Moreover, while the rate of antibiotic prescription was highest after complexly impacted tooth extraction (86.03%), the rate was significantly lower after incisor extraction (77.03%) (P<0.001). There was no significant difference in the rate of antibiotic prescription based on the type or the region of dental institution.
3. Broad-spectrum antibiotic prescription after tooth extraction
Among the antibiotics prescribed after tooth extraction, the proportion of broad-spectrum antibiotics was calculated to be 45.88%.(Table 4) While there were no significant differences in the proportion of broad-spectrum antibiotic prescription based on sex and household income, the rate of broad-spectrum antibiotic prescription in the 19- to 30-yearold group was highest among all age groups (P<0.001). Furthermore, the rate of broad-spectrum antibiotic prescription was significantly higher in patients without systemic disease than in those with diabetes or hypertension (P<0.001), was significantly higher in dental hospitals than in dental clinics (P<0.001), and was significantly higher in rural areas than in urban areas (P<0.001). Lastly, the rate of broad-spectrum antibiotic prescription was significantly higher in 2015 and after completely impacted tooth extraction (P<0.001).
4. Factors affecting broad-spectrum antibiotic prescription
In order to identify the factors affecting broad-spectrum antibiotic prescription, multivariate logistic regression analysis was performed. Using a backward elimination method with odds ratios, we aimed to identify the most appropriate model. Diabetes and hypertension were eliminated in each step, leaving seven explanatory variables including sex, age, household income, type and region of dental institution, year of prescription, and type of tooth extraction that were included in the final analysis.(Table 5)
According to the final regression model (Table 5), females were prescribed broad-spectrum antibiotics at a lower rate than males (P<0.01). All older age groups, compared to the 19- to 30-year-old group, also exhibited a higher likelihood of being prescribed broad-spectrum antibiotics (all P<0.001). Furthermore, compared with the ‘low’ household income group, the ‘medium-high’ and ‘high’ household income groups exhibited a reduced probability of receiving broad-spectrum antibiotic prescriptions (P<0.01), and the probability of broad-spectrum antibiotic prescriptions in dental clinics was lower than in dental hospitals (P<0.001). Based on the region, dental institutions in rural areas exhibited a greater rate of antibiotic prescriptions than those in urban areas (P<0.001). While the probability of broad-spectrum antibiotic prescription was lower in 2012 than in 2011 (P<0.001), the rates thereof were higher in 2013-2015 (P<0.001 for all). Lastly, compared to incisor extraction, other invasive techniques resulted in a higher chance of broad-spectrum antibiotic prescription (P<0.01 for all).
IV. Discussion
This study utilized a large-scale dataset of 503,725 cases of tooth extraction to evaluate patterns of antibiotic prescription after tooth extraction and factors affecting broad-spectrum antibiotic prescription in Korea. No previous study has performed a nationwide, large-scale cohort analysis of antibiotics prescribed after tooth extraction in Korean dental clinics and hospitals.
The most frequently prescribed antibiotic after tooth extraction was penicillin (45.25%), which was in agreement with similar studies in South Africa, Germany, and the United States91214. Among these studies, the South African study14 reported that the rate of penicillin prescription was 80.9%, which was markedly higher than in Korea. The values in the German study (51.4%) and the American study (68%) were similar to that noted in Korea in the present study912, but those studies assessed the rate of antibiotic prescription for all dental procedures, not limited to tooth extractions. The second-most frequently prescribed antibiotic varied largely among the different countries. While penicillin with beta-lactamase inhibitors was the second-most frequently used antibiotic in this study (18.76%), clindamycin was the second-most frequently prescribed antibiotic in both the German (34.9%) and American (15.64%) studies912. Moreover, dental clinics in the Czech Republic also frequently prescribed clindamycin (25.1%)7. The use of lincomycin-derivatives (including clindamycin) in our study was merely 0.21%, and was <5% in the UK and Norway, showing varying frequencies among different countries323. In South Africa, while macrolides were the second-most frequently prescribed antibiotic following tooth extraction, they merely accounted for 3.3% of all prescribed antibiotics14. In the UK, the second-most frequently prescribed antibiotic was metronidazole, accounting for 28.3% of all antibiotic prescriptions23. While metronidazole was the third-most frequently prescribed antibiotic in our study (12.29%), the frequencies of metronidazole prescription in Germany, the US, and South Africa were all <1%91214. Thus, while the use of penicillin as the primary antibiotic in dental settings seems to be the general rule, the use of other antibiotics was markedly variable across countries. These differences are likely due to differences in educational programs, health policies, demographics, and clinical experiences. Furthermore, in this study, the more invasive tooth extraction techniques resulted in a greater frequency of broad-spectrum antibiotic prescription (i.e., penicillins with beta-lactamase inhibitors or second- to fourth-generation cephalosporins), and these outcomes were in agreement with a previous study17.
In the present study, the rate of antibiotic prescription after tooth extraction was 81.85%, which was markedly higher than the 11.0% reported in the South African study14. In Korea, the rate of antibiotic prescription even exceeded 80% after exposed molar extraction, while the highest rate in the South African study was 54.5% (after impacted tooth extraction in patients with chronic disease). In an Australian study, the rate of antibiotic prescription after third molar extraction ranged between 19% and 75% depending on associated symptoms24, while approximately 25% of patients in a Belgian study were given antibiotics after surgical extraction of a third molar20. Thus, the rate of antibiotic prescription in Korea was markedly higher than in other countries, which is consistent with another Korean study that previously described habitual antibiotic prescription after tooth extraction without consideration for potential misuse16. Moreover, 45.88% of antibiotics prescribed after tooth extraction were broad-spectrum antibiotics, raising concerns about the potential misuse of antibiotics.
In this study, the rate of antibiotic prescription was higher in males than in females, as previously reported17. However, there was no significant difference in the proportion of broad-spectrum antibiotic prescription between males and females. Furthermore, a younger age was associated with higher rates of both antibiotic prescription and broad-spectrum antibiotic prescription. This is likely because older patients tend to have simple tooth extractions due to periodontal disease while tooth extractions in younger patients often involve invasive techniques to extract impacted teeth, such as third molars.
The rates of overall antibiotic and broad-spectrum antibiotic prescription in patients with systemic disease (diabetes and hypertension) were lower than in healthy individuals, although this phenomenon may be partly attributed to a large proportion of patients with systemic disease being elderly who have lower rates of antibiotic prescription as described earlier. Thus, diabetes and hypertension were not significant factors affecting the rate of broad-spectrum antibiotic prescription in a regression model that incorporated all identified confounders, including age. Furthermore, patients with systemic disease sometimes use medications prescribed from their medical clinics rather than dental clinics, which may have contributed to the low rate of antibiotic prescription.
Comparison of antibiotic usage between dental clinics and dental hospitals showed that while there was no difference in the rate of antibiotic prescription, dental hospitals exhibited a greater frequency of broad-spectrum antibiotic prescription. This is likely because cases involving invasive procedures with a high risk of dental infection are often transferred from dental clinics to dental hospitals. Compared to 2011, rates of both antibiotic prescription and broad-spectrum antibiotic prescription were higher in 2015. While this may be due to an increase in antibiotic prescription over time, it may also be explained by the increasing age of participants. Therefore, temporal changes in antibiotic prescription habits cannot be characterized solely based on the findings of our study and additional time series analyses are required.
The use of antibiotics should be limited to severe cases (i.e., those with suspected dental infections), and more specifically, the use of broad-spectrum antibiotics should be minimized1321. Recently, misuse of antibiotics has been highlighted as the main reason for increased antibiotic-resistance1025. In an effort to investigate factors relating to the prescription of broad-spectrum antibiotics after tooth extraction, the following criteria were concluded to be statistically significant: sex (male), older age, household income (low), type of dental institution (dental hospital), region of dental institution (rural), year of prescription (2015), and type of tooth extraction (completely impacted tooth extraction).
Despite these findings, there were some limitations to this study. First, only antibiotics prescribed on the day of the tooth extraction procedure were included in the analysis. Thus, any antibiotic prescribed prior to or after the date of surgery was not taken into consideration. In addition, tooth extraction for orthodontic treatment is not covered by the NHIS, and those procedures were therefore were not included in this study. Moreover, since the NHIS dataset primarily serves administrative purposes, information that may be crucial to a research study might not always be available. For example, the specific name of tooth extracted or the reason for tooth extraction were not included. Lastly, the large number of participants in this study allows for more accurate representation of the status of antibiotic prescription in Korean dental institutions, but also makes the P-values exceedingly small, which may lead to biased conclusions. Despite these limitations, this study utilized the NHIS–NSC dataset—which is representative of the entire Korean population—to analyze antibiotic prescription patterns after tooth extraction while controlling for confounders such as sociodemographic variables and systemic disease. Using this resource minimizes recall bias and allows for accurate representation of the course of prescription and treatment provided to patients, making the outcomes of this study highly reliable.
V. Conclusion
This study demonstrates that the rate of antibiotic prescription after tooth extraction in Korea is higher relative to other countries, and broad-spectrum antibiotics are also more frequently used. These trends may be key contributors to antibiotic resistance. Our findings highlight the necessity of a standardized guideline for antibiotic prescription in dental clinics and the need for individual clinicians to minimize unnecessary antibiotic prescription, particularly following tooth extraction. Additional studies should be performed to describe changes in the rates of antibiotic prescription as well as to understand the mechanisms contributing to the high rate of antibiotic prescription in Korea.
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