Antibiotic Over-Prescription by Dentists in the Treatment of Apical Periodontitis: A Systematic Review and Meta-Analysis

Citation: Méndez-Millán, J.A.; León-López, M.; Martín-González, J.; Saúco-Márquez, J.J.; Cabanillas-Balsera, D.; Segura-Egea, J.J. Antibiotic Over-Prescription by Dentists in the Treatment of Apical Periodontitis: A Systematic Review and Meta-Analysis. Antibiotics 2024,13, 289. https:// doi.org/10.3390/antibiotics13040289 Academic Editor: Giuseppe Lizio Received: 27 February 2024 Revised: 13 March 2024 Accepted: 21 March 2024 Published: 22 March 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). antibiotics Systematic Review Antibiotic Over-Prescription by Dentists in the Treatment of Apical Periodontitis: A Systematic Review and Meta-Analysis Juan A. Méndez-Millán, María León-López, Jenifer Martín-González, Juan J. Saúco-Márquez, Daniel Cabanillas-Balsera * and Juan J. Segura-Egea * Department of Stomatology (Endodontic Section), School of Dentistry, University of Sevilla, C/Avicena s/n, 41009 Sevilla, Spain; [email protected] (J.A.M.-M.); [email protected] (M.L.-L.); [email protected] (J.M.-G.); [email protected] (J.J.S.-M.) *Correspondence: [email protected] (D.C.-B.); [email protected] (J.J.S.-E.) Abstract: After pulp infection and necrosis, the passage of microbial antigens into the periapical space causes apical periodontitis (AP). Most of the clinical forms of AP can be managed without prescribing antibiotics, only with root canal treatment and abscess drainage or, where appropriate, tooth extraction. However, the scientific literature provides evidence of inappropriate antibiotic prescriptions by dentists in the management of apical disease. Objectives: The aim of this systematic review and meta-analysis was to analyze the global pattern of antibiotic prescription in the treatment of apical disease. Methods: PRISMA Guidelines were followed to carry out this systematic review. The research question was as follows: What is the pattern of antibiotic prescription by dentists in the treatment of the different clinical forms of apical periodontitis? A systematic search was conducted on MEDLINE/PubMed, Wiley Online Database, Web of Science and Scopus. All studies reporting data about the pattern of antibiotic prescription by dentists in the treatment of apical disease were included. The meta-analyses were calculated using the Open Meta Analyst version 10.10 software. Random-effects meta-analyses were performed. The risk of bias was assessed using the Newcastle–Ottawa Scale. The certainty of evidence was assessed using GRADE. Results: The search strategy identified 96 articles and thirty-nine cross-sectional studies fulfilled the inclusion criteria. The overall percentage of antibiotic prescriptions by dentists in cases of symptomatic AP was 25.8%, and 31.5% in cases of asymptomatic AP with sinus tract present. The percentage of dentists prescribing antibiotics in cases of acute apical abscess with no/mild symptoms was 47.7%, whereas, in cases of acute apical abscess with moderate/severe symptoms, 88.8% of dentists would prescribe antibiotics. Endodontists prescribe antibiotics at a lower rate than general practitioners. The total risk of bias was considered moderate, and the final rating for the certainty of the evidence was low. Conclusions: Dentists worldwide are over-prescribing antibiotics in the management of apical disease. It is necessary to improve antibiotic prescribing habits in the treatment of endodontic infections, as well as educational initiatives to encourage the rational and appropriate prescription of antibiotics in periapical diseases. Keywords: antibiotics; apical abscess; apical disease; apical periodontitis; endodontic infection; meta-analysis; periapical disease; prescription; systematic review 1. Introduction The infection and necrosis of the pulp, with the subsequent passage of antigens into the periapical space, cause endodontic periapical disease [ 1 ]. A rapid onset, spontaneous pain, the extreme sensitivity of the tooth to pressure, and edema of the affected tissues characterize the periapical acute inflammatory reaction, named symptomatic apical periodontitis [ 2 ]. Without treatment, symptomatic apical periodontitis evolves into an acute apical abscess, with an accumulation of purulent discharge in the periapical space, swelling, extrusion of the tooth from the alveolus, abnormal mobility, and finally dissemination, Antibiotics 2024,13, 289. https://doi.org/10.3390/antibiotics13040289 https://www.mdpi.com/journal/antibiotics Antibiotics 2024,13, 289 2 of 17 causing osteomyelitis and cellulitis [ 3 ], potentially leading to the death of the patient [ 4 ]. However, a fatal outcome is fortunately uncommon and is usually associated with an immunocompromised status. Currently, the development and application of new diagnostic and therapeutic technologies in endodontics, as well as the use of antibiotics when indicated, have reduced mortality due to systemic dissemination of apical abscesses to almost zero. Treatment of symptomatic apical periodontitis and acute apical abscess requires achieving adequate drainage by opening the pulp chamber. When the purulent discharge has destroyed the periosteum and the abscess is already in the submucosal phase, causing swelling of the intraoral soft tissues, it must be incised with a scalpel blade to establish drainage [ 5 ]. If the patient is immunocompetent, this intervention resolves the clinical picture. However, in immunocompromised patients, or when there are systemic symptoms or the purulent discharge progresses and expands, the prescription of systemic antibiotics is indicated [ 6 ]. On the contrary, asymptomatic apical periodontitis and chronic apical abscesses do not require antibiotic treatment [6,7]. Since the discovery of antibiotics and their introduction into clinical practice in the 1940s, antibiotics have been used in the treatment of endodontic infections, both systemically and topically [ 8 , 9 ]. Since then, bacteria, both pathogenic and commensal saprophytes, have been exposed to antibiotics. At first, they were sensitive to them, but over time, they have developed resistance [ 10 ]. Considering that dentists prescribe approximately 10% of all common antibiotics, the impact of dentists on antimicrobial resistance can be considerable [ 11 ]. A survey carried out in the UK in 2004 revealed that 40% of general dental practitioners prescribed three antibiotics each week, and 15% prescribed them on a daily basis [ 10 ]. Literature provides evidence of inadequate prescribing practices by dentists for a number of factors, ranging from inadequate knowledge to social factors [12–14]. Moreover, several surveys carried out with dentists from different countries have shown that antibiotics are being prescribed inappropriately in the treatment of periapical pathology [ 13 , 15 – 20 ]. To improve the prescription of antibiotics in the treatment of endodontic infections, the European Society of Endodontology (ESE) published an official position based on scientific evidence established by a committee of experts [ 6 , 9 ]. In addition, awareness campaigns led by dental and medical associations have been carried out throughout the world. This study aims to carry out a systematic review with meta-analysis to investigate the global pattern of antibiotic prescription by dentists in the treatment of apical disease. 2. Results Figure 1shows the flowchart of the strategy followed to search for the studies selected for this review, according to PRISMA 2020 instructions. The initial search resulted in 96 published studies. After the removal of duplicate studies (n = 27), 69 studies were screened for titles and abstracts, and five that did not investigate antibiotic prescriptions were excluded, leaving 64 for reading the full text. The eligibility criteria determined the exclusion of 25 studies (Table 1) for the following reasons: (a) Two studies did not allow data extraction on the antibiotic prescription habits of dentists [ 21 , 22 ]; (b) Five studies provided data from surveys carried out on dental students, rather than dentists [ 23 – 27 ]; (c) Nine studies did not provide data from surveys, but from medical records of patients treated with antibiotics [ 28 – 36 ]; and (d) Nine studies did not specify the diagnosis of the treated periapical pathology [37–45]. Antibiotics 2024,13, 289 3 of 17 Antibiotics 2024, 13, x FOR PEER REVIEW 3 of 18 Figure 1. Flowchart of the search strategy, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines 2020. The eligibility criteria determined the exclusion of 25 studies (Table 1) for the following reasons: (a) Two studies did not allow data extraction on the antibiotic prescription habits of dentists [21,22]; (b) Five studies provided data from surveys carried out on dental students, rather than dentists [23–27]; (c) Nine studies did not provide data from surveys, but from medical records of patients treated with antibiotics [28–36]; and (d) Nine studies did not specify the diagnosis of the treated periapical pathology [37–45]. Table 1. Excluded studies and reasons for their exclusion. Reason for Exclusion Excluded Studies Studies that did not allow extraction of data on the antibiotic prescription habits of dentists Yu et al., 2020 [21] Kim et al., 2018 [22] Studies that provided data from surveys carried out on dental students, rather than dentists Jain et al., 2015 [23] Doshi et al., 2017 [24] Struzycka et al., 2019 [25] Figure 1. Flowchart of the search strategy, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines 2020. Table 1. Excluded studies and reasons for their exclusion. Reason for Exclusion Excluded Studies Studies that did not allow extraction of data on the antibiotic prescription habits of dentists Yu et al., 2020 [21] Kim et al., 2018 [22] Studies that provided data from surveys carried out on dental students, rather than dentists Jain et al., 2015 [23] Doshi et al., 2017 [24] Struzycka et al., 2019 [25] Salvadori et al., 2019 [26] Arican et al., 2021 [27] Antibiotics 2024,13, 289 4 of 17 Table 1. Cont. Reason for Exclusion Excluded Studies Studies that did not provide data from surveys, but from medical records of patients treated with antibiotics Kandemir et al., 2000 [28] Tanwir et al., 2015 [29] Asmar et al., 2016 [30] Lalloo et al., 2017 [31] Bjelovucic et al., 2019 [32] Al Asmar Ramli et al., 2020 [33] Alzahrani et al., 2020 [34] Carlsen et al., 2021 [35] Di Giuseppe et al., 2021 [36] Studies that did not specify the diagnosis of the treated periapical pathology Preus et al., 1992 [37] Mainjot et al., 2009 [38] Kaptan et al., 2013 [39] Bidar et al., 2015 [40] Buttar et al., 2017 [41] Madarati et al., 2018 [42] Roberts et al., 2019 [43] Khalil et al., 2022 [44] Vengidesh et al., 2023 [45] 2.1. Characteristics of the Included Studies Finally, 39 studies fulfilled the inclusion criteria and were selected for the systematic review and meta-analysis [13,15–20,46–77]. Table 2shows the characteristics of the included studies (authors and year, country, number of respondents, and percentage of total and prescribers), together with the main outcomes, indicating the percentage of antibiotic prescriptions in each clinical situation. All studies were cross-sectional surveys and level 4 evidence, according to the Center for Evidence-Based Medicine at Oxford [78]. Table 2. Included studies: authors and year, country, number of respondents and percentage of the total, and prescribers, together with the main outcomes and the percentage of antibiotic prescriptions in each clinical situation. Authors and Year Country Respondents (% of Total) P Antibiotic Prescription in Each Clinical Situation (%) A B C D Whitten et al., 1996 [74] USA 651 (43.4%) EN 35.6 29.2 67.3 96.6 Jaunay et al., 2000 [57] Australia 66 (61%) GP 0 0 39.4 98.5 Palmer et al., 2000 [66] UK 929 (60.1%) GP ----- 26 69.6 90 Yingling et al., 2002 [73] USA 1606 (50.1%) EN 18 11.9 53.9 99.2 Salako et al., 2004 [68] Kuwait 168 (84%) GP 25.0 ------ ----- 85.1 Al Haroni & Skaug 2006 [46] Yemen 150 (53.6%) GP ----- 72 70 78 Kakoei et al., 2007 [59] Iran 113 EN 26.5 27.4 44.2 85.0 Rodríguez-Núñez et al., 2009 [18] Spain 140 (31.1%) EN 14.3 21.4 52.9 94.3 Segura-Egea et al., 2010 [75] Spain 127 (64%) DS 30.7 59.8 70.9 94.5 Skucaite et al., 2010 [70] Lithuania 1532 (53.8%) GP ----- ------ 60 84 Nabavizadeh et al., 2011 [65] Iran 93 (77.5%) GP ----- 581.721 ----- 74.2 Vessal et al., 2011 [72] Iran 219 (48.6%) GP ----- 32.9 77.2 75.3 Antibiotics 2024,13, 289 5 of 17 Table 2. Cont. Authors and Year Country Respondents (% of Total) P Antibiotic Prescription in Each Clinical Situation (%) A B C D Kumar et al., 2013 [60] India 216 (87.8%) GP 44.9 69.4 56.9 92.1 Sivaraman et al., 2013 [69] USA 987 (21%) GP 42 39 68 99 Garg et al., 2014 [54] India 552 (34.5%) GP 38.2 46.9 59.1 90.2 Jayadev et al., 2014 [58] India 304 (79.8%) GP 3.6 15.0 7.2 56.4 Iqbal 2015 [56] Saudi Arabia 157 (78.5%) GP 42.0 46.5 59.2 77.1 Peric et al., 2015 [67] Croatia 220 (50%) GP ----- ------ ----- 85.0 Alattas & Alyami 2017 [48] Saudi Arabia 195 (98%) GP 31.3 28.2 20.5 81.5 AlRahabi & Abuong 2017 [47] Saudi Arabia 75 (85%) GP 28.0 34.7 62.7 82.7 Germack et al., 2017 [55] USA 687 (22.9%) EN 6.4 29.7 43.7 95.9 Al Masan et al., 2018 [16] UK 79 (60%) GP 27.8 19.0 71.9 78.5 Alonso-Ezpeleta et al., 2018 [50] Spain 67 (91.2%) EN 7.5 25.4 37.3 95.5 Bolfoni et al., 2018 [15] Brazil 615 (4.4%) GP 6.2 20.5 11.5 90.1 Maslamani & Sedeji 2018 [62] Kuwait 227 (75.6%) GP 8.4 16.3 36.1 ----- Abraham et al., 2020 [76] UAE 106 GP 17.9 26.4 22.6 91.5 Abraham et al., 2020 [76] UAE 22 EN 22.7 22.7 13.6 100 Deniz-Sungur et al., 2020 [17] Turkey 1007 (5.6%) GP 23.0 26 35 97 Mende et al., 2020 [63] Lithuania 198 (93.0%) GP 16.7 ------ 8.1 90.4 Sovic et al., 2020 [71] Croatia 83 (92%) GP 26.5 16.9 51.8 85.5 Alobaid et al., 2021 [49] Saudi Arabia 38 (63.3%) GP 18.4 23.7 76.3 73.7 Dibaji et al., 2021 [51] Iran 400 (100%) GP 90.7 81.0 86.2 97.3 Domínguez-Domínguez et al., 2021 [13]Spain 190 (95%) GP 5.8 39.0 28.9 91.1 Drobac et al., 2021 [53] Serbia 158 (25.2%) GP 12.7 13.3 31.0 96.2 Licata et al., 2021 [61] Italy 563 (52.6%) GP 43 21.5 62 78.3 Šimundi´c-Munitic et al., 2021 [64]Croatia 657 (24.0%) GP 0.8 2.0 14.0 82.8 Abuhassna et al., 2022 [77] Saudi Arabia 555 (61.1%) GP 9.5 22.3 52.4 83.4 Dias et al., 2022 [20] Colombia 193 (60.3%) GP 74.1 78.2 94.3 96.4 Dias et al., 2022 [20] Colombia 109 (34.1%) EN 28.4 45.9 87.2 98.2 López-Marrufo et al., 2022 [52] Spain 77 (77%) EN 5.2 15.6 26.0 100 Shemesh et al., 2022 [19] Israel 1310 (17.5%) GP 23.0 4.4 17.6 81.3 P: Prescriber; GP: general practitioner. EN: endodontist. DS: dental surgeon. A: Symptomatic apical periodontitis, no swelling, no/mild symptoms. B: Asymptomatic apical periodontitis, sinus tract, no/mild symptoms (chronic apical abscess). C: Acute apical abscess, swelling, no/mild symptoms. D: Acute apical abscess, swelling, moderate/severe symptoms. Regarding the prescribers, seven studies included in the sample only endodontists [18,50,52,55,59,73,74] , two studies [ 20 , 76 ] included two separated samples, endodontists and general practitioners, considered as two different studies in the meta-analysis, one study included only dental surgeons [75], and the rest included general practitioners. In most of the studies, the main outcomes were the percentage of antibiotic prescriptions in each of the four clinical situations of periapical endodontic disease. However, nine studies missed data regarding any of the clinical forms of apical periodontitis [46,58,62,63,65–68,70]. Antibiotics 2024,13, 289 6 of 17 2.2. Meta-Analysis of Antibiotic Prescription in Symptomatic Apical Periodontitis Thirty-four studies, two of them considered doubly [ 20 , 76 ], including 12,917 respondents, provide data about the percentage of antibiotic prescriptions in cases of symptomatic apical periodontitis, no swelling and no/mild symptoms. Figure 2A shows the forest plot of the corresponding meta-analysis. The overall percentage of antibiotic prescriptions in this clinical situation was 25.8% (95% CI = 19.2–32.3%; p< 0.001). Heterogeneity value was I2= 99.0% (p< 0.001). Antibiotics 2024, 13, x FOR PEER REVIEW 6 of 18 Figure 2. Forest plot of the included studies in the meta-analysis for prescription of antibiotics by general practitioners in the treatment of apical disease. (A) Symptomatic apical periodontitis; (B) asymptomatic apical periodontitis or chronic apical abscess; (C) acute apical abscess with no/mild symptoms; (D) acute apical abscess with moderate/severe symptoms. 2.3. Meta-Analysis of Antibiotic Prescriptions in Asymptomatic Apical Periodontitis or Chronic Apical Abscess Thirty-five studies, two of them considered doubly [20,76], including 13,738 respondents, provide data about the percentage of antibiotic prescriptions in cases of a chronic apical abscess (asymptomatic apical periodontitis, sinus tract presence and no/mild symptoms). Figure 2B shows the forest plot of the corresponding meta-analysis. The overall percentage of antibiotic prescriptions in this clinical situation was 31.5% (95% CI = 25.4– 37.7%; p < 0.001). Heterogeneity value was I2 = 99.0% (p < 0.001). 2.4. Meta-Analysis of Antibiotic Prescription in Acute Apical Abscess with No/Mild Symptoms Thirty-seven studies, two of them considered doubly [20,76], including 15,360 respondents, provided data about the percentage of antibiotic prescriptions in cases of acute apical abscess with no/mild symptoms. Figure 2C shows the forest plot of the corresponding meta-analysis. The overall percentage of antibiotic prescriptions in this clinical situation was 47.7% (95% CI = 39.0–56.4%; p < 0.001). Heterogeneity value was I2 = 99.0% (p < 0.001). Figure 2. Forest plot of the included studies in the meta-analysis for prescription of antibiotics by general practitioners in the treatment of apical disease. (A) Symptomatic apical periodontitis; (B) asymptomatic apical periodontitis or chronic apical abscess; (C) acute apical abscess with no/mild symptoms; (D) acute apical abscess with moderate/severe symptoms. 2.3. Meta-Analysis of Antibiotic Prescriptions in Asymptomatic Apical Periodontitis or Chronic Apical Abscess Thirty-five studies, two of them considered doubly [ 20 , 76 ], including 13,738 respondents, provide data about the percentage of antibiotic prescriptions in cases of a chronic apical abscess (asymptomatic apical periodontitis, sinus tract presence and no/mild symptoms). Figure 2B shows the forest plot of the corresponding meta-analysis. The overall percentage of antibiotic prescriptions in this clinical situation was 31.5% ( 95% CI = 25.4–37.7% ; p< 0.001). Heterogeneity value was I2= 99.0% (p< 0.001). 2.4. Meta-Analysis of Antibiotic Prescription in Acute Apical Abscess with No/Mild Symptoms Thirty-seven studies, two of them considered doubly [ 20 , 76 ], including 15,360 respondents, provided data about the percentage of antibiotic prescriptions in cases of acute apical abscess with no/mild symptoms. Figure 2C shows the forest plot of the corresponding meta-analysis. The overall percentage of antibiotic prescriptions in this clinical situation was 47.7% (95% CI = 39.0–56.4%; p< 0.001). Heterogeneity value was I 2 = 99.0% (p< 0.001). Antibiotics 2024,13, 289 7 of 17 2.5. Meta-Analysis of Antibiotic Prescription in Acute Apical Abscess with Moderate/ Severe Symptoms Thirty-eight studies, two of them considered doubly [ 20 , 76 ], including 15,629 respondents, provide data about the percentage of antibiotics prescriptions in cases of acute apical abscess with moderate/severe symptoms. Figure 2D shows the forest plot of the corresponding meta-analysis. The overall percentage of antibiotic prescriptions in this clinical situation was 88.8% (95% CI = 86.8–90.8%; p< 0.001). Heterogeneity value was I2= 97.0% (p< 0.001). 2.6. Meta-Analysis of Antibiotics Prescription by Endodontists The prescription pattern of the subgroup of studies that included only endodontists [18,20,50,52,55,59,73,74,76] , was analyzed (Figure 3). In symptomatic apical periodontitis, 17.5% (95% CI = 8.6–26.5%; p< 0.001) of endodontists prescribed antibiotics. Antibiotics 2024, 13, x FOR PEER REVIEW 7 of 18 2.5. Meta-Analysis of Antibiotic Prescription in Acute Apical Abscess with Moderate/Severe Symptoms Thirty-eight studies, two of them considered doubly [20,76], including 15,629 respondents, provide data about the percentage of antibiotics prescriptions in cases of acute apical abscess with moderate/severe symptoms. Figure 2D shows the forest plot of the corresponding meta-analysis. The overall percentage of antibiotic prescriptions in this clinical situation was 88.8% (95% CI = 86.8–90.8%; p < 0.001). Heterogeneity value was I2 = 97.0% (p < 0.001). 2.6. Meta-Analysis of Antibiotics Prescription by Endodontists The prescription pattern of the subgroup of studies that included only endodontists [18,20,50,52,55,59,73,74,76], was analyzed (Figure 3). In symptomatic apical periodontitis, 17.5% (95% CI = 8.6–26.5%; p < 0.001) of endodontists prescribed antibiotics. Figure 3. Forest plot of the included studies in the meta-analysis for prescription of antibiotics by endodontists in the treatment of apical disease. (A) Symptomatic apical periodontitis; (B) asymptomatic apical periodontitis or chronic apical abscess; (C) acute apical abscess with no/mild symptoms; (D) acute apical abscess with moderate/severe symptoms. Antibiotics 2024,13, 289 8 of 17 The percentage of endodontists who prescribed antibiotics in cases of asymptomatic apical periodontitis was 25.4% (95% CI = 17.6–33.1%; p< 0.001). In the case of acute apical abscess with no/mild symptoms, 48.3% (95% CI = 38.0–58.5%; p< 0.001) of endodontists prescribed antibiotics. Finally, 96.8% (95% CI = 95.1–98.4%; p< 0.001) of endodontists prescribed antibiotics in the treatment of acute apical abscesses with moderate/severe symptoms. 2.7. Risk of Bias The risk of bias was evaluated for each study (Table 3). Twenty-three studies were classified as high risk of bias [ 13 , 16 – 20 , 46 , 49 , 50 , 52 – 54 , 56 , 58 , 59 , 61 , 66 – 69 , 71 , 74 , 76 ], thirteen had a moderate risk of bias [ 15 , 48 , 55 , 57 , 60 , 63 – 65 , 70 , 72 , 73 , 75 , 77 ], and three studies reported low risk of bias [ 47 , 51 , 62 ]. The sum of points assigned to the 39 included studies was 170 out of a possible maximum of 312. Therefore, the total risk of bias was considered moderate. Table 3. Quality assessment of individual studies and risk of bias. The maximum total score with the sum of the 39 studies would be 312. Each * is one point. Selection Outcome Authors and Year Representativeness of the Sample (Maximum: 3) Sample Size Calculation (Maximum: 1) Non-Respondents (Maximum: 2) Assessment (Maximum: 2) Risk of Bias Whitten et al., 1996 [74] * * ** High Jaunay et al., 2000 [57] *** * * Moderate Palmer et al., 2000 [66] * * High Yingling et al., 2002 [73] * * * ** Moderate Salako et al., 2004 [68] * ** * High Al-Haroni & Skaug 2006 [46] ** * High Kakoei et al., 2006 [59] * * High Rodríguez-Núñez et al., 2009 [18] * * ** High Segura-Egea et al., 2010 [75] *** * ** Moderate Skucaite et al., 2010 [70] ** * * * Moderate Nabavizadeh et al., 2011 *** * * * Moderate Vessal et al., 2011 [72] ** * * * Moderate Kumar et al., 2013 [60] * ** ** Moderate Sivaraman et al., 2013 [69] * * ** High Garg et al., 2014 [54] ** * * High Jayadev et al., 2014 [58] ** ** High Iqbal et al., 2015 [56] * * * High Peric et al., 2015 [67] * * High Alattas & Alyami 2017 [48] ** ** ** Moderate AlRahabi & Abuong 2017 [47] *** ** ** Low Germack et al., 2017 [55] ** * ** Moderate Al Masan et al., 2018 [16] * ** High Alonso-Ezpeleta et al., 2018 [50] * ** High Bolfoni et al., 2018 [15] ** * * ** Moderate Maslamani & Sedeqi 2018 [62] *** * * ** Low Abraham et al., 2020 [76] * * ** High Deniz-Sungur et al., 2020 [17] ** * * High Mende et al., 2020 [63] ** * ** Moderate Sovic et al., 2020 [71] * ** * High Antibiotics 2024,13, 289 9 of 17 Table 3. Cont. Selection Outcome Authors and Year Representativeness of the Sample (Maximum: 3) Sample Size Calculation (Maximum: 1) Non-Respondents (Maximum: 2) Assessment (Maximum: 2) Risk of Bias Alobaid et al., 2021 [49] * * High Dibaji et al., 2021 [51] *** ** ** Low Domínguez-Domínguez et al., 2021 [13] ** ** High Drobac et al., 2021 [53] * * * High Licata et al., 2021 [61] * * * High Šimundi´c-Munitic et al., 2021 [64]** * * ** Moderate Abuhassna et al., 2022 [77] ** * * ** Moderate Dias et al., 2022 [20] * * * * High López-Marrufo et al., 2022 [52] * * ** High Shemesh et al., 2022 [19] * * ** High TOTAL 57 10 44 59 170 (Moderate) 2.8. GRADE Assessment of the Certainty of Evidence Figure 4shows the GRADE assessment of certainty level. Initially, the certainty of evidence was rated as low since all included studies were cross-sectional surveys. Taking into account that the overall risk of bias was moderate, it was classified as serious. Antibiotics 2024, 13, x FOR PEER REVIEW 9 of 18 Drobac et al., 2021 [53] * * * High Licata et al., 2021 [61] * * * High Šimundić-Munitic et al., 2021 [64] ** * * ** Moderate Abuhassna et al., 2022 [77] ** * * ** Moderate Dias et al., 2022 [20] * * * * High López-Marrufo et al., 2022 [52] * * ** High Shemesh et al., 2022 [19] * * ** High TOTAL 57 10 44 59 170 (Moderate) 2.8. GRADE Assessment of the Certainty of Evidence Figure 4 shows the GRADE assessment of certainty level. Initially, the certainty of evidence was rated as low since all included studies were cross-sectional surveys. Taking into account that the overall risk of bias was moderate, it was classified as serious. Figure 4. GRADE assessment of certainty level. Regarding inconsistency, it was rated as serious because, in all cases, heterogeneity was >95%. Indirectness was rated as not serious because all studies provide direct evidence about antibiotics prescription in apical periodontitis. Imprecision was rated as not serious because the 95% confidence intervals in all cases were between 0.75 and 1.25. As far as publication bias is concerned, it occurs when the publication of research results is influenced, in addition to the quality of the research, by the tested hypotheses and the importance and direction of the results. In the case of surveys on antibiotic prescription, in which the result is objective data, it has not been considered that publication bias could be important. There were no other considerations that modified the degree of certainty, and the final rating for the certainty of the evidence was low. 3. Discussion The aim of this study was to analyze the global pattern of antibiotic prescription by dentists in the management of apical periodontitis. For this purpose, a systematic review and meta-analysis were performed, including the available evidence. The main conclusion was that, unfortunately, and generally, dentists inappropriately prescribe antibiotics in the treatment of apical periodontitis. More specifically, antibiotics are being overprescribed. In three of the clinical forms of apical periodontitis (in systemically healthy patients), it is not necessary to prescribe antibiotics; however, the percentages of dentists who prescribe them are important. Thus, in symptomatic apical periodontitis with no swelling and no/mild symptoms, in asymptomatic apical periodontitis with chronic apical abscess and sinus tract present, with no/mild symptoms, and in acute apical abscess with Figure 4. GRADE assessment of certainty level. Regarding inconsistency, it was rated as serious because, in all cases, heterogeneity was >95%. Indirectness was rated as not serious because all studies provide direct evidence about antibiotics prescription in apical periodontitis. Imprecision was rated as not serious because the 95% confidence intervals in all cases were between 0.75 and 1.25. As far as publication bias is concerned, it occurs when the publication of research results is influenced, in addition to the quality of the research, by the tested hypotheses and the importance and direction of the results. In the case of surveys on antibiotic prescription, in which the result is objective data, it has not been considered that publication bias could be important. There were no other considerations that modified the degree of certainty, and the final rating for the certainty of the evidence was low. Antibiotics 2024,13, 289 16 of 17 39. Kaptan, R.F.; Haznedaroglu, F.; Basturk, F.B.; Kayahan, M.B. Treatment approaches and antibiotic use for emergency dental treatment in Turkey. Ther. Clin. Risk Manag. 2013,9, 443–449. [CrossRef] 40. Bidar, M.; Gharechahi, M.; Soleimani, T.; Eslami, N. 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