INTRODUCTION

The discovery and large-scale use of antibiotics since the middle of last century has enormous impact on the treatment of infections, leading to the survival of thousands of people who would otherwise have died, mainly during the second world war ¹ . Due to advances in molecular methods in microbiology, especially at the beginning of the current century, “new pathogens” have been detected in different types of infections that affect humans. However, the development, approval, and launch of new antibiotics have not kept pace with this evolution, and several “new microorganisms” already have multiple resistance to traditional antimicrobials ² . The emergence and spread of antibiotic-resistant pathogens have become important public health problems, requiring global action from the different health areas ³ . It is estimated that infectious diseases will be the main cause of human mortality in the coming decades, mainly due to the growing number of microorganisms that are multi-resistant to antimicrobials ⁴ .

A broad range of bacterial resistance genes has been detected through molecular methods in samples obtained directly from infected root canals ⁵ . Although the presence of a resistance gene in a sample does not necessarily imply phenotypic resistance, proteomics studies have detected the expression of resistance factors such as TetR and Beta-lactamase in endodontic infections ^{6, 7} . As the unnecessary use of antibiotics can contribute to selecting these resistant microorganisms, antibiotics should be prescribed with great caution.

The American Association of Endodontics (AAE) and the European Society of Endodontology (ESE) frequently revise the guidelines for endodontists regarding proper antibiotic prescription. There is general consensus that in most clinical endodontic situations, it suffices to provide local treatment with removal or reduction of the infection source, without using systemic antibiotics ^8-10 .

Different studies around the world have shown that dentists still prescribe antibiotics unnecessarily in endodontics ^11-14 . There is a clear discrepancy between the recommended protocols for prescribing antimicrobials for patients who really need them and current practices among dentists in different parts of the world ¹⁵ . For most Latin American countries, including Colombia, there are few studies on whether antibiotics are prescribed correctly for endodontic purposes.

Thus, the aim of this study was to investigate, through an online questionnaire, how professionals with different levels of academic education, who provide endodontic treatment in Colombia, prescribed antibiotics.

MATERIALS AND METHOD

This study was approved by the institutional ethics committee at Universidad Santo Tomas under number 1-18-30082018. A questionnaire ( Table 1 ) was created through Google forms and e-mailed to 559 dentists registered in the Federation of Colombian Dentistry database. The answers were received from February 21 to November 13, 2018. The questionnaire enquired about gender, age, length of professional experience, workplace, region of the country, weekly mean number of patients, monthly mean number of antibiotic prescriptions, clinical situations in which antibiotics are prescribed, duration of antibiotic prescriptions, prescription of loading dose, conduct for patients allergic to penicillins, and management in case of failure of the first-choice antibiotic. The antibiotics listed in the different clinical situations were amoxicillin, amoxicillin with clavulanic acid, azithromycin, cephalexin, clindamycin, erythromycin, penicillin v, and metronidazole.

RESULTS

A total 320 (57.2%) questionnaires were answered, 193 (60.3%) by general practitioners, 109 (34.1%) by specialists, and 18 (5,6%) by professionals with Master’s or PhD degrees. Most dentists who answered the questionnaire were > 25 years old (n = 269; 84.1%), women (61.6%), and had more than 10 years of professional experience in dentistry (48.4%) ( Table 2 ).

Regarding the prescription of antibiotics, 257 professionals (80.3%) prescribe antibiotics for 7 days, and only 6 (1.9%) suspend the prescription after the symptoms disappear. Comparison among the groups for prescription time showed no statistical difference (p > 0.05), suggesting that the level of training does not influence this decisión ( Table 3 ). More than half of the respondents prescribe antibiotics in up to 3 cases per month, and only 7% do not prescribe them. Regardless ofthe clinical situation and the professional training, amoxicillin is the most frequently prescribed antibiotic. Only in acute periradicular abscess with systemic involvement, the association of amoxicillin with clavulanic acid was the most frequently reported prescription. Also, 243 professionals (75.9%) responded that they do not prescribe an attack dose. Clindamycin was the most frequently recommended antibiotic in case of allergy to penicillin (n = 120; 37.5%), followed by erythromycin (n = 97; 30.3%) and azithromycin (n = 76; 23.8%).

Comparing the three groups of professionals, only the variable “2nd choice in case of allergy to penicillin” showed a significant difference (p < 0.01), with specialists in endodontics presenting the highest frequency of clindamycin prescription (54.1%). In the other groups, Master’s or PhD and clinicians, azithromycin (44.4%) and erythromycin (37.8%) were the most frequently prescribed alternatives. When the antibiotic does not have the desired effect, 52.5% of the professionals choose to change the antibiotic, without significant differences among groups.

There were significant differences in antibiotic prescription among groups for irreversible pulpitis with symptomatic apical periodontitis and symptomatic acute apical periodontitis (p < 0.01). For irreversible pulpitis with symptomatic apical periodontitis, 140 dentists (43.7%) said they prescribe antibiotics (57.5% general practitioners, 20.1% specialists, and 38.9% with Master’s or PhD degrees), while for symptomatic acute apical periodontitis, 183 (57.2%) prescribe antibiotics (74.1% clinical, 28.4% specialists and 50.0% with Master and PhD). In cases of abscesses, clinicians prescribe significantly more antibiotics than specialists and professionals with Master’s or PhD degrees, not only for chronic cases (78.2%, 45.9%, and 50%, respectively, p < 0.001), but also for acute cases with localized intraoral edema/pain (94.3%, 87.2%, and 66.7%, respectively, p < 0.05). In cases of root perforation, 61.1% of clinicians prescribe some antibiotic, against 26.6% of specialists and 50% of professionals with Master’s or PhD degrees (p < 0.01).

DISCUSSION

Healthcare professionals often use systemic antimicrobials to treat or prevent infections. However, there is still a global threat to the effectiveness of these agents related to their indiscriminate use, resulting in the emergence of resistant microorganisms ¹⁶ . This concern also applies to endodontics, since antibiotic resistance by bacteria isolated from infected root canals has been frequently reported ¹⁷ . Moreover, the number of deaths related to endodontic infections refractory to antibiotic treatment is significant ¹⁸ .

Endodontic infections are polymicrobial, which means that multiple species and virulence factors are involved ⁷ . Sometimes, the immune system cannot suppress this type of infection, and antibiotics are required ¹⁸ . However, the prescription of antibiotics in endodontics should be limited to certain clinical conditions, with the aim of preventing the spread of infection and the development of secondary infections in medically compromised patients. As verified in the present study, many professionals lack knowledge about the proper use of antibiotics in endodontics. In this context, the main contribution of this study was to recognize and point out the magnitude of this problem among Colombian dentists.

The present study was based on a questionnaire about antibiotic prescription in different clinical situations, which was answered by 320 dentists with different levels of training. Studies using similar questionnaires have been conducted in different countries ^{11,12,14,19, 20} . However, this was the first study to investígate antibiotic prescription habits among dentists in Colombia. The response rate was acceptable (54.7%), compared to similar studies in Spain (31.1%) ¹¹ , Norway (27.2%) ¹⁹ , United States (22.9%) ²⁰ , and Brazil (4.4%) ¹⁴ .

In this type of study, it is important to record the level of professional training and geographic location in order to design continuing education strategies, if necessary. The current study compared different regions of Colombia, but found no significant difference among them regarding prescription or level of professional training.

The greatest misunderstandings in prescribing antibiotics occurred among general practitioners. Considering all clinical conditions that do not require antibiotics, 60% of general practitioners, on average, prescribed them, while only 34% of endodontics specialists did so. The mean for professionals with Master’s or PhD degrees was 45%, which contradicts expectations, considering their higher level of education. Another alarming finding was for avulsion conditions, which do require antibiotic therapy, but for which 44% of general practitioners reported they did not prescribe antibiotics. The same occurred with 25% of specialists and 39% of professionals with Master’s and PhD degrees. Specific training in endodontics is the most likely explanation for the fact that specialists prescribe more accurately and better than other professionals. In the present study, professionals with different levels of education prescribe antibiotics for irreversible pulpitis (21.2%) and irreversible pulpitis with symptomatic apical periodontitis (43.7%), which is a matter of concern. Dentists prescribe antibiotics to reduce the patient’s pain, though there is no evidence in the literature justifying it ²¹ . In irreversible pulpitis with acute apical periodontitis, the pulp remains vital, with no infection or signs and symptoms of systemic involvement. In these cases, there is only an inflammatory process in the pulp, and therefore, antibiotics are not indicated ²¹ . The level of professional training showed a statistical difference in this case ( Table 4 ). A low percentage was found for this situation in studies in other countries such as Lithuania (19.4%) ¹² and Brazil (6.2%) ¹⁴ , while the percentage was higher in a study in India ²² . The significant difference between the results of the present study and those observed in Lithuania ¹² and Brazil ¹⁴ may be related to the fact that the present study included general practitioners who perform endodontic treatment, while the other studies included only specialists in endodontics. Due to the short half-life of antibiotics, a minimum serum inhibitory concentration is essential for the success of antibiotic therapy. Therefore, a higher initial dose (attack dose) is usually recommended to ensure antibiotic penetration into bone tissue in a concentration high enough to eliminate the microorganisms in the infection site. The present findings showed that more than 70% of all interviewed professionals do not prescribe attack doses. Different results were found in other countries ^{14, 20} , where most professionals do prescribe the attack dose.

Regarding the second-choice antibiotic in cases of penicillin allergy, most professionals choose clindamycin (37.5%), regardless of training level. A similar rate was found in Brazil (33%) ¹⁴ . However, differences were found in intragroup analysis in which professionals with Master’s or PhD degrees prescribe more azithromycin; specialists prescribe more clindamycin; and clinicians prescribe more erythromycin. Current recommendations suggest azithromycin instead of clindamycin in these cases ²³ . The problem with clindamycin is the risk of infection by Clostridioides difficile, and the consequent development of pseudomembranous colitis. It is important to emphasize that not only clindamycin, but also many other broad-spectrum antibiotics have been associated with this type of adverse reaction, and the risk increases with longer treatment periods and greater number of antibiotics administered ²⁴ .

Systemic antibiotics are unnecessary in most cases in endodontics, including acute abscesses located without systemic involvement ^{18, 25} . However, antibiotic therapy is a crucial coadjuvant to treat cases of cellulite with signs of systemic effects, such as lymphadenopathy, limited mouth opening (trismus), fever, loss of appetite, and general malaise. These symptoms suggest that the patient’s immune system is not controlling the infection, and the microorganisms may spread to other anatomical spaces ²³ . In the present study, most respondents prescribe antibiotics for acute periradicular abscesses with systemic involvement, although the prescription frequency was lowest among the professionals with higher qualifications ( Table 4 ). In these most critical situations, respondents’ antibiotic of choice was amoxicillin associated with clavulanic acid, as has been recommended ²³ . The association of these two drugs provides a greater spectrum of action, including penicillin-resistant strains.

It is clear that clinicians should keep in mind that antibiotics should be indicated as a therapeutic adjunct to local treatment to help prevent the spread of infection in severe cases ⁹ . Continuing medical and dental education should be encouraged in order to improve the indication of systemic antimicrobials and prevent erroneous prescriptions, reducing the probability of development of bacterial resistance ¹⁵ . There is a clear need to improve antibiotic recommendations as well as knowledge of pulpal and periradicular diseases, which are a problem not only locally, but also globally.

A limitation of the present study is that the professionals were not asked about why they did or did not prescribe antibiotics, as was done in a previous study ²⁰ . Such answers could help identify the degree of information or misinformation about the prescription of antibiotics. However, the longer the questionnaire, the less accurate the information provided ²⁶ .

CONCLUSIONS

The greatest misunderstandings in prescribing antibiotics occurred among general practitioners. Considering all clinical conditions that do not require antibiotics, 60% of general practitioners, on average, indicated antibiotics, while only 34% of specialists in endodontics did so. This information reinforces the need to create continuing education programs for Colombian dentists, in order to avoid unnecessary prescriptions, thereby reducing the development of microbial resistance to antibiotics.