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Antibiotic Use by Members of the American Association of Endodontists in the Year 2000: Report of a National Survey
JOURNAL OF ENDODONTICS Copyright © 2002 by The American Association of Endodontists
Printed in U.S.A. VOL. 28, NO. 5, MAY 2002
Antibiotic Use by Members of the American Association of Endodontists in the Year 2000: Report of a National Survey Nicole M. Yingling, DMD, B. Ellen Byrne, RPh, DDS, PhD, and Gary R. Hartwell, DDS, MS
had been no improvement in 25 years. Unless these trends change, our generation and those to come may not have effective antibiotics for use in the management of true orofacial infections.
The purpose of this study was to determine the prescribing habits of active members of the American Association of Endodontists (AAE) with regard to antibiotics. A one-page, double-sided questionnaire was sent to the active members of the AAE living in the United States. The 1999 mailing list of 3203 members was obtained from the AAE, and the return rate was 50.1% (1606 surveys). With a sample size over 1000, the study was able to distinguish differences to within 0.5% with power ⴝ 80% (at alpha ⴝ 5%). The data were analyzed using descriptive statistics and chi-square tests of independence. Penicillin VK, 500 mg, 4 times a day, was the first choice antibiotic prescribed by 61.48% of respondents. Clindamycin (Cleocin®), 150 mg, 4 times a day, was selected by 29.59%. For those patients with a penicillin allergy, 57.03% prescribed clindamycin and various erythromycin preparations were prescribed by 26.65%. A loading dose was used by 85.14%. The average duration of antibiotic therapy was 7.58 days. Those respondents involved in academics, either part-time or full-time, were significantly more likely to prescribe penicillin VK, 500 mg, 4 times a day at a rate of 85% versus those in part-time or full-time private practice at a rate of 67%. For cases of irreversible pulpitis, 16.76% of responding endodontists prescribed antibiotics. For the scenario of a necrotic pulp, acute apical periodontitis, and no swelling, 53.93% prescribed antibiotics. Almost 12% prescribed antibiotics for necrotic pulps with chronic apical periodontitis and a sinus tract. For the most part, the majority of the members of the AAE were selecting the appropriate antibiotic for use in orofacial infections, but there are still many who are prescribing antibiotics inappropriately. Although there were trends of improvement in some areas with regards to prescribing antibiotics, there were other areas where there
The deaths of four midwestern children due to methicillin-resistant Staphylococcus aureus (MRSA) infections in August 1999 brought attention to the increase in drug-resistant infections seen in the general population (1). The Center for Disease Control (CDC) has reported that 50% of S. aureus infections are methicillin-resistant, up from 2% in 1974 (1). The indiscriminate use of antibiotics has led to this problem. It has been proposed to develop a general policy to implement new guidelines for antibiotic use. Since 1994, the American Society for Microbiology (ASM) Task Force has recommended that restraint in the indiscriminate prescribing of antibiotics should be the immediate response by practicing physicians, dentists, and veterinarians (2). Although hospitals, agriculture, day care centers, and long-term health care facilities have all been strongly accused of being responsible for contributing to the drug resistance problem today, dentistry’s contributions to the problem can be substantial because dentists prescribe approximately 10% of all common antibiotics (3). In 1977, Dorn et al. (4, 5) discussed trends in treatment of endodontic emergencies based on a questionnaire answered by diplomates of the American Board of Endodontics. The study was repeated in 1988 by Gatewood et al. (6). Whitten et al. (7) surveyed diplomates of the American Board of Endodontics and general dentists in 1996 to determine treatment and drug prescribing practices in endodontics. These three surveys all included general questions, with regard to antibiotic use, by diplomates of the American Board of Endodontics. The purpose of this study was to ask more specific questions with regard to antibiotic prescribing habits of all members of the American Association of Endodontists (AAE) rather than just limiting it to the American Board of Endodontics. MATERIALS AND METHODS A one-page, double-sided questionnaire was sent to the active members of the AAE living in the United States (Fig. 1). A cover letter and postage-paid return envelope were also included. The 396
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FIG. 1. Antibiotic survey sent to members of the AAE.
1999 mailing list of 3274 members was obtained from the AAE. Some questions were based on those asked in the previous surveys (4 –7), and the questionnaire was reviewed by dental researchers
and endodontic faculty for appropriateness and clarity. The sample size was arrived at by a power calculation. With over 1000 samples, the study was able to distinguish differences to within 0.5%
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TABLE 1. Description of respondents n Year graduated Year graduated Age (yr) Gender
Dental Endo Male Female Northeast Midatlantic Southeast Great Lakes Midwest Western Other Full-time private Part-time private Academics only Part-time Faculty
Region of practice
Category of practice
Treatments per week (n)
Mean
1595 1562 1577 1416 163 269 252 240 260 195 362 21 1364 80
1979 1985 46.75 89.68% 10.32% 16.82% 15.76% 15.01% 16.26% 12.20% 22.64% 1.31% 86.22% 5.06%
42 96
2.65% 6.07%
1586
34.88
SD
Range
9.05 8.65 8.59
1955–1997 1961–2000 28–68
16.57
0–140
TABLE 2. Antibiotic-related topics n Prescriptions for Antibiotics per week (n) Days of prescription (n) Loading dose Change strategy
Change prescription by day of week Culture Recent changes in regimen
Yes No Change antibiotic Add second antibiotic Other Yes No Yes No Yes No
with power ⫽ 80% (at alpha ⫽ 5%). The data were analyzed using descriptive statistics and groups were compared by using a chisquare test of independence. RESULTS Of the 3274 surveys mailed, 1677 surveys were returned. A total of 71 were returned as undeliverable, and the others (n ⫽ 1606) were found to be usable. The overall response rate was 50.1%. The results of the survey are presented in Tables 1– 8. Note that in some instances the percentages may not add up to 100%, because some questions allowed multiple responses and the sample size (n) for each question may be different due to improperly completed or partially completed surveys. Demographics Table 1 describes the demographics of the respondents. The mean year of graduation from dental school was 1979. The mean year of graduation from endodontic training was 1985. The mean age of the respondents was 47 yr of age. Male respondents accounted for 89.7% and females 10.3% of the total. As shown in
1531 1581 1352 236 1606 1606 1601 153 1411 61 1533 210 1335
Mean
SD
Range
9.25 7.58 85.14% 14.86% 58.90% 34.93% 20.67% 9.78% 90.22% 3.83% 96.17% 13.59% 86.41%
9.45 1.74
0–80 1–28
TABLE 3. Antibiotic preference with no medical allergies First Choice
Antibiotic Penicillin VK, 500 mg, qid Amoxicillin, 500 mg, tid Cephalexin (Keflex姞), 500 mg, qid Ampicillin, 500 mg, qid Clindamycin (Cleocin姞), 150 mg, qid Other
n
%
932 417 43 35 29 60 1516
61.48 27.51 2.84 2.31 1.91 3.96 100.00
Table 1, the nation-wide proportion of respondents by region of the United States was evenly distributed. The majority of respondents, 86.22%, declared themselves to be in full-time private practice. Only 2.65% were in a full-time academic environment, 6.07% in part-time academics, and 5.06% in part-time private practice. The average number of patients treated in 1 week was 34.88. Antibiotic-Related Topics The respondents of this survey wrote an average of 9.25 prescriptions per week for antibiotics, with a range of 0 to 80 (Table
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TABLE 4. Antibiotic preference with no medical allergies Second Choice
Antibiotic Clindamycin (Cleocin姞), 150 mg, qid Clindamycin (Cleocin姞), 300 mg, qid Amoxicillin, 500 mg, tid Cephalexin (Keflex姞), 500 mg, qid Penicillin VK, 500 mg, qid Other
n 387 205 190 140 117 269 1308
% 29.59 15.67 14.53 10.70 8.94 20.57 100.00
2). The average duration of antibiotic therapy was 7.58 days. The small standard deviation in this response indicated that almost all prescribe for between 5 and 10 days. Cephalosporins and clindamycin (Cleocin®) were mostly written for 5 to 7 days, whereas penicillin and amoxicillin were generally written for 7 to 10 days. A loading dose of twice the normal dose was reported by 85.14% of those surveyed. If improvement was not seen within 2 to 3 days of initiation of antibiotic therapy, 58.90% of respondents changed antibiotics, 34.93% added a second antibiotic, and 20.67% used some other strategy. Some examples of other strategies were to wait longer, prescribe steroids, reopen the tooth to reinstrument and search for missed canals, and/or change the intracanal dressing. Survey item #14 asked if antibiotics were prescribed differently depending on the day of the week. Almost all, 90.22% responded negatively. Interestingly, 72 responded that they would prescribe antibiotics if a weekend or holiday were upcoming. This survey reported that only 3.83% of the respondents cultured drainage from a tooth or from an incision and drainage (I & D) procedure. Some endodontists, 13.59%, reported that they had changed their prescription regimens in the last 12 to 18 months. Comments submitted indicated two main switches: to either clindamycin or to a new generation macrolide, such as azithromycin (Zithromax®) and clarithromycin (Biaxin®). Antibiotic References Penicillin VK, 500 mg, 4 times a day, was the first-choice antibiotic for patients with no medical allergies, by 61.48% of respondents (Table 3). The second-choice antibiotic for nonpenicillin-allergic patients was clindamycin, 150 or 300 mg, 4 times a day, at 45.26% (Table 4). The first and second drug of choice for patients with an allergy to penicillin was clindamycin 150 mg, 4 times a day (35.54% and 13.19%, respectively) (Tables 5 and 6). In this study, 26.65% prescribed erythromycin, base or salt. Antibiotic Usage Table 7 lists the percentage of respondents who prescribed antibiotics for various pulpal and periapical diagnoses. For cases of irreversible pulpits with moderate/severe symptoms and irreversible pulpitis with acute apical periodontitis and moderate/severe symptoms, 3.47% and 13.29% of respondents, respectively, prescribed antibiotics. In cases of a necrotic pulp, chronic apical periodontitis, no swelling, and no other symptoms, antibiotics were prescribed by 18.85%. In the scenario of necrotic pulp, acute apical periodontitis, moderate/severe symptoms but no swelling, 53.93% prescribed antibiotics. For a case of necrotic pulp, chronic apical
TABLE 5. Antibiotic preference with medical allergies Antibiotic Clindamycin (Cleocin姞), 150 mg, qid Clindamycin (Cleocin姞), 300 mg, qid Erythromycin Ethylsuccinate (EES姞), 400 mg, qid Erythromycin Base, 500 mg, qid Erythromycin Base, 250 mg, qid Cephalexin (Keflex姞), 500 mg, qid Azithromycin (Zithromax姞), 250 mg, qid Clarithromycin (Biaxin姞), 500 mg, bid Ciprofloxacin (Cipro姞), 500 mg, bid Metrondiazole (Flagyl姞), 500 mg, qid Clarithromycin (Biaxin姞), 250 mg, bid Other
First Choice n
%
344 208 94
35.54 21.49 9.71
90 74 54 28 20 10 10 7 29 968
9.30 7.64 5.58 2.89 2.07 1.03 1.03 0.72 3.00 100.00
TABLE 6. Antibiotic preference with medical allergies
Antibiotic
Second Choice n
Clindamycin (Cleocin姞), 150 mg, qid Erythromycin Ethylsuccinate (EES姞), 400 mg, qid Erythromycin Base, 500 mg, qid Clindamycin (Cleocin姞), 300 mg, qid Cephalexin (Keflex姞), 500 mg, qid Azithromycin (Zithromax姞), 250 mg, qid Clarithromycin (Biaxin姞), 500 mg, bid Metrondiazole (Flagyl姞), 500 mg, qid Erythromycin Base, 250 mg, qid Metrondiazole (Flagyl姞), 250 mg, qid Ciprofloxacin (Cipro姞), 500 mg, bid Clarithromycin (Biaxin姞), 250 mg, bid Other
%
153 13.19 147 12.67 130 11.21 126 10.86 111 9.57 86 7.41 85 7.33 72 6.21 70 6.03 47 4.05 46 3.97 22 1.90 65 5.60 1160 100.00
TABLE 7. Situations in which antibiotics were prescribed
Situation Irreversibile pulpitis; mod/severe preop symptoms Irreversibile pulpitis with acute apical peridontitis; mod/severe preop symptoms Necrotic pulp with chronic apical periodontitis; no swelling, no/mild preop symptoms Necrotic pulp with acute apical periodontitis; no swelling, mod/severe preop symptoms Necrotic pulp with chronic apical periodontitis; sinus tract present, no/mild preop symptoms Necrotic pulp with acute apical periodontitis; swelling present, mod/severe preop symptoms Total number of prescribing dentists:
Prescribe Antibiotics n
%
53
3.47
203
13.29
288
18.85
824
53.93
182
11.91
1516
99.21
1528
periodontitis, asymptomatic but with a sinus tract, 11.91% prescribe antibiotics. In the case of a necrotic pulp, acute apical periodontitis, swelling, and other moderate/severe symptoms, 99.21% of respondents prescribed antibiotics.
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TABLE 8. Situations with routinely prescribed antibiotics (N ⴝ 1606) Situation
n
I&D of a diffuse intraoral swelling, extraoral 1444 swelling present I&D of a diffuse intraoral swelling, no extraoral 1114 swelling Avulsions 986 I&D of a localized intraoral swelling, no extraoral 720 swelling Endodontic surgeries 599 Retreatments, silver points 434 Retreatments, gutta-percha 247 Postop pain after instrumentation and/or 202 obturation Perforations (before or after repair) 150
% 89.91 69.36 61.39 44.83 37.30 27.02 15.38 12.58 9.34
FIG. 2. The proportion of endodontists that prescribe penicillin VK by year of graduation from endodontic residency. The vertical height of the bars is proportional to the number of graduates in that year.
DISCUSSION Table 8 lists other endodontic treatment situations and the percentage of respondents who prescribe antibiotics routinely for each situation. Incision and drainage of a diffuse intraoral swelling with extraoral swelling prompted 89.91% to prescribe antibiotics. The same scenario without the extraoral swelling resulted in 69.36% prescribing antibiotics. Routine prescription of antibiotics for avulsions was performed by 61.39%. Antibiotics were prescribed by 44.83% of the respondents for I & D of a localized intraoral swelling. Thirty-seven percent prescribed antibiotics routinely for endodontic surgeries. For silver point and gutta-percha retreatment cases, 27.02% and 15.38% prescribed antibiotics. Postoperative pain after instrumentation or obturation resulted in 12.58% of respondents prescribing antibiotics. Finally, 9.34% prescribed antibiotics before or after a perforation repair. One question asked “Is there any one or more particular factor surveyed that has a significant impact on whether penicillin VK 500 mg, 4 times a day was prescribed for therapeutic reasons or not?” The answer was yes, but after all of the variables were put through a multiple logistic regression analysis (i.e. making the predictor variables compete against one another) only year of graduation from endodontic residency and the type of practice (part-time versus full-time, academics or private practice) were statistically significant with regard to this question. The other variables were no longer significant. Further analysis showed that the four practice categories could be collapsed into two: part-time and full-time academics became “academics” and part-time and full-time private practice became “private practice.” Figure 2 shows two lines, both indicating an increasing trend toward prescribing penicillin VK the more recently the endodontists had graduated from their residency programs. The solid line with the filled squares represents the private-practice endodontists. Their preference for penicillin VK as first choice is significantly less than endodontists in academic environments. The dotted line with empty circles shows the proportion for academic endodontists. At the bottom of the figure, there is a bar graph indicating the number of respondents who graduated from endodontic residency programs in any particular year. The graph (Fig. 2) shows that there is a good cross-sectional representation from all year groups. This analysis indicates that if one is involved in academics, there is about an 85% probability that penicillin VK 500 mg, 4 times a day would be the first therapeutic choice. If one is in private practice, there is a 67% chance that the first choice would be penicillin.
The survey instrument has historically been successful in obtaining pertinent information on the practice of endodontics. The population sampled in this study was very large, 3274 members of the AAE. A large percentage of this target population was practicing endodontists, and it should be noted that no attempt was made to survey practicing endodontists who were not members of the AAE. The overall response rate of 50.1% is considered to be an acceptable rate of return for surveys. Questions were designed to glean a variety of information relative to the types of antibiotics used and the prescribing habits of endodontists as determined by years in practice, gender, work status, area of the country, and differences between practitioners who have been recently trained versus those with more time in practice. However, part of survey, item #2, regarding years in practice and item #13, regarding single or multiple appointments, were eliminated from analysis. In hindsight, these questions were found to be poorly worded, and no conclusions could be drawn from the results obtained by these questions because of the ambiguity that existed. Antibiotic-Related Topics Fifteen respondents submitted comments that patients and referring general practitioners often “demand” antibiotics be prescribed for every endodontic scenario. These endodontists felt compelled to prescribe them for “medical-legal” reasons and to decrease the risk of losing referrals. Some of these fifteen, ⬍0.1% of the total surveyed, commented that they prescribe to all patients with instructions not to fill the prescription unless swelling developed. In reality, an infection must be persistent or systemic to justify the need for antibiotics: i.e. fever, swelling, lymphadenopathy, trismus, or malaise in a healthy patient. Antibiotics are also more likely to be needed in an immunocompromised patient or a patient in poor health. The decision to prescribe antibiotics should not be influenced by patient demand, expectation of referring dentists, “just in case” situations, or because it is the day before a weekend or holiday. These reasons constitute inappropriate use of antibiotics. Odontogenic infections are polymicrobial involving a combination of Gram-positive, Gram-negative, facultative anaerobes and strict anaerobic bacteria. Orofacial infections typically have a rapid onset and short duration, 2 to 7 days or less, particularly if the cause is treated or eliminated (8). The average length of antibiotic
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prescriptions in this study was 7.58 days with a range of 5 to 10 days. The proper dose and duration of an antibiotic is enough when there is sufficient evidence that the patient host defenses have gained control of the infection. When the infection is resolving or has resolved, then the drug should be terminated (8). It is prolonged use of antibiotics or an ineffective dose that can contribute to the development of resistant microbial species. If resistant species are already present, it won’t matter how long the antibiotic is used; it will still be ineffective. A 5 to 7 day course would probably be appropriate for most endodontic infections, as long as the patient was monitored every 24 to 28 h. An antibiotic loading dose should be used whenever the half-life of the antibiotic is longer than 3 h or whenever a delay of 12 h or more is unacceptable to achieve therapeutic blood levels (8). Most antibiotics useful in orofacial infections have half-lives less than 3 h, but the acute nature of orofacial infections requires therapeutic blood levels far sooner than 12 h (8). A loading dose of 1 to 2 grams for the penicillins, cephalosporins, and erythromycin ensures rapid elevation of antibiotic blood levels. This dose of erythromycin may produce epigastric distress in some patients (9). A loading dose was appropriately used by 85.14% of endodontists in this survey. Only 3.83% of the respondents cultured drainage from a tooth or from an I & D procedure. This is much less then the 10.6% reported by Dorn et al. in 1977 (4) and the 28.3% reported by Lane and Grossman in 1971 (10). Culturing is rarely indicated for endodontic infections, because there is rarely a single causative organism, but is indicated if the infection persists or is present in a medically compromised patient. Comments submitted indicated that this was the procedure being used by 22 of the respondents.
Antibiotic Preferences The list of antibiotics included in the survey identifies those most often prescribed by dentists for the management of orofacial infections. The list included penicillins, erythromycin, cephalosporins, tetracycline, metronidazole, and the newer, longer-acting, macrolides (11, 12). Penicillin VK, 500 mg, 4 times a day was the first-choice antibiotic for patients who were not allergic to penicillin, being used by 61.48% of respondents (Table 3). This number is in agreement with Whitten et al.’s (7) results of 58.4%. The second-choice antibiotic for nonpenicillin-allergic patients was clindamycin, 150 or 300 mg, 4 times a day at 45.26% (Table 4). Penicillin VK has been found to be effective against most aerobic and anaerobic organisms present in orofacial infections and since the 1940s, continues to be the drug of choice in nonallergic, immunocompetent patients (13). It is a narrow spectrum antibiotic for infections caused by aerobic Gram-negative cocci and anaerobes. It is bactericidal and has a 1% to 10% hypersensitivity rate. If taken with food, absorption may be delayed (14). It should be taken every 6 h. It is low in cost and toxicity (15). Clindamycin is a broader spectrum antibiotic than penicillin but is still narrow in its specificity toward oral pathogens. It is bacteriostatic or bactericidal, depending on drug concentration, infection site, and microorganism. It is 90% absorbed from the gastrointestinal tract in the oral form and has peak serum concentration within 60 min. The recommended dose for adults is 150 to 450 mg, 4 times a day for orofacial infections (14). There is a 1% rate of pseudomembranous colitis. Clindamycin is appropriate for penicillin-allergic patients even though, historically, it is believed that there is a higher risk of pseudomembranous colitis than any other
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antibiotic. The risk of pseudomembranous colitis has now been shown not to be any higher for clindamycin than for other antimicrobials. At best, clindamycin would occupy a third place after ampicillin and cephalosporins as a causative agent for pseudomembranous colitis (16). People at risk for pseudomembranous colitis are the elderly and those who have recently taken one or more courses of antibiotics. Considering its low but serious risk of pseudomembranous colitis, broader spectrum, and being 4 to 5 times more costly than penicillin, there does not seem to be a need to prescribe clindamycin as frequently as the results of this survey indicated. Penicillin is effective with less risk, less cost, and less contribution to antimicrobial resistance. If an infection were found to be resistant to penicillin, with or without the adjunct of metronidazole, one could change to clindamycin. If the patient fails to respond to this treatment, consultation with an oral surgeon is recommended. The patient may need to be admitted to the hospital for administration of closely regulated, “limited use” antibiotics. Amoxicillin, a penicillin derivative with a broader spectrum, is a good choice for immunocompromised patients (13). It was prescribed by 27.51% of respondents as first drug of choice for patients with no medical allergies. It is a good drug for orofacial infections because it is readily absorbed and can be taken with food. Due to the longer half-life and more sustained serum levels, amoxicillin is taken 3 times a day and costs only slightly more than penicillin. However, its broad spectrum is more than is required for endodontic needs, and its use in a healthy individual may contribute to the global antibiotic resistance problem. The first and second drug of choice for patients with an allergy to penicillin was clindamycin 150 mg, 4 times a day (35.54% and 13.19%, respectively) (Tables 5 and 6). When both dosage regimens of clindamycin, 150 mg and 300 mg are combined, 57.03% of respondents prescribe clindamycin, compared with only 21.6% in Whitten et al.’s study (7). Their top choice for penicillin-allergic patients was erythromycin, base or salt, at 63.5%. In this study only 26.65% prescribed erythromycin, base or salt. Erythromycin, a macrolide, has a similar spectrum of activity to that of penicillin for Gram-positive microorganisms but is not as effective against anaerobes usually involved in dental infections. It carries a high incidence (10%) of gastrointestinal upset (11, 14). Erythromycin inhibits the hepatic metabolism of numerous drugs leading to a decrease in their clearance and resulting in an increased effect and/or toxicity. This drug interaction can occur with such drugs as carbamazepine, digoxin, theophylline, triazolam, and warfarin (14). Azithromycin and clarithromycin are semisynthetic derivatives of erythromycin that have been modified to create a broader spectrum of antibacterial activity and improved tissue penetration (17). In addition, they have a longer elimination half-life resulting in decreased dosing schedules and lower incidence of gastrointestinal distress and abdominal cramping. Of the endodontists surveyed, 13.59% reported they had changed their prescription regimens in the last 12 to 18 months (Table 2). Comments indicate two main switches: to clindamycin and to new generation macrolides, such as azithromycin and clarithromycin. This is most likely due to the patient-friendly once or twice a day dosing schedule and fewer gastrointestinal side effects with the new macrolides. Five endodontists “empirically” found that erythromycin, cephalexin (Keflex®), and penicillin were no longer effective against orofacial infections and decided to change. Metronidazole (Flagyl®) is an antibiotic that is very effective against obligate anaerobes but not against facultative anaerobic bacteria. If penicillin is not effective after 2 to 3 days of use, then
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metronidazole has been recommended as a supplemental medication (13). Proper dosage and duration of this combination is important for effective treatment without increasing the likelihood of antibiotic resistance. A loading dose of 1000 mg of penicillin VK should be followed by 500 mg every 6 h for 5 to 7 days. If there is no improvement after 2 to 3 days, then a supplemental 500 mg loading dose of metronidazole should be administered followed by 250 mg every 6 h for 7 to 10 days. Pharmacology reference texts (14, 18) were used to determine the appropriate prescription regimens for all the antibiotics listed on the survey instrument (Fig. 1).
Antibiotic Usage Table 7 lists the percentage of respondents who prescribe antibiotics for various pulpal and periapical diagnoses. Because a medical history could not be provided and specific details of the symptoms could not be included in every question, interpretation of this data must be considered in light of these limitations. The first category was for irreversible pulpitis with moderate/severe symptoms and the second category was for the same with an acute apical periodontitis component. Combined, 16.76% of the responding endodontists prescribed antibiotics for these cases. These pulps are still vital. There is no infection or signs of systemic involvement. Antibiotics are not indicated in either situation. These numbers are almost identical to the results of Dorn et al. (4) in 1977 and Gatewood et al. (6) in 1988. This finding is almost 50% less than that found by Whitten et al. (7) only 5 yr ago. The third scenario was necrotic pulp, chronic apical periodontitis, no swelling, and no or mild symptoms. Again, in a healthy patient, there is no indication for antibiotic use, and treatment should be limited to nonsurgical root canal therapy. In Whitten et al. (7), 35.7% prescribed antibiotics, but in this survey there was improvement to 18.85%. Although this was a significant improvement, this is still inappropriate usage of antibiotics. The fourth category was necrotic pulp, acute apical periodontitis, no swelling, and moderate/severe symptoms. The proper treatment for this case is debridement of the root canal space and analgesics. Again, comparing the Dorn et al. (4), Gatewood et al. (6), and Whitten et al. (7) studies, which reported 30.0%, 33.1%, and 67.3% prescription for antibiotics respectively, this survey’s result was 53.93%, which fits in the same range as previous studies. This again is over-usage of antibiotics. Interestingly, 11.91% still prescribed antibiotics for asymptomatic cases of necrotic pulp, chronic apical periodontitis, and cases with sinus tracts (the fifth scenario). Although reduced from 29.2% in Whitten et al. (7), indicated treatment should consist of nonsurgical root canal therapy with analgesics if needed for pain but no antibiotics. If the patient were medically compromised and the sinus tract did not close within a few weeks or the patient experienced a flare up with systemic involvement, then antibiotics would be indicated. The last situation described a case of a necrotic pulp, acute apical periodontitis (abscess), swelling, and moderate to severe symptoms of an infection. Those prescribing antibiotics in the previous studies (4, 6, 7) ranged from 87.6% to 96.6%. The results of the present survey were comparable at 99.21% and appropriately so. If one interprets that systemic involvement was present in this case, then antibiotics are indicated in conjunction with debridement of the root canal space and an I & D procedure. The interesting point in this survey is that the prescribing habits of endodontists with regards to irreversible pulpitis, necrotic pulps with no systemic involvement, and sinus tracts has not changed in
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almost 25 years. If endodontists are over-prescribing, what are the prescribing habits of general dentists? Why are endodontists prescribing antibiotics for any of the first five scenarios in Table 7? If it were because the patient was immunocompromised, then maybe this would be acceptable. If it was because of insufficient training or fear of litigation, then this is clearly an inappropriate use of antibiotics. Nonsurgical root canal therapy without antibiotics is usually adequate to treat cases of irreversible pulpitis, acute and chronic apical periodontitis, draining sinus tracts, and localized swellings. The pulpal circulation is compromised in these cases, and systemic antibiotics will not reach therapeutic concentrations in the pulp. Removing the source of the infection by performing nonsurgical root canal therapy will usually allow healing of any periradicular lesion or inflammation to occur. Analgesics are indicated for pulpitis pain and pain from periapical inflammation, not antibiotics. Table 8 lists other endodontic treatment situations and the percentage of respondents who prescribe antibiotics routinely for each situation. The majority reported using antibiotics for incision and drainage of a diffuse intraoral swelling with or without extraoral swelling present and for avulsion cases. For most of these scenarios, prescription of antibiotics is appropriate. For the case of I & D of a localized intraoral swelling, 44.83% prescribed antibiotics. As long as the offending tooth was debrided or extracted, and the patient was otherwise healthy, antibiotics are not indicated in this situation. Removing the source of the infection and changing the local environment during the I & D by increasing the oxygen tension and irrigating facial space with saline is all that is required to help the host defenses eliminate the pathogens. Endodontic surgeries are generally performed on healthy tissues to address a very localized area of pathosis. With good, sterile surgical technique in a nonimmunocompromised patient, antibiotics are not indicated, but in this survey 37.30% of respondents routinely prescribed antibiotics for surgeries. Nonsurgical retreatment of endodontically treated teeth has been associated with a higher incidence of flare-ups (19). The more conservative approach in these situations is to inform the patient to report any postoperative signs of infection, and then an antibiotic can be prescribed rather than to prescribe antibiotics just in case. Antibiotics were prescribed by 27.02% of the respondents for silver point retreatments and by 15.38% for gutta-percha retreatments. Postoperative pain after instrumentation or obturation is usually associated with periradicular inflammation, not periradicular infection. Prescribing antibiotics for pain due to the inflammatory process is inappropriate and ineffective. Analgesics are indicated for postop pain. Twelve and a half percent of the surveyed respondents in this survey reported prescribing antibiotics for postoperative pain. Antibiotics were also prescribed by 9.34% before or after perforation repair procedures. There are many variables that can affect the outcome of a perforation repair, such as location in relation to the gingival sulcus or furcation and length of time elapsed since the perforation occurred. The indications for antibiotics in this scenario are not clear-cut, but a favorable prognosis is likely in the case of an immediate repair of a perforation that is not communicating with the gingival sulcus. In this situation antibiotics would not be required. Even in these categories of “other” endodontic treatment procedures there are still tendencies to indiscriminately prescribe antibiotics when they are not really indicated. Antibiotic therapy is an art and a science. There are so many confounding variables, such as suspected pathogen, ability to es-
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tablish drainage, pharmacokinetic properties of the drug, mechanism of action of the antibiotic, virulence of the infection, the current health status of the host, and host defense mechanisms, that it is not possible to make antibiotic therapy into a mechanistic technological science (9). The most important decision for the dental practitioner to make is not which antibiotic to use but whether to use one at all. Most endodontic situations are resolved by nonsurgical endodontics and accompanying incision and drainage procedures when indicated. When the decision is made to use an antibiotic, it is important to adhere to basic principles of antibiotic dosing: (a) use high doses for short durations; (b) use an oral antibiotic loading dose; (c) achieve blood levels of the antibiotic at 2 to 8 times the minimum inhibitory concentration; (d) use frequent dosing intervals; and (e) determine duration of therapy by remission of disease (8). The use of antibiotics for minor infections, or in some cases in patients without infections, could be a major contributor to the world problem of antimicrobial resistance. This research was supported in part by the Alexander Fellowship Fund. The authors thank Dr. Al Best and Ms. Stacey S. Cofield from the Department of Biostatistics at Virginia Commonwealth University for their invaluable assistance in statistical analysis and Ms. Vivian Hyo Lee of the Virginia Commonwealth University School of Dentistry for her dedicated research support.
References 1. CDC Morbidity and Mortality Weekly Report, August 20, 1999. 2. Harrison JW, Svec TA. The beginning of the end of the antibiotic era?
Part I. The problem: abuse of the “miracle drugs.” Quintessence Int 1998;29: 151– 62. 3. Pallasch TJ. Global antibiotic resistance and its impact on the dental community. J Cal Dent Assoc 2000;28:215–33. 4. Dorn SO, Moodnik RM, Feldman MJ, Borden BG. Treatment of the endodontic emergency: a report based on a questionnaire. Part I. J Endodon 1977;3:94 –100. 5. Dorn SO, Moodnik RM, Feldman MJ, Borden BG. Treatment of the endodontic emergency: a report based on a questionnaire. Part II. J Endodon 1977;3:153– 6. 6. Gatewood RS, Himel VT, Dorn SO. Treatment of the endodontic emergency: a decade later. J Endodon 1990;16:284 –91. 7. Whitten BH, Gardiner DL, Jeannsonne BG, Lemon RR. Current trends in endodontic treatment: report of a national survey. J Am Dent Assoc 1996; 127:1333– 41. 8. Pallasch TJ. How to use antibiotics effectively. J Cal Dent Assoc 1993; 21:46 –50. 9. Pallasch TJ. Antibiotic myths and reality. J Cal Dent Assoc 1986;14: 40 –5. 10. Lane AJ, Grossman LI. Culturing root canals by endodontic diplomates: a report based on a questionnaire. Oral Surg 1971;32:461. 11. Moore PA. Dental therapeutic indications for the newer long-acting macrolide antibiotics. JADA 1999;130:1341–3. 12. Montgomery EH, Kroeger DC. Use of antibiotics in dental practice. Dent Clin North Am 1984;28:433–53. 13. Prescription for the future: responsible use of antibiotics in endodontic therapy. AAE Endodontics Colleagues for Excellence, 1999:1– 8. 14. Wynn RL, Meiller TF, Crossley HL. Drug information handbook for dentistry. 6th ed. Hudson: Lexi-Comp, Inc., 2001. 15. Olsen AK, MacEdington E, Kulild JC, Weller RN. Update on antibiotics for the endodontic practice. Compendium Contin Educ Dent 1990;11:328 –32. 16. Jaimes EC. Lincocinamides and the incidence of antibiotic-associated colitis. Clin Ther 1991;13:270 – 80. 17. Bahal N, Nahata MC. The new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin. Ann Pharmacother 1992;26: 46 –55. 18. United States Pharmacopeial Convention, Inc. Drug information for the health care professional. Vol I. 20th ed. Englewood, CO: Micomedex Inc., 2000. 19. Trope M. Flare-up rate of single-visit endodontics. Int Endod J 1991; 24:24 –7.
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Antibiotic Use by Members of the American Association of Endodontists in the Year 2000: Report of a National Survey Nicole M. Yingling, DMD, B. Ellen Byrne, RPh, DDS, PhD, and Gary R. Hartwell, DDS, MS
had been no improvement in 25 years. Unless these trends change, our generation and those to come may not have effective antibiotics for use in the management of true orofacial infections.
The purpose of this study was to determine the prescribing habits of active members of the American Association of Endodontists (AAE) with regard to antibiotics. A one-page, double-sided questionnaire was sent to the active members of the AAE living in the United States. The 1999 mailing list of 3203 members was obtained from the AAE, and the return rate was 50.1% (1606 surveys). With a sample size over 1000, the study was able to distinguish differences to within 0.5% with power ⴝ 80% (at alpha ⴝ 5%). The data were analyzed using descriptive statistics and chi-square tests of independence. Penicillin VK, 500 mg, 4 times a day, was the first choice antibiotic prescribed by 61.48% of respondents. Clindamycin (Cleocin®), 150 mg, 4 times a day, was selected by 29.59%. For those patients with a penicillin allergy, 57.03% prescribed clindamycin and various erythromycin preparations were prescribed by 26.65%. A loading dose was used by 85.14%. The average duration of antibiotic therapy was 7.58 days. Those respondents involved in academics, either part-time or full-time, were significantly more likely to prescribe penicillin VK, 500 mg, 4 times a day at a rate of 85% versus those in part-time or full-time private practice at a rate of 67%. For cases of irreversible pulpitis, 16.76% of responding endodontists prescribed antibiotics. For the scenario of a necrotic pulp, acute apical periodontitis, and no swelling, 53.93% prescribed antibiotics. Almost 12% prescribed antibiotics for necrotic pulps with chronic apical periodontitis and a sinus tract. For the most part, the majority of the members of the AAE were selecting the appropriate antibiotic for use in orofacial infections, but there are still many who are prescribing antibiotics inappropriately. Although there were trends of improvement in some areas with regards to prescribing antibiotics, there were other areas where there
The deaths of four midwestern children due to methicillin-resistant Staphylococcus aureus (MRSA) infections in August 1999 brought attention to the increase in drug-resistant infections seen in the general population (1). The Center for Disease Control (CDC) has reported that 50% of S. aureus infections are methicillin-resistant, up from 2% in 1974 (1). The indiscriminate use of antibiotics has led to this problem. It has been proposed to develop a general policy to implement new guidelines for antibiotic use. Since 1994, the American Society for Microbiology (ASM) Task Force has recommended that restraint in the indiscriminate prescribing of antibiotics should be the immediate response by practicing physicians, dentists, and veterinarians (2). Although hospitals, agriculture, day care centers, and long-term health care facilities have all been strongly accused of being responsible for contributing to the drug resistance problem today, dentistry’s contributions to the problem can be substantial because dentists prescribe approximately 10% of all common antibiotics (3). In 1977, Dorn et al. (4, 5) discussed trends in treatment of endodontic emergencies based on a questionnaire answered by diplomates of the American Board of Endodontics. The study was repeated in 1988 by Gatewood et al. (6). Whitten et al. (7) surveyed diplomates of the American Board of Endodontics and general dentists in 1996 to determine treatment and drug prescribing practices in endodontics. These three surveys all included general questions, with regard to antibiotic use, by diplomates of the American Board of Endodontics. The purpose of this study was to ask more specific questions with regard to antibiotic prescribing habits of all members of the American Association of Endodontists (AAE) rather than just limiting it to the American Board of Endodontics. MATERIALS AND METHODS A one-page, double-sided questionnaire was sent to the active members of the AAE living in the United States (Fig. 1). A cover letter and postage-paid return envelope were also included. The 396
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FIG. 1. Antibiotic survey sent to members of the AAE.
1999 mailing list of 3274 members was obtained from the AAE. Some questions were based on those asked in the previous surveys (4 –7), and the questionnaire was reviewed by dental researchers
and endodontic faculty for appropriateness and clarity. The sample size was arrived at by a power calculation. With over 1000 samples, the study was able to distinguish differences to within 0.5%
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TABLE 1. Description of respondents n Year graduated Year graduated Age (yr) Gender
Dental Endo Male Female Northeast Midatlantic Southeast Great Lakes Midwest Western Other Full-time private Part-time private Academics only Part-time Faculty
Region of practice
Category of practice
Treatments per week (n)
Mean
1595 1562 1577 1416 163 269 252 240 260 195 362 21 1364 80
1979 1985 46.75 89.68% 10.32% 16.82% 15.76% 15.01% 16.26% 12.20% 22.64% 1.31% 86.22% 5.06%
42 96
2.65% 6.07%
1586
34.88
SD
Range
9.05 8.65 8.59
1955–1997 1961–2000 28–68
16.57
0–140
TABLE 2. Antibiotic-related topics n Prescriptions for Antibiotics per week (n) Days of prescription (n) Loading dose Change strategy
Change prescription by day of week Culture Recent changes in regimen
Yes No Change antibiotic Add second antibiotic Other Yes No Yes No Yes No
with power ⫽ 80% (at alpha ⫽ 5%). The data were analyzed using descriptive statistics and groups were compared by using a chisquare test of independence. RESULTS Of the 3274 surveys mailed, 1677 surveys were returned. A total of 71 were returned as undeliverable, and the others (n ⫽ 1606) were found to be usable. The overall response rate was 50.1%. The results of the survey are presented in Tables 1– 8. Note that in some instances the percentages may not add up to 100%, because some questions allowed multiple responses and the sample size (n) for each question may be different due to improperly completed or partially completed surveys. Demographics Table 1 describes the demographics of the respondents. The mean year of graduation from dental school was 1979. The mean year of graduation from endodontic training was 1985. The mean age of the respondents was 47 yr of age. Male respondents accounted for 89.7% and females 10.3% of the total. As shown in
1531 1581 1352 236 1606 1606 1601 153 1411 61 1533 210 1335
Mean
SD
Range
9.25 7.58 85.14% 14.86% 58.90% 34.93% 20.67% 9.78% 90.22% 3.83% 96.17% 13.59% 86.41%
9.45 1.74
0–80 1–28
TABLE 3. Antibiotic preference with no medical allergies First Choice
Antibiotic Penicillin VK, 500 mg, qid Amoxicillin, 500 mg, tid Cephalexin (Keflex姞), 500 mg, qid Ampicillin, 500 mg, qid Clindamycin (Cleocin姞), 150 mg, qid Other
n
%
932 417 43 35 29 60 1516
61.48 27.51 2.84 2.31 1.91 3.96 100.00
Table 1, the nation-wide proportion of respondents by region of the United States was evenly distributed. The majority of respondents, 86.22%, declared themselves to be in full-time private practice. Only 2.65% were in a full-time academic environment, 6.07% in part-time academics, and 5.06% in part-time private practice. The average number of patients treated in 1 week was 34.88. Antibiotic-Related Topics The respondents of this survey wrote an average of 9.25 prescriptions per week for antibiotics, with a range of 0 to 80 (Table
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TABLE 4. Antibiotic preference with no medical allergies Second Choice
Antibiotic Clindamycin (Cleocin姞), 150 mg, qid Clindamycin (Cleocin姞), 300 mg, qid Amoxicillin, 500 mg, tid Cephalexin (Keflex姞), 500 mg, qid Penicillin VK, 500 mg, qid Other
n 387 205 190 140 117 269 1308
% 29.59 15.67 14.53 10.70 8.94 20.57 100.00
2). The average duration of antibiotic therapy was 7.58 days. The small standard deviation in this response indicated that almost all prescribe for between 5 and 10 days. Cephalosporins and clindamycin (Cleocin®) were mostly written for 5 to 7 days, whereas penicillin and amoxicillin were generally written for 7 to 10 days. A loading dose of twice the normal dose was reported by 85.14% of those surveyed. If improvement was not seen within 2 to 3 days of initiation of antibiotic therapy, 58.90% of respondents changed antibiotics, 34.93% added a second antibiotic, and 20.67% used some other strategy. Some examples of other strategies were to wait longer, prescribe steroids, reopen the tooth to reinstrument and search for missed canals, and/or change the intracanal dressing. Survey item #14 asked if antibiotics were prescribed differently depending on the day of the week. Almost all, 90.22% responded negatively. Interestingly, 72 responded that they would prescribe antibiotics if a weekend or holiday were upcoming. This survey reported that only 3.83% of the respondents cultured drainage from a tooth or from an incision and drainage (I & D) procedure. Some endodontists, 13.59%, reported that they had changed their prescription regimens in the last 12 to 18 months. Comments submitted indicated two main switches: to either clindamycin or to a new generation macrolide, such as azithromycin (Zithromax®) and clarithromycin (Biaxin®). Antibiotic References Penicillin VK, 500 mg, 4 times a day, was the first-choice antibiotic for patients with no medical allergies, by 61.48% of respondents (Table 3). The second-choice antibiotic for nonpenicillin-allergic patients was clindamycin, 150 or 300 mg, 4 times a day, at 45.26% (Table 4). The first and second drug of choice for patients with an allergy to penicillin was clindamycin 150 mg, 4 times a day (35.54% and 13.19%, respectively) (Tables 5 and 6). In this study, 26.65% prescribed erythromycin, base or salt. Antibiotic Usage Table 7 lists the percentage of respondents who prescribed antibiotics for various pulpal and periapical diagnoses. For cases of irreversible pulpits with moderate/severe symptoms and irreversible pulpitis with acute apical periodontitis and moderate/severe symptoms, 3.47% and 13.29% of respondents, respectively, prescribed antibiotics. In cases of a necrotic pulp, chronic apical periodontitis, no swelling, and no other symptoms, antibiotics were prescribed by 18.85%. In the scenario of necrotic pulp, acute apical periodontitis, moderate/severe symptoms but no swelling, 53.93% prescribed antibiotics. For a case of necrotic pulp, chronic apical
TABLE 5. Antibiotic preference with medical allergies Antibiotic Clindamycin (Cleocin姞), 150 mg, qid Clindamycin (Cleocin姞), 300 mg, qid Erythromycin Ethylsuccinate (EES姞), 400 mg, qid Erythromycin Base, 500 mg, qid Erythromycin Base, 250 mg, qid Cephalexin (Keflex姞), 500 mg, qid Azithromycin (Zithromax姞), 250 mg, qid Clarithromycin (Biaxin姞), 500 mg, bid Ciprofloxacin (Cipro姞), 500 mg, bid Metrondiazole (Flagyl姞), 500 mg, qid Clarithromycin (Biaxin姞), 250 mg, bid Other
First Choice n
%
344 208 94
35.54 21.49 9.71
90 74 54 28 20 10 10 7 29 968
9.30 7.64 5.58 2.89 2.07 1.03 1.03 0.72 3.00 100.00
TABLE 6. Antibiotic preference with medical allergies
Antibiotic
Second Choice n
Clindamycin (Cleocin姞), 150 mg, qid Erythromycin Ethylsuccinate (EES姞), 400 mg, qid Erythromycin Base, 500 mg, qid Clindamycin (Cleocin姞), 300 mg, qid Cephalexin (Keflex姞), 500 mg, qid Azithromycin (Zithromax姞), 250 mg, qid Clarithromycin (Biaxin姞), 500 mg, bid Metrondiazole (Flagyl姞), 500 mg, qid Erythromycin Base, 250 mg, qid Metrondiazole (Flagyl姞), 250 mg, qid Ciprofloxacin (Cipro姞), 500 mg, bid Clarithromycin (Biaxin姞), 250 mg, bid Other
%
153 13.19 147 12.67 130 11.21 126 10.86 111 9.57 86 7.41 85 7.33 72 6.21 70 6.03 47 4.05 46 3.97 22 1.90 65 5.60 1160 100.00
TABLE 7. Situations in which antibiotics were prescribed
Situation Irreversibile pulpitis; mod/severe preop symptoms Irreversibile pulpitis with acute apical peridontitis; mod/severe preop symptoms Necrotic pulp with chronic apical periodontitis; no swelling, no/mild preop symptoms Necrotic pulp with acute apical periodontitis; no swelling, mod/severe preop symptoms Necrotic pulp with chronic apical periodontitis; sinus tract present, no/mild preop symptoms Necrotic pulp with acute apical periodontitis; swelling present, mod/severe preop symptoms Total number of prescribing dentists:
Prescribe Antibiotics n
%
53
3.47
203
13.29
288
18.85
824
53.93
182
11.91
1516
99.21
1528
periodontitis, asymptomatic but with a sinus tract, 11.91% prescribe antibiotics. In the case of a necrotic pulp, acute apical periodontitis, swelling, and other moderate/severe symptoms, 99.21% of respondents prescribed antibiotics.
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TABLE 8. Situations with routinely prescribed antibiotics (N ⴝ 1606) Situation
n
I&D of a diffuse intraoral swelling, extraoral 1444 swelling present I&D of a diffuse intraoral swelling, no extraoral 1114 swelling Avulsions 986 I&D of a localized intraoral swelling, no extraoral 720 swelling Endodontic surgeries 599 Retreatments, silver points 434 Retreatments, gutta-percha 247 Postop pain after instrumentation and/or 202 obturation Perforations (before or after repair) 150
% 89.91 69.36 61.39 44.83 37.30 27.02 15.38 12.58 9.34
FIG. 2. The proportion of endodontists that prescribe penicillin VK by year of graduation from endodontic residency. The vertical height of the bars is proportional to the number of graduates in that year.
DISCUSSION Table 8 lists other endodontic treatment situations and the percentage of respondents who prescribe antibiotics routinely for each situation. Incision and drainage of a diffuse intraoral swelling with extraoral swelling prompted 89.91% to prescribe antibiotics. The same scenario without the extraoral swelling resulted in 69.36% prescribing antibiotics. Routine prescription of antibiotics for avulsions was performed by 61.39%. Antibiotics were prescribed by 44.83% of the respondents for I & D of a localized intraoral swelling. Thirty-seven percent prescribed antibiotics routinely for endodontic surgeries. For silver point and gutta-percha retreatment cases, 27.02% and 15.38% prescribed antibiotics. Postoperative pain after instrumentation or obturation resulted in 12.58% of respondents prescribing antibiotics. Finally, 9.34% prescribed antibiotics before or after a perforation repair. One question asked “Is there any one or more particular factor surveyed that has a significant impact on whether penicillin VK 500 mg, 4 times a day was prescribed for therapeutic reasons or not?” The answer was yes, but after all of the variables were put through a multiple logistic regression analysis (i.e. making the predictor variables compete against one another) only year of graduation from endodontic residency and the type of practice (part-time versus full-time, academics or private practice) were statistically significant with regard to this question. The other variables were no longer significant. Further analysis showed that the four practice categories could be collapsed into two: part-time and full-time academics became “academics” and part-time and full-time private practice became “private practice.” Figure 2 shows two lines, both indicating an increasing trend toward prescribing penicillin VK the more recently the endodontists had graduated from their residency programs. The solid line with the filled squares represents the private-practice endodontists. Their preference for penicillin VK as first choice is significantly less than endodontists in academic environments. The dotted line with empty circles shows the proportion for academic endodontists. At the bottom of the figure, there is a bar graph indicating the number of respondents who graduated from endodontic residency programs in any particular year. The graph (Fig. 2) shows that there is a good cross-sectional representation from all year groups. This analysis indicates that if one is involved in academics, there is about an 85% probability that penicillin VK 500 mg, 4 times a day would be the first therapeutic choice. If one is in private practice, there is a 67% chance that the first choice would be penicillin.
The survey instrument has historically been successful in obtaining pertinent information on the practice of endodontics. The population sampled in this study was very large, 3274 members of the AAE. A large percentage of this target population was practicing endodontists, and it should be noted that no attempt was made to survey practicing endodontists who were not members of the AAE. The overall response rate of 50.1% is considered to be an acceptable rate of return for surveys. Questions were designed to glean a variety of information relative to the types of antibiotics used and the prescribing habits of endodontists as determined by years in practice, gender, work status, area of the country, and differences between practitioners who have been recently trained versus those with more time in practice. However, part of survey, item #2, regarding years in practice and item #13, regarding single or multiple appointments, were eliminated from analysis. In hindsight, these questions were found to be poorly worded, and no conclusions could be drawn from the results obtained by these questions because of the ambiguity that existed. Antibiotic-Related Topics Fifteen respondents submitted comments that patients and referring general practitioners often “demand” antibiotics be prescribed for every endodontic scenario. These endodontists felt compelled to prescribe them for “medical-legal” reasons and to decrease the risk of losing referrals. Some of these fifteen, ⬍0.1% of the total surveyed, commented that they prescribe to all patients with instructions not to fill the prescription unless swelling developed. In reality, an infection must be persistent or systemic to justify the need for antibiotics: i.e. fever, swelling, lymphadenopathy, trismus, or malaise in a healthy patient. Antibiotics are also more likely to be needed in an immunocompromised patient or a patient in poor health. The decision to prescribe antibiotics should not be influenced by patient demand, expectation of referring dentists, “just in case” situations, or because it is the day before a weekend or holiday. These reasons constitute inappropriate use of antibiotics. Odontogenic infections are polymicrobial involving a combination of Gram-positive, Gram-negative, facultative anaerobes and strict anaerobic bacteria. Orofacial infections typically have a rapid onset and short duration, 2 to 7 days or less, particularly if the cause is treated or eliminated (8). The average length of antibiotic
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prescriptions in this study was 7.58 days with a range of 5 to 10 days. The proper dose and duration of an antibiotic is enough when there is sufficient evidence that the patient host defenses have gained control of the infection. When the infection is resolving or has resolved, then the drug should be terminated (8). It is prolonged use of antibiotics or an ineffective dose that can contribute to the development of resistant microbial species. If resistant species are already present, it won’t matter how long the antibiotic is used; it will still be ineffective. A 5 to 7 day course would probably be appropriate for most endodontic infections, as long as the patient was monitored every 24 to 28 h. An antibiotic loading dose should be used whenever the half-life of the antibiotic is longer than 3 h or whenever a delay of 12 h or more is unacceptable to achieve therapeutic blood levels (8). Most antibiotics useful in orofacial infections have half-lives less than 3 h, but the acute nature of orofacial infections requires therapeutic blood levels far sooner than 12 h (8). A loading dose of 1 to 2 grams for the penicillins, cephalosporins, and erythromycin ensures rapid elevation of antibiotic blood levels. This dose of erythromycin may produce epigastric distress in some patients (9). A loading dose was appropriately used by 85.14% of endodontists in this survey. Only 3.83% of the respondents cultured drainage from a tooth or from an I & D procedure. This is much less then the 10.6% reported by Dorn et al. in 1977 (4) and the 28.3% reported by Lane and Grossman in 1971 (10). Culturing is rarely indicated for endodontic infections, because there is rarely a single causative organism, but is indicated if the infection persists or is present in a medically compromised patient. Comments submitted indicated that this was the procedure being used by 22 of the respondents.
Antibiotic Preferences The list of antibiotics included in the survey identifies those most often prescribed by dentists for the management of orofacial infections. The list included penicillins, erythromycin, cephalosporins, tetracycline, metronidazole, and the newer, longer-acting, macrolides (11, 12). Penicillin VK, 500 mg, 4 times a day was the first-choice antibiotic for patients who were not allergic to penicillin, being used by 61.48% of respondents (Table 3). This number is in agreement with Whitten et al.’s (7) results of 58.4%. The second-choice antibiotic for nonpenicillin-allergic patients was clindamycin, 150 or 300 mg, 4 times a day at 45.26% (Table 4). Penicillin VK has been found to be effective against most aerobic and anaerobic organisms present in orofacial infections and since the 1940s, continues to be the drug of choice in nonallergic, immunocompetent patients (13). It is a narrow spectrum antibiotic for infections caused by aerobic Gram-negative cocci and anaerobes. It is bactericidal and has a 1% to 10% hypersensitivity rate. If taken with food, absorption may be delayed (14). It should be taken every 6 h. It is low in cost and toxicity (15). Clindamycin is a broader spectrum antibiotic than penicillin but is still narrow in its specificity toward oral pathogens. It is bacteriostatic or bactericidal, depending on drug concentration, infection site, and microorganism. It is 90% absorbed from the gastrointestinal tract in the oral form and has peak serum concentration within 60 min. The recommended dose for adults is 150 to 450 mg, 4 times a day for orofacial infections (14). There is a 1% rate of pseudomembranous colitis. Clindamycin is appropriate for penicillin-allergic patients even though, historically, it is believed that there is a higher risk of pseudomembranous colitis than any other
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antibiotic. The risk of pseudomembranous colitis has now been shown not to be any higher for clindamycin than for other antimicrobials. At best, clindamycin would occupy a third place after ampicillin and cephalosporins as a causative agent for pseudomembranous colitis (16). People at risk for pseudomembranous colitis are the elderly and those who have recently taken one or more courses of antibiotics. Considering its low but serious risk of pseudomembranous colitis, broader spectrum, and being 4 to 5 times more costly than penicillin, there does not seem to be a need to prescribe clindamycin as frequently as the results of this survey indicated. Penicillin is effective with less risk, less cost, and less contribution to antimicrobial resistance. If an infection were found to be resistant to penicillin, with or without the adjunct of metronidazole, one could change to clindamycin. If the patient fails to respond to this treatment, consultation with an oral surgeon is recommended. The patient may need to be admitted to the hospital for administration of closely regulated, “limited use” antibiotics. Amoxicillin, a penicillin derivative with a broader spectrum, is a good choice for immunocompromised patients (13). It was prescribed by 27.51% of respondents as first drug of choice for patients with no medical allergies. It is a good drug for orofacial infections because it is readily absorbed and can be taken with food. Due to the longer half-life and more sustained serum levels, amoxicillin is taken 3 times a day and costs only slightly more than penicillin. However, its broad spectrum is more than is required for endodontic needs, and its use in a healthy individual may contribute to the global antibiotic resistance problem. The first and second drug of choice for patients with an allergy to penicillin was clindamycin 150 mg, 4 times a day (35.54% and 13.19%, respectively) (Tables 5 and 6). When both dosage regimens of clindamycin, 150 mg and 300 mg are combined, 57.03% of respondents prescribe clindamycin, compared with only 21.6% in Whitten et al.’s study (7). Their top choice for penicillin-allergic patients was erythromycin, base or salt, at 63.5%. In this study only 26.65% prescribed erythromycin, base or salt. Erythromycin, a macrolide, has a similar spectrum of activity to that of penicillin for Gram-positive microorganisms but is not as effective against anaerobes usually involved in dental infections. It carries a high incidence (10%) of gastrointestinal upset (11, 14). Erythromycin inhibits the hepatic metabolism of numerous drugs leading to a decrease in their clearance and resulting in an increased effect and/or toxicity. This drug interaction can occur with such drugs as carbamazepine, digoxin, theophylline, triazolam, and warfarin (14). Azithromycin and clarithromycin are semisynthetic derivatives of erythromycin that have been modified to create a broader spectrum of antibacterial activity and improved tissue penetration (17). In addition, they have a longer elimination half-life resulting in decreased dosing schedules and lower incidence of gastrointestinal distress and abdominal cramping. Of the endodontists surveyed, 13.59% reported they had changed their prescription regimens in the last 12 to 18 months (Table 2). Comments indicate two main switches: to clindamycin and to new generation macrolides, such as azithromycin and clarithromycin. This is most likely due to the patient-friendly once or twice a day dosing schedule and fewer gastrointestinal side effects with the new macrolides. Five endodontists “empirically” found that erythromycin, cephalexin (Keflex®), and penicillin were no longer effective against orofacial infections and decided to change. Metronidazole (Flagyl®) is an antibiotic that is very effective against obligate anaerobes but not against facultative anaerobic bacteria. If penicillin is not effective after 2 to 3 days of use, then
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metronidazole has been recommended as a supplemental medication (13). Proper dosage and duration of this combination is important for effective treatment without increasing the likelihood of antibiotic resistance. A loading dose of 1000 mg of penicillin VK should be followed by 500 mg every 6 h for 5 to 7 days. If there is no improvement after 2 to 3 days, then a supplemental 500 mg loading dose of metronidazole should be administered followed by 250 mg every 6 h for 7 to 10 days. Pharmacology reference texts (14, 18) were used to determine the appropriate prescription regimens for all the antibiotics listed on the survey instrument (Fig. 1).
Antibiotic Usage Table 7 lists the percentage of respondents who prescribe antibiotics for various pulpal and periapical diagnoses. Because a medical history could not be provided and specific details of the symptoms could not be included in every question, interpretation of this data must be considered in light of these limitations. The first category was for irreversible pulpitis with moderate/severe symptoms and the second category was for the same with an acute apical periodontitis component. Combined, 16.76% of the responding endodontists prescribed antibiotics for these cases. These pulps are still vital. There is no infection or signs of systemic involvement. Antibiotics are not indicated in either situation. These numbers are almost identical to the results of Dorn et al. (4) in 1977 and Gatewood et al. (6) in 1988. This finding is almost 50% less than that found by Whitten et al. (7) only 5 yr ago. The third scenario was necrotic pulp, chronic apical periodontitis, no swelling, and no or mild symptoms. Again, in a healthy patient, there is no indication for antibiotic use, and treatment should be limited to nonsurgical root canal therapy. In Whitten et al. (7), 35.7% prescribed antibiotics, but in this survey there was improvement to 18.85%. Although this was a significant improvement, this is still inappropriate usage of antibiotics. The fourth category was necrotic pulp, acute apical periodontitis, no swelling, and moderate/severe symptoms. The proper treatment for this case is debridement of the root canal space and analgesics. Again, comparing the Dorn et al. (4), Gatewood et al. (6), and Whitten et al. (7) studies, which reported 30.0%, 33.1%, and 67.3% prescription for antibiotics respectively, this survey’s result was 53.93%, which fits in the same range as previous studies. This again is over-usage of antibiotics. Interestingly, 11.91% still prescribed antibiotics for asymptomatic cases of necrotic pulp, chronic apical periodontitis, and cases with sinus tracts (the fifth scenario). Although reduced from 29.2% in Whitten et al. (7), indicated treatment should consist of nonsurgical root canal therapy with analgesics if needed for pain but no antibiotics. If the patient were medically compromised and the sinus tract did not close within a few weeks or the patient experienced a flare up with systemic involvement, then antibiotics would be indicated. The last situation described a case of a necrotic pulp, acute apical periodontitis (abscess), swelling, and moderate to severe symptoms of an infection. Those prescribing antibiotics in the previous studies (4, 6, 7) ranged from 87.6% to 96.6%. The results of the present survey were comparable at 99.21% and appropriately so. If one interprets that systemic involvement was present in this case, then antibiotics are indicated in conjunction with debridement of the root canal space and an I & D procedure. The interesting point in this survey is that the prescribing habits of endodontists with regards to irreversible pulpitis, necrotic pulps with no systemic involvement, and sinus tracts has not changed in
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almost 25 years. If endodontists are over-prescribing, what are the prescribing habits of general dentists? Why are endodontists prescribing antibiotics for any of the first five scenarios in Table 7? If it were because the patient was immunocompromised, then maybe this would be acceptable. If it was because of insufficient training or fear of litigation, then this is clearly an inappropriate use of antibiotics. Nonsurgical root canal therapy without antibiotics is usually adequate to treat cases of irreversible pulpitis, acute and chronic apical periodontitis, draining sinus tracts, and localized swellings. The pulpal circulation is compromised in these cases, and systemic antibiotics will not reach therapeutic concentrations in the pulp. Removing the source of the infection by performing nonsurgical root canal therapy will usually allow healing of any periradicular lesion or inflammation to occur. Analgesics are indicated for pulpitis pain and pain from periapical inflammation, not antibiotics. Table 8 lists other endodontic treatment situations and the percentage of respondents who prescribe antibiotics routinely for each situation. The majority reported using antibiotics for incision and drainage of a diffuse intraoral swelling with or without extraoral swelling present and for avulsion cases. For most of these scenarios, prescription of antibiotics is appropriate. For the case of I & D of a localized intraoral swelling, 44.83% prescribed antibiotics. As long as the offending tooth was debrided or extracted, and the patient was otherwise healthy, antibiotics are not indicated in this situation. Removing the source of the infection and changing the local environment during the I & D by increasing the oxygen tension and irrigating facial space with saline is all that is required to help the host defenses eliminate the pathogens. Endodontic surgeries are generally performed on healthy tissues to address a very localized area of pathosis. With good, sterile surgical technique in a nonimmunocompromised patient, antibiotics are not indicated, but in this survey 37.30% of respondents routinely prescribed antibiotics for surgeries. Nonsurgical retreatment of endodontically treated teeth has been associated with a higher incidence of flare-ups (19). The more conservative approach in these situations is to inform the patient to report any postoperative signs of infection, and then an antibiotic can be prescribed rather than to prescribe antibiotics just in case. Antibiotics were prescribed by 27.02% of the respondents for silver point retreatments and by 15.38% for gutta-percha retreatments. Postoperative pain after instrumentation or obturation is usually associated with periradicular inflammation, not periradicular infection. Prescribing antibiotics for pain due to the inflammatory process is inappropriate and ineffective. Analgesics are indicated for postop pain. Twelve and a half percent of the surveyed respondents in this survey reported prescribing antibiotics for postoperative pain. Antibiotics were also prescribed by 9.34% before or after perforation repair procedures. There are many variables that can affect the outcome of a perforation repair, such as location in relation to the gingival sulcus or furcation and length of time elapsed since the perforation occurred. The indications for antibiotics in this scenario are not clear-cut, but a favorable prognosis is likely in the case of an immediate repair of a perforation that is not communicating with the gingival sulcus. In this situation antibiotics would not be required. Even in these categories of “other” endodontic treatment procedures there are still tendencies to indiscriminately prescribe antibiotics when they are not really indicated. Antibiotic therapy is an art and a science. There are so many confounding variables, such as suspected pathogen, ability to es-
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tablish drainage, pharmacokinetic properties of the drug, mechanism of action of the antibiotic, virulence of the infection, the current health status of the host, and host defense mechanisms, that it is not possible to make antibiotic therapy into a mechanistic technological science (9). The most important decision for the dental practitioner to make is not which antibiotic to use but whether to use one at all. Most endodontic situations are resolved by nonsurgical endodontics and accompanying incision and drainage procedures when indicated. When the decision is made to use an antibiotic, it is important to adhere to basic principles of antibiotic dosing: (a) use high doses for short durations; (b) use an oral antibiotic loading dose; (c) achieve blood levels of the antibiotic at 2 to 8 times the minimum inhibitory concentration; (d) use frequent dosing intervals; and (e) determine duration of therapy by remission of disease (8). The use of antibiotics for minor infections, or in some cases in patients without infections, could be a major contributor to the world problem of antimicrobial resistance. This research was supported in part by the Alexander Fellowship Fund. The authors thank Dr. Al Best and Ms. Stacey S. Cofield from the Department of Biostatistics at Virginia Commonwealth University for their invaluable assistance in statistical analysis and Ms. Vivian Hyo Lee of the Virginia Commonwealth University School of Dentistry for her dedicated research support.
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