ORIGINAL CONTRIBUTIONS

Evidence-based recommendations
for antibiotic usage to treat
endodontic infections and pain
A systematic review of randomized controlled trials

Anita Aminoshariae, DDS, MS, Dipl (American Board ABSTRACT

M
ultidrug-resistant (MDR) bacterial strains scribing antibiotics for endodontic infection or pain.
are a global health care problem.1 The Methods. The authors prepared and registered a protocol
genetic changes of these drug-resistant on PROSPERO. They conducted electronic searches in
microbes have been linked to excessive MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.
prescribing of antibiotics by health care providers.2 gov. In addition, the authors hand searched the bibliogra-
This link also has occurred with antibiotics prescribed for phies of all relevant articles, the gray literature, and text-
orofacial infections, including endodontic infections.3 books for randomized controlled clinical studies. The
Unfortunately, the environmental development of gen- authors independently selected the relevant articles.
erations of antibiotic-resistant microbes has resulted from Results. The overall quality of the studies was fair with a
human application of antibiotics via underuse, overuse, low risk of bias, but 2 studies had a moderate risk of bias.
and misuse across many years.4 Therefore, every dental Conclusions. The best available clinical evidence signals
clinician needs to be knowledgeable about exactly which no indications for prescribing antibiotics preoperatively or
clinical conditions warrant the prescription of antibiotics. postoperatively to prevent endodontic infection or pain
The authors of a systematic review published in 2015 unless the spread of infection is systemic, the patient is
reported the presence of antimicrobial-resistant genes in febrile, or both. Generally, an accurate diagnosis coupled
the oral cavity, especially those resistant to tetracycline with effective endodontic treatment will decrease microbial
and beta-lactam antibiotic agents in saliva, supragingival flora enough for healing to occur.
biofilm, and acute endodontic infections.5 Indiscriminate Practical Implications. To help decrease the number of
administration of antibiotics in situations for which there drug-resistant microbes, oral health care providers should
is no evidence to support their use could result in an not prescribe antibiotics when they are not indicated.
MDR strain that is resistant to more than 1 agent in 3 or Key Words. Endodontics; antibiotics; pain; flare-ups;
more categories of antibiotics.6 randomized controlled clinical trials.
In keeping with using evidence-based principles in JADA 2016:-(-):---
clinical practice, we explored the scientific evidence for http://dx.doi.org/10.1016/j.adaj.2015.11.002
prescribing antibiotics to treat endodontic infections or
pain using randomized controlled clinical studies, which
are considered the criterion standard with the highest METHODS
level of evidence.7,8 We used the PICO (population [P], We prepared and registered the protocol on PROSPERO
intervention [I], comparison [C], and outcome [O]) (registration number CRD42015026945). We conducted
format to frame the following clinical question: In pa- electronic searches in MEDLINE, Scopus, Cochrane Li-
tients undergoing root canal treatment for an infected brary, and ClinicalTrials.gov, and we used strict inclusion
root canal system, does antibiotic treatment result in the and exclusion criteria. We also searched the gray litera-
reduction of pain and flare-ups?9 Therefore, the purpose ture for randomized controlled clinical studies. We
of our study was to discuss the latest indications for excluded non–English-language articles that did not have
prescribing antibiotics for endodontic infections and English-language abstracts.
pain reduction. Key search terms included “endodontics,” “root canal
treatments,” “antibiotics,” “randomized-controlled-clin-
Copyright ª 2016 American Dental Association. All rights reserved. ical studies,” and “pain and/or flare-ups.” In addition, we

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 ORIGINAL CONTRIBUTIONS

manually searched the bibliographies of all relevant ar- initiation or continuation of root canal treatment.”20 We
ticles, the gray literature, and textbooks for randomized found only 2 prospective, cohort, randomized, double-
controlled clinical studies. Two reviewers (A.A., J.C.K.) masked, placebo-controlled clinical studies in which re-
independently selected the relevant articles. In cases of searchers addressed this topic.17,19 The authors of these
disagreement, we discussed the divergence and then studies reported that the preoperative administration of
agreed on the final outcome. antibiotics was ineffective in alleviating pain in pulpal
The inclusion criteria for this review were as follows: tissue, periapical tissue, or both.17,19
- articles whose authors described randomized Pickenpaugh and colleagues19 examined the effect
controlled clinical trials and reported reduction of pain, of administration of prophylactic amoxicillin on the
flare-ups, or both, published in peer-reviewed English- occurrence of endodontic flare-ups in patients with
language journals from January 1990 through September necrotic pulps with asymptomatic periapical periodon-
2015; titis. The authors randomly divided 70 participants into 2
- in vivo human studies; double-masked treatment groups who had a diagnosis of
- articles whose authors used pain and increased or necrotic pulp with asymptomatic periapical periodonti-
reduced severity of the infection as measurements to tis. One group received 3 grams of amoxicillin orally 1
compare patients undergoing endodontic therapy with hour before endodontic treatment and the other received
antibiotics with patients undergoing endodontic therapy 3 g of placebo orally during the same time. The authors
without antibiotics; reported that prophylactic administration of antibiotics
- articles whose authors provided the sample size of the was ineffective and unrelated to the incidence of an
study; endodontic flare-up (P ¼ .80).
- articles whose authors measured the effect of pain In a prospective, randomized, double-masked study,
reduction, flare-ups, or both, as a primary objective. Nagle and colleagues17 explored the effect of oral
Exclusion criteria consisted of studies that did not administration of penicillin on pain in patients with
meet the previously listed inclusion criteria, as well as untreated teeth with a diagnosis of symptomatic irre-
animal studies and laboratory studies. versible pulpitis. The investigators randomly divided 40
We used a data extraction sheet based on the participants with a diagnosis of irreversible pulpitis into
Cochrane Consumers and Communication Review 2 groups, 1 receiving a 7-day oral dose of penicillin V
Groups data extraction template.10 We used the potassium (500 milligrams, 4 times per day) or receiving
AMSTAR checklist,11 the Oxford Systematic Review a 7-day dose of placebo. The participants also were
Appraisal Sheet,7,8 Critical Appraisal Skills Programme,12 instructed to initially take 1 600-mg tablet of ibuprofen
and the Grading of Recommendations Assessment, every 4 to 6 hours as needed for pain and to take 30 mg
Development and Evaluation system13 for grading evi- of acetaminophen with codeine (2 tablets every 4 to 6
dence to ensure the accuracy of this data analysis in this hours) only if the ibuprofen did not relieve their pain.
systematic review. We used the Cochrane Collaboration’s Each participant received a 7-day diary to record
tool for assessing risk of bias to assess the methodological symptoms and the number and type of pain medication
quality of the included studies.14 taken. The investigators performed the administration
in a double-masked manner, and the participants did
RESULTS not receive endodontic treatment. The investigators
Owing to the variety of research methodologies, di- reported that the administration of penicillin was inef-
agnoses, and antibiotic regimens we evaluated in our fective in reducing pain (P > .05). Thus, the best avail-
investigation, it was not possible to standardize the able evidence dictates that antibiotics should not be
research data and to apply meta-analysis. The figure prescribed preoperatively for patients with untreated,
presents a flowchart of the systematic review process symptomatic, irreversible pulpitis. The overall quality
according to the Preferred Reporting Items for Sys- of the research was good, and both studies17,19 had a
tematic Reviews and Meta-analyses.9 low risk of bias (Table 215-19).
Our review focused on 2 primary clinical situations Postoperative administration. We found only 3 re-
involving the use of systemic antibiotics: the adminis- ports of prospective, cohort, randomized, double-
tration of antibiotics preoperatively and the administra- masked, placebo-controlled clinical studies regarding this
tion of antibiotics postoperatively to prevent pulpal and topic.15,16,18 Administration of antibiotics has been re-
periapical pain or flare-ups after endodontic treatment ported to be ineffective and unrelated to the incidence or
(Table 17,8,15-19). levels of posttreatment pain or flare-ups.15,16,18
Administration of antibiotics to prevent pulpal
and periapical pain or flare-ups before and after
treatment. Preoperative administration. An endodon- ABBREVIATION KEY. AB: Attrition bias. DM: Double-
tic flare-up is defined as “an acute exacerbation of an masked. MDR: Multidrug-resistant. RSG: Random sequence
asymptomatic pulpal or periradicular pathosis after the generation. SR: Selective reporting.

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 ORIGINAL CONTRIBUTIONS

In a randomized
controlled clinical trial, Records identified through Additional records identified
Fouad and colleagues16 database searching through other sources
investigated the effect (n = 69) (n = 1)
of penicillin on the
reduction of symptoms
and healing in patients
with a localized acute
Records after duplicates removed
apical abscess. Forty par- (n = 70)
ticipants who had a diag-
nosis of a necrotic pulp
and symptomatic peri-
apical periodontitis,
localized acute apical Records screened Records excluded
abscess, or both, received (n = 70) (n = 52)
appropriate endodontic
treatment. The in-
vestigators, using a
double-masked protocol, Full-text articles assessed
randomly assigned par- Full-text articles excluded
for eligibility
(n = 13)
ticipants to 1 of 3 groups: (n = 18)
1 group received penicillin
V potassium (500 mg,
2 tablets immediately
taken postoperatively
Studies included in
followed by 4 times per qualitative synthesis
day for 7 days), 1 group (n = 5)
received placebo, and 1
group received neither.
The investigators re-
ported that patients with
localized periapical pain Studies included in
quantitative synthesis
or swelling generally
(meta-analysis)
recovered quickly with (n = 0)
the appropriate end-
odontic treatment but
demonstrated no benefit Figure. Flow diagram of the literature search, according to the Preferred Reporting Items for Systematic Reviews
from the addition of and Meta-analyses. Source: Moher and colleages.9
penicillin. The in-
vestigators stated that all participants received 600 mg of received no medication. The researchers performed
ibuprofen 4 times daily for 24 hours. The investigators did evaluations in a double-masked fashion. They deter-
not report whether the participants’ need for additional mined statistical differences in the 3 groups by using
analgesia differed among the 3 groups. Also, 10 patients c2 tests, which demonstrated no significant differences
dropped out of the study and did not complete the treat- (P ¼ .68) among the 3 groups. The researchers reported
ment. Five of these 10 patients were in the group that did that prescribing penicillin prophylactically to control
not receive penicillin, and they returned with flare-ups. symptoms after treatment is not recommended or indi-
In a randomized, double-masked, placebo-controlled cated in cases of pulp necrosis and asymptomatic peri-
study, Walton and Chiappinelli15 investigated the pro- apical pathosis.
phylactic administration of penicillin to prevent flare-ups Henry and colleagues,18 in a prospective, randomized,
after endodontic treatment. The researchers randomly double-masked, placebo-controlled study, explored the
divided 80 participants who had a diagnosis of pulp effect of penicillin on patients with postoperative pain
necrosis and asymptomatic periapical periodontitis into 3 and swelling in symptomatic necrotic teeth. The 41
groups: group A received prophylactic administration of participants had reported for emergency endodontic
2 g of penicillin V and an additional 1 gram 6 hours after care and had received a diagnosis of pulp necrosis and
the treatment was completed, group B received placebo symptomatic periapical periodontitis. Each participant
with the same instructions as group A, and group C received the appropriate endodontic treatment.

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 ORIGINAL CONTRIBUTIONS

TABLE 1
Profile of outcome data and level of evidence in included studies.
STUDY SAMPLE STUDY TYPE DIAGNOSIS INTERVENTION OUTCOME RISK OF LEVEL OF
SIZE BIAS* EVIDENCE†
Walton and 80 Randomized, Pulp necrosis and Administration Administration of þ/–; DM‡; 1
Chiappinelli,15 double-masked, asymptomatic periapical of antibiotic penicillin did not RSG§; SR¶
1993 placebo-controlled periodontitis after endodontic reduce pain
study treatment
Fouad and 40 Randomized, Necrotic pulp and Administration Endodontic treatment þ/–; DM; 1
Colleagues,16 double-masked, symptomatic periapical of antibiotic was effective, with no AB#; RSG;
1996 placebo-controlled periodontitis, acute apical after endodontic demonstrable benefit SR
study abscess, or all of these treatment from penicillin
Nagle and 40 Prospective, Untreated symptomatic Administration Administration of –; DM; RSG 1
Colleagues,17 randomized, irreversible pulpitis of prophylactic penicillin did not
2000 double-masked, antibiotic before reduce pain
placebo-controlled treatment
study
Henry and 41 Randomized, Necrotic pulp with Administration Administration of –; DM; RSG 1
Colleagues,18 double-masked, symptomatic periapical of antibiotic penicillin did not
2001 placebo-controlled periodontitis after endodontic reduce pain
study treatment
Pickenpaugh 70 Randomized, Necrotic pulp with Administration Administration of –; DM; RSG 1
and double-masked, asymptomatic periapical of prophylactic amoxicillin did not
Colleagues,19 placebo-controlled periodontitis antibiotic before influence the incidence
2001 study treatment of endodontic flare-up
* Risk of Bias: –, low; þ/–, moderate.
† The Oxford Center for Evidence-based Medicine has updated its level of evidence scale. Refer to Center for Evidence-based Medicine7 and Howick
and colleagues.8
‡ DM: Double-masked.
§ RSG: Random sequence generation.
¶ SR: Selective reporting.
# AB: Attrition bias (incomplete outcome data).

TABLE 2
Risk of bias.
STUDY SELECTION SELECTION PERFORMANCE DETECTION ATTRITION REPORTING RISK OF
BIAS (RANDOM BIAS (ALLOCATION BIAS BIAS BIAS BIAS BIAS
SEQUENCE CONCEALMENT)
GENERATION)
Walton and Low Low Low Low Low Moderate Moderate
Chiappinelli,15 1993
Fouad and Low Unknown Low Low High Moderate Moderate
Colleagues,16 1996
Nagle and Low Low Low Low Low Low Low
Colleagues,17 2000
Henry and Low Low Low Low Low Low Low
Colleagues,18 2001
Pickenpaugh and Low Low Low Low Low Low Low
Colleagues,19 2001

Participants randomly received a 7-day oral dose of prevent infection and pain. The quality of the research
either penicillin (500 mg every 6 hours) or a placebo regarding postoperative medication with antibiotics was
control in a double-masked manner. The investigators as follows: 2 sets of investigators15,16 reported a moderate
reported that administration of penicillin postoperatively risk of bias and 1 group of investigators18 reported a low
did not significantly (P > .05) reduce pain, percussion risk of bias (Table 215-19).
pain, swelling, or the number of analgesic medications
used for symptomatic necrotic teeth with periapical DISCUSSION
radiolucencies. Overall, the best available clinical evidence indicates that
On the basis of the best available evidence, antibiotics there are no evidence-based reasons for prescribing
should not be prescribed postoperatively for patients antibiotics to prevent infection either before or after
with untreated symptomatic irreversible pulpitis to endodontic treatment unless there are sound and

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 ORIGINAL CONTRIBUTIONS

documented reasons for doing so (Table 17,8,14-19). Sys- populations are needed to address these concerns.
tematic administration of antibiotics does not relieve Another limitation may be that the 5 studies originated
painful pulpitis15-19 nor does it resolve localized peri- from only 2 dental schools. Although the implication is
radicular symptoms.15,16,18,19 The overall quality of the that more such research should be done on this impor-
studies was fair: 3 articles had low risk of bias (Table 2),17- tant topic, it is important to recognize the possibility that
19
and 2 studies had moderate risk of bias (Table 2).15,16 this unintended bias may have slanted the study design.
Specifically, the investigators of the 2 studies15,16 with Thus, more studies on these important subjects are
moderate risk of bias did not report whether and how warranted from other research groups and institutions.
much additional analgesia was consumed by the partic-
ipants, and 1 of these studies16 had an attrition bias that CONCLUSION
could have skewed the results. The use of systemic antibiotics generally is not indicated
The best available evidence does not mean that the during endodontic treatment to alleviate pain or decrease
studies are flawless and perfect.21 Having an evidence- the presence of infection. Generally, an accurate diag-
based approach indicates using the best available study nosis coupled with effective endodontic treatment will
results. At this time, the results of these studies represent decrease the number of microbes enough to result in a
the best clinically relevant research. healing outcome. To help limit the number of microbes
The results of our systematic review correspond with that are drug resistant, dental health care providers
the results of Keenan and colleagues22 who conducted a should not indiscriminately prescribe antibiotics when
Cochrane Systematic Review in an attempt to find evi- they are not indicated. n
dence concerning the effectiveness of prescribing anti-
biotics for patients experiencing irreversible pulpitis. The Dr. Aminoshariae is the director, Undergraduate Endodontics, School of
results of our investigation also correspond with the re- Dental Medicine, Case Western Reserve University, 2123 Abington Rd.,
sults of other studies,23,24 although these studies exhibited A280, Cleveland, OH 44106, e-mail [email protected]. Address correspon-
a lower level of evidence. Torabinejad and colleagues23 dence to Dr. Aminoshariae.
Dr. Kulild is a professor emeritus, Department of Endodontics, School of
reported that antibiotics were less effective than analge- Dentistry, University of Missouri-Kansas City, Kansas City, MO.
sics in reducing emergencies between appointments. In
another study,24 the investigators reported that the Disclosure. Drs. Aminoshariae and Kulild did not report any disclosures.
incidence of postoperative pain was unrelated to antibi- 1. Alanis AJ. Resistance to antibiotics: are we in the post-antibiotic era?
otics and that postoperative pain after obturation was Arch Med Res. 2005;36(6):697-705.
lower than that after a complete cleaning and shaping 2. Dellit TH, Owens RC, McGowan JE Jr, et al. Infectious Diseases So-
ciety of America and the Society for Healthcare Epidemiology of America
(5.83% versus 21.76%). In other words, effective end- guidelines for developing an institutional program to enhance antimicro-
odontic treatment will decrease the number of microbes, bial stewardship. Clin Infect Dis. 2007;44(2):159-177.
and antibiotics are not necessary for a healing outcome. 3. Rôças IN, Siqueira JF Jr. Detection of antibiotic resistance genes in
samples from acute and chronic endodontic infections and after treatment.
However, the results of our systematic review do not Arch Oral Biol. 2013;58(9):1123-1128.
correspond with the results of Morse and colleagues25-27 4. Davies J, Davies D. Origins and evolution of antibiotic resistance.
and Abbott and colleagues.28 These investigators25-28 Microbiol Mol Bio Rev. 2010;74(3):417-433.
treated every candidate in their studies with antibiotics. 5. Moraes LC, Só MV, Dal Pizzol Tda S, Ferreira MB, Montagner F.
Distribution of genes related to antimicrobial resistance in different oral
Thus, they did not have any control groups (that is, environments: a systematic review. J Endod. 2015;41(4):434-441.
patients treated with placebo), and consequently, their 6. Davies J, Davies D. Origins and evolution of antibiotic resistance.
reports do not add to the evidence-based scientific Microbiol Mol Biol Rev. 2010;74(3):417-433.
7. Centre for Evidence-based Medicine. Oxford Centre for Evidence-
literature. based Medicine: levels of evidence (March 2009). Available at: http://www.
The routine use of antibiotics in conjunction with cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-
endodontic treatment should be discouraged and is not 2009/. Accessed November 16, 2015.
8. Howick J, Chalmers I, Gloasziou P, et al; Oxford Centre for Evidence-
in line with following the principles of an evidence-based based Medicine (OCEBM) Levels of Evidence Working Group. OCEBM
practice. The exception would be when the spread of Levels of Evidence. Oxford Centre for Evidence-based Medicine. Available
infection is systemic and the patient is febrile.29 Thus, at: http://www.cebm.net/index.aspx?o¼5653. Accessed November 16, 2015.
conducting a detailed evaluation of each patient’s med- 9. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items
for systematic reviews and meta-analyses: the PRISMA statement. Ann
ical and dental history along with vital signs, performing Intern Med. 2009;151(4):264-269.
a thorough clinical examination, followed by deter- 10. Cochrane Consumers and Communication. Consumers and
mining an accurate diagnosis and a plan for appropriate Communication Group resources for authors. Tools, templates and
checklists. Review stage. Data extraction template. 2013. Available at:
treatment are all important factors for creating a favor- https://cccrg.cochrane.org/author-resources. Accessed November 16, 2015.
able environment in which healing can occur. 11. Shea BJ, Grimshaw JM, Wells GA, et al. Development of AMSTAR:
The limitations of the studies reviewed were that most a measurement tool to assess the methodological quality of systematic
of the investigators used empirical regimens regarding reviews. BMC Med Res Methodol. 2007;7(1):10.
12. Masood M, Thaliath ET, Bower EJ, Newton JT. An appraisal of the
dosage, frequency, and type of antibiotic prescribed. quality of published qualitative dental research. Community Dent Oral
Randomized controlled clinical trials with large study Epidemiol. 2011;39(3):193-203.

JADA ( )
- - http://jada.ada.org - 2016 5
 ORIGINAL CONTRIBUTIONS

13. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging 23. Torabinejad M, Kettering JD, McGraw JC, Cummings RR,
consensus on rating quality of evidence and strength of recommendations. Dwyer TG, Tobias TS. Factors associated with endodontic inter-
BMJ. 2008;336(7650):924-926. appointment emergencies of teeth with necrotic pulps. J Endod. 1988;
14. Higgins J, Green S, eds. Cochrane Handbook for Systematic Reviews of 14(5):261-266.
Interventions. Version 5.1.0 (updated March 2011). The Cochrane Collab- 24. Torabinejad M, Dorn SO, Eleazer PD, et al. Effectiveness of various
oration; 2011. Available at: http://community.cochrane.org/handbook. medications on postoperative pain following root canal obturation.
Accessed November 16, 2015. J Endod. 1994;20(9):427-431.
15. Walton RE, Chiappinelli J. Prophylactic penicillin: effect on post- 25. Morse DR, Furst ML, Lefkowitz RD, D’Angelo D, Esposito JV.
treatment symptoms following root canal treatment of asymptomatic A comparison of erythromycin and cefadroxil in the prevention
periapical pathosis. J Endod. 1993;19(9):466-470. of flare-ups from asymptomatic teeth with pulpal necrosis and asso-
16. Fouad AF, Rivera EM, Walton RE. Penicillin as a supplement in ciated periapical pathosis. Oral Surg Oral Med Oral Pathol. 1990;69(5):
resolving the localized acute apical abscess. Oral Surg Oral Med Oral 619-630.
Pathol Oral Radiol Endod. 1996;81(5):590-595. 26. Morse DR, Furst ML, Belott RM, Lefkowitz RD, Spritzer IB,
17. Nagle D, Reader A, Beck M, Weaver J. Effect of systemic penicillin on Sideman BH. Prophylactic penicillin versus penicillin taken at the first sign
pain in untreated irreversible pulpitis. Oral Surg Oral Med Oral Pathol of swelling in cases of asymptomatic pulpal-periapical lesions: a compar-
Oral Radiol Endod. 2000;90(5):636-640. ative analysis. Oral Surg Oral Med Oral Pathol. 1988;65(2):228-232.
18. Henry M, Reader A, Beck M. Effect of penicillin on postoperative 27. Morse DR, Furst ML, Belott RM, Lefkowitz RD, Spritzer IB,
endodontic pain and swelling in symptomatic necrotic teeth. J Endod. 2001; Sideman BH. Infectious flare-ups and serious sequelae following end-
27(2):117-123. odontic treatment: a prospective randomized trial on efficacy of antibiotic
19. Pickenpaugh L, Reader A, Beck M, Meyers WJ, Peterson LJ. Effect of prophylaxis in cases of asymptomatic pulpal-periapical lesions. Oral Surg
prophylactic amoxicillin on endodontic flare-up in asymptomatic, necrotic Oral Med Oral Pathol. 1987;64(1):96-109.
teeth. J Endod. 2001;27(1):53-56. 28. Abbott AA, Koren LZ, Morse DR, Sinai IH, Doo HS, Furst ML.
20. American Association of Endodontists. Glossary of terms: end- A prospective randomized trial on efficacy of antibiotic prophylaxis in
odontics. 2011. Available at: https://www.aae.org/patients/your-office-visit/ asymptomatic teeth with pulpal necrosis and associated periapical
glossary-of-terms.aspx#endodontics. Accessed November 16, 2015. pathosis. Oral Surg Oral Med Oral Pathol. 1988;66(6):722-733.
21. Sackett DL. Evidence-based medicine. Semin Perinatol. 1997;21(1):3-5. 29. Ellison S. The role of phenoxymethylpenicillin, amoxicillin, metro-
22. Keenan JV, Farman AG, Fedorowicz Z, Newton JT. Antibiotic use for nidazole and clindamycin in the management of acute dentoalveolar ab-
irreversible pulpitis. Cochrane Database Syst Rev. 2005;(2):CD004969. scesses: a review. Br Dent J. 2009;206(7):357-362.

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