The Use of Antibiotics in Odontogenic

Infections: What Is the Best Choice?

A Systematic Review
ao Roig Martins, DDS,* Otacı́lio Luiz Chagas Jr, DDS, MS, PhD,y
Jo~
^
Bibiana Dalsasso Velasques, DDS,z Angelo Niemczewski Bobrowski, DDS,x
Marcos Britto Correa, DDS, PhD,k and Marcos Antonio Torriani, DDS, MS, PhD{
Purpose: Odontogenic infections are a common problem in dentistry, and their treatment often requires
the use of antibiotics besides the removal of the source of infection, which frequently makes it more diffi-
cult for clinicians to make a decision regarding the choice of antibiotic. This study aimed to answer the
following questions through the Patient, Intervention, Comparison, Outcome (PICO) format: When
should antibiotics be used in dental infections (DIs)? Which are the most effective drugs? How long should
antibiotics be administered?
Materials and Methods: This was a systematic review using the PubMed, Scopus, and Cochrane data-
bases without restriction as to the period researched. The variables analyzed in each article were the num-
ber of odontogenic infections in each study, type of study, surgical intervention performed, antibiotics
administered, statistical differences between groups studied, and patients’ evolution after treatment.
Results: The search included 1,109 articles. After the full reading of 46 articles, 16 were included in the
final review and 30 were excluded. A sample of 2,197 DI cases was obtained, in which 15 different anti-
biotics were used, with a 98.2% overall cure rate.
Conclusions: The studies showed that antibiotics were prescribed only in situations of regional and/or
systemic body manifestations. In the case of DIs, once drainage has been performed and/or the cause of
infection has been removed, all antibiotics tested are equally effective with respect to clinical cure, and the
choice of antibiotics is not as successful as the local intervention treatment procedure. When the real need
for antibiotic therapy is detected, antibiotics should be used for the shortest time possible until the pa-
tient’s clinical cure is achieved.
Ó 2017 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 75:2606.e1-2606.e11, 2017

Dental infections (DIs) are a common problem, and
their treatment is sometimes debatable in dentistry.
They can range from low-level local infections, which
are usually easily treated without more serious conse-
quences, to severe life-threatening infections in the
fascial spaces, especially in patients in an immunocom-
promised or weak condition.1
Removal of the source of infection and surgical
drainage are the most important steps in DI treatment.
Nevertheless, in many cases the use of antibiotics is

Received from Federal University of Pelotas, Pelotas, Brazil.
*Author, University Hospital.
yAssociate Professor, Oral and Maxillofacial Surgery Residency
Program, University Hospital.
zResident, Oral and Maxillofacial Surgery Residency Program,
University Hospital.
xFormer Resident, Oral and Maxillofacial Surgery Residency
Program, University Hospital.
kAdjunct Professor, Federal University of Pelotas.
{Titular Professor, Oral and Maxillofacial Surgery Residency
Program, University Hospital.
Conflict of Interest Disclosures: None of the authors have any
relevant financial relationship(s) with a commercial interest.
Address correspondence and reprint requests to Dr Torriani:
School of Dentistry, Federal University of Pelotas–UFPel, Rua
Gonçalves Chaves, 457, Third Floor, RS 96015-560, Brazil; e-mail:
marcostorriani@gmail.com
Received March 14 2017
Accepted August 9 2017
Ó 2017 American Association of Oral and Maxillofacial Surgeons
0278-2391/17/31121-7
http://dx.doi.org/10.1016/j.joms.2017.08.017

2606.e1
MARTINS ET AL
required.1 It is incorrect, however, to think that every
infection requires antibiotics. There are situations in
which they are not helpful or are even contraindi-
cated. The dental surgeon’s lack of knowledge on
various principles of drug therapy with antibiotics
can lead him or her to unnecessarily opt for antibiotics,
thus characterizing a patient overtreatment situation.
Antibiotic overuse and improper indication by dentists
have been well documented. The US Centers for Dis-
ease Control and Prevention estimates that approxi-
mately one third of all prescribed antibiotics are
unnecessary.2
This study aimed to perform a systematic literature
review regarding the choice of antibiotics in odonto-
genic infection treatment. We hypothesized that if
the source of infection were removed, no considerable
differences between antibiotics would be found. This
article aimed to answer the following questions: 1)
In which DI treatment situations should antibiotics
be used? 2) Which drugs are the most effective? 3)
How long should antibiotics be administered?
Materials and Methods
For the purpose of obtaining answers to the afore-
mentioned questions, we designed and implemented
a systematic review based on The Cochrane Collabora-
tion’s recommendations for systematic reviews. The
study population included all English-language publi-
cations that addressed systemic antibiotic use in DI sit-
uations, without restriction as to the period
researched.
To be included in the study sample, publications had
to follow choice criteria as listed in Table 1. Descriptive
literature reviews, clinical reports, series of clinical re-
ports, and expert opinions were excluded. Cases of al-
veolitis, periodontitis, and infected odontogenic cysts
were not thought to be odontogenic infection cases.
The variables analyzed in each article included in this
systematic review were the number of odontogenic in-
fections in each study, type of study, surgical interven-
tion performed, antibiotics administered, statistical
differences between the groups studied, and
patients’ evolution after treatment. To search for
Table 1. CHOICE CRITERIA FOR FINAL INCLUSION
Specification of antibiotics used
Indication of No. of patients treated
Mention of whether incision and drainage and/or
removal of cause were performed
Description of patients’ evolution according to
intervention performed
Report of clinical follow-up of patients treated
Martins et al. Antibiotics and Odontogenic Infections. J Oral Max-
illofac Surg 2017.
2606.e2
articles, the PubMed (http://www.ncbi.nlm.nih.gov/
pubmed), Scopus (http://www.scopus.com/search/
form.url?zone=TopNavBar&origin=searchadvanced),
and Cochrane (http://cochrane.bireme.br/portal/php/
index.php) databases were used.
SEARCH STRATEGY
After a brief reading on the topic, a search was per-
formed using the following key words: ‘‘tooth and bac-
terial infections,’’ ‘‘periapical abcesses,’’ ‘‘periodontal
abcess,’’ ‘‘infection control, dental,’’ ‘‘pericoronitis,’’
‘‘odontogenic infections,’’ and ‘‘anti-bacterial agents.’’
Search lines adapted to each database are shown
in Table 2.
STUDY SELECTION
For all articles found, the titles and abstracts were
read by 2 previously trained reviewers (J.R.M. and
^ .N.B.). For initially selected articles, the full texts
A
were read, and they were submitted to the application
of our exclusion (Table 3) and inclusion (Table 1)
criteria for final inclusion. After the analyses were
compared, disagreements between reviewers were
settled through further discussion with senior evalua-
tors (M.A.T. and O.L.C.).
DATA COLLECTION
Once the complete reading of the articles was per-
formed, the following information of interest was
Table 2. LINE OF SEARCH USED FOR EACH DATABASE
Database Line of Search
PubMed ((((((((tooth[MeSH Terms]) AND bacterial
infections[MeSH Terms])) OR periapical
abscesses[MeSH Terms]) OR periodontal
abscess[MeSH Terms]) OR infection
control, dental[MeSH Terms]) OR
pericoronitis[MeSH Terms]) OR
odontogenic infections[Title/Abstract])
AND anti-bacterial agents[MeSH Terms]
Scopus (TITLE-ABS-KEY(tooth and ‘‘bacterial
infection’’) OR TITLE-ABS-KEY(periapical
abscess) OR TITLE-ABS-KEY(pericoronitis)
OR TITLE-ABS-KEY(periodontal abscess)
OR TITLE-ABS-KEY(odontogenic
infection)) AND TITLE-ABS-KEY(anti-
bacterial agents)
Cochrane (tooth AND bacterial infections) OR
periapical abscesses OR periodontal
abscess OR infection control, dental OR
pericoronitis OR odontogenic infections
AND anti-bacterial agents
Martins et al. Antibiotics and Odontogenic Infections. J Oral Max-
illofac Surg 2017.
2606.e3
Table 3. EXCLUSION CRITERIA FOR FINAL INCLUSION
Descriptive reviews in literature, reports of clinical cases,
series of clinical cases, and expert opinions
Studies involving cases of alveolitis, periodontitis, and
infected odontogenic cysts
Martins et al. Antibiotics and Odontogenic Infections. J Oral Max-
illofac Surg 2017.
obtained: number of DI cases, type of study, local inter-
vention performed, antibiotics used, and patient out-
comes. All data were collected and tabulated using a
Microsoft Excel spreadsheet (Microsoft Office Profes-
sional Plus 2010; Microsoft, Redmond, WA).
QUALITY EVALUATION
Included articles were submitted to methodologic
quality assessment, which included PRISMA
(Preferred Reporting Items for Systematic Reviews
and Meta-Analyses),3 CONSORT (Consolidated Stan-
dards of Reporting Trials),4 QUOROM (Quality of Re-
porting of Meta-Analyses),5 MOOSE (Meta-analysis of
Observational Studies in Epidemiology),6 and STROBE
(Strengthening the Reporting of Observational Studies
in Epidemiology)7 statement criteria, to check the
strength of the scientific evidence available in the cur-
rent literature for clinical decision making. The classi-
fication of potential risk of bias of each study followed
the criteria used by Bobrowski et al,8 namely, popula-
tion (sample) random selection, inclusion and exclu-
sion criteria definitions, follow-up loss reports,
validated measurements, and statistical analysis.
Studies that included all the aforementioned criteria
were classified as having a low risk of bias, those that
did not include 1 criterion were classified as having a
moderate risk of bias, and those that did not include
2 or more criteria were classified as having a high
risk of bias.
Results
The study, updated up to December 6, 2015, yielded
1,109 results. After article titles and abstracts were
read and duplicates were excluded, 46 potentially rele-
vant articles were obtained, which were fully ac-
cessed, analyzed, and submitted to the application of
our inclusion and exclusion criteria. Thirty articles
were excluded after full reading. These are listed in
Table 4 along with the reasons for exclusion. Sixteen
studies were included in the final systematic review
sample (Table 5). The selection and assessment pro-
cess flowchart is shown in Figure 1.
As for the quality assessment determining the risk of
bias in each included study, 6 articles showed a low
risk of bias, 4 showed a moderate risk, and 6 showed
ANTIBIOTICS AND ODONTOGENIC INFECTIONS
a high risk. The articles and their respective assess-
ments are shown in Table 6.
After common data grouping, a sample of 2,197 DIs
from 16 studies, in which the number of patients
ranged from 21 to 759 per article, was obtained. All
cases involved local intervention, whether drainage,
removal of cause, or both. Of the patients, 55 were
treated with local interventions whereas 2,142 were
treated with 1 or more of the 15 antibiotics mentioned
in the studies. The overall cure rate with the antibi-
otics of choice was obtained from the included
studies’ reporting on how many patients were cured
and how many showed treatment failure, with 98.2%
of patients cured. Treatment failure occurred in 39
cases, 66.7% of which had been treated with
drugs in the macrolide group (roxithromycin in 5,
erythromycin in 8, and azithromycin in 13), 7.9%
with b-lactam antibiotics (ampicillin in 1 and
amoxicillin-clavulanate in 6), and 15.3% with novobi-
ocin (in 6), and the therapeutic approach had to be
revised. However, the latter situation was reported in
only 2 studies. Treatment with ampicillin failed in 1 pa-
tient, who was afterward prescribed clindamycin, and
6 patients who did not respond to novobiocin were
administered penicillin. All of the patients showed suc-
cessful results with the new therapy.9,10
Drugs in the b-lactam antibiotic group were the
most used in the assessed studies, especially the peni-
cillin subgroup. Tables 7 and 8 show the number of ar-
ticles in which each antibiotic was used, the number
of patients treated with each antibiotic, and the num-
ber of patients with treatment failure.
Six studies reported adverse antibiotic effects in their
findings, including nausea, vomiting, dizziness, itchy
skin, and gastrointestinal disorders, the latter being
the most frequent. The criteria used to evaluate patient
outcomes were based mainly on clinical features (pain,
swelling, fever, and lymphadenopathy), although some
studies used additional tests for assessment, such as
blood counts, leukocyte counts, and urine tests.
Discussion
The study aimed to perform a systematic literature
review on the use of antibiotics in DI treatment. We
believed that if the source of infection were removed,
there would be no significant differences in antibiotic
choice. The aim of the study was to determine when to
use antibiotics in DIs, which drug is the most effective,
and how long the drug should be administered.
Despite controversies, DIs have known treatment
pathways, and the results of this systematic review
allow setting some principles of treatment for this
type of clinical picture.
To discuss the issues involving antibiotic therapy in
DIs, it was assumed that for any local interventions
MARTINS ET AL 2606.e4

Table 4. ARTICLES EXCLUDED AFTER ELIGIBILITY ASSESSMENT AND REASONS FOR EXCLUSION

Authors Year Type of Study Reason for Exclusion*

Cope et al11 2014 Systematic review 1

Chi et al12 2014 Retrospective 2
Farmahan et al13 2014 Retrospective 2, 3
Loyola-Rodrigues et al14 2014 Laboratorial 4
Kara et al15 2014 Retrospective 2, 3, 4
Fedorowicz et al16 2013 Systematic review 5
Rasteniene et al17 2015 Retrospective 3
Gr€onholm et al18 2013 Retrospective 2
Lee and Kanagalingam19 2011 Retrospective 2
Flynn20 2011 Systematic review 1
Saito et al21 2011 Retrospective 2, 3
Akinbami et al22 2010 Prospective 2, 3
Rao et al23 2010 Prospective 3
Carter and Layton24 2009 Retrospective 2
Marioni et al25 2008 Retrospective 3
Warnke et al26 2008 Retrospective 3
Youssef et al27 2007 Literature review 2
Al-Nawas and Maeurer28 2008 Prospective 3
Ndukwe et al29 2007 Prospective 3, 7
Rega et al30 2006 Retrospective 2
Flynn et al31 2006 Prospective 6
Flynn et al32 2006 Prospective 7
Marioni et al33 2006 Retrospective 2, 3
Uluibau et al34 2005 Retrospective 2, 3
Wang et al35 2005 Retrospective 2, 3
Bross-Soriano et al36 2004 Retrospective 2, 3
Matthews et al37 2003 Systematic review 1
Bridgeman et al38 1995 Retrospective 2, 3, 4, 7
Har-El et al39 1994 Retrospective 2, 3
Lo Bue et al40 1993 Randomized clinical trial 7
* The reasons for exclusion were as follows: 1) failed to collect data from cases without checking reference articles, 2) did not
mention antibiotics used in treatment or their dosage, 3) did not describe separate evolution of patients for each antibiotic
group, 4) did not include clinical follow-up of patients who underwent antibiotic therapy, 5) did not deal with dental infections,
6) mentioned only results from other studies, and 7) included clinical situations not considered by method.
Martins et al. Antibiotics and Odontogenic Infections. J Oral Maxillofac Surg 2017.

performed in patients—basically drainage (incision or removal of the cause, such as exodontics or

channel route) and removal of the cause of infection
(mainly extraction and endodontics)—as well as for
all studies in this review, including prospective
studies, medically compromised patients were not
included. In an ideal treatment situation, drainage
and removal of the cause of infection are performed
during the first contact with the patient; however,
there are situations that do not allow this to happen.
Local intervention was used as part of treatment in
all study analyses, but some studies involved cases in
which drainage was not possible or necessary and
removal of the cause as a single local intervention
was performed.41,42 However, in a DI at an advanced
stage, the opposite often occurs: An abscess that
could be drained is present, but the patient offers
unfavorable clinical conditions for the procedure for
endodontics. In such cases, drainage must be
performed immediately, postponing the removal of
the infection focus until clinical conditions are more
favorable.10,43,44
The first question this systematic review sought to
answer regarding the use of antibiotics in DIs was
when to use them. All studies included in the review
involved DIs at stages at which there were either
regional or systemic manifestations of the organism
to the infection. Brennan et al45 compared a group
receiving penicillin with a group receiving no antibi-
otics in patients with a toothache who had sought
emergency assistance; they found that the use of anti-
microbials did not prevent DI development, thus
showing that antibiotics commonly prescribed for a
toothache do not prevent the development of
 2606.e5
Table 5. ARTICLES INCLUDED IN FINAL REVIEW

No. of No. of DIs: ATBs SSD Between

Authors DIs Type of Study Surgical Intervention Administered Groups Patient Evolution and Comments

Igoumenakis et al46 179 Prospective Extraction or no intervention 91: AMP-SULB, MET, and Yes There was a statistically
(2015) exodontia significant association
86: AMP-SULB and MET between extraction and
infection resolution time.
Cachovan et al47 (2011) 31 Double-blind randomized I&D and/or removal of cause 15: MXF No MXF showed faster pain
clinical trial (extraction, RCT) during 16: CLI reduction and clinical
study improvement, but both were
effective.
Matijevic et al48 (2009) 90 Randomized clinical trial I&D and/or removal of cause 30: AMX Yes The ATB groups showed a
(extraction) during study 30: CEF reduced treatment time
30: surgical treatment only compared with patients who
were treated with only surgery.
Al-Nawas et al49 (2009) 21 Randomized clinical trial I&D during study 10: MXF No AMX-CLAV showed remission of
11: AMX-CLAV clinical signs and symptoms in
a shorter period than MXF.
Chardin et al41 (2009) 81 Double-blind randomized Patients without need for 42: AMX for 3 days No There were no differences in
clinical trial drainage; removal of 39: AMX for 7 days AMX treatment for 3 or 7 days.
cause during study
Rush et al50 (2007) 60 Randomized clinical trial I&D and/or removal of 31: CLI No The groups showed similar
cause (extraction, RCT) 29: AMP-SULB results.
during study

ANTIBIOTICS AND ODONTOGENIC INFECTIONS

Kuriyama et al51 (2005) 112 Prospective study
Al-Belasy and Hairam44 60 Randomized clinical trial
(2003)
Adriaenssen52 (1998) 292 Randomized clinical trial
I&D during study; removal 65: PNC V or AMX No Patients who underwent I&D had
of cause after study 24: PNC V and MET a faster evolution than those
2: ERI who underwent drainage
9: MET through the pulp chamber,
6: ERI and MET, 400 mg regardless of ATB used. All
6: AMX-CLAV ATBs were clinically effective.
I&D and removal of cause as 20: AZI Yes The ATB groups had a reduced
soon as conditions were 20: ERI treatment time compared with
favorable during study 20: without ATBs patients who underwent only
surgery. AZI reduced swelling
in a shorter period than ERI.
Patients without need for 144: AZI No The groups showed similar
immediate drainage; 148: AMX-CLAV results.
removal of cause during
study
 MARTINS ET AL
Martin et al53 (1997) 759 Prospective I&D and/or removal of cause 546: AMX Not applicable In 748 patients, resolution of
(extraction) during study 141: CLI signs and systemic symptoms
72: ERI presented from 2 to 3 days.
Eleven patients did not show
improvement because of
drainage failure at the first
consultation and underwent a
new drainage procedure.
Fazakerley et al54 100 Double-blind randomized Drainage through incision 33: AMX Yes Within 2 days, CFD showed a
(1993) clinical trial or canal during study 33: CFD statistically significantly
34: PNC V greater remission in pain,
temperature, and edema. After
5 days, all ATBs produced the
same results.
Deffez et al55 (1992) 176 Double-blind randomized When needed, I&D during 85: ROX Not applicable ATB efficacy was the same with
clinical trial study 91: ERI or without associated surgery.
Mangundjaja and 106 Double-blind randomized I&D during study; removal 54: AMP No The groups showed similar
Hardjawinata9 (1990) clinical trial of cause after study 52: CLI results.
Gilmore et al43 (1988) 55 Double-blind randomized I&D during study; removal 27: PNC V Not applicable The groups showed similar
clinical trial of cause after study 28: CLI results.
Hood56 (1978) 24 Randomized clinical trial I&D and removal of cause 18: MET Not applicable The groups showed similar
during study 19: PNC G and PNC V results.
Brown et al10 (1958) 51 Noncontrolled clinical Surgery when conditions 51: NVB Not applicable Of the patients, 45 responded
study were favorable during positively to ATBs and showed
study resolution of the case. Six
patients did not respond well,
and ATB therapy was changed
to PNC.
Abbreviations: AMP, ampicillin; AMX, amoxicillin; ATB, antibiotic; AZI, azithromycin; CEF, cephalexin; CFD, cephradine; CLAV, potassium clavulanate; CLI, clindamycin; DI, dental
infection; ERI, erythromycin; I&D, incision and drainage; MET, metronidazole; MXF, moxifloxacin; NVB, novobiocin; PNC, penicillin; RCT, root canal therapy; ROX, roxithromy-
cin; SSD, statistically significant difference; SULB, sulbactam.
Martins et al. Antibiotics and Odontogenic Infections. J Oral Maxillofac Surg 2017.

2606.e6
2606.e7
FIGURE 1. Flow diagram for study selection.
Martins et al. Antibiotics and Odontogenic Infections. J Oral Maxillofac Surg 2017.
infection. These findings appear to confirm that anti-
biotic therapy recommendation in situations in which
there is no regional or systemic involvement is unnec-
essary; rather, antibiotics are recommended only in cir-
cumstances in which the patient’s immune defenses
are unable to control infection, which can be deter-
mined through signals and clinical symptoms indi-
cating its spread, such as pronounced edema
(cellulite), limited mouth opening, tachycardia,
dysphagia, general malaise, and fever.57 Other studies
have confirmed the role of local intervention. Igoume-
nakis et al46 conducted a prospective study and found
a statistically significant association between the in-
fected element’s extraction and the infection’s resolu-
tion time, suggesting that in life-threatening cases,
extraction of the involved tooth should be considered,
even when it is restorable. Al-Belasy and Hairam44 and
Matijevic et al48 reported that a total of 55 patients
with clinical signs and symptoms that could have justi-
fied antibiotic therapy were treated with drainage and/
or removal of the cause and even so obtained clinical
ANTIBIOTICS AND ODONTOGENIC INFECTIONS
condition resolution. However, the same patients,
when compared with groups of patients who were
prescribed antibiotics plus local intervention, showed
clinical sign and symptom remission within a signifi-
cantly longer period, which is proof that, when prop-
erly prescribed, antibiotics are excellent adjuvants and
should be used in these situations. Otherwise, the pre-
scriber will give no chance for the organism to control
the infection, contribute to resistant bacterium selec-
tion, and subject the patient to the many adverse ef-
fects that these drugs can cause, increasing
treatment costs.
The second question was which drug is the most
effective. The findings of this review show that such
questioning only makes sense from the moment the
antibiotic therapy is performed in association with
some local intervention. The articles included in the
study showed that when drainage and/or removal of
the cause of infection was properly carried out, all
the tested antibiotics were equally effective with
respect to clinical cure. Only 2 studies found
MARTINS ET AL 2606.e8

Table 6. QUALITY ASSESSMENT OF INCLUDED ARTICLES

Random Definition of Reporting of Estimated

Selection in Inclusion and Loss to Validated Statistical Potential
Authors Year Population Exclusion Criteria Follow-Up Measurements Analysis Risk of Bias

Igoumenakis et al46 2015 Yes Yes Yes Yes Yes Low

Cachovan et al47 2011 Yes Yes No Yes Yes Moderate
Matijevic et al48 2009 Yes Yes No Yes Yes Moderate
Al-Nawas et al49 2009 Yes Yes Yes Yes Yes Low
Chardin et al41 2009 Yes Yes Yes Yes Yes Low
Rush et al50 2007 Yes No No No Yes High
Kuriyamaet al51 2005 Yes Yes No Yes Yes Moderate
Al-Belasy and Hairam44 2003 Yes Yes Yes Yes Yes Low
Adriaenssen52 1998 Yes Yes No Yes Yes Moderate
Martin et al53 1997 Yes Yes No Yes No High
Fazakerley et al54 1993 Yes Yes Yes Yes Yes Low
Deffez et al55 1992 Yes Yes No Yes No High
Mangundjaja and 1990 Yes Yes Yes Yes Yes Low
Hardjawinata9
Gilmore et al43 1988 Yes Yes No Yes No High
Hood et al56 1978 Yes Yes No No No High
Brown et al10 1958 Yes No No Yes No High
Martins et al. Antibiotics and Odontogenic Infections. J Oral Maxillofac Surg 2017.

statistically significant differences between antibi-
otics, but these referred to the clinical sign and symp-
tom remission period rather than final treatment
efficacy.44,54 Therefore, it is reasonable to infer that
antibiotics do not differ as to their degree of efficacy
but rather with reference to the total treatment
period, even when the continued increase in
bacterial resistance episodes is considered.
This review shows that the correct diagnosis and
local intervention should be given the greatest atten-
tion by the surgeon, with the choice of antibiotic play-
ing a secondary role, provided that the antibiotic used
fits in with the action spectrum that has been proved
effective in DI treatment. The safety of antibiotic use
and the product cost, besides the prescriber’s clinical
experience, should be taken into account.
The articles in our study showed that penicillin is
the most used and, therefore, first-choice drug, which
can be associated with b-lactamase inhibitors if
needed. Flynn et al58 reported that 19% of the micro-
organisms collected from their patients were peni-
cillin resistant, and approximately 21% of their pa-
tients had treatment failure with penicillin.
Conversely, Kuriyama et al51 reported that clinical out-
comes had not changed, showing a good clinical
response even when 37.5% of the micro-organisms
collected from their patients were penicillin resistant.
These data show that the presence of antibiotic-

Table 7. NUMBER OF PATIENTS TREATED WITH b-LACTAM ANTIBIOTICS AND NUMBER OF ARTICLES IN WHICH THEY
WERE MENTIONED

AMX AMX-CLAV AMP AMP-SULB PNC V PNC G CEF CFD

No. of articles in which antibiotic was used 5 5 2 2 3 1 1 1

No. of patients treated with antibiotic 690 157 54 208 104 19 30 33
No. of patients with treatment failure 0 6 1 0 0 0 0 0

Note: Kuriyama et al51 stated that a group of 65 patients were given either AMX or PNC V but did not specify how many patients
received which antibiotic. These patients are not included in this table. In addition, there were drug combinations in some
studies, so a patient may have been prescribed more than 1 antibiotic mentioned in this table.
Abbreviations: AMP, ampicillin; AMX, amoxicillin; CEF, cephalexin; CFD, cephradine; CLAV, potassium clavulanate; PNC, peni-
cillin; SULB, sulbactam.
Martins et al. Antibiotics and Odontogenic Infections. J Oral Maxillofac Surg 2017.
2606.e9 ANTIBIOTICS AND ODONTOGENIC INFECTIONS

Table 8. NUMBER OF PATIENTS TREATED WITH ANTIBIOTICS OTHER THAN b-LACTAM ANTIBIOTICS AND NUMBER OF
ARTICLES IN WHICH THEY WERE MENTIONED

MXF CLI MET ERI AZI ROX NVB

No. of articles in which antibiotic was used 2 5 2 5 2 1 1

No. of patients treated with antibiotic 25 268 218 191 164 85 51
No. of patients with treatment failure 0 0 0 8 13 5 6

Note: There were drug combinations in some studies, so a patient may have been prescribed more than 1 antibiotic mentioned in
this table.
Abbreviations: AZI, azithromycin; CLI, clindamycin; ERI, erythromycin; MET, metronidazole; MXF, moxifloxacin; NVB, novo-
biocin; ROX, roxithromycin.
Martins et al. Antibiotics and Odontogenic Infections. J Oral Maxillofac Surg 2017.

resistant bacteria does not necessarily mean there will
be treatment failure. However, in the case of failure or
allergy, clindamycin and the macrolide class of drugs,
particularly azithromycin, are viable alternatives,
together with moxifloxacin, which has shown prom-
ising results in clinical trials. Furthermore, Farmahan
et al57 reported that 95% of patients were discharged
before antibiogram results were obtained. This finding
may raise questions regarding the therapeutic value of
culture and sensitivity tests in any odontogenic infec-
tion situation, which perhaps could be more
adequately used in more serious situations in which
there is evidence of the need to use more spe-
cific drugs.
The third question that this systematic review
sought to answer was how long antibiotics should be
given. On the basis of the literature reviewed, one
cannot make a decision based on scientific evidence
as to the optimal duration of antibiotic therapy in
DIs. Two studies analyzed this theme. Chardin et al41
compared amoxicillin treatment for 3 and 7 days and
found no statistically significant differences between
groups, suggesting that patients’ exposure to antibi-
otics should be reduced. Similarly, Martin et al53 re-
ported that of 759 patients who underwent drainage
and/or removal of the cause and in whom antibiotic
therapy had been initiated on the first day, 98.6%
showed infection resolution within 2 or 3 days and
had drug treatment interrupted without the need for
any other new intervention; they claimed that in
most DI cases, the duration of antibiotic therapy can
be limited to 2 or 3 days safely, once some local inter-
vention has been performed. By knowing that the pro-
longed use of antibiotics only serves the purpose of
selecting resistant bacterial species,57 these studies
may point out that, once drainage and/or removal of
the cause of infection has been performed, antibiotic
therapy does not require a long cycle but rather only
the patient’s follow-up to evaluate his or her evolution,
preferably on a daily basis; its duration should be
defined in accordance with clinical sign and
symptom remission. These findings show that clinical
parameters are the major indicators of the odonto-
genic infection picture evolution; however, additional
tests should be performed when necessary.
Sources of bias in this systematic review include
publication bias (unpublished studies were not read)
and language (only articles in English were analyzed).
Nonrandomized and nonblinded clinical trials are
more likely to show favorable results in the treatment
group than in the control group.59 According to Schulz
et al,60 inadequate randomization methods can over-
state the estimated effect of treatment by up to 41%,
and when these methods are not well described, the
effect may be approximately 30%. Although all clinical
trials included in our study were randomized—most of
which were double blinded—some did not clearly
describe their randomization methods. Two prospec-
tive studies were included that, although having
met all criteria, did not show methods as selective as
their clinical trials.
This study faced some restrictions. The ideal study
to answer the guiding questions would have been a
double-blinded randomized clinical trial to test all ma-
jor antibiotics under the same conditions at different
treatment times. Because there are no such studies, an-
swers to these questions based on conclusions from
different studies that tested different antibiotics
were sought.
In conclusion, in DI cases, once drainage and/or
removal of the cause of infection has been performed,
all antibiotics tested were equally effective with
respect to clinical cure. Therefore, most of the sur-
geon’s attention should be directed toward proper
drainage and/or removal of the infection focus inas-
much as the choice of antibiotics is not as successful
in the treatment as local action. Antibiotics are only
recommended in regional and/or systemic body mani-
festation situations and should be used as an aid to
fight infection once the major treatment is surgical.
When the real need for antibiotic therapy is deter-
mined, this should be administered for the shortest
possible period until the clinical cure of the patient
is obtained. We suggest that further randomized
MARTINS ET AL
clinical trials using rigorous methods should be per-
formed to expand knowledge on antibiotic use in
DI treatment.
References
1. Gill Y, Scully C: Orofacial odontogenic infections: Review of
microbiology and current treatment. Oral Surg Oral Med Oral Pa-
tol 70:155, 1990
2. Swift JQ, Gulden WS: Antibiotic therapy—Managing odonto-
genic infections. Dent Clin N Am 46:623, 2002
3. Moher D, Liberati A, Tetzlaff J, et al: Preferred Reporting Items
for Systematic Reviews and Meta-Analyses: The PRISMA state-
ment. J Clin Epidemiol 62:1006, 2009
4. Moher D, Jones A, Lepage L, CONSORT Group (Consolidated
Standards for Reporting of Trials): Use of the CONSORT state-
ment and quality of reports of randomized trials: A comparative
before-and-after evaluation. JAMA 285:1992, 2001
5. Moher D, Cook DJ, Eastwood S, et al: Improving the quality of
reports of meta-analyses of randomized controlled trials: The
QUOROM statement. Quality of Reporting of Meta-Analyses.
Lancet 354:1896, 1999
6. Stroup DF, Berlin JA, Morton SC, et al: Meta-analyses of observa-
tional studies in epidemiology: A proposal for reporting. Meta-
analysis of Observational Studies in Epidemiology (MOOSE)
group. JAMA 283:2008, 2000
7. von Elm E, Altman DG, Egger M, et al: The Strengthening the Re-
porting of Observational Studies in Epidemiology (STROBE)
statement: Guidelines for reporting observational studies. Lan-
cet 370:1453, 2007
8. Bobrowski AN, Sonego CL, Chagas Junior OL: Postoperative
infection associated with mandibular angle fracture treatment
in the presence of teeth on the fracture line: A systematic review
and meta-analysis. Int J Oral Maxillofac Surg 42:1041, 2013
9. Mangundjaja S, Hardjawinata K: Clindamycin versus ampicillin in
the treatment of odontogenic infections. Clin Ther 12:242, 1990
10. Brown R, Thomassen PR, Singler JM: The use of novobiocin for
treatment of infections of odontogenic origin. Oral Surg Oral
Med Oral Patol 11:598, 1958
11. Cope A, Francis N, Wood F, Mann MK, Chestnutt IG: Systemic an-
tibiotics for symptomatic apical periodon-titis and acute apical
abscess in adults. Status and date: New, published 6, 2014.
12. Chi TH, Tsao YH, Yuan CH: Influences of patient age on deep
neck infection: clinical etiology and treatment outcome. Otol
Head Neck Surg 151:586, 2014
13. Farmahan S, Tuopar D, Ameerally PJ: The clinical relevance of
microbiology specimens in head and neck space infections of
odontogenic origin. Br J Oral Maxillofac Surg 52:629, 2014
14. Loyola-Rodriguez JP, Garcia-Cortes JO, Martinez-Martinez RE,
et al: Molecular identification and antibiotic resistant bacteria
isolated from primary dentition infections. Aust Dent J 59:497,
2014
15. Kara A, Ozsurekci Y, Tekcicek M, et al: Length of hospital stay
and management of facial cellulitis of odontogenic origin in chil-
dren. Pediatr Dent 36:18E, 2014
16. Fedorowicz Z, Van Zuuren EJ, Farman AG, et al: Antibiotic use
for irreversible pulpitis. Cochrane Database Syst Rev 12, 2013
17. Rasteniene_ R, P uriene_ A, Aleksej
uniene_ J, et al: Odontogenic
maxillofacial infections: A ten-year retrospective analysis. Surg
Infect 16:305, 2015
18. Gr€onholm L, Lemberg KK, Tj€aderhane L, et al: The role of unfin-
ished root canal treatment in odontogenic maxillofacial infec-
tions requiring hospital care. Clin Oral Invest 17:113, 2013
19. Lee YQ, Kanagalingam J: Deep neck abscesses: the Singapore
experience. Eur Arch Oto Rhino Laryngol 268:609, 2011
20. Flynn TR: What are the antibiotics of choice for odontogenic in-
fections, and how long should the treatment course last? Oral
Maxillofac Surg Clin N Am 23:519, 2011
21. Saito CTMH, Gulinelli JL, Mar~ao HF, et al: Occurrence of odonto-
genic infections in patients treated in a postgraduation program
on maxillofacial surgery and traumatology. J Craniofac Surg 22:
1689, 2011
2606.e10
22. Akinbami BO, Akadiri O, Gbujie DC: Spread of odontogenic in-
fections in Port Harcourt, Nigeria. J Oral Maxillofac Surg 68:
2472, 2010
23. Rao DD, Desai A, Kulkarni RD, et al: Comparison of maxillofacial
space infection in diabetic and nondiabetic patients. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 110:e7, 2010
24. Carter LM, Layton S: Cervicofacial infection of dental origin pre-
senting to maxillofacial surgery units in the United Kingdom: a
national audit. Br Dent J 206:73, 2009
25. Marioni G, Rinaldi R, Staffieri C, et al: Deep neck infection with
dental origin: analysis of 85 consecutive cases (2000 -2006). Acta
Otolaryngol 128:201, 2008
26. Warnke PH, Becker ST, Springer IN, et al: Penicillin compared
with other advanced broad spectrum antibiotics regarding anti-
bacterial activity against oral pathogens isolated from odonto-
genic abscesses. J Craniomaxillofac Surg 36:462, 2008
27. Youssef W, D’innocenzo R, Mehra P: Antibiotic therapy in the
management of severe odontogenic infections: a comparison
of two treatment regimens. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 106:505, 2008
28. Al-Nawas B, Maeurer M: Severe versus local odontogenic bacte-
rial infections: comparison of microbial isolates. Eur Surg Res 40:
220, 2008
29. Ndukwe KC, Ugboko VI, Akinwande JA, et al: Bacterial infec-
tions of the head and neck fascial spaces in Nigerians. West
Afr J Med 26:126, 2007
30. Rega AJ, Aziz SR, Ziccardi VB: Microbiology and antibiotic sensi-
tivities of head and neck space infections of odontogenic origin.
J Oral Maxillofac Surg 64:1377, 2006
31. Flynn TR, Shanti RM, Levi MH, et al: Severe odontogenic infec-
tions, part 1: Prospective report. J Oral Maxillofac Surg 64:
1093, 2006
32. Flynn TR, Shanti RM, Hayes C: Severe odontogenic infections,
part 2: prospective outcomes study. J Oral Maxillofac Surg 64:
1104, 2006
33. Marioni G, Castegnaro E, Staffieri C, et al: Deep neck infection in
elderly patients. A single institution experience (2000–2004).
Aging Clin Exp Res 18:127, 2006
34. Uluibau IC, Jaunay T, Goss NA: Severe odontogenic infections.
Aust Dent J 50:S74, 2005
35. Wang J, Ahani A, Pogrel MA: A five-year retrospective study of
odontogenic maxillofacial infections in a large urban public hos-
pital. Int J Oral Maxillofac Surg 34:646, 2005
36. Bross-Soriano D, Arrieta-G omez JR, Prado-Calleros H, et al: Man-
agement of Ludwig’s angina with small neck incisions: 18 years
experience. Otol Head Neck Surg 130:712, 2014
37. Matthews DC, Sutherland S, Basrani B: Emergency management
of acute apical abscesses in the permanent dentition: a system-
atic review of the literature. J Can Dent Assoc 69:660, 2003
38. Bridgeman A, Wiesenfeld D, Hellyar A, Sheldon W: Major maxil-
lofacial infections. An evaluation of 107 cases. Aust Dent J 40:
281, 1995
39. Har-El G, Aroesty JH, Shaha A, Lucente FE: Changing trends in
deep neck abscess: a retrospective study of 110 patients. Oral
Surg Oral Med Oral Pathol 77:446, 1994
40. Bue AL, Sammartino R, Chisari G, et al: Efficacy of azithromycin
compared with spiramycin in the treatment of odontogenic in-
fections. J Antimicrob Chemother 31:119, 1993
41. Chardin H, Yasukawa K, Nouacer N, et al: Reduced susceptibility
to amoxicillin of oral streptococci following amoxicillin expo-
sure. J Med Microbiol 58:1092, 2009
42. Andriaenssen CF: Comparison of the efficacy, safety and tolera-
bility of azithromycin and co-amoxiclav in the treatment of acute
periapical abscesses. J Int Med Res 26:257, 1998
43. Gilmore WC, Jacobus NV, Gorbach SL, et al: A prospective
double-blind evaluation of penicillin versus clindamycin in the
treatment of odontogenic infections. J Oral Maxillofac Surg 46:
1065, 1988
44. Al-Belasy F, Hairam AR: The efficacy of azithromycin in the treat-
ment of acute infraorbital space infection. J Oral Maxillofac Surg
61:310, 2003
45. Brennan MT, Runyon MS, Batts JJ, et al: Odontogenic signs and
symptoms as predictors of odontogenic infection: A clinical
trial. J Am Dent Assoc 137:626, 2006
2606.e11
46. Igoumenakis D, Giannakopoulos N, Parara E, et al: Effect of caus-
ative tooth extraction on clinical and biological parameters of
odontogenic infection: A prospective clinical trial. J Oral Maxil-
lofac Surg 73:1254, 2015
47. Cachovan G, B€ oger RH, Giersdorf I, et al: Comparative efficacy
and safety of moxifloxacin and clindamycin in the treatment
of odontogenic abscesses and inflammatory infiltrates: a phase
II, double-blind, randomized trial. Antimicrob Agents Chemo-
ther 55:1142, 2011
48. Matijevic S, Lazi Z, Kuljı́c-Kapulica N, Nonkovic Z: Empirical
antimicrobial therapy of acute dentoalveolar abscess. Vojnosanit
Pregl 66:544, 2009
49. Al-Nawas B, Walter C, Morbach T, et al: Clinical and microbiolog-
ical efficacy of moxifloxacin versus amoxicillin/clavulanic acid
in severe odontogenic abscesses: a pilot study. Eur J Clin Micro-
biol Infect Dis 28:75, 2009
50. Rush DE, Abdel-Haq N, Zhu J, et al: Clindamycin Versus Unasyn
in the Treatment of Facial Cellulitis of Odontogenic Origin in
Children. Clin Pediatr (Phila) 46:154, 2007
51. Kuriyama T, Absi EG, Williams DW, Lewis MAO: An outcome
audit of the treatment of acute dentoalveolar infection: Impact
of penicillin resistance. Br Dent J 198:759, 2005
52. Andriaenssen CF: Comparison of the Efficacy, Safety and Tolera-
bility of Azithromycin and Co-amoxiclav in the Treatment of
Acute Periapical Abscesses. J Intern Med Res 26:257, 1998
ANTIBIOTICS AND ODONTOGENIC INFECTIONS
53. Martin MV, Longman LP, Hill JB, Hardy P: Acute dentoalveolar in-
fections: An investigation of the duration of antibiotic therapy.
Br Dent J 183:135, 1997
54. Fazakerley MW, McGowan P, Hardy P, Martin MV: A comparative
study of cephradine, amoxycillin and phenoxymethylpenicillin
in the treatment of acute dentoalveolar infection. Br Dent J
174:359, 1993
55. Deffez J, Scheimberg A, Rezvani Y: Multicenter Double-Blind
Study of the Efficacy and Tolerance of Roxithromycin versus
Erythromycin Ethylsuccinate in Acute Orodental Infection in
Adults. Diagn Microbiol Infect Dis 15:1335, 1992
56. Hood FJC: The place of metronidazole in the treatment of acute
oro facial infection. J Antimicrob Chemother 4:71, 1978
57. Pallasch TJ: Pharmacokinetic principles of antimicrobial ther-
apy. Periodontol 2000 10:511, 1996
58. Flynn TR, Shanti RM, Levi MH, et al: Severe odontogenic infec-
tions, part 1: Prospective report. J Oral Maxillofac Surg 64:
1093, 2006
59. Jadad AR, Moore RA, Carroll D, et al: Assessing the quality of re-
ports of randomized clinical trials: Is blinding necessary? Con-
trol Clin Trials 17:112, 1996
60. Schulz KF, Chalmers I, Hayes RJ, Altman DG: Empirical evidence
of bias: Dimensions of methodological quality associated with
estimates of treatment effects in controlled trials. JAMA 273:
408, 1995