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Available online at www.sciencedirect.com

British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx

Use of metronidazole as part of an empirical antibiotic

regimen after incision and drainage of infections of the
odontogenic spaces
Rishi Bali, Parveen Sharma, Shivani Gaba ∗
Department of OMFS, D.A.V. Dental College and M.M. General Hospital, Yamunanagar, Haryana 135001, India

Accepted 4 September 2014

Abstract

The combination of amoxicillin/clavulanate and metronidazole is a widely-accepted empirical regimen for infections of the odontogenic spaces.
Once adequate drainage has been established micro-organisms are less likely to grow and multiply, particularly anaerobes. This may obviate
the need for anaerobic coverage after drainage in healthy hosts. We studied 60 patients in this randomised prospective study, the objective
of which was to evaluate metronidazole as part of an empirical antibiotic regimen after drainage of infections of the odontogenic spaces.
Samples of pus were sent for culture and testing for sensitivity. Amoxicillin/clavulanate and metronidazole were given to all patients. After
incision and drainage the patients were randomly allocated to two groups. In the first group both antibiotics were continued, and in the second
metronidazole was withdrawn. The groups were compared both clinically and microbiologically. There were no significant differences between
the groups in the resolution of infection. Thirteen patients (n = 6 in the 2-antimicrobial group, and n = 7 in the amoxicillin/clavulanate group)
showed no improvement during the 48 h postoperatively. Overall there was need to substitute another antibiotic for amoxicillin/clavulanate
in only 6 cases. Six patients in the amoxicillin/clavulanate group required the addition of metronidazole after drainage. We conclude that in
healthy subjects metronidazole is not necessary in the period after drainage, but its prescription should be based on assessment of clinical and
laboratory markers of infection.
© 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Keywords: Odontogenic; Space infection; Antibiotics; Empirical

Introduction provides excellent anaerobic coverage and is an effective

Systemic antimicrobial treatment has been an important
adjunct to surgery in the management of infections of the
odontogenic spaces. A rational approach to selection of
appropriate antibiotics is based on scientific data and con-
temporary experience of the microbiology of oral infection,1
and the combination of amoxicillin/clavulanic acid and met-
ronidazole has become widely accepted.2 Metronidazole
∗ Corresponding author. Fax: +91 01732 227155.
E-mail address: dr.shivanigaba@gmail.com (S. Gaba).
http://dx.doi.org/10.1016/j.bjoms.2014.09.002
0266-4356/© 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
supplement to penicillins.
The use of antibiotics should be restricted to reduce
the development of bacterial resistance and to minimise
adverse reactions. We therefore designed a study to find out
which antibiotics were optimal in the management of these
infections. Once adequate drainage has been established by
incision of the infected space, the environment alters and may
discourage multiplication of micro-organisms, particularly
anaerobes. This might obviate the need for metronidazole to
be continued after drainage. We have therefore evaluated the
withdrawal of metronidazole after incision and drainage had
been completed.

Please cite this article in press as: Bali R, et al. Use of metronidazole as part of an empirical antibiotic regimen after incision and drainage
of infections of the odontogenic spaces. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.002
YBJOM-4344; No. of Pages 5
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2 R. Bali et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx

Patients and methods pus, improvement in mouth opening, and dysphagia or dys-
pnoea (if symptoms were present). Improvement in systemic
This double-blind, randomised prospective study was done variables including heart rate, body temperature, and respi-
during the period October 2011–October 2013, and we stud- ratory rate were assessed using the criteria for the systemic
ied 60 patients with infections of the odontogenic spaces. inflammatory response syndrome (SIRS).4 Laboratory tests
Patients were excluded if they were allergic to penicillins, if included microbiological cultures, white cell count (WCC),
they were taking antibiotics at the time or had had incision and and concentration of C-reactive protein (CRP).
drainage elsewhere, if they were medically compromised, or Measurements were made postoperatively at 24, 48, and
if they were pregnant. 72 h, and 7 days.
Pus was aspirated and sent for culture and sensitivity test-
ing before antimicrobial treatment was started. The anaerobic
Analysis of data
transport medium used was HiCultureTM transport swabs (a
modification of Stuart’s medium) with alternative thiogly-
A database was constructed using Microsoft Excel
collate medium. The isolation and culture techniques were
(Microsoft, Redmond, WA). The statistical analysis was done
based on the standard protocol recommended by the Clinical
with the help of SPSS software (version 15.0, SPSS Inc,
Laboratory Standards Institute.3
Chicago). Results are expressed as number (%) or mean (SD),
Antibiotics were started for all patients before incision
as appropriate. The significance of differences was assessed
and drainage in the form of amoxicillin 1000 mg/clavulanate
using Student’s t test, the Mann-Whitney U test, or the chi
200 mg injected intravenously 8-hourly together with an
square test, as appropriate.
intravenous infusion of metronidazole 500 mg 8-hourly.
Probabilities of less than 0.05 were accepted as significant.
Appropriate anaesthesia was decided in consultation with the
anaesthetist. The site was incised and drained, and the focus
of infection removed with copious irrigation. The diagnosis
Results
of which spaces were involved was confirmed intraopera-
tively. Drainage was maintained with a corrugated rubber
Clinical results
drain. Postoperatively patients were randomly allocated to
two groups by block randomisation.
The mean age of the patients in the 2-drug group was 33
In one group amoxicillin/clavulanate and metronidazole
(13) years and in the amoxicillin/clavulanate alone group 34
were continued after drainage, and in the second group
(13) years, with equal numbers of men and women. The
only amoxicillin/clavulanate was continued, and metroni-
anatomical sites of the infections are shown in Table 1.
dazole was stopped. In all patients the site was regularly
These differences did not differ significantly, and neither
irrigated with hydrogen peroxide, saline, and povidone iodine
did differences in size of swelling, perception of pain, dis-
(Betadine® ). If the swab showed that the organism grown was
charge of pus, or improvement in dysphagia, at any time.
resistant to amoxicillin/clavulanate, an effective antibiotic
Only 3 patients (2 in the 2-antimicrobial group and 1 in
was substituted.
the ampicillin/clavulanate alone group) complained of mild
As soon as the clinical and the laboratory findings indi-
dyspnoea on admission. Fourteen and 16 patients, respec-
cated that the infection was under control the antimicrobials
tively, initially presented with trismus (interincisal distance
were given orally rather than intravenously. Patients were fol-
<20 mm).
lowed up for 4 weeks. The clinical and laboratory findings
Twenty-one and 23 patients in the 2 groups, respectively,
were monitored by staff who were unaware of the antibiotic
(44/60) fulfilled the criteria for SIRS, and 14 patients in
regimen given postoperatively. The treatment was considered
and 17 patients, respectively, had temperatures of >38 ◦ C
to have been effective if the patients’ condition improved
(100.4 ◦ F) on admission. None of these differences was sig-
within 48 h. Those patients who showed no clinical improve-
nificant, and nor were any differences between WCC or
ment after 48 h had their wounds explored again. The decision
concentrations of CRP (Tables 2 and 3). Only 13 patients
to substitute, add, or discontinue any antibiotic was made by
(n = 6 and n = 7 in the 2 groups, respectively) showed no
a third party (between 48 and 72 h) based on clinical and
improvement clinically or microbiologically during the first
laboratory findings, and the results of culture and sensitivity
48 h postoperatively.
testing.

Collection of data Microbiological findings

Patients’ age, sex, focus of infection, and number and type
of spaces involved were recorded. We compared clinical
variables including change in degree of swelling (measured
by thread and scale), changes in the amount of pain (mea-
sured by visual analogue score), presence or absence of
Results of cultures are shown in Tables 4 and 5. Most
aerobic organisms in both groups were sensitive to amox-
icillin/clavulanate, and there was no significant difference
between them. Anaerobic organisms were sensitive to amox-
icillin/clavulanate in 13 cases in each group, but slightly

Please cite this article in press as: Bali R, et al. Use of metronidazole as part of an empirical antibiotic regimen after incision and drainage
of infections of the odontogenic spaces. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.002
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R. Bali et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx 3

Table 1 Table 3
No (%) of spaces involved (n = 30 in each group). Mean (SD) white cell count (×109 /L) (n = 30 in each group).
Site Amoxicillin/clavulanate Amoxicillin/clavulanate Time Amoxicillin/clavulanate Amoxicillin/clavulanate
plus metronidazole alone after incision and plus metronidazole alone after incision and
drainage drainage
Submandibular 7 (23) 6 (20) Before operation 13.2 (3.1) 12.4 (1.8)
Buccal 5 (17) 5 (17) After operation (day)
Submental 0 1 (3) 1 12.3 (2.4) 12.2 (2.5)
Infraorbital 3 (10) 5 (17) 2 11.2 (3.0) 10.7 (2.9)
Superficial 1 (3) 0 3 10.0 (2.3) 9.4 (1.5)
temporal 7 8.6 (1.0) 8.3 (0.9)
Vestibular 0 1 (3)
Submandibular 2 (7) 3 (10) There were no significant differences between the groups.
and submental
Submandibular 2 (7) 1 (3) Table 4
and Aerobes isolated in the 2 groups (n = 30 in each).
submasseteric Isolate Amoxicillin/clavulanate Amoxicillin/clavulanate
Submandibular 2 (7) 3 (10) plus metronidazole alone after incision and
and pterygo- drainage
mandibular
Streptococcus spp. 17 (57) 12 (40)
Submandibular 1 (3) 0
Lactococcus garvieae 2 (7) 1 (3)
and left
Enterobacter cloacae 0 1 (3)
pharyngeal
Leclercia 0 1 (3)
Infratemporal and 1 (3) 0
adecarboxilata
buccal
Sphingomonas 1 (3) 0
Peritonsillar and 0 1 (3)
paucimobilis
left pharyngeal
Staphylococcus 0 1 (3)
Submandibular, 4 (13) 1 (3)
haemolyticus
buccal, and
Propionibacterium 0 1 (3)
pterygo-
propionicum
mandibular
Haemophilus 0 1 (3)
Submandibular, 1 (3) 0
parainfluenzae
pterygo-
Candida spp. 1 (3) 0
mandibular, and
No growth 10 (33) 12 (40)
left pharyngeal
Superficial 0 1 (3) There were no significant differences between the groups.
temporal and
submasseteric
Infratemporal, (1) 2 (7) amoxicillin/clavulanate had to be replaced by another antibi-
submasseteric, otic in only 6 cases.
and pterygo-
mandibular

There were no significant differences between groups. Discussion

The mainstay of the management of infections of the odonto-

more were sensitive to metronidazole than to amoxi- genic spaces remains timely aggressive incision and drainage
cillin/clavulanate. Again the difference was not significant.
Six patients in the amoxicillin/clavulanate alone group Table 5
required additional metronidazole after drainage, and Anaerobes isolated in the 2 groups (n = 30 in each).
Isolate Amoxicillin/clavulanate Amoxicillin/clavulanate
plus metronidazole alone after incision and
Table 2 drainage
Mean (SD) C-reactive protein concentrations (mg/L) (n = 30 in each group).
Peptostreptococcus 7 (23) 7 (23)
Time Amoxicillin/clavulanate Amoxicillin/clavulanate
S aureus subsp. 3 (10) 3 (10)
plus metronidazole alone after incision and
anaerobius
drainage
S saccharolyticus 2 (7) 2 (7)
Before operation 119.0 (43.0) 106.9 (36.2) Prevotella spp. 2 (7) 2 (7)
After operation (day) Bacteroides capillosus 1 (3) 0
1 131.1 (45.9) 118.4 (43.5) Fusobacterium 1 (3) 2 (7)
2 94.4 (55.7) 74.5 (61.0) nucleatum
3 56.1 (41.7) 39.3 (39.0) Veillonella spp. 0 1 (3)
7 9.3 (9.6) 6.5 (8.4) No growth 14 (47) 13 (43)

There were no significant differences between the groups. There were no significant differences between the groups.

Please cite this article in press as: Bali R, et al. Use of metronidazole as part of an empirical antibiotic regimen after incision and drainage
of infections of the odontogenic spaces. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.002
YBJOM-4344; No. of Pages 5
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4 R. Bali et al. / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx–xxx
with removal of the cause.5–7 A suitable antibiotic is a neces-
sary adjunct. Initiation of antimicrobials soon after diagnosis
and before operation can shorten the period of infection
and minimise associated risks such as bacteraemia.8–10
All the patients in this study were initially given amox-
icillin/clavulanate and metronidazole. Early infections are
primarily caused by aerobic streptococci that are sensitive to
penicillin, whereas in long-standing infections the predom-
inant microorganisms are anaerobes, so metronidazole was
added to the penicillin.10–12
Other publications support the fact that incision and
drainage rid the infected space of toxic purulent material
and decompresses the tissues, which allows better perfusion
of blood-laden antibiotics and increased oxygenation of the
infected area.13 This opens up hitherto closed areas and pock-
ets, making them amenable to copious irrigation with an
antianaerobic solution (hydrogen peroxide), and might obvi-
ate the need to continue metronidazole after drainage.
The submandibular space was the most common one
involved in both single and multiple space infections, fol-
lowed by the buccal space in both groups. Our results
correlate well with those of previous studies.14–16
Assessment of patients showed that 44/60 (73%) patients
fulfilled the criteria for SIRS. Temperature is both a good
predictor of acute infection and a way to monitor a patient’s
response to treatment,17 and more than half the patients were
febrile. Many authors have reported fever on admission in
patients with these infections.15,18,19
There was no significant difference in systemic improve-
ment at any time, denoting equivalent improvement in both
groups. Most patients showed some improvement in local
and systemic variables up to 48 h after the start of treatment,
except 6 in the 2-antimicrobial group and 7 in the other group.
All these patients were febrile, and discharge of pus persisted
after incision and drainage.
CRP and WCC are important markers in the evaluation of
the patient’s response to treatment.7,20–22 On admission the
mean concentration of CRP was 119.0 (43.0) mg/L in the 2-
drug group and 106.9 (36.2) mg/L in the other group. These
values correlate well with those of previous studies.20,21 On
day 2 there was a decline in concentrations in most patients
except for 6 and 7 in the 2 groups, respectively. These were
the same patients with persistent discharge of pus and fever.
Haematological investigations showed that 20 patients in
the 2-drug group and 21 in the other group had WCC of
12.0 × 109 /L on admission.
CRP concentration, WCC, and temperature correlate
with clinical improvement, and their decrease towards the
reference ranges signifies resolution of infection with no sig-
nificant differences between the 2 groups.
Of 60 specimens of pus tested, 46 contained bacte-
rial pathogens while 14 showed no growth. The reason
for the lack of growth can be because these abscesses are
caused by bacteria that are organised in biofilms, which
may not grow on traditional water-based culture media, and
Please cite this article in press as: Bali R, et al. Use of metronidazole as part of an empirical antibiotic regimen after incision and drainage
of infections of the odontogenic spaces. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.002
fastidious microorganisms1 (particularly anaerobes) are
highly sensitive and may not survive the transport period. Of
46 specimens that grew bacteria, 13 contained aerobic bacte-
ria, 8 had anaerobic bacteria, and 25 had mixed aerobes and
anaerobes. This is similar to the results of other studies.17,18,23
Streptococci were the most common aerobic, and Pep-
tostreptococci the most predominant anaerobic, isolates.
These findings are consistent with those of previous
reports.21,24 Leclercia adecarboxylata was identified in a
patient with peritonsillar and lateral pharyngeal abscesses;
this is an uncommon pathogen at this site.25
Sensitivity to amoxicillin/clavulanate was studied for
both aerobes and anaerobes whereas metronidazole was
studied for anaerobes only. Seventy one per cent of the
total aerobic, and 45% of anaerobic, strains were sensitive
to amoxicillin/clavulanate, while 73% of anaerobic strains
were sensitive to metronidazole. Eighteen of 33 anaerobic
strains were resistant to amoxicillin/clavulanate, and 9/33
were resistant to metronidazole. Fourteen of 18 strains that
were resistant to amoxicillin/clavulanate were sensitive to
metronidazole. These findings substantiate the addition of
metronidazole to amoxicillin/clavulanate for treatment of
infections of the odontogenic spaces.
All 13 patients whose improvement was delayed had the
abscesses re-explored and we analysed the reasons in detail.
In the 2-drug group, 3/6 had single space infections and 3
had involvement of multiple spaces. Patients with infections
of single spaces had grown organisms that were resistant
to both drugs. After substitution with an appropriate drug,
they responded rapidly. The patients with involvement of
multiple spaces had organisms that were resistant to amox-
icillin/clavulanate. When this was changed they responded
rapidly. Although these patients had organisms that were
sensitive to metronidazole they did not improve after 48 h.
In the group given amoxicillin/clavulanate alone after
drainage, 1/7 patients had an infection of a single space
whereas other six had involvement of multiple spaces. The
patient with only a single space affected had grown orga-
nisms that were resistant to amoxicillin/clavulanate and was
therefore given an appropriate drug. In the other six patients,
improvement was delayed because all 6 patients had at least
2 or more spaces involved. The presence of deep pockets in
one of these spaces in which the growth of anaerobic bacteria
could not be disrupted adequately might have been responsi-
ble. Secondly, in all 6 the anaerobic strains were resistant to
amoxicillin/clavulanate and necessitated additional metroni-
dazole. All these patients recovered uneventfully.
It was found that half of the 12 patients with multiple
spaces infected in the amoxicillin/clavulante group required
the addition of metronidazole after drainage. However, no
patient with involvement of only a single space required
it. Overall we had to substitute another drug for amoxi-
cillin/clavulanate in only 6 patients (10%).
The interpretation of cultures that showed “no growth”
in terms of whether there were no viable organisms, or they
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could not be cultured, was a limitation of our study. This could
have been overcome if these samples had been examined by
DNA probes or polymerase chain reaction.
We conclude that metronidazole is not always necessary
after drainage of infected odontogenic spaces. The use of met-
ronidazole under these circumstances in otherwise healthy
patients should not be a rule, but it should be based on
assessment of clinical and laboratory markers of infection.
It should be withdrawn as soon as these markers indicate that
the infection is resolving.
Conflict of interest
None declared.
Ethics statement/confirmation of patient permission
The study design was approved by the Board of Studies of
the University. An informed consent was obtained from all
the patients.
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