Int. J. Oral Maxillofac. Surg.

2014; 43: 6874

http://dx.doi.org/10.1016/j.ijom.2013.05.019, available online at http://www.sciencedirect.com

Systematic Review
Dental Implants

Do antibiotics decrease implant J. Ata-Ali, F. Ata-Ali, F. Ata-Ali

Public Dental Health Service, Valencia
University Medical and Dental School,
Valencia, Spain

failure and postoperative

infections? A systematic review
and meta-analysis
J. Ata-Ali, F. Ata-Ali, F. Ata-Ali: Do antibiotics decrease implant failure and
postoperative infections? A systematic review and meta-analysis. Int. J. Oral
Maxillofac. Surg. 2014; 43: 6874. # 2013 International Association of Oral and
Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Abstract. The purpose of this study was to systematically review and perform a
comprehensive meta-analysis of the current literature to answer the following
question: among patients receiving dental implants, does the use of antibiotics,
when compared with a control group, reduce the frequency of implant failure and
postoperative infection? A manual and electronic PubMed search of the literature
was made to identify randomized controlled trials (RCTs) on the efficacy of
antibiotics compared with a control group (not receiving antibiotics or receiving
placebo). Four RCTs were included in the final review. These four RCTs grouped a
total of 2063 implants and a total of 1002 patients. Antibiotic use significantly
lowered the implant failure rate (P = 0.003), with an odds ratio of 0.331, implying
that antibiotic treatment reduced the odds of failure by 66.9%. The number needed
to treat (NNT) to prevent one patient from having an implant failure was 48 (95%
confidence interval 31109). In contrast, antibiotic use did not significantly reduce
the incidence of postoperative infection (P = 0.754). Based on the results of this
meta-analysis, and pending further research in the field, it can be concluded that
there is evidence in favour of systematic antibiotic use in patients receiving dental
implants, since such treatment significantly reduces implant failure. In contrast,
antibiotic use does not exert a significant preventive effect against postoperative
infection. Our recommendations for future research focus on the performance of
Key words: dental implants; infection; disease;
large-scale RCTs to identify the best choice of antibiotic, timing of administration, antibiotic; meta-analysis; implant surgery.
and dose. Increased effort is also required to reach consensus and define the most
effective antibiotic treatment protocol for patients who are allergic to beta-lactams Accepted for publication 24 May 2013
and for those who are not. Available online 26 June 2013

Dental implants are an effective, safe and reasons.1 The biological complications the implant abutment, and proves easier
predictable solution for those who have of dental implants are classified as early to diagnose due to the lack of osseointe-
lost a tooth or teeth due to dental caries, or late.24 Early failure is defined as gration.5 It is believed that a certain
periodontal disease, injury, or other failure occurring up until connection of number of early dental implant losses

0901-5027/01068 + 07 $36.00/0 # 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

are due to bacterial contamination at
implant insertion.6
It is still debated whether early dental
implant failure and postoperative infection
can be reduced by antibiotic prophylaxis.
While it is important to minimize implant
failure, there are concerns associated with
the widespread use of antibiotics, since
adverse events may occur.7 A number of
authors have reported that systemic anti-
biotic use does not reduce the implant
failure rate.79 In contrast, other investi-
gators have found such treatment to reduce
implant failure.10,11
The role of antibiotic use in the setting
of implant placement and its effects on
implant failure and postoperative infection
are unclear.12 Antibiotic over-prescription
has a negative impact on general health
and the economy. Proper selection of the
antibiotic regimen in clinical practice is
therefore very important.13 The use of
antibiotics in implant surgery in healthy
patients and its correlation to failure and
success rates remain poorly documented
in the literature. It is widely agreed by
health authorities that overall antibiotic
use should be reduced, and that antibiotics
should be prescribed for life-threatening
infections to reduce the emergence of
resistant bacterial strains.14 The decision
to administer prophylactic antibiotics is
based on various factors, including the
general condition of the patient, the sur-
gical site and extension, the preoperative
diagnosis, and even surgeon prefer-
ences.15 Penicillin is considered to be
active against aerobic and anaerobic
microorganisms commonly associated
with oral infections, and the results of
different studies support the use of
short-term penicillin prophylaxis in oral
procedures.16
The purpose of the present study was to
systematically review the current literature
and to perform a comprehensive meta-ana-
lysis of this literature to answer the follow-
ing question: among patients receiving
dental implants, does the use of antibiotics,
when compared with a control group,
reduce the frequency of implant failure
and postoperative infection?
Materials and methods
This meta-analysis complies with the
QUOROM (Quality of Reporting of
Meta-analyses) statement.17
Search strategy for the identification of
studies
The PubMed (MEDLINE) database of
the United States National Library of
Do antibiotics decrease implant failure?
Medicine was used for a literature search
of articles published up until December
2012. The following search terms were
used in different combinations: dental
implants, antimicrobial agents, anti- the electronic and manual searches were
biotics, prophylactic antibiotics, and
infection. The search was completed
with a review of the references of the
selected articles in order to identify addi-
tional studies not found in the initial lit-
erature search.
In addition, a manual search (up until
December 2012) was made of the follow-
ing journals: British Journal of Oral and
Maxillofacial Surgery, Clinical Implant
Dentistry and Related Research, Clinical
Oral Investigations, Clinical Oral Implants
Research, European Journal of Oral
Implantology, Implant Dentistry, Interna-
tional Journal of Oral and Maxillofacial
Implants, International Journal of Oral and
Maxillofacial Surgery, Journal of Clinical
Periodontology, Journal of Oral Implan-
tology, Journal of Oral and Maxillofacial
Surgery, Journal of Periodontology, Med-
icina Oral, Patologa Oral y Ciruga Bucal,
and Oral Surgery, Oral Medicine, Oral
Pathology, Oral Radiology, and Endodon-
tology.
Study selection criteria
Before starting the study, a series of inclu-
sion and exclusion criteria were estab-
lished using a protocol. Full-text articles
chosen were assessed for the following
inclusion criteria: (1) patients subjected
to dental implant surgery; (2) randomized
controlled trials (RCTs); (3) the presence
of a control group (not receiving antibio-
tics or receiving placebo); (4) systemic
antibiotic treatment, with specification
of the type of antibiotic, the administered
dose, and the duration of treatment; and
(5) specification of the implant failure and
postoperative infection rates. Antibiotic
administration was defined as presence/
absence, independently of the timing of
administration (preoperatively, postopera-
tively, or both). Studies were excluded if
randomization was not performed, if
growth factors were used, if no control
group was included, if antibiotic admin-
istration was not carried out via a systemic
route, or if bone augmentation procedures
were required concomitant to implant pla-
cement. Case series, retrospective studies,
and articles published as abstracts only
were excluded. No restrictions were
placed on the year or language of publica-
tion.
Authors were contacted for clarification
of missing information when necessary. In
cases of more than one publication on the
69
same patient group for the same follow-
up, only the study nearest to the objectives
of this review or with the largest sample
was included. All articles selected from
independently assessed by the first and
second authors of this study, in accordance
with the established inclusion criteria.
Any disagreements between the reviewing
authors were resolved by consensus, or by
consulting the last signing author of this
study.
Quality and risk of bias assessment
Two reviewers independently and in
duplicate evaluated the quality of the
included RCTs as part of the data extrac-
tion process.
The recommendations of the Cochrane
Handbook for Systematic Reviews of
Interventions 5.0.0 were followed.18 Four
main quality criteria were examined: (1)
concealment of allocation; (2) assessor
blinding; (3) patient blinding; and (4)
compliance with follow-up (withdrawals
in the case of a clear explanation for
removals and dropouts in each treatment
group).
After analyzing this information for
each of the RCTs, the publications were
grouped into the following categories:19
(A) low risk of bias (possible bias not
seriously affecting the results) if all the
criteria were met; (B) high risk of bias
(possible bias, seriously weakening the
reliability of the results) if one or more
criteria were not met.
Statistical analysis
The primary outcome variable was
implant failure and the secondary outcome
variable was postoperative infection. The
meta-analysis was based on the inverse
variance calculation method of DerSimo-
nian and Laird, taking the odds ratio (OR)
as the measure of effect. Results were
obtained for a fixed effects model.
The OR estimations are accompanied
by the corresponding 95% confidence
interval (95% CI), standard error, and
P-value of the factor null effect contrast
(OR = 1) for solution of the meta-analy-
sis, including the QA association statis-
tic. The Forest plot shows the OR value
and corresponding confidence interval
for the RCTs and the global cluster
value. The relative size of each symbol
reflects the weight attributed to each
study, on the basis of sample size. A
logarithmic scale was used to visualize
symmetrical intervals.
70 Ata-Ali et al.

Number of citations identified

2099

Eliminated duplicated
citations
911

Total single citations screened

1188

Citations excluded based

on title or abstract (not
relevant, retrospective
studies, reviews)
1180

Citations selected for full-text review

8

Full-text articles excluded: 4

Dent et al. 199710
Laskin et al. 200011
Anitua et al. 200921
Karaky et al. 201122

Total RCTs included in the meta-analysis

4

Low risk of bias: High risk of bias:

9
Esposito et al. 2008 Abu Ta a et al. 200824
7
Esposito et al. 2010 Caiazzo et al. 201123

Fig. 1. Flowchart of the systematic review process.

A funnel plot was used to assess pub-
lication bias.20 The QH heterogeneity sta-
tistic and corresponding P-value for the x2
test are provided. The number needed to
treat (NNT), calculated as the reciprocal of
absolute risk reduction, was defined as the
number of implants that must be placed
with antibiotic use to prevent one implant
failure.12 A significance level of 5% was
established in the analyses (a = 0.05).
Results
Study selection and description
All articles included in the review were
RCTs and were published in English. Four
publications were excluded on applying
the defined study criteria: Dent et al.10
failed to specify the number of included
patients, mention being limited to the
number of implants involved. In relation
to the administered antibiotics, this author
did not describe the dose or the duration of
treatment. Laskin et al.11 conducted a
study across 32 research centres, and each
professional was free to chose the type of
antibiotic for use (penicillins or penicillin
derivatives, cephalosporins, erythromy-
cin, and other non-specified antibiotics).
These authors likewise did not describe
the dose or the duration of treatment. The
study published by Anitua et al.21 was
excluded because the implants were humi-
dified with plasma rich in growth factors
before implantation, and Karaky et al.22
failed to include a control group in their
study.
Finally, four RCTs fulfilled the inclu-
sion criteria and were thus selected for
inclusion in the meta-analysis7,9,23,24
(Fig. 1). Table 1 summarizes the reviewed
articles, while Table 2 describes the
implant failure and postoperative infection
criteria of each included RCT.
Due to the small number of studies
included in the meta-analysis, the evalua-
tion of publication bias was not considered
relevant. Regarding the need for bone
augmentation procedures concomitant to
implant placement, we directly obtained
further information from Abu-Taa et al.24
and Caiazzo et al.,23 who confirmed that
the need for bone augmentation consti-
tuted an exclusion factor. This information
was already contained in the other two
included publications.7,9
Primary outcome variable: implant failure
The four RCTs comprised a total of 2063
implants: 1077 in the antibiotic treatment
group and 986 in the control group. With
 Do antibiotics decrease implant failure? 71

Table 1. Summary of reviewed articles.

Antibiotic treatment and Gender Mean age Number of Number of
Author, year timing of administration (M/F) (years) patients implants
Esposito et al.9 Amoxicillin 2 g given 80/78 47.8 158 341
1 h preoperatively
No antibiotic (placebo) 62/96 47.9 158 355
24
Abu Taa et al. Amoxicillin 1 g at 1 h preoperatively 23/17 60 40 128
and 2 g a day for 2 days postoperatively
No antibiotic (without placebo) 20/20 57 40 119
Esposito et al.7 Amoxicillin 2 g given 1 h preoperatively 114/138 49.1 252 489
No antibiotic (placebo) 122/132 47.6 254 483
Caiazzo et al.23 Amoxicillin 2 g at 1 h before surgery 13/12 52 25 35
Amoxicillin 2 g at 1 h before surgery and 12/13 45 25 36
2 g a day for 7 days following surgery
Amoxicillin 2 g a day started after surgery 7/18 42 25 48
and continued for 1 week after surgery
No antibiotic (without placebo) 10/15 43 25 29

Table 2. Criteria defining implant failure and postoperative infection.

Author, year Definition of implant failure
9
Esposito et al. Implant mobility of each implant measured manually and/
or any infection dictating implant removal
24
Abu Taa et al. Presence of signs of infection and/or radiographic peri-
implant radiotransparencies that could not respond to a
course of antibiotics and/or judged a failure after perform-
ing explorative flap surgery by an experienced periodontist
Esposito et al.7 Implant mobility of each implant measured manually and/
or any infection dictating implant removal
Caiazzo et al.23 Mechanical implant removal because of lack of
osseointegration
a
Criteria of infection from Sawyer and Pruett.25
Criteria of infection
Any biological complications such as wound dehiscence,
suppuration, fistula, abscess, and osteomyelitis, etc.
Purulent drainage (pus) or fistula together with pain or
tenderness, localized swelling, redness, and heat or fever
(>38 8C)a
Any biological complications such as wound dehiscence,
suppuration, fistula, abscess, osteomyelitis, etc.
Internal and external oedema, internal and external
erythema, pain, heat, and exudate

these data, two-tailed x2 testing yielded a
power of 90.3% in defining failure propor-
tions of 0.01 and 0.03 in the groups as
being significantly different, with a 95%
confidence level.
In order to analyze the implant failure
rate, we first used a homogeneity test to
show that the four studies were suitable for
obtaining a combined effect measure
(QH = 3.67, P = 0.298). On examining
the implant failure rate individually in
each RCT, only one study23 was seen to
show a statistically significant difference
between the antibiotic group and the con- Secondary outcome variable:
trol group. postoperative infection rate
However, the result of the x2 test applied
The four RCTs comprised a total of 1002
to the four included RCTs showed antibio-
patients: 525 in the antibiotic treatment
tic treatment to reduce the risk of implant
group and 477 in the control group. With
failure (OR = 0.331, 95% CI 0.1570.696),
these data, two-tailed x2 testing yielded a
this result being statistically significant
power of 84.8% in defining proportions of
(P = 0.003, QA = 8.49). The NNT to pre-
0.05 and 0.1 in the groups as being signifi-
vent one patient having an implant failure is
cantly different, with a 95% confidence
48 (95% CI 31109). It can be concluded
level.
that antibiotic administration lowers the
On examining the postoperative infec-
odds of implant failure by 66.9%. The
tion rate, we first used a homogeneity test
Forest plot is shown in Fig. 2.
to show that the four studies were suitable

Fig. 2. Meta-analysis Forest plot for implant failure. The scale is logarithmic; the vertical axis is located at OR = 1; the geometric symbol
represents the OR value, with its confidence interval. In the individual studies, the size of the symbol is proportional to the study sample size.
72 Ata-Ali et al.
Fig. 3. Meta-analysis Forest plot for postoperative infection. The scale is logarithmic; the vertical axis is located at OR = 1; the geometric symbol
represents the OR value, with its confidence interval. In the individual studies, the size of the symbol is proportional to the study sample size.
Table 3. Quality assessment and risk of bias.
Study Allocation
Esposito et al.9 Concealed
Abu-Taa et al.24 Unclear
Esposito et al.7 Concealed
Caiazzo et al.23 Unclear
for obtaining a combined effect measure
(QH = 2.79, P = 0.424). On evaluating the
postoperative infection rate individually
for each RCT, none of the studies were
seen to show a statistically significant
difference between the antibiotic group
and the control group.
The result of the x2 test applied to the
four included RCTs showed antibiotic
administration not to be associated with
a decrease in the incidence of postopera-
tive infection (OR = 1.091, 95% CI 0.629
1.893), this result failing to reach statis-
tical significance (P = 0.754, QA = 8.49).
The Forest plot is shown in Fig. 3. The
OR values of the individual studies are
seen to vary around 1, with confidence
intervals containing 1 in all cases. It is
therefore concluded that antibiotic admin-
istration exerts no effect (either positive or
negative) upon the probability of post-
operative infection.
Quality assessment of trials and risk of
bias
Table 3 summarizes the quality of the
included RCTs. Two studies7,9 had a
low risk of bias, while the other two23,24
presented a high risk of bias.
Discussion
The purpose of the present study was to
answer the question: among patients
receiving dental implants, does the use
of antibiotics, when compared with a con-
trol group, reduce the frequency of
implant failure and postoperative infec-
tion? Regarding the implant failure rate,
three of the four RCTs included in the
Assessor blinding Patient blinding
Yes Yes
No No
Yes Yes
No No
meta-analysis found no significant differ-
ences between the two study groups. How-
ever, when the four trials were combined
in the meta-analysis, the final analysis
comprised 1002 patients with a total of
2063 implants, and a statistical power of
90.3%; antibiotic treatment in this case
was shown to significantly lower the fail-
ure risk by 66.9%. As an illustration of the
magnitude of the effect on implant failure,
these results show that antibiotic treatment
would prevent one patient from experien-
cing an early implant loss out of every 48
patients receiving antibiotics. In contrast,
antibiotic use after implant placement
exerted no statistically significant effect
upon the postoperative infection rate.
The basic idea of antibiotic prophylaxis
is two-fold: to provide an adequate drug
level in the tissues before and during any
procedure, and to ensure the shortest glo-
bal administration period possible.26 The
initial dose should be administered before
the operation; failure to do so is consid-
ered to be associated with an increased
wound infection rate.27 However, the
duration of postoperative antibiotic
administration remains controversial and
varies in different studies from 1 to 7
days.28 Two of the four studies included
in this meta-analysis administered short-
term antibiotics 1 h prior to implant place-
ment.7,9 One study administered 1 g of
amoxicillin 1 h prior to implant place-
ment, and 2 g a day for 2 days postopera-
tively.24 Caiazzo et al.23 presented
different forms of antibiotic administra-
tion (Table 1). The selection of the appro-
priate antimicrobial agent depends on
identification of the pathogens that are
most likely to be associated with the
Withdrawals Risk of bias
Yes, reasons given Low
None High
Yes, reasons given Low
None High
surgical procedure. Penicillin is effective
against most oral pathogens. It is consid-
ered the antibiotic of first choice in
preventing infection during intraoral pro-
cedures.28 In this meta-analysis, all the
included RCTs used amoxicillin as the
antibiotic treatment. In routine practice
it is common to encounter patients with
a history of allergy to penicillin and other
beta-lactam antibiotics, since about 10%
of the population reports such an allergy.29
Further RCTs should therefore be carried
out using a different drug of choice (e.g.,
clindamycin), with a view to treating
patients with an allergy to penicillin. In
this context, clindamycin is increasingly
used as a prophylactic antibiotic in max-
illofacial surgery.30
Caiazzo et al.23 reported no significant
differences among the four groups ana-
lyzed (three groups were administered
antibiotics in different regimens and the
fourth was a control group). However, on
analyzing the study of Caiazzo et al.23 in
the present meta-analysis, significant dif-
ferences were observed on applying what
we regard as the most appropriate statis-
tical test in this case (Fishers exact test),
since Caiazzo et al.23 compared the failure
percentages of each study group. The suc-
cess rate in the antibiotic treatment group
was 100%, versus 93.1% in the control
group (P = 0.037). In a systematic review
published by Sharaf et al.,12 a single dose
of preoperative antibiotic coverage was
found to slightly decrease the failure rate
of dental implants. The meta-analysis of
Esposito et al.31 found that there is some
evidence that 2 g of amoxicillin given
orally 1 h preoperatively significantly
reduces failures of dental implants placed

under ordinary conditions. However, these
authors comment that it is still unknown
whether postoperative antibiotics are ben-
eficial and which antibiotic is most effec-
tive. The meta-analysis published by
Esposito et al.31 included the study of Ani-
tua et al.,21 in which plasma rich in growth
factors was used. In our meta-analysis, the
use of plasma rich in growth factors was an
exclusion criterion, since this technique
does not yet constitute routine practice in
dental implant placement. Specifically, our
meta-analysis aims to serve as a guide for
preventing implant failure based on the
recommendation to administer antibiotics
during implant placement.
The main limitation of this meta-analy-
sis is the small number of articles that were
available for review. Funnel plots may not
be useful for small numbers of studies (for
example, a small study effect may be
difficult to detect among fewer than 10
studies).18 This is why no evaluation of
publication bias was made in this meta-
analysis. As an inclusion criterion, we
accepted those studies that used antibio-
tics, independently of the timing of admin-
istration (preoperatively, postoperatively,
or both). We are aware that this also
constitutes a limitation, and that it would
have been desirable for all the studies to
use antibiotics involving the same timing
of administration. A variable to be taken
into account in interpreting the results of
this meta-analysis is the methodological
quality of the included studies. In this
context, two trials7,9 had a low risk of
bias, while the other two23,24 had a high
risk of bias. Nonetheless, of the 1002
patients included in the meta-analysis,
the high-quality RCTs7,9 contributed a
total of 822 patients.
Based on the results of this meta-ana-
lysis, and pending further research in this
field, it can be concluded that there is
evidence in favour of systematic antibiotic
use among patients receiving dental
implants, since such treatment signifi-
cantly reduces implant failure. In contrast,
antibiotic use does not exert a significant
preventive effect against postoperative
infection. This review shows that much
remains to be done, including the perfor-
mance of further randomized, double-
blind controlled trials with larger sample
sizes, in order to establish whether anti-
biotic treatment offers benefits, and to
define which drugs and administration
regimens are most effective. Increased
effort is also required to reach consensus
and define the most effective antibiotic
treatment protocol for patients who are
allergic to beta-lactams and for those
who are not.
Do antibiotics decrease implant failure?
Funding
None.
Competing interests
None declared.
Ethical approval
Not required.
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Coulthard P, Grusovin MG. Interventions Tel: +0034963868501
for replacing missing teeth: antibiotics at E-mail: javiataali@hotmail.com