ANTIBIOTICS TO PREVENT COMPLICATIONS FOLLOWING DENTAL IMPLANT
TREATMENT
Esposito M, Coulthard P, Oliver R, Thomsen P, Worthington HV
This review should be cited as: Esposito M, Coulthard P, Oliver R, Thomsen P, Worthington HV.
Antibiotics to prevent complications following dental implant treatment (Cochrane Review). In: The
Cochrane Library, Issue 1, 2006. Oxford: Update Software.
A substantive amendment to this systematic review was last made on 15 March 2003. Cochrane
reviews are regularly checked and updated if necessary.
A B S T R A C T
Background: Some dental implant failures may be due to bacterial contamination at implant insertion.
Infections around biomaterials are difficult to treat and almost all infected implants have to be
removed. In general, antibiotic prophylaxis in surgery is only indicated for patients at risk of infectious
endocarditis, for patients with reduced host-response, when surgery is performed in infected sites, in
cases of extensive and prolonged surgical interventions and when large foreign materials are
implanted. To minimise infections after dental implant placement various prophylactic systemic
antibiotic regimens have been suggested. More recent protocols recommended short term prophylaxis,
if antibiotics have to be used. With the administration of antibiotics adverse events may occur, ranging
from diarrhoea to life-threatening allergic reactions. Another major concern associated with the
widespread use of antibiotics is the selection of antibiotic-resistant bacteria. The use of antibiotics in
implant dentistry is controversial. It would be useful to know whether prophylactic antibiotics are
effective in reducing failures of dental implants.
Objective: To assess the beneficial or harmful effects of the administration of prophylactic antibiotics
for dental implant placement versus no antibiotic/placebo administration and if antibiotics are of
benefit, to find which type, dosage and duration is the most effective.
Search strategy: We searched the Cochrane Oral Health Group's Trials Register, the Cochrane
Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. We handsearched several
dental journals. No language restrictions were applied. Personal contacts and manufacturers of dental
implants were contacted to identify unpublished trials. Most recent search: March 2003.
Selection criteria: Randomised controlled clinical trials (RCTs) with a follow up of at least 3 months
comparing the administration of various prophylactic antibiotics regimens and no antibiotics/placebo
to patients undergoing dental implant placement. Outcome measures were prosthesis failures, implant
failures, postoperative infections and adverse events (gastrointestinal, hypersensitivity).
Data collection and analysis: Screening of eligible studies, assessment of the methodological
quality of the trials and data extraction were to be conducted in duplicate and independently by two
reviewers. Results were to be expressed as random effects models using weighted mean differences
for continuous outcomes and relative risk for dichotomous outcomes with 95% confidence interval.
Heterogeneity was to be investigated including both clinical and methodological factors.
Main results: No RCTs were identified.
Reviewers' conclusions: There is not appropriate scientific evidence to recommend or discourage
the use of prophylactic systemic antibiotics to prevent complications and failures of dental implants.
Even though the present review did not assess the effectiveness of prophylactic antibiotics for patients
at risk for endocarditis, it seems sensible to recommend the use of prophylactic antibiotics for patients
at high and moderate risk for endocarditis, with immunodeficiencies, metabolic diseases, irradiated in
the head and neck area and when an extensive or prolonged surgery is anticipated.
B A C K G R O U N D
Dental implants are widely used for replacing missing teeth. Despite the high success rates published
in the literature, implant failures do occur (Esposito 1998a). It is believed that a certain number of
early dental implant losses are due to bacterial contamination at implant insertion (Esposito 1998b). It
is known that infections around biomaterials are very difficult to treat and almost all infected implants
have to be removed sooner or later (Esposito 1998b). The likelihood of an infection around dental
implants is influenced by the surgical skill (traumatic and prolonged surgery is more likely to favour
infections) and to the degree of asepsis. In general, antibiotic prophylaxis in surgery is only indicated
in the following situations: patients at risk of infectious endocarditis, patients with reduced hostresponse, when surgery is performed in infected sites, in cases of extensive and prolonged surgical
interventions and when large foreign materials are implanted.
In order to minimise infections after dental implant placement various prophylactic systemic antibiotic
regimens have been suggested. Initially, antibiotics were recommended preoperatively and up to 10
days postoperatively, one of the most commonly followed protocols being the administration of 2 g of
phenoxymethylpenicillin (penicillin-V), per os, about 1 hour preoperatively and then 2 g twice a day
for 10 days (Adell 1985). More recent protocols (Flemmig 1990) recommended short term prophylaxis:
2 g of penicillin-V (or Amoxicillin or Augmentin) administered per os, 1 hour prior to surgery and 500
mg of penicillin-V four times a day for 1 day. The prolongation of the prophylaxis should not be
extended beyond the first three postoperative days since it may not provide additional protection, if
antibiotics have to be used.
While on one hand it is important to minimise risk of implant failures, on the other it is sensible to
minimise the use of antibiotics since adverse events may occur. Complications most commonly
associated with the use of antibiotics range from diarrhoea to life-threatening allergic reactions.
Another major concern associated with the widespread use of antibiotics is the selection of antibioticresistant bacteria. The use of antibiotics in implant dentistry is controversial and some controlled
clinical trials yielded contradictory results (Dent 1997; Gynther 1998; Laskin 2000). It would be useful
to know whether prophylactic antibiotics are effective in reducing postoperative infections and failures
of dental implants and which is the most effective antibiotic, at what dose and duration.
O B J E C T I V E S
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PRIMARY OBJECTIVE
There is no difference in the proportion of prosthetic failures, implant failures,
postoperative infections and adverse events between groups of patients receiving
antibiotic treatment, and those receiving a placebo or no antibiotic treatment.
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SECONDARY OBJECTIVE
There is no difference in the proportion of prosthetic failures, implant failures,
postoperative infections and adverse events between groups of patients receiving
different antibiotic treatments, or different doses/duration of the same antibiotic.
C R I T E R I A
F O R
C O N S I D E R I N G
S T U D I E S
F O R
T H I S
R E V I E W
Types of studies
Randomised controlled clinical trials with a follow up of at least 3 months.
Types of participants
Any group of patients undergoing dental implant placement.
Types of intervention
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Administration of prophylactic antibiotics versus no antibiotics/placebo.
Administration of different antibiotics.
Administration of different doses or different duration of the same antibiotic.
Types of outcome measures
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Prosthesis could not be placed or prosthesis failure if secondary to implant failures.
Implant mobility and removal of stable implants dictated by progressive marginal bone
loss or infection.
Postoperative infections.
Adverse events (gastrointestinal, hypersensitivity).
S E A R C H
S T R A T E G Y
F O R
I D E N T I F I C A T I O N
O F
S T U D I E S
See: Cochrane Oral Health Group search strategy
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For the identification of studies included or considered for this review detailed search
strategies were developed for each database to be searched. These were based on the
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search strategy developed for MEDLINE (OVID) but revised appropriately for each
database. The search strategy combined a sensitive search strategy for randomised
controlled clinical trials (RCTs) (as published in Appendix 5c in the Cochrane Reviewers'
Handbook). The search strategy used a combination of controlled vocabulary and free
text terms based on the following:
#1 randomised controlled trial.pt.
#2 controlled clinical trial.pt.
#3 randomized controlled trials.sh.
#4 random allocation.sh.
#5 double blind method.sh.
#6 single blind method.sh.
#7 latin square.ti,ab.
#8 crossover.ti,ab.
#9 (split adj (mouth or plot)).ti,ab.
#10 or/1-9
#11 (ANIMAL not HUMAN).sh.
#12 10 not 11
#13 clinical trial.pt.
#14 exp clinical trials/
#15 (clin$ adj25 trial$).ti,ab.
#16 ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).ti,ab.
#17 placebos.sh.
#18 placebo$.ti,ab.
#19 random$.ti,ab.
#20 research design.sh.
#21 or/13-20
#22 21 not 11
#23 22 not 12
#24 12 or 22
#25 exp Dental Implants/
#26 exp Dental Implantation/ or dental implantation.mp.
#27 exp Dental Prosthesis, Implant-Supported/
#28 ((osseointegrated adj implant$) and (dental or oral)).mp. [mp=title, abstract,
registry number word, mesh subject heading]
#29 dental implant$.mp. [mp=title, abstract, registry number word, mesh subject
heading]
#30 (implant$ adj5 dent$).mp. [mp=title, abstract, registry number word, mesh subject
heading]
#31 dental-implant$.mp. [mp=title, abstract, registry number word, mesh subject
heading]
#32 (((overdenture$ or crown$ or bridge$ or prosthesis or prostheses or restoration$)
adj10 (Dental or oral)) and implant$).mp. [mp=title, abstract, registry number word,
mesh subject heading]
#33 "implant supported dental prosthesis".mp. [mp=title, abstract, registry number
word, mesh subject heading]
#34 ("blade implant$" and (dental or oral)).mp. [mp=title, abstract, registry number
word, mesh subject heading]
#35 ((endosseous adj5 implant$) and (dental or oral)).mp. [mp=title, abstract, registry
number word, mesh subject heading]
#36 ((dental or oral) adj5 implant$).mp. [mp=title, abstract, registry number word,
mesh subject heading]
#37 25 or 26 or 27 or 28 or 29 or 30 or 32 or 33 or 34 or 35 or 36
#38 24 and 37
SEARCHED DATABASES
The Cochrane Oral Health Group's Trials Register (to March 2003)
The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
Issue 2, 2003)
MEDLINE (1966 to March 2003)
EMBASE (1980 to March 2003)
Last electronic search was done on 21 March 2003.
The bibliographies of identified RCTs and review articles were checked for studies outside the
handsearched journals. PubMed was independently searched using the 'related articles' feature.
Personal references were also searched.
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LANGUAGE
Non-English papers were to be included. The Cochrane Oral Health Group was to attempt
to have non-English papers translated.
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UNPUBLISHED STUDIES
Personal contacts were used to identify ongoing or unpublished RCTs. Fifty-five oral
implant manufacturers were written to in an attempt to identify unpublished or ongoing
studies. We asked for unpublished and ongoing RCTs on a internet discussion group
(implantology@yahoogroups.com). Authors of the identified RCTs were to be contacted.
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HANDSEARCHING
Details of the journals being handsearched by the Oral Health Group's ongoing
programme are given on the web site: http://www.cochrane-oral.man.ac.uk.
The following journals have been identified as being important to be handsearched for this review:
British Journal of Oral and Maxillofacial Surgery, Clinical Implant Dentistry and Related Research,
Clinical Oral Implants Research, Implant Dentistry, International Journal of Oral and Maxillofacial
Implants, International Journal of Oral and Maxillofacial Surgery, International Journal of Periodontics
and Restorative Dentistry, International Journal of Prosthodontics, Journal of the American Dental
Association, Journal of Biomedical Materials Research, Journal of Clinical Periodontology, Journal of
Cranio-Maxillo-Facial Surgery, Journal of Dental Research, Journal of Oral Implantology, Journal of
Oral and Maxillofacial Surgery, Journal of Periodontology, Journal of Prosthetic Dentistry, Plastic and
Reconstructive Surgery. Where these have not already been searched as part of the Cochrane Journal
Handsearching Programme, the journals were handsearched by one of the reviewers.
M E T H O D S
O F
T H E
R E V I E W
The titles and abstracts (when available) of all reports identified were scanned independently by two
reviewers. For studies appearing to meet the inclusion criteria, or for which there were insufficient
data in the title and abstract to make a clear decision, the full report was obtained and assessed
independently by two reviewers to establish whether the studies met the inclusion criteria or not.
Disagreements were to be resolved by discussion. Where resolution was not possible, a third reviewer
was to be consulted. All studies meeting the inclusion criteria then were to undergo validity
assessment and data were to be extracted. Studies rejected at this or subsequent stages were to be
recorded in the table of excluded studies, and reasons for exclusion recorded.
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QUALITY ASSESSMENT
The quality assessment of the included trials was to be undertaken independently and in
duplicate by two reviewers based on what was written in the articles.
Three main quality criteria were to be examined:
1) Randomisation and allocation concealment, recorded as:
(A) Adequate
(B) Unclear
(C) Inadequate
(D) Not used
2) Blindness of participants and assessors, recorded as:
(A) Yes
(B) No
(C) Unclear
3) Completeness of follow up (is there a clear explanation for withdrawals and drop outs
in each treatment group?) assessed as:
(A) Yes
(B) No.
After taking into account the additional information provided by the authors of the trials,
studies were to be grouped into the following categories:
A. Low risk of bias (plausible bias unlikely to seriously alter the results) if all criteria were
met.
B. Moderate risk of bias (plausible bias that raises some doubt about the results) if one
or more criteria were partly met.
C. High risk of bias (plausible bias that seriously weakens confidence in the results) if
one or more criteria were not met as described in the Cochrane Reviewers' Handbook 6.7.
DATA EXTRACTION
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Data were to be extracted by two reviewers independently using a specially designed
data extraction form. Any disagreement was to be discussed and a third reviewer
consulted where necessary. Authors were to be contacted for clarification or missing
information. Data were to be excluded until further clarification would be available if
agreement could not be reached.
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For each trial the following data were to be recorded:
Year of publication, country of origin, setting and source of study funding.
Details of the participants including demographic characteristics and criteria for inclusion.
Details on the type of intervention.
Details of the outcomes reported, including method of assessment and time intervals.
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DATA SYNTHESIS
For each outcome, all of which were binary, the estimate of effect of an intervention was
to be expressed as relative risks together with 95% confidence intervals.
Clinical heterogeneity was to be assessed by examining the types of participants, interventions and
outcomes in each study with a planned subgroup analysis considering type, dose and duration of
antibiotics. Meta-analyses were to be done only with studies of similar comparisons reporting the
same outcome measures. Relative risks were to be combined for the binary data using a random
effects model. The significance of any discrepancies in the estimates of the treatment effects from the
different trials was to be assessed by means of Cochran's test for heterogeneity and any
heterogeneity was to be investigated.
Sensitivity analyses were to be undertaken to examine the effect of concealed randomisation and
outcome assessor being blind on the assessment of the overall estimates of effect. In addition, the
effect of including unpublished literature on the review's findings was to be examined.
D E S C R I P T I O N
O F
S T U D I E S
No randomised controlled clinical trial was identified.
M E T H O D O L O G I C A L
Q U A L I T Y
No randomised controlled clinical trial was identified.
R E S U L T S
No randomised controlled clinical trial was identified.
D I S C U S S I O N
No randomised controlled clinical trials were identified so it is not possible to provide any evidencebased indications to patients and clinicians interested in this issue. The only available data on whether
it would be beneficial to use preoperative antibiotics undergoing dental implant placement are those
from two controlled clinical trials (CCTs) that yielded opposite results. In one prospective trial,
described in two follow-up articles (Dent 1997; Laskin 2000), the use of various prophylactic antibiotic
regimens (dosages and regimens were not described) versus no antibiotics was tested for 2,973
implants (the number of patients was not reported); the conclusion was that implants in patients who
received preoperative antibiotics had significantly higher survival rates. In the other CCT (Gynther
1998), designed as a retrospective study, 1 g of phenoxymethylpenicillin was administered 1 hour
preoperatively and every 8 hours for 10 days in 147 patients. The control group comprised 132
patients who did not receive any antibiotics. The two groups were treated in different periods
(antibiotics group between 1980 and 1985 and non-antibiotic group between 1991 and 1995). No
statistically significant differences with respect to postoperative infections or implant survival were
observed. Unfortunately, both studies were highly biased in their methodology, so the validity of their
conclusions can be questioned.
The most recent recommendations by the American Heart Association for the prevention of
endocarditis (Dajani 1997) suggested the use of 2 g of amoxicillin 1 hour before the intervention in
patients at high and moderate risk for endocarditis (prosthetic cardiac valves, any congenital cardiac
malformations, surgically constructed systemic pulmonary shunts, acquired valvular dysfunction,
hypertrophic cardiomyopathy, mitral valve prolapse with valvular regurgitation and/or thickened
leaflets), a second dose being not necessary. For individuals allergic to penicillins, 600 mg of
Clindamycin can be administered instead 1 hour prior to the procedure. In addition, it may be of
clinical sense to use prophylactic antibiotic therapy for patients with immunodeficiencies, metabolic
diseases (diabetes), irradiated in the head and neck area and when extensive and prolonged implant
surgery is anticipated.
R E V I E W E R S '
C O N C L U S I O N S
Implications for practice
There is not appropriate scientific evidence to recommend or discourage the use of prophylactic
systemic antibiotics to prevent complications and failures of dental implants. Even though the present
review did not aim to assess the effectiveness of prophylactic antibiotics for patients at risk for
endocarditis, it seems sensible to recommend the use of prophylactic antibiotics for patients at high
and moderate risk for endocarditis, in patients with immunodeficiencies, metabolic diseases and
irradiated in the head and neck area and when extensive and prolonged surgeries are anticipated for
placements of dental implants or abutments.
Implications for research
There is the need for randomised controlled clinical trials on this topic. A large, double-blind, placebo
controlled randomised clinical trial assessing whether the use of a single dose of 2 g of amoxicillin 1
hour before implant placement decreases postoperative complications and implant failures could be an
appropriate starting point.
A C K N O W L E D G E M E N T S
We wish to thank Sylvia Bickley (Cochrane Oral Health Group) for her assistance with literature
searching and Luisa Fernandez (Cochrane Oral Health Group) for her help with the preparation of this
review. We would also like to thank the following referees: Ian M Brook, Matteo Chiapasco, AnneMarie Glenny, Lee Hooper, Ian Needleman.
P O T E N T I A L
C O N F L I C T
O F
I N T E R E S T
None known.
R E F E R E N C E S
Additional references
Adell 1985
Adell R, Lekholm U, Branemark PI. Surgical procedures. In: Branemark PI, Zarb GA, Albrektsson T,
editor(s). Tissue-integrated prostheses Chicago: Quintessence Publishing Co., Inc, 1985:211-32.
Dajani 1997
Dajani AS, Taubert KA, Wilson W, Bolger AF, Bayer A, Ferrieri P. Prevention of bacterial endocarditis.
Recommendations by the American Heart Association. Journal of the American Medical Association
1997;227(22):1749-1801.
Dent 1997
Dent CD, Olson JW, Farish SE, Bellome J, Casino AJ, Morris HF et al. The influence of preoperative
antibiotics on success of endosseous implants up to and including stage II surgery: a study of 2,641
implants. Journal of Oral and Maxillofacial Surgery 1997;55 (Suppl. 5):19-24.
Esposito 1998a
Esposito M, Hirsch JM, Lekholm U, Thomsen P. Biological factors contributing to failures of
osseointegrated oral implants. (I) Success criteria and epidemiology. European Journal of Oral
Sciences 1998;106:527-51.
Esposito 1998b
Esposito M, Hirsch JM, Lekholm U, Thomsen P. Biological factors contributing to failures of
osseointegrated oral implants. (II) Etiopathogenesis. European Journal of Oral Sciences
1998;106:721-64.
Flemmig 1990
Flemmig TF, Newman MG. Antimicrobials in implant dentistry. In: Newman MG, Kornman K, editor(s).
Antibiotics/antimicrobial use in dental practice Chicago: Quintessence Publishing Co., Inc, 1990:187200.
Gynther 1998
Gynther GW, Kondell PA, Moberg LE, Heimdahl A. Dental implant installation without antibiotic
prophylaxis. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics
1998;85:509-11.
Laskin 2000
Laskin DM, Dent CD, Morris HF, Ochi S, Olson JW. The influence of preoperative antibiotics on success
of endosseous implants at 36 months. Annals of Periodontology 2000;5:166-74.
C O V E R
S H E E T
Antibiotics to prevent complications following dental implant treatment
Reviewer(s)
Contribution of Reviewer(s)
Esposito M, Coulthard P, Oliver R, Thomsen P, Worthington HV
Conceiving, designing and co-ordinating the review (Marco
Esposito (ME)).
Developing search strategy and undertaking searches (ME, Paul
Coulthard (PC)).
Screening search results and retrieved papers against inclusion
criteria (ME, PC).
Writing the review (ME).
Providing general advice on the review (PC, Helen Worthington
(HW), Peter Thomsen (PT), Richard Oliver (RO)).
Performing previous work that was the foundation of current
study (ME, HW, PC).
Issue protocol first published
2003 issue 2
Issue review first published
2003 issue 3
Date of last minor amendment
17 April 2003
Date of last substantive
amendment
15 March 2003
Most recent changes
Information not supplied by reviewer
Date new studies sought but
none found
Information not supplied by reviewer
Date new studies found but not
yet included/excluded
Information not supplied by reviewer
Date new studies found and
included/excluded
Information not supplied by reviewer
Date reviewers' conclusions
section amended
Information not supplied by reviewer
Contact address
Dr Marco Esposito
The University of Manchester
Higher Cambridge Street
Manchester
UK
M15 6FH
Telephone: +44 161 275 6714
Facsimile:
E-mail: marco.esposito@manchester.ac.uk
Cochrane Library number
CD004152
Editorial group
Cochrane Oral Health Group
Editorial group code
ORAL
S O U R C E S
O F
S U P P O R T
External sources of support
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Swedish Medical Research Council (9495) SWEDEN
Internal sources of support
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Sahlgrenska Academy at Goteborg University SWEDEN
The University Dental Hospital of Manchester UK
S Y N O P S I S
No strong evidence to either recommend or discourage the use of antibiotics to prevent infections
when having a dental implant inserted.
Missing teeth can sometimes be replaced with dental implants to which a crown, bridge or denture can
be attached. Bacteria introduced during placement of implants can lead to infection. No reliable
evidence of the effects of preoperative antibiotics for patients receiving implants was found. Some
people are prone to infection, including those with immunodeficiencies or metabolic diseases (like
diabetes), people at risk of endocarditis (a heart infection) and people who have received radiotherapy
to the head and neck area. For these patients, preoperative antibiotics might be beneficial. These
recommendations are not based on evidence from the review, but on subjective clinical sense and
experience.
K E Y W O R D S
Humans; *Antibiotic Prophylaxis; Bacterial Infections[*prevention & control]; Dental
Implants[*adverse effects]; Dental Restoration Failure