Download Effect of systemic antibiotics on clinical and patientreported

Wah Ching Tan
Marianne Ong
Jie Han
Nikos Mattheos
Bjarni E. Pjetursson
Alex Yi-Min Tsai
Ignacio Sanz
May C.M. Wong
Niklaus P. Lang
on Behalf of the ITI
Antibiotic Study Group
Effect of systemic antibiotics on
clinical and patient-reported outcomes
of implant therapy – a multicenter
randomized controlled clinical trial
Authors’ affiliations:
Wah Ching Tan, Marianne Ong, National Dental
Centre Singapore, Singapore, Singapore
Jie Han, Peking University School of Stomatology,
Beijing, China
Nikos Mattheos, Griffith University, Gold Coast,
Queensland, Australia
Nikos Mattheos, May C.M. Wong, Niklaus P. Lang,
Faculty of Dentistry, The University of Hong Kong,
Hong Kong SAR, China
Bjarni E. Pjetursson, Faculty of Odontology,
University of Iceland, Reykjavik, Iceland
Alex Yi-Min Tsai, Department of Periodontology,
School of Dental Medicine, National Taiwan
University, Taipei, Taiwan
Ignacio Sanz, Universidad Complutense de Madrid,
Madrid, Spain
ETEP Research Group
Key words: complications, dental implants, failures, implant dentistry, patient-reported
Corresponding author:
Dr. Wah Ching Tan, BDS, MDS, Dr.med.dent.
Consultant, National Dental Centre Singapore
5 Second Hospital Avenue
Singapore 168938
Singapore
Tel.: +65 98553559
Fax: +65 64766071
e-mail: [email protected]
bruising and bleeding were obtained over 14 days. ANOVA was performed for the VAS. Chi-square
outcomes, success, survival, systemic antibiotics
Abstract
Objectives: To determine the effect of various systemic antibiotic prophylaxis regimes on patientreported outcomes and postsurgical complications in patients undergoing conventional implant
installation.
Material and methods: Three hundred and twenty-nine healthy adults in need of conventional
implant installation were randomly assigned to one of four groups: (i) preoperatively 2 g of
amoxycillin 1 h before surgery (positive control, PC), (ii) postoperatively 2 g of amoxycillin
immediately following surgery (test 1, T1), (iii) preoperatively 2 g of amoxycillin 1 h before and
500 mg thrice daily on days 2 and 3 after surgery (test 2, T2), (iv) preoperatively 2 g of placebo 1 h
before surgery (negative control, NC). Subjects were examined clinically by blinded examiners over
8 weeks after implant installation. In addition, Visual Analogue Scales (VAS) for pain, swelling,
tests were applied for postsurgical complications.
Results: All VAS scores were low for all groups and decreased over time (P < 0.001). There were no
significant differences for the VAS scores between the various groups at any time point (P > 0.05).
There was only a significant difference in flap closure at week 4, where NC had 5% of the subjects
not achieving complete wound closure compared to 0% for the three other groups (P = 0.01), with
no other significant differences for any postsurgical complications (P > 0.05).
Conclusion: For standard single implant placement, prophylactic systemic antibiotics either before
or after, or before and after the surgical procedure do not improve patient-reported outcomes or
prevalence of postsurgical complications.
Conflicts of interest: The authors declare no conflict of
interest.
Date:
Accepted 24 November 2012
To cite this article:
Tan WC, Ong M, Han J, Mattheos N, Pjetursson BE, Tsai
AY-M, Sanz I, Wong MCM, Lang NP. Effect of systemic
antibiotics on clinical and patient-reported outcomes of
implant therapy – a multicenter randomized controlled
clinical trial.
Clin. Oral Impl. Res. 00, 2013, 1–9
doi: 10.1111/clr.12098
The use of prophylactic antibiotics against
postsurgical infection has largely been advocated. However, the effects of such measures
remain obscure, and controversial beneficial
outcomes have been reported in randomized
controlled clinical trials so far for oral surgical procedures (Monaco et al. 2009; Siddiqi
et al. 2010; Pasupathy & Alexander 2011). In
the field of oral implant dentistry, the use of
systemic antibiotics remains a controversial
issue, and various antibiotic regimes have
been propagated without providing scientific
© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
evidence for them. Some authors (Laskin
et al. 2000) reported higher survival rates
with the application of preoperative antibiotics, while others (Gynther et al. 1998) found
no difference in postoperative infection and
survival rates of implants with pre- and posttreatment antibiotics when compared to a
control group without them. Moreover, no
additional benefits were found with the use
of antibiotics when compared to controls in a
recent randomized controlled clinical trial
(Abu-Ta’a et al. 2008). No significant advan-
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Tan et al Systemic antibiotics and implant dentistry
tages pertaining to postsurgical infection
were found with the use of perioperative
antibiotics for implant surgeries, provided
proper asepsis was established. Furthermore,
a multicenter placebo-controlled randomized
clinical trial (RCT) (Anitua et al. 2009) on
antibiotic prophylaxis with placement of single dental implants confirmed no statistically
significant differences for postsurgical infection, adverse events, and implant failures
between the groups.
These two RCTs were analyzed together
with two further RCTs from Italy (Esposito
et al. 2008, 2010a) in a recent Cochrane systematic review (Esposito et al. 2010b) with a
follow-up of at least 3 months comparing various prophylactic antibiotic regimes against
administration of a placebo. A statistically
significantly higher number of patients with
implant failures was reported in the placebo
group, with a risk ratio of 0.4. The authors
concluded that there is some evidence suggesting that the use of preoperative antibiotics
may reduce implant failures. It has to be realized, however, that the degree of oral cleanliness prior to implant installation was not
well documented in these studies.
At present, there is still a lack of largescale multicenter studies to support or refute
the need of antibiotic prophylaxis with conventional implant placement. Some authors
recommended antibiotic prophylaxis with the
procedure based on cohort studies and anecdotal experience (Dent et al. 1997). With the
increasing demand for oral implants worldwide and the development of antibiotic resistance due to indiscriminate usage, the use of
antibiotics with conventional implant therapy should be reevaluated and proper guidelines for implant installation established.
The question of whether or not the potential
benefit of antibiotic prophylaxis with conventional implant therapy outweighs the risk of
developing antibiotic resistance remains to
be determined. Moreover, there are no data
on the effect of perioperative administration
of systemic antibiotics in implant surgery on
patient-reported outcomes.
As demonstrated in a retrospective cohort
study (Powell et al. 2005), the prevalence of
infection following periodontal surgery was
low (2.09%). It was concluded that, although
perioperative antibiotics were commonly
used when performing regenerative and
implant procedures, data from this and other
studies suggested that there may be no benefit in using antibiotics for the sole purpose of
preventing postsurgical infections. Likewise,
it may be assumed that the use of perioperative antibiotics in implant installation may
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Clin. Oral Impl. Res. 0, 2013 / 1–9
be of questionable value owing to the low
prevalence of infection associated with
implant installation.
Based on the limitation of the present evidence available due to the lack of RCTs with
a large subject pool, there is no clear evidence to recommend or contraindicate the
use of antibiotics to prevent infections with
oral implant placement. Neither is there any
established protocol of pre-, peri-, or postoperative administration of antibiotics.
Hence, the aims of the present multicenter
RCT were to determine the effects of various
systemic antibiotic prophylaxis regimes on
patient-reported outcome measures (PROMs)
and prevalence of postsurgical complications
in patients undergoing conventional implant
installation.
Material and methods
Subject population
Three hundred and twenty-nine healthy
adults were consecutively admitted to seven
study centers (National Dental Centre Singapore (NDC), Singapore; The University of
Hong Kong, Faculty of Dentistry, Hong Kong
SAR; Peking University School of Stomatology, Beijing, PR China; Griffith University,
Gold Coast, Queensland, Australia; Universidad Complutense de Madrid, Madrid, Spain;
National Taiwan University, Taipei, Taiwan
& University of Iceland, Reykjavik, Iceland)
worldwide for conventional oral implant
therapy. The subjects were recruited between
August 2009 and October 2011.
Ethical aspects
The study protocol was submitted to and
approved by the respective institutional
review boards of the seven institutions. The
subjects were all informed about the purpose
of the study and the risks and benefits associated with it. Informed consent was obtained
for all patients.
The following admission criteria to the
study were observed:
without the need of simultaneous bone
augmentation (bucco-lingual dimension
7 mm, mesio-distal dimension 7 mm
and height 8 mm)
Exclusion criteria
Subjects with any of the following exclusion
criteria at baseline were excluded from the
study:
a Medically compromised subjects (ASA classification III–V)
b Subjects requiring antibiotic prophylaxis
prior to dental treatment
c Subjects aged <19 years
d Heavy smokers or previous heavy smokers
(quit <5 years; 20 cigarettes/day)
e Allergic to amoxycillin or penicillin antibiotics
f Use of any form of antibiotics in the last
3 months
g Pregnant, intend to conceive or breast-feeding woman
h Single tooth edentulous space in the maxilla or mandible with inadequate pristine
bone volume for standard oral implant
placement, with a possible need for bone
augmentation (bucco-lingual dimension
<7 mm, mesio-distal dimension <7 mm,
and height <8 mm).
The interventions involved conventional
implant installation with or without antibiotic prophylaxis. The oral implants were
placed into pristine bone, without any simultaneous bone augmentation. Only one
implant system (Straumannâ Institute, Basel,
Switzerland) was used to minimize confounding factors that might affect the outcome. The
implants used had a moderately rough (SLA)
surface and were in the range of 8–12 mm in
length. The diameters of the implants were
3.3, 4.1 or 4.8 mm. The implants were either
Standard Plusâ or Bone Levelâ implants. A
one-stage implant installation protocol was
employed with the placement of healing abutments, without the need for a second-stage
procedure to expose the implant.
Investigator calibration
Inclusion criteria
a Medically healthy adults (ASA classification I–II), aged 19 years
b Preferably nonsmokers or previous smokers
(quit 5 years), light smokers with <20
cigarettes/day
c No allergies to amoxycillin or penicillin
antibiotics
d Single tooth edentulous space in the maxilla or mandible with adequate pristine
bone for a standard oral implant placement
The study was a blinded randomized controlled clinical trial (RCT) with four treatment arms. Prior to commencement of the
study, a 2-day investigator and examiner
standardization and calibration meeting was
held at the National Dental Centre Singapore, Singapore.
Clinical procedures
The subjects were randomly assigned to one
of four groups (2 test and 2 control groups):
© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Tan et al Systemic antibiotics and implant dentistry
Group 1 (positive control, PC): 2 g of
amoxycillin preoperatively, 1 h prior to
conventional implant placement.
Group 2 (test 1, T1): 2 g of amoxycillin
immediately postoperatively.
Group 3 (test 2, T2): 2 g of amoxycillin
preoperatively, 1 h prior to implant placement and 500 mg three times a day
(8 hourly) on days 2 and 3.
Group 4 (negative control, NC): 2 g of a placebo preoperatively, 1 h prior to implant
placement without any antibiotics.
The medications were prescribed by a designated clinical coordinator in each center,
who was not involved as a surgeon or examiner. With this scheme, the investigators, the
examiners and the surgeons were blinded,
although the patients were not.
Randomization and Allocation concealment
All patients were recruited for comprehensive
dental care. Periodontal and endodontic
health was established prior to surgical interventions. Following a hygienic phase, all
patients were reevaluated for their oral health
and healing response to periodontal therapy,
and a surgical treatment plan was established. Following this, the patients were
entered into the study using randomization
tables allocating the patient a number with a
corresponding envelope. The randomization
tables were prepared for each center separately by a biostatistician (MCMW). Blocked
randomization was performed in blocks of
eight, whereby at every block of eight enrollments, there were two subjects randomly
assigned to one of the four intervention
groups. The envelope contained the allocation to one of the four groups and was
opened 1 h prior to the surgical intervention
by a registered dental surgery assistant owing
to the fact that one test and the two control
groups had to take the medication prior to
implant placement. In this way, the allocation to one of the treatment groups remained
obscure to the operating surgeon.
The parameters examined included:
•
•
Primary outcome variable: Patientreported outcomes: VAS score on pain,
swelling, bruising and bleeding.
Secondary outcome variables: Clinical
recordings of flap closure, pain, swelling,
suppuration, and implant stability by calibrated examiners.
The sequence of events is presented in
Fig. 1.
Statistical and analytical methods
Statistical analysis
Sample size calculation and power analysis
For the sample size calculation, the power
analysis was performed for a one-way fixed
effects analysis of variance (ANOVA) with 4
levels. The criterion for significance was set
at a = 0.05 (type I error) and at b = 0.20 (type
II error). The analysis of variance is nondirectional (i.e., two-tailed) indicating that an
Chi-square (or Chi-square exact) tests were
used to compare the percentage distribution
of postsurgical complications at weeks 1, 2,
4, and 8 among the 4 treatment groups.
Repeated measures ANOVA were performed
on the VAS scores with the use of multivariate tests (Wilk’s Lambda) for the effect of
time and the interaction effect between treatment groups and time (all effects considered
to be fixed). The above analyses were per-
Baseline (Recruitment)
- consent
- baseline probing depths on adjacent teeth
- implant site analysis (stent fabrication, radiographs)
- randomisation
Positive control
(PC)
Pre-operative
antibiotics
Test Group 1 (T1)
Post-operative
antibiotics
Test Group 2 (T2)
Pre- and postoperative
antibiotics
Negative Control
(NC)
No antibiotics, preoperative placebo
Standard Implant Placement
- pre-operation 0.2 % chlorhexidine for 1 minute
- crestal incision
- 1-stage implant placement
- 1 implant system: Straumann ® SLA
- record: bone dimension, buccal bone thickness, soft tissue
dimension, bone quality
Day 1 – Day 6,
VAS scale on swelling,
bruising, bleeding and pain
(patient self-assessment)
Outcome variables
Subjects were examined clinically by calibrated examiners at week 1, 2, 4, and 8 following implant installation for postoperative
complications. In addition, Visual Analogue
Scales (VAS) on a score of 0-10 were obtained
from the patients from day 1 through 7 and
day 14.
The surgeons involved had no access to the
data collection sheets or the group allocation,
while the examiners had no access to the
patients’ treatment records or group allocation.
effect in either direction will be interpreted.
If an effect of 2.5 VAS units difference (largest mean – smallest mean) among the four
treatment groups is expected, the sample size
is 45 cases per group. However, if an effect of
2.0 VAS units is expected, the sample size is
70 cases per group. Calculating a dropout rate
of 20%, n = 84 per group resulting in a power
of 0.80 for an effect size of 2.0 VAS units at a
level of significance of a = 0.05.
-
Review visits at 1 week, 2 weeks, 1 month
Complications (pain, swelling, suppuration, flap closure, implant
stability)
VAS scale (swelling, bruising, bleeding, pain) (Day 7,14 only)
1 month
Prosthodontic management (at 8 weeks)
- impression-taking, issue of crown
- record: implant stability, pain, swelling, purulent discharge
Fig. 1. Sequence of Events.
© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
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Clin. Oral Impl. Res. 0, 2013 / 1–9
Tan et al Systemic antibiotics and implant dentistry
formed using SPSS. To analyze the possible
center effect, a random effect for center (different centers considered to be a random
sample of centers) was added to the above
repeated measures ANOVA using SAS.
Results
The surgical procedures of all 329 subjects
were uneventful. 329 SLA Straumannâ
implants were installed in a nonsubmerged
healing modality. 81 subjects were positive
control (PC), 82 subjects were test group 1
(T1), 86 subjects were test group 2 (T2), and
80 subjects were the negative control (NC).
Distribution of the subjects
Upon analyzing the data, there were no significant differences (all P > 0.05) in subject
profile among the four treatment groups in
terms of age, gender, smoking status, sites of
implantation profile, and implant dimensions
(Table 1).
The subjects were comparable in the four
treatment groups in terms of demographic
characteristics and clinical parameters as
well.
The percentage of patients who took analgesics did not differ significantly (P > 0.05)
between the groups over the different postoperative days (Table 2).
Postsurgical complications
Suppuration
Flap closure
There was only one statistically significant
difference (P = 0.01) for flap closure at week
4, where NC had 5% of subjects not achieving complete wound closure compared to 0%
for the three other groups. There was no significant difference in the other time points
(P > 0.05) among the 4 groups either
(Table 3).
Pain
There was no statistically significant difference in the experience of pain between the 4
treatment groups at any time (P > 0.05;
Fig. 2). The experience of pain was present in
17.1% of all the subjects at 1 week. Pain perception decreased over time, and at week 8,
none of the subjects complained of pain.
Swelling
There was no statistically significant difference in swelling of the operation site
between the four treatment groups at any
time (P > 0.05; Fig. 3). Swelling was present
in 21.4% of all the subjects at 1 week, with
T2 having the highest proportion of 27.1%
and NC having the lowest proportion of
17.5%. This decreased over time, and at
week 8, only 0.6% of the subjects had swelling noted clinically.
Table 1. Baseline characteristics of the subjects and clinical parameters in different groups
Age (Mean)
Gender (%)
Male
Female
Smoking status (%)
Non-smoker
Previous smoker
Light smoker
Smoker
Characteristics of the edentulous sites
Alveolar Bone Width B-L (Mean, mm)
Alveolar Bone Width M-D (Mean, mm)
Buccal Bone Plate Thickness (Mean, mm)
Soft Tissue Thickness (Mean, mm)
Bone Quality (%)
I
II
III
IV
Diameter of the implants used (%)
3.3 mm
4.1 mm
4.8 mm
Length of the implants used (%)
8 mm
10 mm
12 mm
*
Chi-square exact test.
4 |
Clin. Oral Impl. Res. 0, 2013 / 1–9
PC
(n = 81)
T1
(n = 82)
T2
(n = 86)
NC
(n = 80)
Total
(n = 329)
P
48.8
47.8
46.9
45.1
47.1
0.25
50.6
49.4
57.3
42.7
54.7
45.3
58.8
41.2
55.3
44.7
0.74
81.5
9.9
6.1
2.5
80.5
8.5
9.8
1.2
80.2
7.0
12.8
0.0
80.0
10.0
7.5
2.5
80.6
8.8
9.1
1.5
0.83*
8.08
11.08
1.81
2.37
7.81
11.44
1.75
2.39
7.88
11.00
1.88
2.54
7.85
11.79
1.70
2.26
7.91
11.33
1.79
2.39
0.84
0.52
0.59
0.28
2.5
41.2
52.5
3.8
1.2
38.3
50.6
9.9
1.2
40.0
50.6
8.2
1.2
40.0
52.5
6.3
1.5
39.9
51.5
7.1
0.96*
2.5
43.2
54.3
3.7
32.9
63.4
4.6
32.6
62.8
1.3
40.0
58.7
3.0
37.1
59.9
0.64*
14.8
65.4
19.8
18.3
64.6
17.1
12.8
69.8
17.4
12.7
72.1
15.2
14.6
68.0
17.4
0.91
There was no statistically significant difference in suppuration of the operation site
between the four treatment groups at any
time (P > 0.05; Table 3). Less than 1% of all
the subjects yielded suppuration of the operation site. T1 and NC groups showed no suppuration of the sites throughout the 8-week
follow-up.
Implant stability
There was no statistically significant difference in implant stability between the four
groups at any time (P > 0.05; Table 3). At
week 1, one implant of the PC was slightly
mobile, but became stable thereafter. In the
NC group, two implants were slightly mobile
after 2 weeks and one of them became stable
thereafter. The second yielded slight mobility
also after 4 weeks, but no more after
8 weeks. At 8 weeks, another implant in
group NC was slightly mobile and was lost.
Patient-reported outcome measures
All the VAS scores reported by the patients
were low. Results from the repeated measures
ANOVA showed that there was no statistically significant difference between the 4
treatment groups for bleeding, swelling, pain,
and bruising (all P > 0.05; Figs 4–7). There was
a significant time effect, where the mean VAS
scores decreased over time (P < 0.001). However, no significant interaction effect between
the treatment groups and time suggested that
the decrease in the mean VAS scores in different treatment groups was not significantly different from each other for all the variables
assessed. When adjusted for the center effect,
the same results remained that no statistically
significant differences existed among the 4
treatment groups for all outcomes, but for a
significant time effect (data not reported).
Discussion
The present study failed to identify any statistically significant differences in patientreported outcomes between the two treatment and the two control groups. This, in
turn, means that the administration of pre-,
peri-, or postsurgical prophylactic antibiotics
did not influence the wound healing pattern
and the subjective variables at all. It has to
be kept in mind, however, that all the centers participating in this study applied high
standards of infection control practices for
the implant surgical procedures. Moreover,
the patients had been treated periodontally
prior to the implant installation, and chlorh-
© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Tan et al Systemic antibiotics and implant dentistry
Table 2. Percentages of subjects who took analgesics.
PC
T1
T2
NC
Total
P-value
*
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 14
57.5
46.9
54.7
60.8
54.9
0.33
31.3
27.2
25.6
36.3
30.0
0.45
23.8
16.0
18.6
27.5
21.4
0.28
12.5
13.6
4.7
16.3
11.7
0.11
6.3
7.4
2.4
12.5
7.1
0.09
5.0
6.3
1.2
10.0
5.5
0.10*
2.5
5.0
1.2
8.8
4.3
0.07*
0.0
1.3
1.2
3.8
1.5
0.34*
Chi-square exact test.
Table 3. Percentages of subjects with post-surgical outcome variables in the different groups at
weeks 1, 2, 4, and 8 after surgery
PC (n = 81)
Flap Closure
1 week
96.3
2 weeks
93.8
4 weeks
100.0
8 weeks
100.0
Pain
1 week
19.8
2 weeks
3.7
4 weeks
0.0
8 weeks
0.0
Swelling
1 week
21.0
2 weeks
4.9
4 weeks
2.5
8 weeks
1.2
Suppuration
1 week
0.0
2 weeks
1.2
4 weeks
1.3
8 weeks
0.0
Implant stability
1 week
98.7
2 weeks
100.0
4 weeks
100.0
8 weeks
100.0
T1 (n = 82)
T2 (n = 86)
96.3
96.3
100.0
100.0
96.5
96.5
100.0
100.0
13.6
2.5
0.0
0.0
NC (n = 80)
Total (n = 329)
P
95.0
96.2
94.9
98.7
96.0
95.7
98.8
99.7
0.94
0.85
0.01*
0.24
17.6
2.3
0.0
0.0
17.5
1.3
1.3
0.0
17.1
2.4
0.3
0.0
0.78
0.88
0.24
N/A
19.8
3.7
1.2
1.3
27.1
5.8
3.5
0.0
17.5
2.5
1.3
0.0
21.4
4.3
2.2
0.6
0.48
0.80
0.81
0.61
0.0
0.0
0.0
0.0
0.0
1.2
0.0
1.2
0.0
0.0
0.0
0.0
0.0
0.6
0.3
0.3
N/A
1.00
0.49
1.00
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
97.5
98.7
98.7
99.7
99.4
99.7
99.7
0.47
0.38
0.47
0.47
*Statistically significant; Chi-square exact test.
Fig. 2. Percentages of subjects with pain during examination at Weeks 1, 2, 4, and 8 after surgery.
exidine mouthrinses were applied prior to
surgery. Consequently, a high degree of oral
cleanliness was achieved.
Because there is no data on the effect of
perioperative administration of systemic antibiotics in implant surgery on patient-reported
outcomes in the literature, this study provides evidence that perisurgical antibiotic
Fig. 3. Percentages of subjects with swelling during
examination at Weeks 1, 2, 4 and 8 after surgeries.
prophylaxis does not provide beneficial
effects on bruising, swelling, bleeding, or
pain. This statement applies to straightforward implant installations in patients with
no residual periodontal disease and in a clean
oral environment.
The present study has further demonstrated that the perioperative administration
of prophylactic antibiotics did not show any
© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
statistically significant differences in clinical
parameters such as flap closures, suppuration, swelling, implant stability, and pain on
palpation. Regarding implant stability, one
implant in the NC group was mobile at
8 weeks and lost thereafter. Likewise, in the
PC group, one implant was slightly mobile
after 1 week and gained stability thereafter.
While the two T1 and T2 groups did not
reveal any mobile implants at any time, the
NC group presented two more implants with
slight mobility that reached stability thereafter. Hence, it may be speculated that these
slightly mobile implants were in the process
of gaining biological bonding (osseointegration) during the early weeks of healing, while
mechanical stability was lost as a result of
bone resorption in the area of implant
threads (Abrahamsson et al. 2004; Lang et al.
2011). Because both positive and negative
controls were affected by very few implants
yielding slight mobility, this phenomenon
may not be attributable to the administration
of prophylactic antibiotics.
Moreover, these findings are in agreement
with results from two RCTs (Abu-Ta’a et al.
2008; Anitua et al. 2009). One of these compared the effects of the T2 antibiotic regime
in the present study to the NC group, and
the second RCT compared the PC group antibiotic regime of the present study to the NC
group. In the first study (Abu-Ta’a et al.
2008), 40 patients received 1 g of amoxycillin
one hour before and 2 g postoperatively for
2 days, while the control group (n = 40)
received a placebo drug. No significant
advantages regarding postoperative infections
were reported. The second RCT (Anitua et al.
2009) reported on 52 patients with and 53
patients without presurgical (one hour before)
administration of 2 g of amoxycillin. Again,
no statistically significant differences in postsurgical infection rates were observed.
The results of the present study were not
identical to those of additional two RCTs. In
the third RCT (Esposito et al. 2008), 158
patients were given 2 g of amoxycillin one
hour prior to implant installment, thus representing the PC group of the present study.
They were compared with 158 placebocontrolled (NC) patients. Three patients in
the antibiotic test group and two patients in
the placebo group presented with postsurgical
infections. However, eight patients in the
control group lost nine implants, while only
two implants in two patients were lost in the
test group. Although not statistically significant, a slight beneficial effect of perioperative
antibiotic administration was claimed. The
fact that 10 patients of 316 lost an implant
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Tan et al Systemic antibiotics and implant dentistry
PC
T1
T2
NC
Total
Day 1
Day 2
Day 3
1.03
0.36
0.18
0.94
0.31
0.15
0.80
0.27
0.12
0.85
0.27
0.19
0.90
0.30
0.16
Effects
Treatment groups
Time
Treatment groups * Time
Day 4
0.09
0.09
0.10
0.13
0.10
Day 5
0.07
0.05
0.08
0.08
0.07
Day 6
0.04
0.04
0.05
0.08
0.05
p-value
0.963
<0.001
0.737
Day 7
0.04
0.05
0.05
0.04
0.04
Day 14
0.04
0.08
0.06
0.01
0.05
Day 6
0.31
0.34
0.32
0.49
0.36
p-value
0.564
<0.001
0.719
Day 7
0.26
0.23
0.27
0.32
0.27
Day 14
0.12
0.11
0.03
0.08
0.09
Fig. 4. Mean VAS of bleeding (Bleeding-VAS) from Day 1 to Day 14.
PC
T1
T2
NC
Total
Day 1
Day 2
Day 3
2.10
1.82
1.28
1.99
1.83
1.45
2.05
1.91
1.21
2.15
2.10
1.61
2.07
1.92
1.39
Effects
Treatment groups
Time
Treatment groups * Time
Day 4
0.83
0.98
0.80
1.20
0.95
Day 5
0.52
0.59
0.56
0.81
0.62
Fig. 5. Mean VAS of swelling (Swelling -VAS) from Day 1 to Day 14.
postoperatively represents a relatively high
failure rate (3%) for the time being. The reasons for these infections may have been a
6 |
Clin. Oral Impl. Res. 0, 2013 / 1–9
suboptimal periodontal infection control
prior to implant installation or unsatisfactory
oral hygiene practices. In the present study
with emphasis on comprehensive dental care
and pre-implantation infection control, only
one implant was lost of 329 resulting in a
failure rate of 0.3%. Moreover, initial
implant losses failing a successful incorporation may be attributed to other reasons than
infection, such as confounders from the surgical procedure. The high failure rate (3%)
would suggest that this was the case in the
study discussed (Esposito et al. 2008), and
hence, implant losses should not be taken as
evidence for the beneficial effect of prophylactic antibiotic coverage.
In the fourth and last RCT cited (Esposito
et al. 2010a), a total of 252 test and 254 control patients were enrolled, again, testing the
regime of the PC group in the present study
against negative controls (NC) receiving placebo. Four patients in the test and eight
patients in the control group experienced
signs of infection with no statistically significant difference. Five patients in the test
group experienced the loss of seven implants,
and 12 patients with 13 implant losses were
encountered in the control group. Again, it
has to be realized that the failure rate
through infection was 4% in that study. As
mentioned above, initial implant losses may
be attributed to other reasons than infection,
such as confounders from the surgical procedure. Hence, implant losses should not be
taken as evidence for a beneficial effect of
prophylactic antibiotic coverage as well, even
though “trends clearly favoured the antibiotic
group” (Esposito et al. 2010a).
Although the prophylactic antibiotic regime
was not the same in the four RCTs (one study
compared T2 of the present study to NC,
three studies compared PC to NC), they were
meta-analyzed in a recent systematic review
(Esposito et al. 2010b) for the survival (incorporation) rate of implants under prophylactic
antibiotics. The number needed to treat
(NNT) to prevent one patient from losing an
implant was calculated as NNT = 33.
In light of the fact that early implant failures may be attributed to a variety of aspects
including host–parasite, surgical or even prosthetic factors, one implant loss in the present
study of over 300 implants may have
occurred entirely by chance, and hence, a preventive effect of the perisurgical antibiotic
regimen may be highly questionable.
Because implant survival (incorporation
rate) is very high in today’s clinical practice,
most of the studies addressing this parameter
in relation to perioperative antibiotic prophylaxis must be considered as underpowered
(Esposito et al. 2010b). Only the meta-analysis of four underpowered studies (Abu-Ta’a
© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Tan et al Systemic antibiotics and implant dentistry
PC
T1
T2
NC
Total
Day 1
Day 2
Day 3
2.05
1.08
0.80
1.87
1.05
0.69
1.87
1.11
0.84
1.91
1.44
1.21
1.93
1.17
0.88
Effects
Treatment groups
Time
Treatment groups * Time
Day 4
0.49
0.55
0.57
0.97
0.64
Day 5
0.36
0.32
0.42
0.84
0.48
Day 6
0.21
0.25
0.29
0.45
0.30
p-value
0.143
<0.001
0.365
Day 7
0.19
0.25
0.18
0.37
0.25
Day 14
0.09
0.15
0.03
0.12
0.10
Day 5
0.18
0.27
0.22
0.36
0.26
Day 6
0.13
0.22
0.18
0.25
0.19
p-value
0.679
<0.001
0.890
Day 7
0.12
0.15
0.14
0.19
0.15
Day 14
0.04
0.04
0.03
0.03
0.03
Fig. 6. Mean VAS of pain (Pain-VAS) from Day 1 to Day 14.
PC
T1
T2
NC
Total
Day 1
Day 2
Day 3
0.82
0.64
0.42
0.54
0.49
0.39
0.74
0.62
0.44
0.78
0.68
0.62
0.72
0.61
0.47
Effects
Treatment groups
Time
Treatment groups * Time
Day 4
0.32
0.37
0.32
0.51
0.38
Fig. 7. Mean VAS of bruising (Bruising -VAS) from Day 1 to Day 14.
et al. 2008; Esposito et al. 2008, 2010a; Anitua et al. 2009) revealed a risk ratio of 0.4
(95% CI: 0.19–0.84) for early implant failures.
As indicated above, these implant failures
cannot be taken as evidence of the beneficial
effect of perisurgical prophylactic antibiotics,
© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
owing to the presumptive surgical confounders. In the meta-analysis of the four studies
mentioned, the risk ratio for postsurgical
infection was 0.74 (95% CI: 0.37–1.47). In
this relevant parameter for the effect of perioperative antibiotic administration, statistical
significance was not reached indicating basically a lack of benefit from the antibiotic
regimes.
Because the primary goal of the present
study was to determine the effects of various
systemic antibiotic prophylaxis regimes on
patient-reported outcome measures (PROMs)
and postsurgical complications in patients
undergoing conventional implant installation, the power calculation had to be based
on clinically meaningful differences in the
patient-reported outcome measures rather
than on survival rates of implants.
In the present study, no technical complications were diagnosed within the observation period irrespective of the group
allocation of the patients. This may be due to
the fact that only one implant system was
used, thus minimizing the various possibilities of technical complications. On the other
hand, biological complications (mucositis,
peri-implantitis) have to be considered as
generic and not related to implant systems
(Abrahamsson et al. 1998; Albouy et al. 2008,
2009). In the present study, one case of surgical complication (flap opening), one case of
suppuration, two cases of swelling, and one
case of implant mobility were identified in
over 300 implant installations amounting to
a short-term success rate of 98.5%. This may
be testimony of a very meticulous presurgical
periodontal and carefully performed surgical
procedures leaving the oral cavity in a status
of cleanliness.
In the present study, three regimens of
amoxycillin were chosen as this drug is a
suitable first-line antimicrobial agent demonstrating a high level of antimicrobial activity
in patients with dento-alveolar infections
(Kuriyama et al. 2007). Amoxycillin is indicated in the treatment of patients with mild
to moderate infections caused by susceptible
strains of microorganisms. The preoperative
dosage is 2 g, one hour before treatment (Wilson et al. 2007).
The preoperative dosage of amoxycillin
applied in the present study was based on the
antibiotic dosage recommendation by the
American Heart Association (AHA) for prevention of infective endocarditis (Wilson
et al. 2007). The single-dose regime used
postoperatively was to test whether a postoperative dose is equally effective compared to
the positive control. The regime used in the
7 |
Clin. Oral Impl. Res. 0, 2013 / 1–9
Tan et al Systemic antibiotics and implant dentistry
T2 group was modified from the old AHA
recommendation for prevention of infective
endocarditis.
None of the patient-reported or clinical outcomes differed in any of the three antibiotic
groups. This, in turn, means that there was
no superiority for any of the prophylactic
regimes. This is in agreement with previous
studies (Morris et al. 2004; Binahmed et al.
2005), where the authors reported that the use
of various antibiotic regimes did not affect
clinical outcomes after implant installation.
Up to now, predominantly 2 g of amoxycillin
one hour prior to surgery has been recommended without scientific evidence. The
results of the present study suggest that the
post- and perisurgical administration of
prophylactic antibiotics may elicit the same
subjective and clinical effects.
In conclusion, the results of the present
study question the necessity of applying perisurgical antibiotic prophylaxis either before,
at the time of or after implant installation.
Because most of the patients recruited for the
study belonged to the category of straightforward difficulty for surgical implant installation, the conclusions have to be limited to
such patients.
To what extent antibiotics may be indicated for augmentation procedures (advanced
category) remains to be explored. Likewise,
the potential influence of antibiotic prophylaxis in patients with untreated periodontitis
and poor oral hygiene or poor operation room
asepsis has to be determined.
Wacker, Straumann AG, Basel, Switzerland,
is gratefully acknowledged.
Appendix
The ITI Antibiotic Study Group
Acknowledgements:
This study has
been supported by a research grant of the ITI
Foundation (Project 616-2009) and the
Clinical Research Foundation (CRF) for the
Promotion of Oral Health, Brienz,
Switzerland.
The cooperation of the staff of the centers
involved in the study is highly appreciated:
National Dental Centre Singapore,
Department of Restorative Dentistry,
ACORN secretariat; The University of Hong
Kong, Faculty of Dentistry, Implant
Dentistry; Peking University School of
Stomatology, Beijing, PR China, Department
of Periodontology; National Taiwan
University, Taipei, Taiwan, Department of
Periodontology; Griffith University, Gold
Coast, Queensland, Australia, Department of
Periodontology; University Complutense of
Madrid, Spain, Department of
Periodontology; University of Iceland,
Reykjavik, Department of Reconstructive
Dentistry. The cooperation of Mr. Martin
National Dental Centre Singapore, Singapore:
Wah Ching Tan, Chu Guan Koh, Mervyn Ng,
Marianne Ong, Ching Ching Tan, Li Beng
Wong, Gui Feng Shen, Jia Yin Chen, Ping
Liang, Audrey Ho
The University of Hong Kong, Hong Kong
SAR PR China: Niklaus P. Lang, Martina
Lulic, Boyd W.K. Tsang, May C.M. Wong
Peking University School of Stomatology,
Beijing PR China: Jie Han, Huang Xin Meng
Griffith University, Gold Coast, Queensland, Australia: Nikos Mattheos
Universidad Complutense de Madrid,
Spain: Ignacio Sanz, David Herrera, Mariano
Sanz, Fabio Vignoletti
National Taiwan University, Taipei,
Taiwan: Alex Yi-Min Tsai, Cheing-Meei Liu,
Po-Yao Chang, Che-Chang Tu
University of Iceland, Reykjavik, Iceland:
Bjarni E. Pjetursson
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