Non‐surgical periodontal therapy with systemic … aggressive...aggressive periodontitis are...
Transcript of Non‐surgical periodontal therapy with systemic … aggressive...aggressive periodontitis are...
Review Article
Non-surgical periodontaltherapy with systemicantibiotics in patients withuntreated aggressiveperiodontitis: a systematicreview and meta-analysis
Keestra JAJ, Grosjean I, Coucke W, Quirynen M, Teughels W. Non-surgical
periodontal therapy with systemic antibiotics in untreated aggressive periodontitis
patients: a systematic review and meta-analysis. J Periodont Res 2014;
doi: 10.1111/jre.12252 . © 2014 John Wiley & Sons A/S. Published by John
Wiley & Sons Ltd
Objective: The purpose of this meta-analysis is to evaluate the effectiveness of
different systemic antibiotics in combination with scaling and root planing
(SRP) compared to SRP alone in patients with untreated aggressive periodonti-
tis.
Background: In patients with aggressive periodontitis, SRP is often combined
with the use of systemic antibiotics. However, the effectiveness of these anti-
biotics over time and differences in effectiveness between different antibiotics
are hardly known.
Material and Methods: The MEDLINE-PubMed database was searched from
their earliest records until January 20, 2014. Several journals were hand
searched and some authors were contacted for additional information. The fol-
lowing outcome measures were analysed: mean probing pocket depth reduction,
mean clinical attachment level gain and mean bleeding on probing change.
Extracted data were pooled using a random effect model. Weighted mean differ-
ences were calculated and heterogeneity was assessed.
Results: The search yielded 296 abstracts. Ultimately, 101 articles were selected of
which 14 articles met the eligibility criteria. Systemic antibiotics showed a signifi-
cant (p < 0.05) additional pocket depth reduction for moderate (0.36 � 0.22 mm
at 3 mo, 6 mo 0.42 � 0.22 mm and 12 mo 0.88 � 0.27 mm) and deep pockets
(0.74 � 0.36 mm at 3 mo, 6 mo 0.85 � 0.55 mm and 12 mo 1.26 � 0.81 mm)
and a significant clinical attachment gain for moderate (0.26 � 0.18 at 3 mo,
6 mo 0.52 � 0.15 and 12 mo 0.83 � 0.38) and deep pockets (0.59 � 0.18 at
3 mo, 0.96 � 0.21 at 6 mo and 1.00 � 0.80 at 12 mo).
Conclusion: For the treatment of patients with aggressive periodontitis, sys-
temic antibiotics combined with non-surgical periodontal therapy resulted in
J. A. J. Keestra1,2, I. Grosjean1,2,
W. Coucke3, M. Quirynen1,2
W. Teughels1,2,41Department of Oral Health Sciences,
Periodontology, KU Leuven & University of
Leuven, Leuven, Belgium, 2Department of
Periodontology, University Hospitals Leuven,
Leuven, Belgium, 3Department of Clinical
Biology, Scientific Institute of Public Health,
Brussels, Belgium and 4Fund for Scientific
Research Flanders (FWO), Egermontstraat,
Brussels, Belgium
Johan Anton Jochum Keestra, DDS,
Department of Oral Health Sciences,
Periodontology, KU Leuven – University of
Leuven and Department of Periodontology,
University Hospitals Leuven Kapucijnenvoer 33,
B-3000 Leuven, Belgium
Tel: +(32) 16 332485
Fax: +(32) 16 332484
e-mail: [email protected]
Key words: aggressive periodontitis; non-
surgical periodontal therapy; systemic
antibiotics
Accepted for publication November 01, 2014
J Periodont Res 2014All rights reserved
© 2014 John Wiley & Sons A/S.
Published by John Wiley & Sons Ltd
JOURNAL OF PERIODONTAL RESEARCH
doi:10.1111/jre.12252
a significant additional effect compared to non-surgical therapy alone. There
is a visible trend that showed metronidazole + amoxicillin is the most potent
antibiotic combination.
Introduction
Periodontitis is an inflammatory dis-
order that leads to the destruction of
the tooth supporting structures. This
destruction is caused by an imbalance
between a wide range of microorgan-
isms, host response and essential
modifying factors (1). Inflammation,
loss of connective tissue attachment
and loss of alveolar bone support are
the clinical signs. Periodontitis is
divided into aggressive periodontitis
(characterized by a rapid loss of clini-
cal attachment and alveolar bone)
and chronic periodontitis (character-
ized by a progressive loss of clinical
attachment and alveolar bone) (2).
Today the treatment goals are to
resolve inflammation and reduce the
infection so that a clinical condition is
created, which is compatible with
periodontal health (3).
Aggressive periodontitis is charac-
terized by a rapid loss of clinical
attachment and alveolar bone affect-
ing adolescents and young adults (4).
It is subclassified as localized or gen-
eralized in relation to the extent of
the periodontal destruction. In a
recent article, Albandar proposed a
new case definition for patients with
aggressive periodontitis (5). The fol-
lowing distinctive criteria are recom-
mended:
1 An early age onset, usually before
25 years of age. The age of onset
might be a predictor of the disease’s
severity.
2 Loss of periodontal tissue occurs at
multiple permanent teeth. The tis-
sue loss occurs because of a micro-
bial infection.
3 The periodontal destruction is
detectable clinically and radio-
graphically. Typically, the lesions
are depicted radiographically as
vertical bone loss at the proximal
surfaces of posterior teeth. The pat-
tern of bone loss is usually similar
bilaterally. In advanced cases, the
lesions may be depicted radiograph-
ically as a horizontal loss of the
alveolar bone.
4 There is a relatively high progres-
sion rate of periodontal tissue loss.
5 The primary teeth may also be
affected.
6 Clinically healthy except for the
presence of periodontitis.
The major differences with respect
to the classification of Armitage (2)
are that some primary and secondary
features, such as familial aggregation,
elevated proportions of Aggregatibact-
er actinomycetemcomitans or Por-
phyromonas gingivalis, hyper-
responsive macrophage phenotypes
and phagocyte abnormalities, are not
considered anymore.
The treatment and maintenance for
aggressive periodontitis are challeng-
ing for periodontists. There are still
no established protocols and guide-
lines (6). The first step in the treat-
ment of aggressive periodontitis is a
non-surgical periodontal therapy. This
therapy consists of scaling and root
planing (SRP) and oral hygiene
instructions combined with the
adjunctive use of systemic antibiotics.
This SRP can be done within 24 h or
within 1 wk, which is called full
mouth disinfection. The SRP can also
be done over a longer period, which
is called staged SRP. Systemic antibi-
otics help the immune system by sup-
pressing the target microbial species.
It is currently well established that
systemic antibiotics should not be
administered without previous disrup-
tion of the biofilm (7). The possible
antibiotic regimens for aggressive
periodontitis that have been reported
in the literature are penicillins (amoxi-
cillin, AMOX), tetracyclines (doxycy-
cline [DOX], tetracycline, TET),
macrolides (azithromycin, AZI) and
nitroimidazole (metronidazole, MET).
Evidently, the ultimate goal in the
treatment of aggressive periodontitis
is to create a clinical condition, which
is necessary to save and maintain as
many teeth as possible (6).
The reason why systemic antibiotics
are given in combination with the ini-
tial non-surgical periodontal therapy
is to suppress pathogenic bacteria and
create a health-associated biofilm. If
the use of systemic antibiotics is con-
sidered, the clinician needs to take
into account the patient’s compliance,
adverse effects and bacterial resistance
(8–11). The EU (12,13) and WHO
(14) have made some recommenda-
tions to prevent bacterial resistance
worldwide. The key points are, avoid
antibiotics whenever possible and use
narrow-spectrum antibiotics if possi-
ble (11). It is highly necessary to
develop evidence-based clinical proto-
cols that will help and guide the clini-
cian in his decision when and what
kind of systemic antibiotic regimen
should be used. As a step towards this
protocol, this meta-analysis evaluates
if there are differences between the
effectiveness of the different types of
systemic antibiotics in combination
with SRP vs. SRP alone in patients
with untreated aggressive periodonti-
tis and whether the effect is consistent
over time.
Material and methods
The following systematic review was
conducted in agreement with the rec-
ommendations of the Cochrane Col-
laboration (15) and the principles of
the PRISMA (Preferred Reporting
Items for Systemic Reviews and
Meta-Analyses) statement (16).
Focused question (PICO)
The focused question that has been
used was: “Do systemic antibiotics
combined with SRP vs. SRP alone in
untreated aggressive periodontitis
patients have an additional effect on
the clinical outcomes”.
2 Keestra et al.
Search strategy
The MEDLINE-PubMed database
was searched from their earliest
records until January 20, 2014. The
following search terms were used:
Periodontal diseases [MESH] AND
Anti-Infective Agents [MESH] and
Metronidazole [MESH] AND Peri-
odontal diseases [MESH]. In addition,
a manual search was performed of
issues from the past 10 years of the
Journal of Clinical Periodontology,
Journal of Periodontal Research
and Journal of Periodontology.
Study inclusion and exclusion
criteria
The selection process was performed
by two masked reviewers (I.G. and
J.K.). The studies were analysed
according to inclusion criteria:
1 Studies were limited to randomized
controlled clinical trials of at least
more than 1 mo duration.
2 The population was limited to sub-
jects with aggressive periodontitis
(2).
3 The interventions of interest were
full mouth SRP (SRP within 1 wk)
or staged SRP (SRP more than a
week apart) with or without the use
of systematic antibiotics.
4 No specific systemic antibiotics
were excluded.
5 Only papers in the English lan-
guage were included.
Only studies that met all inclusion
criteria were analysed according to
the exclusion criteria:
1 History of refractory periodontitis.
2 Combination of local and systemic
antibiotics.
3 Primary outcome of interest were
not analysed.
4 Duplicated studies.
Outcome variables
The primary outcomes were probing
pocket depth (PPD) reduction and
clinical attachment level change. Clin-
ical attachment level change and PPD
reduction were if possible divided into
moderate (4–6 mm) and deep pockets
(> 6 mm). The secondary outcome
was bleeding on probing (BOP)
change.
Data extraction
The title and abstract of studies of
possible relevance for the review were
obtained and screened independently
by two masked reviewers (I.G. and
J.K.). Papers without abstracts but
with titles suggesting relevance to the
subject of the review were selected for
full text screening. The selected full
text papers were independently read
in detail to check whether they passed
the inclusion/exclusion criteria. The
references of full text articles were
screened for any relevant additional
articles. The papers that fulfilled all
the selection criteria were processed
for data extraction. Discrepancies
with regard to the inclusion or exclu-
sion of studies were resolved by dis-
cussion between the reviewers (I.G.
and J.K.). The extracted data
included year of publication, design
of the study, number of patients per
study arm, length of follow-up, type
of antibiotic, dosage of the antibiotic,
duration of the antibiotic regimen,
timing of the antibiotic in relation to
SRP and primary and secondary out-
come measures at 3, 6, 9 and 12 mo.
Quality assessment
A quality assessment of the methodol-
ogies of all included studies was con-
ducted. It was based on the
randomized controlled trial checklist
of the Cochrane Center, the CON-
SORT guidelines (17), the Delphi list
(18) and the checklist as proposed by
Van der Weijden et al. (19). The fol-
lowing seven criteria were used: selec-
tion bias, allocation bias, performance
bias, detection bias, defined inclusion/
exclusion criteria, attrition bias and
reporting bias. When all these criteria
were fulfilled, the article was classified
as a low risk of bias (L). When one
or two of these criteria were assessed
as high risk of bias or unclear, the
study was regarded to have a moder-
ate potential risk of bias (M). The
risk of potential bias was high, when
three or more criteria had a high or
unclear risk of bias (H). The risk of
bias was evaluated independently by
two masked reviewers (I.G. and J.K.).
If there was any disagreement, it was
resolved by discussion.
Statistical analyses
Data of the included studies were
extracted and entered into a data-
base. Mean values and SDs were
extracted from the data. If no SD
was available it was recalculated by
the formula (SE = SD/√n) with n the
sample size. When intermediate
assessments were performed, the 3, 6,
9 or 12 mo data were considered. If
there were insufficient data available,
the corresponding authors were con-
tacted for additional data. The avail-
able data were recalculated to present
data such as mean BOP change,
mean clinical attachment level gain
and mean PPD reduction. Clinical
attachment level gain and PPD
reduction were also presented for
moderate (4–6 mm) and deep pockets
(> 6 mm). The I2 statistic was used
to assess the heterogeneity between
the studies. Because of observed het-
erogeneity mean differences were
combined for continuous data using
random effects models meta-analysis.
Study weights were determined by the
sample size (20).
Results
The initial search resulted in a total
of 6738 articles (Fig. 1). After screen-
ing the titles, 296 abstracts were
included for further analysis. Analysis
of the abstracts resulted in 101 poten-
tial articles. In the third phase, the
full text articles of the remaining 101
articles were evaluated, of which 44
articles (21–64) did not pass the inclu-
sion criteria (Table 1). Another 43
articles (65–107) were excluded
because they were about patients with
chronic periodontitis. Screening of the
reference lists of full text articles did
not result in any additional articles.
In Table 2 the main characteristics of
the 14 included articles (108–121) are
summarized. Four authors have pro-
vided additional results, which were
Non-surgical periodontal therapy with systemic antibiotics 3
not present in the articles (111,117–119). These 14 included articles repre-
sent 13 studies. These studies were
divided in to the following groups: az-
ithromycin (AZI; two studies), DOX
(two studies), MET (one study),
MET+AMOX (10 studies) and TET
one study. The quality evaluation was
based on seven criteria (17–19). The
potential risk of bias in the 13 studies
included was low in eight, moderate
in two and high in four studies
(Table 2).
Probing pocket depth reduction
At 3 mo, 386 patients out of 13 stud-
ies could be analysed (Fig. 2 and
Table S1). A statistically significant
mean difference of 0.34 � 0.11 mm
and heterogeneity I2 = 26%, in favour
of the use of a systemic antibiotic was
observed. AZI (0.36 � 0.33 mm, one
study, 32 patients and I2 = NA) and
MET+AMOX (0.39 � 0.16 mm, eight
studies, 248 patients and I2 = 38%)
showed a statistically significant mean
difference when compared to the con-
trol group. DOX, MET and TET did
not show a statistically significant
mean difference when compared to
the control group. However, it should
be noted that for AZI, MET and
TET only one study was available.
At 6 mo, 290 patients out of 10 stud-
ies could be analysed. A statistically
significant mean difference of
0.51 � 0.11 mm and heterogeneity
I2 = 28%, in favour of the use of a sys-
temic antibiotic was observed. MET
(1.16 � 0.56 mm, one study, 23
patients and I2 = NA) and MET+A-
MOX (0.51 � 0.09 mm, seven studies,
214 patients and I2 = 0%) showed a
statistically significant mean difference
when compared to the control group.
DOX and AZI did not show a statisti-
cally significant mean difference when
compared to the control group. How-
ever, it should be noted that for DOX,
AZI and MET only one study was
available. At 9 mo, no studies could be
analysed.
At 12 mo, 65 patients out of two
studies could be analysed. A statisti-
cally significant mean difference of
0.51 � 0.38 mm and heterogeneity
I2 = 42%, in favour of the use of a
systemic antibiotic was observed. At
12 mo, only results for MET+AMOX
were available.
Probing pocket depth reduction
moderate pockets
At 3 mo, 191 patients out of six
studies could be analysed (Fig. 3 and
Table S2). A statistically significant
mean difference of 0.36 � 0.22 mm
and heterogeneity I2 = 81%, in
favour of the use of a systemic anti-
biotic was observed. MET+AMOX
(0.43 � 0.22 mm, four studies, 135
patients and I2 = 76%) showed a
statistically significant mean differ-
ence when compared to the control
group. AZI did not show a statisti-
cally significant mean difference
when compared to the control
group.
At 6 mo, 190 patients out of six
studies could be analysed. A statisti-
cally significant mean difference of
0.42 � 0.22 mm and heterogeneity
I2 = 55%, in favour of the use of a
systemic antibiotic was observed.
MET+AMOX (0.50 � 0.21 mm, four
studies, 134 patients and I2 = 45%)
showed a statistically significant mean
difference when compared to the con-
trol group. AZI did not show a statis-
tically significant mean difference
when compared to the control group.
At 9 mo, 24 patients out of one
study could be analysed. No statisti-
cally significant mean difference
(0.65 � 0.94 mm, one study, 24
patients and I2 = NA), in favour of
the use of a systemic antibiotic (AZI)
was observed.
At 12 mo 54 patients out of two
studies could be analysed. A statisti-
cally significant mean difference of
0.88 � 0.27 mm and heterogeneity
I2 = 0%, in favour of the use of a sys-
temic antibiotic was observed.
MET+AMOX (0.89 � 0.28 mm, one
study, 30 patients and I2 = NA)
showed a statistically significant mean
difference when compared to the con-
trol group. AZI did not show a statis-
tically significant mean difference
when compared to the control group.
However, it should be noted that for
both antibiotics only one study was
available.
Probing pocket depth reduction
deep pockets
At 3 mo, 191 patients out of six stud-
ies could be analysed (Fig. 4 and
Table S3). A statistically significant
mean difference of 0.74 � 0.36 mm
and heterogeneity I2 = 73%, in favour
of the use of a systemic antibiotic
was observed. MET+AMOX (0.88 �0.27 mm, four studies, 135 patients
and I2 = 42%) showed a statistically
significant mean difference when com-
Electronic search:
Periodontal diseases [MESH] AND Anti-Infective Agents [MESH]Metronidazole [MESH] AND Periodontal diseases [MESH]
6738 articles
Screening titles:
296 abstracts
Screening abstracts:
Screening full text:
101 full text articles
Total 14 articles included
6442 titles excluded
195 abstracts excluded
44 full text articles excluded
43 chronic periodontitis articles excluded
Fig. 1. Search strategy.
4 Keestra et al.
pared to the control group. AZI did
not show a statistically significant
mean difference when compared to
the control group.
At 6 mo, 190 patients out of six
studies could be analysed. A statisti-
cally significant mean difference of
0.85 � 0.55 mm and heterogeneity
I2 = 88%, in favour of the use of a
systemic antibiotic was observed.
MET+AMOX (1.09 � 0.39 mm, four
studies, 134 patients and I2 = 66%)
showed a statistically significant mean
difference when compared to the con-
trol group. AZI did not show a statis-
tically significant mean difference
when compared to the control group.
At 9 mo, 24 patients out of one
study could be analysed. No statisti-
cally significant mean difference
(0.62 � 1.65 mm, one study, 24
patients and I2 = NA), in favour of
the use of a systemic antibiotic (AZI)
was observed.
At 12 mo, 54 patients out of two
could be analysed. A statistically sig-
nificant mean difference of 1.26 �0.81 mm and heterogeneity I2 = 0%,
in favour of the use of a systemic anti-
biotic was observed. MET+AMOX
(1.40 � 0.91 mm, one study, 30
patients and I2 = NA) showed a statis-
tically significant mean difference when
compared to the control group. AZI
did not show a statistically significant
mean difference when compared to the
control group. However, it should be
noted that for both antibiotics only
one study was available.
Table 1. Characteristics of the 44 excluded articles
Study Reason for exclusion
Preus et al. (2013) (21) Two different control groups
Rodrigues et al. (2012) (22) No control group
Haas et al. (2012) (23) Only radiographic results
Haas et al. (2012) (24) Only microbiological results
Basegmez et al. (2011) (25) Useful clinical results, more information needed. Could not contact the author
Schmidt et al. (2011) (26) No control group
Varela et al. (2011) (27) The same patients – Heller et al. (116)
Serrano et al. (2011) (28) Using different types of antibiotic regimens (amoxicillin/doxycycline)
T€uter et al. (2010) (29) Useful clinical results, more information needed. Could not contact the author
Mestnik et al. (2010) (30) Mestnik et al. (111) – long-term results
Cionca et al. (2010) (31) The same patients – Cionca et al. (77)
Valenza et al. (2009) (32) No control group
Machtei et al. (2008) (33) Differences between two antibiotic regimens, no control group
Akincibay et al. (2008) (34) Differences between two antibiotic regimens, no control group
Novak et al. (2008) (35) Combination systemic and local antibiotics
Moreira et al. (2007) (36) Comparing two different SRP protocols
Kaner et al. (2007) (37) Using different timing moments of antibiotic regimen
Moeintaghavi et al. (2007) (38) Clinical results based on pockets ≥ 5 mm, author could not give extra information
Emingil et al. (2006) (39) Same clinical results – Emingil et al. (72)
Guerrero et al. (2005) (40) The same patients – Griffiths et al. (117)
Vergani et al. (2004) (41) Useful clinical results, more information needed. Could not contact the author
Blandino et al. (2004) (42) Useful clinical results, more information needed. Could not contact the author
Emingil et al. (2004) (91) The same patients – Emingil et al. (43)
Kamma et al. (2000) (44) No control group
Palmer et al. (1999) (45) The same patients – Palmer et al. (104)
Tinoco et al. (1998) (46) SRP in combination with modified Widman flap surgery
Flemmig et al. (1998) (47) Clinical result with/without AA/PG, could not contact the author for more information
Noyan et al. (1997) (48) No control group with SRP
Sefton et al. (1996) (49) The same patients – Smith et al. (98)
Yilmaz et al. (1996) (50) No control group with SRP
Haffajee et al. (1995) (51) Antibiotics in combination with modified Widman flap surgery
Sax�en et al. (1993) (52) Useful clinical results, more information needed. Could not contact the author
Loesche et al. (1992) (53) Clinical outcome: periodontal surgery yes/no
Loesche et al. (1991) (54) Clinical outcome: periodontal surgery yes/no
Chin et al. (1988) (55) The same patients – Al-Joburi et al. (107)
Quee et al. (1987) (56) Useful clinical results, more information needed. Could not contact the author
Joyston-Bechal et al. (1986) (57) Useful clinical results, more information needed. Could not contact the author
Loesche et al. (1984) (58) Control group not comparable with test group
Joyston-Bechal et al. (1984) (59) Useful clinical results, more information needed. Could not contact the author
Lindhe et al. (1983) (60) Three antibiotic periods during treatment
Lindhe et al. (1983) (61) Two antibiotic periods during treatment
Loesche et al. (1981) (62) Control group not comparable with test group
Helld�en et al. (1979) (63) Two antibiotic periods during treatment
Listgarten et al. (1978) (64) Two antibiotic periods during treatment
AA, Actinobacillus actinomycetemcomitans; PG, Porphyromonas gingivalis.
Non-surgical periodontal therapy with systemic antibiotics 5
Table
2.Characteristics
ofthe14included
articles
6 Keestra et al.
Non-surgical periodontal therapy with systemic antibiotics 7
Clinical attachment level gain
At 3 mo, 386 patients out of 13 studies
could be analysed (Fig. 5 and Table
S4). A statistically significant mean dif-
ference of 0.40 � 0.30 mm and hetero-
geneity I2 = 85%, in favour of the use
of a systemic antibiotic was observed.
MET+AMOX (0.50 � 0.40 mm, eight
studies, 248 patients and I2 = 91%)
showed a statistically significant mean
difference when compared to the con-
trol group. AZI, DOX, MET and TET
did not show a statistically significant
mean difference when compared to the
control group. However, it should be
noted that for AZI, MET and TET
only one study was available.
At 6 mo, 290 patients out of 10
studies could be analysed. A statisti-
cally significant mean difference of
0.36 � 0.10 mm and heterogeneity
I2 = 0%, in favour of the use of a
systemic antibiotic was observed.
MET+AMOX (0.36 � 0.10 mm,
seven studies, 214 patients and
I2 = 0%) showed a statistically signifi-
cant mean difference when compared
to the control group. AZI, DOX and
MET did not show a statistically sig-
nificant mean difference when com-
pared to the control group. However,
it should be noted that for AZI, DOX
and MET only one study was avail-
able. At 9 mo, no studies could be
analysed.
At 12 mo, 65 patients out of two
studies could be analysed. A statisti-
cally significant mean difference of
0.46 � 0.37 mm and heterogeneity
I2 = 60%, in favour of the use of a
systemic antibiotic was observed. At
Study or Subgroup1 Azithromycin
Emingil et al. 2012Subtotal (95% CI)
2 Doxycycline
Baltacioglu et al. 2011Xajigeorgiou et al. 2006Subtotal (95% CI)
3 Metronidazole
Xajigeorgiou et al. 2006Subtotal (95% CI)
4 Metronidazole + Amoxicillin
Silva-senem et al. 2013 & Heller et al. 2011Beliveau et al. 2012Mestnik et al. 2012Aimetti et al. 2012Oliveira et al. 2012Griffiths et al. 2011Baltacioglu et al. 2011Yek et al. 2010Xajigeorgiou et al. 2006Subtotal (95% CI)
5 Tetracycline
Palmer et al. 1996Subtotal (95% CI)
Total (95% CI)
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 3 mo control
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 6 mo control Test 9 mo control Test 12 mo control
Fig. 2. Probing pocket depth reduction.
Study or Subgroup1 Azithromycin
Emingil et al. 2012Haas et al. 2008Subtotal (95% CI)
2 Metronidazole + Amoxicillin
Casarin et al. 2012Mestnik et al. 2012Aimetti et al. 2012Griffiths et al. 2011Subtotal (95% CI)
Total (95% CI)
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 3 mo control
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 6 mo control Test 9 mo control Test 12 mo control
Fig. 3. Probing pocket depth reduction moderate pockets.
8 Keestra et al.
12 mo, only results for MET+AMOX
were available.
Clinical attachment level gain
moderate pockets
At 3 mo, 159 patients out of five
studies could be analysed (Fig. 6 and
Table S5). A statistically significant
mean difference of 0.26 � 0.18 mm
and heterogeneity I2 = 43%, in favour
of the use of a systemic antibiotic was
observed. MET+AMOX (0.27 �0.19
mm, four studies, 135 patients and
I2 = 57%) showed a statistically sig-
nificant mean difference when com-
pared to the control group. AZI did
not show a statistically significant
mean difference when compared to
the control group. However, it should
be noted that for AZI only one study
was available.
At 6 mo, 158 patients out of five
studies could be analysed. A statisti-
cally significant mean difference of
0.52 � 0.12 mm and heterogeneity
I2 = 14%, in favour of the use of a
systemic antibiotic was observed.
MET+AMOX (0.52 � 0.15 mm, four
studies, 134 patients and I2 = 32%)
showed a statistically significant
mean difference when compared to
the control group. AZI did not show
a statistically significant mean differ-
ence when compared to the control
group. However, it should be noted
that for AZI only one study was
available.
At 9 mo, 24 patients out of one
study could be analysed. No statisti-
cally significant mean difference
(0.41 � 1.75 mm, one study, 24
patients and I2 = NA), in favour of
the use of a systemic antibiotic (AZI)
was observed.
Study or Subgroup1 Azithromycin
Emingil et al. 2012Haas et al. 2008Subtotal (95% CI)
2 Metronidazole + Amoxicillin
Casarin et al. 2012Mestnik et al. 2012Aimetti et al. 2012Griffiths et al. 2011Subtotal (95% CI)
Total (95% CI)
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 3 mo control
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 6 mo control Test 9 mo control Test 12 mo control
Fig. 4. Probing pocket depth reduction deep pockets.
Study or Subgroup1 Azithromycin
Emingil et al. 2012Subtotal (95% CI)
2 Doxycycline
Baltacioglu et al. 2011Xajigeorgiou et al. 2006Subtotal (95% CI)
3 Metronidazole
Xajigeorgiou et al. 2006Subtotal (95% CI)
4 Metronidazole + Amoxicillin
Silva-senem et al. 2013 & Heller et al. 2011Aimetti et al. 2012Mestnik et al. 2012Beliveau et al. 2012Oliveira et al. 2012Griffiths et al. 2011Baltacioglu et al. 2011Yek et al. 2010Xajigeorgiou et al. 2006Subtotal (95% CI)
5 Tetracycline
Palmer et al. 1996Subtotal (95% CI)
Total (95% CI)
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 3 mo control
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 6 mo control Test 9 mo control Test 12 mo control
Fig. 5. Clinical attachment level gain.
Non-surgical periodontal therapy with systemic antibiotics 9
At 12 mo, 54 patients out of two
studies could be analysed. A statisti-
cally significant mean difference of
0.83 � 0.38 mm and heterogeneity
I2 = 0%, in favour of the use of a sys-
temic antibiotic was observed.
MET+AMOX (0.85 � 0.39 mm, one
study, 30 patients and I2 = NA)
showed a statistically significant mean
difference when compared to the con-
trol group. AZI did not show a statis-
tically significant mean difference
when compared to the control group.
However, it should be noted that for
both antibiotics only one study was
available.
Clinical attachment level gain deep
pockets
At 3 mo, 159 patients out of five
studies could be analysed (Fig. 7 and
Table S6). A statistically significant
mean difference of 0.59 � 0.18 mm
and heterogeneity I2 = 12%, in favour
of the use of a systemic antibiotic
was observed. MET+AMOX (0.63 �
0.25 mm, four studies, 135 patients
and I2 = 34%) showed a statistically
significant mean difference when com-
pared to the control group. AZI did
not show a statistically significant
mean difference when compared to
the control group. However, it should
be noted that for AZI only one study
was available.
At 6 mo, 158 patients out of five
studies could be analysed. A statisti-
cally significant mean difference of
0.96 � 0.21 mm and heterogeneity
I2 = 14%, in favour of the use of a
systemic antibiotic was observed.
MET+AMOX (0.94 � 0.28 mm, four
studies, 134 patients and I2 = 34%)
showed a statistically significant
mean difference when compared to
the control group. AZI did not show
a statistically significant mean differ-
ence when compared to the control
group. However, it should be noted
that for AZI only one study was
available.
At 9 mo, 24 patients out of one
study could be analysed. No statisti-
cally significant mean difference
(0.52 � 2.71 mm, one study, 24
patients and I2 = NA), in favour of
the use of a systemic antibiotic (AZI)
was observed.
At 12 mo, 54 patients out of two
studies could be analysed. A statisti-
cally significant mean difference of
1.00 � 0.80 mm and heterogeneity
I2 = 0%, in favour of the use of a
systemic antibiotic was observed.
MET+AMOX (1.03 � 0.84 mm, one
study, 30 patients and I2 = NA)
showed a statistically significant mean
difference when compared to the con-
trol group. AZI did not show a statis-
tically significant mean difference
when compared to the control group.
However, it should be noted that for
both antibiotics only one study was
available.
Bleeding on probing change
At 3 mo, 333 patients out of 11
studies could be analysed (Fig. 8
and Table S7). A statistically signifi-
Study or Subgroup1 Azithromycin
Haas et al. 2008Subtotal (95% CI)
2 Metronidazole + Amoxicillin
Aimetti et al. 2012Casarin et al. 2012Mestnik et al. 2012Griffiths et al. 2011Subtotal (95% CI)
Total (95% CI)
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 3 mo control
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 6 mo control Test 9 mo control Test 12 mo control
Fig. 6. Clinical attachment level gain moderate pockets.
Study or Subgroup1 Azithromycin
Haas et al. 2008Subtotal (95% CI)
2 Metronidazole + Amoxicillin
Aimetti et al. 2012Casarin et al. 2012Mestnik et al. 2012Griffiths et al. 2011Subtotal (95% CI)
Total (95% CI)
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 3 mo control
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Mean differenceIV, Random, 95% CI
–1 –0.5 0 0.5 1
Test 6 mo control Test 9 mo control Test 12 mo control
Fig. 7. Clinical attachment level gain deep pockets.
10 Keestra et al.
cant mean difference of
9.38 � 4.70% and heterogeneity
I2 = 81%, in favour of the use of a
systemic antibiotic was observed.
MET+AMOX (10.07 � 5.85%,
seven studies, 219 patients and
I2 = 89%) showed a statistically sig-
nificant mean difference when com-
pared to the control group. AZI,
DOX, MET and TET did not show
a statistically significant mean differ-
ence when compared to the control
group. However, it should be noted
that for AZI, DOX, MET and TET
only one study was available.
At 6 mo, 266 patients out of nine
studies could be analysed. A statisti-
cally significant mean difference of
6.84 � 3.81% and heterogeneity
I2 = 18%, in favour of the use of a
systemic antibiotic was observed.
MET+AMOX (8.85 � 5.51 mm, six
studies, 190 patients and I2 = 43%)
showed a statistically significant mean
difference when compared to the con-
trol group. AZI, DOX and MET did
not show a statistically significant
mean difference when compared to
the control group. However, it should
be noted that for AZI, DOX and
MET only one study was available.
At 9 mo, no studies could be analy-
sed.
At 12 mo, 65 patients out of two
studies could be analysed. A statisti-
cally significant mean difference of
12.76 � 10.35% and heterogeneity
I2 = 32%, in favour of the use of a
systemic antibiotic was observed. At
12 mo, only results for MET+AMOX
were available.
Discussion
In the literature, evidence is available
about the additional effect of sys-
temic antibiotics in combination with
SRP for the treatment of patients
with aggressive periodontitis when
compared to only SRP. This review
has tried to evaluate systematically
the current available evidence and
has tried to compare the effectiveness
of different types of systemic antibi-
otics as well as their long-term
effects (up to 1 year). Thirteen clini-
cal studies could be included from
which the data were obtained and
used to calculate the mean difference
in clinical improvement for PPD,
clinical attachment level and BOP
change. PPD and clinical attachment
level difference were additionally
analysed for initially moderate pock-
ets (4–6 mm) and deep pockets
(> 6 mm).
The meta-analysis for the mean
PPD difference showed statistically
significant differences when compared
to SRP at 3, 6 and 12 mo in favour
of the adjunctive use of systemic
antibiotics (0.34 � 0.11, 0.51 � 0.11
and 0.51 � 0.38 mm). The analysis
was hampered by the fact that the
follow-up period from most of the
studies was only 3–6 mo. When anal-
ysing only the studies that had
results at 3, 6 and 12 mo
(108,111,116), the clinical additional
difference of these studies was similar
at 3 mo (0.33 � 0.33 mm), higher at
6 mo (0.63 � 0.27 mm) and similar
at 12 mo (0.51 � 0.38 mm) when
compared to the overall effect. Over-
all, it seems that the initial effect of
the adjunctive systemic antibiotics on
the mean PPD difference remains
stable for at least 1 year. Addition-
ally only two studies of MET+A-
MOX were available at 12 mo and
unfortunately no other systemic anti-
biotic regimen was available. It
became clear that only for MET+A-
Study or Subgroup
1 AzithromycinEmingil et al. 2012Subtotal (95% CI)
2 Doxycycline
Xajigeorgiou et al. 2006Subtotal (95% CI)
3 Metronidazole
Xajigeorgiou et al. 2006Subtotal (95% CI)
4 Metronidazole + Amoxicillin
Silva-senem et al. 2013 & Heller et al. 2011Oliveira et al. 2012Casarin et al. 2012Aimetti et al. 2012Beliveau et al. 2012Mestnik et al. 2012Griffiths et al. 2011Xajigeorgiou et al. 2006Subtotal (95% CI)
5 Tetracycline
Palmer et al. 1996Subtotal (95% CI)
Total (95% CI)
Mean differenceIV, Random, 95% CI
–20 –10 0 10 20
Test 3 mo control
Mean differenceIV, Random, 95% CI
–20 –10 0 10 20
Mean differenceIV, Random, 95% CI
–20 –10 0 10 20
Mean differenceIV, Random, 95% CI
–20 –10 0 10 20
Test 6 mo control Test 9 mo control Test 12 mo control
Fig. 8. Bleeding on probing change.
Non-surgical periodontal therapy with systemic antibiotics 11
MOX there is evidence that the mean
PPD difference when compared to
SRP could be obtained for up to
1 year.
The meta-analysis for the mean
PPD difference in moderate and deep
pockets showed a similar outcome as
for mean whole mouth PPD reduction
albeit more pronounced. When analy-
sing only the studies that had results
at 3, 6 and 12 mo (111,119), the clini-
cal additional difference for the mod-
erate pockets in these studies was
higher at 3 mo (0.73 � 0.32 mm) and
6 mo (0.74 � 0.28 mm) and similar at
12 mo (0.88 � 0.27 mm), for the deep
pockets in these studies was higher at
3 mo (1.28 � 0.90 mm) and 6 mo
(1.35 � 0.71 mm) and similar at
12 mo (1.26 � 0.81 mm) when com-
pared to the overall effect. Based on
these studies, it seems that the initial
effect of the systemic antibiotics on
the mean PPD difference of moderate
and deep pockets remains stable for
at least 1 year. Additionally only one
study using AZI (119) and one using
MET+AMOX (111) were available at
12 mo. It became clear that only for
MET+AMOX the mean PPD differ-
ence when compared to SRP could be
obtained for up to 1 year.
The meta-analysis for the mean
clinical attachment level difference
showed statistically significant differ-
ences when compared to SRP at 3, 6
and 12 mo in favour of the use of
antibiotics (0.41 � 0.32, 0.36 � 0.11
and 0.46 � 0.37 mm). The analysis
was also hampered by the fact that
the follow-up period from most of
the studies was only 3–6 mo. When
analysing only the studies that had
results at 3, 6 and 12 mo (108,111),
the clinical additional difference of
these studies was higher at 3 mo
(0.63 � 0.35 mm) and 6 mo
(0.49 � 0.27 mm), and similar at
12 mo (0.46 � 0.37 mm) when com-
pared to the overall effect. Overall, it
seems that the initial effect of the sys-
temic antibiotics on the mean clinical
attachment level difference remains
stable for at least 1 year. Addition-
ally, only two studies using MET+A-
MOX were available at 12 mo and
unfortunately no other antibiotics
were available. It became clear that
for MET+AMOX the mean clinical
attachment level difference when com-
pared to SRP could be obtained for
up to 1 year.
The meta-analysis for the mean
clinical attachment level difference in
moderate and deep pockets showed a
similar outcome as for mean whole
mouth clinical attachment level differ-
ence albeit more pronounced. When
analysing only the studies that had
results at 3, 6 and 12 mo (111,119),
the clinical additional difference for
the moderate pockets in these studies
was higher at 3 mo (0.61 � 0.36 mm)
and 6 mo (0.58 � 0.32 mm) and simi-
lar at 12 mo (0.83 � 0.38 mm), for
the deep pockets in these studies was
higher at 3 mo (1.09 � 0.66 mm) and
6 mo (1.05 � 0.69 mm) and similar at
12 mo (1.00 � 0.80 mm) when com-
pared to the overall effect. Based on
these studies, it seems that the initial
effect of the systemic antibiotics on
the mean clinical attachment level dif-
ference of moderate and deep pockets
remains stable for at least 1 year.
Additionally only one study using
AZI (119) and one using MET+A-
MOX (111) were available at 12 mo.
It became clear that only for
MET+AMOX the mean clinical
attachment level difference when com-
pared to SRP could be obtained for
up to 1 year.
The meta-analysis for the mean
BOP difference showed statistically
significant differences when compared
to SRP at 3, 6 and 12 mo in favour
of the use of antibiotics (9.38 �4.70%, 6.84 � 3.81% and 12.76 �10.35%). The analysis was ham-
pered by the fact that the follow-up
period from most of the studies was
only 3–6 mo. When analysing only
the studies that had results at 3, 6
and 12 mo (108,111), the clinical
additional difference of these studies
was higher at 3 mo (12.38 � 8.76%)
and 6 mo (15.16 � 9.01%) and
similar at 12 mo (12.76 � 10.35%)
when compared to the overall effect.
Overall, it seems that the initial
effect of systemic antibiotics on the
mean BOP difference remains stable
for at least 1 year. Additionally only
two studies of MET+AMOX were
available at 12 mo and unfortunately
no other antibiotics were available.
It became clear that for MET+A-
MOX the mean clinical attachment
level difference when compared to
SRP could be obtained for up to
1 year.
The 13 studies included in this
review represent a large amount of
data that could be of high value. The
quality of the articles were analysed
based on seven criteria (17–19). Over-
all, the studies with a high risk of bias
were also accepted for the meta-analy-
sis. To check if the studies with a high
risk of bias (110,114,115,121) had
some impact on the final outcomes,
the meta-analysis for the clinical out-
comes: overall PPD difference, overall
clinical attachment level difference
and overall BOP difference were recal-
culated. This having done resulted in
an overall PPD difference at 3 mo
(0.29 � 0.09 mm), 6 mo (0.49 � 0.14
mm) and 12 mo (0.51 � 0.38 mm),
overall clinical attachment level differ-
ence at 3 mo (0.25 � 0.11 mm), 6 mo
(0.35 � 0.11 mm) and 12 mo (0.46
� 0.37 mm) and overall BOP differ-
ence at 3 mo (10.30 � 6.98%), 6 mo
(7.30 � 4.23%) and 12 mo (12.76 �10.35%). For the overall PPD differ-
ence, clinical attachment level differ-
ence and BOP difference, the
difference was initially less but at
12 mo almost the same as the results
with none of the studies excluded.
Overall, the studies with a high risk
of bias could bias the results. How-
ever, more studies will give more con-
clusive results.
The findings of this meta-analysis
should be interpreted with caution
because the meta-analysis had some
limitations. There were no restrictions
for the study population made. In
addition, there was only a limited
amount of data (13 studies) available.
In the 13 studies there were only four
different antibiotics used. For AZI
(109,119), DOX (115,120), MET (120)
and TET (121) just one or two studies
were available compared with 10 stud-
ies (108,110–118,120) for the combi-
nation MET+AMOX. As yet there is
no general consensus on which spe-
cific systemic antibiotic should be
used. Nearly all the studies had a fol-
low-up period of 6 mo. Unfortu-
12 Keestra et al.
nately, just three studies
(108,111,116,119) showed the results
at 12 mo. As only three studies had a
12 mo follow-up period and because
of the previous discussed limited
availability of data it is dangerous to
give long-term conclusions about the
effect of antibiotics.
Since the data of our previous
study Keestra et al. (122) were avail-
able it was possible to compare the
effectiveness of MET+AMOX in
chronic vs. patients with aggressive
periodontitis. When analysing the
data, the PPD difference for moderate
pockets in patients with chronic peri-
odontitis was 0.60 � 0.15 mm at
3 mo, 0.50 � 0.23 mm at 6 mo and
0.60 � 0.24 mm at 12 mo. While in
patients with aggressive periodontitis,
it was 0.43 � 0.22 mm at 3 mo, 0.50
� 0.21 mm at 6 mo and 0.89 �0.28 mm at 12 mo. The PPD differ-
ence for deep pockets in patients with
chronic periodontitis was 0.92 �0.49 mm at 3 mo, 0.79 � 0.27 mm at
6 mo and 1.00 � 0.53 mm at 12 mo.
In patients with aggressive periodonti-
tis, the results were 0.88 � 0.27 mm
at 3 mo, 1.09 � 0.39 mm at 6 mo
and 1.40 � 0.91 mm at 12 mo. The
clinical attachment level difference for
moderate pockets in patients with
chronic periodontitis was 0.42 �0.18 mm at 3 mo, 0.33 � 0.14 mm at
6 mo and 0.40 � 0.22 mm at 12 mo.
While in patients with aggressive peri-
odontitis, it was 0.27 � 0.19 mm at
3 mo, 0.52 � 0.15 mm at 6 mo and
0.85 � 0.39 mm at 12 mo. The clini-
cal attachment level difference for
deep pockets in patients with
chronic periodontitis was 0.67 �0.55 mm at 3 mo, 0.48 � 0.53 mm
at 6 mo and 0.80 � 0.48 mm at
12 mo. In patients with aggressive
periodontitis the results were 0.63 �0.25 mm at 3 mo, 0.94 � 0.28 mm
at 6 mo and 1.03 � 0.84 mm at
12 mo. The number of studies on
which these data are based was simi-
lar for both periodontal conditions.
Based on these data it seems that
the effect of MET+AMOX in
patients with aggressive periodontitis
is lower at 3 mo compared to the
effect in patients with chronic peri-
odontitis. However, the effect of
MET+AMOX is higher at 6 and
12 mo in patients with aggressive
periodontitis than in patients with
chronic periodontitis.
In the past 3 years, four systematic
reviews have been published about
systemic antibiotics in combination
with SRP for the treatment of
patients with periodontitis. The sys-
tematic review from Zandbergen et al.
(123) focused on the effect of
MET+AMOX in combination with
SRP without making the distinction
between patients with aggressive peri-
odontitis and patients with chronic
periodontitis. Two other reviews from
Sgolastra et al. (124) deal with DOX
and MET+AMOX (125) in combina-
tion with SRP for the treatment of
patients with chronic periodontitis.
Only one other review, also from Sgo-
lastra et al. (10), focused on systemic
antibiotics in combination with SRP
for the treatment of patients with
aggressive periodontitis. However,
only MET+AMOX was included in
the meta-analysis. A disadvantage of
the latter meta-analysis is that for cal-
culating the PPD, clinical attachment
level and BOP, 3 and 6 mo follow-up
data were pooled and used for the
meta-analysis. As far as the data of
the current meta-analysis can be com-
pared to this meta-analysis, the data
appear similar.
In 2014 Preus et al. (11) emphasized
that extreme care should be taken
when the usage of systemic antibiotics
in patients with periodontitis is con-
sidered. These authors addressed four
items that might be potential caveats
in recent reviews (10,123–125). One of
these was the overall treatment strat-
egy. In the literature, many different
non-surgical periodontal treatment
options are available. In Table 2 a
subdivision has been made between
studies using a full mouth SRP and
staged SRP approach. A subanalysis
was tried to see if there is a difference
in outcome depending on the SRP
approach. Regrettably, too few studies
were available to make a reasonable
conclusion. Additionally, there are no
studies available that compared a full
mouth SRP and systemic antibiotics
to staged SRP and systemic antibiot-
ics. Perhaps further research should
focus on the most effective non-surgi-
cal periodontal therapy instead of the
most effective systemic antibiotic regi-
men.
The results of this meta-analysis
support the additional effect of the
usage of systemic antibiotics in
patients with aggressive periodontitis.
These systemic antibiotics support the
immune system by suppressing the
target microbial species and causes a
delayed microbial infection, better
infection control and, in the end, an
improved periodontal healing. The
widespread usage of systemic antibiot-
ics in the dental practice is not some-
thing that should be promoted.
Therefore, the clinical additional ben-
efit should be balanced against the
side effects such as bacterial resis-
tance, nausea, thrush, gastrointestinal
intolerance, antibiotic hypersensitivity,
vomiting and diarrhoea. As men-
tioned in the introduction the WHO
(14) and EU (12,13) made some rec-
ommendations to prevent bacterial
resistance. The bacterial resistance
may be a neglected problem, which
was already proven in 2005 by Van
Winkelhoff. The study showed a
major susceptibility difference profile
between periodontal pathogens iso-
lated from patients with periodontitis
in Spain and the Netherlands (126).
Currently it is impossible to define
which microbiological profiles would
necessitate the use of adjunctive sys-
temic antimicrobials. At the fourth
European Workshop on Periodontol-
ogy, Herrera et al. in 2002 defined
these specific clinical situations, as
patients with deep pockets, patients
with progressive or “active” disease,
or with specific microbiological pro-
files (127). In the consensus statement
of the sixth European Workshop on
Periodontology, it was posed that the
use of systemic antibiotics in peri-
odontitis should be restricted to cer-
tain patients and certain periodontal
conditions such as in aggressive peri-
odontitis or in severe and progressing
forms of periodontitis (9).
Based on the findings of this meta-
analysis, systemic antibiotics com-
bined with non-surgical periodontal
therapy resulted in a significant addi-
tional effect for the treatment of
Non-surgical periodontal therapy with systemic antibiotics 13
patients with aggressive periodontitis.
Because of the limited availability of
different antibiotic regimens with an
adequate quantity of studies, there
remains only one antibiotic regimen,
MET+AMOX. Therefore, it is not
possible to draw the conclusion that
MET+AMOX is the best performing,
but there is a visible trend. The anti-
biotic regimens AZI, DOX, MET,
TET did not show any significant
additional effect. The effect of
MET+AMOX on patients with
aggressive periodontitis is lower at
3 mo but higher at 6 and 12 mo com-
pared to the patients with chronic
periodontitis. For long-term stability,
more long-term studies are needed to
prove the firmness of the additional
effect. However, based on currently
available data, the clinical benefit of
MET+AMOX is not lost over a per-
iod of 1 year and even seems to
increase. Their prescription, however,
should be considered on a case-by-
case basis and limited as much as pos-
sible, considering the risks of indis-
criminate use of systemic antibiotics
in the world.
Acknowledgements
This paper has been prepared without
any sources of institutional, private
or corporate financial support, and
there are no potential conflicts of
interest.
Supporting Information
Additional Supporting Information
may be found in the online version of
this article:
Table S1 PPD reduction.
Table S2 PPD reduction moderate
pockets.
Table S3 PPD reduction deep pock-
ets.
Table S4 CAL gain.
Table S5 CAL gain moderate pock-
ets.
Table S6 CAL gain deep pockets.
Table S7 BOP change.
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