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Journal of Clinical Periodontology / Volume 51, Issue 8 / p. 997-1004

ORIGINAL ARTICLE Open Access   

Do systemic amoxicillin and metronidazole during the non-surgical peri-

implantitis treatment phase prevent the need for future surgical
treatment? A retrospective long-term cohort study

Jarno Hakkers , Tine E. Vangsted, Arie Jan van Winkelho", Yvonne C. M. de Waal

First published: 04 June 2024

https://doi.org/10.1111/jcpe.14024

Abstract

Aim
The aim of this retrospective long-term follow-up of a 3-month RCT was to
assess whether non-surgical peri-implantitis treatment with adjunctive systemic
antibiotics in#uenced the need for additional surgical treatment.

Materials and Methods

Patients enrolled in an aftercare programme following non-surgical peri-
implantitis treatment, with or without systemic amoxicillin and metronidazole,
were analysed. Data had previously been collected pre-treatment (T0) and 3
months after treatment (T1) and were additionally collected during subsequent
aftercare visits, until the $nal assessment (T2). Primary outcome was the need
for additional surgical peri-implantitis therapy during the aftercare programme,
analysed via Kaplan–Meier analysis and Cox regression. Secondary outcomes
involved clinical parameters, assessed using parametric and non-parametric
tests.

Results
Forty-$ve patients (22 AB− group, 23 AB+ group) were included. The mean
:
 follow-up time between T1 and T2 was 35.9 months (SD = 21.0). 73.9% of the AB+
group and 50.0% of the AB− group did not receive additional surgical therapy
(log-rank test, p = .110). The adjusted Cox regression model did not provide a
signi$cant result for antibiotics (β = .441, 95% CI = 0.159–1.220, p = .115).
Univariable regression analysis highlighted the in#uence of baseline peri-
implant pocket depth on the need for surgical treatment (β = 1.446, 95% CI =
1.035–2.020, p = .031).

Conclusions
Systemic amoxicillin and metronidazole administered during non-surgical peri-
implantitis treatment do not seem to prevent the need for additional surgical
therapy in the long term, during a structured aftercare programme.

Clinical Relevance

Scienti!c rationale for study: There is limited scienti$c evidence to

evaluate the long-term e"ects of non-surgical peri-implantitis treatment
supplemented with systemic antibiotics.

Principal !ndings: Administration of systemic amoxicillin and

metronidazole during non-surgical peri-implantitis treatment did not
signi$cantly lower the number of patients requiring additional surgical
peri-implantitis treatment during the long-term follow-up period.

Practical implications: In the long term, systemic antibiotics do not seem

to prevent the need for an additional surgical intervention after non-
surgical peri-implantitis treatment. However, individually selected cases
may bene$t from additional systemic antibiotics as part of the non-
surgical treatment phase.

1 INTRODUCTION
Peri-implantitis is a multifactorial pathological condition occurring in the tissues
that surround dental implants, characterized by mucosal in#ammation and
subsequent progressive peri-implant bone loss (Berglundh et al., 2018). Non-
:
 surgical and surgical treatment interventions aim at reducing this in#ammatory
process, decreasing the probing pocket depth (PD) and halting peri-implant bone
reduction. It has been demonstrated that clinical parameters, such as bleeding
scores (BS), tend to improve after non-surgical sub-marginal instrumentation (NSI),
but treatment sites frequently show residual or recurrent signs of in#ammation
(Ramanauskaite et al., 2021). Therefore, additional therapeutic measures that aim
at improving the outcome of non-surgical peri-implantitis treatment are frequently
investigated. One such measure is the administration of adjunctive systemic
antimicrobials.

The available literature is inconsistent with regard to the bene$ts of adjunctive

antibiotics during the non-surgical treatment phase. Short-term studies (with a 3-
month follow-up) suggest that the clinical bene$ts of adjunctive antibiotics are
limited. Systemically administered amoxicillin and metronidazole tend to improve
BS and peri-implant PD, but not signi$cantly more than NSI alone (De Waal et
al., 2021; Polymeri et al., 2022). In the systematic review by Liñares et al. (2023), it
was concluded that NSI with adjunctive systemic antibiotics might enhance PD
reduction, especially in deeper pockets. This conclusion is based on three RCTs with
a 12-month follow-up. However, the results between these three studies were not
consistent. Shibli et al. (2019) observed an improvement in peri-implant PD in
patients who received NSI with adjunctive systemically administered amoxicillin and
metronidazole. However, no signi$cant di"erences in PD, clinical attachment levels
(CAL) and proportions of red complex pathogens could be detected after 1 year
when this result was compared with the control group (NSI with a placebo). Similar
results were reported by Almohareb et al. (2020) who observed an equal reduction
in severe peri-implant symptoms after NSI was supplemented with either
photodynamic therapy or systemic amoxicillin and metronidazole, after 6 months.
On the other hand, Blanco et al. (2022) did report signi$cant additional
improvements in clinical, radiographic and microbiologic parameters, 12 months
after NSI was supplemented with systemic metronidazole. It should be noted that,
in this study, NSI was followed by granulation tissue removal and soft tissue
curettage. Whether this therapy is a form of non-surgical treatment can be
debated. In short, these $ndings seem to con$rm the notion that there are
insu%cient data present to support a speci$c antibiotic protocol to treat peri-
implantitis using non-surgical therapy (Feres et al., 2023).

When NSI has not succeeded in reinstating peri-implant health (residual probing
depths ≤5 mm, no bleeding on probing ≥1 probing site and no suppuration on
:
 probing), a surgical treatment approach is indicated. While the routine prescription
of antimicrobials is not recommended, speci$c cases exhibiting severe peri-
implantitis (e.g., initially deep pockets ≥7 mm, extensive suppuration) might bene$t
from systemic antibiotics during non-surgical peri-implantitis therapy (Herrera et
al., 2023). This could potentially reduce the need for additional peri-implantitis
surgery. It is desirable to prevent the burden of peri-implantitis surgery and/or the
possible necessity for implant removal if this is clinically feasible. The desired
bene$cial e"ects of a systemic antibiotic therapy should however be weighed
against the potential side e"ects of the drugs (Herrera et al., 2023).

The purpose of this study was to evaluate the long-term e"ects of systemically
administered amoxicillin and metronidazole, administered in addition to non-
surgical sub-marginal instrumentation and focus on the need for additional surgical
therapy during the aftercare programme. It is hypothesized that there is no
signi$cant di"erence in need for additional surgical therapy between patients who
received non-surgical peri-implantitis treatment with or without adjunctive systemic
amoxicillin and metronidazole (null hypothesis).

2 MATERIALS AND METHODS

2.1 Study design
This study is a retrospective cohort study with a mean follow-up of 36 months
assessing the long-term clinical e"ectiveness of systemic amoxicillin and
metronidazole as an adjunctive treatment to NSI. The primary aim was to evaluate
whether adjunctive systemic antibiotics prevents the need for additional surgical
therapy in the long term. This study presents the long-term follow-up results of a
cohort of patients who previously participated in a 3-month RCT (De Waal et
al., 2021).

2.2 Participants
Data were retrospectively collected from patient $les of the The Hague Clinic for
Periodontology, The Netherlands. Patients who had previously received NSI for peri-
implantitis (marginal bone loss ≥2 mm combined with bleeding and/or suppuration
on probing and peri-implant probing depth ≥5 mm) with (AB+) or without (AB−)
systemic antibiotics were included (De Waal et al., 2021). Clinical and radiographic
data had previously been collected prior to NSI (T0) and 3 months after NSI (T1).
After treatment evaluation, patients were invited to participate in an individually-
:
 tailored supportive peri-implant care programme, including oral hygiene coaching
and professional mechanical plaque removal with an interval of 3–4 months. The
need for additional surgical peri-implantitis treatment was assessed during each
visit by an experienced periodontist (TV) based on the following criteria:
peri-implantitis PD > 5 mm;

concomitant bleeding and/or suppuration on probing.

The clinical e"ect of the additional treatment was monitored afterwards until the
last available follow-up visit (T2). Approval for this study was granted by the review
board of the University Medical Center Groningen (no. 20220007), and its
composition adhered to the Declaration of Helsinki. The formulation of the
manuscript followed the STROBE guidelines.

2.3 Intervention
The non-surgical intervention is described in detail by De Waal et al. (2021). In brief,
patients underwent thorough mechanical cleaning of both implants and teeth in up
to $ve sessions administered by skilled dental hygienists. Implants were cleansed
supra- and submucosally using an air polisher with a sub-gingival tip (EMS Air-#ow®
with erythritol-based powder containing chlorhexidine) and ultrasonic instruments
(PL1 and PL2 instruments, EMS Piezon®), focusing solely on exposed screw threads.
Teeth were cleansed supra- and subgingivally utilizing ultrasonic instruments (EMS
Piezon®) and hand instruments (Hu-friedy). Throughout each session, patients
received personalized oral hygiene instructions, including electric toothbrush
usage, interdental brush application with 1% chlorhexidine gel (Corsodyl®,
GlaxoSmithKline) at implants, and implant-speci$c #ossing with either Oral-B®
super#oss (Proctor & Gamble Company) or Meridol® #oss (Colgate-Palmolive
Company). After NSI, patients were randomly allocated to receive additional
systemic antibiotics (systemic amoxicillin and metronidazole) (500/500 mg, three
times daily for 7 days, AB+) or not (AB−).

2.4 Outcomes
The primary outcome variable was de$ned as ‘the need for additional surgical
therapy after NSI (yes/no)’. Surgical treatment was de$ned as either surgical peri-
implantitis treatment or implant removal.

Secondary outcome variables were changes between T0, T1 and T2 in mean peri-
implant and periodontal full-mouth probing pocket depths (PDs), BS, suppuration
:
 scores (SS) and plaque scores (PS). Furthermore, the clinical treatment success
(yes/no) on T2 was evaluated on patient and implant level and was de$ned as a
composite treatment outcome based on the end points of the non-surgical step of
peri-implantitis treatment as stated by Herrera et al. (2023):
residual probing depths ≤5 mm;

no bleeding on probing ≥1 probing site;

no suppuration on probing.

2.4.1 Clinical parameters

The clinical parameters were scored at six sites per tooth or implant by one
experienced periodontist (TV). The presence of plaque was visually analysed using a
dental probe and scored as either present or absent. The PD was assessed in mm
using a Hu-Friedy® PCPUNC156 periodontal probe. Subsequent bleeding and/or
suppuration was scored as either present or absent.

2.5 Sample size

This study aimed at retrieving data from all 57 patients who completed the 3-month
follow-up of the previous RCT (De Waal et al., 2021). No literature speci$cally
assessing the need for surgical treatment after non-surgical peri-implantitis therapy
is currently present, and thus, a convenience sample was used that could serve as a
benchmark for future research.

2.6 Statistical methods

The primary outcome was evaluated using a Kaplan–Meier analysis. A log-rank test
was performed to evaluate when and how often the indication for peri-implantitis
surgery was made between the AB+ and AB− groups and whether this was
statistically di"erent. The data were analysed by calculating the di"erence in
months between T1 and T2. For patients who received additional surgical treatment
during this timeframe, the number of months that passed between T1 and the date
of surgery was also calculated. The surgery date then replaced the T2 date, thus
creating a data set where the months until surgical treatment served as a cut-o"
point. Cox regression was used to analyse to what extent the e"ect of antibiotics
was in#uenced by other variables over time. Crude analysis was adjusted using the
variables ‘mean full-mouth PS at T0 (%)’, ‘mean peri-implant radiographic bone loss
at T0 (mm)’ and smoking status, based on the available literature (De Waal et
:
 al., 2016; Lee et al., 2022; Vilarrasa et al., 2023). Furthermore, to explore other
variables that might potentially in#uence the need for surgery, separate univariable
regression analyses were performed. Variables that showed a signi$cant result
were incorporated in a multiple regression analysis. The secondary outcomes BS,
SS and PS were scored as a percentage. For the outcome variable PD, mean scores
were calculated for all included implants and teeth. These parameters were
collected on T0, T1 and T2. Within-subjects analyses for the normally distributed
data were analysed using a repeated measures ANOVA. Data that were not
normally distributed were analysed using the Friedman test. Post hoc analyses
were performed using the Bonferroni correction (normally distributed data) and
Wilcoxon signed-rank tests (non-normally distributed data). To assess potential
attrition bias, the data underwent analysis by comparing the baseline patient
characteristics and the baseline clinical parameters of the patients who were lost to
follow-up with those who participated in the follow-up programme, for which
independent samples t-tests and Chi-square tests were used. Descriptive statistics
were analysed using SPSS (IBM, Armonk, NY, USA). Kaplan–Meier $gures were
drafted using GraphPad Prism (Dotmatics, Boston, MA, USA).

3 RESULTS
Figure 1 displays the #ow chart outlining the study's follow-up. Among the initial 57
patients, 12 individuals did not partake in the aftercare programme at The Hague
Clinic for Periodontology. Consequently, there are no available data from these
patients, resulting in a $nal dataset of 45 patients. Patient characteristics are
detailed in Table 1. The $ndings with regard to the attrition bias analysis are
presented in Table 2. No signi$cant di"erences were observed between the
patients who participated in the aftercare programme and the patients who were
lost to follow-up.

FIGURE 1

Open in !gure viewer PowerPoint


Flow chart with regard to data retrieval.

TABLE 1. Patient characteristics and treatment success at di"erent time points.

:
 Characteristics AB− group AB+ group

Number of patients (n = 45) 22 23

Number of implants that received NSI at T0 (n = 98) 48 50

Age (years; mean [SD]) 54.9 59.4

(11.5) (10.8)

Gender; F (female)/M (male) 18/4 11/12

Current smoking status

Yes 5 4

No 17 19

Surgical follow-up treatment of dentition

Surgical resective treatment; n patients 3 1

Surgical regenerative treatment; n patients 2 1

Dental extractions; n patients 7 8

Follow-up treatment of implants

Non-surgical retreatment; n patients 2 0

Surgical therapy; n patients 11 6

Type of surgical therapy; n patients

Abbreviation: NSI, non-surgical sub-marginal instrumentation.

TABLE 2. Attrition bias analysis.

Characteristics Patients included (n = Patients lost to follow-up (n p-value

45) = 12)

a
Gender; F (female)/M 29/16 4/8 .097
(male)
b
Age (years; mean [SD]) 57.20 (11.29) 54.58 (10.55) .880

b
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 PD (mean; mm [SD]) 5.73 (1.38) 5.71 (1.18) b
.530
b
BS (mean; % [SD]) 89.28 (16.68) 94.56 (10.13) .060
b
SS (mean; % [SD]) 10.41 (13.67) 14.85 (14.58) .904
b
PS (mean; % [SD]) 44.36 (28.67) 34.22 (31.30) .667

Abbreviations: BS, bleeding scores; PD, pocket depth; PS, plaque scores; SS, suppuration scores.
a
Chi-square test.
b
Independent samples t-test.

The average follow-up duration between T1 and T2 for the study population was
35.9 months (standard deviation [SD] = 21.0; range = 6.0–80.0). Figure 2 depicts the
Kaplan–Meier analysis, evaluating the necessity for additional peri-implantitis
surgery for both the AB+ and AB− groups. Overall, 62.2% of the study participants
did not receive additional surgical therapy, comprising 50.0% of AB− group patients
and 73.9% of AB+ group patients. Observation of the Kaplan–Meier curves indicates
a di"erence in the number of indicated surgeries during the initial 36 months. In the
AB+ group, there is an increase in the number of surgeries happening after this
timeframe, suggesting a potential period of approximately 3 years during which
antibiotics, within a robust postoperative care protocol, seem to exhibit an e"ect in
this patient cohort. However, the overall outcome did not reach statistical
signi$cance (log-rank test, p = .110). Table 3 shows the output of the Cox regression
models. The covariates did not seem to be time-dependent (proportional hazards
assumption based on raw analysis of the survival curves and by introducing a
dichotomous time indicator; p > .05 in all models). Adjusting the crude analysis did
not signi$cantly alter the hazard ratio for future surgery with regard to adjunctive
antibiotic treatment during NSI (β = .441, 95% CI = 0.159–1.220, p = .115). Univariable
analyses highlighted a signi$cant result with regard to the baseline peri-implant PD.
However, this did not substantially alter the result for antibiotics after incorporation
into the multiple regression model (β = .464, 95% CI = 0.169–1.269, p = .135).
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 FIGURE 2

Open in !gure viewer PowerPoint


Survival curves for the antibiotics (AB+) group and the group that did not receive antibiotics (AB−).

TABLE 3. Cox regression.

Outcome variable Crude model Adjusted model

β 95% CI p-value β 95% CI p-value

Antibiotics (y/n) .459 0.169–1.244 .126 .441 0.159–1.220 .115

Univariable regression analysis Multiple regression analysis

β 95% CI p-value β 95% CI p-value

Gender (m/f) .939 0.347–2.543 .902

Smoking (y/n) 1.170 0.380–3.598 .784

Antibiotics (y/n) .459 0.169–1.244 .126 .464 0.169–1.269 .135

a
FMPS (%) .986 0.963–1.010 .246
b
PIBL (mm) 1.141 0.878–1.483 .322
c
PIPD (mm) 1.446 1.035–2.020 .031 1.422 1.027–1.969 .034
d
PISup (y/n) 1.057 0.407–2.746 .909
e
SuccT1 (y/n) .470 0.152–1.452 .190
f
PISC (months) .669 0.232–1.924 .455

a
Mean full-mouth plaque scores at T0 (%).
b
Mean peri-implant radiographic bone loss at T0 (mm).
c
Mean peri-implant pocket depth at T0 (mm).
d
Peri-implant suppuration at T0 (y/n).
e
Treatment success at T1 (y/n).
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 f Frequency of peri-implant supportive care after T1 (months).

Table 4 represents the clinical data on the periodontal and peri-implantitis

parameters with the corresponding p-values. In both groups, there was a signi$cant
reduction in peri-implantitis PD and BS from T0 to T1. Subsequently, there was a
further decrease from T1 to T2, reaching signi$cance in the AB− group but not in the
AB+ group (Δ PD T1 – T2 in AB− and AB+ equals −1.2 vs. −0.6 mm, respectively; Δ BS
T1 – T2 in AB− and AB+ equals −28.0% vs. −18.5%, respectively). Moreover, both
groups experienced a signi$cant reduction in peri-implantitis SS and PS between T0
and T1. Although a decrease was observed between T1 and T2, only the reduction in
peri-implantitis PS in the AB− group was signi$cant. A marginal increase in peri-
implantitis PS is evident in both groups at T2. The data on periodontal parameters
highlight that the most substantial changes occurred between T0 and T1.

TABLE 4. Parameters and corresponding p-values regarding the clinical peri-

implantitis and periodontal data.

Parameters AB− group (n = 22) AB+ group (n = 23)

T0 T1 T2 T0 T1 T2

Peri-implantitis parameters

PD (mean; mm 5.9 (1.5) 4.5 (1.4) 3.3 (1.4) 5.6 (1.3) 3.9 (1.3) 3.3 (0.7)
[SD])

BS (mean; % 95.6 59.9 31.9 83.3 47.3 28.8

[SD]) (8.3) (29.6) (23.4) (20.3) (31.8) (28.9)

SS (median; % 4.2 0.0 (0.0) 0.0 (0.0) 6.7 0.0 (5.6) 0.0 (0.0)
[IQR]) (16.7) (16.7)

PS (median; % 44.5 0.0 (0.0) 2.1 44.4 0.0 5.6

[IQR]) (58.3) (22.2) (33.3) (16.7) (33.3)

Periodontal parameters

PD (mean; mm 3.1 (0.5) 2.4 (0.4) 2.5 (0.4) 3.1 (0.6) 2.3 (0.4) 2.4 (0.3)
[SD])

BS (mean; % 47.2 17.8 16.9 40.2 14.1 12.1

:
 [SD]) (19.2) (10.7) (15.9) (16.7) (9.7) (8.3)

SS (median; % 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
[IQR])

PS (median; % 41.8 6.0 7.8 36.8 9.0 8.3

Main test p-values Post hoc analyses p-values

AB− group AB+ group AB− group (n = 22) AB+ group (n = 23)
(n = 22) (n = 23)
T0 ➔
➔ T0 ➔
➔ T1 ➔
➔ T0 ➔
➔ T0 ➔
➔ T1 ➔
➔
T1 T2 T2 T1 T2 T2
Peri-implantitis parameters
a
PD <.001 <.001 <.001 <.001 .013 <.001 <.001 0.153
a
BS <.001 <.001 .007 <.001 <.001 <.001 <.001 .144
b
SS <.001 <.001 .005 .040 .715 .015 .003 .125
b
PS <.001 <.001 <.001 <.001 .033 <.001 <.001 .550

Periodontal parameters
a
PD <.001 <.001 <.001 <.001 1.000 <.001 <.001 .279
a
BS <.001 <.001 <.001 <.001 1.000 <.001 <.001 .928
b
SS .068 .174 NA NA NA NA NA NA
b
PS <.001 <.001 <.001 <.001 .715 <.001 <.001 .709

Abbreviations: BS, bleeding scores; NA, not applicable; PD, pocket depth; PS, plaque scores; SS,

suppuration scores.
a
Repeated measures ANOVA, post hoc Bonferroni corrections.
b
Friedman test, post hoc Wilcoxon signed-rank tests.

4 DISCUSSION
The aim of this study was to retrospectively evaluate the di"erence in need for
:
 additional peri-implantitis surgery after NSI with or without adjunctive amoxicillin
and metronidazole. The data show that there is no signi$cant di"erence in need for
additional surgical peri-implantitis treatment between the AB+ and AB− group, and
therefore, the null hypothesis should be accepted. It is worth noting that this
$nding might be in#uenced by the broad range in follow-up time. In this sense,
despite retaining the null hypothesis, it is important to underline the trend that the
systemic antimicrobial therapy with amoxicillin and metronidazole reduced the
indication for peri-implantitis surgery for 36 months after NSI in this study. There is
a 23.9% di"erence in indicated surgeries in favour of the antibiotics group
throughout the entire follow-up period. Furthermore, the adjusted Cox regression
model also did not provide a signi$cant result regarding the in#uence of systemic
amoxicillin and metronidazole to the need for additional surgical peri-implantitis
during the follow-up. In addition, irrespective of the systemic antibiotics, univariable
regression showed that baseline peri-implant PD signi$cantly increased the hazard
of having to undergo surgery during the follow-up after NSI in this cohort (β = 1.422,
95% CI 1.027–1.969, p = .034). This could be attributed to the fact that non-surgical
treatment alone typically leads to a reduction in PD of approximately 0.5–1.0 mm
(Renvert et al., 2019), indicating that initially deep pockets are unlikely to decrease
to a level where surgical intervention is deemed to be unnecessary.

The majority of the surgeries in the AB− group were performed early during the
follow-up phase compared with the AB+ group, indicating that several cases were
deemed to be treated non-successfully on, or shortly after, 3 months. This is
supported by Renvert et al. (2019), who concluded that conventional non-surgical
mechanical debridement as a monotherapy (i.e., not supplemented with additional
decontamination protocols) generally does not su%ce. However, both groups in the
present study showed a reduction in clinical parameters during the follow-up
period and the clinical parameters seemed to reduce to a similar level for both the
AB− and the AB+ group. This $nding emphasizes the need to prospectively explore
the extent to which a thorough post-treatment protocol can e"ectively manage
peri-implantitis over the long term. Similar observations were made by Hentenaar
et al. (2021) who analysed the non-surgical peri-implantitis treatment using either
an air polishing device or piezoelectric ultrasonic scaling. Although the e"ects of
both therapies were limited after 3 months, a gradual improvement of peri-implant
parameters was observed in successfully treated patients after 12 months when
supportive treatment and oral self-care reinforcement was performed after 6 and 9
months.
:
 In the initially performed randomized controlled trial, De Waal et al. (2021) did not
observe signi$cant bene$ts in the group that received systemic antibiotics with
regard to the clinical and microbiological outcomes. Despite this, both groups
displayed notable clinical improvements 3 months after non-surgical treatment. The
observed e"ect seems to persist in the remaining cohort. This observation is
corroborated by analogous clinical studies, which failed to demonstrate a
noteworthy advantage of systemic antibiotics as an adjunct to non-surgical peri-
implantitis treatment (Almohareb et al., 2020; Polymeri et al., 2022; Shibli et
al., 2019). In contrast, Blanco et al. (2022) evaluated the bene$cial e"ects of
metronidazole as an adjunct to non-surgical mechanical debridement and observed
signi$cant additional improvements in radiographic, clinical and microbiological
parameters after 12 months of follow-up. Still, in that study, only 56.3% of the test
group met the success criteria as opposed to 25% in the control group. The
justi$cation for routinely prescribing systemic antibiotics as a complement to non-
surgical peri-implantitis treatment could therefore be questioned, in light of the
general principles of antibiotic stewardship and the public health goal to curtail the
unnecessary utilization of antibiotics in dentistry (Herrera et al., 2023).

Aside from improvements in clinical aspects such as reduced bleeding tendency

and minor PD reduction, achieving complete resolution of severe peri-implantitis
cases appeared di%cult in the present study. In the AB+ group, the indications for
additional surgical therapy were made later on during the aftercare programme. It
seems that systemic antibiotics as an adjunct to NSI provide a short-term reduction
in clinical in#ammatory parameters, but are unable to suppress peri-implant
pathology on a longer term. Similar results were presented by Gomi et al. (2015),
who supplemented full-mouth scaling and root planing in periodontitis and peri-
implantitis patients with azithromycin and observed that after 6 months,
periodontal pathogens increased again around implants. All patients in our study
also presented with both peri-implantitis and periodontitis at baseline, which were
both treated simultaneously. A wide array of studies has focused on the association
between peri-implantitis and periodontitis, and it seems that both the presence and
the history of periodontitis are positively associated with a susceptibility of
developing peri-implantitis (Dreyer et al., 2018). Treating periodontal pathology and
maintaining a healthy periodontium is therefore of vital importance to maintain
healthy peri-implant tissues.

Several limitations to the study must be addressed. For one, the results should be
interpreted with caution given that the data presented were retrieved
:
 retrospectively. This means that there was no uniform policy regarding the data
storage in the patient $les. As the aftercare programme was individually tailored,
no clear duration of the follow-up was determined. This resulted in a wide range of
follow-up frequencies and total span of the follow-up period. Furthermore,
treatment success was based on clinical parameters alone, due to the absence of
radiographic recordings. Therefore, it was not possible to monitor the extent of any
peri-implant bone loss that could have occurred during the follow-up. The number
of patients included in this study could be considered limited. This was caused by
the fact that several patients did not adhere to the aftercare programme and could
therefore not provide reliable data, resulting in a convenience sample of 45
patients. However, when evaluating Table 2, it seems that the group that was lost to
follow-up shows overall similarities with the evaluated patient cohort, indicating
that the in#uence of attrition bias could be considered minimal.

5 CONCLUSION
Within the limitations of this study, it seems that the use of amoxicillin and
metronidazole as an adjunct to NSI did not prevent the need for additional surgical
peri-implantitis treatment in this patient cohort on the long term, but might have a
bene$cial e"ect during the $rst 3 years after NSI if supportive peri-implant aftercare
is also provided. Therefore, the e"ect of systemic antibiotics seems to be
temporary in nature, delaying the moment that peri-implantitis surgery is indicated.
Furthermore, deeper baseline PDs seemingly increased the need for surgery after
NSI in this patient cohort.

AUTHOR CONTRIBUTIONS
JH drafted the article, interpreted the data and initiated the project. TEV performed
clinical examinations and surgical procedures, and contributed to the article
revision. AJVW was involved in substantial contribution to article revision. YCMDW
was involved in project initiation, data interpretation, study design and article
revision.

FUNDING INFORMATION
The authors did not receive any external funding.

CONFLICT OF INTEREST STATEMENT

:
 The authors declare no con#icts of interest.

DATA AVAILABILITY STATEMENT

The data that support the $ndings of this study are available from the corresponding
author upon reasonable request.

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