It was a systematic review and network meta-analysis aimed to evaluate the efficacy of adjunctive locally delivered antimicrobials, compared to sub gingival instrumentation alone or plus a placebo, on changes in probing pocket depth (PPD) and clinical attachment level (CAL), in patients with residual pockets during supportive periodontal care.

2. Chen-Ying Wang, Yu-Hao Yang, Hua Li, Ping-Yi Lin, Yu-Ting Su, Mark Yen-Ping Kuo, Yu-
Kang Tu
Adjunctive local treatments for patients withresidual pockets during
supportive periodontal care: A systematicreviewand network meta-
analysis
03 OCTOBER 2020

3. AIM
It was a systematic review and network meta-analysis aimed
to evaluate the efficacy of adjunctive locally delivered
antimicrobials, compared to sub gingival instrumentation
alone or plus a placebo, on changes in probing pocket depth
(PPD) and clinical attachment level (CAL), in patients with
residual pockets during supportive periodontal care.

4. CLINICAL RELEVANCE
Scientific rationale
A large number of adjunctive local antimicrobial agents have been used
for treating residual pockets, and this network meta-analysis compared
the treatment effects of these agents on probing pocket depth (PPD)
reduction and clinical attachment level (CAL) gain.
Principle findings
Adjunctive local antimicrobial agents achieved small additional
treatment effects on PPD reduction compared with scaling and root
planing (SRP) alone for a follow-up period of up to 6 months.
Tetracycline fiber (TCF) and chlorhexidine chip (CHC) were ranked best
among all adjunctive therapies.

5. Practical implications
The use of adjunctive local antimicrobial agents may be clinically
beneficial if significant reduction of PPD compared to SRP alone can be
achieved. It may reduce the probability of further tooth loss. TCF and
CHC achieved superior results than other antimicrobials.

6. INTRODUCTION
According to Tonetti, Greenwell, and Kornman;2018:
Periodontitis is a disease characterized by microbially associated,
host mediated inflammation that results in loss of periodontal attachment.
Supragingival professional mechanical plaque removal and sub gingival
instrumentation comprising scaling and root planing (SRP) are the first
two steps of periodontal therapy for patients with periodontitis.
(Sanz et al. 2020)
Its efficacy has been well documented in several systematic reviews in
terms of gains in clinical attachment levels (CAL) and reductions in
probing pocket depth (PPD).

7. The maintenance phase of periodontal therapy is required after SRP to
prevent the recurrence of disease and prolong the favourable results of
the active treatments. However, residual pockets may still exist during
maintenance, especially, in sites, where thorough debridement and
complete removal of calculus is hard to attain, such as those with initial
deep PPD or adjacent to anatomical structures (e.g., developmental
grooves, fossae, furcation area, root concavities).
Several methods have been introduced to treat residual pockets, such as
antimicrobials, host modulation, and regenerative therapy.
Antimicrobials, administered systemically or locally, have been the most
commonly used agents and their effects have been investigated in
numerous studies.

8. Systemic administration of antibiotics as adjuncts to SRP for treating
residual pockets has shown favourable outcomes. Even though, adverse
effects, such as gastrointestinal disturbances or development of
antimicrobial resistance, and the low compliance of patients are major
concerns.
Sustained-release local antimicrobial agents may enhance the results of
mechanical debridement yielding additional PPD reduction.
Antimicrobial photodynamic therapy (aPDT), which has a potential
bactericidal effect against various periodontal pathogens has also been
used as an adjunct to SRP in the maintenance phase.
Several systematic reviews have evaluated the advantage of adjunctive
therapy to SRP in the treatment of periodontitis.

9. These reviews had limitations:
1. Most reviews were not aimed at residual pockets in maintenance
care.
2. None of these reviews was able to determine the relative efficacy of
different antimicrobial agents because some of these antimicrobial
agents have not been directly compared by any trials.
The relative effectiveness of adjunctive antimicrobial agents on the
treatment of residual pockets is still unclear.

10. So this is a systematic review and network meta-analysis, traditional
meta-analysis undertakes pair-wise comparisons between treatments, but
when the number of available treatments is large, pair-wise comparisons
may be inefficient or unfeasible. Network meta-analysis combines both
direct and indirect evidence to compare multiple treatments
simultaneously. It provides a consistent statistical framework for direct
and indirect comparisons of different treatments.

11. MATERIALS AND METHODS
Literature search was performed with electronic databases and by hand
until May 31st, 2020. Primary outcome was the changes in PPD. The
treatment effects between groups were estimated with weighted mean
differences (WMD) with 95% confidence intervals (CI) and prediction
intervals (PI) by using random-effects network meta‐analysis.
Criteria for considering studies in this review:
PICOS framework was used to formulate research question,
Population: Non-medically compromised patients with residual pockets
during supportive periodontal care.
Interventions: For the test group, an adjunctive locally delivered
antimicrobial was used either in single or repeated sessions as adjuncts to
SRP.
Comparisons: Control groups received SRP, alone or with a placebo.
Outcomes: Primary outcome is PPD reduction. Secondary outcome is
CAL gain.

12. Data collection, extraction, and management
Data was extracted and entered into a spreadsheet software:
(a) authors’ names, journal name, year of publication;
(b) characteristics of participants (number of patients per group, age
distribution, sex);
(c) type and duration of interventions;
(d) outcome measures;
(e) source of funding and conflicts of interest, if available.
They also divided the included studies into three groups based on the
follow-up period: short-term follow-up (≤ 3 months), medium-term
follow-up (4–6 months), and long-term follow-up (> 6 months).
In a follow-up period more than 12 months, only the results at the 12
month were used in the meta-analysis.

14. RESULTS
Twenty-two studies were included. Significantly greater PPD reduction
was achieved in chlorhexidine chip group (WMD: 0.65mm, 95%
CI: 0.21–1.10) and tetracycline fiber group (WMD: 0.64 mm, 95%
CI: 0.20–1.08) over 6-month follow-up. Other adjunctive antimicrobial
agents achieved non-significant improvements compared to scaling and
root planing alone.
All differences between adjunctive therapies were statistically
non-significant. Similar findings were observed for CAL gain.

15. Characteristics of studies included in the network meta-analysis.
N: Sample size; PPD: Probing pocket depth; CAL: Clinical attachment
level; SRP: scaling and root planing; NR: Not reported;
Multi(n): multicenter study(number of centers); PDT: Photodynamic
therapy.

23. Summary of all pairwise comparisons in terms of PPD reduction and
CAL gain.
Short-term follow-up

24. Medium-term follow-up

25. Long-term follow-up

26. Discussion
The network meta-analysis suggested that the adjunctive use of TCF and
CHC provides significantly additional clinical benefits to the treatment
of patients in the maintenance phase of periodontitis for a follow-up
period of up to 6 months. Other adjunctive antimicrobial agents showed
only limited clinical improvement.
Residual pocket depth after the initial cause-related therapy is related to
further attachment loss, there is significant increase in the probability of
tooth loss.
The efficacy of repeated SRP in residual pockets is rather limited, as only
11-16% of sites with poor responses to previous SRP might be brought to
a successful treatment endpoint.

27. In another study evaluating the outcome of re-instrumentation of residual
pockets, overall probability of achieving PPD ≤ 4 mm was about 45%,
while for sites with a PPD of > 6 mm, the probability was only 12%.
Periodontal surgery is an efficient method in treating deep periodontal
defects, but it can cause significant stress, pain and discomfort.
Non-surgical adjunctive treatments provide an alternative to periodontal
surgery to reduce the risk of tooth loss.
Antimicrobial Agents
Some antimicrobials require an effective concentration being maintained
for a sufficiently long duration at their target sites. The concentration
required for efficacy is often estimated from the Minimum Inhibitory
Concentration (MIC).

28. Antimicrobial agents in solid formulation generally maintains MIC
longer than gel type. MTZ is reported to maintain MIC within 24 hours,
whereas MIN can maintain its concentration about 4 days. In contrast,
the concentration of CHC remains above MIC for up to 9 days. Sustained
concentration of TCF can be maintained over 10 days. This may partly
explain why TCF and CHC achieved superior results when compared
with other antimicrobial agents in gel solution.
Photodynamic Therapy
The effectiveness of PDT depends on three factors: photosensitizer,
visible light, and oxygen. Different types of photosensitizer, light
application devices, output power, wavelengths, and duration of
exposure have been reported. Some photosensitizers may not be able to
attain sufficiently high concentrations to be absorbed by bacteria.

29. The microenvironment of residual pockets that contain less oxygen than
healthy sites might also hinder the effectiveness of PDT. Here, adjunctive
PDT achieved additional benefits only in 3-month follow-up. No studies
reported adverse events during the application of PDT.
Inconsistency different frequencies of PDT application.
Chondros et al. applied PDT only once at baseline as an adjunct to SRP,
and no additional benefits in PPD reduction and CAL gain were achieved
while significant PPD reduction and CAL gain were achieved after a
single use of adjunctive PDT in other studies.
Lulic et al. performed repeated applications of PDT five times at 14-day
intervals and found significant PPD reduction and CAL gain in 6 months
of follow-up. However, in a study comparing different frequencies of
PDT application (once vs twice with a 1-week interval), no significant
difference was observed.

30. According to previous studies, after SRP, subgingival microbiota
containing large numbers of pathogenic microorganisms repopulate
within 2 months in the absence of improved plaque control. More
recently, various studies have indicated that the application of adjunctive
antimicrobial agents results in significant reduction of bacteria for a 6
month follow-up period. Therefore, in a person whose oral hygiene can
be adequately achieved, locally delivered antimicrobial agents may help
in maintaining a low concentration of microorganisms for a longer
period of time than SRP alone does.

31. In the follow-up period shorter than 6 months, all adjunctive treatments
showed superior results to SRP alone, but no significant differences were
observed between different adjunctive treatments. Other factors, such as
ease of handling, probability of adverse events, or development of
resistant bacteria, may be taken into consideration. Typically, a gel-like
biomaterial is easier than fiber or chip materials to inject into the sulcus.
Adverse events may occur during or after the placement of local
antimicrobial agents. Generally, most studies have not reported severe
adverse events. The most commonly reported events were temporary
discomfort in the tooth and gingival tissue (i.e., gingival redness, tooth
pain, tooth hypersensitivity, stomatitis). The discomfort is alleviated or
subsided even without the use of analgesics in a short period of time.
Periodontal pathogens may develop antibiotic resistance when with
antibiotics are systemically or locally administered, whereas PDT and
CHC should be free of this consideration.

32. CONCLUSION
Adjunctive local antimicrobial agents achieved small additional PPD
reduction and CAL gain in residual pockets for a follow-up of up to 6
months. Tetracycline fiber and chlorhexidine chip achieved better results
than other antimicrobials.

33. REFERENCES