Locally Applied Antimicrobial Therapy
use of locally applied antimicrobial therapy (LAA) has expanded to become
almost routine by some dental offices (ADA code 4381) in conjunction with
scaling and root planing (S/RP) for periodontal treatment. If there is no or
limited clinical significance derived from the use of these products the
cost associated with these procedures would represent wasted benefit dollars
which could be used for more proven therapies. Stakeholders in this discussion
include general dentists, periodontists, patients, payers and product
key question that needs to be answered is whether the use of LAA in conjunction
with S/RP results in a clinically significant way to improve the periodontal
condition. Is it effective for routine use when treating periodontal disease?
This paper is a literature search, a met analysis, reviewing many papers (some
collated many articles) involving more than 5000 patients. More than 700
articles were selected that had been published in English in peer reviewed
journals ie: j.perio, j. clinical perio, and j. perio research.
8 references contained the many articles encompassed in the selected
are many products used for LAA along with S/RP including tetracycline, minocycline,
metronidazole, chlorhexidine, combination of metronidazole and amoxicillin, and
products are delivered in various forms including: impregnated strings, chips, rinses,
intra-crevicular injection etc. The following studies were reviewed in the development
of this position paper to determine the efficacy of these agents when delivered
in conjunction with S/RP.
LOCAL ANTI-INFECTIVE THERAPY: PHARMACOLOGICAL AGENTS. A SYSTEMATIC REVIEW
studies, 3,705 subjects. Conclusions – S/RP alone resulted in significantly
reduced probing depths and gains in clinical attachment level. Findings from
the met-analysis indicate that the average amount of PD reduction achieved by
the addition of sustained-release antimicrobials to S/RP is quite small, although
highly statistically significant. Is this amount of an additional PD reduction
worth the extra time and expense required to insert the antimicrobial system?
(per authors, p92, pp 3 )
LOCALLY DELIVERED DOXYCYCLINE DURING SUPPORTIVE PERIODONTAL THERAPY: A 3 YEAR
reductions in bleeding on probing (BOP), pocket depths (PD), and residual attachment
loss (RAL) and the mean counts of a number of target species between baseline and
3 years were documented for both treatment groups Whereas plaque scores
remained unchanged, a statistically significant difference in favor of the
adjunctive doxycycline therapy was found between the two groups only at the 3
month examination for BOP, PD, and RAL and for a minority of bacterial species
at 2 years.
short-term effects on clinical parameters were found with the adjunctive use of
locally delivered doxycycline, repeated applications annually had no clinical
microbiologic effects beyond those observed with mechanical debridement alone
in maintenance patients. (study’s conclusion)
IMPACT OF LOCAL ADJUNCTS TO SCALING AND ROOT PLANING IN PERIODONTAL DISEASE
THERAPY: A SYSTEMIC REVIEW.
the locally administered adjunctive antimicrobials, the most positive results
occurred for tetracycline, metronidazole, and chlorhexidine. Adjunctive local
therapy generally reduced pocket depth (PD) levels. Differences between
treatment and S/RP only groups in the baseline-to-follow-up period typically
favored treatment groups but usually only modestly (e.g. from about 0.1 mm to
nearly 0.5 mm) even when the differences were statistically significant.
Effects for clinical attachment levels (CAL) gains were smaller and statistical
significance less common. The marginal improvements in PD and CAL were a
fraction of the improvement from SRP alone.
such improvements, even if statistically significant, are clinically meaningful
remains a question. A substantial agenda of future research to address this and
other issues (e.g. costs, patient-oriented outcomes) is suggested. (study’s
& 5) TREATMENT OF PERIODONTITIS BY LOCAL ADMINISTRATION OF MINOCYCLINE
MICROSPHERES; A CONTROLLED TRIAL
DELIVERED MINOCYCLINE MICROSPHERES FOR THE TREATMENT OF PERIODONTITIS IN
clinical studies, similar format and method. Baseline measurement; S/RP alone;
with microspheres. Measurements at baseline, 1,3,6 and 9 months. Experimental
patients seen multiple times and S/RP only at beginning.
results were statistically significant. However, clinical significance was very
CLINICAL AND MICROBIOLOGICAL CHANGES ASSOCIATED WITH THE USE OF COMBINED
ANTIMICROBIAL THERAPIES TO TREAT “REFRACTORY” PERIODONTITIS
of 14 subjects with refractory periodontitis. Patients treated with S/RP,
locally delivered tetracycline and systemically administered amoxicillin and
metronidazole and professional removal of supragingival plaque weekly for 3
modest clinical improvements after 6 months but regrowth of bacteria after.
EFFECTIVENESS OF ANTIMICROBIAL ADJUNCTS TO SCALING AND ROOT-PLANING THERAPY FOR
of many papers involving use of tetracycline. Minocycline, Metronidazole, combination
of metronidazole and amoxicillin, Chlorhexidine, and other antimicrobials. All were
used in treatment with S/RP.
key question is whether S/RP accompanied by an antimicrobial agent, as a
supplemental of adjunct treatment, results in improved outcomes that persist
over time in adults with chronic periodontitis when compared with S/RP alone.
the antimicrobials investigated, studies of locally applied tetracyclines and
minocyclineand locally delivered chlorhexidine- have fairly consistent results
in moderately large studies that often reach statistical significance;
improvements observed in these studies typically average in the neighborhood of
0.3mm to 0.6 mm. The question remains, the authors note, whether such
improvements are clinically meaningful.
AMERICAN ACADEMY OF PERIODONTOLOGY STATEMENT OF LOCAL DELIVERY OF SUSTAINED OR
CONTROLLED RELEASE ANTIMICROBIALS AS ADJUNCTIVE THERAPY IN THE TREATMENT OF
existing data appear insufficient to conclude that adjunctive sustained or
controlled release locally delivered antimicrobial (LDA) treatment can either
reduce the need for surgery or improve long-term tooth retention, or is cost
effective. Additional studies are needed to support the use of LDA in special
review of the published papers representing many studies revealed that S/RP is effective
in the routine treatment of periodontal disease. Addition of LAA was tested to determine
if adjunctive therapy would add to improvement. The studies involved use of many
different agents in a variety of delivery systems. Results were measured at
baseline and various intervals.
studies showed some improvement with S/RP alone that was clinically
significant. Most studies reported no significant improvement with adjunctive
therapy involving LAA. A few studies claimed some “statistically significant”
improvement of between 0.3mm to 0.6mm. The majority of the studies reported
that any improvements were of little or no clinical significance for treatment
of non-surgical periodontitis.
clinical trials have demonstrated that manual probing without benefit of a
stint results in a standard error of measurement for PD and Cal of +/- 1.0 mm” (from
C.Cobb, Presentation at AADC workshop, 5/11). When allowing for the standard
error of the measurement, the results of the studies are no better than SRP
additional paper titled “Treatment of Periodontitis by Local Administration of Minocycline
Microspheres: A Controlled Trial” (Williams RC, Paquette D et al, J Periodontol,
November 2001) was presented and reviewed. This paper studied patients with
more advanced chronic periodontal disease and, therefore, was not included in
our review to determine the efficacy of adjunctive use of LAA for routine
treatment of nonsurgical periodontal disease patients. However, it is presented
to show an important possibility of bias which could influence researchers. The
following statement is from the
at the end of the report:
study was supported by a grant from OraPharma, Inc.,Warminster Pennsylvania. Drs.Cochran,
Offenbacher, Van Dyke and Williams are members of the Scientific Advisory Board
for Orapharma, Inc., and in that role have been given equity in the company.
Drs. Santucci, Rodda, and Lessern are in the Clinical Research Division of Orapharma,
is not to say that the research is not valid, only that both researchers and
readers should be aware of the possible conflict of interest which could
influence the findings. Papers #4 & 5 were conducted by many of the same
on review of the published papers as summarized above, scientifically based evidence
does not support the use of locally applied antimicrobial therapy as adjunctive
therapy for the routine treatment of periodontal disease. Additional studies
are recommended to determine the value of LAA for the treatment of periodontal
disease with specific recalcitrant pockets that have not responded to conventional
periodontal treatment modalities.
ANTI-INFECTIVE THERAPY: PHARMACOLOGICAL AGENTS. A SYSTEMATIC REVIEW Philip
J. Hanes and James P. Purvis Ann Periodontal, Vol 8, No1, Dec 2003
DELIVERED DOXYCYCLINE DURING SUPPORTIVE PERIODONTAL THERAPY: A 3 YEAR STUDY Anna
Bogren, Ricardo P. Tales, Gay Torresyap, Anne D. Haffajee, Sigmund S. Socransky,
and Jan L. Wennstrom. J.Perioontol, Vol 79, No.5, May 2008
OF LOCAL ADJUNCTS TO SCALING AND ROOT PLANING IN PERIODONTAL DISEASE THERAPY: A
SYSTEMIC REVIEW. Bonito AJ, Lux L, Lohr KN, J.Periodontol, 2005 Aug,76(8):
OF PERIODONTITIS BY LOCAL ADMINISTRATION OF MINOCYCLINE MICROSPHERES; A
CONTROLLED TRIAL Williams RC, Paquette D, J. Periodontol, 2001 Nov;
DELIVERED MINICYCLINE MICROSPHERES FOR THE TREATMENT OF PERIODONTITIS IN
SMOKERS Paquette D, Williams RC, J.Clin Periodontol, 2003 Sep;30(9):787-94
AND MICROBIOLOGICAL CHANGES ASSOCIATED WITH THE USE OF COMBINED ANTIMICROBIAL
THERAPIES TO TREAT “REFRACTORY” PERIODONTITIS. Haffajee, Adul NG, et al. J.
Clin Periodontol, 2004 Oct;31 (10):869-77
OF ANTIMICROBIAL ADJUNCTS TO SCALING AND ROOT-PLANING THERAPY FOR PERIODONTITIS
Evidence report/technology assessment: Number 88 RTI International UNC
ACADEMY OF PERIODONTOLOGY STATEMENT OF LOCAL DELIVERY OF SUSTAINED OR
CONTROLLED RELEASE ANTIMICROBIALS AS ADJUNCTIVE THERAPY IN THE TREATMENT OF
statement was developed under the direction of the Task Force on Local delivery
of Antimicrobials as Adjunct Therapy and approved by the Board of Trustees of
the American academy of Periodontology
in May 2006.
Michael D.L. Weisenfeld (Chair and Principal Author)