International Dental Journal (2004) 54, 3–14

Topical and systemic antibiotics in

the management of periodontal
diseases*
Andrea Mombelli
Geneva, Switzerland
Lakshman P. Samaranayake
Hong Kong, PR China

Both systemic and topical antibiotics are increasingly used in the manage- Antibiotic therapy of
ment of periodontal infections. Whilst these drugs are used mostly on an periodontal diseases:
empirical basis, some contend that rational use of antibiotics should be the Rationale and principles
norm due to their wide abuse and consequential global emergence of
antibiotic resistance organisms. Here we review the rationale and principles The major cause of both gingivitis
of antimicrobial therapy, treatment goals, drug delivery routes and various and periodontitis is the formation
antibiotics that are used in the management of periodontal diseases. The of bacterial biofilms (dental plaque)
pros and cons of systemic and local antibiotic therapy are described on oral hard tissues. Regular
together with practical guidelines for their delivery. The available data mechanical removal of bacterial
indicate, in general, that mechanical periodontal treatment alone is ad- plaque from these surfaces is the
equate to ameliorate or resolve the clinical condition in most cases, but mainstay of prevention and manage-
adjunctive antimicrobial agents, delivered either locally or systemically, can ment of periodontal disease. Clinical
enhance the effect of therapy in specific situations. This is particularly true studies have shown repeatedly that
for aggressive (early onset) periodontitis, in patients with generalised periodontal diseases can be success-
systemic disease that may affect host resistance and in case of poor fully treated most of the time by
response to conventional mechanical therapy. Locally delivered antibiotics thorough scaling and planing of the
together with mechanical debridement are indicated for non-responding root surfaces, and results can be
sites of focal infection or in localised recurrent disease. After resolution of maintained over long periods,
the periodontal infection, the patient should be placed on an individually provided the patient has a high level
tailored maintenance care programme. Optimal plaque control by the of oral hygiene and receives regu-
patient is of paramount importance for a favourable clinical and microbio- lar professional maintenance to
logical response to any form of periodontal therapy. remove newly formed subgingival
Key words: Periodontal disease, antibiotics, systemic, local delivery deposits. So what is the role of
chemotherapy in the management
*Prepared for, and approved by, the FDI Commission by the authors of periodontal disease?
Data from several clinical trials
suggest that the outcome of peri-
odontal therapy is correlated with
the presence or absence of certain
micro-organisms, notably Porphyro-
monas gingivalis and Actinobacillus
actinomycetemcomitans, after therapy1–5.
Positive sites seem to be at greater
risk for further attachment loss6–10,
Correspondence to: Professor Lakshman P. Samaranayake, Chair of Oral Microbiology,
and the absence of specific patho-
University of Hong Kong, Faculty of Dentistry, 34 Hospital Road, Hong Kong, PR China. gens has a negative predictive value
Email: [email protected] for further attachment loss 11,12.
© 2004 FDI/World Dental Press
0020-6539/04/01003-12
4

Mechanical therapy alone cannot isms considered most important in non-target micro-organisms. Hence
eliminate these micro-organisms the aetiology of the disease. for effective antimicrobial therapy
completely in every subject13,14. Further conditions that need to be of periodontal disease, the agent in
There are a number of reasons why fulfilled are: question should be available at a
this is the case. First, the pathogens • Adequate concentrations of the sufficiently high concentration not
may be inaccessible to mechanical drug to inhibit or kill the target only within the periodontal tissues,
intervention due to their ability to organisms can be reached and but also outside, in the environ-
invade periodontal tissues or dentine maintained over a sufficiently ment of the periodontal pocket.
tubules. They may also reside in long time at diseased sites The foregoing implies that treat-
sites inaccessible to periodontal • Such drug dosage has no major ment of periodontal diseases by
instruments such as root concavi- local or systemic adverse effects antimicrobials alone will probably
ties or furcations. In addition, • Data from properly controlled not suffice and mechanical instru-
treated sites may become longitudinal studies substantiate mentation to disrupt the biofilm
recolonised by the same, or other a favourable clinical outcome and to remove the bulk of bacte-
pathogenic bacteria persisting else- of therapy with the agent rial deposits must precede antimi-
where within the oral ecosystem • Finally, the drug regimen has a crobial therapy.
(e.g. dorsum of the tongue, the documented practical advantage
tonsils). Complementing mechani- over conventional treatment
cal therapy with local or systemic alternatives such as better out- Endogenous and exogenous
antimicrobial therapy may enhance come, less adverse effects, infection and treatment goals
the treatment effect and may thus simplicity and being cheaper and Infections are classified either as
be advantageous. faster. exogenous or endogenous depend-
On the other hand, the wide- ing on whether the infective strain/s
spread and rampant use of antibi- originate from external source or
otics especially in the developing Main features of periodontal
internally from the commensal
world has led to the realisation that infections
flora, respectively18. In the latter situ-
antibiotics are magic bullets that The recognition of periodontitis as ation the innocuous commensal
need to be used rationally and spar- a microbial infection is a fundamen- switches to a parasitic existence due
ingly. Over the years, bacteria have tal issue for any chemotherapeutic to various opportunities offered
developed a remarkable array of treatment concept. The term infec- either by the host or the environ-
mechanisms to withstand antibiotic tion refers commonly to the pres- ment thus causing disease, and these
agents and have developed increas- ence and multiplication of micro- are hence called opportunistic
ing resistance to these, formerly organisms in the body. Antibiotics infections. On the contrary, exog-
potent, agents. For instance when and antiseptics can kill bacteria, but enous pathogens are transmitted to
penicillin was introduced in the early these agents will neither eliminate healthy subjects via vectors, which
1950s almost 90% of Staphylococccus calculus, nor remove bacterial may be diseased humans or animals,
aureus were sensitive to the drug debris from tooth surfaces – or healthy carriers that show no
whilst currently an equal propor- crucial elements according to the signs of infection. In the context of
tion of the organisms are resistant classical view of periodontal disease. periodontal infections A. actinomy-
to the drug in many parts of the The periodontal pathogens reside cetemcomitans and P. gingivalis are
world. Further, the use of anti- in great numbers outside of the regarded by some as true exog-
biotics may disturb the delicate diseased tissues, within biofilms of enous pathogens due to their low
ecological balance of the intestinal complex architecture. A connective prevalence in periodontally healthy
flora and permit the proliferation matrix of extracellular polymers is individuals (mainly in the West). In
of resistant organisms that may known to modify the penetration addition, there is data to indicate:
initiate new infections that are worse and the activity of topically or • Transmission from parents to
than the original offenders. In systemically delivered antimicro- children, or between spouses,
addition, all antimicrobial agents, bials15,16. Several mechanisms, such leading to disease
being extraneous chemicals carry as diffusion barriers, and selective • Markedly heightened immune
with them an inherent risk of decomposition of agents lead to response towards these bacteria
toxicity. an increased resistance of bacteria relative to commensal pocket
Hence the prescription of any in biofilms17. Another obstacle for flora
antimicrobial agent for periodon- drug penetration into this micro- • Clinical studies showing elimi-
tal therapy should be a carefully cosm is the destruction, inactivation nation of A. actinomycetemcomitans
weighted decision. In order to be or degradation of the prescribed and P. gingivalis with appropri-
useful a drug must not only show antimicrobial agents prior to reach- ate mechanical treatment and
in vitro activity against the organ- ing their target by the commensal, adjunctive antibiotic therapy
International Dental Journal (2004) Vol. 54/No.1
 5

Table 1 Comparison of local and systemic antimicrobial therapy

Issue Systemic administration Local administration

Drug distribution Wide distribution Narrow effective range

Drug concentration Variable levels in different body High dose at treated site, low levels
compartments elsewhere

Therapeutic potential May reach widely distributed micro-organisms May act locally on biofilm associated
better bacteria better

Problems Systemic side effects Re-infection from non-treated sites

Clinical limitations Requires good patient compliance Infection limited to the treated site
Diagnostic problems Identification of pathogens, choice of drug Distribution pattern of lesions and patho
gens, identification of sites to be treated

(from Mombelli 2002 39, with permission)

leading to resolution19. pathogenesis of periodontal disease. distributed throughout the whole

On the contrary it is well recog- The presence of some bacterial mouth as has been shown in some
nised that most micro-organisms species that antagonise the growth patients13,21, including non-dental
associated with periodontal diseases of the potential pathogens may be sites, such as the dorsum of the
are detected frequently in low beneficial for periodontal health. tongue or tonsillary crypts22–26. An
numbers in health also, and the Therefore it may be advantageous obvious disadvantage of systemic
view that A. actinomycetemcomitans to eliminate only the target patho- therapy is that only a small propor-
and P. gingivalis cause true infec- gens using narrow spectrum anti- tion of the total dose actually
tions has been opposed because biotics for periodontal therapy. reaches the subgingival microflora
cross-sectional studies indicate they Furthermore, it is tempting to and the periodontal pocket, whist
are broadly prevalent in various speculate that the new develop- the remainder is lost within the
population groups, particularly in ments in probiotics where an total body mass. Furthermore, side
developing countries. If the latter ecological niche is artificially seeded effects and adverse drug reactions
two organisms are true exogenous with ‘healthy’ commensals that are greater with systemic drugs than
pathogens, then their elimination ward-off putative pathogens may those delivered locally. In addition,
should be a primary objective of also play a role in the management patient non-compliance may not be
therapy. This is not a realistic goal of periodontal diseases in future. a significant factor in locally deliv-
for an opportunistic infection. Here, ered agents.
local ecological conditions need to The main challenge for the local
change radically, and continuous Drug delivery routes mode of drug delivery is to main-
control of these conditions will be There are two major routes of drug tain a high concentration of the
necessary after treatment to prevent delivery into the periodontal pocket: drug within a well-confined area
the re-emergence in high numbers systemic, and direct local placement. for a prolonged period. With a
of potential pathogens. Each mode has potential advan- simple mouthrinse or supragingival
The healthy human gingival tages and disadvantages (Table 1): irrigation it is not possible to
crevice and the diseased perio- Antimicrobial agents can be applied predictably deliver an agent to the
dontal pocket is a veritable jungle locally at levels that cannot be deeper parts of a periodontal
of a multitude of flora. Some 500 reached by the systemic route. defect27,28. Agents brought into peri-
bacterial species have been identi- Local placement may also be suit- odontal pockets by subgingival
fied, and there is evidence for the able for agents that are too toxic to irrigation are washed out rapidly
presence of an additional large be delivered by the systemic route by the gingival fluid. It has been
segment of thus far unidentified (e.g. antiseptic agents), and may be estimated that the half-time of a
micro-organisms20. The analysis of particularly successful if the target non-binding drug placed into a
the pocket flora frequently indi- organisms are confined to a clini- pocket is about one minute29. To
cates a simultaneous presence of cally visible focus. On the other maintain the necessary concentra-
several putative pathogens as well hand, systemic antibiotics penetrate tion of a drug within the periodontal
as the presence of commensal and affect all microbial eco-niches pocket, the flushing action of the
micro-organisms, suggesting that of the oral cavity irrespective of crevicular fluid flow has to be
either synergistic or antagonistic diseased or healthy sites. This may impeded by a sustained drug
interactions between micro-organ- be a distinct advantage in situations release from a relatively large
isms play an important role in the where the periodontopathogens are reservoir. Within the constraints of

Mombelli and Samaranayake: Antibiotics in the management of periodontal diseases

6

a periodontal pocket, and given the down of periodontal tissues32. An limited to a skin rash, more severe
tonus of the periodontal tissues, added advantage is their firm reactions may induce swelling and
the carrier must maintain its physi- adsorption to tooth surfaces and tenderness of joints). Systemic
cal stability for an appropriate slow release over time33. The nitro- tetracycline therapy may lead to
period without being prematurely imidazoles (metronidazole and gastrointestinal symptoms such as
dislodged. Products such as drug- ornidazole) affect only the obligate epigastric pain, vomiting or diarrhoea,
laced gels rapidly disappear after anaerobes, including P. gingivalis and essentially due to disturbances of
instillation into periodontal pock- other black pigmenting Gram- the commensal intestinal flora, and
ets unless they change their viscos- negative organisms, but not A. sometimes due to candidal super-
ity immediately after placement30,31. actinomycetemcomitans, a facultative infection. It should not be used in
Viscous and/or biodegradable anaerobe. The tetracyclines and children (up to 8 years) due to
devices show an exponential decrease nitro-imidazoles are used both as unsightly deposition on calcifying
of their concentration in gingival systemic and topical agents18. areas of teeth leading to yellow
fluid. discolouration. Systemic clindamycin
as well as metronidazole may also
Single or multiple antibiotics? be accompanied by gastrointestinal
Antimicrobial agents in disturbances, leading to varying
Due to the complex nature of the
periodontal therapy degrees of nausea, headache,
subgingival microbial niche contain-
Since the appearance of potent ing several putative periodonto- anorexia, vomiting and diarrhoea.
chemotherapeutic agents selectively pathogens with varying antimicro- The disulfiram (or antabuse) effect
active against bacteria in the late bial susceptibility, combination of metronidazole is especially note-
1930s and early 1940s, various drug therapy has been advocated34. worthy, and the drug should never
substances with presumed anti- There are advantages and disad- be taken with alcohol (Table 2).
microbial properties have been vantages to this approach. A
proposed and sporadically tested combination of drugs may have a Systemic antimicrobial therapy
for the treatment of periodontal wider spectrum of activity and their
diseases. However, a surprisingly overlapping antimicrobial spectra General comments
small number of antimicrobial may reduce the emergence of Favourable clinical response to
agents have been tested thoroughly bacterial resistance. Further, due to systemic antimicrobial therapy of
for use in periodontal therapy. The the synergistic activity of two periodontal diseases has been
drugs more extensively investigated complementary agents, the drugs claimed repeatedly in numerous
for systemic use include tetracycline, can be given at a lower concentra- reports. Due to lack of randomi-
minocycline and doxycycline, eryth- tion, thereby reducing the toxicity sation and controls, unclear status
romycin, clindamycin, ampicillin, and side effects of high level of patients at baseline (treatment
amoxicillin, and the nitro-imidazole dosing. A synergistic effect against history, disease activity, composi-
compounds metronidazole and A. actinomycetemcomitans has been tion of subgingival microbiota),
ornidazole. The drugs investigated noted in vitro between metronida- non-standardised maintenance after
for local application include tetra- zole and its hydroxy metabolite35,36 therapy, short observation periods,
cycline, minocycline, doxycycline, and between the latter two or insufficient sample size, a large
metronidazole and chlorhexidine. compounds and amoxicillin37. With number of these presentations does
The penicillins were the first some drug combinations there may, not withstand stringent quality
group of antimicrobials used in however, also be antagonistic drug criteria for evidence-based medi-
periodontal therapy. Of these, interaction (e.g. tetracycline and cine. The cross-comparison between
amoxicillin has been popular due metronidazole) or increased adverse studies is often very difficult as the
to its broad spectrum of activity reactions. selection of subjects, sample size,
against periodontal pathogens. As adverse reactions (Table 2) range of study parameters and
Subsequently, some workers have are relatively common, antibiotics outcome variables have not been
also used the penicillinase resistant should be prescribed only if indi- standardised or documented prop-
penicillins such as clavulanate- cated and other modes of therapy erly38. In most studies, systemic
potentiated penicillin (Augmentin). are inadequate. Although the antibiotics have been used as an
Tetracycline-HCl with a broader- penicillins are among the least toxic adjunct to scaling and root planing,
spectrum of activity than penicillins of antibiotics, clinicians should be and the effect of mechanical therapy
became a popular choice in the aware of possible hypersensitivity plus the systemic antibiotics is
1970s, both due to the latter prop- reactions, which may lead to life compared with mechanical treat-
erty and their ability to inhibit threatening anaphylactic episodes in ment alone. In studies evaluating
collagenase activity, which is highly sensitised persons (in general, the effect of antimicrobials in
thought to interfere with the break- reactions to penicillins are mild and refractory periodontitis or recur-
International Dental Journal (2004) Vol. 54/No.1
 7

Table 2 Adverse effects of antibiotics used in the treatment of periodontal diseases

Antimicrobial agent Frequent effects Infrequent effects

Penicillins hypersensitivity (mainly rashes),nausea, diarrhoea haematological toxicity, encephalopathy,

pseudomembranous colitis (ampicillin)
Tetracyclines gastrointestinal intolerance, Candidiasis, dental photosensitivity, nephrotoxicity,intracranial
staining and hypoplasia in childhood, nausea, hypertension
diarrhoea, interaction with oral contraceptives
Metronidazole gastrointestinal intolerance, nausea, antabus peripheral neuropathy,furred tongue
effect, diarrhoea, unpleasant metallic taste
Clindamycin rashes,nausea, diarrhoea pseudomembranous colitis,hepatitis

(from Mombelli 2002 39, with permission)

rent abscess formation, a control tion with periodontal surgery over associated periodontitis25,34,37,56–60.
group is often lacking, due to surgery alone51,52. In cases with Such combination therapy suppressed
obvious ethical reasons. The follow- rapidly progressive periodontitis A. actinomycetemcomitans below
ing is an outline of antimicrobial metronidazole seemed to improve detection levels in many cases. One
use in clinical trials that are related clinical conditions for up to six study compared the adjunctive
to three distinct disease entities, months which is beyond the effect benefits to mechanical therapy of
namely, chronic and aggressive obtained with mechanical treatment amoxycillin and metronidazole
periodontitis in the adult patient, alone50,53. alone and combined61. Treatment
‘refractory’ periodontitis and, A limited number of patients effects were different and always
aggressive localised periodontitis. with advanced adult periodontitis greatest in patients receiving the
For a detailed review the reader is were treated with clindamycin with- combination therapy, supporting
referred to Mombelli39. out concurrent mechanical therapy, this approach for the management
except oral hygiene instruction. of advanced chronic periodontal
Chronic and aggressive perio- Despite this limited treatment regi- disease.
dontitis in the adult patient men, clinical and microbiological The foregoing implies that
There are many clinical trials where parameters improved over the chronic periodontitis can be treated
chronic and aggressive periodontitis following six months. P. gingivalis in general without systemic antibi-
in the adult patient has been appeared to be particularly suscep- otics. The adjunctive use of antibi-
managed by a combination of tible to clindamycin therapy; this otics should be limited to advanced
mechanical debridement, the intro- species was, at six months, no or aggressive disease. Adjunctive
duction of proper oral hygiene longer detected. Other organisms, metronidazole plus amoxicillin
procedures and antibiotics. The however, were resistant to appears to be a good choice for A.
antibiotics used in these trials clindamycin and were found at actinomycetemcomitans-positive patients.
include tetracycline, metronidazole, slightly higher levels after six Whilst combination therapy may
clindamycin, amoxicillin plus months54. yield favourable outcomes, the
clavulanic acid and a combination Systemic amoxicillin plus advantages and disadvantages
of the above. As stated, many of clavulanic acid, tetracycline HCl, or should be carefully weighed due to
these trials are not properly placebo placebo therapy, given for 30 days relatively frequent occurrence of
controlled. Trials performed in the in conjunction with subgingival gastro-intestinal side effects, i.e.,
late 1970s have shown minor debridement and modified Widman diarrhoea62,63.
differences in the change of mean flap surgery, were compared in
probing depths and attachment adults with progressive periodon- ‘Refractory’ periodontitis
levels between patients receiving titis55. In this study, adjunctive A number of antibiotics have also
tetracycline or placebo as an systemic tetracycline, or amoxicillin been used in the management of
adjunct to mechanical therapy40–44. plus clavulanic acid therapy yielded refractory periodontitis and these
Several trials have tested metro- significantly greater mean pocket include tetracycline group drugs,
nidazole in conjunction with scaling reduction and clinical attachment clindamycin and nitroimidazoles.
and root planing. The results were gain at 10 months post-treatments Mixed results have been docu-
equivocal. Some reported that compared to the placebo regimen. mented with tetracycline therapy in
systemic metronidazole yielded Combinations of metronidazole several studies in adult patients with
marginally better responses than with amoxicillin, Augmentin or ‘refractory’ periodontitis. While a
scaling alone 44–50, while others ciprofloxacin have been used few double blind studies have
found no improvement in patients successfully in the treatment of shown significant reductions in
receiving metronidazole in conjunc- advanced A. actinomycetemcomitans probing pocket depth compared
Mombelli and Samaranayake: Antibiotics in the management of periodontal diseases
8

with placebo controls, with systemic titis not responding to conventional tal patients and eliminates the
tetracycline64–66 others have reported therapy, the favourable effects periodontopathic flora under certain
recurrence of disease activity after reported have been rather transient circumstances. Systemic antibiotics
prolonged therapy 34,58,67,68. One with wide individual variations in should always be used as an
reason for such failure appears to the treatment responses. It is likely adjunct to mechanical periodontal
be the incomplete eradication of that the major reason for failure of treatment. Even if tooth surfaces
the putative causative agent A. therapy is the re-emergence of appear to be free of calculus, the
actinomycetemcomitans from the sub- putative pathogens that have been pockets should be re-instrumented
gingival niches24,34,69. Furthermore, incompletely eradicated. to disrupt the subgingival biofilm
systemic tetracycline therapy may and to reduce the bacterial load as
lead to superinfection by other Aggressive localised periodontitis much as possible.
opportunistic pathogens4,70,71 includ- Several regimens including the Antimicrobial adjunctive therapy
ing fungal species such as Candida72. adjunctive administration of tetra- ideally follows mechanical re-instru-
The metabolic effects of tetracy- cyclines or metronidazole have been mentation. In general, the relative
cline in inhibiting collagenase tested for the treatment of juvenile, success of initial mechanical therapy
production32 is difficult to quantify aggressive localised periodontitis. should be evaluated before antibi-
and this too may have contributed A beneficial effect of systemic otics are prescribed. The initial treat-
to the outcome of these trials. tetracycline therapy on clinical ment plan is then updated, taking
Systemic clindamycin, together attachment and alveolar bone into consideration the general and
with scaling led to a significant levels in juvenile periodontitis has local clinical reactions of the peri-
improvement in patients treated for been shown1,42,78,79. However, as odontal tissues to scaling and root
active periodontal disease despite many as one quarter so treated may planing and the quality of the
previous conventional periodontal experience disease reactivation, even patient’s oral hygiene. If the oral
treatment and systemic tetracycline if their dentition is professionally hygiene seems to be adequate but
therapy73,74. However, the disease cleaned every three months after pocket depths have not decreased
recurred in some patients possibly therapy79. significantly and if bleeding on
due to re-emergence of P. gingivalis, In one study, mechanical treat- probing, or even suppuration,
which was incompletely eliminated. ment with adjunctive systemic tetra- persist in several sites further
Two systemic antimicrobial thera- cycline reduced A. actinomycetem- mechanical therapy supplemented
pies were prescribed in another comitans only partially, while debri- by an antibiotic should be consid-
study on the basis of microbio- dement plus metronidazole (200 ered. Often it will be indicated to
logical susceptibility testing of the mg TID, 10 days) suppressed the start with the antibiotic therapy in
whole subgingival microbiota. same organism below detection the evening after completion of
Refractory adult periodontitis levels for up to 18 months80. As these interventions. Exceptions to
patients, who in the past had been metronidazole is active only against this rule are patients with acute signs
subjected to periodontal surgery, strict anaerobes, these result are of disease, such as periodontal
systemic tetracycline administration rather surprising and could be due abscesses, or acute necrotising
and supportive periodontal therapy, to the hydroxy metabolite of gingivitis, with fever and malaise.
were retreated with scaling and root metronidazole that is active against In such cases, systemic antimicro-
planing in conjunction with either subgingival A. actinomycetemcomitans35,37. bial therapy starts in parallel to
clindamycin or amoxicillin plus The favourable clinical and mechanical debridement.
clavulanic acid. Over a two-year microbiological results obtained Systemic antimicrobials should,
evaluation period, the difference in with adjunctive metronidazole plus as far as possible, be prescribed
the proportions of sites losing amoxicillin in the treatment of rationally after the antimicrobial
attachment following either clinda- advanced periodontitis, particularly sensitivity of the putative patho-
mycin or amoxicillin plus clavulanic when associated with A. actino- gens has been ascertained. These
acid therapy was not significant75. mycetemcomitans, suggest that this laboratory tests, when performed,
Finally, significant improvements form of therapy may also be a should be comprehensive and
in clinical parameters have also good choice for aggressive local- sensitive enough to determine the
been demonstrated after mechani- ised periodontitis. presence and relative proportion
cal debridement combined with of the most important periodontal
systemic metronidazole and organisms. Microbial samples from
Practical guidelines for
ornidazole in patients with recur- the deepest pocket in each quad-
rent periodontal disease76,77. systemic antibiotics in rant can provide a good picture of
In conclusion, although various periodontal disease prevalence and relative importance
antibiotic regimes have been tested Systemic antibiotic therapy improves of putative pathogens in the oral
for the management of periodon- the clinical conditions of periodon- flora 13,81. The microbiological
International Dental Journal (2004) Vol. 54/No.1
 9

samples should, however, not be periodontitis. Unfortunately however the cemental surfaces and penetrates
taken directly from suppurating in many of these trials the test into soft periodontal tissues. When
sites because this may evoke tech- procedure is not directly compared multiple sites are treated salivary
nical problems in the laboratory, to the most obvious alternative, concentrations of tetracycline may
and results may not be accurate. scaling and root planing. Thus, in reach 8-51mg/l. It is salutary to
Empirical therapy, using historical general most of these studies show note that under these conditions
data of antibiotic sensitivity patterns a net positive effect of the drug, the serum concentrations remained
is quite common, as the antimi- yet they do not demonstrate a value below detection level85,86.
crobial profiles of most putative of antibiotic over and above Many clinical studies have been
periodontal pathogens are fairly mechanical treatment. The poten- performed with the monolithic
predictable. tially most valuable area for local Actisite fibres, three of which are
However, it should be noted antimicrobial delivery is in recur- most notable87 in a multi-centre trial
that the emergence of resistance to rent or persistent periodontal of 107 periodontitis patients,
beta lactam drugs or even metro- lesions; so far only few studies have showed that fibre therapy signifi-
nidazole is not uncommon in addressed this issue directly. We cantly decreased pocket depth,
periodontopathogens. review below the predominant increased attachment levels, and
Combination therapy (e.g. metro- products available today for local decreased the bleeding tendency to
nidazole plus amoxicillin) appears antimicrobial therapy that fulfil the a greater extent than the control
more appropriate to predictably basic pharmacokinetic requirements procedures. In another multi-
eliminate periodontal pathogens of sustained drug release. centre study in periodontal mainte-
such as A. actinomycetemcomitans nance patients needing treatment
compared with monotherapy. of localised recurrent periodontitis
There is evidence to support syste- Tetracyclines the effect of fibre therapy was
mic antibiotic therapy in cases of P. Tetracycline group drugs including evaluated as an adjunct to scaling
gingivalis and/or A. actinomycetem- tetracycline, minocycline and doxy- and root planing 88. After six
comitans associated aggressive forms cycline have been incorporated into months, sites treated with scaling
of periodontitis as well as in gener- a number of delivery vehicles such and root planing plus tetracycline
alised refractory periodontitis as non-resorbable plastic copoly- fibre showed a significantly higher
patients with evidence of ongoing mer, biodegradable polymers, and attachment level, significantly more
disease despite optimal mechanical microspheres. In the early devel- pocket depth reduction and less
therapy. opment phase, semi-solid viscous bleeding on probing than scaling
After resolution of the perio- media, hollow devices such as and root planing alone. A third large
dontal infection, the patient should dialysis tubing, and solid devices scale multi-centre study demon-
be placed on an individually tailored such as acrylic strips, collagen, or strated that the results obtained
maintenance care programme. poly-OH-butyric acid strips, were within three months after therapy
Optimal plaque control by the also tested for tetracycline delivery. were maintained over one year and
patient is of paramount importance Tetracycline releasing devices that the combined treatment with
for a favourable clinical and micro- have been used mainly in trials of fibre and scaling had a significantly
biological response to systemic anti- adult periodontitis patients. Of lower incidence of disease recur-
microbial therapy82. these the most widely used is the rence than any of the other tested
Actisite periodontal fiber (ALZA, treatment modalities89.
Palo Alto, CA, USA; Solco, The efficacy of a 2% minocy-
Local delivery of anti-
Birsfelden, Switzerland), a mono- cline ointment (Dentomycin; Cyana-
microbials in periodontal
lithic thread of a biologically inert, mid, Lederle Division, Wayne, NJ,
disease
non-resorbable plastic copolymer USA) has been assessed in a series
As in systemic delivery modes (ethylene and vinyl-acetate) contain- of clinical trials90 evaluating the
described above, a variety of meth- ing 25% tetracycline hydrochloride safety and efficacy of subgingivally
ods have been devised to topically powder. The fibre is packed into applied minocycline ointment, in a
deliver antimicrobial agents into the periodontal pocket, secured randomised, double-blind study in
periodontal pockets and subjected with a thin layer of cyanoacrylate Belgian adults with moderate to
to numerous studies. A number of adhesive and left in place for 7 to severe periodontitis. All patients
these studies are also difficult to 12 days83,84. Due to continuous were treated by conventional scal-
interpret due to variable degrees delivery of tetracycline, a local ing and root planing at baseline
of quality control. Most informa- concentration of the active drug in following which they received
tion on the therapeutic efficacy of excess of 1000mg/l can be main- either the test or a control oint-
local delivery devices is derived tained throughout that period. In ment on four consecutive sessions
from trials in patients with chronic addition the drug diffuses on to at an interval of two weeks (base-
Mombelli and Samaranayake: Antibiotics in the management of periodontal diseases
10

line and 2, 4, 6). A significantly probing depth reductions were cant difference between metroni-
greater reduction of probing depth similar at nine months after local dazole gel application and scaling
was observed at weeks 4 and 12 in delivery of doxycycline hyclate or and root planing could be shown98.
the test group. Subsequently the traditional scaling and root planing
same group evaluated the long-term in patients undergoing supportive Chlorhexidine gluconate
effects of this procedure, used periodontal therapy 94. A multi-
Due to the wide popularity of
intermittently as an adjunct to centre study yielded slightly better
chlorhexidine gluconate in oral
subgingival debridement in chronic clinical results when treating patients
hygiene maintenance this antiseptic
periodontitis and noted clinical and with advanced chronic periodonti-
was a choice candidate for incor-
microbiological improvement over tis with no more than 45 minutes
porating into delivery devices. A
a 15-month period. Others have of debridement plus Atridox than
degradable gelatine chip contain-
assessed the efficacy of weekly after up to four hours of thorough
ing 2.5mg chlorhexidine (PerioChip,
local application of minocycline conventional deep scaling and root
Perio Products, Jerusalem, Israel),
ointment for eight weeks after planing95.
has been the most extensively tested
placement of expanded polytetra-
delivery device in this category.
fluoroethylene membranes to guide
Metronidazole Soskolne et al.99 evaluated the safety
regeneration of periodontal tissue91.
and efficacy of PerioChip in
Although bacterial colonisation of Due to its selective antimicrobial patients with moderate periodon-
treated sites could not be prevented, features against the obligate titis and found that the average
the mean clinical attachment gain anaerobes, metronidazole has been pocket depth reduction in the
of the test group was significantly selected as a potential agent for treated sites with the chip was
greater than that of the control local antimicrobial therapy by significantly greater than in the sites
group. several investigators. Again dialysis receiving mechanical treatment only.
Williams et al.92 have studied the tubing, acrylic strips, and poly-OH- Similar results have been reported
subgingival delivery of 10% butyric acid strips have been tested in another study when the
minocycline in bioabsorbable as solid devices for delivery of chlorhexidine chip was used as an
microcapsules in patients with metronidazole. However, the most adjunct to scaling and root planing
moderate to advanced periodonti- extensively tested and used device in comparison to mechanical treat-
tis. They found that placement of for metronidazole application is a ment alone100.
minocycline microspheres plus scal- gel consisting of a semi-solid The efficacy of three commer-
ing and root planing provided suspension of 25% metronidazole cially available local delivery systems
more significant and prolonged benzoate in a mixture of glyceryl as adjuncts to scaling and root plan-
probing depth reduction than scal- mono-oleate and sesame oil (Elyzol ing was tested in patients with
ing and root planing alone or the Dental Gel, Dumex, Copenhagen, persistent periodontal lesions101,102.
latter procedure plus the vehicle. Denmark). Applied with a syringe The treatment modalities included
Doxycycline, another tetracy- inserted into the pocket, the gel scaling and root planing alone and
cline group drug, has also been increases in viscosity after place- in conjunction with the application
evaluated by a number of workers. ment. Studies have shown that 40% of 25% tetracycline fibres, or 2%
A two syringe mixing system of the applied gel remains in place, minocycline gel, or 25% metroni-
(Atridox, Block Drug, Jersey City, while 60% was immediately lost dazole gel. Although all three
NJ, USA) has been introduced and into the oral environment96. locally applied antimicrobial systems
tested in a series of trials. One In a large multi-centre study of seemed to offer some benefit over
syringe contains the delivery vehi- 206 patients with untreated adult scaling and root planing alone, the
cle, which is a bioabsorbable, periodontitis, the clinical response regimen of scaling and root plan-
flowable polymeric formulation of to subgingival application of the ing plus tetracycline fibre placement
poly(DL-lactide), and the other metronidazole gel was compared yielded the greatest reduction in
contains doxycycline hyclate. When with the effect of subgingival scal- probing depth up to six months
reconstituted by mixing, the prod- ing97. No significant differences were after treatment. Suppuration was
uct contains 10% w/w doxycycline found between the test and the most effectively reduced in the scal-
hyclate. In large clinical trials control group in terms of reduction ing plus tetracycline fibre group,
involving adults with moderate to in probing depth and bleeding on followed by the minocycline group.
severe periodontitis the drug probing or the total cultivable
regimen was equally effective as bacteria and the proportions of
scaling and root planing in reduc- Local vs. systemic delivery of
anaerobic bacteria. These results
ing the clinical signs of adult antibiotics?
were confirmed in another control-
periodontitis over a nine-month led, randomised, blind study of a A key issue requiring clarification
period93. Attachment level gains and total of 164 subjects as no signifi- refers to the selection of a local
International Dental Journal (2004) Vol. 54/No.1
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or a systemic delivery approach Conclusions 399.

whenever the use of an antibiotic is 6. Slots J, Bragd L, Wikström M et al.
Mechanical periodontal treatment The occurrence of Actinobacillus
indicated. As little direct evidence alone is adequate to meliorate or actinomycetemcomitans Bacteroides gingi-
for a comparison of various meth- resolve the clinical condition in most valis and Bacteroides intermedius in
ods of treatment is available so far, cases, but adjunctive antimicrobial destructive periodontal disease in
well founded decision algorithms agents, delivered either locally or adults. J Clin Periodont 1986 13: 570–
to choose specific methods of 577.
systemically, can enhance the effect
intervention for distinct clinical situ- 7. Bragd L et al. The capability of Actino-
of therapy in specific situations.
ations are yet to be devised. In Systemic antibiotics have a useful
bacillus actinomycetemcomitans Bacter-
patients with rapidly progressing oides gingivalis and Bacteroides interme-
role as adjuncts to mechanical treat- dius to indicate progressive periodon-
periodontitis, Bernimoulin et al.103 ment particularly in progressive titis; a retrospective study. J Clin
were unable to show significant adult and early onset periodontitis. Periodont 1995 14: 95–99.
differences between systemic admin- 8. Slots J, Listgarten MA. Bacteroides
Patients with generalised systemic
istration of amoxycillin-clavulanic gingivalis Bacteroides intermedius and
disease that may affect host resist-
acid or tetracycline fibres as an Actinobacillus actinomycetemcomitans in
ance may also benefit from
adjunct to mechanical therapy. systemic antibiotics together with
human periodontal diseases. J Clin
Others have reported better results Periodont 1988 15: 85–93.
mechanical oral hygiene procedures. 9. Fine D. H. Microbial identification
of scaling and root planing supple- Locally delivered antibiotics are and antibiotic sensitivity testing an
mented with locally applied metro- indicated for non-responding sites aid for patients refractory to perio-
nidazole than adjunctive systemic
of focal infection or in localised dontal therapy. J Clin Periodont 1994
metronidazole, in patients with 21: 98–106.
recurrent disease. Mechanical
adult periodontitis104,105. debridement prior to antimicro- 10. Rams TE, Listgarten MA, Slots J.
Micro-organisms such as P. bial therapy, and mechanical plaque
The utility of 5 major putative perio-
gingivalis show different patterns of dontal pathogens and selected clini-
control after therapy, are essential cal parameters to predict periodon-
intra-oral distribution from subject for treatment success. tal breakdown in adults on mainte-
to subject21,80. It could be argued
Finally, administration of systemic nance care. J Clin Periodont 1996 23:
that local therapy would be particu-
antibiotics should be a carefully 346–354.
larly indicated in patients where the 11. Wennström JL et al. Actinobacillus
weighed decision as emergence of
presence of periodontopathogens resistant flora is a worldwide prob- actinomycetemcomitans Bacteroides gingi-
is limited to a few diseased sites as lem of enormous concern.
valis and Bacteroides intermedius: Pre-
opposed to a broad non-specific dictors of attachment loss? Oral
distribution in both diseased and Microbiol and Immunol 1987 2: 158–
163.
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