Chlorhexidine

1. Periodontology 2000, Vol. 15, 1997, 55-62
Printed in Denmark .All rights reserved
Copyright 0 Munksgaard 1997
PERIODONTOLOGY 2000
ISSN 0906-6713
Chlorhexidine:
is it stillthe goldstandard?
CHRISTOPHERG.JONES
The dental profession has used chlorhexidine for
over two decades. It is recognized as the primary
agent for chemical plaque control, its clinical effi-
cacy and side effects being well known to the pro-
fession.The literature relating to the use of chlorhex-
idine in plaque control is immense; the proof of the
agent’s efficacy in such a role is beyond dispute, and
the different formulations of chlorhexidine (mouth-
wash, gel and more recently spray) are used routine-
ly in both general dental practice and also in the
periodontal departments of teaching institutions. In
addition to having gained the acceptance of the den-
tal profession, chlorhexidine has also been recog-
nized by the pharmaceutical industry as the positive
control against which the efficacy of alternative anti-
plaque agents should be measured. Thus, chlorhex-
idine deservedly has a place in the dental armory
used to treat or prevent periodontal disease, and has
earned its eponym of the gold standard.
However, familiarity breeds contempt. Much of
the research that has investigated chlorhexidine as
an antiplaque agent has taken place against a back-
ground of sublime ignorance as to the mode of ac-
tion of the agent. It is an antibacterial, yes, but what
makes chlorhexidine unique? What property of the
chlorhexidine molecule permits the agent to be the
standard against which other antiplaque agents are
assessed?
This chapter outlines the latest thinking regarding
the mode of action of chlorhexidine as an antiplaque
agent. The clinical literature relating to the use of
chlorhexidine is reviewed briefly and these data are
related to the proposed mode of action, especially
in terms of an optimum treatment regimen. Finally,
chlorhexidine is compared with other antiplaque
agents and its position as the gold standard is dis-
cussed.
Chlorhexidine-mode of action
Antibacterial activity
Chlorhexidine is an antimicrobial agent. It is a cat-
ionic bisbiguanide with broad antibacterial activity,
low mammalian toxicity and a strong affinity for
binding to skin and mucous membranes (22).Chlor-
hexidine has a wide spectrum of activity en-
compassing gram-positive and gram-negative bac-
teria, yeasts, dermatophytes and some lipophilic vi-
ruses (22). Its antimicrobial activity is of the
membrane-active type, used to describe an anti-
microbial agent that damages the inner (cytoplas-
mic) membrane.
The antibacterial action of the biguanides has
been reviewed by Woodcock (56) and related to the
mechanism of action of chlorhexidine proposed by
Russell & Chopra (48) and Denton (22).Interestingly,
and critically, chlorhexidine shows different effects
at different concentrations; at low concentrations
the agent is bacteriostatic, whereas at higher con-
centrations the agent is rapidly bactericidal. The ac-
tual levels at which the bacteriostatic and bacteri-
cidal effects manifest themselves vary between bac-
terial species (22).
The antibacterial mode of action of chlorhexidine
is thought to be as follows. The bacterial cell is
characteristically negatively charged. The cationic
chlorhexidine molecule is rapidly attracted to the
negatively charged bacterial cell surface, with speci-
fic and strong adsorption to phosphate-containing
compounds. This alters the integrity of the bacterial
cell membrane and chlorhexidine is attracted to-
wards the inner cell membrane. Chlorhexidine binds
to phospholipids in the inner membrane, leading to
increased permeability of the inner membrane and
55

2. Jones
leakage of low-molecular-weight components, such
as potassium ions.
At this bacteriostatic (sublethal) stage, the effects
of chlorhexidine are reversible; removal of excess
chlorhexidine by neutralizers allows the bacterial cell
to recover (22). This implies that the structural
changes to the cytoplasmic membrane caused by
low levels of chlorhexidine are minor compared with
the gross damage caused by higher concentrations
(bactericidal) levels of the agent.
Increasing the concentration of chlorhexidine
causes progressively greater damage to the mem-
brane, reflected in the size of the permeable species
lost from the cell (36, 46). As the concentration of
chlorhexidine increases, leakage of low-molecular-
weight cytoplasmic components falls, reflecting the
coagulation and precipitation of the cytoplasm by
the formation of phosphated complexes such as
adenosine triphosphate and nucleic acids (22).Elec-
tron micrographs show the cytoplasm of such cells
to be chemically precipitated; this bactericidal stage
is irreversible (22).
It has been difficult to demonstrate specific bind-
ing sites in the membrane for chlorhexidine, mainly
due to the several different effects the agent causes
by disrupting the membrane and also due to the
paucity of data in this area. Working with alexidine
and chlorhexidine, Chawner & Gilbert (18, 19) sug-
gest that there may either be specific binding sites
for these molecules in the bacterial membrane or
different intramolecular interactions of the two mol-
ecules at the membrane, the differences in the end-
group substitution between the biguanides affecting
their ability to produce lipid domains in the cell
membrane. Russell (47)and Russell & Furr (49)have
suggested that the outer membrane in some mutant
Escherichia coli strains may confer some mechanism
by which the bacteria are less susceptible to chlor-
hexidine, whereas the inner membrane does not
seem to be involved. The difference in effects of
chlorhexidine on the outer and inner membranes
suggests some degree of specificity of the action of
chlorhexidine on the membrane(s).
Antiplaque mode of action
How do the bacteriostatic and bactericidal actions of
chlorhexidine help us to understand why chlorhex-
idine is considered the gold standard among anti-
plaque agents? How can the bactericidal and bac-
teriostatic effects of this membrane-active agent be
translated into antiplaque activity.
Addy (1)and Kornman (35)ascribe chlorhexidine’s
superior antiplaque activityto its property of persist-
ence (substantivity);indeed, Kornman (35) differen-
tiates antiseptics into first- and second-generation
antiplaque agents, depending on whether or not
they exhibit the ability to persist within the oral
cavity.
At physiological pH, chlorhexidine is a large di-
cationic molecule, (1,6-di(4-chlorophenyl-diguani-
do)hexane, with the positive charge distributed over
the nitrogen atoms on either side of the hexamethyl-
ene bridge. Thus, chlorhexidine has the ability to ad-
sorb onto negatively charged surfaces, such as bac-
terial cell walls, where it exerts its bacteriostatic and
bactericidal effects.
Chlorhexidine also binds to the different surfaces
within the mouth (teeth and mucosa) and also to the
pellicle and saliva; for example, after a single rinse
with chlorhexidine, the saliva itself exhibits antibac-
terial activityfor up to 5 hours (44,451, whereas per-
sistence at the oral surfaces has been shown to sup-
press salivary bacterial counts for over 12hours (51).
Thus, although chlorhexidine is able to bind to dif-
ferent anionically charged elements within the oral
cavity it also, importantly, maintains its antibacterial
activity for several hours (5,44, 51, 52).
Given that plaque formation occurs on the tooth
surface, paradoxically, the binding of chlorhexidine
to the pellicle-covered tooth surface was considered
to be small compared with that involved in chlorhex-
idine-protein interactions at other oral surfaces (12,
21). Indeed, Waaler & Rolla (55)considered that nei-
ther the teeth nor the tongue were of major import-
ance as receptor sites for chlorhexidine in preventing
the accumulation of sucrose-enhanced plaque for-
mation.
This led to speculation that it was the interaction
of chlorhexidine at sites other than the tooth sur-
faces that was important for chlorhexidine’s anti-
plaque effect. This involved a “reservoir” of chlor-
hexidine slowly desorbing from all oral surfaces, re-
sulting in a bacteriostatic milieu in the mouth (26).
Rolla & Melsen (46) postulated that chlorhexidine,
desorbed from the oral mucosa, might have three
mechanisms of plaque inhibition: an influence on
pellicle formation by blocking the acidic groups on
the salivary glycoproteins, thus reducing the protein
adsorption to the tooth surface; an influence on the
adsorption of plaque onto the tooth surface by bind-
ing to the bacterial surface in sublethal amounts and
an influence on the formation of plaque by precipit-
ating the agglutination factors in saliva and dis-
placing calcium from the plaque matrix.
However, Jenkins et al. (29) showed that plaque
56

3. ~
growth on enamel inserts was inhibited equally well
by 0.2%chlorhexidine applied topicallyor by rinsing.
They considered, through electron microscopy of the
enamel inserts, that chlorhexidine achieved its anti-
plaque effect as a result of an immediate bactericidal
action at the time of application, followed by a pro-
longed bacteriostatic action as a result of chlorhex-
idine adsorbing to the pellicle-coated enamel sur-
face. Thus, bacterial attachment to the enamel sur-
face is not entirely inhibited, but bacterial growth is
delayed by the bacteriostatic effects at the surface.
This implied that tooth surface-bound chlorhexidine
was of greater importance in preventing plaque for-
mation than was first thought.
It may be worth attempting to explain the differ-
ence in these findings to that of Wader & Rolla (55);
this may lie in the findings of Davies (21), who con-
sidered that sucrose enhancement of plaque forma-
tion may reduce the effects of chlorhexidine, such
that the low “bacteriostatic” levels of chlorhexidine
are no longer able to penetrate the cellwall of plaque
bacteria grown in the presence of excess sucrose.
Based on the work by Jenkins et al. (291,it is worth
reappraising the concept of an oral reservoir of
chlorhexidine as the basis of the antiplaque activity
of this antiseptic. For this oral reservoir to create a
“bacteriostatic milieu”,there must be adsorption of
chlorhexidine to the oral mucosa and saliva at the
time of application, followed by a progressive de-
sorption over time, resulting in a reduction in the
bacterial challenge to the tooth surface through irre-
versible adsorption of chlorhexidine to the bacterial
cell. The chlorhexidine must move from the mucosa,
saliva etc. to the bacterial cell.
The methods of analysis of desorbed chlorhex-
idine (9-11, 13,25) do not distinguish between “free”
chlorhexidine (if such an entity can occur in a mouth
awash with proteinaceous material), reversibly
bound chlorhexidine and irreversibly protein-bound
chlorhexidine. So, there is no evidence that chlor-
hexidine slowly desorbs from the oral surfaces at all;
it is always likely to be bound to saliva, epithelial
cells, pellicle, bacteria etc.
In addition, unless one believes there is a prefer-
ential removal from the saliva (by chlorhexidine) of
the bacteria that are able to begin colonizing the
tooth surface, one cannot easily explain why the oral
reservoir has an antiplaque effect. Although chlor-
hexidine may reduce the salivary bacterial counts -
a single rinse with chlorhexidine can reduce the oral
flora by over 90% for several hours (5, 44, 51, 52) -
many millions of bacteria present in the saliva and
on the oral surfaces are still not affected.As the oral
Chlorhexidine: the gold standard?
cavity cannot be sterilized,there must be a continual
challenge to the tooth surface by bacteria that are
able to begin the process of plaque formation. As the
salivary bound chlorhexidine patently has not eradi-
cated putative plaque-forming bacteria, it would
seem logical therefore to assume that the process of
plaque prevention occurs at the tooth surface itself -
by tooth-bound chlorhexidine.
Clinical data
This chapter does not review the vast amount of
clinical data relating to chlorhexidine antiplaque ef-
fect in clinical trials. Addy (11,Kornman (35),Lang &
Brecx (37) and Jones (30) have reviewed the clinical
data supporting chlorhexidine as an antiplaque and
antigingivitis agent. However, it would seem appro-
priate to discuss the clinical data pertaining to chlor-
hexidine’s mode of antiplaque action.
To give a very brief overview of two decades of
research into chlorhexidine gluconate as an anti-
plaque agent, Loe & Schiott (42, 43) showed that
rinsing with 10 ml of 0.2%w/v chlorhexidine gluco-
nate mouthwash for 1minute twice daily completely
prevented the formation of plaque and gingivitis.
Once rising with chlorhexidine was terminated,
plaque formed once more. These workers also
showed that a single topical application of 2% wlv
chlorhexidine to the teeth also prevented plaque for-
mation.
Cumming & Loe (20) showed that plaque control
could also be achieved by lowering the concen-
tration of chlorhexidine whilst increasing the volume
of the solution. Cumming & Loe (20)concluded that
the optimal dosage of chlorhexidine was 400 ml of a
0.025% to 0.05% solution in an oral irrigator, and a
50 ml volume of a 0.075% to 0.1% mouthwash.
Brecx et al. (15)showed that three daily rinses with
0.12%chlorhexidine gluconate matched the effect of
optimally performed mechanical oral hygiene tech-
niques, whereas Lang et al. (381, comparing several
differentregimens using mouthwashes with different
chlorhexidine concentrations, concluded that reg-
ular daily application of 0.1% or 0.2% chlorhexidine
mouthwash significantly reduced the development
of plaque and gingivitis. These data were supported
by Segreto et al. (53), who showed that 15 ml of
either 0.12% or 0.2% chlorhexidine mouthwash was
significantly clinically better than placebo mouth-
wash when used alongside toothbrushing. Grossman
et al. (27) and Banting et al. (6) showed the clinical
efficacy of long-term, twice-daily rinsing with 15 ml
57

4. Jones
of 0.12%chlorhexidine gluconate mouthwash, used
alongside oral hygiene measures.
Extending the work of Cumming & Loe (20),
Lang & Raber (39) considered that 300 ml of 0.01%
chlorhexidine mouthwash, delivered once daily by
oral irrigator, was a suboptimal level of chlorhex-
idine (30 mg) for plaque control compared with the
40 mg per day delivered by 10 ml of a 0.2% mouth-
wash solution, twice daily. However, in a further
study Lang & Ramseier-Grossman (40) concluded
that 400 ml of 0.02% chlorhexidine, applied over 1
minute once daily, was the minimum at which an
optimal level of plaque control could be achieved
using an oral irrigator. However, Brownstein et al.
(16), using a split-mouth design, showed that once
daily irrigation with 200 ml of 0.06% chlorhexidine
gluconate had no significant effects on supragingival
plaque, but it did affect gingival bleeding.
Assessing a gel formulation as an alternative
means of delivering chlorhexidine to the teeth and
oral cavity has proven more problematic (31,32), as
much depends on the ability of the patient to deliver
the gel to the appropriate areas of the mouth, the
skill of the patient in toothbrushing (if toothbrushing
is performed at an optimal level,for example by den-
tal students, what effect can an antiplaque agent ac-
tually have?) and the compliance of the patient with
the treatment regimen. Chlorhexidine gel does not
easily penetrate to areas away from its site of appli-
cation (50);thus, any assessment of the effects of the
gel depends on the correct amount of gel reaching
the appropriate area of the mouth for the appropri-
ate period of time (54).
Nevertheless, several studies have shown that a
1% chlorhexidine gel is significantly more active
than placebo, or a control substance, in controlling
plaque in different patient groups, and by different
means of application (3, 7, 8, 14, 17, 24, 32, 41).
One other means of delivering chlorhexidine has
been investigated - a spray. Dever (23) used an ob-
solete dental unit to deliver a single daily application
of a 5-ml spray of a 0.2% chlorhexidine mouthwash
into the oral cavity of mentally handicapped
children. Compared with placebo, the chlorhexidine
spray produced a significant reduction in plaque and
gingivitis.Francis et al. (241,comparing the effective-
ness of twice-daily 0.2% chlorhexidine mouthwash
(10 mll with 1%gel (applied by tray) and 1.4 ml of
0.2%chlorhexidine spray,found that the mouthwash
and spray were equivalent, whereas the gel was sig-
nificantly better in preventing plaque and gingivitis
in institutionalized children. Kalaga et al. (33, 34)
also showed equivalence in antiplaque effect be-
~~
tween a 0.2% chlorhexidine spray and mouthwash
and a significantly better effect of 0.2% chlorhex-
idine spray over placebo spray on the oral hygiene
and gingival health of physically and mentally
handicapped adults.
So, what do these disparate data tell us about the
mode of action of chlorhexidine as an antiplaque
agent?Mouthwash and irrigator application of chlor-
hexidine would seem to support an “oral reservoir”
theory in which the binding sites for chlorhexidine
in the oral cavity are saturated by chlorhexidine mol-
ecules, which are slowly released over a period of
time, producing a bacteriostatic milieu. The opti-
mum delivery of solution (either mouthwash or irri-
gation solution) would seem to be those that allow a
minimum of approximately 40 mg of chlorhexidine
to be delivered throughout the mouth - equivalent
to 10 ml of a 0.2%, or 15 ml of a 0.15%,mouthwash
solution - twice daily. Any reduction from these
levels would seem to be translated into a reduction
in clinical effectiveness.
The effectiveness of the gel would seem to be dif-
ficult to explain in terms of an oral bacteriostatic mi-
lieu. As previously pointed out, the gel does not pen-
etrate easily to sites away from its application. How-
ever, it could be that during brushing the gel is
carried (through the physical action of moving the
brush around the mouth) to binding sites around the
oral cavity, from where a slow release will occur. The
“equivocal”nature of the gel clinical data merely re-
flects the relative efficiency with which the gel is
transferred around the mouth in different studies.
However, this theory does not explain the success of
tray application (241, although application to the
gums and gingiva via the tray might permit an oral
reservoir to be attained.
However, if one views the clinical equivalence of
the spray and mouthwash (24, 33) with the spray
being used at one seventh the volume of the mouth-
wash, the idea of a whole-mouth application of
chlorhexidine being necessary for chlorhexidine to
exert an antiplaque effect becomes unlikely. This ap-
plication of small volumes of 0.2% chlorhexidine, by
spray, directly to the teeth, mirrors (in a clinical set-
ting) the work of Jenkins et al. (29),who compared
the effect of topical application and mouthrinsing
with chlorhexidine gluconate on plaque regrowth on
enamel inserts. Indeed, the original work by Loe &
Schiott (43) showed that topically applied chlorhex-
idine prevented plaque formation; unfortunately, the
use of topical 2% chlorhexidine (as opposed to the
0.2% mouthwash formulation) complicated the
interpretation of these findings.
58

5. Chlorhexidine: the gold standard?
All these data suggest that it must be the tooth-
bound chlorhexidine that prevents plaque forma-
tion; the overall amount of chlorhexidine retained
within the mouth helps to reduce the salivary bac-
terial challenge (which may be useful in situations
such as post-operative healing) but is irrelevant in
terms of chlorhexidine’s antiplaque effect.
Mechanism of the antiplaque
effect
For chlorhexidine to exert an antiplaque effectit must
firstbe delivered successfully,in an active form, onto
the tooth surface. Thus, on rinsing with chlorhex-
idine, there is an immediate reduction in the salivary
bacterial counts. This reduction persists for several
hours because of the substantivity of chlorhexidine,
both within the saliva,and from mucosally desorbed
chlorhexidine into the saliva. However, this is irrel-
evant to the inhibition of plaque by chlorhexidine.At
the clean tooth surface a small amount of chlorhex-
idine (relativeto the total amount orallybound) binds
to the pellicle and enamel, where it remains for sev-
eral hours. This tooth surface-bound chlorhexidine
can then interfere with the adherence of bacteria to
the tooth surface through severalmechanisms postu-
lated by Rolla & Melsen (46).
The antiplaque effect of chlorhexidine can be
hypothesized to be as follows.Any bacteria adhering
to the tooth surface are challenged by the chlorhex-
idine at the surface. Depending on the bacterial spe-
cies, and the amount of chlorhexidine attached to
the tooth surface, these microorganisms are either
killed (bactericidal effect) or are simply prevented
from multiplying (bacteriostatic effect).
The influence of the bacteriostatic effect will in-
crease over time as the concentration of chlorhex-
idine at the tooth surface decreases, due to desorp-
tion into bacteria, saliva etc. The persistent, bac-
teriostatic effect of chlorhexidine is what makes
chlorhexidine the gold standard - plaque is pre-
vented from forming because the bacteria attaching
to the tooth surface cannot multiply.
This hypothesis means that chlorhexidine must
adsorb to the tooth surface and remain there in pref-
erence to desorbing into the saliva, while preferen-
tially desorbing from the tooth surface into the bac-
terial membrane. This might be explained by the
work of Hjeljord et al. (28) who found that, in vitro,
reactions of chlorhexidine with soluble and precipi-
tated proteins were reversible, with chlorhexidine
seemingly bound more strongly to precipitated pro-
teins than to soluble proteins. They hypothesized
that the chlorhexidine-protein interaction could in-
volve a slight denaturation of the protein adsorbed
to the teeth, and the slowreversibilityof this reaction
could partly explain the retention and slow release
of chlorhexidine in the oral cavity. Although the
mechanism of this denaturation in the oral cavity re-
mains to be explained (it occurs under conditions of
immunoelectrophoresis in vitro (2811, it follows that
the interaction of chlorhexidine, enamel and pellicle
is stronger than the interaction of chlorhexidine and
saliva but weaker than that of chlorhexidine and
bacteria. As all oral surfaces are covered by pellicle,
the small amount of chlorhexidine bound to the
tooth surface compared with the other oral surfaces
would simply be a function of the relative surface
area of the pellicle covering these surfaces.
Alternatively, it could be that chlorhexidine might
not be desorbed from the tooth surface or the saliva
or mucous membranes at all. This would mean that
chlorhexidine is actually bound “irreversibly”to the
tooth surface (and the saliva and the mucosa) and
its bactericidal and bacteriostatic effects are based
on contact occurring with bacteria that attach to the
tooth surface (or are free in the saliva or that attach
to the mucosa). Only under these circumstances of
chlorhexidine-bacterium interaction is chlorhex-
idine removed from the tooth surface into the bac-
terium; it is never “free”.
Gold standard
The characterization of different antiplaque agents
by both Addy (1)and Kornman (35)in terms of per-
sistence or substantivity can now be modified; per-
sistence per se is not enough for antiplaque activity.
Chlorhexidine’ssuperior antiplaque effect can be ex-
plained in terms of its superior degree of persistence
at the tooth surface or, more correctly, its superior
persistence of antibacterial effect (both bactericidal
and bacteriostatic) at the tooth surface.
Some other antiseptics have an immediate effect
on the oral microorganisms, but once expectorated,
are removed from the mouth, allowing plaque to
build up once again (no adsorption). Other agents
may show a limited persistence, but their chemical
properties mean they are either lost from the tooth
surface faster than chlorhexidine (limited persist-
ence) or they are bound to the surface in such a way
that they cannot interact with a bacterium (irrevers-
ible adsorption).
59

6. Jones
Furthermore, alternative agents may show the
same degree of persistence at the tooth surface as
chlorhexidine, but they may not possess the bacteri-
cidal and bacteriostatic properties of chlorhexidine.
It is this dual antibacterial effect that allows the per-
sistence of the molecule to translated into anti-
plaque effect, due to the period of time over which
bacterial build up and multiplication on the tooth
surface is prevented.
In this regard the dicationic nature of chlorhex-
idine must play a part; in very simple terms this
could perhaps be envisaged as one charged end of
the chlorhexidine molecule binding to the tooth sur-
face and the other remaining availableto initiate the
interaction with the bacterial membrane as the
microorganism approaches the tooth surface - a
“pin-cushion’’effect? Thus, the lack of effectiveness
of alternative antiseptics may be explained in terms
of them lacking a large, rigid, molecule with two
highly charged, interactive, ends.
Optimizing the use of
chlorhexidine
Chlorhexidine’s antibacterial effect is based on its
ability to interact with, and thus disrupt, the bac-
terial cell membrane. However, chlorhexidine does
not distinguish between bacterial protein and other
proteins found within mature plaque. To optimize
the effect of chlorhexidine, this extraneous protein
must first be removed, ideally professionally. Chlor-
hexidine is an antiplaque agent that prevents plaque
formation; its mode of action does not allow it to
remove plaque efficiently.
Because of its propensity to react with anionic
species, it is also important that the formulation of
chlorhexidine within mouthwashes, spray, gel etc. be
taken into account. The chlorhexidine molecule re-
acts with anionic surfactants present in the formu-
lation, thus reducing the activity of the agent (1).
Similarly, chlorhexidine should not be used be-
fore, or immediately after, using toothpaste; interac-
tion with the anionic surfactants found within these
formulations will reduce the effective delivery of
chlorhexidine to the tooth surface in an active form.
Toothpaste should be used prior to using chlorhex-
idine, and the excess toothpaste rinsed away with
water before applying the chlorhexidine.
The tooth surface activity of chlorhexidine can
also explain the side effect of chlorhexidine-associ-
ated tooth staining, a phenomenon that is not
limited to chlorhexidine alone (37). Based on the
work by Addy et al. (2, 4) the staining can be ex-
plained in terms of a local precipitation reaction oc-
curring between tooth-bound chlorhexidine and
chromogens found within foodstuffs and beverages.
The effect may be minimized by limiting the intake
of such foods and beverages during treatment with
chlorhexidine, especially just after using the chlor-
hexidine formulation. It would therefore seem sens-
ible to reduce the intake of tea and coffee during
the immediate period after the morning rinse with
chlorhexidine, for example, as this is when the orally
bound chlorhexidine will be at its highest concen-
tration. Similarly,use of the mouthwash last thing at
night is to be recommended, as no beverages will be
consumed during sleep.
Finally,it is worth considering optimizing the clin-
ical groups for whom chlorhexidine is recom-
mended. Chlorhexidine’s antiplaque activity is only
important in that it is translated into a clinically rel-
evant end-point - preventing gingivitis. Chlorhex-
idine should not be used as “just” an antiplaque
agent; it has therapeutic effects over and above that
of the cosmetic and pseudotherapeutic mouth-
washes and toothpaste.
It would therefore seem reasonable to target
chlorhexidine at the patient groups for whom a clin-
ical effect is most beneficial. These would be pa-
tients who are compromised in terms of oral hy-
giene: patients who, through physical, mental or so-
cial handicaps, cannot (or are unable or unwilling
to) perform mechanical oral hygiene measures to an
adequate level.
For people whose oral hygiene is compromised
because of temporary disability or through lack of
awareness, chlorhexidine should be used for as short
a period as is necessary to optimize their oral hy-
giene, and enhance self-performed mechanical
measures. For elderly people and physically handi-
capped and mentally handicapped people, longer-
term use may be justified, but with professional
supervision and adjunctive mechanical intervention.
In this way, through understanding the agent’s
properties and limitations, chlorhexidine will remain
the gold standard against which other antiplaque
(and antigingivitis) agents can be measured.
Summary
After 20 years of use by the dental profession, chlor-
hexidine is recognized as the gold standard against
which other antiplaque and gingivitis agents are
60

7. Chlorhexidine: the gold standard?
measured. Chlorhexidine’s antiplaque effect is a re-
sult of the dicationic nature of the chlorhexidine
molecule, which affords the agent the property of
persistence of antimicrobial effect at the tooth sur-
face, through both bactericidal and bacteriostatic ef-
fects. Although other antiplaque agents may show
either purely immediate effect, or limited persist-
ence, the degree of chlorhexidine’spersistence of ef-
fect at the tooth surface is the basis of its clinical
efficacy.
Similarly,the cationic nature of the chlorhexidine
molecule is the basis of the most common side effect
associated with the use of the agent - extrinsic tooth
staining. Such tooth staining seems to be the result
of a local precipitation reaction between tooth-
bound chlorhexidine and chromogens found within
foodstuffs and beverages. The cationic nature of the
chlorhexidine molecule also means that the activity
of the agent is rapidly reduced in the presence of
anionic agents, specifically those found within cer-
tain types of toothpaste; thus care is required when
using normal toothbrushing alongside chlorhex-
idine.
By understanding how the chemical properties of
the chlorhexidine molecule can explain the plethora
of clinical efficacy and safety data, the use of chlor-
hexidine can be optimally aimed towards the patient
groups who would most benefit from the superior
therapeutic effect of the agent. Specifically,chlorhex-
idine would seem to be of most value to patients in
whom the ability to perform adequate oral hygiene
procedures has been compromised. In these individ-
uals the delivery of the correct dose of chlorhexidine
to the tooth surface can be optimized through the
judicial use of the several different chlorhexidine for-
mulations now available.
Thus, by understanding the properties and limi-
tations of the chlorhexidine molecule, the dental
profession can ensure that the efficacy of the agent
is maximized, and the side effects associated with
the agent are minimized, allowing chlorhexidine to
rightly remain the gold standard against which other
antiplaque agents are measured.
References
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