Antibiotics in periodontics: right or wrong?

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Commentary
Antibiotics in Periodontics: Right or Wrong?
Arie J. van Winkelhoff* and Edwin G. Winkel*
I
well to measures that aim to reduce the periodontal
bacterial load, and clinical improvement occurs
when the bacterial challenge is compatible with the
host’s immunocompetence. It has also been estab-
lished that systemic antibiotics can significantly
enhance the effects of mechanical periodontal ther-
apy, i.e., scaling and root planing in conjunction with
measures that improve the oral hygiene level.1-3A
minor proportion of the patients with periodontitis
does not respond adequately to mechanical treat-
ment, and factors such as smoking, stress, reduced
immunocompetence and systemic diseases are held
responsible.3These patients are prime candidates for
adjunctive systemic antimicrobial therapy. A com-
bination of metronidazole and amoxicillin (MA) has
shown to be an effective antibiotic regime to combat
Aggregatibacteractinomycetemcomitans-
ously Actinobacillus actinomycetemcomitans) and
Porphyromonasgingivalis-associated
infections.4-6Recently, Cionca et al.7reported on
the adjunctive use of this antibiotic regimen in
conjunction to full-mouth scaling and root planing in
patients with moderate to severe chronic periodon-
titis. Guerreo et al.6used a comparable treatment
protocol in patients with aggressive periodontitis and
showed significantly better improvement of all peri-
odontal parameters in the antibiotic-treated patients
compared to placebo-treated subjects 6 months
post-treatment. In both clinical trials, the so-called
full-mouth disinfection approach was used. This
implies scaling and root planing of all affected teeth
within 48 hours, subgingival irrigation with chlorhex-
idine, and chlorhexidine rinsing for 14 days after
subgingival treatment. This approach is based on the
assumption that untreated periodontal sites may be
the source of infection of already treated lesions.
This hypothesis of intraoral reinfection has never
been proven and cannot be proven based on a
clinical protocol. Moreover, it is very unlikely that
mechanical periodontal treatment results in com-
plete subgingival elimination of key periodontal path-
t is well established that periodontal infections are
caused by bacterial deposits in supra- and sub-
gingival dental plaque. These infections respond
(previ-
periodontal
ogens such as P. gingivalis, Tannerella forsythia
(previously T. forsythensis), or A. actinomycetemco-
mitans at treated sites.8,9This notion makes the
discussion of intraoral reinfection rather superfluous.
In most other studies on MA,2the quadrant-wise
approach of non-surgical treatment was used. In a
meta-analysis, it was shown that conventional quad-
rant scaling and root planing is equally effective as the
48-hour protocol.10Therefore, the beneficial clinical
effects in the Guerrero et al.6and Cionca et al.7
studies can be attributed to the use of adjunctive MA
therapy.
The use of adjunctive MA has been studied in
double-masked, placebo-controlled clinical trials,5-7
andthesestudieshaverevealed that,inchronicaswell
as in aggressive periodontitis, the antibiotics result in
better resolution of the periodontal inflammation, bet-
ter probing depths (PDs), and attachment loss reduc-
tion. All three studies clearly showed that the number
of pockets ‡5 mm was better reduced with antibiotics
comparedtoplacebomedication.Forinstance,Guerrero
et al.6showed that, 6 months after active treatment,
the number of sites changing from ‡5 to £4 mm was
significantly higher in the antibiotic-treated patients
than in the placebo-treated subjects (74% versus
54%; P = 0.008) as were the pockets that changed
from‡4to£3mm(55%versus37%;P=0.038).These
observations show that the number of teeth that
needed further treatment was significantly reduced
by adjunctive antibiotic therapy (Table 1). This phe-
nomenon is not new and has been reported after the
use of systemic metronidazole.11
Cionca et al.7calculated the protective risk for fur-
ther periodontal therapy, defined as more than one
site with PD ‡5 mm post-treatment. Backward, step-
wise logistic regression analysis revealed that, at 6
months, only the use of antibiotics (P = 0.01) but
not plaque score, gender, or smoking, determined
the need for further periodontal treatment. The protec-
tive risk amounted to 8.85. The protective risk of an-
tibiotic use for more than one site with PD ‡5 mm 6
months after treatment amounted to 15.62 (P = 0.01).
This means that a subject using systemic MA as
an adjunct to mechanical periodontal treatment was
* Department of Dentistry and Oral Hygiene, University Medical Center
Groningen, Groningen, The Netherlands.
doi: 10.1902/jop.2009.090276
J Periodontol • October 2009
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protected by a factor of 15.62 from further periodontal
treatment.
ANTIBIOTICS FOR ALL?
Should we treat all patients with destructive peri-
odontal diseases with antibiotics? Haffajee,12in her
response to van Winkelhoff,13summarized some rel-
evantquestionsinrelationtotheadministrationofan-
tibiotics in the treatment of periodontitis. One critical
issue is the concern over which patients would benefit
most from systemic antibiotic administration.
The study of Cionca et al.7does not provide an an-
swer to this particular concern, although Figures 2
and 3 in their article clearly indicate a number of out-
liners. They selected their patients on clinical criteria
only. It is well documented that periodontitis is asso-
ciated with different clusters of specific subgingival
bacterial species.14,15Therefore, it is questionable
whether one single antibiotic regimen will be equally
effective in all periodontitis patients. Therefore, the
statementoftheauthors7that‘‘theuseofsystemican-
tibiotics should not be restricted to specific groups of
periodontal patients, for example those with highly
active diseases or a specific microbiological profile’’
is not based on the authors’ observations. They have
notanalyzedtheclinicalresultsinrelationstobaseline
microbiologicdata.However, dowehave data toindi-
cate that not all patients respond equally well to
MA therapy? Yes, we do. In a randomized, double-
masked, placebo-controlled study, Winkel et al.5
showed that the significantly better improvement in
full-mouth PD reduction in patients that used MA was
mainly produced by patients positive for P. gingivalis
atbaseline(Fig.1).Inaddition,thesignificantlygreater
reduction of sites no longer needing additional treat-
ment (i.e., sites with PD <5 mm) after scaling and root
planingplusantibioticswasproducedbypatientswho
were positive for P. gingivalis at baseline (Fig. 2).
Equallyimportantwasthenotionthatsubjectswithout
detectable P.gingivalisatbaselinerespondedequally
well to placebo and test medication in terms of PD re-
ductionandreductionofthenumberofsites‡5mm.In
other words, the subgingival microbial profile at base-
line may be one determining factor of the clinical ef-
fects of systemic antimicrobial therapy. Therefore,
treatment of P. gingivalis-negative patients with anti-
biotics may be considered overtreatment.
Are They all Equal?
A second issue raised by Haffajee12was the concern
whether all antibiotics are equally effective. The clin-
ical trials in which different systemically administered
antibiotics were studied clearly indicate that this is
not the case. Haffajee et al.16showed clinical superi-
ority of metronidazole over azithromycin. Better clin-
ical outcome with metronidazole and clindamycin
than tetracycline has also been reported in severe
aggressive periodontitis.17
In a double-masked,
Table 1.
Percentage of Sites That Changed From
PD ‡5 to <5 mm and That Had Clinical
Attachment Gain (CAG) ‡2 mm in Patients
Treated With Placebo (P) or MA (test)
Treatment
PD ‡5 to
<5 mm CAG ‡2 mm Evaluation Study
P 24.3*20.2*3 months Winkel et al.5†
Test31.8 25.1
P 54.2*16.1* 6 months Guerrero et al.6‡
Test 74.125.4
* Significantly different (P <0.05) between P and test medication.
† Metronidazole (250 mg) plus amoxicillin (375 mg); both drugs 3 times a
day for 7 days.
‡ Metronidazole (500 mg) plus amoxicillin (500 mg); both drugs 3 times a
day for 7 days.
Figure 1.
Full-mouth PD change after scaling and root planing and placebo (P)
or MA (test [T]) therapy in patients with (+) or without (-)
P. gingivalis (Pg) at baseline. Based on data from Winkel et al.5
Figure 2.
Mean reduction of sites (%) with PD ‡5 mm after scaling and root
planing in subjects with (+) or without (-) P. gingivalis (Pg) at baseline
treated with placebo (P) or MA (test [T]). Based on data from Winkel
et al.5
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placebo-controlled clinical trial,18it was shown that
protected amoxicillin did not improve the clinical out-
come to a measurable extent over a period of 12
months, nor did the antibiotic therapy perform better
in suppressing key periodontal pathogens. In none of
these studies were patients selected on the basis of
subgingival microbiologic profile. Clearly, some anti-
biotics in periodontics are more equal than others.
Maybe Not?
What is the down side of antibiotic administration?
The use of antibiotics has also introduced the
emergence of bacterial resistance to one or multiple
antibiotics. Thisworldwideproblem can notbe under-
estimated. It is mainly caused by abuse, misuse, and
poor compliance to the medication. The use of antibi-
otics is associated with adverse effects in a significant
number of subjects.6-8These range from minor and
transient complaints such as nausea, headache, and
altered taste to pseudomembranous colitis. In addi-
tion, antibiotics can cause interactions with other
medications.
CONCLUSIONS
The systemic use of antibiotics in the treatment of se-
vere periodontitis has proven to be clinically advanta-
geous.There isstrong evidence that not all antibiotics
are equally effective. So far, MA therapy seems to
have the best clinical outcome.2It isnot clear whether
all patients will equally benefit from antibiotics. There
is an indication that the baseline microbial profile de-
termines the outcome of antibiotic-based periodontal
treatment.5We know that periodontitis is not a spe-
cific bacterial disease but a compilation of different
bacterial disorders. This observation should become
part of our thinking when designing new studies with
antibioticsinperiodontics.Wedonotneedmorestud-
ies without a sound microbiologic analysis in relation
to the clinical outcome parameters. The outcome of
these studies should assist clinicians in future deci-
sion-making: as to whether or not to prescribe antibi-
otics and if so, during which stage of periodontal
treatment.
Before we prescribe antibiotics to all periodontitis
patients,weneedtofindoutwhich bacterial profilere-
spondsbesttowhichantibiotic.Ifitistruethatsubjects
without P. gingivalis do not benefit from adjunct MA,
then we need to stop prescribing these potent drugs
for this form of periodontitis. Then, we need to find
out whether or not these subjects respond to an alter-
native antibiotic regimen. Antibiotics for all? No, not
yet.
ACKNOWLEDGMENT
The authors report no conflicts of interest related to
this commentary.
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Correspondence: Dr. Arie J. van Winkelhoff, Department
of Dentistry and Oral Hygiene, University Medical Center
Groningen, Antonius Deusinglaan 1, 9713 AV Groningen,
The Netherlands.E-mail:
umcg.nl.
a.j.van.winkelhoff@med.
Submitted May 15, 2009; accepted for publication May 15,
2009.
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