Volume 79 • Number 10

Moxifloxacin as an Adjunctive Antibiotic

in the Treatment of Severe
Chronic Periodontitis
Arndt Guentsch,* Holger Jentsch,† Wolfgang Pfister,‡ Thomas Hoffmann,§ and Sigrun Eick‡

Background: The impact of moxifloxacin (MOX) was ana-

lyzed in the treatment of severe chronic periodontitis.
Methods: In a randomized, prospective, clinical multicenter
trial, 92 subjects with severe chronic periodontitis were treated
with scaling and root planing (SRP) alone (control group; n =
21), SRP plus adjunctive doxycycline (DOX group; n = 36),
or SRP plus adjunctive MOX (MOX group; n = 35). Probing

P
eriodontitis is an infection that
depth (PD), clinical attachment level (CAL), and bleeding on results from an imbalance between
probing (BOP) were recorded at baseline and at 3, 6, and 12 periodontopathic microorganisms
months after non-surgical periodontal treatment. The load of and the local and systemic host defense
periodontopathogens, the level of interleukin-8, and the activ- and is characterized by a progressive
ities of granulocyte elastase and myeloperoxidase were also destruction of the periodontal tissues.
measured. The progression of the disease is related
Results: All three procedures led to significant reductions in to the colonization of microorganisms,
PD, CAL, and BOP. PD reduction was significantly greater (P including Aggregatibacter actinomyce-
<0.05) in the MOX group (2.46 – 1.17 mm at 6 months and temcomitans (previously Actinobacillus
2.84 – 1.53 mm at 12 months) compared to the DOX group actinomycetemcomitans), as well as
(1.85 – 1.24 mm and 2.19 – 1.13 mm at 6 and 12 months, re- members of the so-called ‘‘red complex’’:
spectively) and the controls (1.77 – 0.57 mm and 1.86 – 0.56 Porphyromonas gingivalis, Tannerella
mm at 6 and 12 months, respectively). Only in the MOX forsythia (previously T. forsythensis),
group was the load of all investigated bacteria and all inflam- and Treponema denticola.1 Effective host
matory parameters reduced at each appointment compared response to bacterial challenge is pri-
to baseline. marily mediated by neutrophils and char-
Conclusions: The adjunctive application of antibiotics im- acterized by an influx of neutrophils into
proved the treatment outcome in subjects with severe chronic the gingival crevice. Neutrophil recruit-
periodontitis. MOX seemed to be more effective than DOX and ment and influx into the gingival crevice
might be an alternative drug in the treatment of periodontal depend on chemotactic agonists, such as
diseases. J Periodontol 2008;79:1894-1903. interleukin (IL)-8, which are synthesized
KEY WORDS and released in the area of inflammation.
Human neutrophil elastase (HNE), a
Dental scaling; doxycycline; moxifloxacin; periodontitis;
neutral serine protease, and myeloper-
root planing.
oxidase (MPO) are stored in the cyto-
plasmic azurophil granules and are
capable of degrading a wide variety of
* Department of Conservative Dentistry, University Hospital of Jena, Jena, Germany.
† Department of Conservative Dentistry and Periodontology, University Hospital of Leipzig, functionally and structurally important
Leipzig, Germany.
‡ Institute of Medical Microbiology, University Hospital of Jena.
molecules in human tissues.2
§ Department of Conservative Dentistry and Periodontology, University Hospital of Dresden, The primary aim of periodontal treat-
Dresden, Germany.
ment is to reduce the infection, resolve
inflammation, and prevent any further
destruction.3 Adjunctive antibiotics can
be used to improve treatment outcomes
in patients with severe chronic peri-
odontitis and aggressive periodontitis.4,5

doi: 10.1902/jop.2008.070493

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J Periodontol • October 2008
Antibiotics that have been studied in periodontal
treatment include tetracyclines (e.g., doxycycline
[DOX]) and metronidazole, frequently combined with
amoxicillin.6 However, problems of bacterial resis-
tance7,8 suggest that alternatives for the currently
used antibiotics may be needed.
Quinolones were introduced for use in urinary tract
infections in the 1970s. They represent one of the
main classes of antibiotics. Advantages of this class
of antibiotics are good penetration into tissues and an-
tibacterial activity within cells. The first and second
generations act only on Gram-negative aerobic bac-
teria.9 Newer quinolones, of which the most important
representative is moxifloxacin (MOX), have improved
activity against Gram-positives and anaerobes.10 In
vitro studies11-13 showed good activity against plank-
tonic microorganisms as well as bacteria located
within a biofilm or intracellularly.
The purpose of the study was to evaluate the impact
of adjunctive systemic MOX compared to the use of
adjunctive systemic DOX, a well-established regimen,
and scaling and root planing (SRP) alone on the suc-
cess of periodontitis treatment. The null hypothesis
was that MOX has no effect on the clinical outcome
of periodontal treatment. The present study focused
on changes in clinical data, inflammatory parameters,
and the load of periodontopathogenic bacteria.
MATERIALS AND METHODS
Subject Population
A total of 102 subjects attending three university
dental-school clinics (Dresden, Jena, and Leipzig;
n = 34 each) were recruited from October 2004 to
December 2005. Subjects with generalized chronic
periodontitis were included when they demonstrated
attachment loss ‡5 mm at >30% of sites and age
‡35 years.
Inclusion criteria. Subjects were without any systemic
condition that could influence the outcome of the
treatment, had ‡20 treatable teeth in occlusion, had
at least five pockets with ‡5 mm in different quadrants
(including one incisor, two premolars, and two mo-
lars), and had radiographic evidence of moderate to
advanced periodontal destruction.
Subjects were excluded if they had known allergies
to quinolones or tetracyclines; had received medica-
tion, such as antibiotics, steroids, or non-steroidal
anti-inflammatory drugs, within the previous 6 months;
had received any periodontal treatment in the previous
12 months; had systemic diseases (e.g., diabetes
mellitus); or were pregnant or nursing.
The study protocol was approved by the Ethics
Committees of the Universities of Dresden, Jena,
and Leipzig. All participants gave their written in-
formed consent.
Guentsch, Jentsch, Pfister, Hoffmann, Eick
Study Design
The study was designed to assess the efficacy of a new
antibiotic (MOX) as an adjunct in periodontal treat-
ment compared to SRP alone (control) and SRP com-
bined with an established antibiotic regimen (DOX).
The primary endpoint of the study was change in
probing depth (PD) 12 months after intervention;
reduction of bleeding on probing (BOP), change in
clinical attachment level (CAL), need for retreatment,
and reduction of periodontopathic bacteria as well as
inflammatory parameters were considered secondary
endpoints. To detect differences in PD of 1.5 – 1.2 mm
with a = 0.05 and a power of 90%, our groups were re-
quired to include ‡18 subjects each. Before the onset
of the study, the plaque index14 had to be <35% after
the hygiene phase, which included supragingival cal-
culus removal and oral hygiene instructions.
The subjects were randomly assigned into the three
treatment groups. The randomization process was
performed independently at each center.
The treatment groups consisted of SRP alone (con-
trol group); SRP combined with orally administered
DOX,i 200 mg on the first day followed by 100 mg/
day for 9 days (DOX group); and SRP combined with
systemically administered MOX,¶ 400 mg, once daily
for 7 days (MOX group).
Each center performed the treatment in the same
standardized manner; subjects received instructions
from an experienced periodontist in oral hygiene.
Treatment started with chlorhexidine rinsing (0.12%)
for 1 minute. Subgingival depuration and root planing
for disrupting the subgingival biofilm were performed
in all four quadrants under local anesthesia as a full-
mouth procedure within 24 hours by the same expe-
rienced periodontist (one calibrated periodontist at
each center). SRP was performed with manual instru-
ments# on all teeth. An ultrasonic instrument** was
only used in the furcation areas. SRP was completed
within 120 minutes. The endpoint of SRP was a tactile
smooth root surface. The subjects began taking the
antibiotics on the first day of the procedure. Subjects
in the control group (SRP) received no antibiotic or
placebo. Subjects in the DOX and MOX groups were
extensively informed about the intake of the pre-
scribed medication.
Subjects were monitored at baseline (1 week before
therapy) and at 3, 6, and 12 months after SRP. At
these appointments, the examiner recorded any med-
ical history change, in particular, that no antibiotic
therapy had been administered; periodontal para-
meters were recorded; and samples were collec-
ted for microbiologic and immunologic analysis. All
i Ratiopharm, Ulm, Germany.
¶ Bayer Vital, Wuppertal, Germany.
# Gracey curets, Hu-Friedy, Leimen, Germany.
** Cavitron SPS, Denstply DeTrey, Konstanz, Germany.
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Moxifloxacin in Periodontal Treatment
subjects received supportive periodontal treatment
and reinforcement of oral hygiene procedures at
3-month intervals for a period of 12 months. Signs of
recurrent inflammation (e.g., suppuration) were pre-
defined stopping criteria, and these subjects were
excluded from the study and retreated.
Clinical Data
PD, CAL, and BOP were recorded at all monitoring
visits. PD and CAL were recorded to the nearest mil-
limeter at six sites per tooth (mesio-buccal, buccal,
disto-buccal, disto-lingual, lingual, and mesio-lin-
gual) using a manual periodontal probe.†† PDs were
subdivided into categories for data analysis: <4 mm
(shallow pockets), 4 to 6 mm (moderate pockets),
and >6 mm (deep pockets). BOP was recorded at
six surfaces per tooth, and the percentage of teeth with
BOP was calculated. The plaque scores were calcu-
lated as the percentage of surfaces examined demon-
strating plaque.
At each center, one calibrated examiner who was
masked to the treatment allocation performed all
periodontal measurements at all visits. A different cli-
nician provided the treatment. The calibration of ex-
aminers included measurements of PD and CAL in five
subjects, who were not participating in this study, and
involved intra- and interexaminer calibration. PD and
CAL were measured in duplicate at a randomly chosen
tooth in each quadrant, and calibration was accepted if
>90% of the measurements were identical.
Collection of Gingival Crevicular
Fluid (GCF) Samples
Calibrated investigators obtained the samples. GCF
samples from each subject were collected from
five periodontal pockets with depths ‡5 mm. Three
pockets (one incisor, one premolar, and one molar)
were selected for determination of periodontopatho-
genic bacteria; two pockets (one premolar and one
molar) were used for the determination of inflamma-
tory parameters. At the selected sites, supragingival
plaque was carefully removed, after which the sample
sites were isolated with cotton rolls and gently air-
dried. Each sterile paper point (ISO 35) was inserted
into the periodontal pocket for 20 seconds. For deter-
mination of inflammatory parameters, the paper point
was placed into 500 ml phosphate buffered saline for
24 hours at 4C after removal from the pocket. The
eluates were centrifuged at 2,000 · g at 20C for 4
minutes to remove cell debridements. The superna-
tants and the paper points were stored at -20C until
assayed for microbiologic analysis. All specimens
were masked for laboratory analysis.
Microflora
DNA was extracted using a DNA extraction system‡‡
according to recommendations of the manufacturer.
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Volume 79 • Number 10
Real-time polymerase chain reaction (PCR) was car-
ried out using a real-time rotary analyzer.§§ The
primers for P. gingivalis, T. forsythia, and T. denticola
were designed as described by Ashimoto et al.;15
those for A. actinomycetemcomitans were designed
as described by Tran and Rudney.16 PCR amplifica-
tion was carried out in a reaction volume of 20 ml con-
sisting of 2 ml template DNA and 18 ml reaction
mixture containing 2 ml 10· PCR buffer, 2.75 mM
MgCl2, 0.2 mM nucleotides, 0.5 mM each primer,
10-4 green dye,ii and 1 U Taq polymerase.¶¶ Nega-
tive and positive controls were included in each batch
of specimens. The positive control consisted of 2 ml
genomic DNA in concentrations ranging from 102
to 107 bacteria of the reference strains, and the neg-
ative control was 2 ml sterile water; each was added
to 18 ml reaction mixture. The cycling conditions
consisted of an initial denaturation step at 95C for
5 minutes, followed by 45 cycles at 95C for 15 sec-
onds, 65C (with the exception of A. actinomycetem-
comitans = 62C) for 20 seconds using a touch-down
for five cycles, and 72C for 20 seconds. The sensi-
tivity and specificity of the method were checked
by well-characterized bacterial strains and subgingi-
val plaque specimens. Furthermore, the specificity
of the amplification was always assayed with melt-
ing curves. For quantification, the results from un-
known plaque specimens were projected on the
counted pure-culture standard curves of the target
bacteria. The numbers of bacteria were classified us-
ing log-stages.
Inflammatory Parameters
Human neutrophil granulocyte elastase activity was
measured with a microplate assay using the chro-
mogenic substrate, N-methoxysuccinyl-Ala-Ala-pro-
Val-pNa.##17 The substrate was dissolved in dimethyl
sulfoxide to 10 mM, and the working solution was
made up to 1 mM by dilution with 0.05 M Tris, pH 7.5.
In brief, 10 ml substrate working solution was added
to 90 ml eluate of the specimen. Absorbency at
405 nm was measured immediately and after incuba-
tion at 37C for 30 minutes in a microplate reader.
One unit was calculated as the amount of enzyme that
hydrolyzed 1 nmol substrate in 1 minute.
MPO activity was assayed after mixing 40 ml eluate
of the specimen with 160 ml substrate containing
0.8 mM O-dianisidine*** and 0.1 mM H2O2. The
change in absorbency was measured at 450 nm for
30 minutes. The results were expressed in units where
†† PCP UNC-15, Hu-Friedy.
‡‡ High Pure PCR Template Preparation Kit, Roche, Mannheim, Germany.
§§ RotorGene 2000, Corbett Research, Sydney, Australia.
ii SYBR Green, Fermentas Life Science, St. Leon-Rot, Germany.
¶¶ Fermentas Life Science.
## Sigma-Aldrich, Taufkirchen, Germany.
*** Bayer Vital.
J Periodontol • October 2008 Guentsch, Jentsch, Pfister, Hoffmann, Eick

Table 1.
PD and CAL During 12 Months (mean – SD)

PD (mm) CAL (mm)

Baseline 3 Months 6 Months 12 Months Baseline 3 Months 6 Months 12 Months

Control group 5.03 – 0.43 3.37 – 0.52 3.27 – 0.37 3.18 – 0.39 5.15 – 0.55 3.80 – 0.75 3.75 – 0.74 3.61 – 0.57

DOX group 5.16 – 0.80 3.24 – 0.70 3.18 – 0.73 3.22 – 0.77 5.64 – 0.91 3.96 – 0.93 3.79 – 0.87 3.90 – 0.86
MOX group 5.17 – 0.61 3.14 – 0.45 3.08 – 0.43 3.07 – 0.45 5.50 – 0.94 3.94 – 0.99 3.76 – 0.93 3.58 – 0.51
Data at 3, 6, and 12 months after periodontal treatment were significantly different from the baseline values (P <0.05). Analyses of changes within the groups
demonstrated only a significant difference between the baseline visit and the 3-month monitoring visit (P <0.5).

one unit of MPO activity is defined as that which de- scribed adjunctive antibiotics (need for retreatment:
grades 1 mM H2O2/minute.18 two subjects at the 3-month monitoring visit and three
The concentration of the chemokine IL-8 was de- subjects at the 6-month evaluation). Two subjects
termined using a commercially available ELISA kit††† from the control group, one subject from the DOX
as described in the manufacturer’s instruction. Each group, and two subjects from the MOX group were un-
100 ml eluate was used for determining IL-8. willing to complete the study. Twenty-one subjects
(10 males and 11 females) in the control group, 36
Data Analysis
subjects (19 males and 17 females) in the DOX group,
The subject was the unit of analysis in all statistical
and 35 subjects (15 males and 20 females) in the
tests. Individual means – SDs were calculated.
MOX group completed the study. Ninety-two subjects
Normal distribution of the clinical data was verified
could be reevaluated after 12 months; therefore, only
with the Kolmogorov-Smirnov test with Liliefors cor-
the data from these subjects, with a mean age of 49.6 –
rection (P >0.1). Differences in clinical parameters
9.4 years, were entered into the analysis. Subjects
among the treatment groups were analyzed using
had a mean of 26.43 – 2.96 teeth. None of the teeth
analysis of variance with univariate repeated mea-
that were monitored required extraction during the
surements. The x2 test was used to detect differences
study. At baseline, there were no significant differ-
regarding the need for retreatment. A P value <0.05
ences in clinical parameters among the three treat-
was considered statistically significant. Differences
ment groups (controls, DOX, and MOX). Less than
within the groups were analyzed using a paired t test.
35% of the subjects were active smokers. The subjects
The resulting unadjusted P values were interpreted
in the antibiotic groups confirmed completion of their
with the Holm-Shaffer a adjustment.
prescribed medication (DOX, n = 36; MOX, n = 35),
Because there was not a normal distribution, the
and none reported any adverse event at any time point
changes in microbiologic and inflammatory parame-
associated with the therapy.
ters between baseline and 3, 6, and 12 months were
analyzed within the groups using the Wilcoxon test.
PD
Here, the Kruskal-Wallis H test was used to determine
All three treatment procedures led to significant de-
significant differences among the three test groups
creases in PD over the course of the study (P <0.05;
specified by using the Mann-Whitney U test for deter-
Table 1). PD reductions were significantly greater in
mination of significant differences between two test
the MOX group than in controls or the DOX group
groups.
at 6 and 12 months after therapy (P <0.05). There
Analyses were performed with statistical soft-
were no significant differences between PD reductions
ware.‡‡‡
observed in the DOX and SRP groups. Analyses of
RESULTS changes within the groups demonstrated that a signif-
icant reduction in PD occurred in every group between
A total of 102 subjects entered the study. The control
the baseline visit and the 3-month monitoring visit
group (SRP alone) consisted of 28 subjects, and the
(Fig. 1). There were no statistically significant dif-
DOX and MOX groups had 37 subjects each. How-
ferences after a-adjustment among the 3-, 6-, and
ever, more subjects completed the study in the antibi-
12-month monitoring visits.
otic groups than in the control group (SRP alone).
Moderate (4 to 6 mm) and deep pockets (>6 mm)
Subjects in the control group needed significantly
were significantly reduced in all groups after the
more treatment intervention (P <0.05). Five subjects
in the control group who withdrew early required fur- ††† BioSource International, Camarillo, CA.
ther periodontal instrumentation (SRP) and were pre- ‡‡‡ SPSS 13.0 for Windows, SPSS, Chicago, IL.

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Moxifloxacin in Periodontal Treatment Volume 79 • Number 10

ferences were only detected be-

tween the control and MOX groups.
CAL
CAL data are presented in Table 1.
Statistically significant CAL gains
were seen in all three groups dur-
ing the study period (Fig. 1). CAL
gains were significantly greater in
the MOX group compared to the
control group (P <0.05).

BOP
No significant differences in changes
in BOP were detected among the
groups. BOP scores at 3, 6, and
12 months after therapy were sig-
nificantly reduced compared to
baseline in all treatment groups
(P <0.05). SRP alone led to a reduc-
tion in BOP from 76.5% – 20.1%
at baseline to 34.4% – 16.3% at
3 months, 25.3% – 21.2% at 6
months, and 28.0% – 15.6% at 12
months. The data for the DOX
group were 79.1% – 27.2% (base-
line), 38.2% – 23.4% (3 months),
27.1% – 17.78% (6 months), and
28.1% – 16.2% (12 months). The
BOP values for MOX were 80.5% –
27.0% (baseline), 25.5% – 12.1%
(3 months), 25.5% – 22.9% (6
months), and 26.3% – 22.4% (12
months).
Oral Hygiene Status
The plaque scores (controls,
64.9% – 25.6%; DOX, 65.2% –
Figure 1. 23.7%; and MOX, 64.6% – 22.8%)
Reduction of PD and gain of attachment after periodontal treatment with or without adjunctive were reduced significantly during
antibiotic medication. A) PD reduction: only the MOX group showed a statistically significant the hygiene phase (P <0.05). The
reduction in PD compared to the control group (*P <0.05) and the DOX group (†P <0.05) after 6 following scores were recorded at
and 12 months. B) There were significant differences in the gain of CAL between the MOX group
‡
and controls after 6 and 12 months ( P <0.05). the baseline examination: controls,
25.4% – 10.6%; DOX, 24.3% –
9.8%; and MOX, 23.9% – 10.4%.
At the end of the study (12-month
treatment. Again, significantly greater PD reductions examination), these values had increased slightly,
were observed in the MOX group compared to the but not significantly, to 30.4% – 10.9% in the control
control (SRP) group (Table 2). group, 31.6% – 12.3% in the DOX group, and 30.7% –
The proportion of PD categories is illustrated in 10.7% in the MOX group. There were no significant dif-
Figure 2. The share of shallow pockets increased ferences among the groups at any time point.
significantly in all treatment groups after therapy, with
no differences among the groups. The proportions Microbiologic Analysis
of moderate and deep pockets were significantly re- In the MOX group, a significant reduction in the load of
duced by all procedures; however, there were signifi- all investigated bacteria was found at each time inter-
cant differences between the SRP and both antibiotic val after treatment compared to baseline. Twelve
groups at 3 and 6 months. After 12 months, these dif- months after treatment, the number of negative

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J Periodontol • October 2008 Guentsch, Jentsch, Pfister, Hoffmann, Eick

Table 2. 3 months after treatment. The numbers

of A. actinomycetemcomitans did not
PD (mm; mean – SD) of Shallow, Moderate,
change at any time. A significant reduc-
and Deep Pockets tion in the load of P. gingivalis was de-
tectable only in the SRP group (Table 3).
Baseline 3 Months 6 Months 12 Months After 3 months, significant differences
Shallow sites (initially <4 mm) among the three groups were registered
Control group 2.22 – 0.26 2.02 – 0.21 2.03 – 0.29 2.01 – 0.28 for T. forsythia (P <0.01) and T. denticola
DOX group 2.52 – 0.28 2.12 – 0.35 2.11 – 0.33 2.14 – 0.37 (P <0.05). After 6 months, the results
MOX group 2.46 – 0.28 2.11 – 0.37 2.10 – 0.34 2.07 – 0.39 were significantly different for A. actino-
mycetemcomitans (P <0.01) and P. gin-
Moderate sites (initially 4 to 6 mm)
givalis (P <0.05), and after 12 months,
Control group 4.68 – 0.19 3.24 – 0.46 3.19 – 0.33 3.11 – 0.35
DOX group 4.70 – 0.27 3.05 – 0.56 3.00 – 0.57 3.05 – 0.61 the results were significantly different
MOX group 4.69 – 0.26 2.99 – 0.39* 2.93 – 0.40* 2.96 – 0.40 only for T. forsythia (P <0.05). Twelve
months after therapy, no significant dif-
Deep sites (initially >6 mm) ferences were found between the two an-
Control group 7.33 – 0.45 4.97 – 1.39 4.61 – 1.21 4.72 – 1.36 tibiotic groups. The results were better
DOX group 7.66 – 0.60 4.25 – 1.35 4.05 – 1.21 4.09 – 1.70
for MOX compared to DOX with regard
MOX group 7.50 – 0.45 4.19 – 1.12* 3.94 – 1.02* 4.01 – 0.93*
to A. actinomycetemcomitans 3 months
No differences among the groups or within the groups were observed in shallow pockets. (P <0.05) and 6 months after treatment
* Significant difference compared to controls (P <0.05).
(P <0.01). Twelve months after therapy,
differences were seen between
one of the antibiotics groups and
the SRP group for T. forsythia
(MOX–control, P <0.05) and P. gin-
givalis (DOX–control, P <0.05).

IL-8 and Neutrophil Enzymes

In the MOX group, a significant re-
duction in the levels of IL-8 and
neutrophil enzymes was found at
each appointment compared to
baseline (IL-8: 3 and 6 months, P
<0.01; 12 months, P <0.05; HNE:
each P <0.01; MPO: each P
<0.01). In the DOX group, a signif-
icant decrease in the level of IL-8
was visible at 6 and 12 months af-
ter treatment (each P <0.05); the
activity of HNE was significantly
lower only up to 6 months after
treatment (each P <0.01). The ac-
Figure 2. tivity of MPO did not change at any
The proportion of PD categories at the monitoring visits. Moderate (4 to 6 mm) and deep pockets time. In the SRP group, a signifi-
(>6 mm) were significantly reduced in all treatment groups. There were significant differences cant reduction in the levels of IL-8
between the groups. The proportion of shallow pockets (<4 mm) increased over time. § P <0.05; was detectable after 6 and 12
significantly different from the control group. months (P <0.05); the neutrophil
enzymes did not show any signifi-
cant differences within this group.
subjects had increased from 43% to 67% for A. actino- Significant differences among the three groups were
mycetemcomitans, from 11% to 40% for P. gingivalis, registered for IL-8 after 6 months (P <0.05). The results
from 6% to 26% for T. forsythia, and from 14% to 29% were different for HNE activity (each P <0.01) at all time
for T. denticola. In the DOX group, a significant de- intervals after therapy; MPO activity never differed sig-
crease in the numbers of P. gingivalis and T. forsythia nificantly among the groups (Table 4). At 12 months
was also observed at 3, 6, and 12 months after treat- after therapy, only the activity of HNE was different be-
ment. T. denticola was significantly reduced only tween the two antibiotic groups, and the activity was

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Moxifloxacin in Periodontal Treatment Volume 79 • Number 10

Table 3. adjunctive antibiotics failed

to demonstrate a benefit,
Effect of SRP With the Adjunctive Use of MOX
other studies supported the
and DOX and Without Antibiotic Use on the Load of clinical benefits of using ad-
A. actinomycetemcomitans, P. gingivalis, T. forsythia, junctive antibiotics in the
and T. denticola in Subgingival Plaque treatment of periodontal dis-
ease. Positive effects of DOX
3 Months After 6 Months After 12 Months After were reported in A. actino-
Baseline* Treatment* Treatment* Treatment* mycetemcomitans–associated
localized aggressive peri-
A. actinomycetemcomitans
odontitis in six subjects.25
MOX group 57/14 54/6 31/0 33/6
The benefits of DOX and
DOX group 61/17 67/25 61/28 50/17
Control group 57/14 57/24 52/10 62/19 metronidazole were also
described in subjects with
P. gingivalis recurrent chronic peri-
MOX group 89/74 63/14 63/20 60/26 odontitis.26-28 An additional
DOX group 92/67 67/17 75/36 64/23 clinical benefit was also ob-
Control group 95/76 67/29 71/29 62/19
served by Grossi et al.,29
T. forsythia who compared systemically
MOX group 94/64 86/39 83/28 74/11 administered DOX and pla-
DOX group 94/57 77/17 86/40 74/34 cebo in Native American
Control group 86/38 90/48 81/38 95/52 subjects with diabetes melli-
T. denticola tus and periodontal disease.
MOX group 86/17 80/14 80/18 71/11 Another clinical study30
DOX group 81/19 56/6 67/14 72/11 investigated the effects of
Control group 81/14 86/19 67/10 71/15 different antimicrobials (met-
* Percentage of subjects with detectable periodontopathogens/percentage of subjects with a load >10
5 ronidazole, metronidazole +
(A. actinomycetemcomitans 104) in at least one of the three sites analyzed. amoxicillin, and DOX) on
clinical outcome in subjects
lower in the MOX group (P <0.01). At the final exami- with generalized aggressive periodontitis. Only met-
nation, differences were seen between the antibiotics ronidazole and the combination with amoxicillin were
groups and the control group for MPO activity (MOX ver- effective in deep pockets. In that study, DOX demon-
sus controls and DOX versus controls; both P <0.05) and strated no additional benefit in the reduction of deep
HNE activity (MOX versus controls; P <0.05). pockets (>6 mm) compared to the control group, in
which subjects were treated with SRP alone. This
DISCUSSION was similar to our observation that there were no sig-
This randomized, clinical trial evaluated the effects of nificant differences in clinical outcomes between the
adjunctive antibiotics (DOX versus MOX) on clinical DOX group and the control (SRP) group. This fact also
outcomes in subjects with severe chronic periodonti- indicates that we had no ‘‘placebo effect,’’ although all
tis. An increased frequency of tetracycline resistance groups were informed about the comparison of differ-
has been reported.19 Furthermore, conflicting results ent antibiotics. The efficacy of antibiotics over pla-
about the clinical benefits of DOX used as an adjunct cebo when used as part of periodontal treatment
to SRP mean that alternatives to DOX should be inves- has been reported.31,32 These studies demonstrated
tigated. 20,21 MOX has been described as an important that antibiotics resulted in better clinical and microbi-
option in the treatment of bacterial infections.9 Data ologic outcomes than placebo. All subjects were care-
from in vitro studies12,13,22 suggested a benefit in fully informed about medication intake, but we had no
treating periodontal infections and paved the way guarantee that the subjects followed our instructions.
for clinical trials to investigate the effects of MOX in Interviews and tablet counts as methods to assess
the treatment of periodontal disease. subject compliance were found to be unreliable.33
The results indicated that the greatest clinical bene- The adjunctive use of an orally administered anti-
fits were achieved if SRP was combined with systemic biotic in addition to SRP was shown to improve the
antibiotics. Significantly greater PD reductions and microbiologic results. The authors focused on deter-
CAL gains were observed in those subjects treated mination of four periodontopathogens: A. actino-
with adjunctive MOX compared to the control group mycetemcomitans, P. gingivalis, T. forsythia, and
(SRP alone). For these reasons, the null hypothesis T. denticola. These bacterial species are known to re-
was rejected. Although some earlier studies23,24 of late strikingly to clinical measures of periodontal

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J Periodontol • October 2008 Guentsch, Jentsch, Pfister, Hoffmann, Eick

Table 4.
Effect of SRP With the Adjunctive Use of MOX and DOX and Without Antibiotic Use on
the Level of IL-8 and the Activities of HNE and MPO in GCF (median [range])

Baseline 3 Months After Treatment 6 Months After Treatment 12 Months After Treatment
IL-8 (pg/site)
MOX group 76.80 (10.19 to 568.46) 32.50 (5.37 to 437.51) 36.57 (4.74 to 429.54) 33.30 (6.14 to 163.77)
DOX group 63.87 (16.18 to 529.80) 63.84 (12.78 to 517.43) 44.07 (17.88 to 376.27) 56.13 (9.98 to 174.36)
Control group 61.44 (8.08 to 451.98) 45.00 (11.91 to 446.94) 44.43 (7.32 to 421.77) 42.24 (8.75 to 164.93)
HNE (mU/site)
MOX group 55.50 (0.00 to 207.50) 6.50 (0.00 to 182.00) 10.00 (0 to 122.00) 8.00 (0 to 215.50)
DOX group 48.00 (0.50 to 214.50) 23.00 (0.40 to 109.50) 23.50 (0.50 to 134.50) 38.50 (0.00 to 193.00)
Control group 41.00 (0.00 to 222.50) 29.00 (0.00 to 147.50) 32.50 (0.00 to 173.50) 38.00 (0.00 to 202.00)
MPO (mU/site)
MOX group 9.236 (3.169 to 14.396) 4.634 (1.540 to 12.677) 6.024 (1.240 to 12.976) 4.694 (1.495 to 13.350)
DOX group 8.281 (0.718 to 13.199) 7.056 (0.025 to 12.540) 6.951 (0.253 to 13.692) 5.247 (0.454 to 14.172)
Control group 7.261 (0.568 to 12.557) 7.006 (0.849 to 12.657) 6.976 (0.993 to 13.305) 6.378 (1.531 to 13.077)
Based on the subject as the unit.

disease and are predictors for treatment outcome.34
Cugini et al.35 analyzed 32 subjects; SRP was effective
in reducing the numbers of P. gingivalis, T. forsythia,
and T. denticola, but none of these species was
completely eliminated from any subject. Studies36-38
conducted using different regimens of antibiotics
demonstrated a benefit to the adjunctive use of antibi-
otics on microbial outcome in periodontal therapy.
Tetracyclines have been used for many years. In
1982, Kornman and Karl36 reported the suppressing
effect of tetracycline HCl on the counts of P. gingivalis.
There are not many reports focusing on the impact of
DOX on microflora. In one study,39 the use of DOX
in half of 39 subjects might have contributed to a
decrease in the microbial flora, but the difference
between the treatment groups was not significant. In
another study including 40 subjects with aggressive
periodontitis, 10 were treated with DOX; there was
no difference in the outcome of these subjects com-
pared to subjects treated with metronidazole alone,
metronidazole + amoxicillin, and no antibiotic.30 To
the best of our knowledge, the present study is the first
clinical study including MOX as an adjunct to non-
surgical periodontal treatment. Only limited data exist
about older quinolones in periodontal treatment. In
A. actinomycetemcomitans–associated periodontitis,
MOX suppressed this species below the detection
level in 22 of 25 cases.40
Comparing the two antibiotic regimens used, MOX
was more effective than DOX because all investigated
periodontal pathogens, IL-8, and the neutrophil en-
zymes MPO and HNE decreased up to 12 months after
treatment with MOX. In the present study, the level of
IL-8 and the activities of neutrophil enzymes as a total
were determined based on a standardized GCF collec-
tion time. As reported recently, data presentation by
use of total IL-8 and total activities of MPO and HNE
better reflects the situation in GCF as well as the exist-
ing clinical periodontal status.41-43 The influence of the
sampling method, i.e., paper points and deep crevicu-
lar washing, on results cannot be totally excluded.
Inflammatory parameters were suppressed after the
use of MOX. Quinolones are known for their modulation
of the immune response,44 e.g., ciprofloxacin promoted
the in vitro killing of A. actinomycetemcomitans by poly-
morphonuclear leukocytes.45
In the present study, clinical outcomes following the
adjunctive use of MOX were evaluated. Our data
showed significantly greater PD reductions and CAL
gains in the MOX group than in the control group treated
with SRP as monotherapy (P <0.05). Additionally, MOX
was more effective than DOX in decreasing periodontal
pathogens, IL-8, and the neutrophil enzymes MPO and
HNE up to 12 months after treatment. Our promising
results indicate that more controlled studies, e.g., dou-
ble masked with placebos, are warranted.
CONCLUSIONS
The adjunctive application of antibiotics improved the
treatment outcome in subjects with severe chronic
periodontitis. The adjunctive application of antibiotics
is essential in improving microbiologic parameters
and reducing IL-8 levels and activity of HNE. More-
over, MOX seemed to be more effective than DOX
and might be considered an alternative adjunct in
the treatment of periodontitis.
ACKNOWLEDGMENTS
The authors are grateful to Dr. Rüdiger Vollandt,
Institute of Medical Statistics, University of Jena, for

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Moxifloxacin in Periodontal Treatment
his help with the statistical analyses. The authors
thank Kerstin Wegner, Nadine Stüwe, and Claudia
Ranke, Institute of Medical Microbiology, University
Hospital of Jena, for technical assistance in the deter-
mination of microflora and inflammatory parameters.
We are indebted to Dr. Philip M. Preshaw, Department
of Periodontology, University of Newcastle upon
Tyne, Newcastle upon Tyne, United Kingdom, for
language corrections and the critical reading of this
paper. This study was supported, in part, by a grant
from the German Society of Periodontology, Regens-
burg, Germany. The authors report no conflicts of in-
terest related to this study.
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Correspondence: Dr. Arndt Guentsch, Department of Con-
servative Dentistry, University Hospital of Jena, Friedrich-
Schiller-University, An der alten Post 4, D-07743 Jena,
Germany. E-mail: arndt.guentsch@med.uni-jena.de.
Submitted September 12, 2007; accepted for publication
March 28, 2008.
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