div>
study.
2.2. Selection of Animals
Only dogs, which were assessed by the veterinarian to
have advanced severe periodontal disease requiring sys-
temic antimicrobial therapy for at least 10 days as an
adjunct to professional periodontal treatment, were con-
sidered for the study. Inclusion also required that dogs
had at least one tooth site of gingival bleeding in addition
to either a gingival pocket of at least 4.0 mm deep and/or
a gingival recession of at least 1.0 mm. Pocket depth was
defined as the distance (mm) between the margin of the
gingiva and the bottom of the deepest pocket at that site.
Gingival recession was defined as the distance (mm)
from the gingival margin to the associated tooth’s apical
cemento-enamel junction.
Dogs that had been treated with local or systemic an-
timicrobial agents or long acting corticosteroids within
the previous 4 weeks, with short acting corticosteroids
within the previous week, and dogs being treated with an
oral antiseptic or an anti-plaque agent were excluded.
Concomitant administration of local or systemic anti-
microbials or corticosteroids was not permitted.
2.3. Clinical Examination and Parameter
Measurements
Prior to treatment (day 0) and at study completion (day
42) all dogs were subjected to a detailed mouth examina-
tion under general anaesthesia. First halitosis and general
oral health were assessed on a visual analogue scale
(VAS, healthy to extremely unhealthy). Then before any
invasive procedures, any two most severely affected
teeth (i.e. not necessarily the same teeth on day 0 and 42)
were selected for subgingival bacteriological sampling
using sterile paper points (Nº. 40, Roeko, Dentsply Bel-
gium). The 2 samples from the same dog were pooled
and later analyzed together.
Following sampling, the Gingival Bleeding Index
(GBI) was assessed whilst probing the tooth-root sites
with a pressure sensitive probe (Florida Probe, Florida
Probe Corporation, Gainesville, Florida) to measure the
gingival pocket depth and to identify any evidence of
gingival recession. For each site, normal gingiva was gi-
ven a GBI score of 0, mild inflammation without bleeding
was scored 1, moderate inflammation with bleeding with-
in 30 seconds was scored 2, whilst severely inflamed
gingiva which spontaneously bled on probing scored 3.
All measurements were undertaken at 50 pre-determined
tooth-root sites, which are reported to be most frequently
and most severely affected in dogs [6]. This included all
labial roots (both mesial and distal of multiple-rooted
teeth) of all investigated teeth and both labial and palatal
side of the upper canine teeth. No root-sites were consid-
ered for any of the first premolar, the second molar and
the third molar teeth. In addition, the height of the upper
canine tooth (mm) was recorded to allow adjustments of
the total mouth periodontal scores for periodontitis (TMPS-P)
for the size of the animal [28].
After all measurements taken on day 0, dental proce-
dures were completed as necessary, including ultrasonic
supragingival scale, subgingival debridement, dental po-
lish and extraction. Further VAS assessments of halitosis
and general oral health were recorded on day 14 on un-
anaesthetized animals. Veterinarians and owners were
requested to report all suspected adverse events for all
treated dogs.
Copyright © 2012 SciRes. OJVM
H. GIBOIN ET AL. 91
2.4. Laboratory Examination
A single laboratory in Belgium (Katholieke Universiteit
Leuven, Leuven) was used to evaluate bacteriological
samples. These were transported by courier in a cool box
to the laboratory. Upon arrival, the samples were plated
on agar plates and incubated for growth. After incubation,
total aerobic colony forming units (cfu) and total anaero-
bic cfu were counted. In addition, within the anaerobic
strains, the black pigmented strains were identified mor-
phologically, and the Porphyromonas gulae and Prevotell a
intermedia were identified via enzymatic tests. All strain
identification was performed by the same laboratory
technician.
If present and identified, one strain per pre-treatment
sample of P. gulae and P. intermedia was tested for an-
timicrobial sensitivity using agar dilution minimum in-
hibitory concentration (MIC) methodology (supplement-
ed Brucella Blood agar) in accordance with CLSI guide-
lines M31-A3 and M11-A8. Antimicrobials tested were
cefovecin, clindamycin, metronidazole and amoxicil-
lin/clavulanate 2 to 1 ratio.
2.5. Investigational Treatment Administration
As 10 days of antimicrobial treatment was required, dogs
randomised to receive cefovecin received a single sub-
cutaneous injection of cefovecin (8 mg/kg bodyweight;
Convenia®, Pfizer Animal Health) followed by 10 days
of oral placebo capsules. Dogs randomised to receive
clindamycin capsules received a placebo subcutaneous
injection followed by 10 days of oral clindamycin cap-
sules (11 mg/kg bodyweight; Antirobe®, Pfizer Animal
Health). The veterinarian administered the subcutaneous
injections to dogs after periodontal treatment on day 0
and the owners administered the capsules once daily.
Owners kept a diary in which capsule administration was
recorded and compliance with treatment could then be
determined.
2.6. Assessment Criteria
The primary efficacy criterion was the percentage of
tooth sites which bled when probed (GBI > 1). This was
measured using a clear and reproducible, GBI scoring
system, validated for veterinary use [28]. Clinically,
bleeding on probing is a well accepted and objective
measure of active gingivitis and current periodontal
pocket inflammation. Statistically, because each dog is
assessed at numerous sites to generate an overall per-
centage, the power for comparison is superior to a vari-
able such as clinical success or bacteriological cure. Fur-
ther, the good reproducibility of the score between dogs
and clinics ensures that high quality data is generated,
permitting robust statistical comparison between treat-
ment groups. Therefore, for both clinical and statistical
reasons, percentage of bleeding on probing was consid-
ered the most suitable parameter for a primary efficacy
endpoint.
Gingival pocket depth, total mouth periodontal scores
(TMPS), the presence of pathogens before and after
treatment, halitosis and general oral health at each ex-
amination were considered as secondary efficacy end-
points.
TMPS for gingivitis (TMPS-G) was calculated ac-
cording Harvey et al. [28] and was a composite of all the
GBI scores for a particular dog, weighted according to
the circumference of the cemento-enamel junction at
each site, giving a final individual score for each dog of
between 0 and 3. TMPS-P was a composite of all the
pocket depth measurements for a particular dog, weight-
ed according to the root surface area at each site and
normalised according to the length of the upper canine.
This allowed comparison of periodontitis in dogs of dif-
ferent sizes.
2.7. Statistical Analysis
For each assessment criterion, two analyses were con-
ducted. One analysis included all treated dogs which
completed the study on day 42 (Intent to Treat analysis:
ITT). A second analysis (Per Protocol analysis: PP) ex-
cluded all animals for which procedures (including
treatment administration and efficacy measurements)
were not conducted to a sufficient standard to enable a
fair comparison. Results are presented for the PP analysis
only unless otherwise stated.
As recommended by EMEA guidelines [29] a
non-inferiority approach to compare cefovecin with
clindamycin was selected for the primary efficacy crite-
rion. For each animal, the percentage of tooth sites with a
GBI > 1 was calculated for both day 0 and 42. Data were
analysed using a mixed linear model using the day 0 re-
sults as a covariate. For the non-inferiority test, the dif-
ference in the mean percentage between the two treat-
ments (cefovecin minus clindamycin) on day 42 was
calculated together with a 95 percent two-sided confi-
dence interval. Thus, if the upper confidence bound on
the difference was less than 10 percentage points, then
cefovecin was considered non-inferior to clindamycin.
The 10% margin was justified based on pilot data which
indicated that 4 weeks after adjunctive treatment with
cefovecin, the percentage of bleeding on probing was
reduced by a further 14% than for surgery alone (data not
shown). Thus it was reasoned that to be clinically rele-
vant, the non-inferiority margin should exclude the effect
of surgery alone; i.e. to be less than 14%. Power calcula-
tions based on preliminary data indicated that a mini-
mum of 50 dogs per treatment group were needed to
Copyright © 2012 SciRes. OJVM
H. GIBOIN ET AL.
Copyright © 2012 SciRes. OJVM
92
3.2. Gingival Bleeding Index
demonstrate non-inferiority with at least 90% power.
All secondary parameters were assessed via the calcu-
lation of the treatment difference and 95% confidence
intervals.
The mean percentages of the GBI scores per animal are
summarized on Figure 1. Before treatment more than
half of the sites bled when probed, and less than 20% of
the sites were considered normal. More than 20% of all
sites had the highest GBI score of 3 in both groups. On
day 42, the number of sites with normal gingiva had
more than doubled in both treatment groups, whilst the
number of most severely affected sites (GBI = 3) was
reduced by more than 75%. Overall, there was a reduc-
tion in the number of bleeding sites in both treatment
groups with no significant difference between cefovecin
and clindamycin (Table 1). Therefore, cefovecin suc-
cessfully achieved non-inferiority to clindamycin.
3. Results
3.1. Evaluation and Completion of Dogs
In total 308 dogs were evaluated for inclusion in the
study. Four dogs were excluded before dental treatment
as they were unsuitable for anaesthesia (n = 2) or their
owners did not want to proceed (n = 2). After periodontal
treatment and bacteriological sampling, 5 dogs did not
continue (2 did not meet inclusion criteria, the probe
failed in 2 and 1 dog did not recover from anaesthesia).
Following periodontal treatment, 150 dogs received
cefovecin and 149 clindamycin. One dog did not com-
plete the study due to owner non-compliance (clindamy-
cin group) and one other dog was excluded because of
concomitant antimicrobial therapy for a non-study re-
lated adverse event (cefovecin group). Hence 297 dogs
completed the study on day 42 and were included for the
ITT analyses. Six further dogs were excluded from all PP
analyses; four dogs were underdosed during the study (1
in cefovecin and 3 in clindamycin group), one dog re-
ceived an unauthorised concomitant therapy, whilst data
was missing for another (both clindamycin group). A
further 25 dogs (14 in cefovecin and 11 in clindamycin
group) were excluded from PP analyses of pocket depth
and TMPS-P due to incorrect probe usage.
3.3. Gingival Pocket Depth
Before treatment, the mean gingival pocket depth was
2.48 mm (cefovecin group) and 2.39 mm (clindamycin
group). Of the total number of tooth root sites measured,
19% had a pocket depth between 3 - 5 mm in both groups
and the proportion of pocket depth larger than 5 mm was
5.3% and 3.9% in the cefovecin and clindamycin group
Of the 299 dogs enrolled into the study, 240 were pu-
rebred (wide range of small, medium and larger breeds)
and the remaining were crossbred. The ages of the dogs
in both groups ranged from 2 to 17 years (mean: 9.3 and
9.2 years for the cefovecin and clindamycin group, re-
spectively). The mean body-weights were 11.6 kg and
11.0 kg for the cefovecin and clindamycin group, respec-
tively. There were 161 female dogs (81 intact and 80
neutered) and 138 male dogs (99 intact and 39 neutered).
In Belgium, 72 dogs were enrolled from 5 practices, and
in France, 227 dogs were enrolled from 15 practices.
Figure 1. Mean percentage of 0, 1, 2 or 3 Gingival Bleeding
Index (GBI) scores per animal in each treatment group be-
fore treatment (day 0) and at the end of the study (day 42).
Table 1. Summary of percentage of sites bleeding on probing before treatment (day 0) and after treatment (day 42).
Treatment
Cefovecin Clindamycin
Treatment Comparison
Day 0* Day 42* Day 0* Day 42* Difference day 42 [95% CI] Non-inferiority demonstrated?
PP1 54.3% 20.3% 53.1% 17.4% 2.91% [0.65 to 6.48] Yes (<10%)
ITT2 54.5% 20.5% 52.7% 17.4% 3.16% [0.35 to 6.67] Yes (<10%)
*Day 0 is presented as a Mean and day 42 as a Least Square (LS) Mean because day 0 datum is used as a covariate in the model to compare the results from day
42. 1PP: per protocol analysis; Number of dogs in the cefovecin group: 148 and 143 in the clindamycin group. 2ITT: intent to treat; Number of dogs in the cefo-
vecin group: 149 and 148 in the clindamycin group.
H. GIBOIN ET AL. 93
respectively (Figure 2). On day 42, a reduction in pocket
depth of 0.51 mm and 0.40 mm was observed for cefo-
vecin and clindamycin, respectively. For the deepest
pockets (5.0 mm) measured on day 0, there appeared to
be a proportionally greater reattachment (approximately
30%) following treatment than for less severe pockets.
There was no statistically significant difference in any
subgroup analysis between treatment groups. Similar
results were obtained for the ITT analysis.
3.4. Total Mouth Periodontal Scores
Dogs in both treatment groups exhibited a very similar
mean score for both TMPS-G and TMPS-P at the begin-
ning of the study (Tab le 2). The high mean pre-treatment
scores corroborate that the study population had moder-
ate to severe periodontal disease, as required by the in-
clusion criteria. On day 42, the TMPS-G score for both
groups was approximately halved whilst the TMPS-P
score for both groups was reduced by approximately
20%. The difference between treatments for both scores
was not statistically significant.
3.5. General Oral Health and Halitosis
General oral health and halitosis improved by more than
80% after treatment for both the cefovecin and clinda-
mycin groups. There was no statistically significant dif-
ference between treatments on days 14 and 42 (p 0.09
at all time points). Similar results were found in the ITT
population.
3.6. Bacteriology
From the 304 dogs assessed for inclusion, 301 bacterial
strains were isolated. Porphyromonas gulae was identi-
fied in the majority of samples collected on day 0 (272
strains), with Prevotella intermedia being identified less
frequently (29 strains). MIC90 values for these strains to
various antimicrobials are presented in Table 3. The P.
gulae strains were highly susceptible to cefovecin, with a
slightly wider susceptibility range for P. intermedia.
After treatment, there was a reduced recovery of both
bacterial species (see Table 4). For P. gulae, the odds
ratio comparing the two treatments was 0.334, indicating
that P. gulae was less likely to be isolated on day 42
from dogs treated with cefovecin than those treated with
clindamycin (p < 0.0001). For P. intermedia this odds
ratio was 0.379, indicating that this species was also less
likely to be isolated on day 42 from dogs treated with
cefovecin. This difference was not statistically significant
(p = 0.25).
Aerobic and anaerobic bacteria were identified in all
isolates. On day 0, anaerobic black pigmented bacteria
were recorded in 145 out of 151 samples in the cefovecin
and in 146 out of 150 in the clindamycin group. On day
42, this ratio was 110 out of 149 and 110 out of 145
samples, respectively.
3.7. Safety Assessments
All dogs that received medication were included in the
Figure 2. Changes in pocket depth during the study period
in all pockets and in the most severely affected pockets. The
top of the black bars shows the pocket depth on day 0, the
top of the white bars shows the pocket depth after treat-
ment on day 42. The black shaded area shows the reduction
n the pocket depth between day 0 and 42. i
Table 2. Summary of Total Mouth Periodontal Scores (TMPS) on day 0 and day 42.
TMPS——Gingivitis TMPS——Periodontitis
Cefovecin Clindamycin Cefovecin Clindamycin
Number of animals 148 143 133 133
Mean day 0* 1.65 ± 0.57 1.61 ± 0.60 1.99 ± 0.87 1.96 ± 0.71
LS Mean day 42 0.83 0.77 1.54 1.60
% reduction 49.7% 52.2% 22.6% 18.4%
Treatment comparison (CI, p-value) 0.065 (–0.02 to 0.15, p = 0.12) –0.056 (–0.15 to 0.04, p = 0.22)
*± standard deviation.
Copyright © 2012 SciRes. OJVM
H. GIBOIN ET AL.
94
Table 3. Summary of activity of antimicrobials against the strains isolated in dogs with periodontal disease, before antimicro-
bial treatment.
Value (µg/ml) for each antimicrobial agent
Bacterial species
(number of strains)
Summary MIC
parameters Cefovecin Clindamycin Metronidazole
Amoxicillin/Clavulanate
2 to 1 ratio
MIC range 0.008 to 1 0.008 to >128 0.008 to >128 0.008 to 2
MIC50 0.031 0.008 0.031 0.125
MIC90 0.062 0.008 0.062 0.25
Porphyromonas gulae (272)
Geo. Mean 0.029 0.011 0.027 0.088
MIC range 0.008 to 4 0.008 to >128 0.016 to 1 0.008 to 2
MIC50 0.125 0.008 0.5 0.062
MIC90 1 >128 1 0.5
Prevotella intermedia (29)
Geo. Mean 0.15 0.053 0.30 0.083
MIC range 0.008 to 4 0.008 to >128 0.008 to >128 0.008 to 2
MIC50 0.031 0.008 0.031 0.125
MIC90 0.125 0.008 0.25 0.25
Total (301)
Geo. Mean 0.034 0.013 0.035 0.087
Table 4. Summary of the number and percentage of samples where Porphyromonas gulae or Prevotella intermedia were iden-
tified before treatment on day 0 and at the end of the study on day 42.
Treatment Treatment comparison
Cefovecin* Clindamycin** 95% confidence interval
Day 0 (%) Day 42 (%) Day 0 (%) Day 42 (%) Odds ratio (p-value) Lower Upper
Porphyromonas gul ae 126 (83.4%) 32 (21.5%) 117 (78.0%) 65 (44.8%) 0.334 (p < 0.0001) 0.20 0.56
Prevotella intermedia 10 (6.6%) 2 (1.3%) 13 (8.7%) 5 (3.5%) 0.379 (p = 0.25) 0.07 2.01
*total number of samples on day 0 = 151; on day 42 = 149; **total number of samples on day 0 = 150; on day 42 = 145.
safety assessments. One dog (clindamycin group) died
before antimicrobial therapy due to post-anaesthetic
complications. There were no abnormal injection sites
reported in any dogs administered either active cefovecin
or placebo. There was no notable difference in the inci-
dence of adverse events between the two treatment
groups. Two dogs in the cefovecin group vomited during
the study period, on a total of 3 occasions; one dog
showed inappetence in the clindamycin group and one
dog was lethargic and had modified feces on one occa-
sion in the cefovecin group. None of these events was
considered to be related to the administration of the me-
dications by the veterinarians.
4. Discussion
Periodontal disease is a very common and potentially
serious infectious dental disease in dogs [1]. Here we
investigated the efficacy and safety of the only veterinary
approved long-acting injectable antimicrobial, cefovecin
in the adjunctive treatment of severe periodontal disease
in dogs.
It has to be noted that the assessment of antimicrobial
efficacy for periodontal treatment is hampered by the
complexity of the disease. While the primary treatment is
professional periodontal therapy, the inclusion of such
therapy could be considered a confounding factor for
antimicrobial treatment comparisons. Nevertheless, ap-
plication of antimicrobials alone is not recommended
[16]. Further, EMEA guidelines recommend that when
assessing a new compound for treatment of a potentially
serious condition, a non-inferiority approach comparing
to a reference product is preferable to a conventional
hypothesis test for superiority using a placebo [29]. Es-
sentially this is designed to demonstrate that the new
compound is “at least as good as” the reference product
by a predefined margin. Here clindamycin (Antirobe®
capsules) was selected as reference product, because it
has been shown to effectively reduce the signs of perio-
dontal disease, including gingivitis and pocket depths
compared to placebo, when used adjunctive to profes-
sional periodontal treatment in dogs [17-19]. It was used
at the recommended European dosage of 11 mg/kg body-
weight orally once a day for at least 10 days.
The dogs included in this study represented a diverse
population encompassing many breeds and a wide age
range. The mean bodyweight suggested that there was a
tendency towards smaller dogs. Indeed, small breed dogs
Copyright © 2012 SciRes. OJVM
H. GIBOIN ET AL. 95
are considered to be particularly susceptible to naturally
occurring periodontal disease. It has been reported that
by the age of 3 years more than 85% of the small dog
population has alterations in their vital organs due to pe-
riodontitis-associated recurrent bacteraemia [11]. As in-
clusion in this study required that the dogs had severe
periodontal disease, it is likely that many also had sys-
temic consequences of their periodontal disease. There is
consensus amongst veterinary and human dentists that
antimicrobial treatment as an adjunct to periodontal
therapy for severe conditions and in patients with sys-
temic diseases is fully justified [13-16]. Not only does
this help to restore the non-pathogenic flora and promote
gingival healing, but also minimises any associated bac-
teraemia.
The primary efficacy endpoint was percentage of
pre-defined tooth-root sites bleeding on probing six
weeks after the initial surgery. At the end of the study the
percentage of sites bleeding on probing was more than
halved in both treatment groups. Further, cefovecin suc-
cessfully met the stringent a priori criteria and efficacy
can be claimed.
Periodontal pocket depth was also considered as a
clinically relevant endpoint for the efficacy analysis,
however, assessment of depth using a probe is by nature
prone to large error and individual variation thereby re-
ducing the power of the study. Further, pocket depth does
not specifically assess current active inflammation, but
rather measures the extent of established damage histori-
cally caused by ongoing periodontal disease. Therefore,
pocket depth was included as a secondary efficacy crite-
rion. Subset analysis of the pocket depth data revealed
that whilst there were no significant treatment differences,
there was proportionally a larger reduction in pocket
measurement in the deepest pockets, with a trend in fa-
vour of cefovecin. This might be due to creating a more
favourable environment for re-attachment of the perio-
dontal membrane by maintaining low supragingival bac-
terial flora following periodontal therapy.
The bacterial species identified during this study were
typical of those associated with canine periodontal dis-
ease [3-5]. There was a high recovery of pathogens be-
fore treatment, with P. gulae being the most frequently
isolated species. After periodontal and antimicrobial
treatment, dogs treated with cefovecin were less likely to
be infected than those treated with clindamycin, although
for both groups there was a reduction in recovery of
pathogens. All P. gulae isolates tested were susceptible
to cefovecin. Whilst fewer P. intermedia strains were
collected, cefovecin still exhibited good in vitro activity
although a few isolates were resistant as defined in the
existing summary of product characteristics (sensitive 2
μg/mL).
There is always the potential for the development of
resistance when using antimicrobial drugs. The suscepti-
bility to cefovecin of pathogens isolated in this study was
very similar to previous results [30]. This indicates that
despite exposure of periodontal pathogens to cefovecin
since its approval in 2006, no MIC shift has occurred.
Therefore, it is likely that the risk of resistance develop-
ment of Porphyromon as spp. and Prevotella spp. through
the use of cefovecin as an adjunctive treatment to perio-
dontal therapy is minimal. Although clindamycin, met-
ronidazol and amoxicillin/clavulanic acid have been used
for a longer period against periodonthopathogens, the
susceptibility of the tested strains to these drugs does not
seem to have changed when compared to previous re-
ports [31,32].
Other secondary parameters included the total mouth
periodontal scores. The scores for gingivitis were ap-
proximately halved after treatment, with no significant
difference between groups. The scores for periodontitis
(TMPS-P) were also reduced after treatment, with no
significant difference between groups. Similarly, general
oral health and halitosis, improved after treatment for
both the cefovecin and clindamycin groups.
Importantly, there were no adverse events reported due
to treatment for either group. While owner diaries docu-
mented a few adverse events, including gastrointestinal
symptoms, these were unrelated to treatment according
to the observing veterinarians. There was no injection-
site reaction reported.
In conclusion, cefovecin at a dose of 8 mg/kg body-
weight administered once subcutaneously was safe and
efficacious in the adjunctive treatment of severe perio-
dontal disease in dogs presented as veterinary patients.
As the only veterinary approved long-acting injectable
antimicrobial, cefovecin enables reliable treatment, espe-
cially in dogs where oral administration may be difficult
following periodontal surgery.
5. Acknowledgements
The authors acknowledge the assistance of the staff at the
clinics involved and the cooperation of the owners which
facilitated the smooth conduct of the studies.
REFERENCES
[1] C. Harvey, “Periodontal Disease in Dogs. Etiopathogene-
sis, Prevalence, and Significance,” The Veterinary Clinics
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1998, pp. 1111-1128.
[2] J. Hardham, K. Dreier, J. Wong, C. Sfintescu and R. Evans,
“Pigmented-Anaerobic Bacteria Associated with Canine
Periodontitis,” Veterinary Microbiology, Vol. 106, No.
1-2, 2005, pp. 119-128.
[3] P. Hennet and C. Harvey, “Aerobes in Periodontal Dis-
ease in the Dog: A Review,” Journal of Veterinary Den-
tistry, Vol. 8, No. 1, 1991, pp. 9-11.
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96
[4] P. Hennet and C. Harvey, “Anaerobes in Periodontal
Disease in the Dog: A Review,” Journal of Veterinary
Dentistry, Vol. 8, No. 2, 1991, pp. 18-21.
[5] P. Hennet and C. Harvey, “Spirochetes in Periodontal
Disease in the Dog: A Review,” Journal of Veterinary
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[6] P. Hennet and C. Harvey, “Natural Development of Pe-
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tomical and Histological Features,” Journal of Veterinary Safety and Efficacy of Cefovecin (Convenia<sup>®</sup>) as an Adjunctive Treatment of Periodontal Disease in Dogs
Open Journal of Veterinary Medicine, 2012, 2, 89-97
http://dx.doi.org/10.4236/ojvm.2012.23016 Published Online September 2012 (http://www.SciRP.org/journal/ojvm)
Safety and Efficacy of Cefovecin (Convenia®) as an
Adjunctive Treatment of Periodontal Disease in Dogs
Henry Giboin, Csilla Becskei, Jacky Civil, Michael R. Stegemann*
Veterinary Medicine Research & Development, Pfizer Animal Health, Zaventem, Belgium
Email: *michael.stegemann@pfizer.com
Received April 30, 2012; revised June 8, 2012; accepted June 15, 2012
ABSTRACT
This study was designed to determine the safety and efficacy of cefovecin (Convenia®; Pfizer Animal Health) when
compared to clindamycin (Antirobe®; Pfizer Animal Health) as an adjunctive therapy to periodontal scaling or surgery
for severe periodontal disease in dogs. A multi-centre, double-masked, randomised study was conducted in 299 dogs
with severe periodontal disease. Clindamycin, administered once daily at 11 mg/kg bodyweight orally for 10 days fol-
lowing dental surgery was compared with a single, subcutaneous injection of cefovecin (8 mg/kg bodyweight) adminis-
tered at the time of dental surgery. The primary efficacy parameter assessed was percentage of tooth-root sites bleeding
when probed (an indicator of gingival inflammation) 42 days after surgery. Two-hundred and ninety-one (291) dogs
were included in the efficacy assessments. Cefovecin was shown to be non-inferior to clindamycin. The percentage of
sites bleeding on probing was reduced from 54.3% to 20.3% for the cefovecin group (53.1% reduced to 17.4% for the
clindamycin group). There were no suspected adverse drug experiences attributed to treatment with cefovecin or clin-
damycin. Cefovecin was shown to be as effective and safe adjunctive treatment for severe periodontal disease in dogs
undergoing periodontal scaling and surgery as clindamycin.
Keywords: Canine; Antibiotics; Dentistry; Porphyromonas gulae; Prevotella intermedia
1. Introduction
Periodontal disease is the most common dental infection
in dogs [1]. It is caused by the accumulation of plaque
and an associated change in periodontal bacterial flora
(from commensal aerobic to pathogenic anaerobic bacte-
ria such as Porphyromonas spp. and Prevotella spp)
[2-5]. Periodontal disease is a collective term for a num-
ber of inflammatory conditions affecting the periodon-
tium around the tooth (attached gingiva, periodontal liga-
ment, cementum of the root and alveolar bone). It pro-
gresses from reversible gingivitis, characterised by in-
flamed and often bleeding gingiva, to periodontitis with
the associated inflammatory tissue damage, the formation
of deep periodontal pockets or gingival recession, loss of
epithelial attachment and bone resorption. The end result
of periodontitis is loss of the tooth due to progressive
destruction of its periodontium [6].
As periodontal disease disturbs the integrity of mucous
membranes, periodontal pathogens can be exported via
the blood stream. In severe periodontal disease, bacte-
raemia may even occur during minimal mechanical dis-
turbance, such as normal mastication, without any pro-
fessional tooth cleaning or surgery [7,8]. Periodontal dis-
ease is associated with myocardial infarction and stroke
in humans [9] and with abscesses in organs, endocarditis
and glomerulonephritis in dogs [10,11].
In dogs, prevention of periodontal disease by home
applied hygiene as in humans is rarely possible and the
effect of poor plaque control is often only managed by
periodontal treatment (e.g. debridement, scaling, polish-
ing). However, mechanical periodontal therapy alone
will not adequately reduce the periodontopathogen load
[12,13]. In severe and progressive cases adjunctive anti-
biotic treatment is justified to augment a reduction in
periodontopathogens and physiological bacterial flora,
thereby facilitating detoxification of the periodontium
from detrimental bacterial toxins and aiding gingival
healing [13-16]. Results from clinical studies in dogs
support this notion, as systemic treatment with clinda-
mycin in periodontal disease significantly decreased
plaque scores, gingivitis and pocket depths compared to
placebo when used as adjunctive therapy to ultrasonic
scaling, root planing and polishing [17-19].
Neither in human nor in veterinary dentistry is there a
consensus in the choice of antimicrobial agent or in the
minimum duration required to successfully treat perio-
*Corresponding author.
C
opyright © 2012 SciRes. OJVM
H. GIBOIN ET AL.
90
dontal infections [13]. Here we show that in a large
clinical study, a single subcutaneous administration of
cefovecin at 8 mg/kg effectively aided healing of the
periodontal tissues after professional periodontal treat-
ment and surgery in dogs.
Cefovecin is an extended-spectrum cephalosporin, ap-
proved for veterinary use in dogs and cats. It is formu-
lated as an injectable solution containing 80 mg/ml cefo-
vecin sodium. Following subcutaneous administration in
dogs, cefovecin has a long elimination half-life (5.5
days), low clearance (0.76 ml/hour/kg) and therapeutic
tissue concentrations are maintained for approximately
14 days [20]. As a consequence, prolonged therapeutic
efficacy can be maintained through injections adminis-
tered at 14-day intervals. Cefovecin, administered as a
subcutaneous injection at 14-day intervals, was highly
effective in the treatment of both superficial and deep
canine pyoderma [21,22] and also of wounds and ab-
scesses in both cats [23,24] and dogs [21,22]. Further-
more, cefovecin was demonstrated to be an effective and
safe treatment for urinary tract infections in dogs [25]
and cats [26].
2. Materials and Methods
2.1. General Study Design
This multi-centre study was conducted in compliance
with VICH guidelines for Good Clinical Practice [27]
(International Co-operation on Harmonisation of Tech-
nical Requirements for Registration of Veterinary Medi-
cal Products) in veterinary practices in Belgium (n = 5)
and France (n = 15). At each site one veterinarian, ex-
perienced in veterinary dentistry made all the observa-
tions, who received training in the procedures before
study start. Approval was obtained from the appropriate
regulatory authorities and the study conformed to local
animal welfare standards. Informed consent was obtained
from the owners of all dogs participating in the study.
Dogs were randomised in a 1:1 ratio to treatment with
either cefovecin or clindamycin in a double-masked
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