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Refractory Periodontitis
Parameter on
“Refractory”
Periodontitis
American Academy of Periodontology, J Periodontol. May 2000
Clinical examination
Photos from: pocketdentistry.com
Photos from: pocketdentistry.com
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Refractory Periodontitis
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• A destructive periodontal disease in patients
who, when longitudinally monitored,
demonstrates additional attachment loss at one
or more sites despite well-executed therapeutic
and patient efforts to stop the progression of
disease
Refractory Periodontitis
Etiology:
• conventional therapy failed to eliminate
microbial reservoirs of infection
• Emergence or superinfection of opportunistic
pathogen
• Unknown factors
Refractory Periodontitis
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Refractory Periodontitis
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Refractory Periodontitis
Not applicable to patients who:
1. Have received incomplete or inadequate
conventional therapy
2. Have identifiable systemic condition that
increases susceptibility to infections
3. Have localized areas of rapid attachment loss
related to local factors
4. Have recurrence of progressive periodontitis of
many years of successful maintenance
Photos from:; www.behance.com; colorbox.com; presentermedia.com
Clinical and microbiological
features of refractory
periodontitis subjects
Colombo et al. (1998)
Clinical and microbiological
features of refractory
periodontitis subjects
• Aim: to compare clinical parameters and the site
prevalence and levels of 40 subgingival species
in successfully treated and refractory
periodontitis subjects
methodology
Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com
94 subjects
CLINICAL EXAM
•Gingival redness
•Suppuration
•BOP
•PI
•PD
•CAL
Baseline
Every 3 mo
Scaling and Root
planing
Modified Widman + Tetracycline
250mg QID for 28 days
methodology
66 successful tx
14
28 refractory pt
CAL > 3 sites,
>2.5mm in 1 year
Photos from:clicker.com; tokeyclub.com; www.scielo.cl;pinterest.com
Checkerboard DNA-
DNA hybridization
Bacterial culture in blood
agar plate
PCR
1
2
Results
<
<
<
<
<
<
Mean PD and CAL in subjects with refractory and
successfully treated  both show great variations
 refractory > successfully treated
Results
Results
Baseline BOP and gingival redness:
 both show great variations and overlap
Fig 3. % of sites
colonized at baseline
by different levels of
the 40 subgingival taxa
-Reject the hypothesis that
periodontal pathogens were
higher or more prevalent in
refractory
-Streptococcus constellatus:
-12.6±3.6 for refractory
-3.7±1.1 for successfully
Results
*
*
*
*
*
Odds Ratio: 8.6
Results
Results
4
3
3
4
• Great heterogeneity in subgigival microflora of
refractory subjects
Results
• Great heterogeneity in subgigival microflora of
refractory subjects
Conclusion
• Refractory subjects CANNOT BE distinguished
through clinical features prior to therapy.
• Refractory subjects had lower prevalence and levels
of the 40 test species in their sites than subjects in the
successfully treated group.
• Putative perio pathogens were found in more sites of
successfully treated than in refractory subjects prior to
therapy.
• Higher frequency of Streptococcus species in
refractory.  S. constellatus in refractory
Subgingival microbial profiles in
refractory periodontal disease
• Socransky et al. (2002)
Aim: to examine subgingival microbial
profiles associated with refractory
periodontitis and to seek such profiles in
periodontally healthy, periodontally well-
maintained elder and untreated
periodontitis subjects
Subgingival microbial profiles in
refractory periodontal disease
Methodology
REFRACTORY
N=36
PERIODONTALLY
HEALTHY
N=27
WELL-
MAINTAINED
N=35
UNTREATED
PERIO
N=115
•TX = SRP +
MWF +
Tetracycline
•Showed full
mouth mean
CAL or >3 sites
w/ >2.5mm after
therapy
•No PPD or CAL
> 4mm
•≥ 66 yrs old
•Regular perio
maintenance q
3-6 mo for an
average of 14.2
years after
perio therapy
•Atleast 4 sites
w/ PD >4mm
and / or CAL
>4mm
Demographics of 4 groups
results
Mean prevalence and level of taxa differed sig. for 4 groups
results
• Perio & refractory –  red and orange complex;  purple
and actinomyces
Results
•ratio of counts of actinoymces sp and counts of red
complex between groups.
•Proportions of taxa of actinomyces and red complex
results
• Clustered analysis showed heterogeneity in the 4 clusters
of refractory group with 8 outlier subjects
results
I -  streptococcus
species of yellow
complex
II – low prevalence
of all taxa;  orange
III – wider
distribution;  A.
naeslundii and V.
parvula
IV-  red and
orange complex; 
B. forysthus strep constellatus in all group
results
Clusters seen in refractory
can also be seen in other
groups
Conclusion
• Refractory perio, on average, have similar
microbiota to that seen in untreated perio
• Refractory perio have heterogenous
subgingival microbiota
• Microbial profiles of refractory is seen in
perio subjects as well as some healthy
and some well maintained
Conclusion
•  prevalence of Streptococcus species is
not seen in refractory groups
• Detection of different microbial profiles 
design individual treatment for each
patient
Comparison of subgingival
microbial profiles of refractory
periodontitis, severe
periodontitis, and Periodontal
Health using the Human Oral
Microbe Identification
Microarray• Colombo et al. (2009)
Comparison of subgingival
microbial profiles of RP,
GRs,PH using the HOMIM
• Aim: to compare subgingival microbiota of
subjects with refractory (RP), treatable
periodontitis (GRs= good responders) or
periodontal health (PH) using the human
oral microbe identification microarray
methodology
Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com
CLINICAL EXAM
•Gingival redness
•Suppuration
•BOP
•PI
•PD
•CAL
Baseline
Every 3 mo
Scaling and Root
planing
Modified Widman + Amox 500mg +
Metro 250mg TID for 14 days
PERIODONTALLY
HEALTHY
N=20
•No PPD > 3mm
or CAL > 2mm
PERIO
N=47
•Atleast 5 sites
with PD and CAL
≥6mm
methodology
Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com
PERIODONTALLY
HEALTHY
N=20
PERIO
N=47
Good Responders
N= 30
Refractory Perio
N=17
•Show mean
attachment loss
and/or > 3 sites w/ ≥
2.5mm
HOMIM
HUMAN ORAL MICROBE
IDENTIFICATION
MICROARRAY
RESULTS
•All clinical parameters (except suppuration) were sig.  in
perio group vs control
•RP showed  mean CAL than GRs
Microbiologic
profiles of 3 groups
at baseline:
Prevalence of
Streptococcus
species
Most species were
seen in perio pt
28% of all
species/genera/
clones is not seen
in PH
 perio pathogen
in RP
Results
Species detected higher in periodontally healthy subjects
Comparison of microbiota
in sites that lost
attachment vs
healthy/gained
attachment
• S. intermedius/
constellatus, S.
anginosus, P. micra,
Selenomonas spp, etc
are higher in sites losing
attachment
Conclusion
• Role of species that play in the initiation
and /or progression of RP, the effect of
periodontal therapy on this unusual
microbiota and the interaction between
these species and oral microorganism are
unknown
Conclusion
• Abx may be effective against pathogenic
bacteria but may not be effective against
unusual species  overgrowth 
continuous perio destruction
• More studies are needed
DETECTION OF
ENTEROCOCCUS FAECALIS
IN SUBGINGVIVAL BIOFILM
OF PATIENT WITH CHRONIC
REFRACTORY
PERIODONTITIS
• Gajan et al. (2010)
DETECTION OF
ENTEROCOCCUS FAECALIS IN
SUBGINGVIVAL BIOFILM OF
PATIENT WITH CHRONIC
REFRACTORY PERIODONTITIS
• Aim: to investigate the presence of E. faecalis in
subgingival biofilm of patients with chronic
refractory periodontal diseases
Enterococcus Faecalis
Photo from: microbiologyinpictures.com
Enterococcus Faecalis
• Normal human commensals adapted to nutrient-
rich, oxygen-depleted and ecologically complex
environments
• 1 of the top 3 nosocomial bacterial pathogen
• strain resistant to antibiotics
• Found in 60% of school children with high caries
and 75% of pt w/ endodontic infection
• Most commonly isolated or detected species
from oral infection
methodology
Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com
100 non-smoking
Chronic
periodontitis
subjects
CLINICAL EXAM
•Gingival redness
•Suppuration
•BOP
•PI
•PD
•CAL
Baseline
Every 3 mo
Scaling and Root
planing
Modified Widman + Tetracycline
250mg QID for 28 days
methodology
Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com
100 non-smoking
Chronic
periodontitis
subjects
73 successful
27 Refractory
methodology
Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com
73 successful  get 27
27 Refractory
•Mean attachment
level gain
•No sites w/ CAL
>2.5mm after 1 yr
of perio therapy
•Mean attachment
loss and/or >3
sites w/ CAL >
2.5mm after perio
therapy
culture in blood agar
plate to determine
presence of E.
faecalis
Result
Successfully Treated Refractory
Periodontitis
Age 41.25±1.7 42.45±2.9
Presence of E.
faecalis *
11.1% 51.8%
* p<0.05
Conclusion
• Within the limitations of this study,
detection of E. faecalis in refractory sites
seem to have a role in pathogenesis of
refractory periodontitis
• Sound knowledge of pathogen can help
develop effective treatment strategies
• Patients with refractory are candidates for
bacterial culturing
How do We Proceed with
Treatment?
Photos from: picgif.com
1. Arrest the disease
2. Slow the progression of disease
• Control may not be possible in all instances 
just slow the progression
Therapeutic Goals
1. Collection of subgingival microbial
samples
2. Selection and administration of an
appropriate antibiotic regimen
3. antimicrobial regimen + conventional
therapies may be used
Treatment Considerations
4. Re-evaluation with microbiological testing
as indicated
5. Identification and attempt to control risk
factors (ex. Smoking)
6. Intensified periodontal maintenance
program  shorter intervals between
appointment with microbiologic testing if
indicated
Treatment Considerations
1. Desired outcome is to arrest or control
the disease
2. If control is not possible, the treatment
objective is to slow the progression of the
disease
Outcome Assessment
THANK YOU 

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Refractory Periodontitis

  • 2. Parameter on “Refractory” Periodontitis American Academy of Periodontology, J Periodontol. May 2000
  • 3. Clinical examination Photos from: pocketdentistry.com
  • 5. Photos from:; makeagif.com, bestanimations.com; gifhell.com; gifsoup.com; beverlyheights.comtoothclub.gov.hk,arestin.com
  • 6. Refractory Periodontitis Photos from:; beverlyheights.comtoothclub.gov.hk,arestin.com; comfortdental4me.com
  • 7. • A destructive periodontal disease in patients who, when longitudinally monitored, demonstrates additional attachment loss at one or more sites despite well-executed therapeutic and patient efforts to stop the progression of disease Refractory Periodontitis
  • 8. Etiology: • conventional therapy failed to eliminate microbial reservoirs of infection • Emergence or superinfection of opportunistic pathogen • Unknown factors Refractory Periodontitis Photos from:; kohaladental.com; photos.com
  • 9. Refractory Periodontitis Photos from: premier34.ru; dentalcompare.com; youtube.com; dentoplant.hu
  • 10. Refractory Periodontitis Not applicable to patients who: 1. Have received incomplete or inadequate conventional therapy 2. Have identifiable systemic condition that increases susceptibility to infections 3. Have localized areas of rapid attachment loss related to local factors 4. Have recurrence of progressive periodontitis of many years of successful maintenance
  • 11. Photos from:; www.behance.com; colorbox.com; presentermedia.com
  • 12. Clinical and microbiological features of refractory periodontitis subjects Colombo et al. (1998)
  • 13. Clinical and microbiological features of refractory periodontitis subjects • Aim: to compare clinical parameters and the site prevalence and levels of 40 subgingival species in successfully treated and refractory periodontitis subjects
  • 14. methodology Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com 94 subjects CLINICAL EXAM •Gingival redness •Suppuration •BOP •PI •PD •CAL Baseline Every 3 mo Scaling and Root planing Modified Widman + Tetracycline 250mg QID for 28 days
  • 15. methodology 66 successful tx 14 28 refractory pt CAL > 3 sites, >2.5mm in 1 year Photos from:clicker.com; tokeyclub.com; www.scielo.cl;pinterest.com Checkerboard DNA- DNA hybridization Bacterial culture in blood agar plate PCR 1 2
  • 17. Mean PD and CAL in subjects with refractory and successfully treated  both show great variations  refractory > successfully treated Results
  • 18. Results Baseline BOP and gingival redness:  both show great variations and overlap
  • 19. Fig 3. % of sites colonized at baseline by different levels of the 40 subgingival taxa -Reject the hypothesis that periodontal pathogens were higher or more prevalent in refractory -Streptococcus constellatus: -12.6±3.6 for refractory -3.7±1.1 for successfully Results * * * * *
  • 21.
  • 22. Results 4 3 3 4 • Great heterogeneity in subgigival microflora of refractory subjects
  • 23. Results • Great heterogeneity in subgigival microflora of refractory subjects
  • 24. Conclusion • Refractory subjects CANNOT BE distinguished through clinical features prior to therapy. • Refractory subjects had lower prevalence and levels of the 40 test species in their sites than subjects in the successfully treated group. • Putative perio pathogens were found in more sites of successfully treated than in refractory subjects prior to therapy. • Higher frequency of Streptococcus species in refractory.  S. constellatus in refractory
  • 25. Subgingival microbial profiles in refractory periodontal disease • Socransky et al. (2002)
  • 26. Aim: to examine subgingival microbial profiles associated with refractory periodontitis and to seek such profiles in periodontally healthy, periodontally well- maintained elder and untreated periodontitis subjects Subgingival microbial profiles in refractory periodontal disease
  • 27. Methodology REFRACTORY N=36 PERIODONTALLY HEALTHY N=27 WELL- MAINTAINED N=35 UNTREATED PERIO N=115 •TX = SRP + MWF + Tetracycline •Showed full mouth mean CAL or >3 sites w/ >2.5mm after therapy •No PPD or CAL > 4mm •≥ 66 yrs old •Regular perio maintenance q 3-6 mo for an average of 14.2 years after perio therapy •Atleast 4 sites w/ PD >4mm and / or CAL >4mm
  • 29. results Mean prevalence and level of taxa differed sig. for 4 groups
  • 30. results • Perio & refractory –  red and orange complex;  purple and actinomyces
  • 31. Results •ratio of counts of actinoymces sp and counts of red complex between groups. •Proportions of taxa of actinomyces and red complex
  • 32. results • Clustered analysis showed heterogeneity in the 4 clusters of refractory group with 8 outlier subjects
  • 33. results I -  streptococcus species of yellow complex II – low prevalence of all taxa;  orange III – wider distribution;  A. naeslundii and V. parvula IV-  red and orange complex;  B. forysthus strep constellatus in all group
  • 34. results Clusters seen in refractory can also be seen in other groups
  • 35. Conclusion • Refractory perio, on average, have similar microbiota to that seen in untreated perio • Refractory perio have heterogenous subgingival microbiota • Microbial profiles of refractory is seen in perio subjects as well as some healthy and some well maintained
  • 36. Conclusion •  prevalence of Streptococcus species is not seen in refractory groups • Detection of different microbial profiles  design individual treatment for each patient
  • 37. Comparison of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and Periodontal Health using the Human Oral Microbe Identification Microarray• Colombo et al. (2009)
  • 38. Comparison of subgingival microbial profiles of RP, GRs,PH using the HOMIM • Aim: to compare subgingival microbiota of subjects with refractory (RP), treatable periodontitis (GRs= good responders) or periodontal health (PH) using the human oral microbe identification microarray
  • 39. methodology Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com CLINICAL EXAM •Gingival redness •Suppuration •BOP •PI •PD •CAL Baseline Every 3 mo Scaling and Root planing Modified Widman + Amox 500mg + Metro 250mg TID for 14 days PERIODONTALLY HEALTHY N=20 •No PPD > 3mm or CAL > 2mm PERIO N=47 •Atleast 5 sites with PD and CAL ≥6mm
  • 40. methodology Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com PERIODONTALLY HEALTHY N=20 PERIO N=47 Good Responders N= 30 Refractory Perio N=17 •Show mean attachment loss and/or > 3 sites w/ ≥ 2.5mm HOMIM
  • 42.
  • 43. RESULTS •All clinical parameters (except suppuration) were sig.  in perio group vs control •RP showed  mean CAL than GRs
  • 44. Microbiologic profiles of 3 groups at baseline: Prevalence of Streptococcus species Most species were seen in perio pt 28% of all species/genera/ clones is not seen in PH  perio pathogen in RP
  • 45. Results Species detected higher in periodontally healthy subjects
  • 46. Comparison of microbiota in sites that lost attachment vs healthy/gained attachment • S. intermedius/ constellatus, S. anginosus, P. micra, Selenomonas spp, etc are higher in sites losing attachment
  • 47. Conclusion • Role of species that play in the initiation and /or progression of RP, the effect of periodontal therapy on this unusual microbiota and the interaction between these species and oral microorganism are unknown
  • 48. Conclusion • Abx may be effective against pathogenic bacteria but may not be effective against unusual species  overgrowth  continuous perio destruction • More studies are needed
  • 49. DETECTION OF ENTEROCOCCUS FAECALIS IN SUBGINGVIVAL BIOFILM OF PATIENT WITH CHRONIC REFRACTORY PERIODONTITIS • Gajan et al. (2010)
  • 50. DETECTION OF ENTEROCOCCUS FAECALIS IN SUBGINGVIVAL BIOFILM OF PATIENT WITH CHRONIC REFRACTORY PERIODONTITIS • Aim: to investigate the presence of E. faecalis in subgingival biofilm of patients with chronic refractory periodontal diseases
  • 51. Enterococcus Faecalis Photo from: microbiologyinpictures.com
  • 52. Enterococcus Faecalis • Normal human commensals adapted to nutrient- rich, oxygen-depleted and ecologically complex environments • 1 of the top 3 nosocomial bacterial pathogen • strain resistant to antibiotics • Found in 60% of school children with high caries and 75% of pt w/ endodontic infection • Most commonly isolated or detected species from oral infection
  • 53. methodology Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com 100 non-smoking Chronic periodontitis subjects CLINICAL EXAM •Gingival redness •Suppuration •BOP •PI •PD •CAL Baseline Every 3 mo Scaling and Root planing Modified Widman + Tetracycline 250mg QID for 28 days
  • 54. methodology Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com 100 non-smoking Chronic periodontitis subjects 73 successful 27 Refractory
  • 55. methodology Photos from:clicker.com; tokeyclub.com; christianberdy.com; Colgate.com; clipartlord.com 73 successful  get 27 27 Refractory •Mean attachment level gain •No sites w/ CAL >2.5mm after 1 yr of perio therapy •Mean attachment loss and/or >3 sites w/ CAL > 2.5mm after perio therapy culture in blood agar plate to determine presence of E. faecalis
  • 56. Result Successfully Treated Refractory Periodontitis Age 41.25±1.7 42.45±2.9 Presence of E. faecalis * 11.1% 51.8% * p<0.05
  • 57. Conclusion • Within the limitations of this study, detection of E. faecalis in refractory sites seem to have a role in pathogenesis of refractory periodontitis • Sound knowledge of pathogen can help develop effective treatment strategies • Patients with refractory are candidates for bacterial culturing
  • 58. How do We Proceed with Treatment? Photos from: picgif.com
  • 59. 1. Arrest the disease 2. Slow the progression of disease • Control may not be possible in all instances  just slow the progression Therapeutic Goals
  • 60. 1. Collection of subgingival microbial samples 2. Selection and administration of an appropriate antibiotic regimen 3. antimicrobial regimen + conventional therapies may be used Treatment Considerations
  • 61. 4. Re-evaluation with microbiological testing as indicated 5. Identification and attempt to control risk factors (ex. Smoking) 6. Intensified periodontal maintenance program  shorter intervals between appointment with microbiologic testing if indicated Treatment Considerations
  • 62. 1. Desired outcome is to arrest or control the disease 2. If control is not possible, the treatment objective is to slow the progression of the disease Outcome Assessment

Editor's Notes

  1. This isa 40 year old patient who came to your office with a chief complaint of bleeding gums when brushing his teeth. Patient claims to be systemically healthy. Clinical exam revealed clinicall attachment loss of 4-6mm
  2. Radiographic exam revealed patient has fairly good amount of one remaining with bone support generally ranging from 60-80%. You gave this patient a diagnosis of generalized moderate with localized severe chornic periodontitis.
  3. After clinical and radiographic
  4. However, despite your attempts to control the infection with conventional periodontal therapy, Additional clinical attachment loss occurred. So you begin to think did I miss out anything?
  5. Superinfection - infection occurring after or on top of an earlier infection, especially following treatment with broad-spectrum antibiotics.
  6. Not applicable to patients who: Have received incomplete or inadequate conventional therapy Have identifiable systemic condition that increases susceptibility to infections Have localized areas of rapid attachment loss related to local factors Have recurrence of progressive periodontitis of many years of successful maintenance
  7. 1st phase: all underwent Checkerboard to compare microbiotia before tx 2nd phase: from 14 refractory, do another checkerboard, bacterial culture and PCR