Antibiotic Resistance Relevance to Dentistry

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Antibiotic ResistanceRelevance to Dentistry

• Andrea Tapp, D.M.D.

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• Resistance and Susceptibility
• Determined by in vitro activity, pharmacologic
  characteristics,
• and clinical evaluation.
• The minimal inhibitory concentration (MIC) can be
  comfortably
• exceeded by doses tolerated by the patient.
• Susceptible - implies their MIC is at a
  concentration attainable in the blood or other
  body fluid at the recommended dose.
• Resistant - MIC is not exceeded by normally
  attainable levels

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• Mechanisms of Resistance
• Accumulation barriers to an antimicrobic due
• to impermeability or active efflux
• Alterations of an antimicrobic target which
  render
• it insusceptible
• Inactivation of an antimicrobic by an enzyme
• produced by the microorganism

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Cell Wall Barriers
Gram negative cell walls present a large
barrier Porins allow access into the cell but
these proteins can become mutated making the cell
less susceptible
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Influx/Efflux

• Bacteria such as streptococci, enterococci, and
  anaerobes lack the necessary oxidative pathways
  for transport of aminoglycosides.
• Some bacteria have energy-dependent efflux
  mechanisms that pump either tetracyclines or
  fluoroquinolones
• from the cell

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Altered Target

• Antimicrobics act by binding and inactivating
  their target,
• which is typically a crucial enzyme or ribosomal
  site.
• Substitutions of one amino acid in a protein can
  alter its
• binding.
• First generation aminoglycosides and quinolones
  only
• bind one site.
• Newer agents bind at multiple sites on their
  target
• making resistance improbable.

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An important example ?-lactam family
In widely divergent gram-pos and gram-neg species
changes in one or more of peptidoglycan
transpeptidase penicillin-binding proteins (PBP)
have been correlated with decreased
susceptibility to multiple ?-lactams Causes
point mutations, substitutions of amino acid
sequence, and synthesis of a new enzyme.
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• Enzymatic Inactivation
• Most powerful and robust of resistance mechanisms
• ?-Lactamases - 100s of enzymes with variable
  activity against ?- lactam substrates
• Typically demonstrate high-level resistance with
• MICs above therapeutic range

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Genetics of Resistance Intrinsic
Acquired Mutational Plasmids and
Conjugation Transposons and Transposition
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Emergence of antibiotic resistant Streptococcus
sanguis in dental plaque of children after
frequent antibiotic therapy Pamela Erickson,
DDS, PhD Mark Herzberg, DDS, PhD Pediatric
Dentistry 21181-185, 1999
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Methods 25 patients randomly chosen from pool
of children between ages three and six who
recently completed 10 days of antibiotic therapy
for otitis media with amoxicillin, Septra
(trimethoprim-sulfamethoxazole) or
erythromycin-sulfisoxazole. Children in the
control group had received no antibiotics within
the past 24 months.
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Samples of supragingival dental plaque were
collected from the buccal surfaces of both
mandibular first primary molars using sterile
cotton swabs. Antibiotic gradient plates were
prepared with THB agar and used to precisely
determine the level of antibiotic
resistance. The same antibiotics were used at
different gradients and those colonies whose
MIC was greater than the expected blood levels
were considered resistant.
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All strains of S. Sanguis were tested for
interactions with human platelets.
There was no effect on the ability of the S.
Sanguis isolates to advere to or induce
aggregation of heterologous human platelets.
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There was no difference in frequency of isolation
of strains of S. sanguis between otitis media and
healthy controls
Antibiotic resistance 60 of all isolates in
the experimental group were resistant to at least
one antibiotic 32 amoxicillin resistant 24
penicillin resistant Resistance to penicillin and
amoxicillin is inversely related to the age Of
the child and length of time since exposure.
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60 of children harbor antibiotic resistant S.
sanguis While antibiotic therapy was associated
with the isolation of resistant strains it was
not associated with a significant long-term
change in the oral flora of these children
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Studies in children have found that 78 - 81 of
rheumatic children on oral penicillin
prophylaxis harbored penicillin resistant
Streptococci(Naiman RA, Barrow JG). The
frequency of resistance decreased with the time
since cessation of therapy and the age of the
child (Sprunt et al). In 1997 the American Heart
Association suggests that if patients are
receiving antibiotics for otitis media or another
problem the dental practitioner should observe
an interval of time between procedures to reduce
the emergence of resistance and for the mouth to
repopulate with antibiotic-susceptible flora.

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Antimicrobial susceptibility of 800 anaerobic
isolates from patients with dentalveolar
infection to 13 oral antibiotics. Williams,
Yanagidawa, Iwahara, Shimizu, Nakagawa Oral
Microbiology Immunology 2007 22 285-288
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A total of 800 Isolates from patients with
dentoalveolar infection were tested for their
susceptibility to amoxicillin, amoxicillin/clavula
nate, cefaclor, cefuroxime, cefcapene, cefdinir,
erythromycin, azithromycin, Telithromycin,
minocycline, levoflaxacin, clindamycin, and
metronidazole Using an agar dilution method.
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With Prevotella species, resistance to
amoxicillin occcurred in 34 of isolates and all
of these resistant strains were found to produce
?-lactamase. Amoxicillin/Clavulanate,
telithromycin, clindamycin, and metronidazole
exhibit high antimicrobial activity against
amoxicillin-resistant strains of Prevotella
species.
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Cervical necrotizing fasciitis 8-years
experience Of microbiology V. Fihman, L.
Raskine, F. Peptitpas, J. Matco Journal of
Clinical Microbiology and Infectious Disease 2008
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158 consecutive patients were admitted for CNF
between December 1998 and June 2007 to a
tertiary care center dedicated to adult
ear-nose-throat emergencies. S. Oraalis and
Prevotella are more frequent in dental CNF,
whereas S. aureus is only found in pharyngeal
CNF.
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The majority of CNF patients received at least
one Antimicrobial therapy before
admission Resistance Penicillin 18 Penicillin
plus beta-lactamase inhibitor 26 Cephalosporin
14 Macrolide or strepogramins 11 Metronidazole
17 No difference was seen with treating with
antibiotic before sampling or at the origin of
the infection
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Antibiotic resistance in general dental
practice-a cause for concern? Louise Sweeney,
Jayshree Dave, Philip Chambers and John
Heritage Journal of Antimicrobial Chemotherapy
(2004) 53, 567-576 University of Leeds, UK
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• 1998 Standing Medical Advisory Committee -
  Dentists
• account for 7 of all community prescriptions of
  
• antimicrobials.
• ?-lactams and erythromycin have higher
  concentrations
• in the serum than in the saliva.
• Azithromycin has higher concentrations in saliva
  than
• serum but depresses the effects of NSAIDs

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Oral Flora ?-hemolytic streptococci are the most
frequent Potentially pathogenic S. aureus,
Enterococcus Faecalis, S. pneumoniae, S.
pyogenes, Neisseria Meningitis, Haemophilus
influenzae, and actinomyces
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Aminopenicilliins

• Amoxicillin resistance has been described in
  Veillonella
• and Prevotella denticola isolated from root
  canals.
• Resistance to amox is not widespread among
  anaerobes
• in deeper sites of the oral cavity (Fosse et
  al).
• Prevotella susceptibility is enhanced when
  amoxicillin
• is combined with clavulanic acid (Fosse et al).

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Penicillins

• 207 isolates of nine species of ?-hemo strep
  include
• S. mutans, S. salvarius, S. oralis, and S. mitis
• only S. mutans was universally susceptibile to
  PCN
• (Teng et al).
• S. oralis and S. mitis show the highest
  resistance
• among ?-hemo strep
• S. pneumoniae can transfer resistance as mosaic
• genes

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Metronidazole

• Dentist are the most frequent prescribers,
  ususally used in
• combination with other antibiotics
• Eight of 97 isolates form odontogenic abscesses
  were resistant
• (Roche Yoshimori)
• Aa - 50 strains tested and 72 were resistant
  (Madinier et al)

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• - hemolytic strep have a high resistance to
• Cephalosporins
• Tetracycline resistance is encoded on the tet
  gene
• Of ?- hemolytic strep isolated from the
  oropharynx
• of children 23 were resistant, majority being
• S. mitis (Konig et al).
• Carriage of both tet(Q) and erm(F) is common
• Of the isolates resistant to tetracycline 67
  were resistant to erythromycin
• Tetracycline resistance is widespread and
• infrequently used in dentistry

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Chlorhexidine Application for more than one week
can cause an increased resistance in S. mutans
and S. sobrinus
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Antibiotic prescriptions
Most frequently prescribed for infections Pen VK
60, erythromycin 14, amoxicillin 12,
metornidazole 8 Amoxicillin 66 for
prophylaxis Lonks et al report a case of
endocarditis caused by isolate of S. mitis
resistant to pcn and cefotaxime
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Moral of the Story..
Avoid broad spectrum antibiotics if
able Prescribe antibiotics judiciously Prescribe
for the appropriate amount and duration
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Questions?