Amoxicillin-Clavulanate in

Dental Infections

IN/CAM/0132/17 Date of preparation December 2017

Overview

Epidemiology of dental infections

Etiology of dental infections and predisposing factors

Principles of treatment

Attributes of an ideal agent

Amoxicillin-clavulanate the potential choice for

dental Infections

Clinical evidence

Summary
Epidemiology of Dental Infections
 Periodontal disease is a major public
health problem

• Person lifetime prevalence of dental abscesses (DAs) has been reported

at 5-46%1,2

• Orthodontic infections place a high burden on patients due to costs of

care and lost days of productivity at work3

1. Ottaviani G et al. Epidemiology and variables involved in dental abscess: survey of dental emergency unit in Trieste. Oral Diseases. 2014;20:499–504.
2. Matthews DC, Sutherland S, Basrani B. Emergency Management of Acute Apical Abscesses in the Permanent Dentition: A Systematic Review of the Literature. J Can
Dent Assoc. 2003;69(10):660.
3. Mohd-Dom T et al. Cost analysis of periodontitis management in public sector specialist dental clinics. BMC Oral Health. 2014;14:56.
 Acute odontogenic infections are the principle
reason for seeking dental care

• The most common emergency odontogenic infections are periapical abscess

(25%), pericoronitis (11%) and periodontal abscess (7%)1

• 7% to 11% of all common antibiotics prescribed (β-lactams, macrolides,

tetracyclines, clindamycin, metronidazole) are for odontogenic infection2
30
% Patients receiving emergency care for

25%
25
odontogenic infections

20

15
11%
10
7%
5

0
Acute periapical abscess Pericoronitis Periodontal abscess

1. López-Píriz R, et al. Management of odontogenic infection of pulpal and periodontal origin. Med Oral Patol Oral Cir Bucal. 2007 Mar 1;12(2):E154-9.
2. Dar-Odeh NS, et al. Antibiotic prescribing practices by dentists: a review. Ther Clin Risk Manag. 2010 Jul 21;6:301-6.
Etiology of dental infections and
predisposing factors
 Etiology of dental infections and
predisposing conditions
Origin Predisposing conditions
• Dental caries • Periodontal biomass
• Pulpitis accumulation
• Periapical abscess • Necrotic pulpal tissue
• Periodontitis/periodontal • Surgical/traumatic tissue
abscess damage
• Pericoronitis
• Deep restorations

Sandor GK, et al. J Can Dent Assoc. 1998 Jul-Aug;64(7):508-14.

 Predisposing risk factors

Cariogenic • Poor oral hygiene

factors • Diet

Odontogenic
infections • Poor oral hygiene
• Smoking
Periodontal
• Hormonal changes
disease
• Diabetes mellitus
factors
• Genetic factors
• Increased age

• Compromised
General immune function
Factors • Smoking

Chow AW. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. (6th edition) Churchill Livingstone; 2000:689-702.
 Periapical infections

• Periapical infections are most commonly initiated as the result of

dental caries, which create lesions in the enamel, enabling bacteria to
reach the pulp 1
• Process:1,2
– Avenues for infection
• Dental caries
• Tooth fracture
• Iatrogenic exposure
• May remain localized, OR Symptomatic
Necrotic teeth with systemic involvement
– Abscess formation at apex
• Symptoms: Slight tenderness to intense, throbbing pain, tooth
becomes tender to percussion and chewing, swelling2
1. Cope A, Francis N, Wood F, Mann MK, Chestnutt IG. Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults. Cochrane Database of
Systematic Reviews 2014, Issue 6. Art. No.: CD010136. DOI: 10.1002/14651858.CD010136.pub2.
2. Matthews DC, Sutherland S, Basrani B. Emergency management of acute apical abscesses in the permanent dentition: a systematic review of the literature. J Can Dent
Assoc. 2003 ;69(10):660.
 Gingivitis

• Pathogenesis: Localized inflammation of the gums

without a loss of the bone that supports the teeth

• Symptoms:
– Erythema
– Swelling
– Bleeding gums with brushing or flossing
– Halitosis

1. Nguyen DH, Martin JT. Common dental infections in the primary care setting. Am Fam Physician. 2008;77(5):797-802.
 Periodontitis

• Pathogenesis1:
– Loss of supportive bone
structure, detachment of the
periodontal ligament from
the tooth Gingival and periodontal
pockets are extensions
• Signs1,2: of the gingival sulcus 3
− Periodontal pocket
– Bleeding on probing
– Suppuration on probing A: Crown of the tooth, covered by enamel
– Alveolar bone loss (seen via dental B: Root of the tooth, covered by cementum
radiographs) C: Alveolar bone
D: Subepithelial connective tissue
– Tooth mobility
E: Oral epithelium
H: Principle gingival fibers
I: Alveolar crest fibers of the PDL
J: Horizontal fibers of the PDL
1. Nguyen DH, Martin JT. Am Fam Physician. 2008;77(5):797-802.
2. Preshaw PM. BMC Oral Health. 2015;15(Suppl 1):S5.
K: Oblique fibers of the PDL
3. https://en.wikipedia.org/wiki/Gingival_and_periodontal_pocket. PDL: periodontal ligament
 Pericoronitis

• Pathogenesis: • Symptoms3:
– Acute, localized infection ― Pain and swelling
caused by food particles and ― Purulence
microorganisms trapped ― Trismus
beneath the gingival flaps of a
partially erupted tooth or an ― Dysphagia
impacted wisdom tooth1 ― Enlarged lymph nodes and fever
• Microbiology similar to
periodontal abscess1,2
– Prevotella spp.
– Fusobacterium spp.
– Porphyromonas spp.
– Bacteroides spp.
1. Chow AW. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases.
(6th edition) Churchill Livingstone; 2000:689-702.
2. Dahlen G. Periodontol 2000. 2002;28:206-239.
3. Tang DT et al. J Oral Maxillofac Surg 2014;72:1235-1243.
Principles of treatment
 Therapeutic success is determined by the control of infection by
removing the source of infection using: surgical debridement and/or
antimicrobial therapy

Odontogenic infections
are mostly polymicrobial

Endodontal Periodontal

Infection of the dental pulp Infection of tooth supporting

initiated by dental caries structures initiated by accumulation
of plaque and calculus

Bruch JM, Treister NS. Oral infections. Clinical Oral Medicine and Pathology. Springer. 2009.pg.no. 82-88.
 Odontogenic infections are mostly polymicrobial
necessitating broad-spectrum antibiotics
Common bacteria in orthodontic infection1,2
Gram positive
facultative anaerobes
Streptococcus viridians
Streptococcus anginosus
Coagulase negative Staphylococci
Lactobacillus spp.

Gram positive anaerobes

Clostridium spp.
Gram negative anaerobes
Peptococcus spp. Fusobacterium spp.
Peptostreptococcus spp. Prevotella spp.
Anaerobic streptococci Veillonella spp.
Actinomyces spp. Bacteroides spp.
Eubacterium spp. B. fragilis

Roughly 50% of odontogenic infections are caused by anaerobic bacteria alone, 44% by a combination
of aerobic and anaerobic bacteria and only 6% by aerobic bacteria alone.3
There is a tendency to increased levels of Gram-negative and anaerobic bacteria as symptoms
become more severe.4

1. Bascones Martínez A et al Consensus statement on antimicrobial treatment of odontogenic bacterial infections. Med Oral Patol Oral Cir Bucal.
2004;9:369-76; 363-9.
2. de Sousa EL, Ferraz CC, Gomes BP, et al. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;96(3):332-9
3. Gregoire C. How are odontogenic infections best managed? J Can Dent Assoc 2010;76:a37.
4. DeAngelis AF et al. Review article: Maxillofacial emergencies: oral pain and odontogenic infections. Emerg Med Australas. 2014;26:336-42.
 Importance of β-lactamase producing bacteria in
dental infections1,2

• β-lactamase producing species are identified in

74–87% of patients with periodontitis1,2
• An increasing proportion of dental infections are
due to β -lactamase-producing anaerobic strains3
• Penicillin resistance is increasing4-6

1. Herrera D et al. Beta-lactamase producing bacteria in the subgingival microflora of adult patients with periodontitis. A comparison between
Spain and the Netherlands. J Clin Periodontol 2000;27:520-5.
2. Van Winkelhoff AJ et al. Beta-lactamase producing bacteria in adult periodontitis. J Clin Periodontol 1997;538-43.
3. Dahlen G. Microbiology and treatment of dental abscesses and periodontal-endodontic lesions. Periodontol. 2000;28:206-239.
4. Baumgartner JC, Xia T. Antibiotic susceptibility of bacteria associated with endodontic abscesses. J Endod. 2003 Jan;29(1):44-7.
5. Kuriyama T, Absi EG, Williams DW, Lewis MA. An outcome audit of the treatment of acute dentoalveolar infection: impact of penicillin resistance.
Br Dent J. 2005 Jun 25;198(12):759-63; discussion 754; quiz 778.
6. Kuriyama T et al. Antimicrobial susceptibility of 800 anaerobic isolates from patients with dentoalveolar infection to 13 oral antibiotics. Oral
Microbiol Immunol. 2007 Aug;22(4):285-8.
 Implications of dental infections: Pathogenicity

Synergistic presence of anaerobes and aerobes promotes

pathogenicity

Mixed colonization O2 depletion by aerobes

Anaerobe proliferation

Toxin/enzyme release, tissue destruction, abscess formation

Sandor GK, Low DE, Judd PL, Davidson RJ. Antimicrobial treatment options in the management of odontogenic infections. J Can Dent Assoc. 1998 Jul-Aug;64(7):508-14.
Prescribing in dental practice

• Key findings from a Belgian survey of antibiotic prescribing in dental

practice1
– Antibiotics were prescribed in 4.2% (1,033) of 24,421 dental patients
from a random sample of 268 dentists
– Treatment was largely empiric using broad-spectrum antibiotics:
• 82% of all prescriptions were for amoxicillin, amoxicillin-clavulanic acid
and clindamycin

Antibiotics were often Antibiotics were often

prescribed in the absence of prescribed without any local
fever (92.2%) treatment (54.2%)

– Antibiotics were prescribed to 63.3% of patients with periapical

abscess but only 4.3% of patients with pulpitis

1. Mainjot A, D'Hoore W, Vanheusden A, Van Nieuwenhuysen JP. Antibiotic prescribing in dental practice in Belgium. Int Endod J. 2009 Dec;42(12):1112-7.
Prescribing in dental practice

• The duration of antibiotic therapy is mainly based on expert

opinion. Most dentists use short-courses of antibiotics (mainly
amoxicillin), lasting 3–5 days for the treatment of infection1-3

• Recent surveys have indicated that misuse of antibiotics is common

amongst dentists throughout the world showing there is a need for
continuing education in the use of antibiotics4

1. Dar-Odeh NS, et al. “Antibiotic prescribing practices by dentists: a review,” Therapeutics and Clinical Risk Management. 2010;6:301–306.
2. Longman LP, Preston AJ, Martin MV, Wilson NH. Endodontics in the adult patient: the role of antibiotics. J Dent. 2000 Nov;28(8):539-48.
3. Roy KM, Bagg J. Antibiotic prescribing by general dental practitioners in the Greater Glasgow Health Board, Scotland. Br Dental J 2000; 188: 674-676.
4. Ocek Z, Sahin H, Baksi G, Apaydin S. Development of a rational antibiotic usage course for dentists. Eur J Dent Educ. 2008 Feb;12(1):41-7.
 Inappropriate antibiotic prescribing in emergency clinics

• US National Hospital Ambulatory Medical Care survey (1997-2007) of patients who visited
emergency department for acute non-traumatic dental condition1
– 56% received at least one antibiotic with or without analgesia
– The proportion of patients who receive antibiotics in this setting is increasing

Analgesic 26% 47.6% 8.8% Antibiotic

The National Center for Disease Control and Prevention estimate that approximately one-third of
all outpatient antibiotic prescriptions are unnecessary2
A survey from Scotland concluded that 75% of antibiotics were inappropriately prescribed in
patients attending the emergency dental clinics3
1. Okunseri C et al. Medications prescribed in emergency departments for nontraumatic dental condition visits in the United States. Med Care. 2012 ;50(6):508-12.
2. Dar-Odeh NS et al., “Antibiotic prescribing practices by dentists: a review,” Therapeutics and Clinical Risk Management. 2010;6:301–306.
3. Dailey YM, Martin MV. Are antibiotics being used appropriately for emergency dental treatment? Br Dent J. 2001 Oct 13;191(7):391-3.
 Rational antibiotic prescribing is needed to
prevent the spread of resistant bacterial strains
in dental and oral clinical practice1

• The addition of a β-lactamase inhibitor such as clavulanic acid to

amoxicillin (amoxicillin-clavulanate) confers resistance to β-lactamases
thereby extending the antibiotic spectrum to anaerobes such as Prevotella
spp., Bacteroides spp. and Staphylococcus spp. which are common in
odontogenic infections2

• The combination of amoxicillin and clavulanic acid is useful for patients

infected with β-lactamase-producing organisms:3,4
• Offering broad spectrum cover against all potentially pathogenic bacteria
that reach the bloodstream4

1. Poveda Roda R et al. Antibiotic use in dental practice. A review. Med Oral Patol Oral Cir Bucal. 2007;12(3):E186-92.
2. Tancawan AL et al. Amoxicillin/clavulanic acid for the treatment of odontogenic Infections: A randomised study
comparing efficacy and tolerability versus clindamycin. Int J Dent. 2015;Article ID:472470.
3. Maestre Vera JR, Gómez-Lus Centelles ML. Antimicrobial prophylaxis in oral surgery and dental procedures. Med
Oral Patol Oral Cir Bucal. 2007 ;12(1):E44-52.
4. Natarajan S. Antibiotic treatment for odontogenic infections. CPJ/RPC . 2004; 137(10): 25-29.
Attributes of an ideal agent
 Attributes of the ideal agent

• Eliminate causative organism(s)1

• Rapid absorption and distribution1

• Consistent high blood level1,2

• Penetration to achieve high level in perioral bone and soft

tissues2

• Low risk of side effects2

1. Kirkwood KL. Alpha Omegan. 2003;96:28-34.

2. Baker KA et al. Dent Clin North Am. 1994;38:689-706.
 Amoxicillin-clavulanate: Mechanism of action
against β-lactamases

• The clavulanate in amoxicillin-clavulanate anticipates this defense mechanism by

blocking the β-lactamase enzymes, thus rendering the organisms susceptible to
amoxicillin’s rapid bactericidal effect at concentrations readily attainable in the
body
Cell death

β-
lactamase
enzyme
inactivation
β-lactamase enzyme
Clavulanic acid
Bacterial cell

Amoxicillin
Peptidoglycan binding
protein(PBPs)
Prescribing Information of AUGMENTIN 625/1000 DUO. GlaxoSmithKline, India. Version: AUG-TAB/PI/IN/2017/01 dated 04-Oct-2017. Prescribing Information of AUGMENTIN
DDS (oral suspension). GlaxoSmithKline, India. Version : AUG-DDS/PI/IN/2017/01 dated 31-Oct-2017. Prescribing Information of AUGMENTIN DUO (oral suspension):
GlaxoSmithKline, India. Version : AUG-SUS/PI/IN/2017/01 dated 31-Oct-2017.
 Clavulanic acid blocks β-lactamase enzymes

• Clavulanic acid is a natural product of the micro-organism

Streptomyces clavuligerus1

• Clavulanic acid binds to the β-lactamase enzyme at the active

site and blocks its activity irreversibly1

• Clavulanic acid is effective against the β-lactamase enzymes

of Gram-positive and Gram-negative pathogens that are of
widespread clinical significance1

• Complementary binding to different PBPs2

1. Neu HC, Fu KP. Clavulanic acid, a novel inhibitor of beta-lactamases. Antimicrob Agents Chemother. 1978;14(5):650-5.
2. Finlay J et al. J Antimicrob Chemother. 2003;52:18–23.
Amoxicillin clavulanate offers broad spectrum coverage
against common pathogens in dental infections1,2,3*

Antibiotic spectrum of amoxicillin-clavulanate in dental infections*$

Gram positive
facultative anaerobes
• Coagulase negative
staphylococci (including
Staphylococcus epidermidis)
• Streptococcus
viridians
Gram positive Gram negative
anaerobes anaerobes
• Clostridium spp. • Bacteroides spp.
• Peptococcus spp. • Fusobacterium spp.
• Peptostreptococcus spp. • Prevotella spp.

*As per Amoxicillin clavulanate tablet BID PI .$As per Amoxicillin clavulanate oral Global Data Sheet
1. Robertson D, Smith AJ. The microbiology of the acute dental abscess. J Med Micro. 2009; 58:155-162.
2. de Sousa EL, et al. Bacteriological study of root canals associated with periapical abscesses. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;96(3):332-9.
3. López-Píriz R, Aguilar L, Giménez MJ. Management of odontogenic infection of pulpal and periodontal origin. Med Oral Patol Oral Cir Bucal 2007;12:E154-9.
 Amoxicillin-clavulanate is effective against the anaerobes
which cause odontogenic infections

Susceptibility of infective micro-organisms to amoxicillin-clavulanate according to

bacterial group*
96% 100%
100
90
78.2%
80
70
% Susceptibility

60
50
40
30
20
10
0
Gram-positive facultative Gram-negative strict Gram-positive facultative
anaerobic cocci (n=125) anaerobic bacilli (n=55) anaerobic bacilli (n=4)

Sixty-four patients with odontogenic infection were selected on the basis of a series of inclusion and exclusion criteria. Samples were collected from lesions under maximally aseptic conditions,
avoiding oral saprophytic contamination. The samples were cultured and incubated under aerobic and anaerobic conditions, followed by bacteriological identification and antibiotic susceptibility
testing.
* The susceptibility patterns may vary with time and geography. Refer to local susceptibility patterns before prescribing
Brescó-Salinas M et al. Antibiotic susceptibility of the bacteria causing odontogenic infections. Med Oral Patol Oral Cir Bucal. 2006;11(1):E70-5.
 Amoxicillin-clavulanate: Pharmacokinetics

• Amoxicillin and
clavulanic acid are:
Both reach peak
Oral • Pharmacokinetically serum levels
compatible Rapidly
administ • Similar absorption absorbed
approximately
one hour after
ration profiles, elimination dosing2
characteristics and
serum half-lives1,2

1. Ball AP et al. Excerpta Medica 1980; ICS 544: 118-121.

2. Witkowski G et al. Eur J Clin Microbiol 1982; 1 (4): 233-237.
 Amoxicillin-clavulanate: Pharmacokinetics

Tissue penetration

Achieves effective level of concentration in

plasma and gingival crevicular fluid above the MIC
of susceptible periodontal anaerobes1,2

1. Isla A et al. Antibiotic therapy in odontogenic infections in children and adolescents: pharmacokinetic/pharmacodynamic analysis. Enferm Infecc Microbiol Clin.
2008;26(10):621-8.
2. Tenenbaum H et al. Amoxicillin and clavulanic acid concentrations in gingival crevicular fluid. J Clin Periodontol. 1997;24(11):804-7.
 Amoxicillin-clavulanate –
A potential choice for Dental Infections
 The spectrum of action of amoxicillin-clavulanate
compares favorably with other antibiotics in odontogenic
infections

Susceptibility trends vary with geography and time. Kindly refer to local susceptibility patterns
Actinomyces actino- Peptostrepto- Prevotella Porphiro- Fusobac- Streptococcus
mycetemcomitans coccus spp. spp. monas spp. terium spp. oralis

Penicillin G +/- + +/- +/- +/- +/-

Amoxicillin + + +/- +/- +/- +

Amoxicillin-
clavulanate + + + + + +
Doxycycline + +/- +/- +/- + +/-
Clindamycin 0 + + + + +
Metronidazole 0 + + + + 0
Macrolides +/- +/- +/- +/- +/- +/-
+ More than 80% sensitive strains. // +/- 30 - 80% sensitive strains. // 0 Less than 30% sensitive strains.
31
López-Píriz R, Aguilar L, Giménez MJ. Management of odontogenic infection of pulpal and periodontal origin. Med Oral Patol Oral Cir Bucal. 2007;12:E154-9.
Clinical evidence
 Augmentin
Dental Study
 Comparable Success rate with Amoxicillin-clavulanic
acid in dental Infections

A multicenter study of patients from 106 dental practices established (303 subjects) 1

Clinical response

Treatment failure

n=153
96%

Patients of either sex, recruited from 106 dental practices in Belgium, were aged between 18 and 75 years and had acute periapical abscesses not requiring drainage,
confirmed by radiology. Azithromycin was administered as a 500-mg tablet orally once daily for 3 days (n = 150) and co-amoxiclav as a 625-mg capsule three times daily,
for 5-10 days (n = 153). Both before and after treatment, masticatory pain, percussion pain, headache, and oedema and redness of soft tissue were graded on a four-
point scale. Success rate with Amoxicillin-clavulanate: 96% and for azithromycin 91% (p=NS) 1

1.Adriaenssen CF. Comparison of the efficacy, safety and tolerability of azithromycin and co-amoxiclav in the treatment of acute periapical abscesses.
J Int Med Res. 1998 Oct-Nov;26(5):257-65.
Augmentin: Dosage in dental infections

Adults and children over 12 years:

One 375 mg tablet thrice daily or one 625 mg tablet twice daily.

Method of Administration

Tablet to be consumed in whole, not to be broken.

To minimise potential gastrointestinal intolerance, administer at the start of a meal. The absorption of
AUGMENTIN is optimised when taken at the start of a meal.

Prescribing Information of AUGMENTIN 625/1000 DUO. GlaxoSmithKline, India. Version: AUG-TAB/PI/IN/2017/01 dated 04-Oct-2017. Prescribing Information of
AUGMENTIN 375. GlaxoSmithKline, India. Version AUG-375/PI/IN/2017/01 dated 04-Oct-2017.
 Summary

• Acute odontogenic infections are the principal reason for

seeking dental care
• Therapeutic success is determined by the control of infection
using surgical debridement and/or broad-spectrum
antimicrobial therapy
• The addition of a β-lactamase inhibitor such as clavulanic acid
to amoxicillin (amoxicillin-clavulanate) confers protection
against to β-lactamases thereby extending the antibiotic
spectrum to anaerobes such as Prevotella spp., Bacteroides
spp. and Staphylococcus spp. which are common in
odontogenic infections
Tancawan AL, et al. Amoxicillin/clavulanic acid for the treatment of odontogenic Infections: A randomised study
comparing efficacy and tolerability versus clindamycin. Int J Dent. 2015;Article ID:472470.
Thank You
 Important Safety Information of Oral Formulations of
Augmentin

• Before initiating therapy with AUGMENTIN, careful enquiry should be made concerning
previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.

• Very common undesirable side effects (≥1/10); Diarrhea (adults)

• Common undesirable side effects (≥1/100 and <1/10); Mucocutaneous candidiasis,

diarrhea (children), nausea, vomiting.

• AUGMENTIN should be avoided if infectious mononucleosis is suspected since the

occurrence of a morbilliform rash has been associated with this condition following the
use of amoxycillin.

Prescribing Information of AUGMENTIN 625/1000 DUO. GlaxoSmithKline, India. Version: AUG-TAB/PI/IN/2017/01 dated 04-Oct-2017.
Prescribing Information of AUGMENTIN DDS (oral suspension). GlaxoSmithKline, India. Version Version: AUG-DDS/PI/IN/2017/01 dated 31-Oct-2017.
Prescribing Information of AUGMENTIN DUO (oral suspension): GlaxoSmithKline, India. Version Version: AUG-SUS/PI/IN/2017/01 dated 31-Oct-2017.
 Full prescribing information available on request from
GlaxoSmithKline Pharmaceuticals Ltd.,
Dr. Annie Besant Road, Worli,
Mumbai- 400 030. (India)

Registered medical practitioners can refer company website

http://india-pharma.gsk.com/en-in/products/prescribing-information/ for full Product Information.
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IN/CAM/0132/17 Date of preparation December 2017