AUGPEN

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Dental Infections Augpen (Co-amoxyclav)

• History
 Etiology
• Mechanism of Action
 Epidemiology • Pharmacokinetics

 Pathophysiology • Antimicrobial Activity

• Advantages of Co-amoxyclav
 History/examination/presentation
• Adverse Effects and Contraindication
 Evaluation • Indications
• Dosage
 Management/Treatment
• Clinical Efficacy (Dental Infections)
• Salient features
 Dental Infections
• Originate in tooth or its supporting structures & spread to the surrounding tissue

• Facial structures compromised: infection originates from necrotic pulp, periodontal pockets pericoronitis

• Dental infections were, historically, a common cause of death

• 1600: London England Bills of mortality reported teeth infections as 5th leading cause of death 

• 1908: dental infections were associated with a mortality of 10 to 40% 

• Fortunately, due to
• Improved dental hygiene
• Modern dentistry
• Antibiotics
• Dental infections are rarely life-threatening today

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Etiology: Dental infections
 Most commonly occur when bacteria invade the pulp and spread to surrounding tissues

 Periodontal infections first involve gingival tissues (gingivitis) and over time, periodontitis

 Periodontal disease:

 mostly results from poor or ineffective dental hygiene

 leading to plaque /calculus accumulation
 Subsequent inflammation of tissues that support teeth, alveolar bone, periodontal ligament, cementum
 This can be due to

 dental caries
 dental trauma
 dental procedures

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Etiology……………....

 Etiology of periodontitis is multifactorial

 Bacteria initiate infection,

 Clinical presentation and outcome of disease are determined by  inflammatory response and

predisposing factors
 Disease progression seems to be regulated by environmental/genetic factors specific in each patient 

 Streptococcus mutans: Primary etiologic agent of dental caries

 This pathogen access bloodstream during dental procedures, causing opportunistic systemic infections

 Thus, bacteremia, through the adhesion to the endocardium, is involved in

 Infective endocarditis

 Peripheral arterial disease 

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Epidemiology

 13% of adults seek dental care for dental infection or toothache within four years 

 1 per 2600 in the US is hospitalized due to dental infections 

 >1 in 5 people have untreated dental caries, and 3 in 4 people had at least one dental restoration

during their life

 Periodontitis is also common, with estimations that 35% of all Americans age 30 to 90 are afflicted 

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Dental Caries

 Prevalence of dental caries varies significantly by socioeconomic factors

 Untreated dental caries were > 2.5 times as common in those living below the poverty level

 Dental caries are present in

 90% of adults and

 42% of children ages 6 to 19 years  

 Dental caries did not appear to vary much with age

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Pathophysiology

 Dental plaque: an example of a biofilm, which occurs naturally on the teeth structures

 Dental biofilm has a diverse composition that stays in microbial homeostasis in healthy oral conditions

 When this microbial homeostasis breaks down, acid-producing and acid-tolerating bacteria prevail

 Microorganisms cause a decrease in pH (breakdown of monosaccharides/disaccharides from sugar-rich foods) 

 Leading to enamel demineralization

  Most associated pathogens are mutans streptococci and lactobacilli 

 Gram-negative organisms, facultative anaerobes, and strict anaerobes are common organisms

 Anaerobes outnumbering aerobic bacteria by a factor of three 

 Pathophysiology………..

Pulpitis and its complications:

 Infection can then invade the pulp, causing pulpitis

 Most dental infections are:

 polymicrobial infections
 spread towards the alveolar bone, causing a periapical abscess
 On the other hand, biofilms can penetrate gingival epithelium

 causing an inflammatory response with neutrophil infiltration

 subsequent destruction of periodontal tissues,
 leading to periodontal disease
 Infection can directly spread to adjacent osseous and deep neck structures causing fascial space infections 

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 History and Physical examination/Presentation

 Dental Caries

 acute or chronic,
 brown-yellow and soft or
 black and hard cavities
 Pulp exposure may be seen

 Incipient caries: more challenging to identify, and represent the first clinical manifestation of caries

 They are white and opaque irregular spots that may appear on any tooth surface

 Patients with reversible pulpitis can present with a severe toothache induced by stimuli, like hot or cold

drinks or food
 Irreversible pulpitis presents as unprovoked tooth pain that usually exacerbates overnight

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Patients with gingivitis and periodontitis will often present with a history of
 Halitosis
 Bleeding after brushing teeth

 Gum pain

 In gingivitis:
 Swollen Gums

 Erythematous with a shiny surface

 Bleed on probing (no periodontal pockets)

 Periodontitis Gingivitis of the upper gum.

 involves migration of junctional epithelium and

 development of periodontal pockets

 Clinical findings of periodontitis :

 Gingival recession
 Dental papilla detachment
 Loss of alveolar bone
 Tooth mobility
 Fremitus 

Advanced periodontitis
 Periapical abscess: may present as a palpable swelling

 Dental abscess : originated from the pulp, periodontal structures, or both

 More serious complaints such as

 Fever
 Facial edema
 Trismus
Pericoronitis of an impacted wisdom
 Dysphagia or dysphonia tooth

 can be symptoms of a more serious dental infection, extended into deep neck spaces

  Patients may be in respiratory distress or hemodynamically unstable with sepsis 

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Evaluation
 Dental infections can be further evaluated using
 Dental radiographs
 Orthopantomography
 CT scans/MRIs
 Imaging studies play an essential role in recognizing
 Source of infection
 Proportions of disease spread
 detect any complications
 Cone-beam CT (CBCT) : useful in assessing periapical disease, pericoronitis and osteomyelitis
 CT with contrast : Shows extent and severity of fascial space infection
 MRI: useful for osteomyelitis and deep space infections of the neck
 Laboratory studies: complete blood count 
 Patients with facial or deep space infections may present with sepsis

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Treatment / Management

 Depends on whether it is a local infection or a severe infection 

 Removal of the source of infection is most important step in treating dental infections

 Dental caries management

 depends on the extent of dental caries

 can range from the insertion of a restorative material, endodontic treatment, to tooth extraction
 Reversible pulpitis: treatment with pulp protection and restorative materials is usually sufficient

 Irreversible pulpitis treatment: root canal and direct or indirect restorations

 Pulp necrosis: treated with a root canal or tooth extraction as the last resource

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Periapical abscess is treatable with

 endodontic treatment
 incision and drainage
 should receive antibiotics in addition to drainage 
 Gingivitis is a reversible condition, that can be treated with professional plaque removal

 chlorhexidine rinses as an adjuvant to mechanical treatment

 Periodontitis may be treated with scaling and may require antibiotics in specific cases

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Antibiotic Therapy for Dental Infections
 Necessary for
 systemic symptoms
 fascial space infections
 infections spread to bony cortex/surrounding soft tissue 
 Penicillin has traditionally been the drug of choice
 Amoxicillin/ Amox-Clav is the most common medication prescribed for dental
infections
 Amoxicillin/ amox-clav is also the recommended medication by the American
Heart Association for prophylaxis against endocarditis associated with dental
procedures
 Antibiotic Therapy………………….

 Metronidazole used with penicillin (Amox-Clav)

 High resistance to macrolides (should not serve as first-line agents)

 Clindamycin and macrolides are also considerations in cases of Penicillin allergy

 Severe infections or immunocompromised patients should get

 anti-pseudomonal antibiotics

 Piperacillin-tazobactam, meropenem, cefepime, imipenem-cilastatin, or metronidazole with

ciprofloxacin can be therapeutic options

Erazo D, Whetstone DR. Dental Infections. [Updated 2021 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK542165/
 Post-operative Infections due to Third Molar Extraction

 One of the most common procedures performed in oral

and maxillofacial surgery clinics

 Postoperative infections are common in patients with

mal hygiene and immuno-compromised state

 Systemic and local antibiotics are associated with lower

incidence of complications

Bratisl Lek Listy 2010; 111(5): 296-8

 AUGPEN
CO-AMOXICLAV

• Augpen IV Injection (1.2 gm/600 mg/300 mg/150 mg)

• Augpen Suspension (Co-amoxiclav-125 +31.25 mg/ 200 + 28.5 mg/ 400 + 57 mg)

• Augpen Drops (Co-amoxiclav 80 mg/ 11.4 mg)

• Augpen tablets (375 mg/625 mg/875)

 Co-amoxiclav: Still going strong

Amoxicillin:  a broad-spectrum, Clavulanic acid: a mechanism-

bactericidal, β-lactam antibiotic  based β-lactamase inhibitor used to
overcome resistance in bacteria that
secrete β-lactamase.

The pharmaceutical Journal, TUESDAY, AUGUST 9, 2011

 A brief history of Co-amoxiclav

 Co-amoxiclav was invented around 1977-78 by British scientists working at Beecham Research

Laboratories

 Filed for US patent protection for the drug combination in 1979

 U.S. Patents 4,441,609 was granted in 1984

 This combination results in an antibiotic with an increased spectrum of action and restored

efficacy against amoxicillin-resistant bacteria that produce β-lactamase

The pharmaceutical Journal, TUESDAY, AUGUST 9, 2011

 Mechanism of action

Amoxicillin

Bacterial
cell lysis

The pharmaceutical Journal, TUESDAY, AUGUST 9, 2011

 Pharmacokinetics
Bolus intravenous injection
Dose administered Amoxicillin (AMX)
Dose Mean peak serum T 1/2 (h) AUC (h.mg/l) Urinary recovery
conc (µg/ml) (%, 0 to 6 h )

AMX/CA 500 500mg 32.2 1.07 25.5 66.5

mg/100 mg

AMX/CA 1000 1000mg 105.4 0.9 76.3 77.4

mg/200 mg

  Clavulanic acid (CA)
AMX/CA 500 100mg 10.5 1.12 9.2 46.0
mg/100 mg

AMX/CA 1000 200mg 28.5 0.9 27.9 63.8

mg/200 mg

British National formulary, 57 edition page 295

 Antibacterial spectrum of clavulanate

 Clavulanate is a broad-spectrum β-lactamase inhibitor,

 Shows activity against many of the chromosomally and plasmid-

mediated β-lactamases of both Gram-positive and Gram-negative

bacteria.

 co-amoxiclav has been shown to enhance the intracellular killing

functions of human polymorphonuclear cells (PMNs)

 In-vivo studies, clavulanate enhanced the activity of amoxicillin

against non-β-lactamase-producing organisms.

Journal of Antimicrobial Chemotherapy (2003) 52, 18–23

 MIC breakpoints for Amoxicillin/Clavulanic acid
Organism Susceptibility Breakpoints (µg/ml)
  Susceptible Intermediate Resistant
Haemophilus influenzae1 ≤1 - >1
Moraxella catarrhalis1 ≤1 - >1
Staphylococcus aureus 2 ≤2 - >2
Coagulase-negative staphylococci 2 ≤ 0.25 - > 0.25

Enterococcus1 ≤4 8 >8
Streptococcus A, B, C, G5 ≤ 0.25 - > 0.25
Streptococcus pneumoniae3 ≤ 0.5 1-2 >2
Enterobacteriaceae1,4 - - >8
Gram-negative Anaerobes1 ≤4 8 >8
Gram-positive Anaerobes1 ≤4 8 >8
Non-species related breakpoints1 ≤2 4-8 >8

1 The reported values are for Amoxicillin concentrations. For susceptibility testing purposes, the concentration of Clavulanic acid is fixed at 2 mg/l.
2 The reported values are Oxacillin concentrations.
3 Breakpoint values in the table are based on Ampicillin breakpoints.
4 The resistant breakpoint of R>8 mg/l ensures that all isolates with resistance mechanisms are reported resistant.
5 Breakpoint values in the table are based on Benzylpenicillin breakpoints.
Product information, Co-amoxiclav for Injection, Wockhardt UK Ltd UK, Renewal: 02/03/09
 In Vitro Antimicrobial Activity

 Data generated from:

 Alexander Project (AP) 1997 – 1998

 International Surveillance Study (ISS) 1997-1998

 Clinical Microbiology Institute (CMI) 1999

 Consultants in Anti-Infectives Surveillance and Testing (CAST) 1999

MICs of Co-Amoxiclav for S-pneumonae

Alexander project 1997-98 in all geographic regions (n=6,048)

 In Vitro Antimicrobial Activity

Penicillin-Intermediate S. pneumoniae
amox/clav amox/clav
amox/clav % Susc. @ % Susc. @
Study N MIC90 < 2.0 µg /mL < 4.0 µg /mL

AP- 1997 19 1 100 100

CAST 87 1 100 100
AP-1998 217 1 100 100
ISS 65 1 100 100

Alexander project 1997-98 in all geographic regions (n=6,048)

 Why to add clavulanic acid ?

The amoxicillin and Clavulanate  combination

Keeps the activity
Keeps of amoxicillin against streptococci,

including pneumococci, 

Restores the activity of amoxicillin against beta-lactamase

producing organisms, such as staphylococci, Escherichia

coli and Haemophilus influenzae, and extended its activity

against klebsiella and Bacteroides fragilis infections

The pharmaceutical Journal, TUESDAY, AUGUST 9, 2011

 Advantages of Co-Amoxiclav over other agents

Efficacy of other agents:

Tetracyclines:
Has broad spectrum, but higher toxicity.
Aminoglycoside: in infections due to Gram-
negative bacterial strains. Also showed
higher toxicities
Fluoroqinolones:
Relatively limited spectrum of activity and
the rapid development of resistance
Cephalosporines:
Cephalosporin alters normal gut flora with
resultant risk of C. difficile.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Oct. 1991, p. 1947-1952; eMedExpert Home > Facts > (Co-amoxiclav)
 Advantages of Co-Amoxiclav
Other advantages

 Co-Amoxclav has an Excellent tissue penetration.

 Its absorption is not affected by food.

 Long-established track record in scientific studies and in practice.

 Very effective for middle ear infection (otitis media). 

 Because of its anaerobic coverage, Co-amoxiclav is an excellent drug for treating infections caused by human

and animal bites.

 It is the first choice for the treatment of otitis media, sinusitis, bronchitis, urinary tract infections and skin and

soft tissue infections.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Oct. 1991, p. 1947-1952; eMedExpert Home > Facts > (Co-amoxiclav)
 Adverse reactions

 Most frequently reported adverse effects were

 diarrhea/loose stools,

 nausea, skin rashes and urticaria,

 vomiting (1%) and

 vaginitis (1%). 

  Less frequently reported reactions include: Abdominal discomfort, flatulence, and headache.

British National formulary, 57 edition page 295

 Use in special population

 Pregnancy

 Use should be avoided during pregnancy, unless considered essential by the physician.
 Lactation

 Both substances are excreted into breast milk, consequently, diarrhoea and fungus infection of the
mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be
discontinued.
 Amoxicillin/clavulanic acid should only be used during breast-feeding after benefit/risk
assessment by the physician in charge.

British National formulary, 57 edition page 295

 Contraindications

 Amoxicillin and clavulanate potassium for tablets are contraindicated in patients with a history of

allergic reactions to any penicillin.

 It is also contraindicated in patients with a previous history of amoxicillin and clavulanate potassium

associated cholestatic jaundice/hepatic dysfunction.

Product information, Co-amoxiclav for Injection, Wockhardt UK Ltd UK, Renewal: 02/03/09
 Precautions

 Periodic assessment of organ system functions, including renal, hepatic and hematopoietic function,

is advisable during prolonged therapy.

 It should not be administered to patients with mononucleosis.

 If superinfections occur (usually involving Pseudomonas or Candida), the drug should be

discontinued and/or appropriate therapy instituted.

British National formulary, 57 edition page 295

 AUGPEN: Therapeutic indications

 Treatment
 Sinusitis, otitis media, recurrent tonsillitis  Prophylaxis against infections associated
 Acute exacerbations of chronic bronchitis
with major surgical procedures in adults, such as
 Bronchopneumonia
those involving the:
 Urinary tract infection, esp. when recurrent or
complicated, but not prostatitis  Gastrointestinal tract
 Osteomyelitis
 Septic abortion, pelvic or purpural sepsis
 Pelvic cavity

 Cellulitis, animal bites  Head and neck

 Pyogenic infections of skin, skin structures
and soft tissues  Biliary tract surgery

 Wound infections

Product information, Co-amoxiclav for Injection, Wockhardt UK Ltd UK, Renewal: 02/03/09
 Dosage & Administration
 The recommended dose is 4,000 mg/250 mg daily divided in two daily
doses i.e. 2 tablets of Augpen ER every 12 hours for 7-10 days

Age Group Dosage

Usually 1.2 g 8 hourly. In more serious infections,

Adults and children > 12 increase frequency to 6 hourly intervals.
years Maximum adult daily dose should not exceed 7.2
g by I.V. route. Maximum single dose is 1.2g.
Usually 30 mg/kg* 8 hourly. In more serious
Children 3 months - 12
infections, increase frequency to 6 hourly
years
intervals.
30 mg/kg* every 12 hours. In premature infants
Infants upto 3 months and in full term infants during the perinatal
period, increase to 8 hours thereafter.
Augpen in Dental Infections
 Amoxicillin and clavulanic acid vs ceftazidime in the surgical extraction of impacted
third molar: a comparative study

 Methodology
One hundred and seven patients with impacted third molar were randomized to receive
either amoxycillin plus clavulanic acid or ceftazidime for 5 days after surgery
 Results
Statistical analysis showed no differences between the two groups
 Conclusion
There is no indication to routinely administrate intramuscular second-choice antibiotic
prophylatic therapy (ceftazidime) in case of surgical extraction of the third molar

Int J Immunopathol Pharmacol. 2012 Jul-Sep;25(3):771-4

 Amoxy-clav for Maxillofacial space infections in
diabetic and nondiabetic patients

 Methodology
A 4-year prospective study was carried out on patients with maxillofacial space infection of
odontogenic origin.
 Results
 The organisms commonly isolated were Streptococcus species with submandibular space being the
most common space involved
 The empirical antibiotic used was amoxicillin plus clavulanic acid combined with metrogyl in 70.27%
cases
 Conclusion
Empirical antibiotic therapy of amoxicillin plus clavulanic acid combined with metrogyl along with
hyperglycemia control and surgical drainage of infection yielded satisfactory resolution of infection in
the diabetic patients as well.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Oct;110(4):e7-12
 Surgical Site Infections in Orthognathic Surgery and risk factors associated

 Methodology

Surgical site infections(SSI) and their risk factors for orthognathic surgeries were documented for upto one year of

follow-up

 Results

The two significantly correlated risk factors with the SSI in multivariate analysis were the length of surgery and the

type of antibiotic prophylaxis.

 Conclusion

It is necessary to recommend an antibiotic prophylaxis combining amoxicillin plus clavulanic acid alongwith other

precautionary measures to limit the rate of SSI in orthognathic surgeries

Rev Stomatol Chir Maxillofac. 2009 Jun;110(3):127-34

 Salient Features

 Amoxicillin is a broad spectrum β-lactam antibiotic used

β-lactam antibiotic to treat bacterial infections caused by
susceptible microorganisms.
 It is usually the drug of choice within the class because it is better absorbed, following oral administration,

than other β-lactam antibiotics.

 Amoxicillin is susceptible to degradation by β-lactamase-producing bacteria, therefore it is often

combined with clavulanic acid,

acid a β-lactamase inhibitor.
 Combination of amoxycillin and clavulanic acid has demonstrated efficacy in ENT infections like

pharyngitis, otitis media, tonsilitis, sinusitis and community acquired pneumonia

 Efficacy has also been demonstrated in Dental infections like maxillofacial space infections,

postoperative infection due to third molar extraction etc