Amoxicillin and Clavulanic acid

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 ß-lactam Antibiotics

 ß-lactam ring in their chemical structure

 Two main groups :
 Penicillins
 Cephalosporins

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 Amoxicillin
Ampicillin like penicillin

Mechanism of Action
Amoxicillin

Inhibits the synthesis of cell wall of bacteria

Rigidity of the bacterium test

Bacteria is killed

Bactericidal
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 Antimicrobial Activity of Amoxicillin

 Good activity against gram positive as well as gram negative

organisms

 Rapid bactericidal action against gram negative organisms

compared to Ampicillin

 The MIC of amoxicillin for Gram positive organisms range from

0.02 to 6 µg/ml and that for gram negative organisms from 0.02
to 8 µg/ml
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 Drawbacks of amoxicillin

 The antimicrobial activity is destroyed by the beta

lactamases produced by bacteria

 Hence, cannot be used in the infections caused by

beta-lactamase producing bacteria

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 What are Beta Lactamases ?
Enzymes produced by bacteria in order to destroy and inactivate the
beta-lactam antibiotics resulting in therapeutic failure in clinical
situations.

Beta lactamase Loss of

antimicrobial
Bacteria activity of an
antibiotic

Beta lactam Destroy the beta

antibiotic lactam ring

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 Which Organisms Produce Beta Lactamses ?
Gram positive, Gram negative, aerobic as well as anaerobic

Beta lactamase producing Staphylococci

organisms E. coli
Klebsiella species
Proteus species
Haemophilins influenzae
Moraxella catarrhalis
Neisseria gonorrhoea
Salmonella species
Shigella species
Bacteriodes species
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 How to Protect Beta Lactam Antibiotics ?
By combining amoxicillin with clavulanic acid, which is a
beta lactamase inhibitor

Amoxicillin reinforced with clavulanic acid

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 How to Protect Beta Lactam Antibiotics ?

Through the use of a beta-lactamase inhibitor, it is

possible to retain the benefits of older useful
agents making them capable of coping with the
beta-lactamase problem and solving it.

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 Clavulanic Acid

 Naturally occuring beta-lactam antibiotic

 It has a very limited and weak antibacterial activity
 It binds progressively an irreversibly with a wide range of
beta-lactamases produced by gram positive & gram
negative, aerobic as well as anaerobic strains

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 Pharmacokinetics

 Amoxicillin and clavulanic acid have similar absorption

profile, elimination characteristics and serum half lives

 Both of them are rapidly absorbed from the gastrointestinal

tract

 Absorption is not affected by food

 Serum half lives are approximately 1 hour for both

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 Pharmacokinetics (Contd.)

 Amoxicillin & clavulanic acid have low protein binding i.e.

18% and 25% respectively

 Both penetrate rapidly into most extracellular fluids, tissues

including lung, pleural & peritoneal fluids

 Both are excreted renally and may accumulate in renal

failure

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 Antimicrobial Spectrum
Gram positive organism
Organism Beta lactamase No beta lactamase
producing producing

Staphylococcus aureus 

Staphylococcus epidermidis
Staphylococcus saprophyticus
Enterococci
Streptococcus pneumoniae
Streptococcus pyogens
Peptococcus
Peptostreptococcus


– 
– 
– 
– 
– 
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 Antimicrobial Spectrum
Gram negative organism
Organism Beta lactamase Beta non lactamase
producing producing
Haemophilus influenzae 
Moraxella catarrhalis 
Escherichia coli 
Klebsiella species  –
Proteus species 
N. gonorrhoea 
Legionella species 
Anaerobes B. fragilis 
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 Indications
 Upper respiratory tract infection
 ENT infection
 Lower respiratory tract infection
 Urinary tract infection
 Skin and soft tissue infection
 Obstetric and gynaecological infection
 Sexually transmitted diseases
 Other infections
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 Upper Respiratory Tract Infections
 Sinusitis : Inflammation of sinusis
 Tonsillitis
 Pharyngitis
 Laryngitis
Organised causing URTI
 Streptococcus pneumoniae
 Haemophilus influenzae
Beta lactamase producing
 Moraxella catarrhalis
 Anaerobes
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 ENT Infection
Otitis Media
Inflammation of cavity of middle ear and is accompanied the
presence of fluid in the middle ear.

Organisms causing ENT infection

 Streptococcus pneumoniae
 Haemophilus influenzae
 Moraxella catarrhalis Beta lactamase producing
 Staphylococcus aureus
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 Lower Respiratory Tract Infection
 Bronchitis  Emphysema
 Bronchiectasis  Lung abscess
 Pneumonia

Organisms causing LRTI

 Streptococcus pneumoniae
 Haemophilus influenzae
 Moraxella catarrhalis Beta lactamase producing
 Klebsiella pneumonia
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 Urinary Tract Infection

 Uncomplicated UTI
 Complicated UTI

Organisms causing UTI

 E. coli
Beta lactamase producing
 Klebsiella
 Proteus
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 Skin and Soft Tissue Infections
 Abscess
 Cellulitis
 Wound infection

Organisms causing SSTI

 Staphylococcus aureus
 Staphylococcus epidermidis
 Streptococcus pyogens Beta lactamase producing
 E. coli
 Klebsiella
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 Obstetric and Gynaecological
 PID
 Salpingitis
 Septic abortion

Organisms causing infection

 Gram positive
Aerobes as well as anaerobes
 Gram negative

Mixed infections are increasing in incidence and infection by beta

lactamase producing strains are frequent.
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 Sexually Transmitted Disease

Major Pathogens

 N. gonorrhoea  gonorrhoea

 H. ducreyi  chancroid  painful, serious genital ulcer

 Chlamydia trachomatis

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 Use in Pregnancy and Lactation

 Animal studies showed no teratogenic effect

 CLAVAM is pregnancy is not recommended unless

considered essential by the physician

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 Adverse Effects

 These as with that of amoxicillin

 Mild in nature

 Diarrhoea, nausea, vomiting

 No adverse effects because of clavulanic acid

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 Strength Available
Oral : Tablet : 375 (250 Amoxy +125 Clav)
625 (500 Amoxy + 125mg Clav)
1000 (875 Amoxy + 125 Clav)
Syrup : 125 Amoxy + 31.25 Clav / 5ml

200 Amoxy +28.5 Clav / 5 ml

Injectable : 1.2 gm (1000 + 200)

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 Dosage

Adults and children over 12 yrs

Mild to moderate: One 375 mg CLAVAM every 8 hrs.

Severe: One 625 mg CLAVAM every 8 hrs.

Children:
40-50 mg/kg/day in 2-3 divided doses.

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 Dosage in Renal Impairment

Mild impairment Moderate impairment Severe impairment

(Creatinine (Creatinine clearance (Creatinine clearance
clearance 10-30 ml/min) < 10 ml/min)
> 30 ml/min)

Adults

Oral No change in 375-750 mg Not more than 375 mg

dosage 12 hourly 12 hourly

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 Injection (1.2 gm)

1 gm of amoxicillin & 200 mg of Clavulanic Acid

Adults and Children
over 12 years
Children aged 3 months
to 12 years
Premature / full-term
infants in the perinatal period
Surgical prophylaxis
Surgery < 1 hour
Surgery > 1 hour
1.2 g every 8 hours (maximum single dose 1.2 g)
1.2 g every 6 hours (maximum adult daily dose 7.2 g) for
more serious infections
30 mg / kg every 8 hours
30 mg / kg every 6 hours, for more serious infections
Initially 30 mg / kg every 12 hours
Increasing to 30 mg / kg every 8 hours
1.2 g at induction of anesthesia
1.2 g at induction of anesthesia, followed by up to
4 x 1.2 g doses in 24 hours 28
 Injection (1.2 gm)

1 gm of amoxicillin & 200 mg of Clavulanic Acid

Renal impairment
Creatinine clearance
CRCL > 30 ml/min Normal dosage
CRCL > 10-30 ml/min 1.2 stat. then 600 mg every
12 hours 12 hours
CRCL < 10 ml/min 1.2 g stat. then 600 mg every
24 hours

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 Injection (1.2 gm)

1 gm of amoxicillin & 200 mg of Clavulanic Acid

Reconstitution

1.2 g vial + 20 ml water for injection & B.P. (final volume)

Administration
Amoxicillin and Clavulanic acid is not suitable for intramuscular injection.

Intravenous injection
This should be used immediately upon reconstitution, and injected over a
period of 3-4 minutes

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 Injection (1.2 gm)

1 gm of amoxicillin & 200 mg of Clavulanic Acid

Intravenous infusion
Reconstituted solution of Clavam IV may be given in a range of different intravenous fluids,
including water for injection I.P. and sodium chloride intravenous infusion I.P. (0.95 w/v)

1.2 g reconstituted solution + 100 ml infusion fluid

 Infusion should be performed over 30 to 40 minute period.

 Solution should be made up to full infusion volume (preferably using a mini-bag or in-line
burette) immediately after reconstitution.
 Residual antibiotic solutions should be discarded.

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 Injection (1.2 gm)

1 gm of amoxicillin & 200 mg of Clavulanic Acid

Stability Period

Reconstituted solution of IV mixed with water for injections

I.P. or sodium chloride intravenous infusion I.P. (0.9% w/v)
should be used for 4 hours at 250C and 8 hours at 50 C.

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Comparison with amoxicillin (Plain)
 Plain amoxicillin can be destroyed (made inactive) by the
production of beta-lactamase enzyme. Whereas clavulanic
acid in A&Cprotects amoxicillin and renders it free for its
activity.

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Comparison with Cefuroxime

 Gram negative coverage of CLAVAM is better than Cefuroxime

 Staphyllococcus coverage of CLAVAM is better than Cefuroxime
 Cefuroxime does not cover the anaerobic pathogens
 Beta-lactam stability of Cefuroxime is poor as compared to CLAVAM

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Comparison with Cefaclor

 Cefaclor does not cover the anaeorbes

 Gram negative coverage of CLAVAM is better than Cefaclor
 Staphylococus coverage of CLAVAM is better than Cefaclor
 Cefaclor does not cover the anaerobic pathogens
 Beta lactam stability of Cefaclor is poor as compared to CLAVAM

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Comparison with Quinolones
 Quinolones have a poor streptococcal coverage

 Quinolones have a poor anaerobic coverage

 Safety in paediatrics not established

 Quinolones cannot be prescribed with theophylline, unlike

CLAVAM

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Comparison with Macrolides

 Macrolides have a poor coverage of H. influenzae and other

gram negative organisms

 Poor patient compliance because of QID dosage

 Anaerobic coverage is poor

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