INTRODUCTION

Greek word

Anti - against

Bios - life

Antibiotics are substances produced by microorganisms, which suppress the growth of or kill other microorganisms at very low concentrations

(K.D Tripathi- 5TH Edition)

Antibiotics are chemical substances produced by microorganisms having the property of inhibiting the growth or destroying other microorganisms in high dilution

(by Waksman)

HISTORY OF

ANTIBIOTICS

PERIOD OF

EMPERICAL

USE

EHRLICH”S

PHASE

of dye and

organometallic

compound

MODERN ERA.

PERIOD OF EMPERICAL

USE

In 17th and 18th century, there were no proper treatment

for diseases.

Chinese use plant and moulds to treat infected

wounds.

In india,Chalmugra oil is used to treat leprosy.

Chinchona bark for fever.

Egyptian use honey + lint used for dressing wound.

EHRLICH’S PHASE

OF DYE AND ORGANOMETALLIC COMPOUND

Ehrlich toyed with idea that if certain dyes could

selectively stain microbes ,they could selectively

toxic to these organism,tried methylene

blue,trypan red etc.

He developed arsenicals-Atoxyl for sleeping

sickness, Arsphenamine for syphilis.

MODERN ERA.

In 1935, Domagk demostrate the

therapeutic effect of Prontosil,

a sulfonamide dye, in pyogenic infection.

Sulfapyridine was first sulfonamide to be

marketed in 1938

Gerhard Domagk

Penicillin was discovered by chance in

1928

Flemings (1929) found that a diffusablesubstance was elaborated by Penicillium mould which destroy staphylococcus on culture plate.

He named this substance PENICILLIN but could not purify it.

Alexander Fleming

In the 1940s Waksman and his

colleagues undertook a systematic

search of Actinomycetes as a source

of antibiotics and discovered Streptomycin in 1944.

All three groups of scientists Domagk,Fleming -chain- Florey and Waksman recieved Nobel Prize for their discoveries.

Selman Waksman

1948- chlortetracycline

In 1957- Nystatin

In 1970- new 4 Quinolones

In 1980- Norfloxacin

In 1998- Smithkine beecham patented

Amoxicillin/clavunate potassium tablets .

CLASSIFICATION…DEPENDING ON CHEMICAL STRUCTURE

1.Sulfonamides and related drugs ( dapsone)2.Diaminopyrimidines( trimethoprim)3.Quinolone ( norfloxacin, ciprofloxacin)4.β-lactum antibiotics ( penicillin, cephalosporin)

5.Tetracyclines ( doxcycycline)6. Nitrobenzene derivative ( chloramphenicol)7. Aminoglycosides ( gentamycin, neomycin)8. Macrolide antibiotics ( erythromycin,Azithromycin)9. Polypeptide antibiotics ( polymyxin- B)

10.Nitrofuran derivatives (furazolidine)

11.Nitroimidazoles (metronidazole)

12. Polyene antibiotics (nystatin, Amphoterin–B)

DEPENDING ON

MECHANISM OF ACTION

TYPE OF ORGANISMS

AGAINST WHICH PRIMARILY

ACTIVEa) Antibacterial- penicillin, Aminoglycosides

b) Antifungal- Griseofulvin, Amphotericin B etc

c) Antiviral- Acyclovir, Zidovudine

d) Antiprotozoal- Chloroquine, metronidazole.

e) Anthelmintic- Niclosamide, Mebendazole.

SPECTRUM OF ACTIVITY

a) Narrow Spectrum – Penicillin–G, Streptomycin, Erythromycin

b) Broad Spectrum - Tetracycline , Chloramphenicol.

TYPE OF ACTION

a) Primarily Bacteriostatic- Sulfonamide, Tetracycline.

b) Primarily Bactericidal- Penicillin, Cephalosporin.

SOURCE OF ANTIBIOTICS

a) Fungi- Penicillin, Griseflovin

b) Bacteria- polymyxin B, Bacitracin

c) Actinomycetes- Aminoglycosides, Macrolides.

SELECTION OF ANTIMICROBIAL

AGENTPateint factor

• Age

• Renal and hepatic function.

• Local factor.

• Drug allergy.

• Imapired host defence.

• Pregnancy

Organism related factor

• Bacteriological sensitivity testing.

• Minimum inhibitory concentration,

• Minimum bactericidal concentration.

• Postantibiotic effect

Drug factor

• Spectrum of activity.

• Type of activity.

• Sensitvity of the organism

• Relative toxicity

• Pharmokinetic profile

• Route of

administration.

IDENTIFICATION OF CAUSATIVE ORGANISM

ANAEROBIC

BACTERIAAEROBIC BACTERIA

Gram-

positive

cocci

Gram-

negative

bacilli

Gram-

positive

cocci

Gram

negative

bacilli

sterptococcsstaphylococc

s

Viridians

b-hemolytics

Haemophilus influenzae

Escheria coli

Klebsiella

Eikenella corroden

streptococcus

Porphyromonas

Fusobacteria

provetella

ORGANISMS RESPONSIBLE FOR APICAL

ABSCESS

1. Streptococci species

2. Streptococci intermedius

3. Streptococci angiosus

4. Streptococci constellatus

5. Bacteroides species

ORGANISMS RESPONSIBLE FOR

PERIODONTAL DISEASE

1. Porphyromonas gingivalis

2. Actinobacillus actinomycetecomitans

3. Borrelia vicenti

4. Prevotella intermedia

5. Fusobacterium

(Mainly gram negative bacteria)

ORGANISMS RESPONSIBLE FOR

DENTAL CARIES

1. Strep. Mutans group

2. Strep. Salivarius

3. Actinomyces species

4. Lactobacilli

Aerobic bacteria plays an important role in theorigin of odontogenic infections.

Anaerobic gram-positive cocci are seen 1/3 of allodontogenic infections.

Gram-negative rods comprises of 50% ofodontogenic infections.

ORGANISM RELATED FACTORS

Clinical diagnosis

Bacteriologic examination

20

Cont…

Minimum Inhibitory Concentration (MIC)

21

MIC- The lowest concentration of an

antibiotic which prevent visible growth of a

bacterium determined in microwell culture

plate

FOR THERAPEUTIC PURPOSES :-

1. Peak concentration of antibiotics

should be three to four times of the

MIC.

2. Therefore the dosage prescribed

must be capable of establishing a

concentration of three to four times the

MIC.

Minimum bactericidal Concentration (MBC)

22

MBC- of antibiotics is determined by

subculturing

from tubes with no visible growth

A small difference between MIC and

MBC indicate

antibodies is primary bacteriocidal,

Large difference indicate bacteriostatic

action.

If sufficient drug is not given to reach

therapeutic levels, sub therapeutic levels

may mask the infection without killing the

microbes.

DRUG FACTORS

Spectrum of activity

Type of activity

Sensitivity of organism

Relative toxicity

Route of administration

Evidence of clinical efficacy

Cost

Pharmacokinetic profile23

Cont…

SPECTRUM ANTIBIOTIC

Narrowest antibacterial spectrum should be

chosen.

1. It minimizes the risk of superinfection.

2. Broad-spectrum antibiotic develop resistant against many

bacteria.

3. Use of narrow-spectrum antibiotics allow larger

proportion of the host flora to be maintained, by reducing

superinfection to minimum.

Type of activity

Use of bactericidal rather than a bacterostatic drug .

Bactericidal drugs are used for patients who are pathologically

immuosuppresed.

Bacterostatic they inhibit growth and reproduction of bacteria by inhibiting

protein synthesis.

Bactericidal they penetrate into bacterial cell and kill them.

Why we use bactericidal drug ?

1. Host resistance

2. Destroying microbes by antibiotic itself

3. Better than bacterostatic drugs

4. Greater flexibility in dosage

Eg:-

Bactericidal drugs such as penicillin or cephalosporin

should be used in immunodeficient patients instead of

bacteriostatic drugs, erythromycin or clindamycin.

If bacteriostatic drugs are given then bacteria in

immunocompromised patients will not be killed and

there will be chances for them to develop resistance.

PROPER TIME INTERVAL

Frequency of dosing is very important.

Each drug has its specific plasma half-life (t1/2), during

which one half of the absorbed dose is absorbed.

Usual and divided dosages is maintained.

PROPER ROUTE OF ADMINISTRATION

Drugs can be administered by variety of

routes but its choice depends on both drugs

as well as patient related factors.

Routes divided into:-

1. Local routes

2. Systemic routes

USE OF LEAST TOXIC ANTIBIOTIC

• Antibiotics are used for killing living bacteria but some

antibiotics kill bacteria's existing in normal flora and

thus are highly toxic.

Less toxic drug must be used which are equally

effective.

Eg:-

Bacteria which cause odontogenic infections areusually sensitive to penicillin and chloramphenicolHence, penicillin is preferable because of lowertoxicity.

• Second choice of drug.

1) Clindamycin

2) Erythromycin

COMBINED USE OF

ANTIBIOTICS Synergism

Reduction in adverse effects

Prevents emergence of resistance

Broadens the spectrum antimicrobial action

32

DISADVANTAGES

Casual outlook

Increased chances of superinfections

Emergence of resistance

Increased cost of therapy

PENICILLIN

History

1928 - Alexander Fleming

Bread mold (Penicillium notatum) growing on

petri dish

1939 - Florey, Chain, and Associates

Began work on isolating and synthesizing large

amounts of Penicillin.

1941 – introduced in antibacterial therapy

PENICILLINS

Beta- lactam antibiotics

Narrow spectrum antibiotics

Bactericidal

These have the greatest activity against gram-positive organisms, gram-negative cocci, and non- lactamase-producing anaerobes. However, they have little activity against gram-negative rods.

They are susceptible to hydrolysis by lactamases.

35

STRUCTURE

The penicillins are classified as -lactam drugs because of their unique four-

membered lactam ring.

All penicillins have the basic structure shown A thiazolidine ring (A) is attached

to a -lactam ring (B) that carries a secondary amino group (RNH–). can be

attached to the amino group.

Structural integrity of the 6-aminopenicillanic acid nucleus is essential for the

biologic activity of these compounds.

If the -lactam ring is enzymatically cleaved by bacterial -lactamases, the

resulting product, penicilloic acid, lacks antibacterial activity.

PENICILLINS

Natural Semi synthetic

38

CELL WALL SYNTHESIS IN

BACTERIA. The first stage, precursor formation, takes place in the cytoplasm. The

product, uridine diphosphate (UDP)- acetylmuramyl-pentapeptide, called a “Park nucleotide” accumulates in cells.

The PEPTIDOGLYCAN residues are linked together forming a long strand and UDP is split off.

The final step is cleavage of terminal D-aniline of peptide chain by transpeptidase; energy so released is utilised for establishment of cross linkage between peptide chains of neighbouring strands.

This cross linking provide stablity and rigidity to the cell wall.

Comparison of the structure and composition of gram-positive and

gram-negative cell walls.

Mechanism of action. Peptidoglycan synthesis(in last step) is inhibited by beta

lactam antibiotics.

Penicillin bind at the active site of the transpeptidase

enzyme that cross – links the peptidoglycan strands.

It does this by mimicking the D-alanyl-D-alanine

residues that would normally bind to this site.

Penicillin irreversibly inhibit the enzyme transpeptidase.

For the action of penicillin and cephalosporin ;these are

collectively termed Penicillin-binding protein (PBS) are

present on cell membrane of bacteria.

Penicillin

Bind (PBP) on the cell wall of susceptible bacteria

Inhibits transpeptidation

Prevents peptidoglycan synthesis

Cell wall deficient forms spheroplasts &

filamentous forms

Autolysis

Cell death (bactericidal action)

CLASSIFICATION-

PENICILLIN-

Natural Penicillins

• Penicillin G

Semi synthetic Penicillins

• Acid-resistant alternative to penicillin G

• (Penicillin V);

• Penicillinase-Resistant Penicillins

• (cloxacillin, Oxacillin, Methicillin)

• Extended-spectrum penicillins

• 1. Aminopenicillin-Ampicillin and Amoxycillin

• 2.Carboxypenicillin

• Carbenicillin, Ticarcillin

• 3.Ureidopenicillins-

• Piperacillin,Mezlocillin.

B-lactamaseinhibitors-

• Clavlanic acid

• Sublactam

CLASSIFICATION

NARROW SPECTRUM PENICILLINS

β-lactamase sensitive

Acid resistant

-Penicillin V (oral)

Acid labile

- Penicillin-G (benzyl

penicillin)(I.M,IV)

- Procaine penicillin-G(I.M,depot inj)

- Benzathine penicillin-G(I.M, depot

inj)

β-lactamase resistant

Acid resistant

- Cloxacillin

- Dicloxacillin

- flucloxacillin

Acid labile

- Methicillin (I.M,I.V)

- Nafcillin (I.M,I.V)

EXTENDED SPECTRUM PENICILLINS

Acid resistant

• Aminopenicillins: Ampicillin, Amoxicillin, Bacampicillin,

Talampicillin

Acid labile (ANTIPSEUDOMONAL PENICILLINS)

• Carboxypenicillins: Carbenicillin, Ticarcillin

• Ureidopenicillins: Piperacillin, Mezlocillin, Azlocillin

BETA LACTAMASE INHIBITORS

• Sulbactam, Tazobactam, Clavulanic acid

Natural penicillins

Penicillin G is a narrow spectrum

antibiotic;

activity is primarily to gram positive bacteria and

few other.

Obtained from fermentations of the mold

Penicillium chrysogenum

Penicillin G (benzylpenicillin)

Penicillium

Cocci- streptococci (except enterococci)

staphylococcus aureus,

(gram negative cocci)

Neisseria gonorrhea

N. meningitis

Bacilli- B.anthracis

Corynebacteriumm diptheria,

Clostridium tetnai.

Actinomyces israelli(moderately sensitive)

Gram negative bacilli- E coli.

proteus.

Activity against these Microrganism-

Pharmacokinetics

It is relatively unstable in acid, thus the

bioavailability is low.

There is poor penetration into the cerebrospinal

(CSF), unless inflammation is present.

Active renal tubular secretion results in a short

half-life.

PharmacokineticsOral administration of Penicillin G:

Acid labile

About one-third of an orally administered dose of PnG is

absorbed from the intestinal tract under favorable conditions.

Gastric juice at pH 2 rapidly destroys the antibiotic.

Parenteral Administration of Penicillin G:

From I.M site absorption is rapid and complete

Peak plasma levels attained in 30min

DISTRIBUTIONPenicillin G is distributed widely, but the

concentration differs in various fluids and tissues.

Its apparent volume of distribution is ~0.35 L/kg.

Approximately 60% of penicillinG in plasma is

reversibly bound to albumin.

Significant amounts appear in liver, bile, kidney,

joint fluid, and lymph.

Cerebrospinal Fluid

Penicillin does not readily enter the CSF but

penetrates more easily with meningeal

inflammation.

The concentration attained usually reaches

5% of the value in plasma and thus is

therapeutically effective against susceptible

microorganisms.

EXCRETIONNormally, penicillin G is eliminated rapidly from the body, mainly by the kidney.

Approximately 60–90% of an intramuscular dose of penicillin G in aqueous solution is eliminated in the urine, largely within the first hour after injection.

The remainder is metabolized to penicilloic acid.

The t1/2 for elimination of penicillin G is ~30 minutes in normal adults.

Approximately 10% of the drug is eliminated by glomerularfiltration and 90% by tubular secretion

Unitage of Penicillin

The IU of penicillin is the specific penicillin activity

contained in 0.6 microgram of the crystalline sodium salt

of penicillin G.

Thus 1g= 1.6 million units

1 million unit= 0.6g

DOSES- 1. Sod.Penicillin G inj-

0.5-5 MU i.m./i.v. 6-12 Hourly

( BENZYL PEN 0.5-1MU in

Repository Penicillin G inj- these are insoluble salts of PnG which must be

given by deep i.m (Never i.v.) slowly at the site of inj.

2. Procaine Penicillin G inj- 0.5-1 MU( i.m) 12-24 hourly as aqueous

suspension.

( PROCAINE PENICILLIN-G 0.5 MU dry powder in vial)

It is a form of penicillin which is a combination of benzylpenicillin and

the local anaesthetic agent procaine. Following

deep intramuscular injection, it is slowly absorbed into the circulation

and hydrolysed to benzylpenicillin — thus it is used where prolonged low

concentrations of benzylpenicillin are required.

This combination is aimed at reducing the pain and discomfort associated

with a large intramuscular injection of penicillin. It is widely used in

veterinary settings.

Fortified procaine penicillin G inj- contain 3 lac U

procaine penicillin and 1 lac U sod. Penicillin G to

provide rapid as well as sustained blood level.

3. Benzathine benzylpenicillin-

Dose- Penidure LA12 Inj (12 lac unit)

It is the drug-of-choice when prolonged low

concentrations of benzylpenicillin are required and

appropriate, allowing prolonged antibiotic action over

2–4 weeks after a single IM dose

USES

58

Streptococcus pneumoniae infections

Meningococcal infections

Syphilis

Prophylaxis against Group A Streptococci

in patients with history of rheumatic heart

disease

Actinomycosis

Trench mouth

Therapeutic uses-

Gingivostomatitis, produced by the synergistic

action of Leptotrichia buccalis and fusospirochetes

that are present in the mouth, is readily treatable

with penicillin.

For simple “trench mouth,” 500 mg penicillin V

given every 6 hours for several days is usually

sufficient

Streptococcal Infections

Pharyngitis is the most common disease produced by S. pyogenes. Penicillin-resistant isolates of this organism have yet to be observed.

The preferred oral therapy is with penicillin V, 500 mg

every 6 hours for 10 days. Equal results are produced by the administration of 600,000 units of penicillin G procaine intramuscularly once daily for 10 days or by a single injection of 1.2 million units of penicillin G benzathine

Streptococcal Toxic Shock and

Necrotizing Fascitis

These life-threatening infections are best treated with

penicillin plus clindamycin (to decrease toxin synthesis).

Pneumococcal Infections

Penicillin G is the drug of choice for infections caused by sensitive strains of S. pneumoniae, but resistance is an increasing problem.

Thus, for pneumococcal pneumonia, a third-generation

cephalosporin or high-dose penicillin G (i.e., 20–24 million units daily by continuous intravenous infusion or in divided boluses every 2–3 hours) should be used until sensitivities are determined.

For parenteral therapy of sensitive isolates, penicillin G or penicillin G procaine is favored.

Therapy should be continued for 7–10 days, including 3–5 days after the patient is afebrile

Streptococcal Pneumonia, Arthritis,

Meningitis, and Endocarditis

These uncommon conditions should be treated with penicillin

G; daily doses of 12–20 million units are administered

intravenously for 2–4 weeks (4 weeks for endocarditis

Infections with Anaerobes

Many anaerobic infections are polymicrobial, and most of the organisms are sensitive to penicillin G.

An exception is the B. fragilis group, 75% of which may be resistant. Pulmonary and periodontal

infections usually respond well to penicillin G.

Mild-to-moderate infections at these sites may be treated with oral medication (either penicillin G or penicillin V 400,000 units four times daily).

Staphylococcal Infections

The vast majority of staphylococcal infections involve penicillinase-producing organisms.

Patients with staphylococcal infection should receive penicillinase-resistant penicillins (e.g., nafcillin or oxacillin).

Staphylococcal infections increasingly involve methicillin-resistant staphylococci, which are resistant to penicillin G,

Meningococcal Infections

Penicillin G is the drug of choice for meningococcal disease.

Patients should be treated with high doses of penicillin given

intravenously

Syphilis

Therapy of syphilis with penicillin G is highly effective.

Primary, secondary, and latent syphilis of<1 year’s

duration may be treated with penicillin G procaine (2.4

million units per day intramuscularly),plus probenecid

(1.0 g/day orally) to prolong the t1/2, for 10 days or

with 1–3 weekly

Intramuscular doses of 2.4 million units of penicillin G

benzathine (three doses in patients with HIV infection)

Adverse effects Hypersensitivity Reactions:

The basis of which is the fact that degradation products of penicillin

combine with host protein and become antigenic.

Jarisch- Herxheimer reaction: Penicillin injected in a syphillitic pateint

(secondary syphillis) may produce shivering , fever,myalgia,

exacerbation of lesions, even vascular collapse. This is due to sudden

release of spirochetal lytic products and last 12-72 hrs. It does not recur

and doesnot need inertuption of therapy.

Other adverse effects

Very high doses of penicillin G can

cause seizures in kidney failure.

Pain at I.M injection site

Nausea on oral ingestion

Thromboplebitis of injected vein

The major draw backs of benzylpenicillin are:

Inactivation by gastric acid

Short duration of action

Poor penetration into the CSF

Narrow spectrum of activity

Susceptibility to Penicillinase

Development of resistance

Possibility of anaphylaxis

Penicillin V ( acid resistance

to Penicillin –G) Orally active

Used for the treatment of bacteremia and oral infections

Higher minimum bactericidal concentration.

• DOSE:

• 250-500 mg. Given 6 hourly.

• Infants:60mg

• Crystapen-V, kaypen, 125, 250mg tab.

Penicillinase-resistant

penicillins(antistaphylococcal penicillins)

These congeners have side chains that protect the beta

lactam ring from attack by staphylococcal penicillinase

Indicated in infections caused by penicillinase producing

staphylococci (drugs of choice, except in MRSA)

Methicillin, Cloxacillin

Oxacillin, Nafcillin, Dicloxacillin

Penicillinase-resistant

penicillins(antistaphylococcal penicillins)Methicillin:

Acid labile

Not used clinically, except to identify resistant strains

MRSA is susceptible to Vancomycin/linezolid and rarely

Ciprofloxacin

It is highly penicillin resistant but not acid resistant- must be

injected.

Adverse reaction- haematuria, albuminuria, reversible

interistial nephritis.

Penicillinase-resistant penicillins…

Cloxacillin: Highly Penicillinase and Acid resistant

More active than methicillin

Less active against PnG sensitive organisms: should not be used as its

substitute

Incompletely but dependably absorbed (oral route)

>90% protein bound, eliminated primarily by kidney, also partly by liver

Plasma half life is about 1hr

Given in staphylococcus infection resistant to benzyl penicillin

Active against a variety of gram-negative bacilli as well.

Dose- 0.25, 0.5 g orally every 6 hourly,

For severe infections 0.25-1g may be injected

i.m or i.v.

BIOCLOX , CLOCILIN 0.25, 0.5g CAP.

0.5g/ vial injection

Ampicillin + cloxacillin –

Ampoxin- (ampicillin 125mg + cloxacillin 250mg)

Roscilox- (ampicillin 125mg + cloxacillin 250mg)

Extended spectrum penicillins.

Aminopenicillins:

Ampicillins:

Active against all organisms sensitive

to PnG; in addition, many gram-

negative bacilli

Extended spectrum penicillins Cont…

Extended spectrum

penicillins Cont…

Pharmacokinetics:

Acid resistant

Oral absorption is incomplete but adequate

Primary excretion is kidney, partly enterohepatic circulation

occurs

Plasma half life is 1hr

Uses:

UTI, RTI, Meningitis, Gonorrhoea, typhoid fever, bacillary dysentery,

Cholisystitis, Subacute bacterial endocarditis and Septicemias

Extended spectrum

penicillinsAdverse effects:

Diarrhoea(it is incompletely absorbed – the unabsorbed drug

irritates the lower intestine as well as causes marked alteration

of bacterial flora)

Rashes

Hypersensitivity

Interactions:

Hydrocortisone –inactivates ampicillin if mixed in the I.V solution

Oral contraceptive –failure of oral contraception

Probenecid –retards renal excretion

Extended spectrum

penicillins Bacampicillin –ester prodrug of ampicillin

Talampicillin, Pivampicillin and Hetacillin are other Prodrugs of ampicillin

DOSE-

Adult- 250- 500 mg every 6 hr

Child- 50-100 mg/kg given in equally divided doses every 6 hr

Maximum- 2-4 g/ day

Roscillin cap 500mg cap- 250 mg, inj 250 mg, inj 500 mg (ranbaxy)

D-syr 125mg/ml, 250mg/ml

Ampillin- Cap 250 mg, Cap 500mg, inj 250mg, 500mg

Ampicillin + cloxacillin –

Ampoxin- (ampicillin 125mg + cloxacillin 250mg)

Roscilox- (ampicillin 125mg + cloxacillin 250mg)

Ampicillin + sulbactam –

Ampitum inj ( ampicillin 1g + sulbactam 0.5g/ml)

( community accguired and hospital accquired pneumonia)

Amoxicillin:

Close congener of ampicillin but not a prodrug

Similar to it in all aspects except: Better oral absorption

Higher and sustained blood levels are produced

Incidence of diarrhoea is lower

Less effective against Shigella and H. influenzae

DOSE-

Amoxylin , 250, 500mg

Novamox 250,500mg

Mox 500mg,500mg

Symoxyl – LB 625 (500mg(amoxicillin )+ 60 million cell( lactobacilli sporogene

Stedmox- Tn(500mg(amoxicillin ) + 500mg( tinidazole)

Moxikind CV- kid (200mg(amoxicillin)+28.5mg( clavunaic acid)

Moxikind CV- 625 (500mg(amoxicillin)+125mg( clavunaic acid)

Agupen LB- (875(amoxicillin trihydrate)+125mg( clavunate K) + 60 million cell( lactobacilli sporogene)

Agupen LB- 625 (500mg(amoxicillin trihydrate)+125mg( clavunate K) + 60 million cell( lactobacilli sporogene)

Extended spectrum

penicillins2. Carboxypenicillins (Carbenicillin, Ticarcillin)

and

3. Ureidopenicillins (Piperacillin)

CARBEPENICILLIN

Penicillin conger.

Special feature- its activity against peudomonas

aeriginosa and indole positive Proteus.

It has Gram-negative coverage which

includes Pseudomonas aeruginosa but

limited Gram-positive coverage

Less active against- salmonella, E.coli,

Enterobacter.

Klebisella and gram positive cocci are remain

unaffected.

Uses-

Burns

Urinary infection.

Septecimia.

Uncomplicated gonorrhea

Pharmacokinetics

It is neither penicillinase resistant nor acid resistant.

Inactive orally.

Excreted rapidly in urine.

t ½ = 1hr

Dose= 1-2 g i.m, 1-5 g i.v.

Trade name-

Pyogen, Carbelin 1g, 5 g per vial inj

Extended spectrum

penicillins

These are called antipseudomonal penicillins

Piperacillin is more potent among these

Carbenicillin is less effective against Salmonella, E. Coli and

enterobacter but not active against Klebshiella and gram-positive

cocci

Piperacillin has good activity against Klebshiella, and is used

mainly in neutropenic/ immunocompromised patients having

serious gram-negative infections and in burns

UREIDOPENICLLINS- (PIPERACILLIN)

t ½ =1 hr.

Dose = 100-150 mg/kg/day.

Trade name=

Piprapen 1g, 2g vials

Pipracil inj 2g, 4g

Pipracillin+tazobactam ( noscomial infection )-

Novacillin plus (pipracillin Na 4g + tazobactam

0.5 g)

Beta-lactamase inhibitorsClavulanic acid, Sulbactam and Tazobactam

They contain beta-lactam ring but themselves, do not have

significant antibacterial activity.

Inactivate bacterial beta-lactamases and are used to

enhance the antibacterial actions of beta-lactam

antibiotics.

Beta-lactamase inhibitors Cont…

Clavulanic acid:

Obtained from Streptomyces clavuligerus.

It has beta lactam ring but no antibacterial activity of its own.

It inhibit wide variety Class II to class V of beta lactamase.

It is a progressive inhibitor : binding with beta lactamase is reversible

intially but becomes covalent later – inhibitition increasing with time.

Called a suicide inhibitor , it gets inactivated after binding to enzyme.

Pharmacokinetics-

Rapid oral absorption.

Bioavailability – 60%

t ½ = 1 hr

Pharmacokinetics matches amoxicillin

with which it is used.

Uses- Addition of clavunic acid restablises the activity of amoxicillin against

beta lactamase producing resistant Staph.aureus, H. inflenza,

N.Gonorrhoeae, E coli proteus, klebisella, salmonella and bacteria

Fragilis.

Coamoxiclav is indicated for

Odontogenic infection

Skin and soft tissue infection.

Respiratory tract infection.

Intra abdominal and gynaecological infection

Dose- Agumentin- Amoxicillin 250mg + Clavunic acid125mg ( TDS)

Agumentin – amoxicillin 1 g & clavunic acid 0.2 g vial. i.m /i.v

6-8 hourly for severe infection.

Adverse effect-

As same as amoxicillin alone.

Poor G.I tolerance.(specially in children)

Other side effect-

Candida stomatitis.

Vaginitis.

Rashes.

some cases of hepatic injury have been

reported

Sulbactam: Semisynthetic beta-lactamase inhibitor

Related chemically as well as in activity to clavulanic acid

It is also a progressive inhibitor

Combined with ampicillin.

On the weight basis , it is less potent than clavunic acid for most

type of enzymes, but the same level of inhibition can be obtained

at the higher concentration achieved clinically.

Oral absorption of sulbactam is inconsistent.

Therefore , it is preferably given parentally.

Dose – Sulbacin,

Ampitum : Ampicillin 1 g & sulbactam 0.5 g per vial inj.

Sulbacin 375 mg tab

Beta-lactamase inhibitors Cont…

Tazobactam:

Similar to Sulbactam

Pharmacokinetics matches with Piperacillin with which it is used for

used in severe infections like peritonitis, pelvic/urinary/respiratory

infections

However, the combination is not effective against piperacillin-

resistant Pseudomonas

They are available only in fixed combinations with

specific penicillins:

Ampicillin + Sulbactam (1g+0.5g I.V/I.M inj)

Amoxycillin + Clavulanic acid (250mg+125mg tab)

Piperacillin + Tazobactam sodium (2g+0.25g I.V/I.M

inj)

DRUG INTERACTION

DRUG INTER ACTIVITY

DRUG

POTENTIAL EFEECT MANAGEMENT

PENICILLIN CLASS Food Decrease / delayed GI

absorption of penicillin

GI Administer penicillin

at least

absorption of oral

penicillin's. 2 hours

before or after a

meal.

Tetracyclines

(doxycycline,

minocycline,

oxytetracycline)

Decreased effects of

penicillin

.Avoid combination.

Warfarin

(Anti coagulant,

thrombolytic)

Increased the effect of

warfarin with larger

dose of IV penicillin

Decrease warfarin dose

if necessary

Methorexate

(Antineoplastic agent)

Increase concentration

of methorexate ,

decrease effect of

penicillin,

Increase risk of

methotrexate toxicity

Monitor sign of toxicity,

Use of alternative

antibiotic (Ceftazidime)

Allopurinol Increased rate

of ampicillin

associated skin

rash

use alternative

drug if rash

develops.

Atenolol Decreased

effects of

atenolol

Separate

administration

times.

Monitor blood

pressure.

Increase

atenolol

dose if

necessary.

Poisioning and overdose-Drug Half life Toxic dose

/serum level

toxicity

Penicillin 30 min 10 million units/d IV,

or CSF > 5 mg/L

Seizures with single

high dose or chronic

excessive doses in

patients with renal

dysfunction

Methicillin 30 min Unknown Interstitial nephritis,

leukopenia

Nafcillin 1.0 h Unknown Neutropenia.

Ampicillin, amoxicillin 1.5 h Unknown Acute renal failure

caused by crystal

deposition

Carbenicillin 1.0–1.5 > 300 mg/kg/d or >

250 mg/L

Bleeding disorders

due to impaired

platelet function;

hypokalemia. Risk of

toxicity higher in

patients with renal

insufficiency

Piperacillin 0.6–1.2 > 300 mg/kg/d “

Ticarcillin 1.0–1.2 > 275 mg/kg/d “

Poisoning and drg overdose, Kent R.Olson. 5th edition.

Refrences-

Essential of medical pharmacology.

K D Tripathi. 5th edition

Manual of pharmacolgy and

therapeutics. Goodman and Glickman .

Poisoning and drug overdose, Kent

R.Olson. 5th edition

Katzung 9th edition.