Antibiotics notes

Microbiology Antibiotics IC1

RMSH 2012

Terminology:

Antibiotics Vs. Antimicrobial

Antibiotics Antimicrobial

Naturally occurring agent produced by a microbe that inhibits or kills another.

Usually anti-bacterial agent.

Any drug that inhibits or kills a bacterium, virus, fungus, etc.

Therapy

Empiric Prophylactic

Treatment of an infection with antibiotics before specific culture has been reported or obtained.

Administration of antibiotics to prevent an infection. As before surgeries.

Anti-bacterial Spectrum

DEF: The range of activity of an anti-microbial against bacteria.

Broad Narrow

Def Anti-bacterial drugs that can inhibit a wide range of Gram+ve and Gram-ve bacteria.

Drugs that are active only against limited range of bacteria.

Pros Poly microbial Unknown aetiology

Minimal disruption of normal flora

Cons Super infection; Cl. Difficile Not suitable for blind therapy

Example Cefapime Gram +ve Gram -ve Anaerobes

Penicillin G Gram +ve only

Bacteriostatic Vs. Bactericidal

Bacteriostatic Bactericidal

Def The level of anti-microbial activity that inhibits the growth of an organism.

The level of anti-microbial activity that kills the organism.

Determination In vitro, testing a standardized [] of an organism against a series of anti-microbial dilutions.

In vitro, testing a standardized [] of an organism against a series of anti-microbial dilutions.

Measurement Minimum Inhibitory Concentration (MIC): Lowest conc. That inhibits the growth of an organism.

Minimum Bactricidal Concentration (MBC): Lowest conc. That kills 99.9% of the organism population.

MOA Halt growth. Kills bacteria.

Irreversible

Example Macrolides

Tetracyclins

Penicillin G

Gentamicin


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Time dependant Vs. Concentration dependant

Time Dependant Concentration Dependant

Increase amount of time the antibiotics bind to microorganism. t>MIC

High conc. At the binding site which eradicates the microorganism. Peak>MIC

Penicillin

Cephalosporin

Carbapenem

Monobactams

Aminoglycosides

Fluroquinolones

Ketolides

Antibiotics Combination:

WHY? WHEN?

Broaden anti-microbial spectrum for empiric therapy.

Treatment of polymicrobial infections.

Prevent emergence of resistant organisms during therapy. (TB)

Achieve synergistic killing effect. (treatment of infective endocarditis)

TYPES..

Antibiotics Synergism Antibiotics Antagonism

Combination of antibiotics that have enhanced bactericidal activity when tested together compared with the action of each of them separately.

Combination of antibiotics in which the activity of one interferes with the activity of the other. The sum of activity when together is less than the sum when each is tested separately.

Aminoglycoside + -lactams e.g. Pseudomonas infections

-lactam + -lactam

Ampicillin + Gentamicin Enterococcal endocarditis

Induction of -lactamase by one agent renders the other agent ineffective.

What is -lactamase?

An enzyme that hydrolyzes the -lactam ring in

-lactam class of antibiotics thus making Ab ineffective.

Penicillin + Gentamicin Viridans streptococcal endocarditis

Vancomysin + Gentamycin

Staphylococcal bacteremia


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Susceptibility Testing: (Defines organism as sensitive or resistant)

DEF: An in vitro test to try and predict the likely success or failure of an antibiotic in vivo.

AIMS:

Aids in bacterial identification.

Predicts host response.

Provides epidemiological data to support blind therapy.

METHODS:

Agar/ Disk Diffusion MIC E test

Lowest conc of an Ab required to inhibit the growth of a bacterium.

An agar based quantitative susceptibility test.

1) Cellulose disk with standard amount of Ab on an agar plate.

2) Ab diffuses into agar and zone sizes reflect susceptibility or resistance.

1) Variable conc of Ab in broth or in agar.

2) Ab serially diluted. 3) When bacteria stop

growth then MIC.

1) A stripe with 2 folds serial dilution of an Ab in an agar.

2) Where smallest clear zone = MIC.

Easy to do. Cheap. Tests 4-6 agents @ one

time.

Determines MIC of selected organism.

Detect changes in susceptibility.

Enables MIC values to be estimated directly.

Not quantitative.

One Ab only per test. One Ab only per test.


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Antibiotics Use:


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Mechanism of Action:

MOA Detailed Example

Inhibition of cell wall synthesis Affect cross linking of peptidoglycan strands and bacteria die by lysis.

-lactams:

Penicillin

Cephalosporin

Carbapenem

Bind to acyl-D-alanyl-D-alanine and block prolongation of peptidoglycan backbone. Activity limited to Gram-positive organisms only.

Glycopeptides:

Vancomycin

Inhibition of nucleic acid synthesis

Interfere with supercoiling of bacterial DNA by inhibiting DNA gyrase and topoisomerase.

Quinolones:

Ciprofloxacin

Affects RNA polymerase so transcription of genetic code cannot occur.

Rifampicine

Breakage in the DNA. Metronidazole

Inhibition of protein synthesis Inhibition of binding of tRNA to 30-S ribosome.

Gentamicin

Tetracycline

Inhibition of binding of tRNA to 50-S ribosome.

Macrolides

Clindamycin

Anti-metabolites Inhibits microbial chemical pathways.

Trimethoprim

Sulphamethoxazole

Isoniazid

Blockage of folate metabolism. Blocks 2 steps in folate metabolism.

Sulfonamide

Trimethoprim


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Commonly Used Antibiotics:

Spectrum:

Broad Narrow

Ab Benzylepenicillin Ampicillin Amoxycillin

Bacteria Gram +ve cocci

Staphylococci

Streptococci

Clostridia Some Gram –ve cocci

Neisseria

Gram –ve bacilli

E-coli

H. influenza

Used in Meningitis

Endocarditis

Cellulitis

UTI

Resp. tract infection

Adv Safe Good oral absorption

Penicillinase Stable Penicillin

Ab Flucloxacillin Co-amoxicalav (calvulonic acid+Amoxicillin)

Properties Not inactivated by -lactamase Stables -lactamase

Used for Sensitive Staph. aureus not MRSA Aerobes & Anaerobes

Generations: (Cephalosporins)

Properties Used for Example

1st Good Gram +ve activity.

Orally active.

Resp. tract infections.

UTI.

Cefaclor

2nd Gram +ve & -ve.

Oral & IV

Resp. tract infections.

Surgical prophylaxis.

Cefuroxime

3rd Good Gram -ve activity

Less Staphylococcal activity.

Has streptococcal activity.

Meningitis.

Health care associated infections (HCAI).

Cefotaxime

IV only:

Examples Properties Used for S/E

Aminoglycosides..

Gentamycin

Amikacin

Streptomycin

Gram -ve bacilli.

Injection only, not absorbed when given orally.

Gram -ve septicaemia.

In combination for Intra-abdominal infection.

Endocarditis.

Toxicities

Renal

Ototoxicity


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Others:

Class Properties Used in

Quinolone

Ciprofloxacine

Levofloxacin

Moxifloxacin

Anti Gram -ve.

New, anti Gram +ve also.

ICU pts

Cystic fibrosis

Metronidazole Anti-protozoal

Anti-anaerobic

Used in combination with other Ab for

Prophylaxis (bowel surgery)

Abdominal sepsis

Trimethoprim

May be combined with sulphonamide (co-trimoxazole)

UTI

Pneumocystis carinii

Glycopeptides

Vancomycin

Teicoplanin

Narrow Spectrum

Gram +ve only

MRSA (I/V not orally)

C. difficile (oral not I/V)

Macrolides

Erythromycin

Clarithromycin

infection with ‘Atypical’ bacteria e.g. legionella, H. pylori, mycoplasma

Failure of anti-microbial chemotherapy. WHY?

• Clinical condition not susceptible to antimicrobial treatment e.g. non-infective cause of fever, viral.

• Resistant organisms.

• Wrong choice of antimicrobial.

• Wrong doses – too low e.g. Gram negative septicemia.

• Inadequate duration – may relapse.

• Wrong route e.g. orally, if absorption of drug poor.

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