Microbiology Terminology: Antibiotics Vs.

Antimicrobial

Antibiotics

IC1

Antibiotics Naturally occurring agent produced by a microbe that inhibits or kills another. Usually anti-bacterial agent.

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

Therapy Empiric Treatment of an infection with antibiotics before specific culture has been reported or obtained. Prophylactic 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 Anti-bacterial drugs that can inhibit a wide range of Gram+ve and Gram-ve bacteria. Poly microbial Unknown aetiology Super infection; Cl. Difficile Cefapime Gram +ve Gram -ve Anaerobes Narrow Drugs that are active only against limited range of bacteria. Minimal disruption of normal flora Not suitable for blind therapy Penicillin G Gram +ve only

Def Pros Cons Example

Bacteriostatic Vs. Bactericidal Bacteriostatic The level of anti-microbial activity that inhibits the growth of an organism. In vitro, testing a standardized [] of an organism against a series of antimicrobial dilutions. Minimum Inhibitory Concentration (MIC): Lowest conc. That inhibits the growth of an organism. Halt growth. Macrolides Tetracyclins RMSH Bactericidal The level of anti-microbial activity that kills the organism. In vitro, testing a standardized [] of an organism against a series of anti-microbial dilutions. Minimum Bactricidal Concentration (MBC): Lowest conc. That kills 99.9% of the organism population. Kills bacteria. Irreversible Penicillin G Gentamicin 2012

Def Determination

Measurement

MOA Example

Microbiology Time dependant Vs. Concentration dependant

Antibiotics

IC1

Time Dependant Increase amount of time the antibiotics bind to microorganism. t>MIC Penicillin Cephalosporin Carbapenem Monobactams

Concentration Dependant High conc. At the binding site which eradicates the microorganism. Peak>MIC Aminoglycosides Fluroquinolones Ketolides

Antibiotics Combination: WHY? WHEN? TYPES.. Antibiotics Synergism Combination of antibiotics that have enhanced bactericidal activity when tested together compared with the action of each of them separately. Aminoglycoside + -lactams e.g. Pseudomonas infections Ampicillin + Gentamicin Penicillin + Gentamicin Vancomysin + Gentamycin Enterococcal endocarditis Viridans streptococcal endocarditis Staphylococcal bacteremia Antibiotics Antagonism 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. -lactam + -lactam 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. 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)

RMSH

2012

Microbiology

Antibiotics

IC1

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 Lowest conc of an Ab required to inhibit the growth of a bacterium. 1) Variable conc of Ab in broth or in agar. 2) Ab serially diluted. 3) When bacteria stop growth then MIC. E test An agar based quantitative susceptibility test. 1) A stripe with 2 folds serial dilution of an Ab in an agar. 2) Where smallest clear zone = MIC.

1) Cellulose disk with standard amount of Ab on an agar plate. 2) Ab diffuses into agar and zone sizes reflect susceptibility or resistance.

Easy to do. Cheap. Tests 4-6 agents @ one time. Not quantitative.

Determines MIC of selected organism. Detect changes in susceptibility. One Ab only per test.

Enables MIC values to be estimated directly.

One Ab only per test.

RMSH

2012

Microbiology Antibiotics Use:

Antibiotics

IC1

RMSH

2012

Microbiology Mechanism of Action:

Antibiotics

IC1

MOA Inhibition of cell wall synthesis

Detailed Affect cross linking of peptidoglycan strands and bacteria die by lysis. Bind to acyl-D-alanyl-D-alanine and block prolongation of peptidoglycan backbone. Activity limited to Gram-positive organisms only. Interfere with supercoiling of bacterial DNA by inhibiting DNA gyrase and topoisomerase. Affects RNA polymerase so transcription of genetic code cannot occur. Breakage in the DNA. Inhibition of binding of tRNA to 30-S ribosome. Inhibition of binding of tRNA to 50-S ribosome. Inhibits microbial chemical pathways. Blockage of folate metabolism. Blocks 2 steps in folate metabolism. RMSH

Example -lactams: Penicillin Cephalosporin Carbapenem Glycopeptides: Vancomycin

Inhibition of nucleic acid synthesis

Quinolones: Ciprofloxacin Rifampicine

Inhibition of protein synthesis

Anti-metabolites

Metronidazole Gentamicin Tetracycline Macrolides Clindamycin Trimethoprim Sulphamethoxazole Isoniazid Sulfonamide Trimethoprim

2012

Microbiology Commonly Used Antibiotics: Spectrum: Broad Benzylepenicillin Gram +ve cocci Staphylococci Streptococci Clostridia Some Gram ve cocci Neisseria Meningitis Endocarditis Cellulitis Safe

Antibiotics

IC1

Ab Bacteria

Narrow Ampicillin Amoxycillin Gram ve bacilli E-coli H. influenza

Used in

UTI Resp. tract infection

Adv

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) 1st Properties Good Gram +ve activity. Orally active. Gram +ve & -ve. Oral & IV Good Gram -ve activity Less Staphylococcal activity. Has streptococcal activity. Used for Resp. tract infections. UTI. Resp. tract infections. Surgical prophylaxis. Meningitis. Health care associated infections (HCAI). Example Cefaclor

2nd 3rd

Cefuroxime Cefotaxime

IV only: Examples Aminoglycosides.. Gentamycin Amikacin Streptomycin Properties Gram -ve bacilli. Injection only, not absorbed when given orally. Used for Gram -ve septicaemia. In combination for Intraabdominal infection. Endocarditis. S/E Toxicities Renal Ototoxicity

RMSH

2012

Microbiology

Antibiotics

IC1

Others: Class Quinolone Ciprofloxacine Levofloxacin Moxifloxacin Metronidazole Properties Anti Gram -ve. New, anti Gram +ve also. Used in ICU pts Cystic fibrosis

Anti-protozoal Anti-anaerobic

Trimethoprim Glycopeptides Vancomycin Teicoplanin Macrolides Erythromycin Clarithromycin

May be combined with sulphonamide (co-trimoxazole) Narrow Spectrum Gram +ve only

Used in combination with other Ab for Prophylaxis (bowel surgery) Abdominal sepsis UTI Pneumocystis carinii MRSA (I/V not orally) C. difficile (oral not I/V) 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.

RMSH

2012