Antibiotics

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  • Words: 405
  • Pages: 28
Faculty: Dr. Alvin Fox

Key Words Sterilization/disinfection/antisepsis

Bacitracin

Antibiotic

Vancomycin

Selective toxicity

beta lactam

Bactericidal

Penicillins

Bacteriostatic

Cephalosporins

Minimal inhibitory concentration (MIC) Monobactam Susceptibility testing

Clavulinic acid

Penicillin binding proteins

Penicillinase/beta lactamase

Autolysins

Polymyxin B

Cycloserine

Resistance

STERILIZATION • All killed • non-selective

Sterilization • autoclaving – 121oC (heat/pressure) * Heat resistant materials

• ethylene oxide – –

Non heat resistant usually equipment

– –

surfaces (e.g operating rooms) not totally effective

• ultra-violet light

Membrane filters

pores bacteria

Disinfection • Liquids that kill bacteria – e.g. phenol based – too toxic for skin surfaces

Antiseptics • Topical (e.g. skin) – e.g. iodine or 70% alcohol – “reduce” bacterial load

ANTIBIOTICS • Selectively toxic for bacteria – bactericidal (killing) – bacteriostatic (growth inhibition) • no harm to patient

Antibiotics • destroy structures – present in bacteria – not present in host

Antibiotics work together with immune system

Minimal inhibitory concentration • lowest level stopping growth • e. g. zone of inhibition around a disk impregnated with antibiotic

• Antibiotics that inhibit cell wall biosynthesis are bactericidal • Without cell wall, osmotic pressure causes bacteria to burst

Peptidoglycan synthesis Cytoplasm

Cell Membrane undecaprenol

sugar amino acid

Cell wall

Cycloserine

– – –

alanine (ala) analog inhibits conversion of L-ala to D-ala inhibits formation of D-ala-D-ala

Cycloserine Analog of alanine

Cytoplasm

X X

sugar amino acid

X X

Bacitracin • Inhibits dephosphorylation

Bacitracin Cell membrane undecaprenol

P P

Vancomycin • binds to D-ala-D-ala • inhibits cross-linking

Vancomycin Cell wall

Beta lactam antibiotics • • •

penicillins cephalosporins monobactams

• inhibit penicillin binding proteins • stop cross-linking

Beta lactams Cell wall

Penicillin binding protein

Cross-linking of peptidoglycan

STRUCTURE OF PENICILLIN O C

S NH

CH O

C

CH N

CH3 C CH

CH3 COOH

Site of penicillinase action. Breakage of the  lactam ring.

Attached to lactam ring • penicillins – 5 membered ring

• cephalosporins – 6 membered ring

• monobactams – no second ring

Chemical modifications change biological activity • Early lactam antibiotics – inactive against Gram negative bacteria • no penetration of outer membrane

Resistance mechansims • Produce beta lactamase (penicillinase) – destroys antibiotic • modified penicillin binding proteins – don’t bind antibiotic

• modified porins – no internalization of antibiotic

Clavulinic acid • beta lactam • binds strongly beta lactamases – inhibits activity

Polymyxin B • binds

– lipid A – phospholipids

• disrupts outer membrane, Gram negative bacteria • toxic to human cells

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