Antimicrobials part 1

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Antimicrobials part 1

• Antibiotic resistance whenever man comes up
  with a better mousetrap, nature comes up with a
  better mouse.

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Antimicrobial Eras

• Pre-antimicrobial era
• - death from simple infections (pneumonia,
  childbirth)
• Antimicrobial era
• - 1940s onwards (1929 Fleming, 1935 Sulpha,
  1940 Florey)
• - decrease in MORBIDITY and MORTALITY but NOT
  an elimination.
• A post antimicrobial era?
• - antibiotic resistance is a worry.

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Source of Antimicrobial Agentsout of the earth
shall come thy salvation

• Major source is other microorganisms.
• - penicillin and Penicillium fungus.
• - gentamicin and Micromonaspora fungus
• Search strategies
• Semisynthetic and synthetic antibiotics

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Selective Toxicity

• Must kill or inhibit microbe with minimum damage
  to host.
• - fundamental property and major limiting
  factor.
• Drug acts on unique metabolic pathway of microbe.
• humans
• fungi Eukaryotes
• parasites
• viruses Claytons Eukaryotes
• bacteria Prokaryotes - side effects

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Antimicrobial Therapy

• HOST
• antibiotic microbe IMMUNE
• SYSTEM
• Antibiotics AUGMENT rather than replace the
  normal recovery process
• Recovery from fulminant infection - decrease
  mortality.
• Expedite recovery - decrease morbidity.
• Prophylactic use - prevent infection

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Choice of Antibiotic eenie, meenie, myni, mo ?

• Ampicillin, cephalexin, septrin, flagyl,
  cefotaxime, flopen, tetracycline, biaxsig,
  cefaclor, ticarcillin OR gentamicin ?
• WELL over a hundred to choose from
• pharmacology
• CONSIDER host factors
• microbial factors
• Small selection - personal choice.
• One suitable - No choice.
• NONE suitable - No Hope.

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Pharmacological Properties

• Spectrum - narrow or broad
• - cidal or static
• - therapy or prophylaxis
• - effect on normal flora
• Site of infection - drug penetrataion
• - toxicity
• Route of administration - topical, oral, IM, IV,
  other
• Dosage - frequency, 1/2 life, compliance
• Cost - who decides / who pays
• - PBS, generic drugs

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Route of administration
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Microbial factors

• Sensitive S - microbe is inhibited.
• Resistant R - microbe unaffected.
• Resistance EITHER - intrinsic and predictable.
• OR - acquired and unpredictable
• mutation transfer

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Microbial FactorsSelective pressure

• Mutations that render bacteria resistant to
  antibiotics are random, BUT antibiotic use
  provides the selective pressure that allows
  mutants to become dominant.

No antibiotics
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Source of Selective Pressureuse and abuse of
antibiotics
Only 7 of human use

• Hospitals
• General Practice
• Animals - agriculture, aquaculture.
• - treatment and growth promotion
• Horror stories - animal bugs to us x 2
• - chicken faeces, fish farms, triclosan

Most for respiratory infections

• - vancomycin avoparcin
• 193 kg 125 000 kg

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Microbial factors continued

• pharmacology
• CONSIDER host factors
• microbial factors
• Lets treat this infection - 2 questions
• - what organism ?
• - is it S or R
• Specimen for culture and sensitivity
• Emperical therapy - most likely organism
• - normally S to.
• - things to consider ?

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Consequences of antibiotic resistance

• R microbes are NOT more virulent.
• Outcome of infection or exposure is worse IF the
  infection requires antibiotic therapy.
• - bypass prophylaxis
• - emperical therapy fails
• - less suitable antibiotic
• - NO antibiotic

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Problem bugs

• MRSA
• VRE
• Streptococcus pneumoniae
• Pseudomonas aeruginosa
• Tuberculosis