Antimicrobial Therapy Unwanted Effects

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Antimicrobial TherapyUnwanted Effects
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Hypersensitivity Reactions

• Response of immune system
• Drug molecules or metabolites act as allergen
• Trigger antibody response
• Exposure to drug after previous sensitisation can
  lead to more serious reactions even life
  threatening

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Hypersensitivity Reactionsincidence

• Most often seen with penicillins
• incidence has been reported as high as 10
• Cross-reactivity
• allergy to one penicillin likely to herald
  allergy to others
• up to 10 incidence of cross-reactivity to
  cephalosporins

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Hypersensitivity Reactionspresentation

• Rashes
• maculopapular. urticarial
• Fever
• Bronchospams
• More serious skin reactions
• Anaphylaxis ( incidence has been reported up to
  0.04)

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Toxicity

• Can occur with any drug
• Particularly concern when administering drugs
  with low therapeutic index
• minimum therapeutic concentration near to maximum
  non-toxic dose
• And toxicity profile of drug
• examples
• Gentamicin
• Vancomycin, teicoplanin

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Superinfections Bacteriological or clinical
evidence of new infection developing during
chemotherapeutic treatment of a primary infection

• Antibacterial drugs affect normal flora
• gastro-intestinal
• genito-urinary
• Reduction of competitive stress
• Increased opportunity for pathogenic colonisation

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Antimicrobial Drug Resistance

• Characteristic acquired by microbe
• Genetic in origin
• Resistance to agent which previously exerted a
  negative effect on growth or survival of microbe
• Particularly problem with bacteria and viruses
• Can acquire multi-drug resistance

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Mechanisms of resistance

• Microbe produces enzymes which inactivate the
  drug
• Changes that prevent entry of drug into microbe
  or which pump out drug faster than entry
• Alteration in target molecule that reduce
  target-drug affinity
• Evolution of metabolic pathways that overcome
  effect of drug

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Acquisition of antibacterial resistance

• Spontaneous mutations
• change in bacterial DNA which confers resistance
• spread by vertical transmission
• mutation passed on to all daughter cells
• Resistance of mycobacterium tuberculosis to
  anti-tubercular therapy

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Acquisition of antibacterial resistance

• Horizontal transmission
• exchange of DNA between non-replicating microbes
• Does not require bacteria to be of same species

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Acquisition of antibacterial resistance

• Conjugation
• plasmid - resistant gene or genes
• copied and transferred to another microbe via sex
  pilus

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Acquisition of antibacterial resistance

• Conjugation

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Acquisition of antibacterial resistance

• Transduction
• spread by viruses which infect bacteria -
  bacteriophages
• Transfection
• uptake of DNA from dead bacteria

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Tutorial work

• What can the healthcare practitioner do to limit
  the development of antimicrobial drug resistance?