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Antimicrobial Therapy Unwanted Effects

This comprehensive overview explores the complexities of antimicrobial therapy, focusing on unwanted effects such as hypersensitivity reactions, toxicity, and the emergence of drug resistance. Hypersensitivity reactions, particularly common with penicillins, can lead to serious risks including anaphylaxis. The potential for superinfections during treatment is also discussed, emphasizing the impact of antibacterial drugs on normal flora. Furthermore, the mechanisms of microbial resistance and the genetic origins of resistance are examined, highlighting the pressing issue of drug-resistant pathogens in modern medicine.

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Antimicrobial Therapy Unwanted Effects

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  1. Antimicrobial TherapyUnwanted Effects

  2. 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

  3. 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

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

  5. 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

  6. SuperinfectionsBacteriological 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

  7. 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

  8. 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

  9. 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

  10. Acquisition of antibacterial resistance • Horizontal transmission • exchange of DNA between non-replicating microbes • Does not require bacteria to be of same species

  11. Acquisition of antibacterial resistance • Conjugation • plasmid - resistant gene or genes • copied and transferred to another microbe via sex pilus

  12. Acquisition of antibacterial resistance • Conjugation

  13. Acquisition of antibacterial resistance • Transduction • spread by viruses which infect bacteria - bacteriophages • Transfection • uptake of DNA from dead bacteria

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