Common Antibiotic Questions and Topics
Transcript of Common Antibiotic Questions and Topics
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Common Antibiotic questions and topics
Kernicterus and sulphonamides displacement of bilibrubin from albuminHepatic coma and formation of ammoniause of non-absorbable antibiotics such as neomycinTetracyclines
GIT absorption (chelate other compounds, eg Ca++, Mg++, Fe++ give before meals)
in renal failure (use doxyclcine: excreted by GIT)
Resistance developing in aminoglycosides
Enzyme degradation amikacin is less susceptible vs tobramycin vs gentamicin
Mechanism of action of antibiotics
aminoglycosides bind to the 30S ribosomal subunit and disrupt bacterial protein
synthesis by misreading of the mRNA template
chloramphenicol binds to the 50S subunit
floxacins (cipro-, nor-, o-) DNA gyrase inhibition (DNA Helix). The double helix must
separate and unwind for replication and the separated strands tend to supercoil ahead of
the separation. Bacterial DNA gyrase imposes a negative supercoil to prevent this
happening. When gyrase is inhibited the process does not function and cell replication is
affected. No effect on cell wall
penicillins and cephalosporins bind to various penicillin binding proteins (PBPs) linked
to a transpeptidase which is inhibited. As this is necessary for the fourth (last) step of
peptidoglycan synthesis in the bacterial cell wall, the cell wall is thus defective and is
autolysed
sulphonamides : synthesis of folic acid from PABA (sulphonamides are analogues of
para amino benzoic acid) only in bacteria that must generate their own folic acid.
Bacteria (and humans) who can use preformed folate are not affected
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tetracyclines bind to the 30S subunits of bacterial ribosomes
trimethoprim : dihydrofolate reductase inhibitor (next step along) therefore synergistic
with sulphonamides
vancomycin inhibits the third stage of bacterial wall peptidoglycan synthesis thus
causing disruption (see penicillin)
Should patients with penicillin hypersensitivity be given cephalosporins
Immunological cross reactivity is seen in up to 20% of patients with penicillin hypersensitivity.
Clinical cross reactivity only seen in 1%. Patients with a mild penicillin reaction may probably be
given cephalosporins safely. Patients with recent severe immediate reactions should probably
NOT be given cephalosporins
Mechanisms of bacterial resistance to antibiotics
Mutation: naturally occurring resistant species e.g. difficulty in antibiotic gaining access to PBPson cell wall with gonococcusTransduction: a viral bacteriophage (invades bacteria) carries DNA material (e.g. plasmidsproducing beta lactamase in resistant staph aureus) from one bacteria to another, thustransferring resistanceTransformation: bacteria picking up free DNA in the environment and incorporating it into thegenetic codeConjugation: transfer by bridges between bacteria of genetic material conferring resistance.Mainly in gram negative bacteria and can take place in the GI tract.(see also recent Standing Medical Advisory Committeee The Path of Least Resistance DOH
8/98)