Common Antibiotic questions and topics

Kernicterus and sulphonamides displacement of bilibrubin from albumin

Hepatic coma and formation of ammonia use of non-absorbable antibiotics such as neomycin

Tetracyclines

• 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
  
  
• 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 PBPs on cell wall with gonococcus

Transduction: a viral bacteriophage (invades bacteria) carries DNA material (e.g. plasmids producing beta lactamase in resistant staph aureus) from one bacteria to another, thus transferring resistance

Transformation: bacteria picking up free DNA in the environment and incorporating it into the genetic code

Conjugation: 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)