Question

Design a strategy to treat a MDR-bacteria-infected patient using one of the drugs other than penicillin or its derivatives (other beta-lactams are OK).

a)     What is your drug?

b)    What is the basic structure of your drug?

c)     What is the cellular target of your drug?

d)    What is its relative half-life?

e)    What side effects does your drug have?

Answer 1

a) Vancomycin- this drug is extensively used to treat MDR.

b) Basic structure of drug (vancomycin)- it is tricyclic glycosylated nonribosomal peptide produced by the Actinobacteria species Amycolatopsis orientalis.

c) CELLULAR TARGET OF THE DRUG- It is a glycopeptide antibiotic which is used for the treatment of serious infections caused by Gram-positive pathogens. Vancomycin inhibits cell wall biosynthesis by targeting the d-Ala-d-Ala terminus of peptidoglycan layer which leads to inhibition of the transpeptidase, which prevents further elongation and cross-linking of the peptidoglycan matrix.

• Vancomycin also inhibits transglycosylase (glycosyltransferase), a second enzyme responsible for cross-linking sugar residues, although this appears to be a less important mechanism compared to inhibition of transpeptidase.

d) Half-life of drug-  The half-life of vancomycin from plasma is 4 to 6 hours.

e) side effects of drug-

• Phlebosclerotic means it is irritating to tissue.
• Nephrotoxicity (rare with current preparations; increased risk if giving with other nephrotoxic drugs such as aminoglycosides).
• Ototoxicity- (it is rare but increased risk if giving with aminoglycosides).
• Hypersensitivity (maculopapular skin rash.)
• Hypotension & “Red Man Syndrome” (flushing due to histamine release).