A patient has a severe infection caused by anaerobic bacteria. A junior doctor writes an order for gentamicin. This approach is likely to have unwanted clinical outcomes because anaerobes: (AIPG 2010)
|A||Cannot metabolize the aminoglycosides, which are all prodrug, to their bactericidal free radical forms.|
|B||Cannot oxidatively metabolize aminoglycosides to moieties that are nontoxic to host cells|
|C||Lack molecular oxygen that is a prerequisite for drug binding to the 50S subunit of bacterial ribosomes|
|D||Lack the ability to transport aminoglycosides from the extracellular milieu|
a. Aminoglycosides which are mainly used for parenteral therapy of severe infections from aerobic gram negative bacilli (e.g.,) E. colt, Serratia, Klebsiella), require oxygen in order for the drug to be transported across the bacterial cell membrane.
b. Such incorporation is necessary for these drugs to exert their bactericidal effects, which arise from binding to the 30S subunit of susceptible bacteria. Ultimately the aminoglycoside ribosomal binding leads to premature termination of bacterial proteins) synthesis and the formation of abnormal bacterial proteins. Such abnormal proteins ultimately insert into the bacterial cell membrane, causing leakiness and cell death.
c. The aminoglycosides are not prodrug, and so metabolism (whether aerobic or otherwise) is not necessary for the formation of an active drug; formation of an oxygen free radical or an aminoglycoside free radical has nothing to do with their antibiotic effects.
d. More over, metabolism by host cells not an important process in the elimination of aminoglycosides, nor reducing host cell toxicity (e.g., to the kidneys or auditory nerve). Renal excretion is the main route of elimination for these drugs, which explains why renal function is such an important consideration in dosing adjustments.