Question

Treatment of mycobacterial infections generally entails a four- to nine-month antibiotic regimen. How is the length of treatment connected to the fact that mycobacterial species tend to grow very slowly?

Answer 1

Since slow growing mycobacteria are extremely hard, drug treatment phase are extremely long. Many species of mycobacteria can become "inactive" for long periods of time, i.e. they do not metabolise. Antibiotics can only be effective, if that bacterium is metabolising. To completely eradicate a mycobacterial infection with antibiotics requires long course of time, enough to act against hibernating as well as active bacteria.

example: An in vitro system provides evidence that various stages occur in the 'shiftdown' and 'shiftup' of M. tuberculosis as the organism enters and exits dormancy.

During the 'shiftdown', the organism apparently goes through two or more stages.

First stage- The organism shifts from rapid to slow replication.

Second stage- A complete shutdown of replication of the organism (dormancy).

During the 'shiftup' process, production of ribonucleic acid (SNA) occurs, followed by the initiation of deoxyribonucleic acid (DNA) synthesis. During dormancy, the metabolic events that occur serve a completely different purpose, suggesting that targets for optimal therapy would be different in an active and dormant disease state and would therefore require different antimicrobics and therapeutic regimens.

Antimycobacterial agents may be divided in two major groups.

The first group consists of antimycobacterials are prodrugs that require some type of activation by the mycobacteria. A prodrug is a compound that is converted to an active derivative by biotransformation or non-enzymatic processes such as hydrolysis, oxidation or reduction. The targets used by these antibiotics are generally involved in the synthesis of unique structures found in the cell envelope of mycobacteria, including mycolic acid, arabinogalactan and lipoarabinomannan.

The second group consists of antimycobacterials have a broader spectrum of activity that do not require activation by mycobacteria. These compounds affect a specific target, such as an enzyme in a metabolic pathwayor a subunit on the bacterial ribosome.

so, the treatment using mixed drugs on mycobaterial infections takes long course of time to completely eradicate the slow growing species.

1. Barrow, Treatment of mycobacterial infections (2001),Rev. sci. tech. Off. int. Epiz., 20 (1), 55-70