Question

Case study: TB Bacteria are capable of developing resistance to antibiotics because they can divide rapidly. Physicians may prescribe a combination of more than one antibiotic to combat antibiotic resistance. For example, patients diagnosed with active tuberculosis are given a combination of isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin for 6 months However, antibiotic resistant strains still emerge for the following reasons: when patients do not complete their full course of treatment; when health-care providers prescribe the wrong treatment, the wrong dose, or wrong length of time for taking the drugs; when the supply of drugs is not always available; or when the drugs are of poor quality. How does taking a combination of drugs (for the appropriate amount of time) avoid development of antibiotic resistance? Why might the quality of the drugs influence the development of antibiotic resistance?

Answer 1

Antibiotic resistance is a serious problem today.

Antibiotic resistance in bacteria can be of two types:

Intrinsic resistance – Resistance of the bacterium against a drug which is intrinsically represented in its genome by nature.

For example, the thick mycolic acid coat around mycobacterium, efflux mechanisms in the membrane which transport the drug out, production of drug degrading enzymes like beta lactamase enzyme against beta lactam antibiotics and many more.

Acquired resistance:

This is the resistance acquired by horizontal transfer of drug resistant genes from other bacteria or spontaneous mutations.

There are many principles behind using combination of drugs to combat microbes.

Drugs may act synergistically i.e. one drug potentiates the effect or concentration of the other drug by facilitating its action or inhibiting its metabolism.

Sequential blockade where the combined drugs block sequential steps in a reaction producing important metabolites for the bacterium.

Further the mutation rates in bacteria vary with drug combination.

Adequate dose is important to attain certain levels of concentration inside the bacterial cell which is required to bring about the desired affect.

Adequate duration of treatment is essential to wipe out the bacterial population completely.

If the dosage is ineffective to kill the bacteria or the duration is inadequate to completely wipeout the population then few survivors will remain on which high selection pressures operate. They undergo spontaneous mutations to develop resistance. This will lead to drug resistance which will be spread eventually to the entire community.

Thus combination of drugs with adequate dosage and adequate duration are important to avoid development of resistance.

As mentioned already, if a drug is of poor quality it will be ineffective in killing the bacteria and wiping out their population. The adverse environment created by the drug will force the bacterium to develop features which will ai its survival. Thus leading to rug resistance.

Hence quality of drugs is very much important in preventing development of resistance.