Selective toxicity, Minimal inhibitory concentration and Minimal lethal concentration

Selective toxicity: Antimicrobial drugs must have selective toxicity. Selective toxicity means the ability of a drug to kill or inhibit the microbial growth with minimal or no damage to the host cell.

Minimal inhibitory concentration (MIC): It is defined as the lowest concentration of an antimicrobial drug that inhibits the visible growth of microbes after overnight incubation. It can be determined by preparing a solution of a drug at increasing concentration and then incubating it with separate batches of cultured microorganism. After incubation, the result is measured either by agar or broth dilution method.

Minimal lethal concentration (MLC): It is defined as the lowest concentration of antimicrobial drug that kills a particular microorganism.

Broad-spectrum antibiotic and narrow-spectrum antibiotic

On the basis of target specificity, antibiotics are classified into two types:

Broad-spectrum antibiotic: Those antibiotics that attack a wide range of pathogens are called broad-spectrum antibiotic.

Advantages:

They are beneficial when an infection is caused by multiple groups of bacteria or when infection is suspected but the causative organism is unknown.

Limitations:

As they attack many different kinds of pathogens, they kill normal bacteria also. They also aid in the development of antimicrobial resistance. Due to the continuous exposure to the same antibiotic, microbes may develop changes in their structure or function and becomes resistant to the antibiotic.

Examples:

Ciprofloxacin, Ampicillin, Rifampin, Tetracyclines, Chloramphenicol, Amoxicillin, Ticarcillin etc.

Narrow-spectrum antibiotic: They are effective against a specific organism. They are helpful when a known organism causes infection.

Advantages:

As they are effective against a particular organism, they will not kill the normal microorganisms of host body. So, it has less ability to cause superinfection. Also, they will develop less antimicrobial resistance.

Limitations:

They can be used only if causative agent is known.

Examples:

Bacitracin, Dapsone, Gentamicin, Methicillin, Clindamycin, Vancomycin, Azithromycin etc.

Therapeutic Index

The therapeutic index (TI) is the ratio of toxic dose to the therapeutic dose. A chemotherapeutic agent that is used for the treatment must have a toxic dose and a therapeutic dose.

The therapeutic dose is defined as the dose of a drug that is required for the clinical treatment of a particular infection. Whereas, toxic dose is defined as the dose of a drug at which it becomes toxic for the host.

A drug, used for the treatment, must have a toxic effect on organism but not on the host. The larger the TI, the safer the drug will be. A higher TI indicates a significant difference between toxic dose and therapeutic dose. With higher TI, a patient would have to take a much higher dose of the drug to reach the toxic level as compared to the dose required in eliciting the therapeutic effect. If the TI is small, it means the difference between the toxic dose and therapeutic dose is very small. In such cases, the drug needs to be monitored very carefully, as a minor increase in the dose of the drug can make it toxic from therapeutic.

For example, penicillin inhibits bacterial cell wall synthesis and as host cell lacks cell wall, so penicillin does not have an effect on host cell. This indicates that penicillin has high TI. But, if the drug inhibits the same process in the host cell also, it is considered to have low TI.

TI has certain limitations as it is not possible to measure the toxic dose of a drug in humans. Although animal studies help in measuring the toxic dose, it can’t be fully accepted for humans. Nevertheless, TI highlights the significance of the margin of safety, as distinct from the potency, in determining the usefulness of a drug.