Why is triclosan not considered an antibiotic?

Question

Triclosan is a chemical often referred to as a "biocide" instead of an "antibiotic". However, its mode of action seems to suggest that it is an antibiotic.

Triclosan binds to bacterial enoyl-acyl carrier protein reductase (ENR) enzyme, which is encoded by the gene FabI. This binding increases the enzyme's affinity for nicotinamide adenine dinucleotide (NAD+). This results in the formation of a stable, ternary complex of ENR-NAD+-triclosan, which is unable to participate in fatty acid synthesis.

This is nearly identical to the action of many other antibiotics, such as penicillins (inhibits cell wall synthesis enzymes), quinolones (inhibit DNA gyrase) or sulfonamides (inhibit folate synthesis).

In fact, this paper describes the mechanism of resistance to triclosan and notes that it is identical to many antibiotics. Why then, is triclosan not classified as an antibiotic and is still prophylatically used in so many places (such as hospitals)?

Answer 1

I agree with @Chris that this is mostly a matter of definitions -

Greenfacts defines biocides as:

According to the Biocides Directive (98/8/EC), biocidal products are those that are intended to destroy, render harmless, prevent the action of, or otherwise exert a controlling effect on any harmful organism by chemical or biological means. Examples include disinfectants, preservatives, antiseptics, pesticides, herbicides, fungicides and insecticides.

and antibiotics as:

Antibiotics are widely used as medication against disease-causing bacteria. However, bacteria can acquire resistance to particular antibiotics through mutation or gene transfer.

So the key difference is that antibiotics act more specific and may induce resistance. Antiseptics such as alcohol stay active, even after repeated use, because they act broadly. Now that triclosan is argued to have a specific molecular target, it may have to be re-defined from a general biocide to antibiotic. This means that its widespread use may be alarming, and I quote from your linked article (Schweizer, 2001):

[Triclosan is used in a] multitude of health care and consumer products [and has] germicidal properties [and has] flooded the market in recent years in response to the public's fear of communicable bacteria.

<sub>Reference
- Schweizer, FEMS Microbiol Lett (2001); 202(1): 1-7</sub>

Answer 2

Triclosan binds to bacterial enoyl-acyl carrier protein reductase (ENR) enzyme, which is encoded by the gene FabI. This binding increases the enzyme's affinity for nicotinamide adenine dinucleotide (NAD+). This results in the formation of a stable, ternary complex of ENR-NAD+-triclosan, which is unable to participate in fatty acid synthesis.

If you notice, you would see that this mechanism is attributed to low concentrations of triclosan when it acts as a bacteriostatic. Disinfectants, IMO cause direct chemical damage to cell (denaturation of proteins/destruction of the membrane etc) unlike antibiotics which inhibit some vital metabolic processes. Triclosan is generally used in the form of a disinfectant (at high concentrations). Even though its enzyme inhibitory properties have been studied, it is not systemically administered in the form of an antibacterial drug.

The terms antibiotics and bactericidal were coined when mechanisms were not really known. Even then, antibiotic is traditionally known as a substance that is produced by one organism (a fungus in case of penicillin) to prevent the growth of the other.

I would like to differ from Christiaan's opinion that antibiotics are substances against which resistance can be developed. It is possible to acquire resistance towards a conventional, broad spectrum, direct damage agent. For instance there are bacteria that can survive heat/UV/γ-rays (which are physical disinfectants). Microbes can also develop resistance to chemical agents and though I cannot cite an example at the moment, I can think about how the cell can achieve it. One way is to develop a stronger cell wall.
Also note that alcohol is not considered a disinfectant at concentrations < 70%. At much lower concentrations alcohol can actually serve as an energy source.

So I think this is the tacitly accepted definition:

Disinfectants are usually synthetic chemicals that inflict direct damage whereas antibiotics are primarily natural chemicals that inhibit some vital metabolic process.

The term bactericidal or biocidal denotes the consequence rather than the nature of the mechanism. Antibiotics can be bactericidal too. Many herbicides are inhibitors of chloroplastidial metabolism.

Answer 3

I think this is mostly a semantic differentiation, when you look up definitions for antibiotics you can find very narrow which only include the classic and modern antibiotics, while others include almost everything which has an bacteriocidal (or also anti-fungal) effect, regardless of the mechanism.

The Wikipedia article on antibiotics contains the following paragraph, which I find pretty good as a definition:

Sometimes the term antibiotic is used to refer to any substance used against microbes, synonymous to antimicrobial. Some sources distinguish between antibacterial and antibiotic; antibacterials used in soaps and cleaners etc., but not as medicine. This article treats the terms as synonymous and according to the most widespread definition of antibiotics being a substance used against bacteria.