028 — How Can Doctors Choose an Antibiotic Before They Know the Culprit?

Antibiotic treatment can begin before the bacterium causing an infection has been identified. So what exactly does a doctor know when choosing the first drug?

Suppose you go to a hospital with a suspected bacterial infection.

A sample can be collected to find out which bacterium is responsible. But cultures and antibiotic susceptibility tests take time. If an infection is serious, or treatment cannot safely be delayed, antibiotics may be started before those results are available.

Think about that for a moment.

The exact culprit is still unknown, yet the weapon has already been chosen.

Most weapons we know require a target. A missile needs coordinates. Yet an antibiotic may be given before anyone knows exactly which bacterium is causing the infection.

Stranger still, this is not simply a blind gamble.

How can you attack an enemy you haven’t identified yet?

The secret is to target features, not names

An antibiotic does not read a bacterium’s name tag before attacking it.

Instead, it targets biological structures and processes that are absent from human cells or sufficiently different in bacteria.

One classic example is the bacterial cell wall.

Many bacteria need to build and maintain a cell wall, while human cells do not have one. Penicillin and other beta-lactam antibiotics interfere with proteins involved in bacterial cell-wall synthesis.

Other antibiotics target bacterial ribosomes.

Ribosomes are the machinery that makes proteins. Human cells have ribosomes too, but bacterial ribosomes are structurally different. Antibiotics such as tetracyclines exploit those differences to interfere with bacterial protein synthesis.

Other antibiotics exploit differences involving DNA replication, RNA synthesis, or folate metabolism.

In other words, an antibiotic does not check an ID card. It looks for biological features that give the suspect away.

It does not ask,

“What’s your name?”

It asks something closer to: “Do you have this structure?” “Do you make proteins this way?”

That is one reason treatment can sometimes begin before the exact bacterial culprit has been identified.

But the doctor isn’t really fighting blind

There is an important twist.

Not knowing the exact bacterium does not mean choosing an antibiotic at random.

Doctors can consider where the infection is occurring, how ill the patient is, which pathogens commonly cause that kind of infection, previous test results, and local patterns of antibiotic resistance.

The culprit’s face may be unknown, but there is already a profile.

You know where the crime happened. You have an idea of which suspects usually appear there. And you may know which weapons are more likely to work against them.

An initial antibiotic can therefore be chosen to cover the most likely bacteria. Once culture and susceptibility results become available, treatment can be changed or narrowed to something more appropriate.

This is the basic idea behind empiric antibiotic therapy.

But this is also where the problem begins

If treatment is not aimed at one precisely identified bacterium, then bacteria that normally live in and on us may also be affected.

The human body is home to vast communities of microorganisms. The gut in particular contains a complex microbial ecosystem. These organisms participate in digestion and metabolism and interact with the immune system in many ways.

A broad-spectrum antibiotic can affect not only the bacterium causing an infection, but also other bacteria that happen to be susceptible to the drug.

Antibiotic treatment can therefore alter the composition of the gut microbiome and, in some people, contribute to side effects such as diarrhoea.

The ability to act before the culprit is precisely identified comes with a trade-off: the biological reach of the treatment may extend beyond the intended target.

And some bacteria survive

Bacteria do not see an antibiotic, think about the problem, and deliberately invent a defence.

In an environment containing an antibiotic, susceptible bacteria may be killed or prevented from growing. Bacteria that already possess resistance, or acquire resistance genes, have a greater chance of surviving.

Those survivors can then reproduce.

And resistance can work in several different ways.

Some bacteria alter the target to which an antibiotic normally binds. Others produce enzymes that destroy or modify the drug. Some reduce the amount of antibiotic that enters the cell, while others use efflux pumps to move the drug back out.

Even more remarkably, some resistance genes can move from one bacterium to another.

Genetic elements such as plasmids can carry resistance genes between bacteria.

The bacteria are not gathering together to teach one another how to defeat antibiotics.

But genetic information that helps bacteria survive can spread through bacterial populations.

So what does an antibiotic actually know about its enemy?

Return to the original question.

How can a doctor choose an antibiotic before knowing exactly which bacterium is responsible?

An antibiotic is not a missile launched only after the culprit’s face has been positively identified.

But neither is it a weapon dropped blindly on everything in sight.

You may not know the culprit’s name, but you can estimate what kind of organism it is and target biological weaknesses associated with it.

Doctors use the location and circumstances of an infection to estimate the most likely range of bacterial causes.

When laboratory results arrive, that range can be narrowed.

Antibiotic treatment can therefore begin with incomplete information and become more precise as new information arrives.