The History of Antimicrobial (Drug) Resistance

Introduction 

Microbes are living organisms that reproduce, thrive, and spread quickly and efficiently increasing their numbers. Microbes include bacteria (Staphylococcus aureus), viruses (colds and influenza, which causes the "flu"), fungi (e.g., Candida albicans, which causes some yeast infections), and parasites (e.g., Plasmodium falciparum, which causes malaria).

Antimicrobial is a general term given to medicines that kill or slow the growth of microbes.

Antimicrobial drug resistance is the ability of a microbe to grow in the presence of a chemical that would normally kill it or limit its growth.

History

In 1928 while working with Staphylococcus bacteria, Scottish scientist Alexander Fleming noticed that a type of mold growing by accident on a laboratory plate was protected from, and even repelled, the bacteria. The active substance, which Fleming called penicillin, was literally an antibiotic—it killed living organisms.

Thus began the age of using natural and, later, synthetic drugs to treat people with bacterial infections. Though not widely popular until the 1940s, antibiotics and other antimicrobials (medicines that kill or slow growth of a microbe) have saved countless lives and blunted serious complications of many feared diseases and infections. The success of antimicrobials against disease-causing microbes is among modern medicine's great achievements.

The Problem

After more than 50 years of widespread use, evolution of disease-causing microbes has resulted in many antimicrobials losing their effectiveness.

As microbes evolve, they adapt to their environment. If something stops them from growing and spreading—such as an antimicrobial—they evolve new mechanisms to resist the antimicrobials by changing their genetic structure. Changing the genetic structure ensures that the offspring of the resistant microbes are also resistant.

Antimicrobial resistance makes it harder to eliminate infections from the body. As a result of a microbe’s ability to survive in spite of antimicrobials, some infectious diseases are now more difficult to treat than they were just a few decades ago. In fact, antimicrobials have helped people so effectively that humans are hurting the protective value of medicines through overuse and misuse. More prudent use of antimicrobials will help to slow the development of resistance.

Causes

Microbes, such as bacteria, viruses, fungi, and parasites, are living organisms that evolve over time. Their primary function is to reproduce, thrive, and spread, quickly and efficiently. Therefore, microbes adapt to their environment and change in ways that ensure their survival. If something stops their ability to spread, such as an antimicrobial, genetic changes can occur that enable the microbe to survive. There are several ways this happens.

Natural [Biological] Causes

Mutation

Microbes reproduce by dividing every few hours, allowing them to evolve rapidly and adapt quickly to new environmental conditions. With each replication, mutations arise, and some of these mutations may help an individual microbe survive exposure to an antimicrobial.

View the illustration: Mutation Causes Drug Resistance

Gene Transfer

Microbes may also acquire genes from each other, including genes that make the microbe drug resistant. 

View the illustration: Gene Transfer Facilitates Drug Resistance

Selective Pressure

In the presence of an antimicrobial, microbes are either killed or, if they carry resistance genes, survive. These survivors will replicate and their progeny will quickly become the dominant type throughout the microbial population.

View the illustration "What is drug resistance?"

Societal Pressures

The use of antibiotics, even when used appropriately, creates a selective pressure for resistant organisms. However, there are additional societal pressures that act to accelerate the increase of antimicrobial resistance.

Inappropriate Use

Selection of resistant microorganisms is exacerbated by inappropriate use of antimicrobials. Sometimes physicians will prescribe inappropriate antimicrobials wishing to placate an insistent patient who has a viral infection or an as-yet undiagnosed condition.

Inadequate Diagnostics

More often, physicians must use incomplete or imperfect information to diagnose an infection and thus prescribe an antimicrobial just-in-case or prescribe a broad-spectrum antimicrobial when a specific antibiotic might be better. These situations contribute to selective pressure and accelerate antimicrobial resistance.

Hospital Use

Critically ill patients are more susceptible to infections and, thus, often require the aid of antimicrobials. However, the heavier use of antimicrobials in these patients can worsen the problem by selecting for antimicrobial-resistant microorganisms. The extensive use of antimicrobials and close contact among sick patients creates a fertile environment for the spread of antimicrobial-resistant germs.

Agricultural Use

Scientists also believe that the practice of adding antibiotics to agricultural feed promotes drug resistance. More than half of the antibiotics produced in the United States are used for agricultural purposes.^{1, 2} However, there is still much debate about whether drug-resistant microbes in animals pose a significant public health burden.

References

1. National Research Council, Committee on Drug Use in Food Animals. The use of drugs in food animals: benefits and risks. Washington (DC): National Academy Press; 1999.
2. Mellon M, Benbrook C, Benbrook KL. Hogging it: Estimates of antimicrobial abuse in livestock. Cambridge (MA): Union of Concerned Scientists; 2001.