How Do Antibiotics Work

The development of antimicrobial drugs represents one of the most important advances in the medicinal sciences. Many infectious diseases which were once considered lethal or untreatable are now easily treated with antimicrobial drugs. These drugs are important not only in the cure of serious infections but in the prevention of infectious diseases as well. Amongst antimicrobial agents, antibiotics have drastically changed modern medicine and extended the average human life by 23 years.¹

What are antibiotics

Antibiotics are antimicrobial drugs that are active against different bacteria and are useful in treating and preventing bacterial infections in humans, animals, and plants. Bacteria are microorganisms that are present everywhere and can cause multiple types of infections, eg. In humans, these bugs may cause pneumonia, tuberculosis, urinary tract infections, meningitis, gastrointestinal infections, typhoid, etc. Antibiotics act by either killing the bacteria or stopping them from reproducing and spreading. Many modern medical procedures, including surgeries, cancer treatment, open heart surgeries, and organ transplants, are made possible and successful due to antibiotics.² 

History of antibiotics

The introduction of antibiotics is one of the greatest medical breakthroughs of the 20^th century. The period between the 1950s and 1970s is considered a golden era for the discovery of new and novel antibiotics.³ Amongst these, penicillin announced the dawn of the antibiotic age. It was discovered by a Scottish scientist Alexander Fleming, Professor of Bacteriology at St. Mary's Hospital in London. In 1928, upon returning from his vacation, Dr. Fleming found a contaminated petri dish with mould (Penicillium) that killed surrounding bacteria. Realising its potential, Fleming identified the mould as the source of a powerful antibiotic, penicillin, revolutionising medicine and paving the way for the era of antibiotics. In the 1940s during World War II, the United States played a major role in developing large-scale production of this drug.⁴ Most of the antibiotics currently used are produced in nature by soil bacteria and fungi. Interestingly, the majority of antibiotics are derived from Streptomyces (a class of bacteria ) isolated from soil samples.⁵

Courtesy Pexels

Since the discovery of penicillin, a large number of antibiotics have been discovered. The following table shows examples of some important antibiotics that have significantly changed the outcomes of bacterial infections: ^6,1

How do antibiotics function?

Antibiotics target bacteria and not human cells. This selective attack is because of major differences between human and bacterial cell structures. eg. bacteria have cell walls and human cells don’t, bacterial enzymes are different from human cells. Antibiotics aim to disrupt the life processes of bacteria without harming the cells of the human body. Once effective concentration builds up in the body, antibiotics work by interfering with bacterial replication and growth.

How do we classify antibiotics?

Antibiotics can be classified by their mechanism of action and antimicrobial spectrum of activity. Spectrum-based classification

The “antimicrobial spectrum of activity” means the range of bacteria an antibiotic can kill or inhibit, and based on this, antibiotics can be either narrow spectrum or broad spectrum. Scientists have broadly categorised bacteria into gram-positive (gm+) and gram-negative (gm-), depending upon the colour they take after being stained with special chemicals. This procedure is called gram staining. Bacteria pick up this stain colour depending on the thickness of their cell wall.⁷

• Narrow-spectrum antibiotics

These antibiotics target a specific type of bacteria eg penicillin G mostly covers gm+ bacteria, isoniazid is specifically used for Mycobacterium Tuberculosis and metronidazole is used for anaerobes causing GIT infections.

•  Broad-spectrum antibiotics

Antibiotics that inhibit or kill a broad range of bacteria are termed broad-spectrum antibiotics. Aminoglycosides are broad-spectrum, bactericidal antibiotics primarily for infections caused by gram negative pathogens. Other examples are amoxicillin, ceftriaxone, and ciprofloxacin, which are used against both gm+ and gm- pathogens.     

Courtesy Unsplash

Mechanism-based classification

Antibiotics are divided into four main groups according to their mechanism of action:

1. Antibiotics that interfere with cell wall synthesis of bacteria

Cell wall synthesis inhibitors represent the most successful and exclusive group of antibiotics. Important examples of this group include β-lactams antibiotics (penicillin, cephalosporin) and glycopeptide antibiotics (vancomycin). These drugs interfere with the synthesis of peptidoglycan cell walls, which provide rigidity and stability to the organism. In the absence of a cell wall the cell bursts due to high pressure from within the cell. Hence all the cell wall synthesis inhibitors are bacteriocidal.⁸

                                             Created by Shazia on PowerPoint

The following table shows examples of important cell wall inhibitors and their spectrum of activity.

2. Antibiotics that interfere with the protein synthesis of bacteria

These antibiotics represent another important group of antibiotics, eg. aminoglycosides, tetra cyclins, macrolides, chloramphenicol, and streptogramin. These drugs stop or slow the growth or production of cells by interfering with the processes that lead directly to the generation of new proteins.⁹ Bacterial proteins are responsible for several vital functions like respiration, metabolism, nutrient uptake, motility and cell attachment. Among these only Aminoglycosides are bactericidal and the rest are bacteriostatic. 

The following table shows different subgroups of protein synthesis inhibitors and their clinical uses:

Created by Shazia on PowerPoint

3. Antibiotics that interfere with the DNA synthesis of bacteria

Fluoroquinolones are the antibiotics that block bacterial DNA synthesis by inhibiting bacterial enzymes (topoisomerase II and topoisomerase IV) involved in this process. Inhibition of these enzymes interferes with the separation of replicated chromosomal DNA into the respective daughter cells during cell division.¹⁰ The drugs are bactericidal and effective mainly against gm- bacteria causing UTI, pneumonia, and sexually transmitted diseases (STD).

Created by Shazia on PowerPoint

4. Antibiotics acting as antimetabolites

Sulphonamides are an important class of antibiotic drugs with a wide range of activity. These antibiotics are effective against gm+ and certain gm- bacteria. Sulphonamides are useful for the treatment of tonsillitis, septicemia, meningitis, dysentery, and urinary tract infections. These drugs, referred to as antimetabolites, interfere with the synthesis of folic acid which is vital for the reproduction of DNA in the bacteria. This group is commonly used in skin and soft tissue infections, burns, urogenital, gastrointestinal, and respiratory tract infections.¹¹

The following flow chart shows different types of sulfonamides.

General side effects of antibiotics

• Nausea
• Vomiting
• Diarrhoea
• Allergic reactions eg. As mild as rash to as serious as anaphylactic shock
• Dizziness
• Fatigue
• Superinfections (especially with broad-spectrum antibiotics)

Phenomena of antibiotic resistance 

The major problem threatening the continued success of antimicrobial drugs is the development of resistant organisms. Since the start of the antibiotic era, antibiotic use in patients and animals has fuelled a major increase in the prevalence of drug-resistant pathogens. The number of deaths directly linked to antibiotic-resistant infections has risen to more than 1.2 million globally in 2019. It is estimated that by 2050 if no proper measures are taken, up to 10 million people will die annually from infections with antibiotic-resistant pathogens. This is one of the biggest challenges facing modern medicine worldwide and is acknowledged by the WHO as a major global health crisis.¹² 

Kevin Outterson said: "Every antibiotic we count on now will be destroyed or significantly impaired by resistance”. To combat antibiotic resistance, changes need to be made by prescribing clinicians and policymakers.

FAQ

1. How quickly do antibiotics work?

The time during which antibiotics work varies depending on the specific antibiotic used, the type of infection, and individual factors like the liver and kidney function of the patient. Some antibiotics may start to alleviate symptoms within a day or two, while others may take longer. The important aspect to keep in mind is to complete the full course of antibiotics as prescribed by a doctor. You may feel better but you must complete the course. Failure to complete the full course may lead to antibiotic resistance.¹³

2. Are antibiotics effective against viral infections?

Antibiotics don’t work against viruses. Viruses may cause infections like colds, flu, or COVID-19. Even for sinus infections, you don’t need to take antibiotics. When antibiotics aren't needed, they won't help you, and the side effects could still cause harm.¹⁴

3. How do we know which antibiotic is suitable for which infection?

Each antibiotic is effective only against certain bacteria hence the choice of antibiotic depends on:

• Which infection you have and which type of bacteria is suspected of causing that infection
• The type of antibiotic also depends upon the results of the culture and sensitivity tests
• Selection of antibiotics also depends upon the age of the patient
• Other factors like liver and kidney function also matter¹⁵

Summary

Antibiotics are antimicrobial drugs that work against bacteria and are used to treat and prevent bacterial infections. These drugs have played a revolutionary role in the treatment of infectious diseases. Antibiotics are grouped based on their antimicrobial spectrum and their mechanism of action. They work by interfering with different functions of bacteria e.g. by stopping the cell wall or DNA synthesis of bacteria, by preventing the protein synthesis of bacteria, and by tampering with the availability of essential nutrients for bacteria. Antibiotic resistance is a major public health problem globally. Responsible use and following medical guidance help to prevent antibiotic resistance and ensure their continued effectiveness.