A History of Antibiotics

V. A. Cyr
Mar 5
9 min read

Now that we have reviewed the subjects of Wound Care and Surgery, we will discuss a treatment that is almost always complimentary to those interventions: Antibiotics. What are antibiotics? How do antibiotics help the body fight off infections? This will be a small review of a large subject, including the immune system, transmission of infections, differences between bacteria and viruses, and the history and types of antibiotics.

The Immune System

The immune system is a collection of cells, tissues, and organs that protect the body from infection and disease. Cells that make up the immune system are white blood cells (WBCs), antibodies (bind to bacteria to destroy them), and cytokines (messengers of the immune system). Tissues include bone marrow (creates blood cells) and mucosa (secretes mucus to trap germs). Organs of the immune system are the skin (physical protection), lymph nodes (drain waste from tissues), spleen (stores WBCs and filters blood), tonsils and adenoids (trap invaders in the throat), and thymus (where T-cells mature). The immune system comprises two types of immunity: innate and acquired. Innate immunity is the protection that a person is born with, where a person’s WBCs know what is not part of the body and attacks it. Acquired immunity is protection gained over time from exposure to germs via getting sick or receiving a vaccination (immunization will be a topic for a future blog post).

Diagram of the immune system (Cleveland Clinic, 2023).

White Blood Cells (Leukocytes)

WBCs comprise a portion of the blood, along with red blood cells and plasma (see A History of Bloodwork). There are many different types of WBCs:

Neutrophils are cells that help protect the body by killing bacteria and foreign debris.
Basophils are cells that produce an allergic response to an allergen (e.g., coughing, sneezing, runny nose).
Eosinophils identify and destroy parasites and cancer cells while assisting basophils with the allergic response.
Monocytes defend against infection by cleaning up damaged cells.
Lymphocytes consist of three types of cells: T cells, B cells, and natural killer cells. These protect the body against viral infection and produce antibodies (protein to fight infection).
- T Cells (T-lymphocytes) help recognize and remove infection-causing cells that have invaded.
- B Cells (B-lymphocytes) produce antibodies to help the immune system prepare to fight an infection.
- Natural Killer Cells attack and kill viral cells like cancer.

The types of WBCs, excluding natural killer cells (NIH, 2025).

Infection Transmission

Infectious agents can be transmitted in many ways. We will review how pathogens are transmitted and explain the differences between infectious agents.

Airborne or Aerosol Transmission occurs when the agent is carried in the air. Examples are measles, tuberculosis, and varicella (chickenpox).
Respiratory or Droplet Transmission is brought from person to person via coughing, sneezing or saliva. Examples are the common cold, the flu, and respiratory syncytal virus.
Contact Transmission can occur from physical touching (e.g., conjunctivitis or pink eye, mononucleosis, athletes foot) or sexual contact (e.g., HIV, hepatitis, gonorrhea).
Formite or Surface Transmission (indirect contact) involves the agent being on a surface (e.g., doorknobs, handrails) for a long time and being touched by the person. This can spread infections like norovirus, rotavirus, and influenzas.
Transfusion or Blood Transmission shares blood-borne pathogens via a blood transfusion. Blood-borne pathogens include hepatitis, HIV, and malaria.
Transcutaneous or Vector Transmission introduces the infection through the skin, usually via insect bites. This is how malaria, West Nile virus, and rabies are spread.
Enteric or Fecal-Oral Transmission occurs when someone ingests infectious agents contaminated with feces (e.g., poliomyelitis, norovirus, typhoid) or contaminated food or water (e.g., cholera, E. coli, salmonella).
Vertical or Maternal-Fetal Transmission refers to pathogens passed from mother to baby in utero (via the placenta) or during childbirth (contact with the mother’s reproductive tract). Examples include HIV, rubella, herpes, and the Zika virus.

A diagram showing the most common modes of transmission (contact, formite, droplet, and airborne) (Conly, 2020).

Definitions

Antibiotics are medications used to treat bacterial infections. The word antibiotic comes from the Greek words meaning “against” (anti) “life” (bios). Antibiotics help the immune system by blocking the bacteria from reproducing or killing the bacteria completely. This allows the WBCs to identify foreign cells, destroy them, and clean out the infection from the body. Infections can be caused by bacterial, viral, fungal or parasitic agents.

Bacterial Infections

Bacteria are cells that can live on their own. They are prokacroates, or the simplest form of living cells. Bacteria are single cells that come in various shapes: rods, spirals, or spherical.

Different shapes of bacteria (Cleveland Clinic, 2022).

There are two types of bacteria: Gram-negative and Gram-positive. Gram refers to the testing done on bacteria in the laboratory, indicating the presence of an outer membrane protecting the cell in Gram-negative bacteria. These are more difficult to treat as an extra layer protects them.

An example of Gram-positive (left) and Gram-negative (right) stained bacteria under a microscope (Microbe Notes, 2022).

Bacteria is spread through airborne and contact methods. Bacterial infections include strep throat (streptococcal pharyngitis), whooping cough (pertussis), and urinary tract infections. Antibiotics are the treatment of choice for bacterial infections.

Viral Infections

Viruses are cells that need a host to survive. They are a cluster of genetic material, either DNA or RNA. DNA is short for deoxyribonucleic acid, a double-stranded molecule chain made of nucleotides (adenine, thymine, guanine, and cytosine). RNA is ribonucleic acid with a short, single-stranded chain of nucleotides (adenine, uracil, guanine, and cytosine). DNA can replicate on its own, while RNA cannot.

The differences between DNA and RNA (ThoughtCo., 2024).

The genetic material in viruses is protected by a protein coat and sometimes an envelope of fat. Viruses come in different shapes and sizes, such as spacecraft designs, spirals, cylinders, and balls.

Various shapes of viruses with examples of which virus uses that structure (Laguipo, 2020).

Viruses are not considered living as they cannot reproduce independently (bacteria can). However, they can survive in different environments for long periods. Viruses only replicate once they have entered into a host cell. Viruses are spread via airborne, contact, and vector transmissions. Viral infections include the common cold (rhinovirus), flu (influenza), and SARS-CoV2 (COVID-19). Infections can sometimes be caused by bacterial and viral agents, like food poisoning, sinus infections and ear infections. Antiviral medications treat viral infections, but the body tends to heal itself more quickly than bacterial infections.

Fungal Infections

Fungus is spread through airborne and contact transmission. Examples include athlete’s foot (tinea pedis), vaginal yeast infection (candidiasis), and ringworm (dermatophytosis). Antifungal medications, such as medicated creams or pills, treat fungal infections.

Parasitic Infections

Parasites are transmitted via the enteric route (contaminated soil, water, and food), blood transfusions, and vectors (insects). Examples include malaria and giardia. Antiparasitic medications (pills) treat parasitic infections.

Types of Antibiotics

This portion will cover the history of antibiotics for bacterial infections only. There are many classes of antibiotics. Antibiotics are either bacteriostatic (restricting cell growth and reproduction) or bactericidal agents (causing bacterial cell death). Most of these medications work against Gram-positive microorganisms (e.g., streptococcal, staphylococcal, etc.), and some work against Gram-negative organisms (e.g., pseudomonadota, chlamydiota). Step and staph infections cause a variety of illnesses in people (e.g, bronchiectasis, pneumonia, food poisoning, etc.). Here are the common types and examples of medications with trade and brand names.

Bacteriostatic Agents

Macrolides: azithromycin (Zithromax), erythromycin (Ery-Tab)
Lincosamindes: clindamycin (Cleocin)
Tetracyclines: doxycycline (Vibramycin-D)
Sulfonamides: sulfamethoxazole (Bactrim, Septra)

Bactericidal Agents

Penicillins: amoxicillin (Amoxil)
Cephalosporins: cephalexin (Kelfex)
Aminoglycosides: gentamicin (Garamycin), neomycin (Neosporin)
Glycopeptides: vancomycin (Firvanq)
Fluoroquinolones: ciprofloxacin (Cipro), levofloxacin (Levaquin)
Urinary anti-infectives: nitrofurantoin (Macrobid)

This diagram shows how the bacteriostatic and bactericidal antibiotics work to stop the cells from multiplying or kill the cells (Stokes et al., 2019).

Antibiotic Resistance & Allergies

Resistance to medications has become increasingly more problematic with the over-prescribing of antibiotics for unnecessary ailments. Misuse of antibiotics has led to antimicrobial resistance (AMR), leaving some infections untreatable (Hutchings et al., 2019). Resistance develops quickly; for example, by the 1930s, there was high resistance to salvarsan (Hutchings et al., 2019). A current example commonly seen is methicillin-resistant staphylococcus aurea (MRSA). Every patient who is admitted into the hospital must be tested for MRSA as it is easily transmitted through contact with an infected person.

There is also a rising number of people with “allergies” to certain antibiotics (i.e., penicillin, sulfa). The misdiagnosis of an allergy to an antibiotic has contributed to the higher usage of other broad-spectrum antibiotics and, therefore, AMR.

Allergies are often mistaken for side effects of a medication. An allergy is life-threatening to a person, while a side effect is sometimes uncomfortable but does not mean that the antibiotic is not adequate for them. An adverse effect is an outcome that occurs when the medication is not compatible with a patient; an allergic reaction (anaphylaxis) is an adverse reaction. Some patients are more sensitive to medication, meaning they may only need a smaller dose than someone else. This is why all treatments should be tailored to the individual.

For example, a patient who believes they have an “allergy” to penicillin (Amoxicillin) must avoid all medications in that class. The patient has experienced side effects that are bothersome, and they believe this means they are reacting negatively to the medication. To treat an infection, the healthcare provider may prescribe them a glycopeptide (Vancomycin) instead. However, a medication like Vancomycin is much more potent and can cause many adverse effects (e.g., kidney damage, hearing loss). Educating patients on the differences between side effects, adverse effects, sensitivities, and allergies can help them with future treatment options.

Origins

The principle behind antibiotics comes from practices that existed over 2000 years ago, such as putting mouldy bread into open wounds to treat infections (see A History of Wound Care). Most antibiotics have been created from natural products. For example, the microbes from the Steptomyces family are used to create aminoglycosides and tetracyclines. Microbes from the soil have functions to develop chemical weapons to kill competitors in the soil defensively or offensively (Hutchings et al., 2019).

In the 1910s, the first synthetic antibiotic, salvarsan, was created from arsenic to treat syphillis (Hutchings et al., 2019). The sulfonamides class of antibiotics followed this drug and are considered the first broad-spectrum antimicrobial used in the clinical setting (Hutchings et al., 2019).

Penicillin, a beta-lactam derived from fungi, was discovered in 1928 by Alexander Fleming (Hutchings et al., 2019). This was a massive revolution in the medical world, as fatal diseases became treatable.

The first commercially available antibacterial was Prontosil, a sulfanomide made in the 1930s (Hutchings et al., 2019).

The Golden Age of antibiotics was from the 1940s to the 1960s. Penicillin (Amoxicillin) was introduced on a large scale for treating bacterial infections (Hutchings et al., 2019). Aminoglycosides (Kanamycin A) and tetracyclines (Tetracycline) were found in the 1940s. Macrolides (Erythromycin), fluoroquinolones (Ciprofloxacin), and glycopeptides (Vancomycin) were introduced in the 1950s. The 1960s had the discovery of lincosamides (Clindamycin) and the clinical usage of azoles (Metronidiazole). Many antibiotics found and made during this time are still in use today. However, their effectiveness is lower because of the rise of AMR.

In the 1970s, carbapenems (Meropenem) and mupirocin (Mupirocin) were discovered. The 1980s had lipopeptides (Daptomycin) and monobactams (Azetreonam).

In the 2000s, some previously discovered drugs, like pleuromutilins (Retapamulin) and oxazolidinones (Linezolid), have become clinically available. In 2012, diarylquinolines (Bedaquiline) became available after being discovered in 2004 (Hutchings et al., 2019).

Fewer and fewer new antibiotics are being discovered and tested in clinical trials because of the faltering usage and resistance. There is now more significant time between discovery and clinical usage of the drugs.

Timeline Throughout History: Antibiotics

Antibiotics are comonly used as prophylactic (prevention) for surgery as well as treatment after an infection begins. What antibiotics have you seen or used in your professional or personal lives?

– V. A. Cyr

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