What's Pencillin?

The grandaddy of all antibiotics


Depending on the source, in 1928 or 1929, Sir Alexander Fleming discovered that "mold juice" could kill bacteria on Petri dishes.  Fleming and others at Oxford University then isolated penicillin from this mold juice.  However, because of World War II, the British couldn't produce penicillin in sufficient quantities, so the United States took over production and made penicillin widely available. 

Before the widespread introduction of antibiotics in the 1940s, people would routinely die of pneumonia, septicemia (blood infections), gonorrhea and more.

  The introduction of penicillin heralded the antibiotic age.

Penicillins: definition

Penicillins are either natural or semisynthetic compounds that are composed of a β-lactam (beta-lactam) ring connected to a thiazolidine ring.  Penicillins also have side chains of variable composition.  These side chains determine the antibacterial activity of each individual penicillin.

There are 5 classes of penicillins:

  • natural penicillins (Penicillin G)
  • aminopenicillins (ampicillin)
  • penicillinase-resistant penicillins (think cloxacillin and nafcillin)
  • antipseudomonal penicillins (think ticarcillin)
  • extended-spectrum penicillins (think piperacillin)

Penicillins: mechanism of action

For the most part, penicillins are bactericidal (as opposed to bacteriostatic) and kill bacteria directly without interfering with reproduction.  Thus, penicillins can quickly kill susceptible bacteria.

Specifically, penicillins bind to penicillin-binding proteins (PBPs) which are peptidases (enzymes) in the walls of bacteria.

  When a penicillin has high affinity for a bacteria's specific PBP, it works better. 

By binding to PBPs, penicillins inhibits peptidoglycan assembly and cross-linking and thus disrupt cell wall structure.  These kinks in the bacterial cell wall cause the bacteria to self-destruct (autolysis).

Most bacterial killing occurs during the exponential growth phase of bacteria reproduction.

For the most part, penicillins are active only against gram-positive bacteria. Gram-negative bacteria have a lipopolysaccharide layer or outer membrane which makes it harder for penicillins to breach the cell wall and access the PBPs.

In order to work at all, the penicillin beta-lactam ring must remain intact.  As a main means of resistance, many bacteria have evolved to produce beta-lactamases, an enzyme that rends the penicillin beta-lactam ring and renders it useless.

Penicillins: treatment

Penicillins are available as tablets, capsules, and solutions for injection.  Penicillins are generally well absorbed from the gastrointestinal tract and widely distributed throughout the body.  For the most part, penicillins are excreted in urine.

Although bacterial resistance patterns seriously inhibit the efficacy of penicillins, in many cases, penicillins can be used to treat a variety of infections including:

  • upper respiratory infections like pneumonia
  • urinary tract infections
  • septicemia
  • bone and joint infections
  • meningitis
  • intra-abdominal infections
  • sexually transmitted infections like gonorrhea and syphilis

Of note, penicillins have been used off-label to treat typhoid fever and Lyme disease.

Penicillins: adverse effects

Common adverse effects of penicillins include mild diarrhea, nausea, vomiting, headache and vaginal yeast.  Occasionally, penicillins can cause generalized rash, hives, and more serious hypersensitivity or allergic reactions like anaphylaxis and acute interstitial nephritis.

The best treatment for penicillin allergy is avoidance.  If you experience adverse effects from penicillin use, please tell your physician before she prescribes such medications.

Although true penicillin allergy resulting in anaphylaxis is rare--occurring in 1 to 5 cases per 10,000 cases of penicillin therapy--because cephalosporins share a similar chemical structure with penicillins, people who are allergic to penicillins are usually not prescribed cephalosporins and vice versa.

In 1940--little more than 10 years after its discovery--the penicillin team which helped discover the drug noticed that bacteria in their lab had microevolved to become resistant to penicillins and were already producing penicillinase (beta-lactamase).  Keep in mind that bacterial resistance is ancient and long predated the discovery of antibiotics.

Today, antibiotic resistance is a major public health care concern and is something that we can all help prevent.  For instance, it's important for all of us to realize that antibiotics are great, but they don't combat all infections--specifically viral infections.  Furthermore, if prescribed an antibiotic by your physician, please complete the entire course of treatment.

Selected Sources

Aoki FY. Chapter 45. Principles of Antimicrobial Therapy and the Clinical Pharmacology of Antimicrobial Drugs. In: Hall JB, Schmidt GA, Wood LH. eds. Principles of Critical Care, 3e. New York, NY: McGraw-Hill; 2005.  Accessed March 24, 2015.

Mosby's Drug Reference for Health Professionals, Second Edition published by Elsevier in 2010.

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