Penicillin is a ß-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins.

Penicillin has a molecular formula R-C₉H₁₁N₂O₄S, where R is a variable side chain.

Contents

1 History 2 Mode of action 3 Variants 3.1 Benzathine penicillin 3.2 Benzylpenicillin (penicillin G) 3.3 Phenoxymethylpenicillin (penicillin V) 3.4 Procaine penicillin 4 Resistance 5 Developments from penicillin 6 See also 7 References

History

Penicillin was originally isolated from the Penicillium chrysogenum (formerly Penicillium notatum) mould. The antibiotic effect was originally discovered by a young French medical student Ernest Duchesne studying Penicillium glaucum in 1896 but his work was forgotten.

It was later rediscovered in 1928 by Alexander Fleming who noticed that a halo of inhibition of bacterial growth in a culture of Staphylococcus around a contaminant blue-green mould. From the culture plate, Fleming concluded that the mould was releasing a substance that was inhibiting bacterial growth. He grew a pure culture and discovered that the fungus was Penicillium notatum - he later named the bacterial inhibiting substance penicillin after the Penicillum notatum that released it. Unfortunately, Fleming was convinced after conducting some more experiments that penicillin could not last long enough in the human body to kill pathogenic bacteria and stopped studying penicillin after 1931. It would prove to be the discovery that changed modern medicine.

Its chemical structure was determined by Dorothy Crowfoot Hodgkin, enabling synthetic production. A team of Oxford research scientists led by Australian Howard Walter Florey and including Ernst Boris Chain and Norman Heatley discovered a method of mass producing the drug. Florey and Chain shared the 1945 Nobel prize in medicine with Fleming for this work. Penicillin has since become the most widely used antibiotic to date and is still used for many Gram-positive bacterial infections.

Mode of action

Main article: beta-lactam antibiotic

Penicillin and other ß-lactam antibiotics work by inhibiting the formation of peptidoglycan cross links in the bacterial cell wall. The beta-lactam moiety of penicillin binds to the enzyme that links the peptidoglycan molecules in bacteria and prevents the bacteria from multiplying (or rather causing cell lysis or death when the bacteria tries to divide.

Variants

Benzathine penicillin

Benzathine penicillin is slowly absorbed into the circulation, after intramuscular injection, and hydrolysed to benzylpenicillin in vivo. It is the drug-of-choice when prolonged low concentrations of benzylpenicillin are required and appropriate, allowing prolonged antibiotic action over 2-4 weeks after a single IM dose. It is marketed by Wyeth under the trade name Bicillin®.

Specific indications for benzathine pencillin include: (AMH, 2004)

• prophylaxis of rheumatic fever
• early or latent syphilis

Benzylpenicillin (penicillin G)

Benzylpenicillin, commonly known as penicillin G, is the gold-standard penicillin - higher tissue concentration of can be achieved than is possible with phenoxymethylpenicillin. These higher concentrations translate to increased antibacterial activity.

Specific indications for benzylpenicillin include: (AMH, 2004)

• bacterial endocarditis
• meningitis
• aspiration pneumonia, lung abscess
• community-acquired pneumonia
• syphilis
• septicaemia in children

Phenoxymethylpenicillin (penicillin V)

Phenoxymethylpenicillin, commonly known as penicillin V, is the orally-active form of penicillin. It is less active than benzylpenicillin, however, and is only appropriate in conditions where high tissue concentrations are not required.

Specific indications for phenoxymethylpenicillin include: (AMH, 2004)

• infections caused by Streptococcus pyogenes
  • tonsilitis
  • pharyngitis
  • skin infections
• prophylaxis of rheumatic fever
• moderate-to-severe gingivitis (with metronidazole)

Procaine penicillin

Procaine penicillin is a combination of benzylpenicillin with the local anaesthetic agent procaine. This combination is aimed at reducing the pain and discomfort associated with a large intramuscular injection of penicillin.

Specific indications for procaine penicillin include: (AMH, 2004)

• respiratory tract infections where compliance with oral treatment unlikely
• syphilis
• cellulitis

Resistance

Antibiotic resistance to penicillin is now common amongst many hospital acquired bacteria. The resistance to penicillin has been partly (maybe mostly) due to the rise of beta-lactamase producing bacteria which secrete an enzyme that breaks down the beta-lactam ring of penicillin, rendering it harmless to the bacteria.

Developments from penicillin

The narrow spectrum of activity of the penicillins, along with the poor activity of the orally-active phenoxymethylpenicillin, led to the search for derivatives of penicillin which could treat a wider range of infections.

The first real step forward was in the form of ampicillin. Ampicillin offered a broader spectrum of activity than either of the original penicillins and allowed doctors to treat a broader range of both Gram-positive and Gram-negative infections. Further developments led to amoxicillin, with improved duration-of-action.

Further development gave us flucloxacillin , important even now for its resistance to beta-lactamases produced by bacteria such as Staphylococcus species. It is still no match for MRSA (Methicillin Resistant Staphylococcus aureus).

The last in the line of true penicillins were the antipseudomonal penicillins, such as ticarcillin , useful for their activity against Gram-negative bacteria. However, the usefulness of the beta-lactam ring was such that related antibiotics, including the mecillinam s, the carbapenem s and, most importantly, the cephalosporins, have it at the centre of their structures.

See also

• Beta-lactam antibiotic

References

• Australian Medicines Handbook (2004). Australian Medicines Handbook 2004 (AMH). Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.