Penicillin was one of the earliest antibiotics to be discovered. In 1928 Sir Alexander Fleming observed that colonies of Penicillium notatum mold contaminating an agar plate inhibited growth of Staphylococcus aureus, and deduced that an antibacterial agent was present.
It was not until 1941, due to work by Howard Florey and Ernst Chain, that penicillin was isolated in sufficient quantities to be used in vivo and the first patient to receive the drug was a British policeman who had a mixed staphylococcal and streptococcal infection. Initially supplies were scarce, and antibiotic excreted by the body in the urine was recycled. Thanks to improved fermentation and isolation techniques, penicillin was widely available in the United States by the end of the 1940's.
The basic structure of penicillin and most derivatives is the beta lactam ring plus a thiazolidine ring. Penicillins usually exist as a Potassium or Sodium salt.
Mechanism of Action
Work by binding to specific proteins (Penicillin Binding Proteins) on the bacterium and so block cell wall synthesis. Hence they are only really active during the replication phase of bacterial growth, so other antibiotics that work through a different mechanism eg against protein synthesis might be preferred (eg Clindamycin, Linezolid), or else combined with a penicillin to act synergistically (eg an aminoglycoside), even if the bug is fully sensitive (the Eagle effect).
Pharmacokinetics and Pharmacodynamics
Spectrum of Activity
Active against gram positive organisms. Resistance to penicillin has never been described in Streptococcus pyogenes, for some mysterious reason. Resistance in Staphylococcus aureus is well recognized in the form of MRSA. Resistance in Pneumococcus is emerging.
Usually due to Beta lactamase enzymes released by resistant bugs that will deactivate beta-lactam antibiotics. Alternatively, defective Penicillin Binding Proteins may be produced. The former mechanism can be circumvented by co-administration of a beta-lactamase inhibitor eg clavulanate. The latter is the mechanism of resistance in Pneumococci.
- Penicillin (including benzylpenicillin, penicillin V, procaine penicillin)
- Often combined with Beta lactamase inhibitors
- Other beta lactams
Probably rarer than reported. Sensitivity is usually to the basic structure so true allergy to one beta-lactam mostly predicts sensitivity to all. If there is a history of immediate anaphylaxis, urticaria or confluent, pruritic rash, then all beta lactams should be avoided; the risk of cross sensitization to monobactams is less, so these might be considered if clinically indicated.
If the history of penicillin allergy is more vague eg non-confluent, non-pruritic rash over a small area or rash developing after 72 hours of exposure, then it is usually reasonable to avoid beta lactams unless serious illness develops, in which case use of a cephalosporin should be considered.
- Anaphylaxis, urticaria, rash.
- Encephalopathy - related to high doses, or high levels in renal impairment.
- Sodium/potassium overload.