Penicillin is one of the earliest discovered and widely used antibiotic agents, derived from the Penicillium mould. In 1928, Sir Alexander Fleming observed that colonies of the bacterium Staphylococcus aureus could be destroyed by the mould Penicillium notatum, proving that there was an antibacterial agent there in principle. In 1943, clinical trials were performed and Penicillin was shown to be the most effective antibacterial agent to date. Penicillin production was quickly scaled up and available in large amounts to treat Allied soldiers wounded towards the end of WWII (D-Day especially). It was seen as a ‘medical marvel’, rapidly destroying the biggest wartime killer, infected wounds. Penicillin has vast capabilities in destroying many of the bacteria that have infected mankind for thousands of years. However, some people have a negative reaction to Penicillin, with hypersensitivity reactions, shock and even death. There are many common infections that Penicillins do not affect. Despite this, Penicillin has saved countless lives since 1928. General Properties. Structurally related to that of the Cephalosporins, Penicillins share the structural feature of a β-lactam ring. The ring is very strained and the bond between the carbonyl and the nitrogen in the β-lactam ring is very liable and hence makes the molecule reactive.  The R-group substituent of the penicillin nucleus can be changed to give the molecule different antibacterial properties.
Penicillins are bactericidal in nature due to the inhibitory action to bacterial cell wall synthesis. The R-group substituent will determine three factors; β-lactamase stability. Absorption. Specificity to bacteria. These three factors govern which Penicillin to use during treatment. The β-lactam ring of Penicillins is known as the 'Achilles heel' to this group of antimicrobial agents. This is because many micro-organisms possess the enzyme β-lactamase. β-lactamase containing micro-organisms can break open the β-lactam ring through the process of hydrolysis rendering the drug useless. However there are Penicillin derivatives that have overcome this problem by sterically hindering the β-lactam ring to prevent hydrolysis e.g. Flucloxacillin.
Absorption is important when concerning side chains because the molecule must be acid stable during oral absorption. Food can also have an effect on the absorption of the Penicillin, therefore some Penicillins must be taken before food, whilst others are not affected. Penicillin V was the first major success in improving the pharmacological properties of Penicillin. Penicillin V has very similar properties to that of Penicillin G (injection only) though Penicillin V is absorbed orally much more effectively. Specificity to bacteria for example increasing the polarity of the side chain will improve the activity against Gram-negative bacteria. Mechanism of Action. When cross-linking of the peptidoglycan polymer occurs, one D-alanine residue is cleaved from the peptidoglycan precursor. This reaction is prevented by Penicillins. Recent studies have shown that this mechanism of action is far more complicated that previously hypothesised. It involves other processes which involve Penicillin binding proteins. The targets for Penicillins are the Penicillin binding proteins (PBP's), They have transpeptidase or carboxypeptidase activity and they act to regulate cell size and shape. Bacteria have individual penicillin binding proteins, each with its own function. These are numbered according to size, PBP 1 is the largest. The PBP 1 of one micro-organism may not share the same function as a PBP 1 in another organism. The β-lactam antibiotics may bind preferentially to different Penicillin binding proteins, and at sublethal concentrations may cause alterations in cell morphology. For example, Amidinopenicillin and Mecillinam will bind preferentially to PBP 2 and cause a generalised effect which will lead to the bacteria adopting a spherical shape.   Penicillins also stimulate the activity of autolysins. Autolysins are enzymes that are responsible for the turnover of cell wall polymers to permit growth of the cells. During normal conditions, these enzymes produce points which are controlled in their shape and to allow for expansion of the cell wall structure size within the peptidoglycan structure. This activity is stimulated by Penicillins, which causes a breakdown of peptidoglycan to lead to osmotic fragility of the cell and then onto cell lysis.
Penicillin G (Benzylpenicillin) Branded names; Crystapen Mechanism of Action and Spectrum of Activity; See notes above Dosage, Form and Strengths; 0.6 – 2.4g daily in divided doses. Higher doses can be given. Injection only, Intravenous or Intramuscular - Vials - 600mg, 2 vial ‘GP’ pack, 1.2g. Activity with other Antimicrobial Agents; Synergy with aminoglycosides (Penicillin G  +  Gentamicin.) Activity enhanced with Clavanic Acid (in theory) Antagonism with bacteristatic drugs (e.g. Tetracyclines, actively growing cells needed.) Resistance Mechanism; β-lactamase present. Precautions and Adverse Effects; Hypersensitivity reaction, diarrhoea, nausea
Penicillin V (Phenoxymethylpenicillin) Branded names; Generic only. Mechanism of Action and Spectrum of Activity; See notes above. Dosage, Form and Strengths; 500mg every 6 hours doubled strength in severe infections. Children under 1 yr 62.5mg every 6 hours doubled strength in severe infections. Children 1 – 5 yrs 125mg every 6 hours, doubled strength in severe infections. Children 5 – 12 yrs 250mg every 6 hours, doubled strength in severe infections. Tablets – 250mg. Oral solution – 125mg/5ml reconstituted with water to 100ml. 250mg/5ml reconstituted with water to 100ml. Activity with other Antimicrobial Agents; Synergy with aminoglycosides (Penicillin V +  Gentamicin.) Activity enhanced with Clavanic Acid (in theory) Antagonism with bacteristatic drugs (e.g. Tetracyclines, actively growing cells needed.) Resistance Mechanism; β-lactamase present. Precautions and Adverse Effects; Hypersensitivity reaction, diarrhoea, nausea. Take an hour before food or on an empty stomach.
Amoxicillin Branded names; Amoxil Mechanism of Action and Spectrum of Activity; See notes above. Dosage, Form and Strengths; Children up to10 yrs 125mg every 8 hours, doubled strength in severe infections. Adults and Children 10 years and over 250mg every 8 hours, doubled strength in severe infections. Capsules – 250mg, 500mg. Oral solution – 125mg/5ml reconstituted with water to 100ml. 250mg/5ml reconstituted with water to 100ml. Capsules – 250mg, 500mg. Oral Solution – 125mg/5ml reconstituted with water to 100ml. 250mg/5ml reconstituted with water to 100ml. Sachets – 3g. Injection – Intravenous – Vials – 250mg, 500mg, 1g. Activity with other Antimicrobial Agents; Synergy with aminoglycosides (Amoxicillin  +  Gentamicin.) Activity enhanced with Clavanic Acid (Co-amoxiclav) Antagonism with bacteristatic drugs (e.g. Tetracyclines, actively growing cells needed.) Resistance Mechanism; Often used with Clavanic Acid using the drug called Co-Amoxiclav. Active against β-lactamase producing organisms. Precautions and Adverse Effects; Hypersensitivity reaction, diarrhoea, nausea.
Flucloxacillin. Branded names; Floxapen Mechanism of Action and Spectrum of Activity; See notes above Dosage, Form and Strengths; 250 – 500mg every 6 hours. Capsules – 250mg and 500mg. Oral solution – 125mg/5ml reconstituted with water to 100ml. 250mg/5ml reconstituted with water to 100ml. Injection – Intravenous and Intramuscular – 250mg vial, 500mg vial, 1g vial. Activity with other Antimicrobial Agents; Synergy with aminoglycosides (Flucloxacillin  +  Gentamicin.) Activity enhanced with Clavanic Acid (in theory) Antagonism with bacteristatic drugs (e.g. Tetracyclines, actively growing cells needed.) Resistance Mechanism; Resistant to staphylococcal β-lactamase. See notes above Precautions and Adverse Effects; Hypersensitivity reaction, diarrhoea, nausea.
Piperacillin. Branded names; Tazocin. Mechanism of Action and Spectrum of Activity; See notes above. Dosage, Form and Strengths; 2.25 – 4.5g every 6 to 8 hours. Injection – Intravenous – Powder for reconstitution – 2.25g (Piperacillin 2g and Tazobactam 250mg), 4.5g (Piperacillin 4g and Tazobactam 500mg). Activity with other Antimicrobial Agents; Synergy with aminoglycosides (Piperacillin  +  Gentamicin.) Activity enhanced with Clavanic Acid (in theory) Antagonism with bacteristatic drugs (e.g. Tetracyclines, actively growing cells needed.) Resistance Mechanism; Often used with Tazobactam. A β-lactamase inhibitor. Precautions and Adverse Effects; Hypersensitivity reaction, diarrhoea, nausea.