Penicillin

Penicillin (sometimes abbreviated PCN) refers to a group of β-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. The name "penicillin" can also be used in reference to a specific member of the penicillin group. All penicillins possess the basic Penam Skeleton, which has the molecular formula R-C9H11N2O4S, where R is a variable side chain.

Mode of action

β-lactam antibiotics work by inhibiting the formation of peptidoglycan cross links in the bacterial cell wall. The β-lactam moiety of penicillin binds to the enzyme (transpeptidase) that links the peptidoglycan molecules in bacteria, and this weakens the cell wall of the bacterium when it multiplies (in other words, the antibiotic causes cell cytolysis or death when the bacterium tries to divide). Scott Williams is generally credited with having postulated this hypothesis. In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases which further digest the bacteria's existing peptidoglycan.

In addition to the quadraceptics of mechanics, the bacterial wall can break down.

Variants in clinical use

The term "penicillin" is often used generically to refer to one of the narrow-spectrum penicillins, particularly benzylpenicillin.

Benzathine benzylpenicillin

Benzathine benzylpenicillin (rINN), also known as 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 L-A.

Specific indications for benzathine pencillin include:

- Prophylaxis of rheumatic fever
- Early or latent syphilis

Benzylpenicillin (penicillin G)

Benzylpenicillin, commonly known as penicillin G, is the gold standard penicillin. Penicillin G is typically given by a parenteral route of administration because it is unstable to the hydrochloric acid of the stomach. Because the drug is given parenterally, higher tissue concentrations of penicillin G can be achieved than is possible with phenoxymethylpenicillin. These higher concentrations translate to increased antibacterial activity.

Specific indications for benzylpenicillin include:

  • 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:

  • - Infections caused by Streptococcus pyogenes
  • - Tonsillitis
  • - Pharyngitis
  • - Skin infections
  • - Prophylaxis of rheumatic fever
  • - Moderate-to-severe gingivitis (with metronidazole)

Procaine benzylpenicillin

Procaine benzylpenicillin (rINN), also known as procaine penicillin, is a combination of benzylpenicillin with the local anaesthetic agent procaine. Following deep intramuscular injection, it is slowly absorbed into the circulation and hydrolysed to benzylpenicillin - thus it is used where prolonged low concentrations of benzylpenicillin are required.

This combination is aimed at reducing the pain and discomfort associated with a large intramuscular injection of penicillin. It is widely used in veterinary settings.

Specific indications for procaine penicillin include:

  • Syphilis
  • Respiratory tract infections where compliance with oral treatment is unlikely
  • Cellulitis, erysipelas

Procaine penicillin is also used as an adjunct in the treatment of anthrax.

Semi-synthetic penicillins

Structural modifications were made to the side chain of the penicillin nucleus in an effort to improve oral bioavailability, improve stability to beta-lactamase activity, and increase the spectrum of action.

Narrow spectrum penicillinase-resistant penicillins

This group was developed to be effective against beta-lactamases produced by Staphylococcus aureus, and are occasionally known as anti-staphylococcal penicillins.

  • Methicillin
  • Dicloxacillin
  • Flucloxacillin
  • Oxacillin

Moderate spectrum penicillins

This group was developed to increase the spectrum of action and, in the case of amoxicillin, improve oral bioavailability.

  • Amoxicillin
  • Ampicillin

Extended Spectrum Penicillins

This group was developed to increase efficacy against Gram-negative organisms. Some members of this group also display activity against Pseudomonas aeruginosa.

  • Piperacillin
  • Ticarcillin
  • Azlocillin
  • Carbenicillin

Penicillins with beta-lactamase inhibitors

Penicillins may be combined with beta-lactamase inhibitors to increase efficacy against β-lactamase-producing organisms. The addition of the beta-lactamase inhibitor does not generally, in itself, increase the spectrum of the partner penicillin.

  • Amoxicillin/clavulanic acid
  • Ampicillin/sulbactam
  • Ticarcillin/clavulanic acid
  • Piperacillin/tazobactam

Adverse effects

Adverse drug reactions

Common adverse drug reactions (≥1% of patients) associated with use of the penicillins include: diarrhoea, nausea, rash, urticaria, and/or superinfection (including candidiasis). Infrequent adverse effects (0.1-1% of patients) include: fever, vomiting, erythema, dermatitis, angioedema, and/or pseudomembranous colitis.

Pain and inflammation at the injection site is also common for parenterally-administered benzathine benzylpenicillin, benzylpenicillin, and to a lesser extent procaine benzylpenicillin.

Allergy/hypersensitivity

Allergic reactions to any β-lactam antibiotic may occur in up to 10% of patients receiving that agent. Anaphylaxis will occur in approximately 0.01% of patients. There is perhaps a 5-10% cross-sensitivity between penicillin-derivatives, cephalosporins and carbapenems; but this figure has been challenged by various investigators.

Nevertheless, the risk of cross-reactivity is sufficient to warrant the contraindication of all β-lactam antibiotics in patients with a history of severe allergic reactions (urticaria, anaphylaxis, interstitial nephritis) to any β-lactam antibiotic.

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