Penicillin 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. Penicillins have the molecular formula R-C9H11N2O4S, where R is a variable side chain.
Antibiotic resistance to penicillin was first observed in 1947, shortly after its introduction. Resistance to penicillin is now common amongst many hospital acquired bacteria. One mechanism of resistance to penicillin is through the production of the β-lactamase enzyme by some bacterial strains, which breaks down the β-lactam ring of penicillin rendering it harmless. Resistance also arises through modifications to the penicillin-binding proteins (PBPs) in the bacterial cell wall. Bacteria resistant to a particular β-lactam antibiotic may sometimes remain sensitive to certain other β-lactam antibiotics.
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 major development was ampicillin, which 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 yielded beta-lactamase-resistant penicillins including flucloxacillin, dicloxacillin and methicillin. These were important for their activity against beta-lactamase-producing 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 and piperacillin, useful for their activity against Gram-negative bacteria. However, the usefulness of the beta-lactam ring was such that related antibiotics, including the mecillinams, the carbapenems and, most importantly, the cephalosporins, have it at the centre of their structures.
Mode of action
Main article: beta-lactam antibiotic
β-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 (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.
Variants in clinical use
The term "penicillin" is often used generically to refer to one of the narrow-spectrum penicillins, particularly benzylpenicillin.
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: (Rossi, 2004)
prophylaxis of rheumatic fever
early or latent syphilis
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: (Rossi, 2004)
infections caused by Streptococcus pyogenes
prophylaxis of rheumatic fever
moderate-to-severe gingivitis (with metronidazole)
Procaine penicillin (Bicillin®) 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: (Rossi, 2004)
respiratory tract infections where compliance with oral treatment is unlikely
Structural modifications were made to the side chain of the penicillin nucleus in an effort to improve oral bioavailability, overcome penicillin-resistance, and increase the spectrum of action.
Narrow spectrum penicillinase-resistant penicillins
This group was developed to be effective against penicillin-resistant Gram-positive organisms, sometime called anti-staph penicillin.
Moderate spectrum penicillins
This group was developed to increase the spectrum of action and, in the case of amoxicillin, improve oral bioavailability.
Broad spectrum penicillins
Clavulanic acid was added to amoxicillin to increase efficacy against β-lactamase-producing organisms.
co-amoxiclav (amoxicillin+clavulanic acid)
Extended Spectrum Penicillins
This group was developed to increase efficacy against Gram-negative organisms.
Adverse drug reactions
Common adverse drug reactions (ADRs) for the penicillins include: diarrhea, nausea, rash, urticaria, superinfection (including candidiasis). (Rossi, 2004)
Infrequent ADRs include: fever, vomiting, erythema, dermatitis, angioedema, pseudomembranous colitis. (Rossi, 2004)
Pain and inflammation at the injection site is also common for parenterally-administered benzathine penicillin, benzylpenicillin, and to a lesser extent procaine penicillin.
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. (Rossi, 2004) 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.
Other useful drug information: Amoxicillin | Acetaminophen | Indomethacin | Effexor | Ketoconazole | Azathioprine | Promethazine
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