Beta-lactam Antibiotic Clinical Use Mode Of Action

β-lactam antibiotics are indicated for the prophylaxis and treatment of bacterial infections caused by susceptible organisms. Whilst, traditionally, β-lactam antibiotics were mainly active only against Gram-positive bacteria, the development of broad-spectrum β-lactam antibiotics active against various Gram-negative organisms has increased the usefulness of the β-lactam antibiotics.

2 Mode of action

All β-lactam antibiotics are bactericidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding protein s (PBPs).

β-lactam antibiotics are analogues of D-alanyl-D-alanine - the terminal amino acid residues on the precursor NAM/NAG-peptide subunits of the nascent peptidoglycan layer. The structural similarity between β-lactam antibiotics and D-alanyl-D-alanine facilitates their binding to the active site of penicillin binding protein s (PBPs). The β-lactam nucleus of the molecule irreversibly binds to (acylates) the Ser₄₀₃ residue of the PBP active site. This irreversible inhibition of the PBPs prevents the final crosslinking (transpeptidation) of the nascent peptidoglycan layer, disrupting cell wall synthesis. Inhibition of PBPs may also lead to the activation of autolytic enzymes in the bacterial cell wall.

3 Common β-lactam antibiotics

3.1 Penicillins

3.1.1 Narrow spectrum penicillins

3.1.2 Narrow spectrum penicillinase-resistant penicillins

3.1.3 Moderate spectrum penicillins

3.1.4 Broad spectrum penicillins

3.1.5 Extended Spectrum Penicillins

3.2 Cephalosporins

3.2.1 First generation cephalosporins

3.2.2 Second generation cephalosporins

3.2.3 Second generation cephamycins

3.2.4 Third generation cephalosporins

Broad spectrum.

ceftriaxoneCeftriaxone (Rocephin®) is a third-generation cephalosporin antibiotic. Ceftriaxone is frequently used in combination with azithromycin for the treatment of community-acquired pneumonia. Rocephin is manufactured by Hoffmann-La Roche pharmaceuticals. antib
cefotaxime

Broad spectrum with anti-Pseudomonas activity.

cefepime
cefpirome

3.2.5 Fourth generation cephalosporins

ceftazidime

3.3 Carbapenems

imipenem
meropenem

3.4 Monobactams

aztreonamAztreonam is a monocyclic beta-lactam antibiotic (a monobactam originally isolated from Chromobacterium violaceum''. It is resistant to beta-lactamases and is useful against gram-negative pathogens. Commonly used in its medicine form as an antibiotic to t

3.5 Beta-lactamase Inhibitors

clavulanic acid
tazobactam

4 Adverse effects

4.1 Adverse drug reactions

Common adverse drug reactions (ADRs) for the β-lactam antibiotics include: diarrhoea, nausea, rash, urticariaUrticaria or Hives is a relatively common form of allergic reaction. Hives are a series of raised red skin welts ranging upwards from 5 mm (about a 1/4 inch) in diameter and often have a pale border. They are caused by direct contact with an allergenic su, superinfection (including candidiasisCandida is a genus of yeasts. In Latin candidus, candida means clear and white, with the whiteness of pure quartz rather than the whiteness of chalk albus . Candida was the name of the clear-thinking, outspoken and candid eponymous heroine of Shaw's 1895). (AMH, 2004)

Infrequent ADRs include: fever, vomiting, erythema, dermatitis, angioedema, pseudomembranous colitis. (AMH, 2004)

Pain and inflammation at the injection site is also common for parenterally-administered β-lactam antibiotics.

4.2 Allergy/hypersensitivity

Allergic reactions to any one β-lactam antibiotic may occur in up to 10% of patients receiving that agent. Anaphylaxis will occur in approximately 0.01% of patients. (AMH, 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.

5 References

Australian Medicines Handbook (2004). Australian Medicines Handbook 2004 (AMH). Adelaide: Australian Medicines Handbook. BooksEnthsiast.com.

Antibiotics Beta-lactam antibiotics

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1 Clinical use