Beta-lactam antibiotic

β-lactam antibiotics are a broad class of antibiotics including penicillin derivatives, cephalosporins, monobactams, carbapenems and β-lactamase inhibitors; basically any antibiotic agent which contains a β-lactam nucleus in its molecular structure. They are the most widely used group of antibiotics available.

Contents

1 Clinical use 2 Mode of action 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 3.2.5 Fourth generation cephalosporins 3.3 Carbapenems 3.4 Monobactams 3.5 Beta-lactamase Inhibitors 4 Adverse effects 4.1 Adverse drug reactions 4.2 Allergy/hypersensitivity 5 References

Clinical use

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.

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 proteins (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 proteins (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.

Common β-lactam antibiotics

Penicillins

Narrow spectrum penicillins

• benzathine penicillin
• benzylpenicillin (penicillin G)
• phenoxymethylpenicillin (penicillin V)
• procaine penicillin

Narrow spectrum penicillinase-resistant penicillins

• methicillin
• dicloxacillin
• flucloxacillin

Moderate spectrum penicillins

• amoxicillin
• ampicillin

Broad spectrum penicillins

• co-amoxiclav (amoxycillin+clavulanic acid)

Extended Spectrum Penicillins

• piperacillin
• ticarcillin
• azlocillin
• carbenicillin

Cephalosporins

Main article: cephalosporin

First generation cephalosporins

Moderate spectrum.

• cephalexin
• cephalothin
• cephazolin

Second generation cephalosporins

Moderate spectrum with anti-Haemophilus activity.

• cefaclor
• cefuroxime
• cefamandole

Second generation cephamycins

Moderate spectrum with anti-anaerobic activity.

• cefotetan
• cefoxitin

Third generation cephalosporins

Broad spectrum.

• ceftriaxone
• cefotaxime

Broad spectrum with anti-Pseudomonas activity.

• ceftazidime

Fourth generation cephalosporins

Broad spectrum with enhanced activity against Gram positive bacteria and beta-lactamase stability.

• cefepime
• cefpirome

Carbapenems

Broadest spectrum of beta-lactam antibiotics.

• imipenem with cilastatin
• meropenem
• ertapenem

Monobactams

Unlike other beta-lactams, there is no fused ring attached to beta-lactam nucleus. Thus, there is less probability of cross-sensitivity reactions.

• aztreonam

Beta-lactamase Inhibitors

No antimicrobial activity. Their sole purpose is to prevent the inactivation of beta-lactam antibiotics by beta-lactamases, and as such, they are co-administered with beta-lactam antibiotics.

• clavulanic acid
• tazobactam
• sulbactam

Adverse effects

Adverse drug reactions

Common adverse drug reactions (ADRs) for the β-lactam antibiotics include: diarrhoea, 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 β-lactam antibiotics.

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. (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.

References

• Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.

de:Β-Lactam-Antibiotikum fr:Antibiotique bêta-lactame ja:Β-ラクタム系