Beta-lactam antibiotics
β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems[1] and carbacephems.[2] Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Until 2003, when measured by sales, more than half of all commercially available antibiotics in use were β-lactam compounds.[3] The first β-lactam antibiotic discovered, penicillin, was isolated from a strain of Penicillium rubens (named as Penicillium notatum at the time).[4][5]
β-lactam antibiotic
Bacteria often develop resistance to β-lactam antibiotics by synthesizing a β-lactamase, an enzyme that attacks the β-lactam ring. To overcome this resistance, β-lactam antibiotics can be given with β-lactamase inhibitors such as clavulanic acid.[6]
Medical use[edit]
β-lactam antibiotics are indicated for the prevention and treatment of bacterial infections caused by susceptible organisms. At first, β-lactam antibiotics were mainly active only against Gram-positive bacteria, yet the recent development of broad-spectrum β-lactam antibiotics active against various Gram-negative organisms has increased their usefulness.
In uninflamed (normal) brain meninges, the penetration of beta-lactam antibiotics is low, at 0.15 of AUCCSF/AUCS ratio (the ratio of area under curve of cerebrosopinal fluid against area under curve of serum).[7]
Adverse effects[edit]
Adverse drug reactions[edit]
Common adverse drug reactions for the β-lactam antibiotics include diarrhea, nausea, rash, urticaria, superinfection (including candidiasis).[8]
Infrequent adverse effects include fever, vomiting, erythema, dermatitis, angioedema, pseudomembranous colitis.[8]
Pain and inflammation at the injection site is also common for parenterally administered β-lactam antibiotics.
Allergy/hypersensitivity[edit]
Immunologically mediated adverse reactions to any β-lactam antibiotic may occur in up to 10% of patients receiving that agent (a small fraction of which are truly IgE-mediated allergic reactions, see amoxicillin rash). Anaphylaxis will occur in approximately 0.01% of patients.[8][9] 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. Rarely, allergic reactions have been triggered by exposure from kissing and sexual contact with a partner who is taking these antibiotics.[10]
A Jarisch–Herxheimer reaction may occur after initial treatment of a spirochetal infection such as syphilis with a β-lactam antibiotic.
β-lactams are classified according to their core ring structures.[33]
By convention, the bicyclic β-lactams are numbered starting with the position occupied by sulfur in the penams and cephems, regardless of which atom it is in a given class. That is, position 1 is always adjacent to the β-carbon of β-lactam ring. The numbering continues clockwise from position one until the β-carbon of β-lactam is reached, at which point numbering continues counterclockwise around the lactam ring to number the remaining to carbons. For example, the nitrogen atom of all bicyclic β-lactams fused to five-membered rings is labelled position 4, as it is in penams, while in cephems, the nitrogen is position 5.
The numbering of monobactams follows that of the IUPAC; the nitrogen atom is position 1, the carbonyl carbon is 2, the α-carbon is 3, and the β-carbon 4.