Information AboutBeta-lactam Antibiotic |
| CATEGORIES ABOUT BETA-LACTAM ANTIBIOTIC | |
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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 β-Lactam antibiotics are Bactericidal , and act by inhibiting the synthesis of the Peptidoglycan layer of bacterial Cell Wall s. 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 Transpeptidase s 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. MODES OF RESISTANCE By definition, all β-lactam antibiotics have a β-lactam ring in their structure. The effectiveness of these antibiotics relies on their ability to reach the PBP intact and their ability to bind to the PBP. Hence, there are 2 main modes of bacterial resistance to β-lactams, as discussed below. The first mode of β-lactam resistance is due to enzymatic Hydrolysis of the β-lactam ring. If the bacteria produces the Enzyme s β-lactamase or Penicillinase , these enzymes will break open the β-lactam ring of the antibiotic, rendering the antibiotic ineffective. The genes encoding these enzymes may be inherently present on the bacterial Chromosome or may be acquired via Plasmid transfer, and beta-lactamase Gene Expression may be induced by exposure to beta-lactams. The production of a β-lactamase by a bacterium does not necessarily rule out all treatment options with β-lactam antibiotics. In some instances, β-lactam antibiotics may be co-administered with a β-lactamase inhibitor. However, in all cases where infection with β-lactamase-producing bacteria is suspected, the choice of a suitable β-lactam antibiotic should be carefully considered prior to treatment. In particular, choosing appropriate β-lactam antibiotic therapy is highly important against organisms with inducible β-lactamase expression. If β-lactamase production is Inducible , then failure to use the most appropriate β-lactam antibiotic therapy at the onset of treatment will result in induction of β-lactamase production, thereby making further efforts with other β-lactam antibiotics more difficult. The second mode of β-lactam resistance is due to possession of altered penicillin binding proteins. β-lactams cannot bind as effectively to these altered PBPs, and as a result, the β-lactams are less effective at disrupting cell wall synthesis. Notable examples of this mode of resistance include methicillin-resistant ''Staphylococcus aureus'' ( MRSA ) and penicillin-resistant '' Streptococcus Pneumoniae ''. Altered PBPs do not necessarily rule out all treatment options with β-lactam antibiotics. COMMON Β-LACTAM ANTIBIOTICS Penicillins ''Main article: Penicillin '' Narrow spectrum penicillins
Narrow spectrum penicillinase-resistant penicillins Moderate spectrum penicillins Broad spectrum penicillins Extended Spectrum Penicillins Cephalosporins ''Main article: Cephalosporin '' First generation cephalosporins Moderate spectrum. Second generation cephalosporins Moderate spectrum with anti-'' Haemophilus '' activity. Second generation cephamycins Moderate spectrum with anti-anaerobic activity. Third generation cephalosporins Broad spectrum. Broad spectrum with anti-'' Pseudomonas '' activity. Fourth generation cephalosporins Broad spectrum with enhanced activity against Gram Positive Bacteria and Beta-lactamase stability. Carbapenems ''Main article: Carbapenem '' Broadest spectrum of beta-lactam antibiotics.
Monobactams Unlike other beta-lactams, there is no fused ring attached to beta-lactam nucleus. Thus, there is less probability of cross-sensitivity reactions. 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. 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
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