Generation of Cephalosporin and Cephalosporins
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Cephalosporin are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as “Cephalosporium.
Indication of cephalosporin:
Cephalosporins are indicated for the prophylaxis and treatment of infections caused by bacteria susceptible to this particular form of antibiotic. First-generation cephalosporins are active predominantly against Gram-positive bacteria, and successive generations have increased activity against Gram-negative bacteria.
Adverse reaction of Cephalosporin:
Common adverse drug reactions (≥ 1% of patients) associated with the cephalosporin therapy include: diarrhea, nausea, rash, electrolyte disturbances, and/or pain and inflammation at injection site. Infrequent ADRs (0.1–1% of patients) include vomiting, headache, dizziness, oral and vaginal candidiasis, pseudomembranous colitis, superinfection, eosinophilia, nephrotoxicity, neutropenia, thrombocytopenia and/or fever.
Mechanism of action
Cephalosporins are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins) but are less susceptible to penicillinases. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin-binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic the D-Ala-D-Ala site, thereby competitively inhibiting PBP crosslinking of peptidoglycan.
Classification of Cephalosporins
Cephalosporins are grouped into “generations” based on their spectrum of antimicrobial activity. The first cephalosporins were designated first generation while later, more extended spectrum cephalosporins were classified as second generation cephalosporins. Each newer generation of cephalosporins has significantly greater gram-negative antimicrobial properties than the preceding generation, in most cases with decreased activity against gram-positive organisms. Fourth generation cephalosporins, however, have true broad spectrum activity.
The newer agents have much longer half-lives resulting in the decrease of dosing frequency.
First generation cephalosporins are moderate spectrum agents. They are effective alternatives for treating staphylococcal and streptococcal infections and therefore are alternatives for skin and soft-tissue infections, as well as for streptococcal pharyngitis.
The first generation cephalosporins are:
Cefazolin is the most commonly used first generation cephalosporin. The other first generation cephalosporins have similar efficacy to Cephalexin, but must be dosed more often, and are therefore not as commonly prescribed.
The second generation cephalosporins have a greater gram-negative spectrum while retaining some activity against gram-positive bacteria. They are also more resistant to beta-lactamase. They are useful agents for treating upper and lower respiratory tract infections, sinusitis and otitis media. These agents are also active against E. coli, Klebsiella and Proteus, which makes them potential alternatives for treating urinary tract infections caused by these organisms. Cefoxitin is a second generation cephalosporin with anaerobic activity, and although seldom used as a therapeutic agent, it may be useful for prophylaxis in gastrointestinal surgery.
The second generation cephalosporins are:
Third generation cephalosporins have a broad spectrum of activity and further increased activity against gram-negative organisms. Some members of this group (particularly those available in an oral formulation) have decreased activity against gram-positive organisms. The parenteral third generation cephalosporins (ceftriaxone and cefotaxime) have excellent activity against most strains of Streptococcus pneumoniae, including the vast majority of those with intermediate and high level resistance to penicillin. These agents also have activity against N. gonorrhoeae. Ceftazidime has useful antipseudomonal activity.
The third generation cephalosporins are:
Fourth generation cephalosporins are extended spectrum agents with similar activity against gram-positive organisms as first generation cephalosporins. They also have a greater resistance to beta-lactamases than the third generation cephalosporins. Many can cross blood brain barrier and are effective in meningitis.
Cefepime has broad gram-negative coverage with somewhat enhanced activity against pseudomonas but slightly lesser activity against pneumococci. Cefpirome is more active against pneumococci and has somewhat lesser activity against pseudomonas. Cefepime and cefpirome are highly active against nosocomial pathogens such as Enterobacter and Acinetobacter and their use should therefore be restricted to the setting of nosocomial sepsis2.
The fourth generation cephalosporins are:
Fifth generation cephalosporin:
The most latest generation of cephalosporin is fifth generation cephalosporin. The fifth generation cephalosporin’s are:
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