Fourth generation cephalosporin

The class A enzymes have Mx values around 30,000. Their substrate specificities are quite variable and a large number of enzymes have emerged in response to the selective pressure exerted by the sometimes abusive utilization of antibiotics. Some of these new enzymes are variants of previously known enzymes, with only a limited number of mutations (1 4) but a significantly broadened substrate spectrum while others exhibit significantly different sequences. The first category is exemplified by the numerous TEM variants whose activity can be extended to third and fourth generation cephalosporins and the second by the NMCA and SME enzymes which, in contrast to all other SXXK (3-lactamases, hydrolyse carbapenems with high efficiency. Despite these specificity differences, the tertiary structures of all class A (3-lactamases are nearly superimposable. 

Enterobacteriaceae Third- or fourth-generation cephalosporin Carbapenems ... 

Newer antimicrobials have not demonstrated superiority in the prevention of SSI and should be reserved for treatment only. Carbapenems, antipseudomonal penicillins, and third-or fourth-generation cephalosporins are not appropriate antibiotics for surgical prophylaxis. Overuse of these antibiotics may contribute to collateral damage and the development of bacterial resistance. 

Because the progression of infection in neutropenic patients can be rapid, empirical antibiotic therapy should be administered quickly to such patients once fever is documented. Currently, the most commonly used initial antibiotic agent is cefipime, a fourth-generation cephalosporin that has good antipseudomonal coverage as well as adequate coverage against viridans streptococci and pneumococci.23... 

In complicated exacerbations with risk of Pseudomonas aeruginosa, recommended therapy includes a fluoroquinolone with enhanced pneumococcal and P. aeruginosa activity (levofloxacin). If IV therapy is required, a /f lactamase resistant penicillin with antipseudomonal activity or a third- or fourth-generation cephalosporin with antipseudomonal activity should be used. 

Fourth-generation cephalosporins (cefepime and cefpirome) are active with respect to a broad spectrum of Gram-positive and Gram-negative aerobes. They have an unusually low affinity with beta-lactamase and the ability to quickly pass through the periplasmatic space. 

Fourth-generation cephalosporins were developed such as cefpirome and cefepime with additional activity against gram negative pathogens and greater stability against beta-lactamases. 

Mechanism of Action A fourth-generation cephalosporin that binds to bacterial cell membranes and inhibits cell wall synthesis. Therapeutic Effect Bactericidal. Pharmacokinetics Well absorbed after IM administration. Protein binding 20%. Widely distributed. Primarily excreted unchanged in urine. Removed by hemodialysis. Half-life 2-2.3 hr (increased in impaired renal function, and in the elderly). 

It is fourth generation cephalosporin used mainly in serious infections including septicaemia and respiratory tract infections and infections acquired from hospitals. It is resistant to many (3-lactamases. 

BROAD-SPECTRUM (THIRD- FOURTH-GENERATION) CEPHALOSPORINS Cefdinir (Omnicef)... 

First-generation cephalosporins cefazolin for parenteral administration cefadroxil or cephalexin for oral administration. Second-generation cephalosporins cefuroxime for parenteral administration cefaclor, cefuroxime axetil, cefprozil, for oral administration. Third-generation cephalosporins ceftazidime, cefotaxime, ceftriaxone for parenteral administration cefixime, cefpodoxime, ceftibuten, cefdinir, cefditoren for oral administration. Fourth-generation cephalosporin cefepime for parenteral administration. Cephamycins cefoxitin and cefotetan for parenteral administration. 

Oral 200, 400 mg capsules powder for 100, 200 mg/5 mL suspension Broad-Spectrum (Third- Fourth-Generation) Cephalosporins Cefdinir (Omnicef)... 

Cephalosporins are semisynthetic antibiotics obtained from the fungus Cephalo-sporium. These bactericidal agents act in a similar way to that of penicillins. There are different types of cephalosporins available first-generation (cefazolin, cefadroxil) second-generation (cefuroxime, cefaclor) third-generation (cefotaxime, cefoperazone) and fourth-generation (cefpirome). 

Adding different side chains extensively modified the parent cephalosporin compound and created a whole family of cephalosporin antibiotics. For the sake of convenience, these drugs are considered as first-, second-, third-, or fourth-generation componnds based on their spectra of bacterial activity and their clinical uses (Table 11-4). 

Fourth-Generation Cephalosporins. The fourth-generation cephalosporin, cefepime, has an extended spectrum of activity against both gram-positive (e.g., methicillin-sensitive S. aureus) and gram-negative organisms (e.g.. Pseudomonas). 

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