Cephalosporins parenteral

E. Squires and R. Qeeland, Microbiology and Pharmacokinetics of Parenteral Cephalosporins, Roche Laboratories, Nudey, N.J., 1985. 

Cefmenoxime (61) is a third generation parenteral cephalosporin whose in vitro antimicrobial spectrum approximates that of cefotaxime. Its side chains consist of the common methyltetrazo lylthio group at C-3 and the familiar oximinoether aminothiazole moiety at C-7. It is synthesized... 

Cefoperazone (66) is a third generation parenteral antipseudomonal cephalosporin containing an acylated C-7 side chain reminiscent of that of piperacillin. One of the simplest syntheses... 

Parenterally administered cephalosporins that are metabolically stable and that are resistant to many types of jS-lactamases include eefuroxime, cefamandole, cefotaxime and cefoxitin, which has a 7a-methoxy group at R. Injectable cephalosporins with anti-pseudomonal activity include cefsulodin and cefoperazone. 

Many dry solid parenteral products, such as the cephalosporins, are prepared by sterile crystallization techniques. Control of the crystallization process to obtain a consistent and uniform crystal form, habit, density, and size distribution is particularly critical for drug substances to be utilized in sterile suspensions. For example, when the crystallization process for sterile ceftazidime pentahydrate was modified to increase the density and reduce the volume of the fill dose, the rate of dissolution increased significantly. 

Reaction of sodio 7-aminocephalosporanic acid with l-(lH)-tetrazoylacetic acid gave intermediate 27. Reaction of this last with 2-mercapto-5-methyl-1,3,4-thiadiazole led to the widely used parenteral cephalosporin, cefazolin (28). 

Oral or parenteral fluoroquinolone, carbapenem, or expanded spectrum cephalosporin... 

All currently recommended regimens are single-dose treatments with various oral or parenteral cephalosporins and fluoroquinolones (Table 46-4). Ceftriaxone is the only parenteral agent recommended by the CDC as a first-line agent for treatment of gonorrhea. 

In penicillin-allergic patients, oral or parenteral clindamycin may be used. Alternatively, a first-generation cephalosporin such as cefazolin (1 to 2 g IV every 6 to 8 hours) may be used cautiously for patients who have not experienced immediate or anaphylactic penicillin reactions and are penicillin skin test negative. In severe cases in which cephalosporins cannot be used because of documented methicillin resistance or severe allergic reactions to /1-lactam antibiotics, IV vancomycin should be administered. 

Cefalexin is a first-generation cephalosporin and therefore an alternative preparation would be Zinnat tablets, which contains cefuroxime, a second-generation cephalosporin. A penicillin such as Augmentin, which contains co-amoxiclav, can be an appropriate alternative since it provides a very similar spectrum of activity. Klaricid contains clarithromycin, which is a macrolide. Utinor contains norfloxacin, which is a quinolone that is effective in uncomplicated urinary-tract infections. Rocephin contains ceftriaxone, which is a third-generation cephalosporin that is available for parenteral administration only. 

Parenteral Serious or severe infections not treatable with other antimicrobials, including the penicillins and cephalosporins. 

Eisenberg JM, Koffer H, Finkler SA. Economic analysis of a new drug potential savings in hospital operating costs from the use of a once-daily regimen of a parenteral cephalosporin. Rev Infect Dis 1984 6 S909. 

Most parenteral cephalosporins have good bioavailability after intramuscular injection, and a few members of each cephalosporin generation have good oral bioavaU-abUity (Table 45.2). The ester prodrugs cefuroxime ax-etil (Ceftin) and cefpodoxime proxetil (Vantin) are oral... 

Urinary excretion is the major elimination path for most cephalosporins. When prescribing cephalosporins to patients with renal failure, practitioners must consider dose reduction or dose interval extension (Table 45.2). Renal tubular secretion contributes to the elimination of some cephalosporins, and an increase in cephalosporin plasma concentrations may occur when probenecid blocks renal tubular secretion of cephalosporins. Biliary elimination is important for some cephalosporins. Cefmetazole, cefoperazone (Cefobid), cefoxitin, and ceftriaxone achieve biliary concentrations greater than those in plasma. After parenteral administration of cefoperazone, 70% of the dose appears in the bile within 24 hours. Practitioners should decrease the dose of cefoperazone when prescribing for patients with hepatic failure or biliary obstruction. Metabolism is not a major elimination path for most cephalosporins. Cefotaxime is one of the few cephalosporins having an active metabolite, desacetyl cefotaxime. 

The pharmacokinetic properties of aztreonam are similar to those of the parenteral cephalosporins (Table 45.2). Aztreonam is not bioavailable after oral administration. During its distribution phase, the drug can achieve therapeutic concentrations in cerebrospinal fluid in the presence of inflamed meninges. Consequently, aztreonam is an alternative antibiotic to the cephalosporins for the therapy of meningitis caused by gram-negative bacilli. 

Cephalosporins are distributed in the body after oral or parenteral administration in same manner as penicillin is distributed. The majority are not metabolized and are eliminated by kidney. 

It is a semisynthetic potent cephalosporin for parenteral administration. It can be administered less frequently because of its long half life. It is used in infections of genitourinary tract, bone, joint and soft tissue infections, septicaemia, endocarditis, gonorrhoea, postoperative chest infections, biliary tract infection and surgical prophylaxis. 

It is a parenteral, semisynthetic third generation cephalosporin. It is not metabolised and approximately 90 percent of drug is excreted by the kidney in unchanged form. It is indicated in lower respiratory tract, skin and soft tissue infection, septicaemia, urinary tract infection and gonorrhoea. 

The presence of an internal salt, a zwitterion or betaine, in cephalosporins enhances their solubity in water, making such agents particularly suitable for parenteral administration. The preparation of one such dmg first involves the replacement of allyl oxygen in the tert-butylcarbonyloxy protected 7-ACA derivative (23-1) by nitrogen in azaindan (23-2) to afford the betaine (23-3). The protecting group is then removed so as to free the amine on the azetidone (23-4) by treatment with trifluoroacetic acid. Reaction with the thiazole free acid (23-5) in the presence of DCC then affords cefpirone (23-6) [26]. 

Cefazolin is the only first-generation parenteral cephalosporin still in general use. After an intravenous infusion of 1 g, the peak level of cefazolin is 90-120 mcg/mL. The usual intravenous dosage of cefazolin for adults is 0.5-2 g intravenously every 8 hours. Cefazolin can also be administered intramuscularly. Excretion is via the kidney, and dose adjustments must be made for impaired renal function. 

Intravenous infusion of 1 g of a parenteral cephalosporin produces serum levels of 60-140 mcg/mL. Third-generation cephalosporins penetrate body fluids and tissues well and, with the exception of cefoperazone and all oral cephalosporins, achieve levels in the cerebrospinal fluid sufficient to inhibit most pathogens, including gram-negative rods, except pseudomonas. 

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. 

Cephapirin, a first-generation cephalosporin, is used in form of benzathine or sodium salts for intramammary treatment of mastitis in dry and lactating cows. In the United States, the benzathine intramammary formulations are sold for use by dairy farmers without a prescription. The benzathine salts are further used for intrauterine treatment of endometritis, whereas the sodium salts for parenteral... 

Cefazolin is a first-generation cephalosporin with antibacterial activity similar to that of penicillin G but it is -lactamase-resistant. It is poorly absorbed from the gastrointestinal tract and, thus, it is primarily administered parenterally. It is widely used for ticatment of mastitis in lactating cows, sheep, and goats and for treatment at drying off by the intramammary route. 

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