Parenterally administered cephalosporin

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. 

It has also been reported that patients with allergic-like events after penicillin treatment have had a markedly risk of events after subsequent cephalosporin antibiotics. Cross-reactivity is not an adequate explanation for this increased risk and the data obtained indicate that cephalosporins can be considered for patients with penicillin allergy <2006MI354.ell>. Comparisons of parenteral broad-spectrum cephalosporins have been tested against bacteria isolated from pediatric patients. The results have indicated that cefepime has been the most broad-spectrum cephalosporin analyzed and it is a very potent alternative for the treatment of contemporary pediatric infections in North America <2007MI109>. The historical safety of the most commonly used oral cephalosporins has been reviewed <2007MIS67>. The antimicrobial spectrum and in vitro potency of the most frequently prescribed orally administered cephalosporins (cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime axetil and cephalexin has also been reviewed <2007MIS5>. 

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. 

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. 

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. 

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. 

Correct answer = A. Most urinary tract infections are due to E. coii and can usually be treated with cotrimoxazole. However, this patient is near term and the sulfa in the cotrimoxazole might put the infant at risk due to kernicterus. Thus, the first generation cephalosporin, cefadroxil, is appropriate since it would be effective orally against penicillinase producing E. coii. Ceftriaxone, while it would be effective, would have to be administered parenterally. Penicillin V is not effective against E. coii. Tetracycline deposits in teeth and skeleton of the fetus and is contraindicated. 

Aminoglycosides are poorly absorbed from the gastrointestinal tract, so when used systemically they must be given parenterally. Note that penicillins or cephalosporins can inactivate aminoglycosides if mixed together in the same solution fiar injection or fiar topical application each drug must be administered separately. If topical fortified cefazolin and fortified tobramycin are used to treat a corneal ulcer, each should be prepared and administered in a separate bottle. 

It should be noted that the classification into generations is not chronological, and so some second-generation compounds came to the market relatively recendy, after the third-generation was firmly established. Within each class there is also a further classification as to whether the compounds are administered orally or parenterally. A contemporary variation of the generation classification has been proposed, but has not found widespread use (85). Another proposal groups cephalosporins according to clinical indication or application (86). 

Cephalosporins are usually administered parenterally. These drugs are the most frequently used for bacterial infections because of their broad activity and low toxicity. The P-lactam antibiotics account for about 60% of the annual worldwide sales of antibiotics amounting to 11 thousand million US dollars. Of this amount, cephalosporins claim 40% and penicillins 20%. 

B. Pharmacokinetics Several cephalosporins are available for oral use, but most are administered parenterally. Cephalosporins with side-chains may undergo hepatic metabolism, but the major elimination mechanism for drugs in this class is renal excretion via active tubular secretion. Cefoperazone and ceftriaxone are excreted mainly in the bile. Most first- and second-generation cephalosporins do not enter the cerebrospinal Uuid even when the meninges are in-Uamed. 

Perhaps one of the most successful second-generation cephalosporins is cefiiroxime (Zinacef ) (Fig. 22.27). Cefiiroxime is stable to bacterial P-lactamases and can be administered either parenterally or orally as its acetoxy-ethoxy ester cefuroxime axetil (Zinnat ). 

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