CEPHALOSPORINS & CEPHAMYCINS

INTRODUCTION: Cephalosporins are similar to penicillins, but more stable to many bacterial β-lactamases and therefore have a broader spectrum of activity. However, there are some strains of E. coli and Klebsiella expressing extended-spectrum β-lactamases and they can hydrolyze most cephalosporins, sparking the burden of antibiotic resistance. Cephalosporins are not active against enterococci and L. monocytogenes. Antimicrobialdrug resistance: Beta-lactamase inhibitors: Penicillins

MOLECULAR CHARACTERISTICS: The nucleus of the cephalosporins, 7-aminocephalosporanic acid, bears a close resemblance to 6-aminopenicillanic acid. The intrinsic antimicrobial activity of natural cephalosporins is low, but the attachment of various functional groups has yielded hundreds of potent compounds of low toxicity. Cephalosporins can be classified into four major groups or generations, depending mainly on the spectrum of antimicrobial activity.

FIRST-GENERATION CEPHALOSPORINS: First-generation cephalosporins include; cefazolin, cefadroxil, cephalexin, cephalothin, cephapirin, and cephradine. These drugs are very active against gram-positive cocci, such as pneumococci, streptococci, and staphylococci. Traditional cephalosporins are not active against methicillin-resistant strains of staphylococci; however, new compounds have been developed that have activity against methicillin-resistant strains.

CLINICAL USES: Oral drugs may be used for the treatment of urinary tract infections and staphylococcal or streptococcal infections, including cellulitis or soft tissue abscess. However, oral cephalosporins should not be relied on in serious systemic infections. Cefazolin penetrates well into most tissues. It is therefore a drug of choice for surgical prophylaxis. Cefazolin may also be a choice in infections for which it is the least toxic drug such as in penicillinase producing E. coli or K. pneumonia, and in individuals with staphylococcal or streptococcal infections who have a history of penicillin allergy other than immediate hypersensitivity.

SECOND-GENERATION CEPHALOSPORINS: Members of the second-generation cephalosporins include cefaclor, cefamandole, cefonicid, cefuroxime, cefprozil, loracarbef, and ceforanide. They are structurally related cephamycins including; cefoxitin, cefmetazole , and cefotetan , which have activity against anaerobes. This is a heterogeneous group with marked individual differences in activity, pharmacokinetics, and toxicity.

In general, they are active against organisms inhibited by first-generation drugs, but in addition they have extended gram-negative coverage. Klebsiella sp including those resistant to cephalothin are usually sensitive. Cefamandole, cefuroxime, cefonicid, ceforanide, and cefaclor are active against H. influenzae but not against serratia or B. fragilis.

CLINICAL USES: The oral second-generation cephalosporins are active against β-lactamase-producing H influenzae or Moraxella catarrhalis and have been primarily used to treat sinusitis, otitis, and lower respiratory tract infections, in which these organisms have an important role. Because of their activity against anaerobes (including many B. fragilis strains) , cefoxitin, cefotetan, or cefmetazole can be used to treat mixed anaerobic infections such as peritonitis, diverticulitis, and pelvic inflammatory disease. Cefuroxime is used to treat community-acquired pneumonia because it is active against β-lactamase-producing H. influenzae or K. pneumoniae and some penicillin-non-susceptible pneumococci. Although cefuroxime crosses the blood-brain barrier, it is less effective in treatment of meningitis than ceftriaxone or cefotaxime and should not be used.

THIRD-GENERATION CEPHALOSPORINS: Third-generation agents include cefoperazone, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, cefixime, cefpodoxime proxetil, cefdinir, cefditoren pivoxil, ceftibuten, and moxalactam .

ANTIMICROBIAL ACTIVITY: Compared with second-generation agents, these drugs have expanded gram-negative coverage, and some are able to cross the blood-brain barrier. Third-generation drugs are active against Citrobacter, S. marcescens, and Providencia (although resistance can emerge during treatment of infections caused by these species due to selection of mutants that constitutively produce cephalosporinase). They are also effective against β-lactamase-producing strains of haemophilus and neisseria. Ceftazidime and cefoperazone are the only two drugs with useful activity against P. aeruginosa. Like the second-generation drugs, third-generation cephalosporins are hydrolyzed by constitutively produced AmpC β lactamase, and they are not reliably active against Enterobacter species. Serratia, Providencia, and Citrobacter also produce a chromosomally encoded cephalosporinase that, when constitutively expressed, can confer resistance to third-generation cephalosporins.

RELATED;

1.  PENICILLINS

2.  SULFONAMIDES

3.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES