Members of the second-generation cephalosporins include cefaclor, cefamandole, cefonicid, cefuroxime, cefprozil, loracarbef, and ceforanide—of which cefaclor, cefuroxime, and cefprozil are available in the USA—and the structurally related cephamycins cefoxitin and cefotetan, which have activity against anaerobes. This is a heterogeneous group with individual differences in activity, pharmacokinetics, and toxicity. In general, second-generation cephalosporins are relatively active against organisms inhibited by first-generation drugs, but, in addition, they have extended Gram-negative coverage. Klebsiella sp (including those resistant to first-generation cephalosporins) are usually sensitive. Cefuroxime and cefaclor are active against H influenzae but not against Serratia or B fragilis. In contrast, cefoxitin and cefotetan are active against B fragilis and some Serratia strains but are less active against H influenzae. As with first-generation agents, no member of this group is active against enterococci or P aeruginosa. Compared with other cephalosporins, cefoxitin shows improved stability in the presence of extended-spectrum β-lactamases produced by E coli and Klebsiella sp. Clinical data are limited, but it may offer an alternative to carbapenems in treating certain infections due to these organisms. Second-generation cephalosporins may exhibit in vitro activity against Enterobacter sp, but resistant mutants that constitutively express a chromosomal β-lactamase that hydrolyzes these compounds (and third-generation cephalosporins) are readily selected, and they should not be used to treat Enterobacter infections.
A. Oral
Cefuroxime axetil is the most commonly used oral cephalosporin in the USA. The usual dosage for adults is 250–500 mg orally twice daily; children should be given 20–40 mg/kg/d up to a maximum of 1 g/d. These drugs are not predictably active against penicillin-non-susceptible pneumococci.
B. Parenteral
After a 1-g intravenous infusion, serum levels are 75–125 mcg/mL for most second-generation cephalosporins. Intramuscular administration is painful and should be avoided. Doses and dosing intervals vary depending on the specific agent (Table 43–2). There are differences in half-life, protein binding, and interval between doses. All are renally cleared and require dosage adjustment in renal failure.
The oral second-generation cephalosporins are active against β-lactamase-producing H influenzae or Moraxella catarrhalis and have been used primarily to treat sinusitis, otitis, and lower respiratory tract infections. Because of their activity against anaerobes (including many B fragilis strains), cefoxitin and cefotetan can be used to treat mixed anaerobic infections such as peritonitis, diverticulitis, and pelvic inflammatory disease. Cefuroxime is sometimes used to treat community-acquired pneumonia because it is active against β-lactamase-producing H influenzae and also many 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 agents include cefoperazone, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, cefixime, cefpodoxime proxetil, cefdinir, cefditoren pivoxil, ceftibuten, and moxalactam. Cefoperazone, ceftizoxime, and moxalactam are no longer commercially available in the USA.