Cephalosporins

The cephalosporins are o group of broad-spectrum antibiotics, which are conve­niently grouped into 3 generations, with increasing activity against Gram-negative aerobes, and somewhat decreasing Gram-positive activity. The table below shows o simplistic grouping based on their spectra of activity.

General Notes

All are active against most streptococci, except Enterococcus spp. (which are all intrinsically resistant). importantly, they also have no activity against Listeria or methicillin-resistant staphylococci. Most penicillin-allergic patients will tolerate cephalosporins. but this group of antibiotics should be avoided if there is a definite history of anaphylaxis after penicillin administration. ln general, the third-generation cepha­losporins are significantly less active against staphylococci than the first- and second­ generation cephalosporins.

First-generation cephalosporins

The first-generation cephalosporins are effective alternatives for treating staphylococ­cal and streptococcal infections. They are therefore alternatives for skin and soft-tis­sue infections, as well as for streptococcal pharyngitis. lt is important to stress that the members of this generation are not indicated for empiric treatment of otitis media or sinusitis. Although these agents have some activity against E. coll. Klebsiella and Pro­teus. their use is limited to urinary tract infections caused by susceptible strains of these organisms.

Second-generation cephalosporins

The second-generation cephalosporins have increased activity against Gram-nega­tive bacteria, including H. influenzae, N. meningitidis and M. catarrhalis. They are therefore useful agents for treating upper and lower respiratory tract infections, sinusitis and otitis media. These agents are also active against E. coll. Klebsiella and Proteus, which makes them potential alternatives for treating urinary tract infections caused by these organisms. Cefoxitin is o second-generation cephalosporin with anaerobic activity, and although seldom used as o therapeutic agent, it may have o role for pro­phylaxis in gastrointestinal surgery.

Third-generation cephalosporins

The third-generation cephalosporins are active against most enteric Gram-negative organisms, including beta-lactamase producers, salmonellae and Shigella; but have less activity against staphylococci. The parenteral third-generation cephalosporins (ceftriaxone and cefotaxime) have excellent activity against most strains of Strepto­coccus pneumoniae, including the vast majority of those with intermediate and high level resistance to penicillin. These agents also have activity against N. gonorrhoeae. Their use should be limited to infections resistant to first choice agents, gonococcal infections and infections caused by penicillin-resistant pneumococci. Ceftazidime hos useful antipseudomonal activity.

Oral third-generation cephalosporins

Those available in South Africa include cefixime, cefpodoxime and ceftibutin. These agents have greater efficacy against Gram-negative organisms than the first- and second-generation cephalosporins, but are less effective against Staphylococcus aureus. They are also active against penicillinases-producing strains of Neisseria gonor­rhoeae. They have no activity against Pseudomonas aeruginosa, enterococci or Campylobacter jejuni/coli. They offer no significant advantage over amoxycillin for otitis media and sinusitis. or over penicillin for pharyngotonsillitis. None of the oral cephalosporins are more active than amoxycillin against penicillin-resistant pneumo­cocci.

Fourth-generation cephalosporins

These drugs have o spectrum of activity, which includes the antipseudomonal activity of Ceftazidime and the Gram-positive activity of cefotaxime and ceftriaxone. Cefepime is o more Gram-negative drug with somewhat enhanced activity against pseudomonas but slightly lesser activity against pneumococci, while cefpirome is more active against pneumococci and hos somewhat lesser activity against pseudomonas. These drugs also have activity against nosocomial pathogens such as Enterobacter and Acinetobacter and their use should therefore be restricted to the setting of nosocomial sepsis.