Discovered in a fashion analogous to penicillins, cephalosporins are natural and semi-synthetic agents. There are a large number of different cephalosporins in use in various parts of the world.
A classification structure evolved based on “generations” the earliest being “first generation” and having similar characteristics. The first generation cephalosporins in common usage in Canada – intravenous cefazolin and oral cephalexin have very similar spectra of activity and clinical indications and can be thought about as a group. This is also generally true for other first generation cephalosporins in use in other parts of the world such as cephadrine, cefapirin and cefaloridine.
The other clinically useful grouping is the original “third generation” cephalosporins. Cefotaxime and ceftriaxone, while having different pharmacokinetics, can be used interchangeably for the majority of indications and decisions about which one is available in a Canadian institution are made predominantly on economic grounds. Ceftriaxone is now dominant because both agents are available in generic form and it has the advantage of long elimination half-life allowing for once-daily dosing.
Cefazolin and Cephalexin
Parenteral cefazolin (Ancef®) and oral cephalexin (Keflex®) are the predominant first generation cephalosporins in Canada. They are active against methicillin-susceptible Staphylococcus aureus and Beta hemolytic streptococci making them useful agents for the therapy of skin and soft tissue infections. They are also active against many strains of E.coli and are commonly used in combination with metronidazole in the therapy of uncomplicated intraabdominal infections. They are also the most commonly used agents for surgical prophylaxis.
Cefuroxime and Cefuroxime axetil
With a spectrum of activity that included most S. pneumoniae, H. influenzae, Moraxella catarrhalis and Beta-hemolytic Streptococci, cefuroxime has been a useful agent for the therapy of respiratory tract infections. It was widely promoted and used as the drug of choice for patients hospitalized with community-acquired pneumonia in Canada until recent shifts toward fluoroquinolones. Caution should be used when using oral broad spectrum cephalosporins such as cefuroxime axetil because of a relatively high incidence of Clostridium difficile associated disease.
Cefotaxime and Ceftriaxone
These third generation cephalosporins have been the “workhorse” antibiotics for the therapy of serious hospital acquired infections in Canada for many years. They have also been the drugs of choice for bacterial meningitis. Unfortunately, resistance is increasing especially amongst nosocomial “nasty” Gram negatives. Extended Spectrum Beta-Lactamases (ESBLs) that hydrolyse the Beta-lactam ring of these agents are common in some parts of the world and increasing in importance in North America. We have seen significant increases in the incidence of ESBLs in Canada in the last few years.
The “antipseudomonal” cephalosporin in common usage in Canada. It is used extensively as empiric therapy for febrile neutropenic leukemia patients. It is generally reserved for this application and the therapy of proven susceptible P. aeruginosa infections.