Moderate-spectrum cephalosporins: cefalexin and cefazolin

Cefalexin and cefazolin have a similar spectrum of antibacterial activity. In terms of gram-positive activity, they are active against streptococci and staphylococci, including beta-lactamase–producing (penicillin-resistant) staphylococci, but inactive against methicillin-resistant Staphylococcus aureus (MRSA), enterococci and Listeria monocytogenes. They are active against a narrow range of aerobic gram-negative bacteria, including wild-type Escherichia coli and some Klebsiella species, but have no activity against anaerobic gram-negative bacteria, including Bacteroides fragilis.

Clinical failures with cefazolin for S. aureus infections have been reported. These failures may be due to cefazolin hydrolysis caused by S. aureus isolates that produce beta-lactamase enzyme subtypes that hydrolyse cefazolin, but not antistaphylococcal penicillins (eg flucloxacillin). Cefazolin hydrolysis has been observed in vitro when using a high bacterial inoculum of S. aureus (which theoretically correlates to infection with a high bacterial burden). However, increased rates of clinical failure with cefazolin have not been observed in large cohort studies, and the prevalence of S. aureus isolates that hydrolyse cefazolin in Australia is unknown.