Antibiotic Q&A: Third-generation vs. first-generation cephalosporins
Melissa Clark, DVM, PhD, DACVCP
Have third-generation cephalosporins lost activity against common gram-positive pathogens?
Illustration of staphylococcus on the surface of skin or a mucus membrane. (Kateryna Kon/Shutterstock.com)Q: Earlier generations of cephalosporins tend to have more gram-positive activity, whereas later generations generally have greater gram-negative activity at the expense of gram-positive activity. How do the spectra of cefpodoxime and cefovecin compare with those of first-generation cephalosporins? Have they lost activity against common gram-positive veterinary pathogens?
A: Like first-generation cephalosporins, cefpodoxime is effective against streptococci and staphylococci (except methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius). It also has efficacy against beta-lactamase negative Escherichia coli, Proteus mirabilis, Proteus vulgaris, and Klebsiella, Serratia, Providencia and Salmonella species. And approximately half of human isolates of beta-lactamase-producing E. coli and Enterobacter, Citrobacter and Morganella species are susceptible. Thus, cefpodoxime has slightly expanded gram-negative coverage compared with first-generation cephalosporins, though it maintains some gram-positive activity (for example, against opportunistic skin flora that cause pyoderma).
Cefovecin is also a third-generation cephalosporin and is more active with lower minimal inhibitory concentrations (MICs) for many bacteria than first-generation cephalosporins. In studies conducted by a sponsor of cefovecin, the MIC90 was 0.25 μg/ml for Staphylococcus intermedius (versus 2 μg/ml for first-generation cephalosporin cephalexin). Cefovecin also demonstrated a MIC90 of 1 μg/ml for many gram-negative organisms (versus 16 μg/ml for first-generation cephalosporins cephalexin and cefadroxil) as well as very low MICs for feline Pasteurella species isolates and Streptococcus canis.1
But, as noted by the manufacturer, cefovecin is heavily protein-bound, and free concentrations may not be sufficient to reach an appropriate time above MIC for E. coli in the plasma in vivo. Therefore, single administrations may only be effective against highly susceptible pathogens (like gram-positive bacteria and Pasteurella species) as well as urinary tract infections (UTIs), since the drug is eliminated in the urine.
In the United States, cefovecin is labeled for the treatment of pyoderma, bite wounds and abscesses. It is also labeled for the treatment of E. coli UTIs in Europe. It is not effective against Pseudomonas or Enterococcus species. In both cases, amoxicillin for Pasteurella species or susceptible UTI, or amoxicillin trihydrate-clavulanate potassium or cephalexin for pyoderma, would be appropriate choices in lieu of third-generation cephalosporins (unless compliance is an obstacle or gram-negative involvement is suspected).
Stegemann MR, Passmore CA, Sherington J, et al. Antimicrobial activity and spectrum of cefovecin, a new extended- spectrum cephalosporin, against pathogens collected from dogs and cats in Europe and North America. Antimicrob Agents Chemother 2006;50(7):2286-2292.
Melissa Cark, DVM, PhD, DACVCP, is an internal medicine resident at the Animal Medical Center in New York, New York.