Comparative microbiological activity and pharmacokinetics of cefprozil

Abstract

In vitro studies on the activity of cefprozil have been conducted in Europe and North America. Against gram-negative bacilli, cefprozil and cefaclor are at least two to four times more active than cephalexin. Cefixime is more active against these organisms. Against gram-positive cocci, cefprozil is at least two to four times more active than cefaclor and cephalexin; cefixime has limited gram-positive activity, and is particularly inactive against staphylococci (MIC90 32 mg/l). Cefprozil is highly active againstStreptococcus pneumoniae (unlike cefixime). Those strains of this genus that display intermediate resistance to pneumococci are more susceptible to cefprozil than cefaclor.Neisseria species andMoraxella catarrhalis are susceptible to cefprozil (MIC90 0.06 and 1 mg/l). β-lactamase-producing strains ofHaemophilus influenzae appear to be susceptible to cefprozil, as the reported MIC90 is 2–4 mg/I. Enterococci,Pseudomonas aeruginosa, and those strains of theEnterobacteriaceae that commonly possess a chromosomal cephalosporinase (e.g.,Providencia, Morganella andEnterobacter) are generally considered to be resistant to cefprozil as well as to other oral cephalosporins. Cefprozil appears to display enhanced stability to the commonly encountered Tem-1 and SHV-1 plasmid-mediated β-lactamases, as found inHaemophilus influenzae, Neisseria gonorrhoeae and theEnterobacteriaceae. Cefprozil is rapidly absorbed, reaching a maximum concentration 0.9 to 1.2 h post-dose. Following oral doses of 250 and 500 mg, the Cmax is 6.2 and 10.0 mg/l respectively. Serum half-lives are generally reported as between 1.2 and 1.4 h, and urine recovery is high, 57–70 %. Ingestion of food has no significant effect on cefprozil pharmacokinetics, but does reduce the serum levels of cefaclor. Studies in severe renal dysfunction suggest that only when the creatinine clearance is under 30 ml/min (when the half-life exceeds 5 h) is there a need for a reduction in the dosage of cefprozil by 50 % or an increase of the dosage interval. Children (over 2 months of age) have very similar pharmacokinetics, the only difference being a slightly shorter cefprozil half-life (ca. 1.0 h). Studies in the elderly suggest that age, per se, does not need an alteration in dosing. The tissue penetration of cefprozil is similar to that of other β-lactams and the blister-fluid model demonstrates that 80 % penetration is found in an inflammatory exudate.