Parameters Characterizing the In Vitro Activity of Cefixime, a New Oral Broad Spectrum Cephalosporin, Against Respiratory and Urinary Pathogens

Summary

The wide and potent in vitro activity of cefixime, a new oral broad spectrum cephalosporin, has been confirmed on a collection of respiratory and urinary pathogens recently isolated in Italy. The new cephem emerged as the most bactericidal of all the comparators tested against several fast as well as slowly-growing gram-negative species including Enterobac-teria, Haemophilus and Moraxella, irrespective of their ability to synthetize β-lactamases. Among the gram-positive species Streptococcus pyogenes and 5. pneumoniae were effectively covered.

Cefixime activity was not adversely influenced by several important variables such as pH (over the range from 5 to 8), inoculum size (from 10⁵ to 10⁸ CFU per ml) and the presence of 50% human serum or urine. Time-kill tests confirmed a pronounced bactericidal potency of the drug especially towards common respiratory pathogens (H. influenzae, M. catarrhalis, S. pneumoniae and S. pyogenes). Killing of urinary strains was optimal at cefixime concentrations reached in urine since eradication, except for Proteus mirabilis, was enhanced with increasing levels of the drug. The absence of an untoward paradoxic effect on the rate of cefixime bactericidal action was confirmed by employing a dynamic bladder model simulating the pharmacokinetic parameters of the drug after a single 200 mg daily dosage. Interactions of cefixime with several other drugs that may be employed in combination therapy were generally prone to provide indifference and synergism while antagonism was never observed. Favorable interactions were also registered when cefixime acted with other antibiotics on partially resistant species such as Staphylococci and Pseudomonas. The new cephem seems to provide excellent opportunities for expanding oral cephalosporin therapy to a wide range of infections produced by susceptible pathogens in the adult and pediatric populations.

Key Words:

• cefixime
• in vitroactivity
• bactericidal effect
• Eagle’s effect
• activity in bladder model
• interaction with other drugs
• cephalosporin.