Combination cefixime/amoxicillin against penicillin-resistant Streptococcus pneumoniae infection.

The rising incidence of antibiotic resistance, including penicillin-resistant Streptococcus pneumoniae (PRSP), has become a great clinical problem in many countries. Cefixime, an orally active third-generation cephalosporin has broad and potent activity against various pathogens, especially gram-negative organisms including beta-lactamase producing strains. However, as with all other oral agents, cefixime is inactive against PRSP. As a possible solution to this problem, the effectiveness of a combination of cefixime and amoxicillin which retains stronger activity against PRSP was evaluated. This combination worked synergistically against S. pneumoniae including PRSP by the checkerboard method with a mean FIC index value of 0.60 and the time-kill kinetic method. Similarly, a synergistic effect was shown in the mouse respiratory tract infection model, with an FED index of 0.29 (cefixime:amoxicillin = 2:1). Additionally, this combination showed excellent activity against mixed organisms including PRSP, in the human serum level simulating kinetic method and mouse respiratory mixed infection models. We review here briefly preclinical studies carried out in our laboratory which demonstrate the synergistic effect of this cefixime plus amoxicillin combination, and suggest the empirical therapeutic potency of this combination for treating community-acquired respiratory tract infections, including PRSP, in the clinical setting.