Combinations of orally administered beta-lactams to maximize spectrum and activity against drug-resistant respiratory tract pathogens: I. Synergy studies of amoxicillin and cefixime with Streptococcus pneumoniae.

Streptococcus pneumoniae strains have emerged that are resistant to penicillin (MICs >0.06 microg/mL) and many other beta-lactams. However, some older compounds such as amoxicillin have potency against these pneumococci with altered penicillin-binding proteins, but are labile to beta-lactamases produced by other prevalent respiratory tract pathogens. The interactions of amoxicillin with an enzyme-stable cephalosporin (cefixime) with a long elimination half-life were examined by the checkerboard dilution method versus 39 S. pneumoniae strains (13 resistant, 15 intermediate, and 11 susceptible to penicillin). Among 24 strains with evaluable drug interaction tests, 17 (71%) demonstrated partial or complete synergy. This favorable interaction produces a cefixime susceptibility category change from resistant or intermediate to susceptible for 16 of 28 strains (57%), when combined with < or = 1 microg/mL amoxicillin. Thus, the use of two currently available oral beta-lactams (amoxicillin twice a day + cefixime once a day; three total doses) appears to be a potential alternative treatment with greater spectrum for community-acquired respiratory tract infections pending clinical trial results.