Can antimicrobial activity be sustained? An appraisal of orally administered drugs used for respiratory tract infections.

Respiratory tract infections (RTIs) represent a major cause of illness worldwide. Therefore, it is of great concern that common RTI pathogens have become increasingly resistant to many of the antimicrobial agents used for therapy. For example, Haemophilus influenzae and Moraxella catarrhalis have become resistant to beta-lactam drugs by producing efficient beta-lactamases (> 35 and 90% of strains, respectively). More recently, pneumococci have become more resistant through the mechanism of altered penicillin-binding proteins (PBPs). The rate of penicillin nonsusceptible isolates has risen to > 25% in the United States (1994-1995). It is important to monitor the resistance characteristics of such pathogens and, if possible, to use regionally acquired data to guide empiric selection of therapeutic agents for RTIs. Currently, some antimicrobials remain effective against the majority of these three bacterial species, as exemplified by amoxicillin/clavulanic acid. Furthermore, amoxicillin alone seems to possess greater inhibition than other orally administered beta-lactams at clinically achievable concentrations against pneumococci with altered PBPs. It is critical that steps are taken to limit resistance problems, particularly through; 1) education of prescribers and the public; 2) initiation of the development of novel drugs with alternative modes of action or stability to existing resistance mechanisms; and 3) by continuing to generate quality susceptibility testing data to guide empiric chemotherapy against bacterial pathogens causing RTI.