Cefdinir is an oral cephalosporin approved by the Food and Drug Administration in 1997 for the treatment of acute exacerbation of chronic bronchitis, pharyngitis-tonsillitis, community-acquired pneumonia, acute maxillary sinusitis, and uncomplicated skin and skin structure infections in adults and adolescents, and acute otitis media, pharyngitis-tonsillitis, and uncomplicated skin and skin structure infections in children. Although cefdinir showed similar activity to other cephalosporins in the early studies, very limited data has been generated over the last decade. In this report, we summarize the contemporary in vitro activity and spectrum of cefdinir in comparison to numerous other orally administrated antimicrobials available for treatment of community-acquired respiratory infections. A total of 8,326 non-duplicate recent clinical isolates, including Haemophilus influenzae (3,438), Moraxella catarrhalis (1,688), and Streptococcus pneumoniae (3,200), were collected from 35 medical centers in North America during 2000 through 2002, and susceptibility tested by reference broth microdilution methods. Pneumococcal susceptibility patterns for beta-lactams and macrolides were also analyzed according to the year of isolation and the age group of the patients. Cefdinir had the greatest activity against H. influenzae among the cephalosporins tested with susceptibility rates of 97.1 to 99.0%. All of the agents tested had complete or near complete activity against M. catarrhalis. Against S. pneumoniae, cefdinir and other cephalosporins showed similar susceptibility patterns, but improved rates were observed in 2002 (78.5-79.4%) when compared to the previous monitored period (71.8-74.5%). This increase in susceptibility was mainly because of a declining the occurrence of high-level penicillin resistance (MIC >/=2 microg/ml) across all age groups. Macrolide resistance also decreased among S. pneumoniae in 2002 when compared to 2000 through 2001; however, resistance to levofloxacin continued to increase from 0.9% in 2000 to 1.4% in 2002. These results indicate a significant change in emerging beta-lactam resistance patterns (including cefdinir) with a decrease possibly influenced by greater pneumococcal vaccine use in children and the elderly. These rates of increased susceptibility could sustain and enhance the clinical activity of orally administered beta-lactams such as cefdinir.