Antimicrobial resistance rates have noticeably increased among commonly isolated species associated with respiratory tract infections and skin and skin structure infections, particularly Streptococcus pneumoniae and Staphylococcus aureus. Cefditoren, an oral 3rd-generation-like cephalosporin, has been shown to be very active against many Gram-positive and Gram-negative species with favorable attributes including bactericidal activity and stability against many beta-lactamase enzymes. Clinical trial data worldwide support the use of cefditoren for infections and species that have been approved by the US Food and Drug Administration (US-FDA). This review and a contemporary study report provide an update of clinical trial and in vitro data for cefditoren especially against pathogens within the spectrum of activity since 2002. A large collection of 7279 clinical isolates collected during 2002 and 2003 from medical centers in North and Latin America and Europe were tested to confirm cefditoren potency and spectrum compared with other oral cephalosporins and other class agents. Isolates were tested at a reference laboratory using reference broth microdilution methods. Cefditoren was shown to be active against nearly all (>99%) isolates of penicillin-susceptible S. pneumoniae isolates (MIC(90), < or = 0.03 microg/mL) and was the most potent orally administered cephalosporin against this organism. Cefditoren was the most active oral cephem tested against Haemophilus influenzae (MIC(90), < or = 0.03 microg/mL) and had >99% activity versus both beta-lactamase-positive and beta-lactamase-negative isolates. The potency of cefditoren (MIC(90), 0.5 microg/mL) was similar to that of amoxicillin/clavulanate and cefdinir (MIC(90), 0.25 microg/mL) when tested against Moraxella catarrhalis. Cefditoren was the most potent cephalosporin tested against oxacillin-susceptible S. aureus with an MIC(90) value of only 1 microg/mL, and it was 100% active against the tested beta-hemolytic streptococci. Using the data generated from the large collection of isolates tested in this global surveillance collection, as well as other summarized supporting studies and clinical trial information, we show that cefditoren has sustained in vitro activity and documented clinical efficacy for indications that have been approved by regulators (US-FDA).