Streptococcus pneumoniae is the most important causative bacterial pathogen in respiratory infections. Globally, increasing levels of resistant strains highlight the need for continued surveillance programs to guide antibiotic choice. The current study compared susceptibility results of 4,788 strains of S. pneumoniae collected during 2001-2002 to susceptibility results from 3,884 strains collected from the same hospitals during 1999-2000. Participant centers were dispersed throughout five regions. By region, the prevalence of penicillin-resistant S. pneumoniae and percentage change from the previous 1999-2000 study was Mexico (26.0%, 12.5%), Brazil (7.9%; 5.5%), Asia (China, Hong Kong, South Korea, Thailand) (44.1%; 0.8%), Europe (France, Germany, Italy, Spain, UK) (11.1%; -0.6%) and South Africa (7.9; -1.8%). Multidrug-resistant (MDR) strains of S. pneumoniae were most frequently isolated from Asia (36.3%) compared with approximately 5% in the other four regions. Increases in the incidence of MDR isolates in Mexico (13.5%), Brazil (1.7%) and Asia (6.1%) were reported with no increases in MDR in South Africa and Europe. Levofloxacin resistance was rarely associated with MDR phenotypes. Levofloxacin maintained an MIC(90) of 1 microg/ml against the isolates collected from all five regions with no change during the study periods, despite differences in levofloxacin resistance rates between regions or nations (0%-3.2%). The prevalence of levofloxacin resistance (MIC > or =8 microg/ml) increased only slightly over the study period in Europe (0.3%-0.7%) and in Asia (3.0-3.2%), but little or no change was seen in Mexico (3.8%-0%) or Brazil or South Africa, where no levofloxacin resistant isolates were detected in either study period.