ately resistant (10) or highly resistant (18) to penicillin. Of the 28 penicillin-resistant strains, two (7.1%) had high-level resistance to ceftriaxone, and 11 (39.3%) were intermediately resistant to ceftriaxone. Twenty (71.4%) of the 28 strains had high-level resistance to erythromycin, and one additional strain was intermediately resistant to erythromycin.Three fluoroquinolones, ciprofloxacin, levofloxacin, and trovafloxacin, were used for susceptibility testing with Etest methodology. The MIC 90 values of these agents were 1.5, 1.5, and 0.19 g/mL, respectively, and the ranges of MICs were 0.38 to 1.5, 0.75 to 1.5, and 0.094 to 0.19 g/mL, respectively.Statistical differences were demonstrated for penicillin susceptibility on the basis of the specimen source of the pneumococci; blood isolates were more susceptible to penicillin than were either respiratory (P ϭ .0085) or ear (P ϭ .0110) isolates. There was no statistical difference in penicillin susceptibility between ear and respiratory isolates.A decline in penicillin susceptibility among S. pneumoniae strains isolated at our center was first seen in 1993. Similar to results of surveys of susceptibility testing at other medical centers [3], our findings indicate that pneumococcal strains that are resistant to penicillin are often resistant to other classes of antibiotics and so deserve to be referred to as multidrug resistant.Newer fluoroquinolones have an expanded spectrum of antibacterial activity that includes multidrug-resistant S. pneumoniae and have been used for the empirical treatment of community-acquired pneumonia [1]. Trovafloxacin was the most active fluoroquinolone tested in the present investigation. The MIC 90 of trovafloxacin was ϳ10fold lower than that of levofloxacin, the other newer fluoroquinolone examined in this study, and ciprofloxacin, an older fluoroquinolone.Significant differences were seen in penicillin susceptibility between blood isolates recovered in the present study and respiratory and ear isolates. Previous work from other centers [4 -7] supports our findings. Bèdos and colleagues [4] acknowledged that the invasive serogroups 1, 3, 4, 5, 7, 11, 15, and 18 rarely carry antibiotic-resistant phenotypes. They theorized that this occurrence could explain the differences in penicillin susceptibility seen between invasive and noninvasive strains.