Publication of the NCCLS M100-S12 document in January 2002 introduced ceftriaxone and cefotaxime MIC interpretative breakpoints of <1 g/ml (susceptible), 2 g/ml (intermediate), and >4 g/ml (resistant) for nonmeningeal isolates of Streptococcus pneumoniae. To estimate the effect of these breakpoint changes on clinical laboratory susceptibility testing results, nonmeningeal pneumococcal isolate (blood and respiratory) data from The Surveillance Network Database-USA, an electronic surveillance database, for the years 1996 to 2000 were collated and studied. Of 9,863 nonmeningeal isolates tested against ceftriaxone, 82.7% were susceptible, 13.2% were intermediate, and 4.1% were resistant by the M100-S11 NCCLS breakpoints (2001); by M100-S12 breakpoints, 95.9% of the isolates were susceptible, 3.1% were intermediate, and 1.0% were resistant. Of 10,777 nonmeningeal isolates tested against cefotaxime, 79.2% were susceptible, 14.3% were intermediate, and 6.5% were resistant by M100-S11 breakpoints; by M100-S12 breakpoints, 93.5% were susceptible, 4.2% were intermediate, and 2.3% were resistant. Overall, the new M100-S12 ceftriaxone and cefotaxime interpretative breakpoints for nonmeningeal isolates of S. pneumoniae decreased the number of isolates interpreted as intermediate by 10% and as resistant by 3 to 4%.Ceftriaxone and cefotaxime MIC interpretative breakpoints for meningeal and nonmeningeal isolates of Streptococcus pneumoniae were published by the NCCLS in the M100-S12 document in January 2002 (12). Previously, a single set of MIC interpretive breakpoints (M100-S11, 2001) for both meningeal and nonmeningeal isolates was used (11). M100-S11 MIC interpretative breakpoints for ceftriaxone and cefotaxime were 0.5 g/ml (susceptible), 1 g/ml (intermediate), and 2 g/ml (resistant) (11). The M100-S12 breakpoints are 0.5 g/ml (susceptible), 1 g/ml (intermediate), and 2 g/ml (resistant) for meningeal isolates and 1 g/ml (susceptible), 2 g/ml (intermediate), and 4 g/ml (resistant) for nonmeningeal isolates for both ceftriaxone and cefotaxime (12). The M100-S12 interpretative guidelines advise laboratories to report both meningeal and nonmeningeal interpretative criteria for pneumococcal isolates recovered from body sites other than cerebrospinal fluid; isolates from cerebrospinal fluid should be reported with meningeal interpretative criteria only (12).The introduction of revised amoxicillin and amoxicillin-clavulanate breakpoints in M100-S10 (10) resulted in greater than twice the number of pneumococcal isolates being interpreted as intermediate to ceftriaxone (10.3%) than to amoxicillin (4.2%) or amoxicillin-clavulanate (4.6%) and greater than six times more isolates being interpreted as resistant to ceftriaxone (14.4%) than to amoxicillin (2.2%) or amoxicillin-clavulanate (1.7%) (4). Similarly, Oteo et al. reported 23.6% of isolates to be cefotaxime intermediate and 4.5% to be cefotaxime resistant compared with 5.6% being amoxicillin intermediate and 3.8% being amoxicillin resistant despite MICs at which 90% of the isolat...