As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, and carbapenems. Changes in the bacterial susceptibility for CZOP were also evaluated with the resistance ratio calculated with breakpoint MIC. Sixteen species (2,363 strains) of Gram-positive bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), methicillin-resistant Staphylococcus epidermidis (MRSE), Staphylococcus haemolyticus, Staphylococcus saprophyticus, Enterococcus faecalis, Enterococcus faecium, Enterococcus avium, Streptococcus pyogenes, Streptococcus agalactiae, penicillin-susceptible Streptococcus pneumoniae (PSSP), penicillin-intermediate resistant S. pneumoniae (PISP), penicillin-resistant S. pneumoniae (PRSP), Streptococcus milleri group and Peptostreptococcus spp. The antibacterial activity of CZOP either against MSSA or MSSE was preferable (MIC90: 2 or 0.5 micrograms/mL) and comparable to those of other cephems. CZOP was also effective on MRSE (MIC90: 16 micrograms/mL) but not on MRSA. CZOP and other cephems had low antibacterial activity against S. haemolyticus (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against S. saprophyticus was comparable to or higher than those of other cephems, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000 (32 vs 1-2 micrograms/mL). The antibacterial activity of CZOP against E. faecalis was comparable to that of cefpirome (CPR; MIC90: 16 micrograms/mL) and higher than those of other cephems. No antibacterial activity of CZOP against E. faecium and E. avium was observed, like other drugs. The antibacterial activity of CZOP against S. pyogenes was as potent as those of cefotiam and CPR (MIC90: < or = 0.063 microgram/mL), and, against S. agalactiae, was also preferable (MIC90: 0.125 microgram/mL). CZOP indicated preferable antibacterial activity either against PSSP, PISP, or PRSP (MIC90: 0.25, 1, or 2 micrograms/mL). The antibacterial activity of CZOP against S. milleri group was also preferable, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000 (4 vs 0.5 micrograms/mL). The antibacterial activity of CZOP against Peptostreptococcus spp. was preferable but weaker than those of cefazolin and cefmetazole. The resistance ratio estimated from breakpoint MIC of CZOP was 95.9% in MRSA, 93.5% in PRSP, 63.3% in PISP, 35.8% in S. haemolyticus, 27.9% in E. faecalis, and 13.3% MRSE. Those resistance ratios were comparable to those for cefepime (CFPM), but E. faecalis showed 91.2% for CFPM. The difference in the resistance ratio of E. faecalis demonstrated that CZOP successfully maintained its antibacterial activity against these species. In correlation of drug susceptibility, 40.3% of PRSP was not inhibited at breakpoint MIC either CZOP or CFPM while 69.2% at breakpoint MIC either CZOP or ceftazidime. In conclusion, the antibacterial activities of CZOP against the Gram-positive bacteria obtained from the 6-year duration study were consistent with the results from the studies performed until the new drug application approval. A decline in the sensitivities of S. saprophyticus, S. milleri group, PISP, and PRSP to CZOP, however, was suggested.