Doripenem (formerly S-4661), a new 1-beta-methyl carbapenem, was challenged with a worldwide collection of 394 drug-refractory isolates. For endemic extended-spectrum beta-lactamase- and stably derepressed AmpC-producing enteric bacilli, the doripenem MICs at which 90% of the isolates were inhibited (MIC90s) were 0.03 to 0.5 microg/ml, generally lower than those of comparator carbapenems. A greater proportion of strains among carbapenem-resistant nonfermentative gram-negative bacilli were inhibited by doripenem at < or =4 microg/ml, and doripenem was the most active carbapenem (MIC90, 1 to 4 microg/ml) against penicillin-resistant streptococci.