We tested ertapenem (MK-0826), a new carbapenem, and 13 other antimicrobials by microbroth dilution against 102 isolates of Streptococcus pneumoniae, selected to include organisms resistant to a variety of drug classes. Ertapenem MICs ranged from < or =0.008 to 4 mg/l, MIC(50)=0.5 mg/l, and MIC(90)=2 mg/l. Based on MIC(90), ertapenem potency was 4-fold greater than cefuroxime, 2-fold greater than amoxycillin/clavulanate, =penicillin, 2-fold less than meropenem and ceftriaxone, and 4-fold less than imipenem. Other drug classes including macrolides, tetracycline and fluoroquinolones were less potent overall than the carbapenems. Linezolid (MIC(90)=1 mg/l) was the only agent tested for which all isolates were fully susceptible. Activity of ertapenem decreased as MICs to penicillins, cephalosporins, other carbapenems and macrolides increased. Isolates resistant to clindamycin, tetracycline or fluoroquinolones showed no obvious decrease in ertapenem activity when compared with susceptible isolates with the majority of isolates resistant to these drug classes inhibited by ertapenem at concentrations less than 1 mg/l. Ertapenem may prove useful as an alternative to ceftriaxone and other agents in the treatment of community-acquired pneumonia (CAP) due to S. pneumoniae, including infections caused by organisms with reduced susceptibilities to other antimicrobial agents.