The in vitro activity of Sch 34343, a new penem antibiotic, was compared with those of imipenem, vancomycin, and eight other antibiotics against gram-positive bacteria. Ninety percent of methicillin-susceptible Staphylococcus aureus and penicillin-susceptible streptococcal isolates were inhibited by Sch 34343 at concentrations of less than or equal to 0.125 micrograms/ml. Listeria monocytogenes isolates were susceptible to the penem at concentrations of less than or equal to 0.25 micrograms/ml. Penicillin-resistant pneumococci and viridans streptococci were relatively resistant to Sch 34343 (MIC for 90% of the isolates, 4 micrograms/ml), as were methicillin-resistant strains of S. aureus (MIC for 90% of the isolates, greater than or equal to 256 micrograms/ml). All 48 strains of Streptococcus faecalis were inhibited by concentrations of less than or equal to 8 micrograms of the drug per ml. Combinations of Sch 34343 with gentamicin demonstrated bactericidal synergism against 5 of 10 enterococcal strains tested in broth media and against 6 of 10 strains tested in 50% pooled human serum. The serum protein binding of Sch 34343 was ca. 65%. The antibacterial activity of Sch 34343 remained stable after 24 h of incubation at 37 degrees C in water or Dextrose-Phosphate broth. However, 63% of bioassayable activity was lost after 24 h of incubation at 37 degrees C in 50% human serum buffered with HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) (pH 7.4).