Bactericidal activity and synergy studies of BAL9141, a novel pyrrolidinone-3-ylidenemethyl cephem, tested against streptococci, enterococci and methicillin-resistant staphylococci

BAL9141 has been reported to have inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA), many enterococci, and streptococci with various resistant patterns. BAL9141 potency was assessed by time–kill curves alone or with subinhibitory concentrations of gentamicin (MIC/4). BAL9141 exhibited bactericidal activity alone against all the streptococci and staphylococci. Among ampicillin-susceptible enterococci, BAL9141 was bactericidal against some strains, but no BAL9141 inhibition was observed of ampicillin-resistant Enterococcus faecium . The activity of BAL9141 with gentamicin was slightly enhanced (not synergy) or indifferent against staphylococci. BAL9141 demonstrated bactericidal action alone against Enterococcus faecalis and some E. faecium strains (− 4.8 to −6.0 log₁₀ CFU/mL), but static effects were also noted. Drug interactions with gentamicin showed early synergy (4–8 h) for all enterococci, and indifference or synergy at 24 h (no antagonism). BAL9141 (≤8 mg/L) showed promising bactericidal activity alone and synergy with gentamicin against some of the vancomycin-resistant enterococci tested.