Killing kinetics of clinical isolates of group B streptococci isolated in Belgium for penicillin alone or in combination with gentamicin

BACKGROUND: Associated with high morbidity and mortality, severe GBS infections should be treated with antimicrobial agents alone or in combination characterized by both a good diffusion at the site of infection and a short bactericidal lag time. Penicillin (P) or another blactam used in combination with an aminoglycoside is usually recommended to start the therapy. MICs to gentamicin (G) of GBS recently isolated in Belgium range from 16 to 256 mg/L (> or = MICs of E.faecalis with low level resistance to G, LLR).
OBJECTIVES: To investigate in vitro, the potential synergism of P+G on strains of GBS isolated in Belgium.
METHODS: According to Etest-AB Biodisk original procedures, for 6 Belgian strains of GBS (G MICs: 16-128 mg/L), we investigated the potential synergism, MICs and time killing curves, between P and G (ratio1:1). In the killing kinetic assays, surviving organisms were enumerated initially and repeatedly after 2, 4, 8 and 20 hours (T2, T4, T8 and T20) at concentrations of P equal to 4 and 16x MICs. Two strains of E.faecalis (1 HighLR and 1 LLR to G) were used as negative and positive control. Each isolate was tested twice.
RESULTS: For GBS the P MICs in the combination were within +/- 1 dilution compared with single drug. As expected, P+G produced enhanced killing at T2 and T4 compared with P alone for G LLR E.faecalis and there was no difference for the G HLR E.faecalis. On the contrary, no accelerated killing was observed for any GBS isolate with the combination even for a concentration of 16xMIC of P; moreover for 3 isolates a reduced killing was observed at T2 in the combination tests compared with P alone.
CONCLUSION: This limited in vitro testing of the combination P+G compared with P alone for Belgian GBS isolates did not show any synergism or accelerated killing. Moreover the killing was reduced at T2 for half of the isolates. Further evaluation should be performed on these strains with other ratio or other b-lactams as ampicillin in combination with G.