HIGH-LEVEL PENICILLIN RESISTANCE AND PENICILLIN-GENTAMICIN SYNERGY IN ENTEROCOCCUS-FAECIUM

Thirty-seven Enterococcus faecium strains with different levels of penicillin susceptibility were studied in time-kill experiments with a fixed concentration (5 mug/ml) of gentamicin combined with different penicillin concentrations (6 to 600 mug/ml). Synergy was defined as a relative decrease in counts of greater than 2 log10 CFU per milliliter after 24 h of incubation when the combination of the antibiotics was compared with its most active component alone. The minimal synergistic penicillin concentrations found were 6 mug/ml for 16 of 16 strains for which penicillin MICs were less-than-or-equal-to 25 mug/ml, 20 to 100 mug/ml for 14 of 17 strains for which penicillin MICs were 50 to 200 mug/ml, and 200 to 500 mug/ml for 4 of 4 strains for which MICs penicillin were >200 mug/ml. Penicillin-gentamicin synergy was observed even in high-level penicillin-resistant E. faecium strains at penicillin concentrations close to one-half the penicillin MIC. The possibility of treating infections caused by high-level penicillin-resistant E. faecium strains with penicillin-gentamicin combinations in particular cases may depend on the penicillin levels attainable in vivo.