Synergistic effect of gentamicin plus ampicillin on enterococci with differing sensitivity to gentamicin: A phenotypic assessment of NCCLS guidelines

Dana C. Dressel, Michelle A. Tornatore-Reuscher, Cynthia R. Boschman, Valentina Stosor, Teresa R Zembower, Michael J. Postelnick, Gary A Noskin, Lance R. Peterson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Between December 1, 1993, and December 1, 1996, we tested 4,411 isolates of Enterococcus sp. at gentamicin concentrations of 500 μg/mL and 2000 μg/mL using agar dilution to phenotypically categorize them into 3 groups: those with a MIC ≤500 μg/mL (n = 3,132; 71%); a MIC >500, but ≤2000 μg/mL (n = 441; 10%); and those with a MIC >2000 μg/mL (n = 838; 19%). Ten unique strains of each phenotype were tested to determine which gentamicin concentration was the best in vitro predictor of synergy with ampicillin. Testing was done by a time-kill method using clinically achievable levels of ampicillin and gentamicin. We found that for the gentamicin MIC ≤500 μg/mL group, 7 of 10 isolates demonstrated synergy with ampicillin as manifested by a ≥2 log10 increase in killing versus the effect of ampicillin alone (at 1/2 the MIC for ampicillin). In the group sensitive to a gentamicin MIC range between >500 and ≤2,000 μg/mL, none of the 10 isolates demonstrated synergy. Absence of synergy was also found in the group resistant to 2,000 μg/mL of gentamicin. Assessment of eight additional enterococcal isolates with reduced sensitivity to ampicillin (MIC from 32-256 μg/mL) found no correlation between gentamicin sensitivity at 500 μg/mL and any in vitro test for synergy, nor with clinical therapeutic outcome. Gentamicin at 2 μg/mL combined with ampicillin was as effective in enhancing killing as a higher level of 4 μg/mL. These findings validate the current NCCLS guideline for predicting synergistic activity against enterococci in strains with usual susceptibility to ampicillin, and suggest that a therapeutic level less than maximal recommended dosing is sufficient when using gentamicin in this setting.

Original languageEnglish (US)
Pages (from-to)219-225
Number of pages7
JournalDiagnostic Microbiology and Infectious Disease
Volume35
Issue number3
DOIs
StatePublished - Nov 1 1999

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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