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Is Penicillin Plus Gentamicin Synergistic against Clinical Group B Streptococcus isolates?: An In vitro Study

Corinne Ruppen1, Agnese Lupo2, Laurent Decosterd3

  • 1Institute for Infectious Diseases, University of BernBern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of BernBern, Switzerland.

Frontiers in Microbiology
|November 8, 2016
PubMed

Insights

Penicillin plus gentamicin shows no synergy against Group B Streptococcus (GBS) in vitro. Gentamicin addition enhances rapid killing by penicillin at low concentrations but is not synergistic for GBS infective endocarditis or joint infections.

Area of Science:

  • Infectious Diseases
  • Microbiology
  • Pharmacology

Background:

  • Group B Streptococcus (GBS) is an emerging cause of invasive infections in non-pregnant adults, particularly the elderly and those with comorbidities.
  • Current recommendations for GBS infective endocarditis (IE) and periprosthetic joint infections (PJI) in adults suggest penicillin plus gentamicin, based on neonatal infection studies.
  • The potential for synergistic activity between penicillin and gentamicin in adult GBS isolates causing IE and PJI requires investigation.

Purpose of the Study:

  • To determine if penicillin and gentamicin exhibit synergistic activity against clinical isolates of Group B Streptococcus (GBS) responsible for infective endocarditis (IE) and periprosthetic joint infections (PJI).
  • To compare the results of checkerboard and time-kill assays (TKAs) for evaluating antimicrobial synergy.

Main Methods:

  • Utilized five GBS isolates (two clinical, three control), including one with high-level gentamicin resistance (HLGR).
  • Performed checkerboard assays to determine fractional inhibitory concentration indices (FICIs).
  • Conducted time-kill assays (TKAs) using penicillin (0.048 and 0.2 mg/L) and gentamicin (4 mg/L or 12.5 mg/L) to assess bacterial killing over time.

Main Results:

  • Checkerboard assays showed median FICIs indicating indifference between penicillin and gentamicin for all tested GBS isolates.
  • TKAs did not demonstrate synergistic killing with penicillin (0.048 or 0.2 mg/L) combined with gentamicin at either concentration.
  • Penicillin alone at 0.2 mg/L was bactericidal within 4-6 hours. Penicillin at 0.048 mg/L combined with gentamicin showed rapid killing within the first 8 hours, but this effect was not synergistic and diminished over 24 hours.

Conclusions:

  • In vitro results suggest that while gentamicin may enhance the speed of bacterial killing by penicillin at low concentrations in the initial hours, true synergistic activity was not observed against these GBS isolates.
  • Penicillin monotherapy demonstrated bactericidal activity within 24 hours.
  • The addition of gentamicin to penicillin does not appear to provide a synergistic benefit for treating GBS IE and PJI in vitro.
Keywords:
Group B StreptococcusStreptococcus agalactiaeaminoglycosidesgentamicinsynergism

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