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In vitro activity of gentamicin as an adjunct to penicillin against biofilm group B Streptococcus
Corinne Ruppen1,2, Andrew Hemphill3, Parham Sendi4,5
1Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
Objectives:
Group B Streptococcus (GBS) increasingly causes invasive disease in non-pregnant adults, particularly in elderly persons and those with underlying diseases. Combination therapy with penicillin plus gentamicin has been suggested for periprosthetic joint infection. The postulated synergism of this combination is based on experiments with planktonic bacteria. We aimed to assess the efficacy of this combination against sessile bacteria.
Methods:
Four different GBS strains were used. We compared results of MICs with those of minimal biofilm eradication concentrations (MBECs), applied chequerboard assays to the MBEC device and calculated the fractional inhibitory concentration index. Synergism was evaluated with time-kill assays against bacteria adherent to cement beads, using penicillin (0.048, 0.2 and 3 mg/L), gentamicin (4 and 12.5 mg/L) and a combination thereof. Results were evaluated via colony counting after sonication of beads and scanning electron microscopy.
Results:
MBEC/MIC ratios were 2000-4000 for penicillin and 1-4 for gentamicin. In chequerboard assays, synergism was observed in all four isolates. In time-kill assays, penicillin and 12.5 mg/L gentamicin showed synergism in two isolates. In the other two isolates 12.5 mg/L gentamicin alone was as efficient as the combination therapy.
Conclusions:
These in vitro investigations show activity of 12.5 mg/L gentamicin, alone or as an adjunct to penicillin, against four strains of biofilm GBS. This concentration cannot be achieved in bone with systemic administration, but can be reached if administered locally. The combination of systemic penicillin plus local gentamicin indicates a potential application in orthopaedic-device-associated GBS infections. Studies with a larger number of strains are required to confirm our results.
Insights
Gentamicin, at 12.5 mg/L, shows efficacy against biofilm Group B Streptococcus (GBS) infections, alone or with penicillin. Local administration is key for treating orthopedic device-associated GBS infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Group B Streptococcus (GBS) causes invasive disease in non-pregnant adults, especially the elderly and immunocompromised.
- Combination therapy of penicillin and gentamicin is proposed for GBS periprosthetic joint infections, but its efficacy against sessile bacteria is unclear.
Purpose of the Study:
- To evaluate the in vitro efficacy of penicillin and gentamicin combination therapy against sessile Group B Streptococcus (GBS) bacteria.
- To compare the activity of antibiotics against planktonic versus biofilm GBS.
Main Methods:
- Minimal biofilm eradication concentrations (MBECs) and time-kill assays were used to assess antibiotic activity against GBS biofilms on cement beads.
- Chequerboard assays determined fractional inhibitory concentration index for synergistic effects.
- Scanning electron microscopy visualized bacterial adherence and eradication.
Main Results:
- Gentamicin exhibited low minimal inhibitory concentration (MIC)/MBEC ratios, indicating good biofilm penetration.
- Synergistic activity between penicillin and gentamicin was observed in chequerboard assays for all GBS strains.
- In time-kill assays, 12.5 mg/L gentamicin alone or with penicillin demonstrated efficacy against biofilm GBS, with some isolates showing equivalent results with gentamicin alone.
Conclusions:
- 12.5 mg/L gentamicin demonstrates in vitro activity against biofilm GBS, supporting its potential use in treating orthopedic device-associated GBS infections.
- Local administration of gentamicin is necessary to achieve effective concentrations in bone, suggesting a combination of systemic penicillin and local gentamicin.
- Further studies with more GBS strains are needed to confirm these findings.
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