Is gentamicin necessary in the antimicrobial treatment for group B streptococcal infections in the elderly? An in vitro study with human blood products

Abstract

Background: According to expert opinions, gentamicin should be administered as an adjunct to penicillin against severe group B streptococcal (GBS) infections. Whether the adjunct is important is of particular interest for elderly patients. Not only is the risk of aminoglycoside nephrotoxicity higher in elderly persons, but their immune defence to bacterial infections may also be impaired.

Method: Time-kill assays with human blood products, such as serum, neutrophilic granulocytes (opsonophagocytic assays) and whole blood from healthy, elderly volunteers were performed to evaluate the effect of gentamicin in combination with penicillin.

Results: In time-kill assays with human serum and in opsonophagocytic assays, we saw a trend for faster killing with the penicillin–gentamicin combination therapy. This effect was seen 4 and 6 h after antibiotic exposure but not at time points evaluated at ≥8 h. In whole blood killing assays, no difference in killing rates was observed with adjunctive gentamicin therapy.

Conclusion: The criteria for synergism were not fulfilled when the effect of penicillin–gentamicin combinations was compared with that of penicillin monotherapy. Rapid killing of GBS within the first few hours was observed in time-kill assays with human blood products. Considering that elderly people are prone to gentamicin nephrotoxicity and that in severe GBS infection a high penicillin dose is administered every 4–6 h, the prolonged use of adjunctive aminoglycosides in these infections requires caution.

Keywords:

• Group B Streptococcus
• Streptococcus agalactiae
• synergism
• aminoglycosides
• gentamicin

Acknowledgements

We thank Dr. Michael Horn and Jris Haener from the Clinical Chemistry University Hospital (Bern, Switzerland), for determining the immunoglobulins in the donor blood and Dr. Thomas Mercier from the Division and Laboratory of Clinical Pharmacology, Service of Biomedicine, Department of Laboratories, Lausanne University Hospital (Centre Hospitalier Universitaire Vaudois, CHUV), Lausanne, Switzerland, for determining antibiotic concentrations used in our experiments. We also thank Moana Mika from the Institute of Infectious Diseases, Bern, Switzerland, for her assistance with the whole blood killing assays, and all the volunteers for their blood donations.

Disclosure statement

The authors declare that they have no conflict of interest.

Funding

This work is supported by the Velux Stiftung (Grant 724), Zurich, Switzerland.