Gentamicin is one of the few aminoglycoside antibiotics which are approved for parenteral use
in Singapore. As with other aminoglycosides, gentamicin is primarily bactericidal against
Gram-negative organisms. It is well known that viral infection increases susceptibility to
bacterial infection; increased rates of Gram-negative bacterial sepsis due to
gastrointestinal tract bacterial translocation have been reported in Ebola and dengue
patients. Gentamicin use in viral infection could thus improve clinical outcome by inhibiting
both viral and opportunistic Gram-negative bacterial infection.
Parenteral aminoglycosides do not cause perturbations or dysbiosis within the human gut
microbiome. This is of importance as dysbiosis would not only increase the risk of
antibiotic-resistant bacteria selection within the intestinal tract, it could also lead to
negative downstream effects on the host response to infection by altering activation states
of both innate and adaptive immunity. Thus, parenteral gentamicin may offer a unique approach
to preventing both viral and downstream secondary Gram-negative bacterial infection, while at
the same time minimizing the potential development of antibiotic resistance.
The overarching goal of this study is to demonstrate that parenteral aminoglycosides exert
broad-spectrum antiviral effects against RNA viruses in humans through their
immunostimulatory properties. Using the live attenuated yellow fever (YF17D; stamaril)
vaccine as an experimental viral infection model, a placebo controlled clinical trial will be
carried out to demonstrate the efficacy of parenteral gentamicin in preventing viremia.