OToole Lab News
January 29, 2013
Greg Anderson, a former post-doc and current Assistant Professor at IUPUI, is the lead author on a current paper from the lab published in Pathogens and Disease. In this work, Greg used a bacterial-epithelial cell co-culture model to test the efficacy of fosfomycin/tobramycin antibiotic combination versus P. aeruginosa biofilms. This study showed that the fosfomycin/tobramycin combination worked as well as tobramycin alone in reducing viable biofilm-grown P. aeruginosa, and when treating at sub-inhibitory levels, reducing inflammatory cytokine production, despite the fact that the fosfomycin/tobramycin combination had 4-fold less tobramycin that the tobramycin-only control. Thus, this combination therapy works well and may reduce some of the potential side effects of aminoglycoside antibiotics. This project was done in collaboration with and was supported by Gilead Sciences, which makes the fosfomycin/tobramycin combination therapy.January 24, 2013
Mike Zegan's M.D., a long-time collaborator, had a recent study in JAMA cited in the Aspergillus News Letter. You can download the paper at the link titled: Mycotic Ulcer Treatment Trial: A Randomized Trial Comparing Natamycin vs Voriconazole. In this report, an international team of scientists showed that, as stated on the website, "Natamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases." This work will likely impact the standard of care for these infections.January 17, 2013
A recent article in Renal
and Urology News highlighted a clinical study showing that sodium citrate
works better than the commonly used heparin as a catheter lock
solution in hemodialysis patients. The
study, published in the American Journal of Health-System Pharmacy by Yon and Low, both clinical
nephrology pharmacists in the Veterans Affairs San Diego Healthcare System, was
based in part on a series of studies led by Robert Shanks Ph.D., a
post-doctoral fellow in my lab and in collaboration with Martha Graber M.D., a
nephrologist at the Dartmouth-Hitchcock Medical Center. Dr. Shanks is now an Associate Professor at
the University of Pittsburgh. Our
studies compared the impact of various catheter lock solutions
on biofilm formation by Staphylococcus
aureus and S. epidermidis, two
bacteria that commonly colonize and infect catheter lines. In a paper we published in 2005, we
showed that heparin actually stimulates biofilm formation by S. aureus on catheter-like material, and
demonstrated the existence of a pathway in the organism that likely responds to
the presence of heparin by enhancing the biofilms typically formed by these
organisms. A subsequent study in 2006
in Nephrology Dialysis Transplantation showed that sodium citrate at
concentrations above 0.5% efficiently inhibits biofilm formation and cell
growth of S. aureus and S. epidermidis, and for those organisms
most typically associated with these infections, so-called coagulase negative
Staphylococci, sub-inhibitory levels of citrate did not promote biofilm
formation. Together, these studies
strongly suggested that a switch from heparin to sodium citrate might reduce
infections in patients on dialysis. The
recent publication
in American Journal of Health-System Pharmacy indeed confirmed this hypothesis in a study of 60 hemodialysis
patients, which showed a reduction in infection from 33% in patients using
heparin to 19% of patients using citrate as a catheter lock
solution. Thus, the studies in the lab have had a positive impact on reducing infections in patients.


