DOI

10.17077/etd.9nwxk194

Document Type

Dissertation

Date of Degree

Spring 2017

Degree Name

PhD (Doctor of Philosophy)

Degree In

Chemical and Biochemical Engineering

First Advisor

Nuxoll, Eric E.

First Committee Member

Nuxoll, Eric E.

Second Committee Member

Guymon, C. Allan

Third Committee Member

Salem, Aliasger K.

Fourth Committee Member

Fiegel, Jennifer

Fifth Committee Member

Stoltz, David A.

Abstract

Upon forming a biofilm, bacteria undergo several changes that prevent them from being eradicated with antimicrobials alone. These biofilms manifest as persistent infections and biofouling in the medical and industrial world, respectively, constituting an ongoing medical crisis and creating a huge financial burden. Biofilms on implanted medical devices cause thousands of patients each year to undergo multiple surgeries to explant and replace the implant, driving billions of dollars in increased health care costs due to the lack of viable treatment options for in situ biofilm eradication. Heat has been used to reliably eliminate biofilms for many years, but the temperatures employed are infeasible for many applications, particularly in vivo medical treatment. Remotely activated localized heat can be applied through a superparamagnetic iron oxide nanoparticle polymer coating when paired with an alternating magnetic field. However, there is very little known about the temperatures required to kill the biofilms and the effects of the heat in conjunction with antibiotics. To better understand the required parameters to effectively kill off bacteria in biofilms a variety of heat treatments were investigated for a variety of Pseudomonas aeruginosa biofilms grown in different conditions. Additionally, these heat treatments were combined with antibiotics to better understand any combined effects of the two orthogonal treatment plans. It was found that heat is an effective method for killing the bacteria in biofilms. Temperatures ranging from body temperature, 37 °C, to 80 °C were used to heat shock the biofilms for 1 to 30 minutes. Higher temperatures for short exposure times yielded similar results to lower temperatures for longer exposure time. Biofilms grown in different conditions did vary in their susceptibility to the heat shocks; however, at the higher temperatures the differences became negligible. Therefore, the more effective treatments were the higher temperature heat shocks with shorter exposure times to maximize bacterial cell death and minimize the potential heat transfer to the surrounding tissue. Regrowth studies indicate a critical post-shock bacterial loading (~103 CFU/cm2) below which the biofilms were no longer viable, while films above that loading slowly regrew to their previous population density. Combined treatments with antibiotics had synergistic effects for all antibiotics across a window of heat shock conditions. Erythromycin in particular, which showed no effect on the biofilm alone, decreased biofilm population by six orders of magnitude at temperatures which had no effect in the absence of antibiotics. These studies will evolve the understanding of biofilms and how to efficiently eradicate them on implant surfaces. The introduction of such a novel coating in conjunction with antibiotics could obviate thousands of surgeries and save billions of dollars spent on explantation, recovery, and re-implantation.

Public Abstract

Each year in the U.S. hundreds of thousands of people develop a biofilm infection on their medically implanted devices. These biofilms are a community of bacteria that attach to a surface and have a protective layer preventing antibiotics from being effective. When a patient gets a biofilm infection the implant needs to be removed via invasive surgery and the patient is left without an implant during a long recovery process. Once the infection has subsided the patient can receive a replacement implant; however, that second implant has twice the likelihood of infection as the first. This leads to poor patient quality of life and costs the U.S. billions of dollars annually. Alternatively, a coating can be placed on the surface of an implant and can be heated wirelessly to kill the bacteria without ever performing an invasive surgery. The required temperatures and exposure times to those temperatures were investigated and combined with antibiotics to determine any combined effect. Higher temperatures for shorter amounts of times were determined to be the most robust treatment and the temperature could be decreased when antibiotics were used at the same time to eradicate the infection. A coating that can be heated wirelessly could improve the lives of thousands of patients and improve quality of life by decreasing the needs for additional surgeries, reducing recovery time, and saving the U.S. millions of dollars in medical expenditures.

Keywords

Antibiotics, Biofilms, Heat Shock, Implant Infections, Pseudomonas aeruginosa

Pages

xvi, 167 pages

Bibliography

Includes bibliographical references (pages 156-167).

Copyright

Copyright © 2017 Erica Noyes Bader Ricker

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