The prevalence of antibiotic resistant bacteria necessitates exploration of alternative approaches to treat hospital and
community acquired infections. The aim of this study was to determine whether bacterial pathogens develop resistance
to antimicrobial photodynamic therapy (aPDT) during repeated sub-lethal challenge. Antibiotic sensitive and resistant
strains of S. aureus and antibiotic sensitive E. coli were subjected to repeat PDT treatments using a methylene blue
photosensitizer formulation and 670 nm illumination from a non-thermal diode laser. Parameters were adjusted such that
kills were <100% so that surviving colonies could be passaged for subsequent exposures. With each repeat, kills were
compared to those using non-exposed cultures of the same strain. Oxacillin resistance was induced in S. aureus using a
disc diffusion method. For each experiment, "virgin" and "repeat" cultures were exposed to methylene blue at 0.01%
w/v and illuminated with an energy dose of 20.6 J/cm2. No significant difference in killing of E. coli (repeat vs. virgin
culture) was observed through 11 repeat exposures. Similar results were seen using MSSA and MRSA, wherein kill rate
did not significantly differ from control over 25 repeat exposures. In contrast, complete oxacillin resistance could be
generated in S. aureus over a limited number of exposures. PDT is effective in the eradication of pathogens including
antibiotic resistance strains. Furthermore, repeated sub-lethal exposure does not induce resistance to subsequent PDT
treatments. The absence of resistance formation represents a significant advantage of PDT over traditional antibiotics.
The nosocomial infection rate has increased dramatically due to emergence of antibiotic resistant bacterial strains such as
methicillin resistant Staphylococcus aureus (MRSA). The primary anatomical site of MRSA colonization is the anterior
nares, and this reservoir represents a primary vector of transmission from non-infected carriers to susceptible individuals.
Antimicrobial photodynamic therapy (aPDT) has been used successfully for topical disinfection in the oral cavity. The
aim of this study was to evaluate the utility of aPDT for nasal MRSA decolonization at the preclinical and clinical level.
The nasal aPDT system consists of a 670 nm diode laser fibre-optically coupled to a disposable light diffusing tip, used
to activate a methylene blue based photosensitizer formulation. Preclinical testing was done both in a custom nasal
reservoir model and on human skin cultures colonized on the epithelial surface with MRSA. Human clinical testing was
performed by clinicians in regions in which the system is approved by the regulatory authority. In vitro testing
demonstrated that aPDT eradicated planktonic MRSA in an energy and photosensitizer concentration dependent manner.
Furthermore, aPDT eliminated sustained colonization of MRSA on cultured human epithelial surfaces, an effect that was
sustained over multiple days post-treatment. In preliminary human testing, aPDT eradicated MRSA completely from the
nose with total treatment times <10 minutes. aPDT is effective against MRSA when used topically in the nose. Energy
dose and photosensitizer parameters have been optimized for the nasal environment. Controlled clinical studies are
currently underway to further evaluate safety and efficacy.
Periodontitis affects half of the U.S. population over 50, and is the leading cause of tooth loss after 35. It is believed to
be caused by growth of complex bacterial biofilms on the tooth surface below the gumline. Photodynamic therapy, a
technology used commonly in antitumor applications, has more recently been shown to exhibit antimicrobial efficacy.
We have demonstrated eradication of the periopathogens Porphyromonas gingivalis, Fusobacterium nucleatum, and
Aggregatibacter actinomycetemcomitans in vitro using PeriowaveTM; a commercial photodisinfection system. In
addition, several clinical studies have now demonstrated the efficacy of this treatment. A pilot study in the U.S. showed
that 68% of patients treated with PeriowaveTM adjunctively to scaling and root planing (SRP) showed clinical attachment
level increase of >1 mm, as opposed to 30% with SRP alone. In a subsequent larger study, a second PeriowaveTM
treatment 6 weeks after initial treatment led to pocket depth improvements of >1.5 mm in 89% of patients. Finally, in the
most recent multicenter, randomized, examiner-blinded study conducted on 121 subjects in Canada, PeriowaveTM
treatment produced highly significant gains in attachment level (0.88 mm vs. 0.57 mm; p=0.003) and pocket depth (0.87
mm vs. 0.63 mm; p=0.01) as compared to SRP alone. In summary, PeriowaveTM demonstrated strong bactericidal
activity against known periopathogens, and treatment of periodontitis using this system produced significantly better
clinical outcomes than SRP alone. This, along with the absence of any adverse events in patients treated to date
demonstrates that PDT is a safe and effective treatment for adult chronic periodontitis.
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