MD Conference Express ICAAC 2011 - (Page 21)
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The Next Wave of Antimicrobial Approaches and Agents
Written by Noelle Lake, MD
A novel approach to treat drug-resistant microorganisms is antimicrobial photodynamic therapy (PDT), which is under investigation in animal models in the lab of Michael R. Hamblin, PhD, Wellman Center for Photomedicine, Massachusetts General Hospital Boston, Massachusetts, USA. PDT involves applying light from a laser, light-emitting diode, or other light source to an infected area that has been sprayed with a pathogenpenetrating photosensitizing agent. The combination of photosensitizer and light results in the generation of cytotoxic reactive oxygen species, which kills bacteria or fungi instantly (Figure 1). “There has never been a single pathogen discovered that is resistant to photodynamic therapy,” Dr. Hamblin said. Figure 1. Mechanisms of Action of Antimicrobial Photodynamic Therapy.
IC PS S PS e O2 Type III O2 PS PS Type I Radicals, OH
F
Virus
Gram-positive bacteria
Gram-negative bacteria
Fungus
Parasites
Reproduced with permission from M. Hamblin, MD. PS=photosynthesizer; IC=inhibitory concentration; F=flourescence.
PDT is safe for human tissue, because the photosensitizing agents penetrate bacteria quickly and take longer to affect eukaryotic cells. It is inexpensive and versatile and involves minimal training for staff and patients. Dr. Hamblin cites a further advantage in treating infections, such as traumatic infections and burns, since systemic antibiotics have trouble reaching damaged tissue. PDT has a broad therapeutic range, including viruses and parasites, and can reach pathogens in biofilms. In addition, Dr. Hamblin projects that PDT may be useful in the treatment of otitis media, necrotizing fasciitis, bacterial cystitis, gastric H. pylori, sinusitis, or any infection where dye and light can be infused. Two interesting areas of PDT research are: (1) the pursuit of ideal photosensitizing agents, such as bacteriochlorins and porphycenes, and (2) assessing the effects of PDT in animal models of infection with bioluminescent organisms. Decreasing bioluminescence (correlating with decreased colony-forming units) and improved survival have been seen with burns in mouse models [Dai et al. Virulence 2001], soft tissue [Gad et al. Photochem Photobiol Sci 2004], and sepsis across a range of pathogens, including MRSA [Dai et al. Lasers in Surg and Med 2010], E. coli, Pseudomonas, Acinetobacter [Dai et al. Antimicrob Agents Chemother 2009], S. aureus [Gad et al. Photochem Photobiol Sci 2004], and Candida [Dai et al. Antimicrob Agents Chemother 2011]. PDT may also stimulate wound healing. Scott F. Singleton, PhD, University of North Carolina, Chapel Hill, North Carolina, USA, is leading a team of researchers in the development of novel antibacterial adjunct agents that inhibit bacterial enzymes that are involved in DNA repair. Their current focus is a RecA inhibitor to combine with and potentiate the effect of DNA-damaging antibiotics. RecA protein of Escherichia coli and other anabolic enzymes are upregulated by intracellular stress that is induced by antibiotic treatment and enable bacteria to survive [Kohanski
Peer-Reviewed Highlights from the
51st ICAAC
Official Peer-Reviewed Highlights from the 51st ICAAC
21
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Table of Contents for the Digital Edition of MD Conference Express ICAAC 2011
MD Conference Express ICAAC 2011
Contents
Infectious Disease Genomics
Emerging Resistance Among Gram-Negative Pathogens
Procalcitonin-Guided Antibiotic Therapy In Patients with Lower Respiratory Tract Infections
Combination Therapy with Flucytosine Improves Survival in AIDS-Related Cryptococcal Meningitis
CXA-201 Effective Against Common ICU Pathogens
Tigecycline Plus Standard Therapy Is More Effective For Treating Infections in Febrile Neutropenic Cancer Patients
Interventions Aimed at Reducing MRSA BSIs Led to Decreased Rates of Nosocomial MSSA BSIs
Is the Effectiveness of aP Vaccine in Pre-Adolescents Insufficient?
TMC435 Effective in the Treatment of HCV Genotype 1 Infection
HIV
Vaccines
Antibiotic Resistance
Drug Discovery
The Conundrum of MDR TB and Combination Therapy
New Drugs to Treat MDR Pathogens
Immunizations in Reproductive Health
Why Can’t Microbes Just Get Along?
The Role of Adjunctive Steroids in the Treatment of Bacterial Meningitis
Human and Animal Viruses Share “One World” and Emerging Zoonotic Infections Continue to Threaten
MD Conference Express ICAAC 2011
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