Low hanging fruit in infectious disease drug development

Kraus, Carl

doi:10.1016/j.mib.2008.09.009

Cited by 35 publications

(25 citation statements)

References 30 publications

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“…Multidrug-resistant (MDR) and pandrug-resistant (PDR) bacterial strains and their related infections are emerging threats to public health throughout the world [89]. These are associated with approximately two-fold higher mortality rates and considerably prolonged hospital admissions [90].…”

Section: Discussionmentioning

confidence: 99%

Ultraviolet blood irradiation: Is it time to remember “the cure that time forgot”?

Hamblin

2016

Journal of Photochemistry and Photobiology B: Biology

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Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However with the development of antibiotics, the use of UBI declined and it has now been called “the cure that time forgot”. Later studies were mostly performed by Russian workers and in other Eastern countries, and the modern view in Western countries is that UBI remains highly controversial. This review discusses the potential of UBI as an alternative approach to current methods used to treat infections, as an immune-modulating therapy and as a method for normalizing blood parameters. Low and mild doses of UV kill microorganisms by damaging the DNA, while any DNA damage in host cells can be rapidly repaired by DNA repair enzymes. However the use of UBI to treat septicemia cannot be solely due to UV-mediated killing of bacteria in the bloodstream, as only 5–7% of blood volume needs to be treated with UV to produce the optimum benefit, and higher doses can be damaging. There may be some similarities to extracorporeal photopheresis (ECP) using psoralens and UVA irradiation. However there are differences between UBI and ECP in that UBI tends to stimulate the immune system, while ECP tends to be immunosuppressive. With the recent emergence of bacteria that are resistant to all known antibiotics, UBI should be more investigated as an alternative approach to infections, and as an immune-modulating therapy.

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Section: Discussionmentioning

confidence: 99%

Ultraviolet blood irradiation: Is it time to remember “the cure that time forgot”?

Hamblin

2016

Journal of Photochemistry and Photobiology B: Biology

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“…This review focuses on the scientific challenges to the discovery of novel small-molecule antibacterials rather than on the commercial and regulatory considerations, which are well covered in a number of reviews (186,197,301,303,345). Rate-limiting steps to the discovery process are discussed, and some perspective on avenues to address those limitations is offered.…”

Section: Introductionmentioning

confidence: 99%

Challenges of Antibacterial Discovery

Silver¹

2011

Clin Microbiol Rev

1,136

961

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SUMMARY The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.

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“…Infectious disease is now the second leading killer in the world, number three in developed nations 8 and fourth in the United States. 9 Worldwide, 17 million people die each year from bacterial infections.…”

Section: Understanding the 'Crisis'mentioning

confidence: 99%

Antibiotics Induced Seizures and Encephalopathy

Cho¹

2018

J Neurocrit Care

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Low hanging fruit in infectious disease drug development

Cited by 35 publications

References 30 publications

Ultraviolet blood irradiation: Is it time to remember “the cure that time forgot”?

Ultraviolet blood irradiation: Is it time to remember “the cure that time forgot”?

Challenges of Antibacterial Discovery

Antibiotics Induced Seizures and Encephalopathy

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