Naked Science Forum

Life Sciences => Cells, Microbes & Viruses => Topic started by: Ylide on 04/03/2004 02:30:32

Title: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Ylide on 04/03/2004 02:30:32
In honor of the new category, does anyone know a good literature source for research on the use of bacteriophagic viruses in antibiotic treatment?  I'm giving a presentation in a few weeks for a class and I want to use that topic.  


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Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: chris on 04/03/2004 04:39:59
A great choice for a topic ! You could start with a few naked scientist references :

http://www.thenakedscientists.com/html/shows/2004.01.11.htm

The above is a good reference because it touches on an extension of bacteriophage therapy - reawakening dormant integrated phages and conferring bactericidal effects upon them.

http://www.thenakedscientists.com/html/shows/2002.01.20.htm click full-length text for the whole story

This is a study in which phage therapy saved the lives of experimental mice challenged with a virulent bacterial strain.

Chris


"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Ylide on 05/03/2004 00:08:52
Thanks Chris!  That's precisely what I'm looking for.  I'm on dialup right now so I only read the text caption at the bottom...do you know any names of researchers or what university they were from so I can do a literature search on them?

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Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: chris on 05/03/2004 03:34:38
Sorry, I buggered up and put the same reference in twice. I've now changed it.

The 2004 link (top one, which also contains a link to the 2002 reference) was by scientists at the university of Warwick - full details in the article.

Chris

P.S. The audio is set up so that dial-up users can receive it as the band width is low (32 kbps). This means that you can listen to the show in the background whilst browsing elsewhere on the site or internet !

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Ylide on 20/04/2004 07:25:27
Did you know they've been using successfully using phage therapy to treat bacterial infections in the Republic of Georgia since the 1940's?    

I also came across a lab that found the enzyme that phages use to lyse the bacyerial cell when it's done replicating and ready to spill the next generation of phages into the environment.  They've isolated it and are successfully using it to destroy bacterial colonies without even involving phages.  



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Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: cuso4 on 20/04/2004 12:39:34
Russia also have been using phage therapy for ages. If I was diagnosed a serious bacterial infection I would insist on using phage therapy instead of antibiotics treatment.

Angel
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: chris on 20/04/2004 14:50:23
Er I don't think you would somehow. If you had meningitis I can't see you accepting a trial medicine in place of something that is known to be a reliable cure for yourself or a loved one.

Phage therapy has its place but is not, by a long chalk, about to usurp the role of standard antimicrobial therapy. It is being developed more as an adjunct to standard therapy, and to tackle more difficult infections where antimicrobial resistance is a problem !

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Ylide on 24/04/2004 08:55:49
Why would you want to use antibiotic treatment if fully developed phage therapy were an option?  Antibiotics are often ineffective, can have bad side effects, and are nonselective for beneficial enterics vs. pathogens.  Phages are generally specific to a species (or at least a genus) and have no documented pathogenic effect eukaryotic cells.  Antibiotic treatment is a back-and-forth war of attrition that involves mutation, response, mutation, response, ad-nauseam.  Why not nip it in the bud with something allegedly less vulnerable to spontaneous resistance.  

In a few cases where bacteria have mutated such that the phage was unable to attack them, the mutations caused them to be less virulent.  The phages sought out the encapsulation layer of the bacteria, the bacteria shed it in a random mutation, and the phages had no "handle" on which to grab, but the lack of encapsulation allowed for the test organism's immune system (bird or mouse, can't remember) to deal with it.  

There's also some really cool work going on that interferes with the chemical methods of communication between bacteria that they use to decide when to transfer genetic material, emit toxins, and reproduce.  The woman who discovered it was featured in Scientific American a few months ago.  I'll dig it up if anyone's interested.



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Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: chris on 26/04/2004 09:12:50
Well for a start there's the problem of tissue penetration. Phages are all well and good if they can reach the site of infection. But in the context of meningitis, for example, where the bugs are within the meninges, access becomes a problem. The antibiotic molecules used are extremely small and have excellent CNS penetration. In the context of a life threatening infection you do not mess around, nor allow the worry of some subsequent diarrhoea influence your choice of therapy.

I've seen a man with bacterial meningitis go from alert, conscious and able to share a joke, to barely rousable with a rash spreading in front of my eyes. Another 30 minutes and he would have been irretrievable. As it was a regular doses of intravenous broadspectrum antibiotics saved his life. And he didn't get any diarrhoea either !

I am a big supporter of phage therapy but everything has its place and it should not be used just because it is new.

(By the way, the inter-bacterial signalling you are referring to, cannnabinoid, is called "quorum sensing".)

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Ylide on 27/04/2004 03:21:58
Yes, the term quorum sensing was in the article.  She also nicknamed it "bacterial esperanto" since it didn't seem to be species-specific.  (or even genus or family specific)

Thanks for the example...I was wondering about tissue penetration while I was researching this.  In things like staph or enteric infections or even tuberculosis, I guess it's not really a problem as it's pretty much open access, but the meninges sure are a pain to get to.  Could you inject a serum of the phage directly into the spinal fluid without too many complications?  I'm curious to know how the phages would seek out the bacteria when they'd have all that area to cover.  Maybe they're sensitive to chemical signals given off by the bacteria?

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Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: alastair84 on 13/05/2004 02:46:09
quote:
Originally posted by cuso4

Russia also have been using phage therapy for ages. If I was diagnosed a serious bacterial infection I would insist on using phage therapy instead of antibiotics treatment.

Angel


omg that makes me laugh! Russia has been trialing bacteriophage technology yes, but phage therapy has no where near come close to any sort of viable effective treatment that rivals antibiotics.
Phage therapy potential was realised ages ago ....50-60years or more? but the first few trials and experiments (many of them in russia) were inconsistant and not conclusive. since then the interest has faded as not many people could produce experiments with decent results. i think some form of bacteriophage tech is used in sewage treatments somewhere?
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Ylide on 13/05/2004 11:40:53
When the bacteria are antibiotic resistant, and its a localized infection (i.e. staph. skin infection or something along those lines) phage therapy is a good option.  Healthcare professionals throwing antibiotics at every little infection is what got us into the problem to begin with...well, that combined with stupid patients that don't finish the entirety of their prescription.



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Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Ylide on 13/05/2004 11:48:41
Oh, and you might want to look into current phage therapy and research before decrying it as archaic and inconclusive.  It's certainly not perfected, but give it time.  It beats throwing more money and time into the back and forth battle of new antibiotic -> resistance -> new antibiotic -> resistance.  

For what it's worth, I read that a lab has isolated the compound used by phages to lyse bacterial cells, synthesized it, and are using it to decimate bacterial colonies very successfully.  Most bacterial defenses against phages involve changing their surface protein markers to avoid attachment or using endonucleases to chop up the invading phage DNA, so this stuff absolutely brutalizes them.





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Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: alastair84 on 13/05/2004 12:38:33
i did, I did a mini-review on phagetherapy. I did not say current phage therapy was "archaic and inconclusive", all i'm saying is that it has a very very long way to go in terms of systemic infection treatment rivalling antibiotics and if anybody things otherwise they are kidding themselves.
Still, there is potential to be realized.
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: chris on 14/05/2004 08:42:53
We're actually quite a bit closer than you think. I recently interviewed a phage researcher from the UK who was come up with an excellent application for bacteriophages that will make a big impact on nosocomial (hospital acquired) infections.

I won't say any more until the piece has been broadcast...because no one is doing what he's got planned, and it's a great story !

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 10/10/2004 01:09:37
Is anyone interested in revisiting bacteriaophage therapy? I just finished the 2003 book on phage therapy and am updating my presentation for Nov. 10, 2004. Below is book review:

GESUND DURCH VIREN - EIN AUSWEG AUS DER ANTIBIOTIKA-KRISE.
German book by Thomas Häusler, Piper, München, September 2003, 275 Seiten - amazon.de Preis: EUR 15,90.

Healthy Through Viruses - a way out of the antibiotic-resistance crisis.

In 1969 the Surgeon General of the United States, William H. Stewart announced that; it is time to close the books on microbial infections! The war against epidemics due to pathogens has been won. Seldom has medical dogma pronounced by the highest ranking medical officer of the USA
been rendered absurd so rapidly. Actually infections due to pathogens did temporarily decrease during the 1960's; however, only to return twenty years later with increased vehemence.

After the political collapse of the Soviet Union the number of cases of consumption doubled there within only seven years.  Today  in the area of Aral Sea one of 300 inhabitants is sick with tuberculosis - a dramatically high number. Between 1972 to 1992 in New York a disease epidemic due to multi-resistant mycobacteria was rampant with approximately 400 new infections per year and it cost an estimated billion dollar to control this outbreak.  Nosocomial infections - hospital acquired infections - and multi-resistant pathogens, terms which until recently were familiar only to experts, are today topics of the public press. And it is not surprising because in Germany  alone 20000 people die annually of nosocomial infections.

The prospects for the future are still gloomier. While it took approximately fifty years for 95 per cent of Staphylococcus aureus strains to become resistant to penicillin, today certain problem bacteria need only a few years to acquire resistance even to totally new classes of antibiotics. Additionally,  the pharmaceutical industry no longer has many success-promising chemical substances in the research pipeline as they had a decade ago.  At the same time; however, the need for effective antibiotics continues to increase:  Ever more patients must be protected against the threat of infections because of weakened immune systems or because they are organ transplant recipients.

New hope is promised by a therapy which is substantially older than penicillin:  treatment with bacteriophages.  On August 2, 1919 their discoverer, the French Canadian Felix d’Herelle, administered a cloudy broth containing Shigella phages to a deathly-ill boy at the Pasteur Institute in Paris, curing him of dysentery. After an early, world-wide boom, this therapy today exists essentially only in the former Soviet republic of  Georgia and is only now again receiving attention in the West, even if many infection control specialists remain sceptical.

This paradigm shift is the background for an unusually well researched, outstandingly well written and scientifically based book by the Swiss journalist Thomas Häusler.  From the beginnings to the present the author, who also holds a doctorate in biochemistry, describes all aspects of a concept (bacteriophage therapy), whose therapeutic potential is not easily communicated during times of AIDS and SARS.

Bacteriophages are actually extremely dangerous viruses, however with an important difference; they have specialized in attacking bacterial cells and they do no harm to animal cells. When a phage discovers a bacterium to which it possesses the correct key - that is to say:  that on the bacterial cell surface there are suitable receptors to which the phage can attach with its tentacle-like extensions - then the phage will inject its hereditary DNA into the bacteria cell within minutes.  Taking-over the bacterial cell’s biochemical apparatus hundreds of phage copies are then produced.  Special enzymes [(Holine and lysine)?] break the cell wall open from the inside, the victim dies, and the released daughter phages attack any remaining bacterial cells like a pack of hungry wolves.

The advantages of the therapy are obvious.  Bacteriophages are very specific parasites and, contrary to antibiotics, do not damage the useful bacteria, which live in and on the body. Due to their mode of action they can not induce resistance, and if a pathogen is insensitive, then it most likely that there exists another virus (phage), which will act as the bacteria killer. Phages are "intelligent" medicines:  They increase just where they are needed (while antibiotics often do not even get to where they are to work).

The high specificity, with which phages look for their bacterial victims, is at the same time also their therapeutic Achilles' heel.  Either the infection control specialist must have a cocktail containing very many different types of phages, or a phage specifically effective against the pathogen of each patient  must be custom-made through detailed microbiological analytical work and must then be mass-produced.  In both cases regulatory authorities tend to loath recognizing such manually manufactured anti-infective agents as medicines.

For chronic infections on outside and internal body surfaces due to multi-resistant pathogens,  which can not be treated with current methods, phage therapy could become a kind miracle medicine. Additionally, phages could bring an end to feeding antibiotics in large-scale animal production.

Throughout the book, interviews with researchers, who are active at the front new developments, are skillfully intertwined with descriptions of actual patient outcomes. The middle part of the book is also outstanding in describing the trails and errors of phage therapy as practiced between 1930 and 1990. Here journalist Häusler points out, what influence political events have on the medical research - from the "Great Patriotic War" of Russia against Nazi Germany to the collapse of the Soviet Union and up to September 11, 2001.  A long list of footnotes, a detailed list of references and numerous instructive illustrations supplement the text excellently.

A book dealing with an explosive topic, as one cannot make it better.  

( Original in German by Hermann Feldmeier at amazon.de

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: chris on 11/10/2004 09:06:34
Sounds great - what's your background ?

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 12/10/2004 01:05:19
I am a retired microbiologist (PhD) with food, drug, cosmetic, toy and environmental microbiology experience both in industries and regulatory agencies. In the early 60's I worked in the summer in a dairy laboratory and because we had a coliform problem we hired a just retired university professor as a consultant. It so happened that I was responsible for growing the cultured buttermilk starters. When they turned to water the professor started telling me all about phages and being of the age where he remembered phage therapy, I was told all about it and he concluded that phage therapy would make a come-back when antibiotic resistance is a major. I tried a few times in the 70's to interest colleagues in using pahges to reduce salmonella in poultry but then went into drug, cosmetic and mediacl device microbiology.

Having had lots of experience with antimicrobial substances and therefore resistance, I always thought about phage therapy. When I retired in 1998 I googled "bacteriophages as antibiotics" and was surprised that it had become a old-new-again research area. Since then I have organized a symposium on phage therapy and public health in Chicago. I have given a number of talks and have appeared on TV.

Reading English, German and French has helped me get a good feeling for the subject. You can see some of my comments/papers at http://www.phages.org and click forum - look for G.W. (Bill) Riedel.

Here in Canada the news reports that actor C. Reeves was in hospital in part for an infected pressure wound - if you go to the Georgian Phage Therapy Center website at http://www.phagetherapy.org it will become clear that that is the type of wound very suitable for phage therapy - IF PHAGES FOR THE PARTICULR organism are available.

Yesterday when I signed on I could not think of a favourite saying. I have written a piece from the point of view of a microbiologist who is well informed about phage therapy and is allowed to die of a superbug infection. The piece ends with:

WHY DID YOU LET ME DIE RATHER THAN PHAGE ME?

I should mention that I DO NOT think phage therapy will replace antibiotics; but because it works by a different mechanism it is important where antibiotic-resistance has become a problem and it is my opinion that the science is sufficiently advanced that it can be used as a last resort (topical and oral preparations only). In Canada that would be under the Special Access Program of our Food and Drugs Act - similar to the treatment of 9 paptients in Hannover, Germany - treatment was apparently successfull in 7 cases. According to Polish work (published in English) with over 1000 patients succes is about 90% with infections caused by a range of pathogens.

Cheers, phdkso - (you guess what that stands for!)

Also see: http://www.cheminst.ca/sections/ottawa/phage.PDF for my handout entitled: PHAGE THERAPY - ON THE THRESHOLD OF LIFE WHERE CHEMISTRY AND BIOLOGY MEET TO CONQUER SUPERBUGS.

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: chris on 14/10/2004 13:16:43
Great stuff. You should write an article about phages and phage therapy for The Naked Scientists columns :

http://www.thenakedscientists.com/HTML/articles/article/columnmenu.htm

That would be one popular article !

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 19/10/2004 02:08:31
Chris:

I will think about writing the paper you suggested. Meanwhile I wonder if members of this group might comment on the moral and ethical issues raised below - I would like to touch on them in my up-coming presentation.

Thanks for any comments.

Superbugs Can be Conquered!


While the mere mention of multiple antibiotic-resistant superbugs may strike humans with fear, for the right bacteriophage they represent opportunity to fulfil their lifecycle, destiny or raison d'être and their presence excite the reproductive machinery of the phage into action. In stealth, moon lander fashion phage soon has commandeered the reproductive system of superbug and in a short time (30 minutes) superbug bursts open releasing more than 200 copies of phage, each looking for a superbug to conquer -- considering that superbug multiplies by dividing in two, while phage produces about 200 offspring for every superbug killed, clearly with those odds superbug is superbug no more and looks more like a victim -- all this is simply to say, that what a cat is to a mouse, the right phage is to a superbug.
While much is being written about the antibiotic-resistant, superbug crisis and 2002 to 2007 has been dubbed the "Window of Superbug Vulnerability" because new effective antibiotics will not likely be available until then, Phage Therapy/Medicine is a technology being used to treat patients in some countries. In view of the patient risk due to antibiotic failure, it is obvious that any discussion of the bacterial antibiotic resistance phenomenon which does not include consideration of the mitigating role phage therapy/medicine can play, is medically and scientifically incomplete and/or worse intentionally or intellectually  dishonest. It is clear that the antibiotic-resistance superbug phenomenon is a human-created, regulatory/scientific misadventure due solely to massive abuse of antibiotics since their discovery. As early as 1945 it was obvious that when natural pathogens are exposed to natural antibiotics they will undergo natural selection and acquire resistance - or as can be seen in ‘Rankin on Thursday: Where communism succeeded ....’
( http://www.scoop.co.nz/stories/HL9910/S00096.htm ): “An elementary application of Evolution 101 tells us that bacteria evolve. In an antibiotic-rich environment, selective pressure favours those bacteria strains that are resistant to antibiotics. It’s virtually a tautology.” However, had we continued to use phage therapy together with antibiotics there might not be the antibiotic-resistant superbug crises today since the two antibacterial methodologies act in completely different modes. Rankin also states that: “The wonder is that we have got away with abusing antibiotic therapy for so long.”  
My latest definition of Phage Therapy/Medicine is that it is a natural, old-new-again (medical ) technology with a 100 year documented scientific history, that was used world-wide before the 1940's, and has a 70 year history of continuous use in the former USSR. There are commercial products on the market in Georgia, Poland and Russia which are used to treat patients on a daily basis.
The issue of knowingly withholding these commercial products from patients suffering from antibiotic-resistant, superbug infections needs to be viewed from legal, ethical and moral standpoints. Clearly, from scientific, ethical, moral, if not legal, points of view knowing that phage therapy products are commercially available will not satisfy the state-of-the-art argument as defence that everything that could be done for patients was done when negative treatment outcomes occur. With information on phage therapy widely available in the scientific, medical and even popular literature and much of it neatly collected and easily accessible by clicking http://www.phage.org - then clicking “links” and going to “phage therapy references” it can be reasonably argued that any scientist, health professional and perhaps even politicians as well as health policy wonks working on the antibiotic-resistance superbug issue or treating superbug infections “ought to have known” that phage therapy/medicine is a currently practised treatment methodology. In other words, as health professionals and health policy professionals we know or ought to know that many of the 44,000 North Americans (see The Killers Within) whose "lives" we prematurely celebrate each year at wakes after they die from antibiotic-resistant superbug infections could have their funerals delayed if we adopted and practised currently commercially available phage therapy technology ---- that ought to be a crime! While some patients, like Canadian Alfred Gertler, from countries where phage therapy is not available can travel to countries such as Georgia to get phage medicine treatment for infections not responding to antibiotics
( http://www.cbsnews.com/stories/2002/09/19/48hours/main522596.shtml ), doctors, relatives and non-mobile patients from such countries face an additional dilemma because commercially available phage therapy products may be legally available for import on a case by case basis upon request to the appropriate regulatory agency under special access programs provided for under pharmaceutical product regulatory legislation  - but can the bureaucratic processes be accomplished in time when a superbug infection rages?
When considering regulatory approval for these products we are not talking about the approval of a new, promising molecule with unproven pharmaceutical potential; but rather we are talking about the re-approval and re-introduction of products/technology which were previously used and which are today quite well understood from a scientific point of view ( http://www.phages.org/PhageInfo.html ). .......


phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 10/11/2004 00:50:35
Hi Phage Fans:
 
Is anyone of this group going to the Livesymposium Biotherapy in Neu Ulm, Germany, Dec. 3-4, 2004?
 
It will cover phage therapy topics - go http://www.cpb.de/congress/index.php?id=248&L=1
 
Here is more:
 
http://www.biotherapie.org/topics.html
 
Topics at the Livesymposium on Biotherapy
 
Maggot Debridement Therapy · MDT as seen in medical literature · Mode of action,latestresearch · Antimicrobial peptides in maggots and their secretions · Indications,contraindications and methods of application · Streamlining MDT by surgical intervention · Prospect of MDT
Microorganisms in infection therapy ·   bacteria and bacteriophages · Virological aspects of phage therapy · Antibodies,Probiotics and Phages against diarrheal disease · Bacteriophages in wound infections · Indications, results and limitations · Prospect of phage therapy

Hirudotherapy · Mode of action of leeches · Indication, application and clinical results of Hirudotherapy · Prospectof Hirudotherapy · Mode of action and clinical application of Krill >> www.blutegel.de

Ichthiotherapy · Mode of action of Kangal-Fish · Indication, application and clinical results of Ichthiotherapy · Prospectof Ichthiotherapy

Forensic aspects of biological therapies



phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: bezoar on 12/11/2004 07:30:26
I've heard of the leeches and maggots, but the fish therapy is new to me.  How does it work?
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Sebastiaan on 12/11/2004 08:37:47
Maybe I should have posted my message in this "subforum"? Anyways, anybody can help me with my question concerning bacteria that become resistant against phages?
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 24/11/2004 02:10:25
Sebastiaan:
I am just rereading the book "Gesund durch Viren/Health through viruses(phages)". The answer to your question, perhaps only in part, is found on page 162: To impregnate the host bacterium with his DNA the phage must be able to get a hold of the object of his advances. This involves compatible proteins on the tail fibres of the phage and the bacterial cell surface. If the bacterium changes cell surface proteins through mutation the phage can no longer dock. Hausler points out that this is a continous race between bacteria strains and phages; however, the phages out-mutate the host bacteria. In applied phage therapy the used of phage cocktails is practiced to decrease the possibility of resistant bacteria surviving. Hope this helps

For detailed explanation I would suggest the new book coming out later this month - Bacteriopahges: Biology and Application - for a preview go to http://www.evergreen.edu/phage/phagebooks.htm
 




phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 26/11/2004 02:14:42
quote:
Originally posted by bezoar

I've heard of the leeches and maggots, but the fish therapy is new to me.  How does it work?



I don't think I had heard of fish therapy either; however, when I googled I found a lot of information at http://biotherapy.md.huji.ac.il/new_page_1.htm . It apparently involves small fish living in hot pools and they like dead tissue.

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 27/11/2004 01:32:56
Hello Phage Fans:

In recent weeks I have been talking to groups of scientists and journalists about phage therapy. This made it necessary to select a number of information sources to empower my audience to become familiar with phage therapy and check-out what I was telling them. Since nobody appeared to have responded to the above question for information sources I thought I will share with you what I came up with:

Did a French-Canadian Microbiologist Discover a Cure for Superbug Infections Almost 100 Years Ago?

How many people will have to die before we give phage therapy a try! I was rereading the recent German book; Gesund durch Viren – Ein Ausweg aus der Antibiotika-Krise/Healthy Through Viruses – a way out of the antibiotic-resistance crisis (for an English review see http://www.evergreen.edu/phage/phagebooks.htm ) when I read news reports about yet another hospital outbreak of superbug infections. While only a few years ago, when Toronto musician Gertler went to Georgia in Eastern Europe, for phage therapy treatment for an antibiotic-resistant foot infection, it was a major adventure, today information and arrangements for such treatment is only a click away at http://www.phagetherapy.org .

While working at the Pasteur Institute in Paris in 1917, the French-Canadian microbiologist, Felix d’Herelle
( http://selections.medecine-sciences.com/archives/Volume0/sms8/EnCouv.pdf ), experienced one of those rare eureka moments when he saw his pathogenic bacteria cultures being lysed  - d’Herelle had discovered parasitic viruses which tend to be highly specialized for specific bacteria strains and which can kill large populations of bacteria relatively quickly without harming humans and animals. He named them bacteriophages – “bacteria eaters” and immediately recognized their potential as cures for bacterial infections at a time when neither sulfonamides nor antibiotics were available. He became a major advocate and practitioner of phage therapy, which was subsequently practiced word-wide to control bacterial infections. However, phage therapy fell into disuse in the West after the introduction of penicillin in the 1940’s. Phage therapy remained a significant medical technology in the former USSR, led by research and production facilities in Georgia ( http://www.phagetherapy.org ), and in Poland
( http://surfer.iitd.pan.wroc.pl/phages/ASM0408.html ).

Recently hundreds of Canadians died of C. difficile infections and each day roughly ten Canadians die of antibiotic-resistant and superbug infections and a similar number of limb amputations are done for such infections. While hubris
( http://www.cbsnews.com/stories/2002/09/19/48hours/main522596.shtml ) may make it possible for some to ignore the massive scientific and application evidence from early years and from Eastern Europe, it is more difficult to ignore more recent work from many countries. For example, in 2000 two researchers from the Texas Tech Department of Microbiology state: “By using bacteriophage we can totally prevent the disease (C. difficile infections) in an animal model. … C. difficile is a perfect disease to be treated with bacteriophage” ( http://www.texastech.edu/news/vistasmag/vistas2000/dust.htm ).

Comprehensive English language information on phage therapy can be found at the following websites: ( http://www.evergreen.edu/phage ,
http://www.mansfield.ohio-state.edu/~sabedon/bib_pt.htm ).

Since the multidrug-resistance superbug phenomenon is strictly a human abuse created problem and is threatening to become the mother of all regulatory-scientific misadventures, it is essential that the regulatory-scientific community assume responsibility for this issue as well as the development and importation of methodologies which might help mitigate this crisis – instead of ignoring phage therapy in the name of hubris, nih (not invented here) and russophobia (http://www.scoop.co.nz/mason/stories/HL9910/S00096.htm ), it is a time to be humble and admit that we actively created the antibiotic-resistant superbug crisis. Letting patients die in the name of hubris, nih and russophobia is surely not good public health policy!

On December 3 and 4, 2004 the “Livesymposium Biotherapy” in Germany
( http://www.cpb.de/congress/index.php?id=248&L=1 ) will be examining the role of phage therapy as a viable treatment methodology for bacterial diseases in the light of ever increasing failure of antibiotics and the emergence of drug-resistant superbugs. In memory of Felix d’Herelle and victims multi-drug-resistant superbug infections the  media should be reporting live from this symposium.

P.S.: To appreciate the seriousness of the antibiotic-resistance superbug crisis the following report is recommended: Infectious Diseases Society of America, Bad Bugs, No Drugs As Antibiotic Discovery Stagnates … A Public Health Crisis Brews at http://www.idsociety.org


phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 28/11/2004 02:50:47
Dear Phage Fans:

I would like to add something to yesterday's note:

While googling "Rankin phage therapy" (see above website for russophobia) I found two comments on Rankin's original article - one critical and the other supportive:

Go to http://www.casi.org.nz/PQList-Archive/1999-10/msg00123.html and http://www.casi.org.nz/PQList-Archive/1999-10/msg00138.html and finally, the following website promoting Georgia has an interesting statement: http://www.georgiapromo.info/virus.html - “The programme revealed that we, humankind had discovered a superior cure (to antibiotics) for bacterial infections a century ago and for some reasons we, people don't know much about it! I find it a crime to know all this and not to inform the rest of the world about it(I added bold as I feel the same way![:(]). Hundreds, thousands of people still die or loose body parts every single day because of this terrible (should be bacteria) virus! Medical statistics say that millions loose lives and become cripples every year of this dangerous virus (again should be bacteria) while the cure is found and is not that far!”

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 12/12/2004 00:53:52
quote:
Originally posted by phdkso

Dear Phage Fans:

I would like to add something to yesterday's note:

While googling "Rankin phage therapy" (see above website for russophobia) I found two comments on Rankin's original article - one critical and the other supportive:

Go to http://www.casi.org.nz/PQList-Archive/1999-10/msg00123.html and http://www.casi.org.nz/PQList-Archive/1999-10/msg00138.html and finally, the following website promoting Georgia has an interesting statement: http://www.georgiapromo.info/virus.html - “The programme revealed that we, humankind had discovered a superior cure (to antibiotics) for bacterial infections a century ago and for some reasons we, people don't know much about it! I find it a crime to know all this and not to inform the rest of the world about it(I added bold as I feel the same way![:(]). Hundreds, thousands of people still die or loose body parts every single day because of this terrible (should be bacteria) virus! Medical statistics say that millions loose lives and become cripples every year of this dangerous virus (again should be bacteria) while the cure is found and is not that far!”

phdkso



phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 12/12/2004 00:54:55
Hi Phage Fans:
 
If I had come across the website of Phage International before it did not strike me; however, I strongly recommend you have a look: http://www.phageinternational.com

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: chris on 11/01/2005 20:12:47
Show featuring Nick Mann, phage expert, includes a link to his audio :

http://www.thenakedscientists.com/html/shows/2004.12.12.htm

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 15/01/2005 01:10:49
Quote
Originally posted by chris

Show featuring Nick Mann, phage expert, includes a link to his audio :

http://www.thenakedscientists.com/html/shows/2004.12.12.htm

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx

Dear Chris:

I read the transcript of this show and feel that it was tragic that phage therapy was treated as a new technology - I think it should have been stressed that it is currently available in Georgia and Poland and perhaps other countries like Russia. It may also soon be available in the Amerias, specifically Mexico - see http://www.phageinternational.com. -- Bill



[A thought for 2005 - Leader**** got us to where we are today and what we see is not very pretty - NO MORE LEADER****!]

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: chris on 20/01/2005 08:53:37
The transcript probably doesn't do it justice.

What's new about it is that Nick has developed a nose spray that delivers a shower of phages to the front of the nose where Staph tends to colonise. This spray can be used to eliminate carriage in individuals colonised by Staphs, including MRSA.

Phage therapy has not been approached in this way before, and that's what is NEW. No one was trying to say that phage therapy per-se is new.

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 06/02/2005 01:56:37
Hi Phage Types:
 
Things seem to have been quiet on this discussion group.
 
On pages 116 and 117 of the book "Gesund durch Viren" it is noted that considerable work was done using phages against typhoid at Los Angeles County Hospital and also in several hospitals in Canada in Montreal and Quebec. This work was published in the following two references:
 
Knouf, E.G. et al. (1946) - Treatment of typhoid fever with type specific bacteriophages, JAMA 32:134-138.
 
Desranleau, J.-M. (1949) - Progess in the treatment of typhoid fever with Vi bacteriophages, Canad J publ Health 40:473-478.
 
I wonder  how many have actually looked at some older references like those. I got copies of them recently because the book said that deaths rates were reduced from the normal 20% to 3of 56 and 2% of almost 100 patients. What surprised me was that these papers describe very high quality work. Phages were administered in IV drips into the blood stream and phage cocktails were used. The only thing I might have changed today is to also administer some phages by mouth at the same time.
 
My main point of this posting is to point out that these papers clearly show that phage therapy is NOT A NEW TECHNOLOGY to North America; but should be treated as a reintroduction of phage therapy to North America. As the professor told me back in the early 60's: phage therapy worked then when used by intelligent medical scientists and it will work now when used by well-informed medical scientists.


phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 02/03/2005 01:52:07
Hello Phage Therapy Fans:

Did you see the news below?

"Hope for Those with Diabetic Foot Ulcers and Other Antibiotic-Resistant Infections; Major Step Forward in Bringing Proven Bacteriophage Therapy to Western World

LOS ALTOS, Calif.--(BUSINESS WIRE)--March 1, 2005--Phage International Inc. announced today that it has entered into a definitive agreement to acquire Phage Therapy Center, Tbilisi, Republic of Georgia, a privately held medical clinic offering bacteriophage therapy to patients from across the globe, and co-developer of PhageBioderm, a revolutionary bioactive medical polymer that is utilized for treating bed sores, burns, and tropical/necrotic ulcers. As PhageBioderm biodegrades, it delivers drugs, antibiotics, or pain medications.

Bacteriophages or phages are viruses that invade bacterial cells. Lytic phages disrupt bacterial metabolism and cause the bacterium to lyse. Like antibiotics, lytic phages have remarkable antibacterial activity.

Bacteriophage therapy have been successfully used to treat bacterial infections in former eastern block countries for over 80 years.

"With the alarming increase in the rate of antibiotic-resistant infections it is fortunate that we have a treatment technology that has proven to be successful in dealing with even the most difficult of infections. We are delighted to be involved in helping to commercialize this treatment technology and ultimately bringing bacteriophage therapy to the western world," said Ronald Goossens, President and CEO of PII.

"We are looking forward to helping more patients and training more physicians in the use of bacteriophage therapy," said Vakhtang Beridze, President of PTC.

The purchase was recorded as a transfer of shares transaction; PTC will continue to operate as a wholly owned subsidiary of PII.

Phage Therapy Center -- Tbilisi, Republic of Georgia, treats antibiotic-resistant infections and has saved people from amputation. The clinic specializes in situations where bacteriophage therapy tends to be superior to standard and advanced therapy (including antibiotics) in the US and Western Europe. Conditions treated include: Diabetic foot ulcers, Tropic ulcers, Osteomyelitis, Bedsores, Burns, Gingivitis, Parodontosis, Stomatitis, and MRSA infections. http://www.phagetherapy.org

Phage International, Inc. -- Los Altos, Ca, a primary enabler of phage therapy, was formed in July of 2004. Its focus is bacteriophage-based human therapy to combat drug-resistant pathogens as well as to provide cost effective treatment for non-resistant pathogens. The company is in the process of opening a number of Phage Therapy Centers. www.phageinternational.com




Whenever a newspaper obituary lists cause of death as "complications" following surgery, chances were that a
doctor guessed wrong in terms of antibiotics -- or the bug had proved resistant to all of them. This was code that
all health care workers, hospital staff, and HMO providers understood but few outside the medical world knew.  
-- Michael Shnayerson and Mark Plotkin, "The Killers Within"

Phage International, Inc.
1278 Miramonte Avenue
Los Altos, California 94024
650-961-7262
www.phageinternational.com"


phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 18/04/2005 00:08:53
I am looking for any new reports of patients suffering from superbug infections who have gone to either Poland or Georgia for phage therapy treatment - reports of patients from U.K. are of specific interest - have there been any reports of U.K. citizens that have received phage therapy treatment in recent years? Thanks for any input.

["Before the evening sun turns red another 22 Cnadians of superbug infections will be dead!"]

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 25/10/2005 20:37:02
Hello All:
 
I recently got an email from what I call a "superbug pimp" - that is someone whose income depends on superbugs and that the superbug crisis does not change or at least changes very slowly. It sort of shocked me and I think the time of hoping that the regulatory-scientific community will reintroduce phage therapy is over. I think politicians have to be approached directly. So below is a model letter I have composed and use. Please feel free to use it and join me in this effort!

Dear ------------

Every day in Canada an estimated 30 Canadian citizens and voters die from antibiotic-resistant superbug infections. That is roughly the same number of Canadians who die of microbial foodborne infections in an entire year. While we fly into space on Russian rockets, use Russian Antonovs to fly our armed forces around the world, drink Russian Vodka and eat Russian Caviar while watching Russian hockey players, dancers and artists ...., we choose to let patients die of superbug infections in the name of hubris when it comes to applying phage therapy just because it has most recently been developed in Russia, Poland and Georgia (Europe). Thus many patients are dying just a phage treatment away from a cure. Yet phage therapy is a scientifically valid medical technology which, according to a letter from the federal health minister, can be made legally available to Canadians under the Special Access Program of the Food & Drugs Act. For individuals who know about phage therapy and have the money and time to travel phage therapy treatment is available in Georgia (Europe), Poland and Mexico (see http://www.phageinternational.com or http://www.relax-well.co.uk/MRSA-information-2.html ).

 In addition to the information attached to this fax, I will deposit a number of Canadian references on the subject in the office of my MP. A google search of Canadian websites gives 564 hits, some are publications of Canadian governments, including the Canadian Public Health Agency and National Defence is a major player in phage therapy research in Canada.. Clearly there is considerable expertise in Canada and as a microbiologist I feel that it is my duty to ensure that I inform those who can be instrumental in implementing a phage therapy program  and a proposal is shown below.

PROPOSAL FOR A PHAGE THERAPY PROGRAM:

THE REGULATORY-SCIENTIFIC COMMUNITY MUST ACKNOWLEDGE THE SUPERBUG CRISIS AS THE HUMAN-MADE MOTHER OF ALL REGULATORY-SCIENTIFIC MISADVENTURES

GOVERNMENTS MUST DECLARE SUPERBUG CRISIS THE PUBLIC HEALTH EMERGENCY THAT IT IS

FORM A PUBLIC/PRIVATE PARTNERSHIP OF ALL RESOURCES WORKING ON PHAGE THERAPY - SOME EXAMPLES: HEALTH CANADA, AGRICULTURE & AGRI FOOD CANADA, NATIONAL DEFENCE CANADA, BIOPHAGE PHARMA INC. ( http://www.biophage.com ), GANGAGEN LIFE SCIENCES INC., OTTAWA ( http://www.gangagen.com/corporateframe.htm )

ASSESS WHAT IS KNOWN AND WHAT RESEARCH NEEDS TO BE DONE

CONSULT WITH GEORGIA, RUSSIA AND POLAND FOR SCIENTIFIC AND MEDICAL EXCHANGES

CONSIDER INVITATION TO PHAGE THERAPY EXPERTS

START IMPORTING PHAGE PREPARATIONS FOR COMPASSIONATE USE UNDER "SPECIAL ACCESS PROGRAM" OF FOOD & DRUGS ACT

FUND TRAVEL FOR PATIENTS TO FOREIGN CLINICS LIKE THE "PHAGE THERAPY CENTER" IN TBILISI, GEORGIA/MEXICO AND POLAND.

The following presentation can be arranged by request:

<< TO PHAGE OR NOT TO PHAGE LET PATIENTS DECIDE!>>

Ethical, scientific and moral considerations of withholding phage therapy treatment from patients with superbug infections

"World War III - Humans versus Superbugs: Today roughly the same number of Canadians will die of antibiotic-resistant and/or superbug infections [22 to 33] than will die of foodborne microbial disease in a whole year [30]. This is based on commonly used statistics ranging from 8,000 to 12,000 such deaths annually. On a worldwide basis 17,000,000 deaths are thought to occur annually due to infections and many of these are acquired in hospitals, making hospitals significant ‘killing fields’ in the war with superbugs. While it took six years during World War II to produce 55,000,000 casualties, this number is exceeded every four years in the war with superbugs, qualifying superbugs once again as the weapons of mass-destruction of humanity."


References: http://www.relax-well.co.uk/MRSA-information-2html ,

http://www.theepochtimes.com/news/5-5-31/29150.html , http://www.cheminst.ca/sections/ottawa/phage.PDF ,

http://www.cheminst.ca/sections/ottawa/news/Ottawanews_spring2003.pdf


Phage therapy jump off websites:

Georgia - http://www.phagetherapy.org

Poland - http://surfer.iitd.pan.wroc.pl/phages/ASM0408.html

                                    USA -http://www.evergreen.edu/phage ,

 http://www.mansfield.ohio_state.edu/~sabedon/bib_pt.htm

http://www.phageinternational.com

Disclaimer: This information was produced as a public good. It is the opinion of the author based on extensive study of published literature and is considered a valid interpretation of that literature; however, readers are encouraged to study the references and additional literature to form their own opinion. This information may be referenced, used or quoted with or without giving credit to the author. It may be distributed, copied or stored by any means. Readers and users are responsible for any outcomes from any use of this information.

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 11/01/2006 02:06:28
Hi Colleagues: I am still working on this document but I thought I might get some feedback from you all:

CALLING ALL DOCTORS, JOURNALISTS AND POLITICIANS.
TO PHAGE OR NOT TO PHAGE LET PATIENTS DECIDE!“

Among the most worrisome of these superbugs is MRSA, or methicillin resistant staphylococcus aureus, a germ once found primarily in hospitals. But it's popping up so often outside of health care settings that it is, ‘arguably, a true pandemic’” -
http://www.usatoday.com/tech/science/discoveries/2005-12-18-superbugs-scientists_x.htm
   
Something to think about: Microbial food borne disease causes the deaths of 30 Canadians and gunfire causes fewer than 200 Canadian deaths annually, while superbug infections cause as many as 12,000 Canadians to experience premature death annually and superbugs also cause a similar number of amputations. Superbugs do not discriminate as illustrated by “Cleaning boss hit by MRSA” ( http://www.thesun.co.uk/article/0,,2-2006000023,00.html ).

By spending some time at the website ( http://tahilla.typepad.com/mrsawatch/headlines/index.html or http://www.mrsawatch.co.uk ) one will soon become impressed by the global impact of the superbug crisis - microbial menaces are thought to kill 17 million people annually, many of these infections are acquired while patients are in hospitals for unrelated diseases! And spending time at websites ( http://www.mrsasupport.co.uk/ or http://www.mrsaactionuk.com/ ) will give an appreciation of public outrage at the health systems and public reaction.
 
During the first six years of this century as many as 72,000 Canadian patients may have experienced premature deaths from infections due to antibiotic-resistant bacteria and/or superbugs. Many of these patients could have had their “funerals delayed” by having their infections cured had they known about bacteriophage therapy and if they had had the money and time to travel to Georgia, Europe ( http://www.phagetherapycenter.com/  or http://www.phageinternational.com ) or Poland
( http://surfer.iitd.pan.wroc.pl/phages/ASM0408.html ). Scientific information on phage therapy is widely available as even a search with Google Scholar for “bacteriophage therapy” or “phage therapy” will yield 9,080 and 14,600 references respectively. In view of such abundance of scientific evidence related to phage therapy as a treatment option for certain bacterial infections how can the medical-scientific community explain the virtual boycott of this technology since World War II and especially since the emergence of the antibiotic-resistance crisis.  A letter dealing with phage therapy dated March 08, 2005 signed by the federal Health Minister states: “any physician, who feels that this type of therapy could be of benefit to a particular patient, can request authorization for use via the Special Access Programme”.

In view of the patient risk due to antibiotic failure, it is obvious that any discussion of bacterial antibiotic-resistance which does not include consideration of  phage therapy is medically and scientifically incomplete and/or worse intentionally or intellectually  dishonest. It is clear that the antibiotic-resistance superbug phenomenon is a human-created, regulatory/scientific misadventure due solely to massive abuse of antibiotics since their discovery as even in 1945 it was obvious that when natural pathogens are exposed to natural antibiotics they will undergo natural selection and acquire resistance. It can be reasonably argued that any scientist, health professional and perhaps even politicians as well as health policy wonks working on the antibiotic-resistance superbug issue or treating superbug infections “ought to know” that phage therapy is a currently available and practised treatment option and patients should at least be provided with adequate information so they can make an informed decision as to whether they want to undergo this treatment option.

While phage will not likely replace antibiotics for treating bacterial infections, they do represent a lifeline for individuals with infections where antibiotic therapy has failed and letting citizens die in the name of hubris is surely not good public health policy. There is adequate scientific evidence for careful oral and external applications of appropriate phages to help reduce the emergence of antibiotic-resistant strains. Compassionate use of appropriate phages seems warranted in cases where bacteria resistant against all available antibiotics are causing life-threatening illness. A recent bureaucratic suggestion that it might take ten years of reinventing-the-wheel type research to mapleleaf phage therapy seems cruel as this could mean that another 120,000 Canadians could die of superbug infections before any patients will be treated in Canada.

Something to watch: The Diabetic Foot Global Conference ( http://www.dfcon.com ) will be held 23 to 25, March, 2006 in Hollywood, Ca and a phage therapy symposium will be part of the program. Phage therapy practitioners from the Elivia Institute, Tbilisi, Georgia and the Wound Care Center in Lubbock, TX ( http://www.woundcarecenter.net ) will be presenters.

   “Too many regulatory-scientific misadventures. It’s a time to be humble! It’s a time to apologize!”
 
This document is a draft which may change without notice. Version date: January 7, 2006. Prepared by G.W. (Bill) Riedel, PhD, MCIC
Disclaimer: This information was produced as a public good. It is based on extensive study of published literature and is the author’s opinion. Readers are encouraged to study the references and additional literature to form their own opinion. This information may be referenced, used or quoted with or without giving credit to the author. It may be distributed, copied or stored by any means. Readers and users are responsible for any outcomes from any use of this information.

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 10/03/2006 02:32:12
Hi to all phagists:

I have always been fond of finding scientific explanations for religious practices or writings - such may be with phage therapy - read on:

The Absurdity of the Superbug Crisis.

The absurdity of the superbug crisis consists of the fact that it can be demonstrated that we had technology, namely bacteriophage therapy, which can cure many superbug infections, long before we created the antibiotic-resistance superbug crisis through massive abuse of antibiotics. In spite of a voluminous literature attesting to the scientific validity and medical effectiveness of phage therapy, there are still phage therapy deniers who would resist the careful deployment of these weapons of mass destructions for specific pathogens in the war with superbugs. Superbugs are winning most battles with an estimated 17 million human casualties due to microbial infections worldwide annually. Many of these infections are acquired by patients after entering hospitals for unrelated illnesses, making hospitals significant killing fields in the war with superbugs.

Phage therapy may even be the scientific explanation for the following passage:
   “Then went he down, and dipped himself seven times in Jordan,
    according to the saying of the man of God: and his flesh came
    again like onto the flesh of a little child, and he was clean.”
   From the Holy Bible (II Kings 5:14)
   
What is Phage Therapy? from Bacteriophage Therapy
by Alexander Sulakvelidze, Zemphira Alavidze, and J. Glenn Morris Jr.
“Prior to the discovery and widespread use of antibiotics, it was suggested that bacterial infections could be prevented and/or treated by the administration of bacteriophages. Although the early clinical studies with bacteriophages were not vigorously pursued in the United States and Western Europe, phages continued to be utilized in the former Soviet Union and Eastern Europe. The results of these studies were extensively published in non-English (primarily Russian, Georgian, and Polish) journals and, therefore, were not readily available to the western scientific community. In this minireview, we briefly describe the history of bacteriophage discovery and the early clinical studies with phages and we review the recent literature emphasizing research conducted in Poland and the former Soviet Union. We also discuss the reasons that the clinical use of bacteriophages failed to take root in the West, and we share our thoughts about future prospects for phage therapy research.
Bacteriophages or phages are bacterial viruses that invade bacterial cells and, in the case of lytic phages, disrupt bacterial metabolism and cause the bacterium to lyse. The history of bacteriophage discovery has been the subject of lengthy debates, including a controversy over claims for priority. Ernest Hankin, a British bacteriologist, reported in 1896 on the presence of marked antibacterial activity (against Vibrio cholerae) which he observed in the waters of the Ganges and Jumna rivers in India, and he suggested that an unidentified substance (which passed through fine porcelain filters and was heat labile) was responsible for this phenomenon and for limiting the spread of cholera epidemics. Two years later, the Russian bacteriologist Gamaleya observed a similar phenomenon while working with Bacillus subtilis, and the observations of several other investigators are also thought to have been related to the bacteriophage phenomenon. However, none of these investigators further explored their findings until Frederick Twort, a medically trained bacteriologist from England, reintroduced the subject almost 20 (1915) years after Hankin's observation by reporting a similar phenomenon and advancing the hypothesis that it may have been due to, among other possibilities, a virus. However, for various reasonsincluding financial difficulties Twort did not pursue this finding, and it was another 2 years before bacteriophages were "officially" discovered by Felix d'Herelle (1917), a French-Canadian microbiologist at the Institut Pasteur in Paris. The emergence of pathogenic bacteria resistant to most, if not all, currently available antimicrobial agents has become a critical problem in modern medicine, particularly because of the concomitant increase in immunosuppressed patients. The concern that humankind is reentering the "preantibiotics" era has become very real, and the development of alternative antiinfection modalities has become one of the highest priorities of modern medicine and biotechnology.”
( http://www.phageinternational.com/phagetherapy/whatisphagetherapy.htm ).

Once one accepts the fact that it requires microscopes to see the world of bacteria and bacteriophages, phage therapy may be compared to any biological control methodology and can conceptually be described as: What a cat is to a mouse the right bacteriophage is to a specific bacterium or superbug. Lytic phages are the weapons of mass destruction in the war with superbugs! And as can be seen above, phage therapy has been going on in nature as a balancing force in the evolution of microbes. Medical phage therapy is simply the intervention of humans to ensure that the balance is in favour of bacteriophages over susceptible bacterial pathogens!

From the Jordan (2 Kings 5:1-14) and Ganges rivers to the phage therapy centers in Georgia
( http://www.phagetherapycenter.com/ , http://www.phageinternational.com ), Poland
( http://surfer.iitd.pan.wroc.pl/phages/ASM0408.html ) and to the Wound Care Center
 ( http://www.woundcarecenter.net ) in Lubbock, Texas, bacteriophages have, are and will continue to cure bacterial disease in spite of what phage therapy deniers say!

Something to watch: The Diabetic Foot Global Conference ( http://www.dfcon.com ) will be held 23 to 25, March, 2006 in Hollywood, Ca and a phage therapy symposium will be part of the program. Phage therapy practitioners from the Elivia Institute, Tbilisi, Georgia and the Wound Care Center in Lubbock, TX ( http://www.woundcarecenter.net ) will be presenters.

References:  http://www.relax-well.co.uk/MRSA-information-2.html ,
 http://www.theepochtimes.com/news/5-5-31/29150.html ,   http://www.cheminst.ca/sections/ottawa/phage.PDF ,
http://www.cheminst.ca/sections/ottawa/news/Ottawanews_spring2003.pdf
Phage therapy jump off websites: Georgia - http://www.phagetherapy.org
Poland -  http://surfer.iitd.pan.wroc.pl/phages/ASM0408.html
USA - http://www.evergreen.edu/phage ,  http://www.mansfield.ohio-state.edu/~sabedon/bib_pt.htm
http://www.phageinternational.com   Israel - http://www.phage-biotech.com/index.html

   “Too many regulatory-scientific misadventures. It’s a time to be humble! It’s a time to
   apologize!”
Disclaimer: This information was produced as a public good. It is the opinion of the author based on extensive study of published literature. Readers are encouraged to study the references and additional literature to form their own opinion. This information may be referenced, used or quoted with or without giving credit to the author. It may be distributed, copied or stored by any means. Readers and users are responsible for any outcomes from any use of this information. Version dated March 5, 2006 and may be revised

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 08/04/2006 01:26:39
Putting another nail into the arguments of phage therapy deniers!

In 2003 the Swiss author Thomas Hausler published an excellent book on phage therapy entitled: Gesund durch Viren - ein Ausweg aus der Antibiotika-Krise, roughly translated Healthy through Viruses - a way out of the antibiotic-resistance crisis. For an English language review of that book see http://www.evergreen.edu/phage/phagebooks.htm . This excellent book is readable by everyone from high school to PhD.

I have just been informed that the English language version of this book will be available in May or June  this year as: Thomas Hausler -Viruses Vs. Superbugs - A Solution to the Antibiotics Crisis? For information on the book go to http://www.macmillanscience.com/1403987645.htm - please print out the UK and US versions of the comments - there are some interesting differences.

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Pol on 16/04/2006 02:48:17
I've had the pleasure to follow this interesting topic for some time (congratulations for the quality of the information), but there are still some essential doubts coming to my mind. For longer than one year I've been working in Quorum Sensing. I seriously consider this and phage therapy interesting (possible) alternatives to antiobiotic treatment. But at the end I always come up to the same point:

- What is the real applicability of those treatments? How long do they have to be at experimental phase till they can be used as a cure? As I said, I've been reading all publications here so I've read that phage therapy has been already used in vivo, but I still don't understand why if it's so promising, it's not commonly used.

I guess the fear to new treatments is in part the answer. But what if that risico is at the end real? The idea that phages are specific, they'll kill bacterial infection and after will become harmless sounds great and sounds to me as good, at least, as using the bacterium bdellovibrio for the same purpose but... what if the virus remains in the body and after it has adversal effects? Or what happens if the patient has an adverse reaction to the virus (As an example I'll use the article about stem cells in Newscientist from March 2006: "the 18-year-old volunteer with a liver disease died from an inflammatory reaction to the virus used to deliver genes.")

I really like a lot this subject but of course as in my research, I understand people who are  just afraid to try it in vivo.

Thanks a lot and congratulations again!!

Tell me and maybe I'll forget it. Teach me and maybe I'll remember. Let me participate and I'll learn
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 07/05/2006 02:02:18
I think that you might be interested in a new website
 just put up at www.bacteriophagetherapy.info - it is by the author
 of the book Viruses vs Superbugs just hitting the shelves - it should answer most of your questions

"It explains lay persons the ropes of phage therapy and has some goodies for the experts. I. e.. a long literature list and also a blog that I would like to develop into a clearing-house for news in the field."

I think all who are interested in phage therapy should buy a copy. Below is my review of the German version of the book which came out in 2003:

Book review: Viruses Vs. Superbugs A Solution to the Antibiotics Crisis? by Thomas Häusler to be released May 2006, Macmillan - http://www.macmillanscience.com/1403987645.htm

Since 2003 German readers have been privileged to be able to read Swiss author Häusler’s book, Gesund durch Viren - ein Ausweg aus der Antibiotika-Krise. Now the imminent release of an updated version of this book entitled, “Viruses vs Superbugs”, will allow a much larger audience to read his fascinating story describing an important epoch in science and medicine that started over one hundred years ago and is still unfolding. This review of the original German version draws on a review originally published in German by Hermann Feldmeier.

In 1969 the Surgeon General of the United States, William H. Stewart announced that the war against epidemics due to pathogens had been won. Seldom has medical dogma pronounced by the highest ranking medical officer of the USA been rendered absurd so rapidly. Actually infections due to pathogens did temporarily decrease during the 1960's; however, only to return twenty years later with increased and ever increasing vehemence. Today it is estimated that as many as 17 million deaths worldwide are caused by microbial infections annually. Nosocomial infections - hospital acquired infections - and multi-resistant pathogens, terms which until recently were familiar only to experts, are today topics of the public press and it is not surprising, because in Germany  alone 20,000 people die annually of nosocomial infections. The Canadian number of victims may be as high as 12,000 annually.

The prospects for the future are still gloomier. While it took approximately fifty years for 95 per cent of Staphylococcus aureus strains to become resistant to penicillin, today certain problem bacteria need only a few years to acquire resistance even to totally new classes of antibiotics. Additionally,  the pharmaceutical industry no longer has  many chemical substances in the research pipeline that will come to market as older antibiotics fail.  At the same time the need for effective antibiotics continues to increase as more patients must be protected against the threat of infections because of weakened immune systems or because they are organ transplant recipients.

New hope is promised by a therapy which is substantially older than penicillin - treatment with bacteriophages.  On August 2, 1919 their discoverer, the French Canadian Felix d’Herelle, administered a cloudy broth containing Shigella phages to a deathly-ill boy at the Pasteur Institute in Paris, curing him of dysentery. After an early worldwide boom this therapy today exists essentially only in some Eastern European countries, including  Georgia and Poland; however, is now again receiving attention in the West, even if many infection control specialists remain sceptical.

This paradigm shift is the background for an unusually well researched, outstandingly well written and scientifically based book by the Swiss journalist Thomas Häusler.  From the beginnings to the present the author, who is also trained in biochemistry, describes all aspects of a concept (bacteriophage therapy), whose therapeutic potential is not easily communicated during times of AIDS and SARS. Bacteriophages are actually viruses highly specialized to attack bacterial cells and they do no harm to animal cells. When a phage discovers a bacterium to which it possesses the correct key - that is, there are suitable receptors on the bacterial cell to which the phage can attach with its tentacle-like extensions - then the phage will inject its hereditary DNA into the bacteria cell.  Taking-over the bacterial cell’s biochemical apparatus hundreds of phage copies are then produced rupturing the bacterial cell as the victim dies, and the released daughter phages attack any remaining bacterial cells like a pack of hungry wolves.

The advantages of the therapy are obvious.  Bacteriophages are very specific parasites and contrary to antibiotics, do not damage the useful bacteria which live in and on the body. Phages are "intelligent" medicines:  They increase just where they are needed while antibiotics often do not even get to where they are needed to work. Once all phage-susceptible bacteria have been killed phages are eliminated from the body.

The high specificity, with which phages look for their bacterial victims, is at the same time also their therapeutic Achilles' heel.  Either the infection control specialist must have a cocktail containing very many different types of phages, or a phage specifically effective against the pathogen of each patient  must be custom-made through detailed microbiological analytical work.  Western regulatory authorities tend to loath recognizing such manually manufactured anti-infective agents as medicines which explains why currently phage therapy is routinely only available at phage therapy centers in Georgia, Europe and Poland.

For chronic infections on outside and internal body surfaces due to multi-resistant pathogens,  which can not be treated with current methods, phage therapy could become a kind miracle medicine if Western regulatory agencies could be convinced to focus regulatory oversight on the process of how phage preparations are isolated and purified rather than the end product.

Throughout the book, interviews with researchers are skilfully intertwined with descriptions of actual patient experiences. The middle part of the book is also outstanding in describing the trails and errors of phage therapy as practised between 1930 and 1990. Here journalist Häusler points out what influence political events have on the medical research - from the "Great Patriotic War" of Russia against Nazi Germany to the collapse of the Soviet Union and up to September 11, 2001. All this is augmented by a long list of footnotes, a detailed list of references and numerous instructive illustrations. Häusler has succeeded in  writing a book that can be read by high school students and yet is useful and of interest to medical and phage therapy experts - an amazing feat!  

Experts from USA, UK, Canada and Israel have praised the new English version as scientific journalism at its best and predict that readers will finish this book utterly convinced that phage therapy will provide alternative treatment for superbug infections even in countries not currently using this technology.

Because of the public health significance of the antibiotic-resistance superbug crisis this book deserves to be on the shelf of every private and public library. Sooner or later many of us will be faced with or know someone suffering from an infection not responding to antibiotics. At that time the stark choice is between death, amputation or an expensive trip to Georgia, Poland. The latter choice is available only  for individuals knowledgeable about phage therapy who have the financial resources and time left! Perhaps this book will bring the message about phage therapy to enough people so that politicians and health officials can no longer ignore the demand for this treatment and that phage therapy will be available as needed when antibiotics fail! For individuals who have the financial means it may be a worthwhile investment to send a copy of the book (or at least a copy of this review) to their elected representatives so they can not say that they did not know that phage therapy is a currently available medical technology when, as some experts prognosticate, superbugs will have caused us to return to the pre-antibiotic era and many medical procedures that routinely rely on the use of antibiotics will no longer be possible!

{ This book review is dedicated to the estimated 76,000 Canadians who have died as well as those who have suffered amputations or  just plainly suffered  from superbug infections since January 1, 2000 - dated May 1, 2006 }


phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 24/06/2006 01:06:32
Take a look at this announcement. It makes Canada the leader of a worldwide bureaucracy in reinventing phage therapy for treating superbug infections and is the most significant endorsement by a wide sector of health related agencies that this technology works and could cure many patients and save many healthcare dollars as well as free-up many hospital beds!

"I am very happy to provide you with an update on the status of the June 2006 "Novel Alternatives to Antibiotics Research Initiative".  All of our hard work has come to fruition, and the Initiative has recently been posted and can be viewed at: http://www.cihr-irsc.gc.ca/e/31302.html

I believe that Judith has informed you about this particular Initiative, and I thought that I would send you an update.  The more people know about this funding opportunity, the better.  We really can't rely on a "build it and they will come" attitude. It will be very important to get the word out to the right people in order for our plans to reach the level of success we desire.   If you know of anyone that might be interested applying to our Initiative, please pass on the information.  Thank you in advance for your help with this matter."

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 30/06/2006 02:16:43
Viruses vs. Superbugs by Thomas Häusler, June 2006

On June 26 at about 7:00 p.m. I was finally able to get a much awaited copy of the book - Viruses vs. Superbugs - a solution to the antibiotic crisis? It turned out to be a fascinating and informative read and is highly recommended for anyone interested in the superbug crisis and the use of bacteriophages to mediate this crisis. I finished the book by June 29, 1:00 pm.

Two thoughts kept going through my mind: 1. Phage therapy research - too little, too late and tooo.... slow! And 2. Superbugs are everybody’s business because superbugs make everybody their business!

This book is a "must read" and I wish you happy reading!


phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 30/06/2006 02:16:43
Viruses vs. Superbugs by Thomas Häusler, June 2006

On June 26 at about 7:00 p.m. I was finally able to get a much awaited copy of the book - Viruses vs. Superbugs - a solution to the antibiotic crisis? It turned out to be a fascinating and informative read and is highly recommended for anyone interested in the superbug crisis and the use of bacteriophages to mediate this crisis. I finished the book by June 29, 1:00 pm.

Two thoughts kept going through my mind: 1. Phage therapy research - too little, too late and tooo.... slow! And 2. Superbugs are everybody’s business because superbugs make everybody their business!

This book is a "must read" and I wish you happy reading!


phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 10/08/2006 01:16:37
Well, I see phage therapy is again reality in the West and I was impressed that we have our priorities right - we will phage veggies not people. I thought this event should be celebrated with the worst kind of poetry ever written. Clearly the younger members can't afford to rise to such an occasion .... As I am TOO OLD TO DIE YOUNG ANYMORE I thought I would humbly jump into the breach:

Biiizzzarrooo..

When superbugs infected the tomatoes
regulators quickly looked at the data
and approved bacteriophages to save the tomatoes

( See  http://www.genengnews.com/news/bnitem.aspx?name=4063128 )

When a hospital a superbug infection to a patient does presenten
at bacteriophage therapy s/he must not denken
because the regulators will genoten
that treating superbug infections of humans with phage therapy is strictly VERBOTEN!
After 100 years we have not had enough time for phage therapy re-inventen
even if many patients dead will abenden! - bizarre... sick....

(See Viruses vs. Superbugs, a solution to the antibiotic crisis?
http://www.bacteriophagetherapy.info ) UC



phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 06/10/2006 02:31:55
This should get you to the US FDA's Docket No. 2002F-0316 - Food Additives Permitted for Direct Addition to Food for Human Consumption; Bacteriophage  Preparation:
 http://www.fda.gov/OHRMS/DOCKETS/98fr/02f-0316-nfr0001.pdf
 
In my opinion this is a very good evaluation of the bacteriophage cocktail for addition to ready-to-eat meats against Listeria monocytogenes and should be read by all.
 
What I am trying to get my mind around is that with all that knowledge within FDA, why would they not be taking the initiative to promote phage therapy for certain superbug infections, for example, bed sores, diabetic foot etc. Surely they can't claim that they did not know that phages are effective for these types of infections??
 
"Re-inventing phage therapy: Too little, too late, too slow, too dear, too bureaucratic, too much hubris, and too little compassion for too many people suffering and dying from superbug infections."

See: http://www.bacteriophagetherapy.info

phdkso
Title: Re: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 05/12/2006 02:24:35
New phage therapy article

There is an article by Kurt Kleiner The new age of the phage in the Toronto Star, Dec 3, 2006, D1

I did an interview and am quoted and have copies - I have not been able to display it; however, there is a link at the following Blog - good luck finding it!

http://sandwalk.blogspot.com/2006/12/bacteriophage-therapy.html
Title: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 18/03/2007 00:48:09
Silicon Valley Business Journal, Jan 5, 07 by Sara Solovitch


Hi All: I had not previously seen the article on phage therapy entitled, "Making business from treatment Western medicine passed by" - see

http://sanjose.bizjournals.com/sanjose/stories/2007/01/08/story4.html

Interesting as it gives specifics about actual treatment activities going on in Georgia!
Title: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Mjhavok on 20/03/2007 02:42:51
This subject is really interesting. I am studying Microbiology at Uni so it relates :-D.
Title: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 03/04/2007 01:17:05
USDA allowance of Bacteriophage Treatment of Salmonella on Livestock

OmniLytics Announces USDA/FSIS Allowance of Bacteriophage Treatment of Salmonella on Livestock
http://home.businesswire.com/portal/site/google/index.jsp?ndmViewId=news_view&newsId=20070329005872&newsLang=en
Title: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 27/05/2007 00:20:24
If you are interested in phage therapy take a look at this website as it develops - http://www.amazingphage.info/
Title: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: NakedScientist on 12/06/2007 09:57:03
Here's an article by Thomas Hausler about the history and use of bacteriophages to combat bacterial infections:

http://www.thenakedscientists.com/HTML/articles/article/virusesvssuperbugs/

TNS
Title: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: phdkso on 03/12/2007 02:09:49
Hi All:
 
I found the November issue of the Contamination Control Newsletter of considerable interest. As a microbiologist with knowledge of phage therapy and the academics of bullshit ( please see http://bullshitcitynorth.blogspot.com ), I noted  that CDC "guidelines do not rule out the use of organs from donors identified as high risk. The CDC recognizes .... that a patient's risk of dying without a transplant is often much higher than the possible risk of acquiring a disease." (From article entitled Four Transpalnt Patients Contact HIV From Donor Organs) --- Interesting, when we all know that FDA and other Western public health regulatory agencies won't use the same reasoning for phage therapy. The other thing worth noting is that organ transplants are of necessity small batches of medical products tailor-made for one or a small group of patients. Again one of the arguments often spouted against phage therapy is that regulatory agencies don't like small batches of tailor-made drugs or therapeutic products. Clearly such arguments are arbitrary, capricious bullshit or perhaps ueberbullshit if made by experts!
 
It might be worthy to note the following:  "staph infections, ... cause an estimated 95,000 severe illnesses annually in the U.S. The Centers for Disease Control and Prevention recently calculated that 19,000 Americans are dying of staph infections each year, about 2,000 more than die of AIDS" (from SHERRY JACOBSON / The Dallas Morning News,  November 30, 2007)
 
Humbug! I rest my case!
Title: How are bacteriophages used as antibiotics, to kill bacteria?
Post by: Karen W. on 06/01/2008 21:46:56
Well for a start there's the problem of tissue penetration. Phages are all well and good if they can reach the site of infection. But in the context of meningitis, for example, where the bugs are within the meninges, access becomes a problem. The antibiotic molecules used are extremely small and have excellent CNS penetration. In the context of a life threatening infection you do not mess around, nor allow the worry of some subsequent diarrhoea influence your choice of therapy.

I've seen a man with bacterial meningitis go from alert, conscious and able to share a joke, to barely rousable with a rash spreading in front of my eyes. Another 30 minutes and he would have been irretrievable. As it was a regular doses of intravenous broadspectrum antibiotics saved his life. And he didn't get any diarrhoea either !

I am a big supporter of phage therapy but everything has its place and it should not be used just because it is new.

(By the way, the inter-bacterial signalling you are referring to, cannnabinoid, is called "quorum sensing".)

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx

Chris, Would Phage therapy be effective against Mycroplasma pnuemoniae bacteria?