Drug-Resistant Syphilis Spreads

[hatrack]

"A fast-spreading mutant strain of syphilis has proved resistant to the antibiotic pills that are offered to some patients as an alternative to painful penicillin shots.

Since the late 1990s, doctors and public health clinics have been giving azithromycin to some syphilis patients because the long-acting antibiotic pill was highly effective and easy to use. Four pills taken at once were usually enough to cure syphilis.

But now researchers at University of Washington in Seattle have found at least 10 percent of syphilis samples from patients at sexually transmitted disease clinics in four cities had a strain resistant to azithromycin. "That suggests that this mutation is pretty widely distributed geographically," said Sheila A. Lukehart, research professor of infectious diseases.

The percentage of samples from San Francisco with the mutant strain jumped from 4 percent in 1999-2002 to 37 percent in 2003, with the increase taking place largely among gay or bisexual men with multiple partners."

EDIT

http://ljworld.com/section/worldnation/story/175084

[NNadir]

1. This problem of drug Resistance is much, much larger than this example.

The evolution of resistant pathogens is partially a function, like most of the other profound environmental problems of which Hatrack so diligently keeps us abreast, of the size of the population, and of short sighted environmental approaches by industry and the public at large.

In the case of antibiotic Resistance, part of the problem stems from the indiscriminate use of antibiotics by industry, in particular the agricultural industry. While azithromycin itself is not, I believe, used in the agricultural industry, the growth of resistance in other options, particularly cephalosporins (a class in which penicillin can be included) have been widely overused.

What is disturbing about this report is that azithromycin is in another antibiotic structural class, macrolide antibiotics. The emergence of new resistant strains in new structural classes is always disturbing since it implies new forms of cross Resistance.

The situation with other pathogens and drug Resistance, in particular HIV is even more disturbing.

[amandabeech]

2. There are other causes, as well, as I recall.

One is over-presciption of antibiotics, including prescribing anti-biotics for viral illnesses.

Another cause that I've read about is the failure of patients to complete the course of antibiotics prescribed to them. People start to feel better and stop taking their medicine, but the bugs are still in their system. Those remaining are more resistant than the bugs that already died.

The article cited in Hatrack's post mentions the failure of many patients to stop the penicillin regimen because of side-effects and I imagine the disappearance of sores.

Does the information on which you base your post, NNadir, also mention these causes?

[hatrack]

3. Check L. Garrett's long, excellent "Betrayal of Trust", "Coming Plague"

Esp. the latter for information on failure to complete drug regimens for tuberculosis.

Overprescription is indeed a big chunk of it, but the process of adaptation would be inevitable (though slower) even if human beings didn't pop (fill-in-the-blank)acillin for every sniffle and hangnail. Rust never sleeps, and neither does evolution.

[amandabeech]

5. Yes, I've read about drug-resistant tuberculosis.

I've read that a big problem is coming out of the Russian prison system, and is slowly spreading west. In fact, I was thinking about TB when I wrote my reply.

As I'm sure you know, TB was an absolute scourge at the turn of the century. In fact, one of my great-grandmothers died of it at a relatively young age leaving three young children.

The problem with TB, unlike syphilis to a certain extent, is that it spreads without intimate contact, and no known physical barrier can prevent its transmission.

I'll probably get flamed like crazy, but I think that drug-resistant TB has the potential to be as great a problem as AIDS.

I'll check out those sources that you recommend.

Thank you for another excellent post, Hatrack.

[LibLabUK]

9. Some thoughts.

"I'll probably get flamed like crazy, but I think that drug-resistant TB has the potential to be as great a problem as AIDS."

There is a vaccination against TB, the BCG (Bacillus Calmette-Guérin). This vaccination commonly given to pupils at secondary school (usually when they're 13-14) in the UK.


Some of my thoughts regarding the generation of resistant strains:

The major contributor to the development of resistant strains is the extremely long duration of the course of antibiotics used to treat TB (usually 6 months). People take the drug for a month, feel better and then stop.

I know the New York health agency (forgive me, I don't know the actual name of the health services in New York) have had some luck by using a system of payments and witnessed administrations. Patients with TB are given a cash incentive to finish the course of medication, and they are visited at home by a health care worker who witnesses them taking the medication.

The Russians are having a problem with TB because their overcrowded and criminally underfunded prison system is acting as a reservoir. TB is widespread amongst the prison population, new inmates eneter the system and get infected. Whilst they're incarcerated they get basic treatment (antibiotics), but on release they stop taking them, either because they can't afford them or they simply don't have a primary healthcare provider.

Until they eliminate the infection from the prison system they won't be able to start tackling the problem in the community.

[amandabeech]

11. I had not heard of a TB vaccine.

Thanks for posting the information. Now if the UN could get behind this vaccine and push for its administration in TB prone areas of the world.

[NNadir]

4. All of these things you mention are true. I based my post on general

knowledge.

Because of the nature of my (paid) work, I'm pretty familiar with issues in pharmaceutical science.

Many physicians feel pressured by patients to "do something," and therefore write unnecessary and ineffective prescriptions. Some physicians are lazy and/or cheap, and don't culture patients. Some are motivated by unscrupulous sales practices and promotions by pharmaceutical companies. (One of my doctors gave me azithromycin for strep, even though cheaper generic medications are more effective.) Some doctors are incompetant; and some are simply arrogant and assume that they can identify diseases by inspection. (There was a very scary report recently on the huge percentage of dermatologists who "misguess" on the pathological nature of unusual skin growths. Many identified melanomas as benign. This is why one should insist on a biopsy.)

Actually, there are now medications that are effective against viruses, Relenza for instance is active against flu viruses, but these treatments have a very different mode of action than antibiotics. It also happens that viruses, depending on their nature, evolve resistance much faster than do bacteria. Thus Relenza resistant strains can be expected if the drug becomes popular.

This is because viruses replicate very quickly. The HIV virus produces 10 billion new copies every single day in a single patient. Moreover, since the virus is an RNA virus, and because it lacks a mechanism for correcting transcription errors, mutant strains, some of which are viable, arise quickly.

Here for instance is a list of identified mutant strains of HIV that have evolved resistance to various drugs known as Protease Inhibitors. (The letters refer to amino acid substitutions in the HIV protease that is responsible for cleaving the GP41 precursor protein into active forms.)

D30N: Nelfinavir. (Agouron/Pfizer).
M46I/I47V/I50V: Amprenavir (BMS).
L10R/M46I/L63P/V82T/I84V: Indinavir (Merck)
M46I/L63P/A71V/V82F/I84V: Ritinovir (Abbott).
Saquinavir: G48V/L90M (Roche)

Most of these drugs are less than ten years old, and some are almost completely ineffective against some of these strains.

Some of the reason for the evolution of these strains is just basic biology, but a large part of it is patient non-compliance, wherein patients, for various reasons, do not follow the protocols for which the drugs were designed. There are some pretty profound ethical issues involved as well; these have to do with cost and the fact that many HIV victims are poor to start or become poor as a result of their disease. The necessity of taking economically dictated "short cuts" has accelerated the development of resistant strains. Indeed, this is an issue with providing these drugs to some countries in the third world. Compliance with protocols assumes an infrastructure that can reliably deliver drugs year after year, dose after dose, in a consistent manner.

It also happens, especially in the case of antibiotics, that many drugs are not completely destroyed metabolically, and are excreted into the environment in detectable quantities. Since sewage is a prime breeding ground for micro-organisms, many of which are pathonogenic, this contributes to the problem since bacteria have a chance to be exposed to antibiotics, and to evolve resistence.

[LibLabUK]

6. Gonna be a bit nitpicky here....

"cephalosporins (a class in which penicillin can be included)"

The penicillins aren't cephalosporins.

Penicillins were originally derived from Penicillium
Cephalosporins were originally derived from Cephalosporiums

Penicillins and cephalosporins are in the same class of antibiotic, the Beta-lactams, they both act by disrupting cell wall synthesis in bacteria.

[NNadir]

7. Right on both scores, Nitpicky and technical designation. I am wrong.

My error comes from the fact that I am a chemist, not a biologist. I am somewhat indifferent to the name of the species from which the drugs are derived. The structure is what matters to me and of course the penicillamine type core is found in both sets of molecules.

In any case, the technical designation is somewhat trivial in the sense that the drug mechanism, acylation of a transpeptidase is identical, and cross resistance is thus a factor for all beta lactams, and indeed any antibiotic that works by mimicing the D-Ala-D-Ala substrate.

[LibLabUK]

8. Ahh..

Sorry, I'm a pedantic microbiologist and couldn't just let a mistake like that lay uncorrected. :)

You're right though, regarding the topic of discussion the designation of the drugs really is trivial.

[NNadir]

10. I hope I didn't make you feel that I objected to being educated.

The microbiologist's take is certainly interesting, and you were correct.

Still, in this particular case, it the chemistry that has the most bearing, or at least the biochemistry.