Last Didactic Lecture of the MPharm

Today I had my last didactic lecture as part of this MPharm degree. It was a lecture on emerging viral diseases. Fits well as it gave the guest lecturer a chance to talk about swine flu. Interesting stuff.

Tomorrow there are student presentations from 1-3 then we have drinks and pizza with the pharmacy staff. I gave my presentation two weeks ago so I just have to sit there and listen. Friday is a research day but we are done our bench work and the draft paper is already done too so things are going smoothly.

Anti-adhesive Therapy: A Possible Solution to Antibiotic Resistance

Antibiotic Resistance – A Growing Problem

When antibiotics became available in the 1930’s and 40’s they were immediately hailed as ‘miracle drugs’. Antibiotics like penicillin revolutionized medical science and the treatment of many diseases leading to improved public health. However, as quickly as the celebration began problems rapidly emerged. Doctors noticed that some diseases, which had once been cured by penicillin, were no longer effectively healed by these miracle drugs. Antibiotic resistance was born. In fact, only seven years after penicillin became widely used some infections could no longer be cured using penicillin.¹ Even more alarming is that by 1971 nearly 100% of some types of bacteria were resistant to penicillin.¹ Over the years new antibiotics have been developed but antibiotic resistance remains to be an issue to this day. The problem of antibiotic resistance is rapidly becoming a major public health issue and as it stands this problem is only going to get worse as time passes. Antibiotic resistance has forced scientists to search for new ways to prevent or cure infections.

A new Approach – Anti-adhesive Therapy

A new approach in the battle against microbial infections involves blocking harmful organisms from attaching to the cells which make up our body. In the past, scientists have focused on discovering ways to kill infecting organisms but the new concept of anti-adhesive therapy takes a new approach to an old problem. The theory behind this new approach is relatively simple and it makes practical sense: if a bacterium can not attach to our cells then it can not grow or multiply – this means it can not cause an infection.^2-4 In order for a bacterium to cause an infection it must take up residence within our body where it grows and multiplies. This means that, in the presence of anti-adhesive therapy, the lone bacterium will not be able to establish itself and it will ultimately waste away without causing harm or disease. Although the concept is simple the way anti-adhesive therapy is proposed to work is actually quite complicated.

How Anti-adhesive Therapy Works

As previously mentioned, bacteria must attach to our cells in order to cause disease. These bacteria have various ways of attaching to our cells but one of the most common ways is by using what scientists call ‘adhesins’.³ These adhesins are like hands which are able to grab on to things around the bacterium to hold it in place. Remarkably, each different species of bacteria has evolved to have very specific adhesins allowing these organisms to find its way to environments which best suit their growth. This specificity means that, for example, when a particular bacterium thrives in a warm and wet environment, like that of your nose, it will express the relevant receptors which allow it to attach to the cells within your nose. Once scientists determine exactly what adhesins a bacterium is using to attach itself, anti-adhesive substances can be made which prevent the bacterium from attaching. A simple analogy to help explain the concept of anti-adhesive therapy uses the example of tying shoe laces. Tying shoe laces is a simple task. However, if you were asked to hold a tennis ball in each hand while trying to tie your shoelaces the task becomes considerably more difficult. In this analogy, your hands represent a bacterium’s adhesins while the tennis balls represent the anti-adhesive therapy. Clearly, holding the tennis balls prevents you from easily accomplishing the task of tying the shoe laces. With anti-adhesive therapy the goal is to prevent bacteria from binding to your cells much like how holding the tennis balls would prevent you from tying your shoes. An ideal anti-adhesive medication will prevent an organism from attaching to a site where it would normally cause infection. Preventing the organism from attaching means it can not cause disease. The diagram on the right shows anti-adhesive therapy in action. Panel A shows the red bacteria binding to their target cells and potentially causing infection. Panel B shows anti-adhesive therapy, represented by green balls, blocking the bacteria from binding.

Benefits of Anti-adhesive Therapy

One of the most beneficial aspects of anti-adhesive therapy is that these agents can be used together with already available therapies like antibiotics. This means that anti-adhesive drugs can work together with other therapies like antibiotics to become more effective than either agent is alone. For example, antibiotics can be used to kill many of the infectious organisms but the ones that are resistant will be unable to establish themselves if anti-adhesive drugs are also present. This concept is called synergy and it already employed in medical practice by using different combinations of antibiotics in order to achieve a much more successful outcome. Clearly, anti-adhesive therapies have the ability to fit right into this treatment strategy.

Another great benefit of this new approach is that it is designed to be very specific. This means when a patient takes an anti-adhesive medication there will be no collateral damage as the anti-adhesive substances are designed to target only the specific invading organism. This specificity also means the side effects associated with treatment would be minimal.

Examples of Past Success with Anti-adhesive Therapy

Although there are currently no anti-adhesive drugs on the market the concept has been proven to work in prevention of urinary tract infections. Urinary tract infections are relatively common infections which are caused by the well known bacterium Escherichia coli – also known as E.coli. For a number of years the relationship between cranberry juice in the prevention or treatment of urinary tract infections had been observed.^5-10 However, the details about how this relationship works had not been determined. A well known study looked into this relationship to see if any benefit were offered by drinking cranberry juice. This study followed patients who drank a glass of cranberry juice every day for six months. This study provided evidence to support the use of cranberry juice in prevention of urinary tract infections.⁵

More recently, it has been determined that cranberry juice contains some anti-adhesive substances.¹⁰ Further research has found that these anti-adhesive substances are the reason that cranberry juice seems to prevent urinary tract infections. A group of researchers tested the ability of E.coli cells to attach to cells of the bladder, as this attachment must occur to cause a urinary tract infection. They found that when using more concentrated solutions of cranberry juice the E.coli cells were less likely to attach.¹⁰ These results suggest that the cranberry juice is preventing the E.coli from attaching to the bladder cells. Since then, scientists have gone on to identify the anti-adhesive substances which are found in cranberry juice.⁶

Won’t Resistance Again Become a Problem?

At this point you might be wondering “isn’t the same problem going to happen – resistance to these new anti-adhesive drugs?” This is a valid concern and something scientists have surely considered. In fact, it is possible that organisms will become resistant to anti-adhesive therapies. However, unlike antibiotics this new approach does not involve killing the infecting organisms. By not killing the bacteria we are not disrupting the bacterial population. This means that the so called ‘resistant bacteria’ will not be singled out and the population will remain relatively normal. In that sense, resistance to anti-adhesives does not seem to be as great of a problem when compared to antibiotic resistance.

What are the barriers to development of Anti-adhesive Therapy?

One of the main barriers to development of anti-adhesive therapies is that pharmaceutical companies are currently not interested in developing new antimicrobial drugs.¹¹ The main reason industry has left this field is that the return on investment is comparatively low since antibiotics are only used for short term treatment. On the other hand, drugs for conditions like diabetes and high blood pressure need to be taken on a daily basis and year round. A second reason that industry is not developing new antimicrobials is that many governments are imposing strict price controls and expensive regulations which have drastically cut into their potential profits.¹¹ As it stands, it is difficult for drug companies to make a profit producing antimicrobial drugs and for this few new antimicrobial medications have been developed.

What’s the Next Step?

The problem of antibiotic resistance is undeniable. One possible solution is the use of anti-adhesive agents to prevent and cure diseases. The recent work with cranberry juice has shown promising results in this new field. Unfortunately, as a new avenue of therapy, pharmaceutical anti-adhesive agents are currently not available on the market. In order to see future development of such drugs we, as tax payers, must lobby our governments to support this vital branch of research. We must insist that our tax dollars are spent to solve the problem of antibiotic resistance before it becomes uncontrollable. By doing so, we can only hope that our efforts in support of this new line of therapy will lead to a cash infusion into the field which might bring about marketable anti-adhesive drugs. Only time will tell if this new approach will be the answer to antibiotic resistance but your support is the first step to making this happen.

References:

1. Ashley D, Brindle M. Penicillin resistance in staphylococci isolated in a casualty department. J Clin Pathol. 1960; 13(4):336–338.
2. Kelly C, Aug;9(8):. JY. Anti-adhesive strategies in the prevention of infectious disease at mucosal surfaces. Expert Opin Investig Drugs. 2000; 9(8):1711-21.
3. Ofek I. A bright future for anti-adhesion therapy of infectious diseases.
Cell Mol Life Sci. 2002; 59(10):1666.
4. Ofek I. Anti-adhesion therapy of bacterial diseases: prospects and problems. FEMS Immunol Med Microbiol. 2003; 38(3):181.
5. Avorn J. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA. 1994; 271(10):751.
6. Foo LY, Lu YR, Howell AB, Vorsa N. The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro. Phytochemistry. 2000; 54:173–181.
7. Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M. A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity,. Phytochemistry. 2005; 66:2281–2291.
8. Jepson R, Craig J. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2008; (1).
9. Johnson B, Lin B, Dinderman M, Rubin R, Malanoski A, Ligle F, et al. Impact of cranberry on Escherichia coli cellular surface characteristics. Biochem Biophys Res Commun. 2008; 377(3):992-994.
10. Pinzón-Arango P, Yatao L, Camesano T. Role of cranberry on bacterial adhesion forces and implications for Escherichia coli-uroepithelial cell attachment. J Med Food. 2009; 12(2).
11. Norrby S, Nord C, Finch R. Lack of development of new antimicrobial drugs: a potential serious threat to public health. Lancet Infect Dis. 2005; 5:115–19.

Curry

My housemate made CURRY for dinner and now the entire house and all of it's contents (including myself) STINK like curry. Nasty.

Today has been a very unproductive study day. I mean I've been sitting in front of my desk but seriously nothing is getting done.

That is all

UWA Pharmacy Student of the Year (PSOTY)

Below is an excerpt from an email I received this morning from my pharmacy practice unit coordinator.

Congratulations. You are receiving this email because you have performed well in a Pharmacy Practice exam or practical session or overall in PP1, PP2 or PP3 to date. You are in the top 9 students for pharmacy practice. As such you are eligible to compete in the UWA Pharmacy Student of the Year Competition.

The competition is on Monday 25^th May 3-5pm. You will have to “perform” in front of your peers….two primary care case scenarios. The winner will be announced as the UWA PSOTY representative – an important addition to your CV! This will also be acknowledged at prize night. You will then represent UWA at the state finals in August. The state prize is a trip to PAC in October (Sydney) – all expenses paid. You will have a 1in 3 chance of winning this (UWA, Curtin and Murdoch). The national winner wins a trip to an international pharmacy conference in Slovenia. What an opportunity

My goal for the term was to be nominated for the PSOTY so I'm pretty happy. I'm not sure if I will compete because I have a lot going on right now and passing my finals is a bit more important. I know it's a great opportunity so I'm still not sure.

Dispensing Exam 1

This Monday we had a final dispensing exam. These are super stressful oral exams which last 45minutes. Some people always fail these because there are so many ways to mess them up. Legal issues, dosing problems, label issues and many other things are an automatic fail. I left the exam feeling good as it seemed to have gone well. We just got the marks today and I got 86%!!! I've never scored that high on one of these exams. That has to be one of the highest marks in the class. I'm very pleased.

Other than that I had a presentation today. It went well. I've got one more presentation tomorrow then one one the next day and that's pretty much it for this term (other than the research project).

Last Compounding Lab II

So I didn't get any pictures of those last two compounds. Anyway, I made some suppositories and a suspension.

That is all.

Last Compounding Lab

Tomorrow is my last compounding lab. This means tomorrow is the last time I will be making compounds as a student. Exciting day! However, I enjoy compounding so it sort of sucks at the same time. Maybe tomorrow I"ll post a picture of my products. Last week me made calamine cream and troches. My calamine cream cracked so I'm going to be getting a zero on that one.

Crunch Time

Things are starting to wrap up at UWA. I just had my last dispensing class. Next Monday we have a 45 minute oral dispensing exam which is going to be extremely stressful. Other deadlines I’ve got for next week include:

Tuesday – Nursing home review presentation
Wednesday – Current developments anti-adhesive presentation
Thursday – Home medicines review presentation.
Then the following Monday I have another practical oral exam (VIVA/OSCE)

All I can say is that I’m stressed. I’ll get through it though. Hopefully my work doesn’t suffer but I’m really running out of gas.