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Full Version: The Terrifying Rise of Antibiotic Resistance
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Since past few years, there has been a growing concern about the discrepancy which exists between antibiotic resistance and the activities of drug manufacturers. Namely, Aaron Kesselheim, M.D., who is an assistant professor at Harvard Medical School, says that the antibiotic resistance is rapidly increasing, but, despite that, drug developers and manufacturers are turning away from the antibiotics development and focus more on other, more profitable products.

Frightening Statistics

In the world of hospital infections, which take $32 billion every year only in US, that trend is not favorable. In the last few years, only two antibiotics for serious infections are developed, and several are still in the process of development. Among them there are only a few which are effective against Methicillin Resistant Staphylococcus Aureus (MRSA) – today’s greatest threat in bacterial world. Global Information, Inc. estimates that there are only 66 companies dealing with antibiotics development and searching for new antibiotics, and more than 85% of them are small companies. Of the total 109 antibiotics that were in the process of development, 70% are in the Phase I (preclinical studies on laboratory animals). It will take 10-15 years for those medications to be approved and distributed to the market.

It is well – known that irrational use of antibiotics is the main causes of increasing antibiotic resistance. It takes a lot of time, money, resources, and professionals to develop and test a new drug, but if it is not conserved and carefully prescribed, all the effort is futile. In that case, the development of bacterial resistance to antibiotic is fast, progressive, and inevitable. Dr. Kesselheim has recently pointed out to this problem, and proposed a new reimbursement system in which an important factor for getting the grants would be a good plan for conservation of antibiotics.

Improving The Efficacy of Antibiotics

One way to address antibiotic resistance is to improve the efficacy of current antibiotics. Scientists from Enbiotix, a newly founded drug development company, claim that silver can be added to current antibiotics in order to improve their efficacy. Silver enhanced antibiotics are especially efficient against gram-negative bacteria, which are generally the most problematic group. Silver also enlarges the spectrum of many antibiotics such as vancomycin. Dr Morones Ramirez from Enbiotix says that silver-enhanced antibiotics have great possibilities, and believes that silver can be easily implemented in standard antibiotics in five years. Of course, the most important step is to investigate the safety of use and the toxicity of silver in laboratory animals, mammals, and finally in humans. Many big companies such as Pfizer are interested in this idea too.

Cubist Pharmaceuticals is a company founded in 1992, which emphasizes greatly the importance of antibiotics development. The scientists from that facility claim that the antibiotics will play an important role in the future. They are focusing their attention mainly on antibiotics for gram-negative bacteria, which they consider a greater concern than MRSA, because of the wide distribution. One of Cubist’s antibiotics against gram-negative bacteria – Ceftolozane, is currently in the Phase III of trials. Another drug they are developing is called Surotomycin, and it is intended for patients suffering from gram-negative infections caused by Clostridium Difficile. Clostridium difficile is a gram-negative, spore-forming bacterium which is responsible for a great number of hospital infections, and it manifests as pseudomembranous colitis.

Using Bacterial Toxins as Targets

Other than focusing on the elimination of bacteria, another approach is to develop the drugs which would target bacterial toxins, thus inactivating their toxic effects. Merck Company is currently testing several medications which are consisted of antibodies targeting the toxins of C. difficile (A and B). Merck is also working on antitoxin antibodies for hepatitis C virus (HCV), human cytomegalovirus (CMV), and human immunodeficiency virus (HIV). GlaxoSmithKline is putting much hope into its drug called Relenza, which is designed to inhibit the function of neuraminidase of influenza virus. Neuraminidase is an enzyme produced by influenza virus which allows it to destruct tissues, spread and attach human cells. They are also dealing with new solutions for malaria, HCV, and infections caused by bacteria. Basilea Pharmaceutica has also several drugs in different phases of clinical and preclinical trial. They have recently raised $89 million in order to intensify their study on carbapenems, a very powerful, broad - spectrum group of antibiotics used in the treatment of gram-negative as well as gram-positive infections.

Microbiome Regulation Approach

It is well known that different pathogenic and non-pathogenic bacteria are fighting for resources in our body. That means that if we could increase the number of non – pathogenic bacteria (commensal bacteria) at the place of infection, we would lower the number of pathogenic bacteria, thus helping our immune system to win the fight against the enemy. Second Genome is a pharmaceutical company which tries to apply this approach by modulation of gut microbiome. That could be particularly useful for hospital infections caused by Clostridium difficile.

With such a low number of pharmaceutical companies interested in antibiotics development, and the rapidly increasing problem of antibiotic resistance, it is unknown for how long are we going to be protected from serious bacterial infections. Scientists suggest that policy changes are needed in order to encourage companies to give more attention to this problem. Also, the control of antibiotic use has to be improved at all levels. Most of the countries have the laws prohibiting the purchase of antibiotics without prescriptions, but the problem lies in the small markets and stores that are still not under a strict surveillance. Unaware of the consequences of their actions, they are using their position in order to get personal benefit.
This year, scientists discover antibiotic-resistant superbugs spreading even through our food and water supply. Its threat, according to a British chief medical officer, can rank with terrorism and global warming.

It is also something to be feared since it takes years to produce an antibiotic while these superbugs are arising out of sources that might be inevitable for us to come across.

Such food sources are primarily from sea foods from Southeast Asia where 5 percent of a test done for prawns from Vietnam contained antibiotics and only 5 percent of these imported goods are being traditionally screened. This can potentially be very harmful.

Poultry and livestock are also in this spectrum. Farmers may have abused the use of antibiotics due to the fear of losing more of their animals when one is possibly infected with a bacterial disease. Aside from therapeutic antibiotics, there are companies who also use growth-promoting antibiotics, which makes resistance more of a problem.

For examples of such bacteria, we’ve got the well-known Methicillin-resistant Staphylococcus aureus (MRSA), but others are already most likely spreading. Another is the multi-drug resistant Mycobacterium tuberculosis which is possibly caused by the New Delhi metallo-beta-lactamase (NDM1), an enzyme making bacteria resistant to beta-lactam antibiotics. Strains of superbug gonorrhea have also emerged and we know of Vancomycin-resistant Enterococcus (VRE).

Such is the case because of the unnecessary prescribing or sometimes the overprescribing of antibiotics, when patients do not complete the entire course of their prescription, and when hygiene and infection control aren’t regularly practiced.

It is a serious concern when some bacteria become resistant to easily available antibiotics since new ones need years to be approved. For the majority, it is like a “ticking time bomb”, but for some, they believe the bomb has already exploded. The continuous lack of antibiotics and the spreading of these infection-causing resistant bugs will later on make most diseases virtually impossible to treat.

As health care professionals and even as regular citizens, we must observe prevention and transmission precautions to at least minimize the spread of disease.
Multi Drug resistance in Mycobactrium tuberculosis

The bacteria which cause disease called tuberculosis (TB) is gram positive bacteria and it can develop resistance to the antimicrobial drugs used to cure this disease. Multidrug-resistant tuberculosis (MDR-TB) is TB that does not respond to at least isoniazid and rifampicin, the two most powerful anti-TB drugs and whenever one someone search for a MDR-TB strain they first test for these two drugs.

The primary source of multidrug resistance is mis-management of TB treatment and person-to-person spreading. Most people with tuberculosis are cured by a strictly followed, six-months drug schedule that is provided to patients with support and supervision. Inappropriate or erroneous use of antimicrobial drugs or use of ineffective formulations of drugs, and premature treatment stoppage can cause drug resistance, which can then be transmitted, especially in crowded settings such as prisons and hospitals.

In few countries, it is becoming increasingly difficult to treat MDR-TB. Treatment choices are limited and expensive, recommended medicines are not always accessible, and patients experience many adverse effects from the drugs. In some cases even more stern drug-resistant tuberculosis might get developed. Extensively drug-resistant TB, XDR-TB, is a form of multi-drug resistant tuberculosis that responds to even smaller amount of available medicines. It has been reported in 92 countries worldwide. WHO defines the cases in India as extensively drug-resistant tuberculosis a severe form of drug-resistant TB. Other terms used in current news reports or scientific journals have not been clear by global TB experts.

The possible solutions to control drug-resistant TB are to:

• One must cure the TB patient the first time found around.
• Make sure adequate infection control systems are available in facilities where patients are treated.
• Make sure the appropriate use of recommended second-line drugs to treat this form of TB.

In recent year (2011-2012) an estimated 450,000 people developed MDR-TB in the whole world. It is estimated that about 9.7% of these cases were XDR-TB.