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Alternative Treatment For Bacterial Infection in Response to Antibiotic Resistance

Brittany A. Christopherson

Abstract: Antibiotic resistance is a continual foe. Despite continual effort to combat infection using antibiotics, little effort has been allotted to finding alternative treatments. Numerous alternatives exist, and present research, though scarce, shows promise. Viable treatments include: herbal and plant extracts, folk remedies, exploiting the placebo effect, and use of already existing over the counter products. This extended commentary attempts to collect the multi-faceted research done in the area of alternative treatments and condense these studies into a quick reference. The examples provided are only a glimpse of what is possible, but are backed by thorough research- many by the rigors of clinical trials.

Introduction

Nature has been taking care of itself in a sort of circle of life: a natural judge, jury, and executioner. Yet humans seem to face a huge battle on a daily basis between themselves and bacteria. Antibiotics continue to be created to try to get ahead of ever changing bacteria. Nature just continues as it has for millennia. Why not return to nature then for answers to the seeming losing battle humans are fighting? From herbs to over-the-counter drugs, answers to antibiotic resistance may lie in alternative treatments. It is time to open the horizons of medicine and explore these amazing treatments. The following paper will explore what is known about alternative treatments by identifying the problem that bacterial resistance to antibiotics poses, summarizing what research has been done thus far in modern medicine, explaining each remedy, and, finally, pulling the findings together to evaluate where to proceed from this point in research of alternative remedies.

Background

Bacterial resistance to antibiotics is a growing concern that is leaving pharmaceutical companies lost for ideas. Antibiotic after antibiotic is produced, but the same result seems to occur soon after: little effectiveness because of bacterial resistance to the new drug. Physicians are left to continue trying tried and true methods such as amoxicillin and penicillin, with little results. Why? Too many years of misuse and overprescribing of antibiotics. While some hope to cling to that widely travelled, but dangerous, road of antibiotic treatment, there is another avenue to turn onto: alternative treatment, more specially, natural remedies and currently existing over the counter treatments, which have the potential to hold great promise for combating bacteria.

Herbal remedies have been shown to exhibit antibacterial properties. In the study Antibacterial Properties of Chinese Herbal Medicines against Nosocomial Antibiotic Resistant Strains of Pseudomonas aeruginosa in Taiwan, over fifty herbs were tested for antibacterial properties in strains of antibiotic resistant bacteria. It was found that “26 of the 58 plant extracts showed antimicrobial activity against all of the test strains. Ten out of the 26 plant extracts possessed broad-spectrum antibacterial properties (96%) against the tested organisms” (Ching-Shen, et al., 2007, p.6). If simple plant extracts can exhibit such power against bacteria, why not explore these remedies further? Research may provide alternatives, and maybe a little much needed hope.

Somethings to consider are the other positives of not utilizing synthetic remedies: economical and ecological implications. Natural treatments are closer to nature and thus leave less of a ecological footprint. Granted, resources for these treatments would have to be used responsibly and not over harvested. Synthetic potions can also be much more costly to develop and mass produce, which these costs are passed onto the consumer with a little extra being put into the pockets of pharmaceutical companies. In tough economic times, health should not have to be what is sacrificed.

Folk remedies provide some positive light. In one research report, “Effect of Folk Remedy, Bainiku-akis, a Concentrate of Prunus mume Juice, on Helicobacter pylori Infection in Humans,” researchers concluded that there is an "antibacterial effect of Bainikuekisu on H. pylori in the human stomach” (Nakajima et al., 2006, p.1). This is an age old native remedy for diarrhea, yet it deserves to not be tossed in the discard pile with all remedies of old.

While often thought to be taboo, the placebo effect might have a place in the discussion of alternative approaches to treating bacterial infection. In several studies, it has been found that placebos actually show very little difference in their effects when compared to active treatments of antibiotics. One such study will be noted later in this commentary. The mental side of recovery is simply amazing and should be researched further because the side effects of antibiotics can sometimes be nearly as insufferable as the infection itself.

Lastly, over the counter products may hold promise for the treatment of infection, without the antibiotic price tag. In a study that will be revisited towards the end of this paper, it was found that an over the counter, or OTC, product, benzoyl peroxide, produced greater relief on its own than two different antibiotic treatments: all while being much more cost effective.

It is increasingly clear that alternatives are far past due. Research has been scarce, but what does exist provides a fresh look at the many possibilities that exist for treating bacterial infection in a world of increasing antibiotic resistance. The following is a collection of just a few of the categories of alternatives that are present, if only antibiotics are pushed aside for a moment as the only effective way to fight an ever more formidable enemy: bacteria.

Medicinal Plants: Tea Tree Oil, St. John's Wart, Spice Extracts

Often plants are taken for granted. Crops feed livestock and humans, flowers grace tables as elegant décor, spices add flavor to food, and garnishes of lemons and parsely add the extra touch to drink and entrees. But could plants also hold answers to the question of alternatives to antibiotics? According to the report entitled “Medicinal Plants for the Prevention and Treatment of Bacterial Infections,” there are over 155 plant species from Thailand alone that have antimicrobial properties (Mahady, 2005). This is an immense number when considering the resources the entire planet may hold. While it would be tedious and overly long to list even a major portion of all the species that have anti-microbial properties, a few are worth mentioning.

One species of plant that may sound fairly familiar is tea tree oil (TTO). Melaleuca alternifolia is the plant that produces this oil (Mayo Clinic, 2009). Tea Tree Oil, or TTO, is often associated with getting soft hair and smooth, scar-free skin. But tea tree oil provides another resource: antimicrobial properties. Yes, the same substance put in luxury shampoo can actually fight microorganisms. Of the microbes studies have found TTO shows activity against, one is none other than Staphylococcus aureus: the common staph infection. Furthermore, it was found that more specifically, TTO could be part of a potential effective treatment of MRSA, as MRSA showed no resistance to small quantities of TTO. The one negative is that like antibiotics, Tea Tree Oil will likely not be a long term fix as untreated populations of MRSA do show signs of producing mutant populations with resistance to tea tree oil (Mahady, 2005).

A second species is Hypericum perforatum. A petroleum ether extract of this plant, often known as St. John’s Wart, shows activity against gram-positive bacteria, especially MRSA (Mahady, 2005). This is no newcomer to the medical field. Actually, St. John’s Wart was used in medicine centuries ago for skin infections (NCCAM, 2005). This is a remedy used centuries ago that is still a viable option in modern medicine. With these findings, curiosity about the viability of age-old remedies being used in medicine today grows.

One last group to note might be that of an immense number of simple food and spice extracts. Oils from anise, basil, carrot, celery, coriander, dill weed, fennel, oregano, parsley and rosemary- just to name a few- offer inhibition of the growth of E. coli. Of these, oregano offers the greatest amount of activity (Mahady, 2005). Aren’t these many things one could find in the kitchen? All of these oils were tested in vitro, so further research is necessary to establish a clinical regimen that includes these essential oils in order to effectively combat bacteria.

While by no means an all inclusive list, this provides a peek at what is possible if only research is conducted in the natural world. If simple kitchen spices can provide an offense in the battle against bacteria, then what isn’t possible, if only a little looking around is done? And this is only the beginning.

Folk Remedy: Japanese apricot Prunus nume

One of the remedies being explored is that of an apricot. Well, more specifically the Japanese apricot Prunus nume. Bainiku-ekisu is a concentrate created from the juice of this fruit. What does fruit juice have to do with bacteria though? A lot, particularly in the treatment spectrum.

A study entitled “Effect of Folk Remedy, Bainiku-akisu, a Concentrate of Prunus mume Juice, on Helicobacter pylori Infection in Humans” chronicles the exploration of the medicinal possibilities of the Japanese apricot Prunus nume and its concentrate Bainiku-ekisu. In vitro, Bainiku-ekisu has been shown to be active against Helicobacter pylori. This is the bacteria that takes up residence in the stomach and can cause gastrointestinal problems. In the study dictated in the letter mentioned above, the amount of H. pylori decreased with treatment of the concentrate, very similar to the response to antibiotics (Nakajima, et al., 2006). This remedy has been used for centuries in Japanese culture, but with these findings, the medical community has had the ball put in their court for providing an alternative to ever less effective antibiotics.

Though in the clinical study the concentrate was shown to have antibacterial properties against Helicobacter pylori, a clinical regimen to optimize the results of this treatment would have to be defined before it can be used mainstream due to a lack of definitive long-term results (Nakajima, et al., 2006). This is a call for researchers to take an opportunity such as this working remedy, and find how to make it most effective for treating infection and replacing a portion of antibiotics that no longer are effective against Helicobacter pylori infection. The problem is developing that regimen, and it will take years and resources to possibly make a defined treatment available. But these findings are a good first step in the right direction.

Root Extract: Cilinervis

Before breaking full force into the depths of bacterial research, a quick trip down the road of parasites might be in order. Malaria seems like a disease of old, but it still is very prominent in the world today. While outbreaks are generally found more often in developing and third-world countries, Malaria is not confined only to those areas, but rather a world-wide issue (CDC, 2010). As Malaria now is joining the arms race with bacterial infections, it is important to find an answer to the treatment question when current pharmaceuticals fail.

Plants and the parasite that causes malaria are fairly similar (Moon & Sim, 2008). Due to this similarity, it is possible that plant products may be able to demonstrate anti-malarial properties. In a study by Moon & Sim, it was found that the extracts from the roots of Pleuropterus ciliinervis showed high anti-malarial activity in vitro. Pleuropterus ciliinervis carries a methanol product in its roots, and this extract is the substance that carries the promise of activity against malaria. In a similar test, this time a clinical study on rats, the prominence of activity against malarial parasites decreased, but the effects upon the infection continued to be substantial (2008). What this means is that malaria, which is a growing problem due to resistance to most first and second line drugs, may be treated with a naturally based remedy that is not within the category of those substances the infection is resistant to already. It offers a little flicker of hope in the fight against malaria.

While malaria is caused by a parasite, rather than bacteria, the implications of finding treatments that do not include synthetic methods is a breakthrough for both fields. This adds to the growing pile of evidence for the importance of further and more intense research into natural answers to the bacteria and antibiotic resistance questions.

Marine Natural Products

“Under the sea, under the sea, down where it’s better, down where it’s wetter…” (Ashman, 1989). It’s the childhood song that parents and children alike get stuck in their heads. While Sebastian was simply trying to convince Ariel to keep her head under the surface, he may have been right about something else: maybe some answers to the bacteria arms race actually lies down there amongst the sand and the sponges. Nature has always provided the balance between forces. Humans have been trying to regain that balance through synthetic means, but now some light is being shed on the idea of returning to that natural order. One place that researchers have begun looking is lying beneath one of the most plentiful resources in the world: water. Underneath the vast seas live extremely diverse species of marine fauna and flora. Greater is the potent defenses these life forms have against the very bacteria that plague humans today. While listing all of the marine products that have been identified just in the past decade would take an immense amount of pages, mentioning a few might be a good start to understanding the benefits of returning to the best defense of all: nature, and more specifically the marine environment.

One product that has been identified is Axinellamines. Axinellamines are a product of certain sea sponges, specifically the Axinella and Stylotella aurantium sponges, as well as certain Caribbean sea sponges. These components of these sponges actually have antibacterial properties, particularly against Helicobacter pylori, as well as preventing fungal spread and abnormal t-cell production (Mancin, et al., 2007). Helicobacter pylori are one of the main types of bacteria responsible for gastrointestinal infection. To be able to find a natural product that is active against these bacteria is quite a new beginning for the medical community.

A second substance determined to have antibacterial properties is glycolipidic tetrasaccharide caminoside. Another product of a sea sponge (Caminus sphaeroconia), glycolipidic tetrasaccharide caminoside has shown promising activity combating Staphylococcus aureus and Enteroccus. S. aureus are the bacteria that cause those renowned staph infections. Also, this substance has been shown as possibly possessing properties that would affect E. coli, without disturbing natural intestinal flora (Mancini, et al., 2007). Antibiotics are well known for the side effect of killing off intestinal flora, friend or foe. This destruction of the good flora increases the chances of another infection and/or a much more significant infection.

Thirdly, there is Polyalkylpyridinium. Polyalkylpyridinium, or Poly-ops, is yet another product of a sea sponge. These alkaloids provide antibacterial properties against Salmonella, as well as other bacteria (Mancin, et al., 2007). Salmonella will be discussed in much greater detail later, but think of the implications of finding a method of combating one of the commonly known infections spread through cross-contamination and improper food handling. While this product will not prevent infection, it provides an alternative to antibiotics which have a long list of disadvantages and side effects.

One last, but by no means insignificant, substance to note is Halocidin. Halocidin is obtained from the hemocytes, which originate from stem cells and are part of a primitive immune system, of a tunicate (Mancini, et al., 2007). A tunicate is a simple sac-like creature that layers the sea floor and functions as a sort of bottom feeder (UCMP, 2006). The best part of discovering the properties of this substance: Halocidin shows hope for battling two of the most feared infections currently: MRSA and VRE (Mancini, et al., 2007).

MRSA is that infection that is spoken of in whispers in hospitals because an outbreak is catastrophic for immuno-compromised patients. MRSA, or Methicillin Resistant Staphylococcus Aureus, is a formidable enemy because it is just that: resistant to the first-line of defense health care offers. MRSA can be, and far too often in hospitals is, fatal (CDC, 2010). VRE, on the other hand, is Vancomycin-Resistant Enterococci. Again, these bacteria cause major problems for the medical community because common defenses have zero effect upon the infection, and time is always ticking (CDC, 2008). With more research and development of a remedy utilizing Halocidin, an answer to these two extremely dangerous bacteria may be closer than though possible.

Four substances of many.The sea holds multitudes of possibilities for treatment of bacterial infection, the research just needs to continue and possibly accelerate to provide more alternatives to the public. Instead of turning to synthetic materials, why not give the very thing that has been providing a world of homeostasis a chance to help humans? Nature just might have a good answer to the human battle with bacteria.

Treating Salmonella

It is a fairly common topic in conversation, particularly the evening news with the contaminated food of the day. It is a fear that the public has that is known only by name. What is this mystery thief in the night? Salmonella. Sounds familiar, especially with the outbreaks in the recent years in various processing plants and produce. The advice seemingly always given at the end of those renowned news stories is to visit one’s primary physician should symptom A, B, or C appear within so many hours. But what treatments are available for this assumed foe? And moreover, are the remedies that a physician will immediately turn to, antibiotics, really any more effective than alternatives?

Before venturing into the treatment options for salmonella infection, or salmonellosis, what is this condition generally characterized by? Salmonella infections are divided into two different categories: gastroenteritis and Typhoid Fever. Gastroenteritis is by far more commonly heard of as this is the type of infection that is spread due to improper food handling and preparation. This condition has an onset of anywhere from a few hours to two days. It is characterized by: nausea, vomiting, diarrhea, abdominal pain, fever, chills, headache, muscle pains, and/or blood in stool. Typhoid Fever, on the other hand, has a much slower onset- five to twenty-one days- and is found to occur predominantly in those returning from a country that has a much higher rate of occurrence of the infection. Typhoid shares one common symptom with its brother infection: diarrhea. Other signs include: mental confusion, coughing, raised rose colored spotty rash on chest, intense fever (above 102°F), slowing of heartbeat, and/or enlargement of liver and spleen (http:www.mayoclinic.com).

With a better idea now of what the infection looks like, how is it treated? Generally, with antibiotics. Why? Because antibiotics have been the go-to medication since their birth as wonder-drugs. But consider for a moment that other options exist. What if one, or all, of those alternatives is actually more effective than antibiotics? Furthermore, what if a placebo--the very base of doing nothing--shows incredibly similar results to current practices utilizing antibiotics? If a placebo can produce similar results to antibiotic treatment of salmonella, then antibiotics lose their necessity as the singular answer to a salmonella infection (or any bacterial infection for that matter until research proves differently on a case-by-case basis).

In a clinical study of 44 pediatric patients, three treatments were utilized to test the effectiveness of antibiotics in treating gastroenteritis type salmonella infections. Two treatments were antibiotics, ampicillin and amoxicillin; the third was a placebo. No change was found in the severity or frequency of diarrhea in patients treated with antibiotics. Recovery time also did not vary between placebo and antibiotics. Furthermore, patients treated with antibiotics were actually more susceptible to bacterial relapse: 53% of each antibiotic treatment groups suffered from returning symptoms. The very symptom the antibiotics were attempting to alleviate- diarrhea- was the most common to reoccur with relapse (Nelson, et al., 1980).  

Since the placebo actually produced more positive results in the big picture of the study, it is exceedingly important to explore alternatives to antibiotics as these often expensive drugs do not produce any more significant results than simply believing oneself healthy. This is not to say that salmonella infections should be left untreated, but why not explore alternative therapies-such as the natural products mentioned above- to treat this condition? After all, even if the remedy itself doesn’t work, it is possible the mental treatment from thinking the treatment is working just might be enough, as it was shown to be in this study.

Treating Acute Otis Media (Ear Infection)

What is one of the major illnesses a parent must watch their child fight? Ear infections, or Acute Otis Media. In recent generations, the natural reaction is to bring the child to the doctor and find oneself walking out with a prescription for the doctor’s choice antibiotic. But is this truly the best option for children, especially in the face of bacteria’s growing resistance to commonly used antibiotics? While antibiotics generally show greater results in treating ear infections, other remedies show comparable results, often with fewer side effects.

In a collection of clinical studies, documented by Vouloumamou, et al., comparing the effectiveness of antibiotics, placebos, and watchful waiting, it was noted that antibiotics generally show better results in combating ear infections. Furthermore, persistence of symptoms beyond two to four days was unlikely with antibiotic treatment, unlike other treatments (2009). It is a huge advantage for antibiotics as a quick recovery time is what is often most strived for due to less time being lost from work and school. If children are able to feel better sooner, parents are able to go back to work much earlier than in situations such as the wait and see method where recovery time is longer, thus causes a greater loss to income from a cut in time at work. Moreover, older children miss less school if they are sick for a shorter period of time. Ear infections are no picnic, and it is very hard for children to concentrate in school if they have the constant pain in one or both ears. This causes students to fall behind if they are sick for extended periods of time. So the remedy that promises the fastest return to health is usually the preferred choice. Antibiotics, as shown in several studies, provide this promise.

Albeit a great advantage stemming from quicker recovery, antibiotics come with a longer list of side effects simply from the nature of the beast, so to speak. In clinical trials, antibiotic treatments were found to be quickly followed by diarrhea, unlike other treatments where gastrointestinal side effects were unlikely (Vouloumamou, et al., 2009). So though children’s ears are feeling better much faster with antibiotics, the side effects that far outlast the brunt of the infection are also a concern because these new symptoms can cause children to still miss school, or take more time out of being in the classroom. The negatives may not necessarily outweigh the positives so it is important to look at both sides of the coin.

Furthermore, in these clinical studies, it was also found that though antibiotics achieved better results, the gap between antibiotic treatment and other treatments was insignificant at best. Therefore, further clinical studies on the effectiveness of alternative treatment, such as simply watchful waiting, are necessary to find the best answer for parents and children when an ear infection happens. Due to small gaps between the effectiveness of antibiotics and other treatments and side effects of antibiotic remedies, further research will determine which treatment truly is a better option for treating children suffering from Acute Otis Media.

So though antibiotics currently seem to be more effective, alternatives are out there and just might be a better answer for parents and children alike. Children cannot afford to miss school, nor parents to miss work. With side effects and recovery time of the three treatments (antibiotics, placebos, and watchful waiting) put side by side, antibiotics are pretty much even keel with the others, and thus is not necessarily the superior cure or always the best answer. There are multiple factors to consider when using antibiotics, particularly with children as allergy and drug resistant bacteria can be fatal at a higher rate than steadfast adults.   

Treating Acne

Acne isn’t necessarily an infection by traditional standards, but comparable. An English clinical study concentrated on the differences between treatments using benzoyl peroxide, an over the counter remedy sold under brand names such as Clearasil, and antibiotics, tetracycline and minocycline (Cortlandt Forum, 2005). This study brings up an interesting point. Are antibiotics, if equal in effectiveness to over the counter remedies, the most cost effective option for the general public, especially in trying economic times? This is a question to be explored eventually, but first the effectiveness question must be answered. The English study mentioned above provides an answer that somewhat contradicts the message pharmaceutical companies and many physicians present: antibiotics are not the answer.

Over the counter, or OTC as is often used in everyday conversation, drugs are a potential alternative to antibiotics due to equal effectiveness in clinical studies. In an English study published in the Cortlandt Forum that took young adults that suffered from moderate acne vulgaris (which is commonly known as just acne), OTC and antibiotic remedies were compared. The OTC drugs tested contained benzoyl peroxide and the antibiotics included were minocycline and tetracycline. While all remedies showed positive results, benzoyl peroxide actually provided more significant results than either of the antibiotics alone. With 60% of participants exhibiting fewer lesions, benzoyl peroxide proved superior to antibiotic therapy, with only 55% and 54% of participants finding relief from treatments of minocycline or tetracycline respectively. Only one therapy afforded a greater percentage of participants reporting a reduction of acne: a combination of benzoyl peroxide and tetracycline, which increased marked improvement to 66% of participants (2005).

These findings raise a few questions, some of which have already been mentioned above. One to revisit now would be the question of economic responsibility. While antibiotic resistance continues to grow and evolve into an ever more formidable beast, why are antibiotics still being used for conditions that are better served by other remedies? Furthermore, why are antibiotics used when other treatments are easier on the general public’s budget? OTC products containing benzoyl peroxide are actually twelve times more cost effective than antibiotic treatments (“OTC Lotion Matches Antibiotics in Treating Acne,” 2005). If alone, OTC treatments are more effective and better on the wallet, why not choose to use those products just around the next aisle corner instead of unnecessary use of antibiotics?

Conclusion

The above paper identified the present research in the field of alternative treatments and presented conclusions that could be drawn thus far. Studies noted included herbal, placebo, and over-the-counter remedies.

If so many alternatives exist, then why hasn’t there been more progress in bringing them to market? The best answer might be simply cost. Research budgets are often too small to take on the task, and without research the necessary evidence to make a treatment a viable option to be made mainstream is simply not there. So the first step is more research. The existing studies have provided a base, and now it is time to build on that foundation. And do so before it is too late. Time is of the essence when it is a matter of health and life.

 

References

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