Question:

1) Briefly describe the issues.

Explain what you’re doing. A type of method that reveals where you looked, what search terms were used, dates and how many papers you have.

2) Give evidence to support or disprove the statements.

You must explain the results of your searches, and put together arguments for and against the literature. Finally, you should discuss whether the findings are valid.

3) Briefly explain what other evidence you would like for this to support the claim or to disprove it.

Answer to Question: UZWRSS153 Evidence And Research In Practice

Introduction

Each antibiotic type is designed to bind to specific proteins within the bacteria cell wall in order disrupt key cellular functions (Kohanski. Dwyer.& Collins 2010. p. 423).

The broad range of antibiotic activities means that they can have the same level of toxicity against different types.

Antibacterial molecule manufacturing by bacteria has been ongoing for many years, long before the advent of human civilization.

Mutation accumulation is the process by which genes that are resistant develop. This allows bacteria to survive even in the presence of toxic molecules.

Multiplication and division of bacteria can cause mutations in their DNA. These mutations, in most cases, have a negative impact on organism survival.

In some cases, however the mutation may have a positive effect upon the survival of bacteria.

An antibiotic can make the bacteria stronger, so a mutation that makes it more resistant to the environment can be a boon for the bacteria. It will also allow the bacteria to grow fast and divide quickly, and eventually dominate the surrounding population (Aminov (2010)).

It’s not surprising, therefore, that most human antibiotics are derived naturally from bacteria such as soil bacteria. The genes that confer resistance have been discovered long before the drug was approved.

While antibiotic resistance has been around for some time, it has only recently that the epidemic is becoming more severe due to rampant human use.

There are a variety of confounding factors that contributed to resistance of the last-line antibiotic. We will be discussing these in this essay.

Search Terms

For the purpose of locating appropriate literature, we used the following search terms: drug resistant bacteria 21st century, overuse and causes of antibiotic resistance, pharmaceutical firms, future, last-line antibiotic resistant mechanisms, challenges. Latest developments. NHS, PHE. NMC. Search engines include CINHAL. PsychInfo. PubMed.

There were 47 search results, 21 of which were the most relevant.

The articles search ranged from 2007 to 2017.

The top themes in the articles selected were: Antimicrobial Resistance Causes (AMR) Public behaviour and perception, Commercial Pressures, Clinical Usage, Regulation, Synthetic Drugs as the Solution

Public Behaviour, Perception

The article’s Chief Medical Officer (CMO), stated in part that it is important to reduce inappropriate antibiotic prescribing.

Lee, Cho and Jeong et. al. (2013. p. 4274), support this view by stating that in cases such intra-abdominal infections and nosocomial pneumonia, following appropriate prescription guidelines (such as carbapenems), for antibiotic effectiveness can reduce the likelihood of new resistance.

It may not be true.

People perceive antibiotics to be an effective and fast treatment for all illnesses.

Hovering is an example of such a behaviour. This means that a patient may not take the prescribed amount of antibiotics.

The person’s immediate health may not be affected by this behavior, but if the hoarding is motivated by a future need, there can be an increase in misuse on non-susceptible bacteria.

You can also purchase the product without a prescription.

There are some countries where antimicrobial access control isn’t universal. Some countries have strict regulations regarding the sale and production.

This leads to a variation in the quality and availability of therapeutic materials, as well as in their cost and availability.

The internet has allowed easy, global access to antibiotics (including those that are restricted like ciprofloxacin & rifampicin) (Khalid. et al. 2016).

Commercial Pressures

In the article, CMO said that every person has a responsibility to prevent infection by maintaining good hygiene.

The NHS recommends that everyone maintains good health and avoids skin conditions and infections.

One must maintain a regular cleansing of the guts, mouths, skin and skin to prevent the ingestion of microbial agents.

Also, it is important to disinfect all surfaces one comes in direct contact with, for example, tables and floors.

While this may be true in some cases, such as when the cooking surface must be kept clean at any time, there is also the possibility of abuse.

For good health, it is impossible to completely eliminate microorganisms and other organisms from an individual or his/her environment (Aliello Larson and Levity, 2007, page137).

Recent studies show that one must have an equipped immune system to be exposed to microorganisms.

One develops an immune system that is capable of producing antibodies and cells that will live in the body all their lives. This can also be used to help with effective vaccination.

These cell groups, along with the immunities they trigger, are normally formed during childhood. However, exposure to other antigens in later life years can supplement the initial immunities.

Advertising that stresses cleanliness is detrimental to children’s immunities.

When a person or child becomes infected, even if they are not as virulent as the microorganisms, they will eventually succumb to disease or even death.

Clinical Use

Dr Susan noted in the article that there was a decline of overall antibiotic prescriptions from doctors.

Public Health England Report (2016) also reported that there was a decrease in antibiotic prescriptions from GPs and clinicians (PHE20016).

But, physicians are the most common source of empirical antibiotic usage in clinical practice.

Doctors applying antibiotics in random doses is due in part to their inability to accurately diagnose and quickly treat infectious diseases.

Multiple lab tests may be required in order to diagnose a specific condition accurately. These may take days to complete.

If a patient is suffering from life-threatening conditions, it is normal for them to require immediate diagnosis.

Sometimes, this situation requires multiple antibiotics to be administered simultaneously with the hope that one can successfully control the disease.

This is a common situation in which antibiotics are over-applied to patients. It can be difficult to manage the drug use by developing and implementing accurate and rapid diagnosis.

However, it is more common for a doctor to apply multiple antibiotics than empirical treatment (Kuehn & IDSA 2013 p. 2385).

According to the Nursing and Midwifery Council Professional Conduct, nurses are expected identify and minimize all risks to their patients. This can be done through participation in antimicrobial management.

This is about promoting appropriate antibiotic therapy and making sure it is used in the right dosage, duration, and route.

Most cases of serial antimicrobial use are due to the patient requesting immediate relief from the illness (Cliodna, McNulty, & Boyle et.al., 2007, p. 810).

On one hand, the patient might demand antibiotics belligerently. On the other, a doctor may over-prescribe an antibiotic to please the patient or get repeat business.

Prescription antimicrobials are usually applied in a predetermined regimen. It dictates the dosage, frequency, and length of time.

Most doctors recommend a period of 5-7 days. Some doctors will extend the time to 14 days.

It is a common assumption that the infectious pathogen can be eradicated by high doses over a longer time period.

Recent studies show that relapse rates for patients who discontinue treatment due to a decrease in symptoms are significantly lower than those who complete the entire treatment program (Ferry, Holm, & Stenlund et.al.

2007 (p. 49) Jansaker FrimodtMoller, Bjerrum, 2016 (p. 727). By limiting the treatment course to the minimal required dosage and duration, the non-combatant organisms’ selective pressure in a patient as well the environment are reduced, and the overall adaptive reaction of the microbial agency is also limited.

Regulatory

Professor Sally argues that the healthcare sector does not want to see any progress in the fight against drug resistance reversed.

Furthermore, she asserts that the sector must do all they can to combat drug resistant infections.

PHE released its annual report for 2015, which provides information and guidance to doctors and clinicians regarding effective ways of avoiding the prescription of unnecessary antibiotics.

There have been changes in regulation over the last ten years that have made it more difficult to meet trial design requirements for approval of new antibiotics. The reasons behind this is complex which has resulted partly due to statistical and scientific concerns and which are propelled by dangerous and irrational extremes by highly embarrassing and public failures in post-marketing due to antibiotic toxicity as was seen with telithromycin(Spellbberg, 2010; Echols, 2012).

The statistical concerns have taken precedence over clinical feasibility and actuality in terms of trial standards.

It was several years before clear guidance on the conduct of trials for new antibiotics was released.

They created nonsensical trial guidelines that were not feasible after the guidance was released (Echols and Spellberg, 2012).

Some experts questioned the effectiveness of antibiotics. They suggested that placebos could be more effective against lethal infections, such as Community Acquired Pneumonia. 2011; Spellbeerg & Talbot et al., 2008).

In the end, proposals were put forward that required that placebos be used in future antibiotic studies for CAP treatment (Pakhale Mulpuru &Verheji et aal.2014).

These and similar suggestions were accepted and discussed. After a prolonged and costly process, the dialogue was finally closed (Spellberg und al. 2011, 2011).

Some of the other unacceptable new trial standards elements were banning patients from receiving new pre-study antibiotics. This was for patients who were going to be enrolled into clinical trials.

This prevented patients suffering from critical illness from being enrolled.

In addition, intravenous therapy was required for studies. This included multiple days of intravenous administration in hospital settings for intra-abdominal infections such as UTI, pneumonia and intra-abdominal.

The requirement to enroll patients who are not seriously ill was also eliminated.

As a result, there was very little patient eligibility at any time.

New criteria were established where patients were only to be evaluated for drug effectiveness if there was evidence of etiologic bacterial infection that led to a pneumonia study that was twice or more large than the original.

This resulted to shrinking of non–inferiority marges due to mathematical arbitrari manipulations that were used in discounting different antibiotic treatment effect best-guesses for various disease sizes. Further, the sizes of the samples were further divided (Spellberg Lewis, et al. 2011, 2011).

The resulting 10-year loss of time spent discussing, debating, deliberating on new antibiotics development was a significant exacerbation of time, cost, risks, and costs. Other economic realities and scientific challenges were also having similar effects.

It was clear that companies and scientists were less willing to work on new antibiotics development.

The result is that antibiotic resistance has increased despite the fact that no new stronger or more effective options have been developed (Spellberg Lewis and co., 2011).

Discussion

Antibiotic resistance can only be defeated if new drugs are developed that can fight bacteria mutations.

The real problem is not the lack of new antibiotics, but the fact that existing antibiotics have developed resistance.

New manufacturing systems are needed to combat antibiotic resistance.

There are two main ways to alter the pool of antibiotics in order to improve discovery and development. (Spellberg Blaser &Guidos, 2011, p. 397)

The first is to alter the screen substrate by searching for new sources for natural chemical substances. This will increase the chance of finding chemical scaffolds that have a novel composition.

This can then be extended to include iterative modification and substitution with the goal of optimizing effects.

Although there has only been one successful microbial culture, this can lead to new metabolomics, biochemical or proteomic studies that may produce new scaffolds for development in the future. (Spellberg). Lewis, et al., 2011).

Experts also recommend enriching chemical scaffold libraries, which are chemically appropriate, to penetrate into bacteria and avoid its efflux (Silver (2011), p. 70).

The second is that instead of screened substrate modifications, the physiological modification may be done on the screening conditions. (Fahnoe Flanagan and Gibson, 2012).

Rich media has been used traditionally on screens for robust microbial growth.

But, the environment is often very hostile. The host’s environment can have a number of negative effects on innate (such changes in pH, complement, phagocytes) and adaptive (such cell and antibody-mediated immunity) defence elements. It also restricts the nutrients that the host factors mediate (such trace element source sequestration and carbon).

It is possible for screening to be done in media that have a higher trace nutrient, pH level, or has altered sources carbon (Spellberg, Talbot, &Brass, et al., 2008, p. 249). This would allow for the identification of promising scaffolds that could be used as therapeutics even if the exact chemical libraries are not available.

Conclusion

According to the article, resistance against last-line antibiotics is a war in which there has been some recent positive progress.

This assertion is supported by many sources as described in the essay.

Additional recommendations include personal hygiene, reducing inappropriate antibiotic prescribing and, by inference, continuing to decrease overall antibiotic prescriptions given by doctors.

The article states that the healthcare sector is doing everything it can to make sure that drug resistance declines.

While the above suggestions seem like sound solutions, their application is disputed.

There are many factors that may challenge the effectiveness of the solutions.

The first is the fact that new antibiotics are almost impossible to clinically test and approve by drug regulatory boards.

The regulation has changed over the past ten year, which has led to a decrease in feasibility of trial design requirements, which allows approval of new antibiotics. (Spellberg & Baser et.al., 2011; Shlaes et.al., 2013; Spellberg 2010, 2010).

With regard to clinical use, secondly, it is due to physicians’ inability to accurately diagnose and quickly identify infectious disease. It is also important to know how resistant the pathogen is to antibiotic therapy.

Third, false advertisements that suggest that one should maintain good overall health. However, the individual must eliminate all microorganisms from their environment.

Finally, the perception by the general public of antibiotics being an effective and quick treatment for many illnesses has led to behaviours that have outstripped the physician’s control.

All things considered, the battle against antibiotic resistant begins with the regulation and monitoring of antibiotic development.

The reform of regulations for new antibiotic development standards requires three elements.

The first element is the necessity of ensuring that traditional designs are relevant and feasible.

European Medicines Agency recently released guidelines that met these goals and set reasonable, achievable, and logical standards for such researches.

New guidelines for trials are expected to be published that emphasize feasibility and clinical and technical rigor. This will allow patients to use non-inferiority meaningful therapeutics (Shlaes & Opiela et.al., 2013, p. 4605).

Second, we should focus on facilitating the development of new antibiotics that meet unmet high impact needs (Rex Eisenstein et Alder, 2013 p. 269).

European Medicines Agency, 2012). They have published draft guidance’s that reflect their support for such novel developments.

Concentrating on resistant bacteria will save time and money.

This is a good option for patients, as it focuses both on the actual unmet need and also helps to prevent misuse and overuse after marketing.

As more molecular diagnostic rapid tests are made available (IDSA 2011, 2011), the feasibility of such researches will increase.

Thirdly, harmonization is required between the US regulatory agencies and other regulators worldwide.

The legal and policy climates in which the EMA operates are quite different to that of other regulatory bodies, such as the Federal Drug Administration or Echols.

To facilitate access to new antibiotics in this era of global village economics, an approach that is consistent across the globe is necessary.

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