Biological, Social, Psychological And Ethical Factors Associated With Antimicrobial Prescribing

The purpose of this article is to discuss two antibacterial drugs, their mode of action and mechanism of resistance. The social, psychological, biological and ethical factors related to antimicrobial prescribing will be addressed and doctor/patient negotiation issues investigated. Antibiotic Prescribing It has been established that sore throats and common colds are two of the most frequent reasons to seek medical care, but are usually self limiting1. Most are viral, without the presence of bacterial infection, meaning antibiotic treatment would be modestly beneficial at best2. In Sarah's case, by use of the National Early Warning Score (Fig 1) it can be determined it is unlikely she has an underlying infection, due to her vital signs being within normal parameters3. Inappropriate and excessive antibiotic prescribing has contributed to the growing public health problem of antimicrobial resistance (AMR)4. AMR is the resistance of a microorganism to an antimicrobial it was previously sensitive to, resulting in ineffective treatment. Through development of new antibiotics, random mutation and natural selection have resulted in resistant traits4. Resistance is described as an inevitable consequence of antibiotic use, but has been accelerated due to excessive use5. Due to AMR rates being strongly linked to prescribing in primary care, GP's are now under pressure to adhere to evidence based practice in order to reduce antimicrobial prescribing2. A no antibiotic prescribing strategy, or a delayed antibiotic prescribing strategy should be agreed for patients with a common cold. This is due to the guidance that sufficient evidence of symptomatic benefit should be sought when prescribing antimicrobials, to prevent exposing patients to needless side effects2. The disturbance of the ecological balance of the microbes of the colon, caused by antimicrobials has resulted in the gram positive hospital superbug Clastridium Difficile5. It is advised that practitioners should offer reassurance, explanation and advise a clinical review if the patient's condition worsens or becomes prolonged2. ?Antibiotic Examples Amoxicillin (Penicillin) Mode of Action Penicillin`s are agents which are classified by their effect on the bacterial cell wall. They are B-Lactam antibacterials6. Amoxicillin is an Aminopenecillin, its structure includes a thiazolione ring which is connected to a B-lactam ring. This plays a major role in the characteristic of penicillin and it's mechanism of action7. The peptidoglycan layer of the cell wall, which surrounds certain bacteria is synthesized in three stages. During the final stage, cross linking is inhibited by the B-lactam of penicillin, which contains structural similarities to the peptidogylcan layer. During the cross-linking process, the B-lactum binds to protein 1A (PBP-1A) of the bacterium, which is located inside its cell wall6. Penicillin then acylate the penicillin-sensitive transpeptidase c-terminal domain by opening the lactam ring. This prevents the formation of the cross-link of the two peptidoglycan strands, inhibiting the final stage of bacterial wall synthesis. The peptidoglycan layer is essential for the bacteria's survival6. The disruption of the cell wall by penicillin results in an inability for the transmembrane gradient to be maintained, rising the osmotic pressure. The bacterium then swells, leading to rupture and death by oncosis. Due to this mechanism of action, the antibacterial effect of B-lactam antibacterials is confined to dividing cells7. The destruction of the bacterium is mediated by bacterial cell wall autolytic enzymes. The binding of these specific proteins within bacteria reduces the action of the natural inhibitor of these lytic enzymes. The result is the destruction of the cell wall6. Resistance Penicillins such as Amoxicillin are inactivated by the enzymes B-lactamases, which hydrolyse and break down the B-lactam ring. Certain Gram-positive bacteria release extracellular B-lactamases, which are situated between the inner and outer cell membranes of the periplasmic space. B-lactamases produced may have different ?spectrums of activity against antimicrobials6. This results in Amoxicillin being less effective against gram-positive cocci than other penicillin's such as Benzylpenicillin which is a broad spectrum antibiotic and is effective against both gram positive and negative organisms (Fig2). Erythromycin (Macrolide) Mode of Action Erythromycin has a similar spectrum of activity to penicillins and is therefore often used as an alternative in the occurrence of penicillin allergy9. It is a 14 membered lactone ring which is categorized as a Macrolide. Macrolides interfere with protein synthesis by penetrating the bacterial cell membrane and binding reversibly to the 50S subunit of the ribosome near the donor site, in turn effecting translocation6. By blocking the tRNA from binding to the donor site, the peptidyl transfer RNA (tRNA) is disconnected from its translocation site. As the peptide cannot shift from the acceptor side to the donor site, subsequent protein synthesis is inhibited7. Protein synthesis is also inhibited by interfering with the 50S subunit assembly and preventing peptide bond formation. The exact method of inhibition depends on the specific chemical structure of the drug molecule9. Due to its mechanism of action erythromycin is only effective against cells which are actively dividing. As clindamycin and chloramphenicol bind to the same 50S subunit of erythromycin, if all three drugs are given concurrently they may compete7. Resistance The two most common forms of resistance have been identified as the excretion of the drug from the cell (efflux mechanism) and the modification of the drug target site. This may include site specific post-transcri ptional modification of 23S rRNA or the mutation of 23S rRNA or ribosomal proteins6-7. A single mutational event in a ribosomal protein gene can result in cell resistance to a macrolide. This is therefore a frequent cause of drug resistance6-7. ?Social, psychological and ethical factors Despite evidence proving the ineffectiveness of antimicrobials for viral infections and the growing public health problem of AMR, antibiotics continue to be overprescribed as much as 40% of the time4. To adequately investigate antimicrobial prescribing, a range of social psychological and ethical factors must be explored. The Biopsychosocial Model has been used to draw together the issues related to antimicrobial prescribing due to its holistic approach to patient care in comparison to the previously used Biomedical Model10. It has been found that antibiotics are poorly understood by the public, with incorrect perception that cold, flu and virus' can be treated by antibiotic prescri ption11. This public perception can be considered a "social norm". As Sarah is so insistent that she needs antibiotics to recover more quickly, she may lack understanding of how antibiotics treat the body. Once established, norms can be hard to change, even when seen to be ineffective or harmful. The issue of social norms can be considered in both the expectations and behaviour of the patient, who may want and/or expect an antibiotic prescri ption, and the doctor who wants to satisfy the patient's wishes5. Doctors may perceive their primary obligation to be to the individual patient, rather than the general public and wish to maintain the doctor patient relationship5. However, other studies have reported the doctor- patient relationship not being a primary concern, listing fear of complications as the primary factor when considering treatment options12. Fear of complications may be due to factors such as under confidence and uncertainty13. Doctors have reported being most fearful of complications for patients with adverse socioeconomic factors such as poor housing, nutrition and those which suffer with substance misuse, as they felt their immune system was more likely to be compromised12. There are also influences by patients' medical histories for example concerns when patients who don't often seek medical attention present12. However in cases of no or delayed antibiotic prescribing, it has been shown that complications are rare19. Many antibiotic prescri ptions are in response to doctors beliefs regarding patients' expectations14. Despite doctor's concerns some studies have found that patient satisfaction was not necessarily related to receiving antibiotics and doctors may actually ?overestimate the pressure to prescribe antibiotics16. These studies found reassurance, information and possibly pain relief were many patient's expectations of their consultation with their doctor17. Good communication skills, thorough diagnostic and treatment explanations have been found to prevent the majority of patient complaints20. A possible consequence of prescribing antibiotics for an acute viral infection is the medicalising of self limiting illnesses, giving the impression that antibiotic prescri ptions are necessary for these kinds of illnesses to the patient, their friends and relatives1. Due to this issue of medicalising, unnecessary prescri ptions have also been shown to promote re- attendance, particularly for similar symptoms1. Another explanation for over prescribing antibiotics is time constraint, doctors work in high pressured environments and may be fatigued, short on time and use antibiotics for a quick solution19. Patients are often also busy, prioritizing immediate treatment, and view antibiotics as the solution11, such as in Sarah's case. These time restrictions make it more difficult for adequate explanations of antibiotics and resistance to be conveyed21. Parsons' classic model suggests doctors provide gatekeeping to the sick role as patient's often see their doctor in order to seek legitimation of an illness for their family/friends or work. This theory places the doctor in the position of power22 . However, pressure from patients and/or relatives may shift this power to the patient. Patients often have overconfidence coupled with misunderstanding on the uses of antibiotics and, fearing illness seek antibiotics for security19. However Doctor's must not only consider the patient's current medical issues, but future ethical factors. Overuse of antibiotics at this stage in the patient's life may have detrimental consequences for the treatment of future illnesses especially with AMR2. Doctors and patients must not only consider the potential consequences for the individual as a result of overuse of antibiotics, but also the ethical issues for global health. If antibiotics are misused, such as when patient's non-compliance to finishing antibiotic courses, remaining bacteria become more resistant to the antimicrobial, and may spread to others. This means the overuse/misuse of antibiotics can not only negatively impact the patient but also contributes to global AMR. ?Doctor/patient negotiation issues According to GMC guidelines, doctors must work in partnership with patients, supporting them to care for themselves and have a key role in decisions about their treatment and care18. Much research has been conducting regarding doctor patient communication skills and the negotiation which leads to the decision making process23. Effective interpersonal skills has proven to increase not only patient satisfaction but also compliance with treatment. It has also been established that should physicians fail to establish a relationship with a patient, they may not be able to gain the necessary information required to provide the most holistic treatment plan23. Mismanagement of decision making can not only effect the patient's medical and emotional wellbeing, but also the doctor patient relationship and their future trust in medical services24. Although both the doctor and the patient share the same goal, the way in which doctors and patients negotiate varies23. It is usually assumed that physicians will assume the dominant role in the decision making role due to the knowledge and status they possess. But with the more recent approach to patient centered, holistic care18, this is not always the case23. Patients are now better informed and often want an active part in their healthcare decisions24. This can create conflict due to the professional physician and well informed patient having opposing views on treatment decisions25, this may have been the case for Sarah. Some more recent literature suggests doctors and patients are equal participants in the negotiation process25. However patients are generally in the more vulnerable position, if they feel unheard or misunderstood, this may compromise their trust in healthcare system as well as reducing the likelihood of compliance.25. Conclusion By exploring current research it can be established that psychological, ethical, social and biological factors contribute to the current global health issue of antimicrobial prescribing. In order for unnecessary antimicrobial prescribing to reduce, public perception of ?antibiotics needs to change and boundaries such as those during doctor/patient negotiation need to be addressed. Education and communication have been established as key factors for good prescribing practice, patient trust, confidence and compliance to treatment. 1 Hayward G, Thompson M, Heneghan C, Perera R, Del Mar C and Glasziou P. Corticosteroids for pain relief in sore throat: systematic review and meta-analysis. 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