A New Antibiotic and the evolution of Resistance

Since their discovery, antibiotics have served as a vehicle for medical and human advancement.  There are medical procedures now performed that would be entirely ineffective or even outrageous without the effects of antibiotics.  The effects of antibiotics have largely infiltrated many parts of our lives, as we are practically ensured protection from infection. Despite the miracles performed by antibiotics in the past, antibiotic resistant infections are now killing more lives than the current epidemics of the globe. These epidemics include HIV in America and Ebola. By the year 2050 the cumulative healthcare costs of these resistant infections will total over 100 trillion dollars to the global economy. That will occur only if we continue down the current path of resistance we are experiencing.  There have been decreased incentives for pharmaceutical companies to produce new antibiotics as lead discovery costs are now around a million dollars, with a very low compound advancement. Investment efforts are allocated elsewhere.

Despite this decreased incentive for development, new technologies and approaches are aiding in the arms race against resistance. Researcher Ling et al. has been using novel culturing techniques through an isolation chip process to identify new antimicrobial compounds.  Through this process he has discovered a compound called teixobactin. This compound is produced by the bacterium Eleftheria terrae, which inhibits the growth of Staphylococcus aureus. The compound is shown to be highly effective against gram negative pathogens, particularly tuberculosis.  However despite advancements in clinical trials, it may take years before a commercial product.

It appears as though another promising antibiotic has been found. But what is more important is understanding the challenges we face in this arms race with evolution. Our current understanding of the cell tells us that this antibiotic targets an irreplaceable component of the cell, and this drug should be effective for years to come.  However, we have already learned this lesson through vancomycin, as we previously thought that cells would not be able to adapt to overcome its inhibitory effect through its critical target area. After the large use however, as one could predict, cells became resistant.  For now, we must utilize our advances as they come to combat infection and save lives.

N Engl J Med 2015; 372:1168-1170March 19, 2015

http://www.nejm.org/doi/full/10.1056/NEJMcibr1500292

Risk-based strategy for outpatient pharmacy practice: Focus on opioids

The mortality rate related to prescription opioid overdoses in recent years have been increasing. About 80% of opioid overdoses happen in patients who are on multiple opioid prescriptions or on high doses of opioids. The current programs established to solve this problem includes patient screening, prescription restrictions and monitoring, provider education, and implementations of substance abuse treatment. None of these approaches really involved pharmacists, who are the medication expert and potential solution to the problem.

This article explored ways to employ pharmacist’s knowledge and accessibility to get pharmacists involved in this arena. The first step of the proposal centered on identifying patients who are at risk. The therapeutic index measures the safety of individual drugs. Patients who are on drugs with a low therapeutic index are classified to require additional attention during prescribing and dispensing.

The second step directly involves the participation of pharmacist through patient counseling. Although patient counseling has been implemented in pharmacies, the frequency and duration of pharmacist counseling are not at the optimal level. Furthermore, most counseling only happen during the dispensing of a new medication and almost never as routine follow-ups. While pharmacists are trained to provide comprehensive counseling and assist in monitoring the health and medication uses of patients, the revenue-oriented priorities of retail practice limits the opportunity for pharmacists to provide direct patient care. Much of the pharmacists’ work time is devoted to the speeding up the processing, confirming and filling of prescriptions.

The article proposed identifying and selecting the at risk patients who are on low therapeutic index medications for extensive counseling and routine follow-ups. This is a great idea because I think follow-ups are very important for patients especially when they are on medications that can have serious consequence if misused. I believe that pharmacists can have a big impact on preventing opioid overdoses by working to optimize patient pain management while making sure that they are safe through appropriate monitoring and guidance.

Holdsworth, MT, Benson, BE, Dole EJ. et al. Risk-based strategy for outpatient pharmacy practice: Focus on opioids. JAPhA. 2015;55(5):553–559.

JAPhA. 2015;55(5):553–559

Resistance to key HIV drug ‘concerningly common’

HIV has different phases through which the drug’s effectiveness decreases. As a first-line drug, Tenofovir, has been becoming less and less effective in population around the world. This raises concern, as first-line drug is needed to last a longer amount of time in  order to have it’s effectiveness in the treatment regimen. Patients in Africa are unable to afford second-line treatment medications even with the best treatment help from the doctors around with world. This causes patient adherence issues. HIV drugs need to be taken 85-90% of its treatment regimen, and if failed, it can cause drug resistance. Drug resistance in one patient can be a concern to other HIV patients as it is transmissible from one person to another. To avoid this, doctors are trying to reach out to patients and diagnose them at an earlier stage to reduce the cost in Africa and help them understand the importance of adherence.

I believe that this drug has a great ability to treat first phase of HIV in patients. But with drug resistance issues and financial needs in third world country, it makes it harder for this resistance to be constricted in one population. Resistance being able to spread from one person to another causes concerns in a population with less resources and becomes more important for the health care professionals in the that area to address that issue to the population. Physicians or pharmacist, the drug experts, are great resources that can help reduce the problem in this population as they can explain the potential side effects and treatment options to the population better than any other health professional.

Resistance to key HIV drug ‘concerningly common’ (2016, January 28). Retrieved February 11, 2016, from http://www.eurekalert.org/pub_releases/2016-01/ucl-rtk012516.php

http://www.eurekalert.org/pub_releases/2016-01/ucl-rtk012516.php

Good news: you might not have a penicillin allergy

If you have a penicillin allergy, you might be mistaken. A study conducted by the American College of Allergy, Asthma, and Immunology has recently found that those diagnosed with chronic urticaria have a three times higher likelihood of self-reporting a penicillin allergy when compared to the general public. Similarly, those who self-report a penicillin allergy also have a three times greater likelihood of having undiagnosed chronic urticaria compared to the public.

Penicillin is one of most widely reported antibiotic allergies (13.6% of patients), according to Silverman, et al. Conversely, only 5% of people given a penicillin skin test are actually allergic. The discrepancy could be due to a misappropriation of symptoms during concurrent use of penicillin. The symptom in question is rash. It has been found that greater than 1% of patients on penicillin develop a rash. This rash is the tell-tale symptom of urticaria. Those with chronic urticaria and are given penicillin are more likely to experience a rash (20.5%). It has been concluded that the highest misattribution of penicillin allergies can be due to undiagnosed urticaria. It is also hypothesized that penicillin exacerbates the effects of urticaria.

In their study, 11,143 patients were looked at, and 12% of these patients had a diagnosis of urticaria. Of the 11,143, 1,516 (13.6%) reported a penicillin allergy, thus 86.4% did not report a penicillin allergy. Of this 86.4%, 446 (4.6%) had chronic urticaria. The percent of patients without chronic urticaria and a self-reported penicillin allergy was 14.5% meaning that those not diagnosed with chronic urticaria are 3.15 times more likely to report a penicillin allergy than those who are diagnosed.

Looking at this data, it can be seen that there are many people who claim to have penicillin allergies. With antibiotic resistance becoming a health threat, more screenings should be used to differentiate those with an actual allergy from those who simply self-report the allergy. This will help prescribers cut down on the number of different antibiotics a patient will take over the course of their lifetime.

Ann Allergy Asthma Immunol. 2016; 1:4.

Gene Identification associated with Epigenetics of Type 2 Diabetes

Type 2 Diabetes is the most prevalent type of diabetes accounting for 90% of all cases.  The disease is also a major risk factor for cardiovascular events.  In a recent study, researchers discovered an epigenetic mechanism that occurs when regulating blood sugar levels.  Epigenetic mechanisms such as DNA methylation has been associated with several processes such as aging or pathologies.  This study provides evidence that DNA methylation of the TXNIP gene is associated with type 2 diabetes.  As many people know, this disease has a genetic component as well as environmental factors.  Many of the environmental factors have been studied in the past, so researchers are beginning to focus on the epigenetics of diabetes.

This study’s aim was to associate type 2 diabetes with DNA methylation.  The setup of the experiment was a two cohort approach which included comparing non-diabetes patients with patients with diabetes, as well as two different groups of diabetics based on their control of blood glucose levels (well-controlled or poorly controlled).  As a result, a new methylation was associated with diabetes and A1C levels.

The study concluded that there is a binding correlation with glucose import and chaperone binding.  Methylation differences in where they bind may alter the regulation of genes which correlate with glucose exposure.  The expression of the TXNIP gene for glucose-responsiveness is elevated in the muscle of pre-diabetics and diabetic patients.  DNA methylation may be able to modulate the expression and work as a biomarker of altered glucose levels.

This article demonstrates the importance of genomics in disease.  Identifying possible genetic components invested in prominent diseases such as diabetes can be a step in the right direction for a cure.  How could pharmacists use these types of studies in their practice?  Pharmacogenomics is a hot topic these days, how could this study benefit diabetes drug development?

Carolina Soriano-Tárraga, Jordi Jiménez-Conde, Eva Giralt-Steinhauer, Marina Mola-Caminal, Rosa M. Vivanco-Hidalgo, Angel Ois, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Sergi Sayols-Baixeras, Roberto Elosua, Jaume Roquer. Epigenome-wide association study identifiesTXNIPgene associated with type 2 diabetes mellitus and sustained hyperglycemia. Human Molecular Genetics, 2016; 25 (3): 609 DOI: 10.1093/hmg/ddv493

Cognitive behavioural therapy as an adjunct to pharmacotherapy for depression

Depression can affect individuals for an acute or chronic period, but there has been little research done to examine the efficacy of antidepressants for over 1 year[1]. This recent article by Wiles et al.[2] examines the efficacy of cognitive behavioural therapy (CBT) in conjunction with pharmacotherapy for improving depression in treatment-resistant patients over a 3-5 year period. Depression is a mood disorder characterized by symptoms like decreased energy, difficulty sleeping, concentrating, or eating, loss of interest in activities, and suicidal thoughts. There are several classes of antidepressants such as SSRIs, SNRIs, and tricyclics available that function by affecting receptors of specific neurotransmitters. Cognitive behavioural therapy is a technique to change thinking and behavior patterns to assist the patient in taking action to solve problems.

248 individuals aged 18-75 year olds with substantial depression who had taken antidepressants for at least 6 weeks participated in this UK study from 2008-2010. Individuals were randomly assigned either normal care or CBT in conjunction with normal care. Severity of depression was scored based on the Beck Depression Inventory, where a lower score indicates less severe depression. The median follow-up period during treatment was 45 months. The group that received both pharmacotherapy and CBT had a mean score of 19 whereas the group that received only pharmacotherapy had a mean score of 23. After therapy ended the average follow-up period was 40 months. Cost-analysis showed that using both therapies in conjunction was cost-effective for the quality-adjusted life year (QALY) gain.

Since CBT in conjunction with pharmacotherapy has been shown to be effective in the long-term, how do you think pharmacists can increase the amount of patients who receive CBT?

  1. Uher R, Pavlova B. Long-term effects of depression treatment. The Lancet Psychiatry. 2016;3(2):95-96.
  2. Wiles, Nicola J et al. Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised control trial. The Lancet Psychiatry. 2016;3(2):137-144.

 

 

Utilizing Brain Waves to Predict Dosing of Anesthesia

A conflicting issue today is that there is no direct way to measure the sedative effects of anesthesia administered by anesthesiologists other than the patient’s level of awareness.  Concentrations in the brain cannot be determined.  A study conducted by Chennu et al., utilized an EEG to experiment a better way to study dose administration of sedative-hypnotics.

It is difficult for scientists to quantitatively measure the consciousness of the brain.  When utilizing anesthetics, measuring level of sedation and the ability to track this parameter is difficult by the variability between individuals and their susceptibility to anesthetics.  Within this study conducted by Chennu et. al., the researchers utilize high-density electroencephalography in tandem with propofol  (a sedative-hypnotic), and the changes in the brain were measured.  An EEG can easily measure brain waves from the surface of the scalp, but it is not universally utilized.  This change could solve the need for reliable anesthesia monitoring during use of a sedative.  The researchers conducted assessments prior to, during and after the administration of the sedative.  The participant’s behavioral responsiveness and the drug concentrations in the blood were measured within these assessments.  All of these experiments were conducted on healthy volunteers.  When administering the propofol, key changes in the brain waves were observed.

The researchers highlight that the alpha waves are compromised during sedation.  There is a spectral connectivity when considering the alpha waves in sedated participants.  This is an indicator of susceptibility to propofol which varies between individuals.  The concentration of drug was measured at each level of sedation.  Correlations were also found between the alpha waves and behavioral impairment.  These results can assist in dosing the patient correctly instead of injecting medication until unconscious.

Chennu S, O’Connor S, Adapa R, Menon DK, Bekinschtein TA. Brain Connectivity Dissociates Responsiveness from Drug Exposure during Propofol-Induced Transitions of Consciousness. PLOS Computational Biology. 2016.

Given the advanced technology present in the medical world, I was surprised that EEGs are not universally utilized when sedating patients for surgery.  The variability between individual patients’ susceptibility to anesthetics such as propofol has been observed in the past.  This article highlights the need that individuals should be receiving different doses of this drug to sedate them accordingly.  This has me thinking of other procedures conducted within the hospital that potentially conducts dosing based on behavioral assessment.

What should pharmacists do if a drug is dosed based on bias or strictly behavioral results?  What is the responsibility of the pharmacist within this type of scenario?

Guidelines for the Zika virus in pregnant women

According to the CDC, the Zika virus is transmitted through a certain type of mosquito that also transmits other viruses that have been found in the United States. Although the Zika virus has not yet been identified in the United States, there have been infections reported throughout the world in people returning from travel to an area that has seen this virus, which could result in disease transfer from human to human rather than from mosquito and human. This increases the risk of the virus entering the United States.

Pregnant women are not thought to be more at risk for this disease or to have more serious symptoms. However, there is currently an outbreak of this virus in Brazil, and there has been an increase in infants born with microcephaly, which is a disease characterized by abnormal brain growth and an underdeveloped head size. Because of this, there are studies underway to see if the Zika virus is the cause, but until then, the CDC is recommending that all pregnant women hold off on traveling to areas that have a Zika virus outbreak, and if they do travel to this area, to wear long sleeved shirts and use insect repellants. There is no vaccine to prevent this infection and there is currently no cure, just the recommendation of rest, fluids and acetaminophen for fever and pain. In addition, if a woman has been tested positive for this virus, she should receive regular ultrasounds to monitor the growth of her baby and talk with a fetal medicine specialist.

MMWR Morb Mortal Wkly Rep. 2016;65(Early Release):1-4.

I thought this article was very interesting because it was proactive, discussing emerging health risks in other areas of the world before they hit the United States. I believe looking at health information from other areas of the world, especially those neighboring the U.S., and initiating studies based on that information should be done more often to help prevent large outbreaks that can turn into epidemics, which were seen with Ebola and the West Nile Virus. In addition, working on preventative measures, such as vaccines, as early as possible is one step that can be made to help prepare for potential disease outbreaks, because it is better to be over prepared than to be working against an epidemic.