This post is part of an ongoing series on HIV/AIDS in recognition of HIV/AIDS awareness month 2022. In this series, we focus our posts on education, research, achievements, and medicine pertaining to the HIV/AIDS epidemic.
Dr. Susan Swindells, editor of the new Clinical Infectious Diseases supplement on long-acting formulations of infectious disease treatments.
Today, we feature a new supplement in Clinical Infectious Diseases, edited by UNMC ID’s Dr. Susan Swindells. This supplement contains articles chronicling and exploring the use of long-acting formulations in the treatment of infectious diseases. This category of therapy associated with HIV treatment is considered one of the major recent successes in HIV infection treatment, and involves the development of long-acting antiretrovial therapies (LA ARTs) which circumvent the need to take a complicated combination of multiple medications each day to remain HIV undetectable.
Researchers and Clinicians have been working to simplify treatment regimens for HIV for over a decade. With early formulations of antiretroviral treatments, people living with HIV (PWH) were prescribed a complicated combination of medications every day, with little room for error. In some cases, this proved problematic as interruptions in medical care such as shifts in insurance coverage, pharmacy shortages, medication side effects, and misunderstandings of dosing schedule by patients could all interrupt treatment and recovery of PWH. Advancements steadily improved over the years, transitioning from many pills per day to the possibility of just one. This particular advancement has significantly improved medication compliance in PWH. However, treatment adherence remains an important and significant public health aspect of this epidemic.
Now, new advancements are allowing injectable formulations of LA ARTs which can treat HIV for up to 8 weeks at a time, eliminating the need for daily medications and further improving treatment adherence. LA ARTs may have other benefits as well. In the introductory article of this supplement, co-authored by Dr. Swindells, it is noted that LA ARTs may be preferable over daily oral medications due to reduced stigma of taking HIV medication, alleviating some socioeconomic barriers to daily medication, and reducing the selection of antimicrobial resistance due to consistent and complete drug exposure. There are also downsides to long-acting therapies however, such as prolonged side effects due to difficulty of treatment discontinuation after an injection which is designed to last multiple weeks. Other disadvantages noted include fear of injections, costs, and efficacy. Nevertheless, many patients prefer LA ARTs, with some studies citing nearly all patients studied preferred the long-acting injectable over their previous oral treatment regimen (see our previous Research Digesthere).
Stay tuned for our next post, where we will dive into this supplement and explore how these same principles are being proposed to treat additional infectious diseases and may change the future of ID.
If you would like to read Dr. Swindell’s introductory article or the rest of this fascinating supplement, check out the full list of articles here.
This post is part of an ongoing series on HIV/AIDS in recognition of HIV/AIDS awareness month 2022. In this series, we focus our posts on education, research, achievements, and medicine pertaining to the HIV/AIDS epidemic.
In this month’s research digest, we will cover recent work by UNMC ID faculty uncovering the link between HIV and various comorbidities associated with infection. HIV research is far from a new topic for this installment (see our previous HIV-focused research digests here and here), which speaks to the commitment of UNMC ID faculty to furthering HIV knowledge and research. Read on for a quick summary of two articles focused on HIV comorbidities dealing with brains and bones, namely HIV-associated neurocognitive disorder and bone fractures.
Dr. Swindells, co-author of a recent paper investigating HIV-associated neurocognitive disorder.
The first paper, co-authored by Dr. Susan Swindells, aims to define the functional similarities and differences between Alzheimer’s disease and HIV-associated neurocognitive disorder. The most common form of dementia in the general population is Alzheimers disease, affecting about 10% of adults age 65 or older. However, in those living with HIV, HIV-associated neurocognitive disfunction becomes even more common, affecting 40-70% of this population. Understanding how and where brain dysfunction occurs in these two diseases could help researchers design new treatments for both conditions. Using functional MRI imaging, that is exactly what the authors studied. They uncovered distinct differences in brain dysfunction in these two diseases, which may also lead to better diagnosis of these conditions in the future. Read the full article here for the details on what these differences were and what they may mean in a broader context.
Dr. Bares, co-author on a recent paper assessing the efficacy of hormone therapy for fracture prevention in WLWH.
The second paper spotlighted here is co-authored by Dr. Sara Bares and investigates the effectiveness of hormone therapy for the prevention of fractures in older women living with HIV (WLWH). This population has been reported to experience fractures at a higher rate than those living without HIV, but no data existed previously to suggest whether estrogen treatment could help prevent fractures in WLWH. The study found that smoking as well as certain demographic factors were associated with increased risk of fracture, but they did not find evidence that hormone therapy or HIV status affected fracture rates. They end with a call for further research of hormone therapy in this population, which may have other benefits beyond fracture prevention. For the full findings, read the paper here.
This post is part of an ongoing series on HIV/AIDS in recognition of HIV/AIDS awareness month 2022. In this series, we focus our posts on education, research, achievements, and medicine pertaining to the HIV/AIDS epidemic.
A computer-generated 3D representation of the HIV virus. Source.
Today, we start a new series of posts on the UNMC ID Blog: Microbe Monday. This is a monthly installment introducing the microbiology behind the pathogens routinely encountered in the clinic. While these posts are geared more towards education, recent research advances and interesting historical context should be broadly interesting to all readers. Our first microbe is the human immunodeficiency virus (HIV). Read on to learn more about this important pathogen.
HIV
HIV is what is known as a retrovirus. This class of virus have the unique ability to convert its genetic material into DNA, much like the DNA that exists in human cells. Once this happens during infection, the viral DNA can hide within human DNA and evade detection for a period of months to years. This is also why HIV is so difficult to cure, with only a handful of cases ever reported. Functionally, there is no current cure for HIV, but this is an active field of research and there are many extremely effective treatments which have revolutionized the medicine of HIV care.
Advanced HIV results in an acquired immunodeficiency syndrome (also known as AIDS). In this syndrome, advanced HIV leads to severe immune system damage and increased susceptibility to multiple different cancers and infection by opportunistic pathogens (microbes which normally do not cause disease in healthy people, but thrive in those with compromised immune function). Advanced HIV is defined when a person with HIV has a reduced CD4 T-cell count (a specific type of immune cell), or diagnosis with one of these cancers or opportunistic infections, even without identified immune dysfunction.
Macrophages, T-cells, nooks and crannies
HIV is first thought of as an infection of T lymphocytes (T-cells), as these are the cells that clinicians use to characterize the severity of HIV infection. T-cells are specialized immune cells responsible for controlling many different aspects of your immune system. They come in two flavors: CD4 and CD8. CD4 T-cells are the primary target of HIV, which is important because these cells act as your immune system’s ‘generals’, coordinating the rest of your immune system to fight infections or cancers. It makes sense then that as these cells start to decline, people with HIV (PWH) start to become increasingly susceptible to infections and malignancy.
HIV (green) seen attached to the surface of a macrophage. Source.
However, it has been recently shown that this virus also infects other cell types. The most recognized example of this is HIV infection of macrophages. These cells are essential components of the ‘front lines’ of the immune response and are present in almost every part of the body. More recent research suggests that there may be additional cellular reservoirs where this virus may hide. Some emerging evidence point to certain types of glia, your brain’s supporting cells, which may inadvertently shield this virus from attack from the immune system or certain antiviral drugs (see this paper and others for further reading). But this is far from settled science, and there is much we still do not know about the mechanics of HIV infection.
The symptoms of HIV infection are unique from most viral infections. In the days and weeks following initial infection, 50-90% of infected individuals will experience a strong flu-like illness, with symptoms like fever, swollen lymph nodes, sore throat, rash, muscle and joint aches and pains, and fatigue. This acute infection quickly resolves as your immune system fights off the initial wave of HIV infection. At this point, the virus goes dormant for a period of months to years where is slowly depletes CD4 T-cell levels with few identifiable symptoms. This continues until the disease becomes advanced, meaning CD4 levels are low enough to lead to opportunistic infection or cancer. Clinical outlook for PWH who remain undiagnosed and/or untreated is poor, with most reaching complete T-cell depletion by 5-10 years after initial infection.
Fortunately, we have many very effective tools to fight these infections in the form of antiretroviral drugs. The way these drugs work varies, but all of them impede the ability of HIV to replicate itself. If treatments are taken consistently and life-long, undetectable HIV viral loads are not only possible, but clinically expected. Importantly, PWH who have undetectable HIV viral loads are unable to transmit the virus to others. This knowledge is the basis of the U=U (undetectable = untransmittable) campaign.
While treatment of HIV has been revolutionized since the onset of the epidemic, this infection remains incurable, making prevention the best medicine. Three main approaches are used currently to improve preventive measures in the population. First, public education with science-backed information is of prime importance. There are preventative measures that can be taken by those at risk of HIV that forms an important first barrier to spreading this infection. Second, since someone can be unknowingly infected with HIV for many years before diagnosis, routine testing is a powerful way to support one’s own and the community’s health. Lastly, certain medications can be prescribed for prevention called PrEP (Pre-Exposure Prophylaxis), when taken regularly, can reduce the risk of contracting HIV by 99%, providing an additional layer of protection to those who may be exposed to HIV. Additionally, the U=U campaign means that if we can initiate and maintain every person with HIV on antiretroviral treatment with an undetectable viral load, this can also significantly contribute to the prevention of onward transmission of HIV.
Conclusion
HIV is serious pathogen and an important consideration for public health. It has been just over 40 years since the first case of AIDS was diagnosed in the United States (June 1981). In this short period of time, advancements in research and clinical practice have dramatically changed the outlook for PWH. Proper use of preventive and treatment measures along with continued support for research on HIV/AIDS has the promise to continue to accelerate our ability to fight this infection.
Beginning with World AIDS Day on December 1st, the month of December is a time to raise awareness and reflect on the impact this epidemic has had on our communities and the world. There has been considerable progress made in the last 40 years on the treatment and support of people living with HIV infection (PWH), including much work conducted here at UNMC. But every inch of progress has been hard-fought, and there is still plenty of work to be done.
This month, in recognition of HIV/AIDS Awareness month, we will focus our posts on education, research, achievements, and medicine pertaining to the HIV/AIDS epidemic. We have many successes to celebrate, and hopefully many more to look forward to in the future of PWH care.
Keep an eye out for upcoming HIV/AIDS awareness posts, and please share what you learn. Together, we can raise awareness and help reach the U.S. Department of Health and Human Service’s goal, Ending the HIV Epidemic in the U.S.
This post is part of a series onAntibiotic Awareness Week 2022. For more information, check out the full post on the Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) blog.
Knowing and implementing TJC and CMS requirements for ASPs is essential for a successful program. Furthermore, TJC recommendations are something to take note of for all facilities, as other accrediting bodies often follow TJC in their requirements. To increase awareness and understanding of these updates, they have been summarized below.
On July 6th, 2022, the Centers for Medicaid and Medicare Services (CMS) released updates to interpretive guidance for their current Conditions of Participation (CoP) for hospital regulatory requirements related to infection prevention and control and antibiotic stewardship programs (ASP), effective immediately. There was no change to the CoP themselves, but CMS clarified what exactly surveyors should be looking for when assessing sites. In addition, The Joint Commission (TJC) released prepublication standards for new and revised requirements addressing antibiotic stewardship for the hospital and critical access hospital programs. These standards were released in July of this year with an effective date of January 1st, 2023. These updates only pertain to hospitals and critical access hospitals, they do not pertain to nursing care centers.
This post is part of a series onAntibiotic Awareness Week 2022, authored by UNMC ID fellow Dr. Mackenzie Keintz. Read on to learn more about growing antimicrobial resistance in the United States and what can be done to stop it.
Antimicrobial resistance has been a growing problem within the United States. Antibiotic resistant bacteria are responsible for 2.8 million infections per year and 36,000 deaths per year1. In addition, antibiotic use can be associated with significant adverse events including infections with Clostridium difficile. There are an estimated 223,900 infections resulting in 12,800 deaths1. Outpatient antibiotic prescriptions account for more than half of all antibiotics prescribed. In 2021 this accounted for 211.1 antibiotic prescriptions in the United States, equivalent to 636 antibiotic prescriptions/ 1000 person. Nebraska has one of the highest outpatient antibiotic prescribing rates in the country with 760 prescriptions/ 1000 persons in 20212.
Drivers of inappropriate prescribing
The drivers of inappropriate antibiotic use have been well described. Qualitative studies have evaluated clinician perceptions on antibiotic resistance and inappropriate antibiotic prescribing. Ninety one percent of clinicians interview viewed inappropriate prescribing as a problem within the United States however only 37% thought that inappropriate prescribing was a problem within their own practice7. Without oversight of clinician prescribing, it is difficult for individuals to know how their prescribing rates compare with peer or national averages.
Clinicians often cite diagnostic uncertainty when prescribing antibiotics, including escalating to a more broad-spectrum agent when a narrow spectrum antibiotic would be sufficient, extending the duration, or giving an antibiotic in a clinical situation that it may not benefit8. This is of high concern in the outpatient setting when clinicians have little objective data when making antibiotic prescribing decisions and have an uncertainty regarding patient follow-up.
Many clinicians also cite patient expectation as a reason for inappropriate antibiotic use. They fear damaging the physician-patient relationship if antibiotics are not prescribed when patients expect them. Time constraints also increase inappropriate antibiotic use as clinicians may not feel as if they have time to explain why antibiotics are necessary8.
Qualitative data on patient antibiotic perception has demonstrated that while patients do frequently expect antibiotics, they are willing to defer to a clinician’s judgement on the subject. These studies also showed that although many patients understand that antibiotics do not treat viral infections, they have difficulty distinguishing between viral and bacterial infections. Furthermore, patients may not understand the significant risk of antibiotic use, both individually and for the population9.
Intervention
Interventions to improve antibiotic prescribing in the ambulatory setting should address the root cause of inappropriate antibiotic use which is often not a gap in knowledge. Some institutional implemented strategies that have been shown to be effective include peer to peer feedback, academic detailing, and communication training10-13.
Strategies for individual clinicians to improve their antibiotic use include identifying resources including to guide their antibiotic decision making such as national guidelines. The Agency for Healthcare Research and Quality (AHRQ) suggests a four-time point decision making process that includes:
1. Does my patient have a condition that requires an antibiotic?
2. Do I need to order any diagnostic tests?
3. If antibiotics are indicated what is the narrowest, safest, and shortest regimen I can prescribe? 4. Does my patient understand what to expect and the follow up plan?14
Prescribers can utilize a delayed prescription method to overcome clinical uncertainty. This strategy should not be used in situations in which antibiotics are never indicated, such as bronchitis or viral respiratory infections, but can be helpful in situations where an antibiotic is sometimes required i.e., sinusitis. This allows the physician to have a contingency plan in place for patients that may not wish to return to the office for evaluation if clear instructions are given to the patient15.
One strategy that has been shown to both decrease inappropriate antibiotic prescribing in acute respiratory infections and increase patient satisfaction includes both negative treatment recommendations (antibiotics will not help this viral infection), positive treatment recommendations (this viral infection can be managed symptomatically with xxx), and a contingency plan (if symptoms are not better in a week or have double worsening antibiotic plan can be revisited)16. In addition to education from individual clinicians, other efforts have been made on a national scale to educate patients about the risk of using antibiotics when not indicated, through campaigns like Be Antibiotic Aware by the CDC. During Antibiotic Awareness Week, think about how you can incorporate the 4 moments of antibiotic decision making into your clinical practice.
Fleming-Dutra, K. E. et al. “Prevalence of Inappropriate Antibiotic Prescriptions among Us Ambulatory Care Visits, 2010-2011.” JAMA, vol. 315, no. 17, 2016, pp. 1864-73, doi:10.1001/jama.2016.4151.
This post is part of a series onAntibiotic Awareness Week 2022. For more information, check out the full post on the Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) blog.
Antimicrobial resistance rates continue to increase in hospitals across the United States. One of the five CDC core actions to combat the spread of antimicrobial resistance is improving the use of antimicrobials. Studies show that providing timely and reliable feedback of information to clinicians regarding their prescribing practices, such as through antimicrobial usage reports, can improve appropriateness of antimicrobial use.
The NHSN AUR Module provides a mechanism for facilities to report and to analyze antimicrobial use and/or resistance data to inform benchmarking, reduce antimicrobial resistant infections through antimicrobial stewardship, and interrupt transmission of resistant pathogens at individual facilities or facility networks.
Reporting antimicrobial use and resistance data will be included in the Public Health and Clinical Data Exchange Objective as a required measure for CMS beginning with the EHR reporting period in CY 2024. As of 2021, only 13 of 54 (24%) eligible facilities in Nebraska report antibiotic use data to NHSN.
This post is part of a series on Antibiotic Awareness Week 2022, authored by Scott Bergman, PharmD, FCCP, FIDSA, BCIDP. Read on to learn more about influential antibiotic stewardship research published this year.
This year for Antibiotic Awareness Week, I want to revisit a few studies that I selected for my presentation at the recent IDWeek conference on Most Influential Papers in Antimicrobial Stewardship from the Past Year. These are by no means ranked in order of quality or impact, but rather tell a story of where we are in terms of research and practice this year.
The first paper I want to highlight is titled “Rural-urban differences in antibiotic prescribing for uncomplicated urinary tract infection” in Infection Control and Hospital Epidemiology.1As we have become more aware of racial disparities in healthcare over the last few years, in Nebraska we have also thought about the difference in antimicrobial stewardship between our urban and rural areas of the state. This study included women 18-44 years old with uncomplicated UTIs from 2010-15 and classified them into groups based on their zip code as either rural or urban (metropolitan statistical areas > 50,000 population). Using insurance claims from the IBM Marketscan database, investigators evaluated whether prescriptions followed IDSA guidelines over this time period. Over 670,000 claims were reviewed to determine that almost half of prescriptions, 46.7%, were not for first-line antibiotics (table 1). To maintain that these were indeed uncomplicated, community-acquired UTIs, patients were excluded if they had been in the hospital within 90 days or received an antibiotic or had another infection with 30 days.
Table 1: Antibiotics prescribed for uncomplicated cystitis
This rate of guideline-discordant prescribing was not significantly different between rural & urban geographical designations. It was in length of therapy where the difference became more apparent – with rural women receiving inappropriate durations 83.9% of the time compared to 74.9% of urban prescriptions (table 2). Regardless of the amount of that difference, neither of these statistics are encouraging. I left feeling that we that we have a lot of education to do for prescribers to feel comfortable giving the antibiotics recommended by guidelines for uncomplicated cystitis over the durations of therapy that are based on evidence.
Table 2: Antibiotic durations of therapy matching guidelines for uncomplicated cystitis
As you can probably guess, the durations prescribed were considered inappropriate for being longer than recommended 99% of the time. While a few days extra of an antibiotic may not seem like a big deal, the adverse effects associated with these courses can really add up, especially when we are talking about almost half a million inappropriate prescriptions in this study.
That brings me to the other important paper from the last year I want to cover, “Estimating daily antibiotic harms: an umbrella review with individual study meta-analysis”, published in Clinical Microbiology and Infection.2This study conducted by Public Health Ontario was a meta-analysis of 71 randomized trials identified from 35 systematic reviews of shorter versus longer fixed durations of therapy ranging from 3 to 14 days. These studies were primarily for treatment of respiratory tract (n=36, 51%) and urinary tract infections (n=29, 41%). If you’ve ever read one of these many trials, you will know that the conclusion is almost always the same – shorter courses are equally effective to longer courses, but the adverse effects are greater in the long duration group. To quantify that, 23,174 patients were pooled in this analysis and 20,345 adverse effects were identified in 19.9% of patients these trials. Other documented harms associated with antibiotics included 5,776 superinfections in 4.8% of patients and 2330 cases of new resistance in 10.6% of patients. Overall, they concluded that each day of antibiotic therapy was associated with a 4% increased odds of having any adverse event. Furthermore, the risk of having a severe adverse event rose incrementally 9% for each subsequent day of therapy.
Combined, these two studies paint a fairly bleak picture for antimicrobial use in 2022, but there are bright spots as well. I don’t have time to elaborate, but I listed a few other studies below that I selected for my presentation on influential papers in antimicrobial stewardship which show benefit of education.
About the Author:
Scott Bergman, PharmD, FCCP, FIDSA, BCIDP
Pharmacy Coordinator, Antimicrobial Stewardship Program – Nebraska Medicine
Clinical Professor, University of Nebraska Medical Center – College of Pharmacy
This post is part of a series on Antibiotic Awareness Week 2022. For more information about how to manage a patient reported penicillin allergy, check out the full post on the Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) blog.
Patient reported antibiotic allergies present clinicians with challenging decisions at the point of prescribing. Approximately half of all patients admitted to the hospital receive antibiotics, and 25% of inpatients who require antibiotics report at least one antimicrobial drug allergy. Specifically, penicillin (PCN) allergy is reported in up to 10% of the general population and up to 16% of inpatients.
Patients with reported PCN allergies often receive more costly and broad-spectrum antibiotics than patients without these reported allergies. Furthermore, many patients with reported PCN allergy are not receiving drugs, such as later-generation cephalosporins and carbapenems, that are safely tolerated despite a PCN allergy.
A 2022 update to the Practice Parameter Update in Drug Allergy is now available from the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the American College of Allergy, Asthma, and Immunology (ACAAI).
Visit the Nebraska ASAP blog to learn more about how to manage a patient reported penicillin allergy.
Dr. Kelly Cawcutt, lead author on a new publication detailing the lessons learned from the COVID-19 pandemic.
From SARS to H1N1 to Ebola and now COVID-19, it is clear that pandemic infectious diseases are likely to be a constant challenge to the healthcare system and humanity for the foreseeable future. Luckily, past pandemics can help us learn to better combat these diseases in the future. This is the case made by a new article authored by Drs. Cawcutt, Kalil, and Hewlett. Their thesis: best summed up by the Winston Churchhill quote “Those who fail to learn from history are doomed to repeat it.”
Dr. Andre Kalil, co-author on this new pandemic preparedness publication.
The article begins with an overview of the impact of pandemics on medicine and society at large. They note that there is a silver lining to these damaging events- namely, they have been shown to accelerate improvements in patient care, especially among critically ill patient populations. We can emerge from pandemics better equipped to handle complex medical cases than we were before they started, but only if we are willing to study and learn from our mistakes.
Dr. Angela Hewlett, also a co-author on this new pandemic preparedness publication.
The next section of the paper explores the specific lessons to be learned from the COVID-19 pandemic. This includes anything from supply chain management to ethics and the use of media, each throughly described. They conclude this section exploring mistakes instead with an exploration of the triumphs of the medical community during the pandemic, as not all lessons learned were negative. We make significant advancements and accomplished incredible feats during the past few years, showing the community’s ability to rise to a challenge.
Next, the authors cover the intensive care unit specifically, outlining lessons learned in the four S’s of surge capacity: Space, Staffing, Stuff, and Systems. For each ‘S’, detailed and actionable considerations are enumerated for better pandemic preparedness in the future.
Lastly, the authors explore some final thoughts regarding the importance of research and addressing inequality in health care. They end with a call to action:
“If history has taught us anything, it is that future pandemics are inevitable. COVID-19 highlighted the critical infrastructure failures in preparedness for a large-scale lethal respiratory viral pandemic and those failures must be the lessons on which future pandemic preparedness strategies are built. This must be a multidisciplinary, broad reaching strategy, and perhaps there are no areas more critical to ensure preparedness than within ICUs.“
To read this article in its entirety, including for specific details regarding how we can better prepare for a future pandemic, see the full text here.
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