We LOVE our UNMC ID Pharmacists! Today marks the end of National Pharmacy Week and we want to share our appreciation and thanks for the hard work and invaluable contributions of our pharmacists at UNMC ID. Our pharmacists are exceptional clinicians giving us the clinical advice we need on antimicrobials and drug interactions. They are also published national experts in Antimicrobial Stewardship and HIV, experienced educators in both the College of Pharmacy and College of Medicine, and phenomenal colleagues all-around. Our division would not function as well as it does without these individuals, and we cannot thank them enough. Join us in giving some love to our pharmacists!
Meet our UNMC ID Pharmacists:
(TOP ROW L-R):
Josh Havens, PharmD, BCPS: Pharmacy Coordinator of the UNMC Specialty Care (HIV) clinic, PI on several clinical studies, coordinator of our Pre-exposure Prophylaxis (PrEP) clinic, and HIV clinic pharmacy rotation preceptor.
Bryan Alexander, PharmD, BCIDP, AAHIVP: Clinical and Antimicrobial Stewardship Pharmacist and coordinator of Outpatient Parental Antimicrobial Therapy (OPAT) program.
Scott Bergman, Pharm.D., FCCP, FIDSA, BCPS, BCIDP: Antimicrobial Stewardship Pharmacy Coordinator, ID Pharmacy Residency Program Director, Pharmacy residency ID rotation education coordinator and preceptor, education award recipient. He is also the current President of the Society of Infectious Diseases Pharmacists.
Andrew Watkins, PharmD: Remote ASP Pharmacist & Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) Outreach Coordinator. He was the inaugural graduate of our ID pharmacy residency program.
(BOTTOM ROW L-R):
Molly Miller, PharmD: ASP/OPAT Pharmacist and recent graduate of our ID pharmacy residency program.
Anthony Podany, PharmD: Clinical Pharmacist at UNMC Specialty Care clinic, HIV clinic pharmacy rotation preceptor, and HIV researcher with many collaboration on AIDS Clinical Trials Group (ACTG) studies.
Kimberly Scarsi, PharmD, MS, FCCP, BCPS-ID: Clinical Pharmacist at UNMC Specialty Care clinic, HIV clinic pharmacy rotation preceptor, HIV principal investigator with many collaboration on AIDS Clinical Trials Group (ACTG) studies and recipient of several research awards. She is also a College of Pharmacy representative on the UNMC Faculty Senate and member of the HIV Medicine Association (HIVMA) board of directors.
Sean Avedissian, PharmD: Assistant Professor, College of Pharmacy, lectures in Infectious Disease and Pharmacokinetics. His primary research interests are related to the pharmacokinetic modeling of antibiotics/antivirals in special populations (HIV, critically-ill)
The content below was provided by Natasha Hongsermeier-Graves, MD/MPH student at UNMC College of Medicine/Harvard School of Public Health. She led a recently published study, collaborating with another UNMC medical student Rohan Khazanchi, and UNMC ID faculty Drs. Jasmine Marcelin and Nada Fadul. (cover image courtesy CDC)
In the early months of the pandemic, it became apparent that the most marginalized and minoritized communities within the UNMC HIV clinic were being disproportionately impacted by COVID-19. In our study recently published in AIDS Care, we set out to explore the sociodemographic and clinical characteristics of 37 individuals at our HIV clinic who had developed COVID-19 as of August 27, 2020.
We performed a retrospective chart review of these patients to collect information on demographics, comorbidities, HIV outcomes, and COVID-19 outcomes.
Ninety-two percent of PWHC had at least one comorbidity, with increased BMI and hypertension being the most common. All 37 had suppressed viral loads prior to diagnosis with COVID-19, and all 37 survived.
Relative to our overall HIV clinic population, groups of patients who were overrepresented among those who became co-infected with SARS-CoV-2 included over twice as many Hispanic patients, three times as many undocumented patients, and four times as many refugee patients. The majority of co-infected patients worked “essential” labor jobs, such as health care, food processing/service, or janitorial work.
Patients with HIV/SARS-CoV-2 Co-Infection (N=37)
HIV Registry (N=1128)
Ethnicity
Not Hispanic or Latinx
24 (64.9)
946 (83.9)
Hispanic or Latinx
13 (35.1)
180 (16.0)
Missing
0 (0)
2 (0.2)
Legal status
Refugee
6 (16.2)
45 (4.0)
Undocumented
5 (13.5)
47 (4.2)
These findings highlight how structural vulnerabilities—which are sociopolitically imposed risk factors like discrimination, legal status, poverty and beyond which impact a patient’s opportunity to achieve optimal health—play a key role in facilitating the inequitable harms of both the HIV epidemic and the COVID-19 pandemic. Although the risk factors for contracting HIV and SARS-CoV-2 may differ, the same marginalized groups are disparately harmed by both viruses.
Structural vulnerabilities including racism, stigmatization, and inequitably distributed health, economic, and educational resources place minoritized and immigrant communities at increased risk of both HIV and COVID-19. For example, the vast majority of Black and Hispanic PWHC in our study worked “essential” jobs, which did not offer paid sick leave, work-from-home flexibility, or adequate personal protective equipment during the pandemic.
As COVID-19 continues to reify longstanding health inequities in the U.S., the need remains for structural interventions to ameliorate the inequitable trajectory of the pandemic. This should include strategic measures like paid leave for essential workers to seek vaccination, mobile vaccination units for patients with housing instability, place-based resource targeting to socially vulnerable neighborhoods, and partnerships with trusted community organizations and leaders.
Natasha Hongsermeier-Graves, pictured left, led this project. She is an MD/MPH student at UNMC College of Medicine/Harvard School of Public Health. She is passionate about advocating for health equity in any way that she can.
Citation: Hongsermeier-Graves N, Khazanchi R, Marcelin JR, Fadul N. Structural vulnerability among patients with HIV and SARS-CoV-2 Co-infection: descriptive case series from the U.S. Midwest. AIDS Care. 2021 Sep 28:1-6. doi: 10.1080/09540121.2021.1981224. Epub ahead of print. PMID: 34579598.
Drs. Kelly Cawcutt & Jasmine Marcelin have served as Co-Directors for Digital Innovation & Social Media Strategy for UNMC ID for several years, and continue to strive to advance communication, amplification, advocacy and education from the Infectious Diseases Division at UNMC, and in the field of Infectious Diseases, as a whole. With that, they also continue to collaborate and publish scholarly articles on the use of social medicine in medicine.
Their recent publication, written with several other social media experts in medicine, provides guidance and insight into how mission-based tweeting can be used effectively, and how to do it. The 5 A’s of Mission Based Tweeting are found below, but please read the entire article for more excellent content!
Marcelin JR et al. Moment vs Movement: Mission-Based Tweeting for Physician Advocacy. J. Hosp. Med 2021;8;507-509.
It’s job hunting season! Usually we love to meet with all of you job seekers in person at IDWeek, and this year our excitement is no different, and we will be waiting to meet you online! This event is FREE for you to attend and you will have the opportunity to meet with our Division Chief Dr. Mark Rupp, as well as several amazing faculty: Drs. Nada Fadul, Rick Starlin, Nico Cortes-Penfield, and Salman Ashraf. Register for the virtual career fair and attend on October 14 at 5pm-8pm EDT/4pm-7pm CDT/2pm-5pm PDT.
Looking for your first position out of fellowship, or your next fulfilling position in your journey? The UNMC ID Division is a robust group comprised of 27 ID physicians, advanced practice providers, pharmacists, and clinical and research support staff. We provide full spectrum infectious disease care at our clinical partner, Nebraska Medicine. Members of the division pursue specialty interests in all areas of infectious diseases including Biopreparedness, Critical Care, Orthopedic ID, HIV, Infection Control, Antimicrobial Stewardship, Occupational Health, Clinical Microbiology, Oncology ID, Solid Organ Transplantation ID, etc. We enjoy productive collaborative relationships with clinicians and scientists in numerous departments. We have a full portfolio of funded research and a robust educational mission including a thriving ID fellowship training program.
Read more about why we are awesome and check out our three open positions: General ID, Community ID, and Immunocompromised ID – https://blog.unmc.edu/infectious-disease/
We are excited to welcome Jeremy Tigh PharmD as a new PGY-2 in our ID Pharmacy Residency Program! He’s the third ID Pharmacy resident we have had and a fantastic addition to our team! Read on to learn a little more about him…
Tell us about the position you recently started I am beginning my second year as a pharmacist resident, specializing in infectious diseases. Over this year I will have comprehensive clinical training in antimicrobial stewardship and infectious diseases pharmacy practice. I will round with the inpatient infectious diseases consult services, participate in antimicrobial stewardship, OPAT, and community outreach stewardship programs, and practice in the HIV clinic longitudinally.
Tell us about your background I grew up in Minden, Nevada, a small town tucked up next to the Sierra Nevada Mountains and Lake Tahoe. I completed my undergraduate studies at Utah State University and majored in cell and molecular biology. After graduating, I worked for a local biotechnology company as a research and development laboratory technician focused on mammalian cell culture. During that time I became increasingly interested in the world of pharmacy and subsequently attended pharmacy school at the University of Utah. After graduating, I left the mountains for the plains and completed my PGY1 pharmacy residency at Nebraska Medicine.
Why did you choose to come work at UNMC When it came to applying to pharmacy residency programs, I wanted a program that offered a robust PGY1 experience but also had a well-established infectious diseases/antimicrobial stewardship program. I had heard good things about UNMC from my faculty mentor who trained there, and she encouraged me to apply. After interviewing, I was drawn by the family-friendly atmosphere of Omaha and the endless opportunities within UNMC. I was fortunate enough to match here for my PGY1, where I was able to get first-hand exposure to the serious medicine and extraordinary care that Nebraska Medicine provides, especially in antimicrobial stewardship and infectious diseases. I’m grateful to be able to stay for another year, where I will get to train under experts in the field and be a part of one of the best programs in the country!
What makes you excited about working in ID I think that it is important to choose a specialty that interests you the most; one that you will not mind spending a lifetime reading about, memorizing information, and teaching. For me, that is infectious diseases! I love the interplay between microbiology, antimicrobial resistance, stewardship, and drug PK/PD. I get the opportunity to learn about patients, but also microorganisms and therapeutics. This appeals to me as a lifelong learner and challenges my natural curiosity as things are constantly evolving. I am motivated by the belief that there are significant therapeutic challenges in this area for patients, physicians, and other healthcare professionals, and that as a pharmacist, I will have a leading role in helping to solve them.
Tell us something about yourself that is unrelated to medicine My wife and I have a four-year-old daughter and are expecting a baby boy this Fall! We also have two black cats named Lottie and Darcy, and a bearded dragon named Poptart.
It is that time of year again, the fresh transition into fall, and for the Infectious Diseases world, the growing excitement for IDWeek. This year, UNMC ID will again be active at throughout the conference.
Where can you find us?
First, follow us on Twitter @UNMC_ID throughout the conference!
Second, we have faculty who will be participating in the mentorship program, so keep your eyes open & please say hello!
Third, there are several presentations from our faculty and fellows, and here is the list of talks! We hope to see you there!
If you missed it, Dr. Andrea Zimmer presented on Thursday, September 23rd on “Transplant Infections”!
Still upcoming presentations from faculty:
Dr. Susan Swindells will be presenting Thursday, September 30, with her session entitled “Challenging HIV cases” (#32)
Dr. Trevor Van Schooneveld has several presentations on October 1st, including “Big Beasts of Skin & Soft Tissue Infections” (#95) and “SSTI Imposters”
Dr. Kelly Cawcutt will be presenting Friday, October 1st in “Competing Priorities Between Antimicrobial Stewardship and Other Hospital Needs”; with her talk entitled “ASP vs IC: Turf War or Battle Buddies?” (#106)
Dr. Nicolas Cortes will be presenting Friday, October 1 with his presentation entitled “What’s New in Orthopedic Infections: Bone Appetit!” (#102)
Dr. Angela Hewlett will be presenting on Friday, October 1st with her session entitled “Update on Natural and Prosthetic Vascular Graft Infections” (#101)
Dr. Marcelin has several presentations on Friday, October 1st and Saturday October 2nd including “
Competing Priorities Between Antimicrobial Stewardship and Other Hospital Needs” (#106); “Leadership in the Time of Social Media (#124), and “ID Divisions in the 21st Century” Strategy & Best Practices for Social Media Engagement”
Dr. Scott Bergman will be presenting Saturday, October 2nd with his presentation entitled ” TDM for Beta-Lactams: Ready for Prime Time?” (#119)
Abstract & Poster Presentations:
Dr. Jonathan Ryder (UNMC ID Fellow) will be presenting “Is There Value of Infectious Diseases Consultation in Candidemia? A Single Center Retrospective Review from 2016-2019” (#988)
Dr. Laura Selby (UNMC ID Fellow) will be presenting “Effect of SARs-Cov-2 mRNA Vaccination in Healthcare Workers with Household COVID Exposure” (#421)
Dr. Sara Bares (UNMC ID faculty) will be presenting “A Multi-faceted, Iterative Program to Increase COVID-19 Vaccine Uptake in a Midwestern HIV Clinic” (#1196)
Dr. M. Salman Ashraf (UNMC ID faculty) will be presenting “Resources Needed by Critical Access Hospitals to Address Identified Infection Prevention and Control Program Gaps” (#954)
Dr. Nicolas Cortes-Penfield (UNMC ID faculty) will be presenting “Infection Prevention and Control Training Needs and Preferences Among Frontline Health Professionals” (#797)
Dr. Andrew B Watkins (UNMC ID Faculty) will be presenting “Implementation and Outcomes of a Program to Coordinate and Administer Monoclonal Antibody Therapy to Long-Term Care Facility Residents with COVID-19” (#501)
Dr. Nada Fadul and Nichole Regan will be presenting “Telemedicine Implementation at a Midwestern HIV Clinic During COVID-19: One Year Outcomes” (#878)
Dr. Fadul will be presenting “Factors Associated with Lack of Viral Suppression Among Women Living with HIV in the United States: An Integrative Review.” (#884)
Dr. Fadul will be presenting “Structural Vulnerability among Patients with HIV and SARS-CoV-2 Coinfection: Descriptive Case Series from the U.S. Midwest” (#464)
Post written by Dr. Kelly Cawcutt & originally posted at https://www.cloroxpro.com/blog/hot-topics-in-healthcare-hais-infection-prevention-post-pandemic/
The COVID-19 pandemic has brought unprecedented changes to healthcare throughout the world. Fraught with high volumes of patients and paucity of resources and testing, combined with personal protective equipment (PPE) and staffing shortages the past year has taught the healthcare community lasting lessons in resilience. The rapidly advancing knowledge around the SARS-CoV-2, the virus that causes COVID-19, has also prompted a shift in the standard of care. In the face of such multifaceted challenges, the world of Infection Prevention and the capacity to monitor and prevent healthcare-associated infections (HAIs), changed.
How, why, and what changes have occurred?
Stevens et al described the impact on HAI prevention efforts as notable due to diversion of human resources for surveillance and case identification, process measures for prevention of HAIs (such as hand hygiene), mitigation resources (lack of real-time feedback), and the lack of adequate supplies of PPE for traditional HAIs resulting in potential increased risk of cross-contamination.
Furthermore, the level of illness of patients affected by COVID-19 combined with the limited PPE resources, resulted in changes in patient care that could be unpredictable at times. In clinical care settings for example, the long length of hospital stay, particularly in the intensive care unit (ICU), was accompanied by longer durations of support devices, such as endotracheal tubes, central venous catheters (CVCs), and urinary catheters. The longer duration of which increased the numbers of opportunities for in the failure of executing process measures to prevent HAIs.
The increased use of prone positioning, even amongst non-ventilated patients, may have negatively impacted visible access to many dressings and device sites for several hours per day. Finally, with PPE limitations, many adjustments were made to decrease required trips and time spent in patient rooms, such as transitioning intravenous medication pumps to outside of patient rooms. Such changes may have positively impacted PPE utilization rates, but may have carried negative counterbalances with increased risks of HAIs due to lack of direct visualization, longer tubing with possible increased risks of contamination, and potential preference for more durable catheters, such as CVCs to minimize risk of dislodgement or need for new access placement. Finally, it was would be remiss to not acknowledge that all of the above were further augmented by the fear and anxiety that resulted from the many unknowns and struggles faced by healthcare workers, and may have increased the risk for error.
We must recognize the impact the pandemic has had on healthcare, with rapid changes in practice, high work burdens with increasing burnout, and the need to move forward. Hardwiring our HAI prevention practices to ensure consistency in both the best and worst of times is critical. Considering how to identify, implement and amplify the positive innovations and changes throughout the field is necessary. Of paramount importance is ensuring robust infection prevention teams have adequate resources for surveillance, mitigation, education and quality improvement.
Thank you to all of the tireless Infection Prevention teams, continuing to strive to provide the safest care for our patients and healthcare teams around the world!
In July 2021 the Center for Disease Control and Prevention (CDC) released their sexually transmitted infections (STI) treatment guideline, an update from 2015.1 Below, senior ID fellow Dr. Jonathan Ryder highlights significant (but by no means comprehensive) changes in this new guideline that can be incorporated into clinical practice and some of the evidence supporting these changes. Part 2 – Bacterial Vaginosis, Trichomonas, Pelvic Inflammatory Disease
Bacterial Vaginosis (BV)
Photomicrograph of vaginal smear with normal epithelia cell and epithelia cell covered with bacteria, known as a clue cell. Image Source: CDC Public Health Image Library https://phil.cdc.gov/Details.aspx?pid=14574
In a fairly interesting and somewhat controversial recommendation given current medical teachings, the CDC guidelines reversed course on counseling against alcohol consumption during treatment with metronidazole. Citing a Norwegian study, the guideline authors comment that no studies have demonstrating convincing evidence of a clear interaction between alcohol and metronidazole causing a disulfiram-like reaction.6 A study supporting this recommendation from 2002 included 12 healthy volunteers randomized to either oral metronidazole 200mg three times daily or placebo followed by drinking 0.4g/kg of ethanol found no difference in blood acetaldehyde levels or any subjective or objective evidence of a disulfiram-type reaction.7
Treatment recommendations for BV remain the same with oral metronidazole 500mg twice daily for 7 days or either topical metronidazole gel or clindamycin cream being the preferred options.
New guidelines recommend a 7-day course of oral metronidazole 500mg twice daily for women with trichomonas, which differs from the prior recommendation of one dose of oral metronidazole 2g. However, in men, the single dose of oral metronidazole 2g is still recommended. The evidence for this change comes from a randomized controlled trial in women with HIV showing increased effectiveness of the 7-day treatment course compared to single dose as well as a meta-analysis including women without HIV showing the same.8 A single dose of oral tinidazole 2g remains an alternative treatment for both men and women.
Pelvic Inflammatory Disease (PID)
The recommended treatment for PID now includes anaerobic coverage, specifically with metronidazole. Based on a randomized controlled trial comparing ceftriaxone and doxycycline with or without metronidazole, the metronidazole group was found to have decreased presence of endometrial anaerobes, less Mycoplasma genitalium, and reduced pelvic tenderness.10 Therefore, the preferred regimen for PID is ceftriaxone 1g daily plus doxycycline 100mg twice daily plus oral metronidazole 500mg twice daily. Cefotetan or cefoxitin with doxycycline are also recommended. Notably, the higher dose ceftriaxone used for gonorrhea above should be used for PID as well when given as an outpatient.
For another summary of the changes, Ina Park, MD has an excellent Twitter thread:
Here's my greatest hits from today’s new @CDCSTD#STI Treatment Guidelines: a 🧵 1)#STI guidelines instead of #STD! 2)Expedited Partner Therapy: not just for “heterosexuals” 👏 3)#HepatitisC: screen all pregnant people 4)Rectal/throat GC/CT: consider for non-MSM like teens 👏 pic.twitter.com/gfEhrWpMKA
Fjeld H, Raknes G. Er det virkelig farlig å kombinere metronidazol og alkohol? [Is combining metronidazole and alcohol really hazardous?]. Tidsskr Nor Laegeforen. 2014;134(17):1661-1663. Published 2014 Sep 16. doi:10.4045/tidsskr.14.0081
Visapää JP, Tillonen JS, Kaihovaara PS, Salaspuro MP. Lack of disulfiram-like reaction with metronidazole and ethanol. Ann Pharmacother. 2002;36(6):971-974. doi:10.1345/aph.1A066
Kissinger P, Mena L, Levison J, et al. A randomized treatment trial: single versus 7-day dose of metronidazole for the treatment of Trichomonas vaginalis among HIV-infected women. J Acquir Immune Defic Syndr. 2010;55(5):565-571. doi:10.1097/QAI.0b013e3181eda955
Howe K, Kissinger PJ. Single-Dose Compared With Multidose Metronidazole for the Treatment of Trichomoniasis in Women: A Meta-Analysis. Sex Transm Dis. 2017;44(1):29-34. doi:10.1097/OLQ.0000000000000537
Wiesenfeld HC, Meyn LA, Darville T, Macio IS, Hillier SL. A Randomized Controlled Trial of Ceftriaxone and Doxycycline, With or Without Metronidazole, for the Treatment of Acute Pelvic Inflammatory Disease. Clin Infect Dis. 2021;72(7):1181-1189. doi:10.1093/cid/ciaa101
In July 2021 the Center for Disease Control and Prevention (CDC) released their sexually transmitted infections (STI) treatment guideline, an update from 2015.1 Below, senior ID fellow Dr. Jonathan Ryder highlights significant (but by no means comprehensive) changes in this new guideline that can be incorporated into clinical practice and some of the evidence supporting these changes. Part 1 – Chlamydia, Gonorrhea, Mycoplasma genitalium:
Preferred treatment regimen for chlamydia is now oral doxycycline 100mg twice per day for 7 days. Oral azithromycin 1g for a single dose is now an alternative regimen instead of a preferred regimen.
There are multiple reasons for this change. First, several randomized controlled trials have shown superiority of doxycycline to azithromycin for treatment of chlamydia, including two trials in men who have sex with men (MSM) with rectal chlamydia and one trial in adolescents with urogenital chlamydia.2-4 Second, there is increasing concern for azithromycin resistance in Neisseria gonorrhea, Streptococcus pneumoniae, Mycoplasma genitalium, Shigella, and Campylobacter infections; thus, by changing recommended therapies, we can reduce the selective pressure on these other pathogens.5
There are a few exceptional instances in which a single dose of azithromycin is preferable to a week of doxycycline: pregnancy and concern for nonadherence.
Prior guidelines recommended treatment of gonorrhea with a single dose of intramuscular ceftriaxone 250mg plus a single dose of oral azithromycin 1g. In late 2020 the CDC released a new update in Morbidity and Mortality Weekly Report (MMWR), which is now reflected in the current guidelines.5The new recommended treatment for uncomplicated gonococcal infections of any site is a single dose of intramuscular ceftriaxone 500mg. However, if the patient weighs ³150kg (300 lb), then 1g of intramuscular ceftriaxone should be administered instead.
The change in therapy for gonococcal infections is due to emerging resistance, antimicrobial stewardship concerns, and pharmacologic reasons. As shown in the figure below, azithromycin resistance in gonorrhea has increased nearly tenfold from 2013 (0.6%) to 2019 (5.1%).5 As mentioned above, continued azithromycin use has raised concerns in antimicrobial stewardship due to increasing resistance in other pathogens as well as its decreased effectiveness against chlamydia. Lastly, higher doses of ceftriaxone are more likely to achieve adequate time above the MIC, especially in the pharynx, a location known to be more difficult to eradicate N. gonorrhoeae, and in gonococcal strains with higher MICs.
Alternative regimens for gonorrheal infections now include higher dose oral cefixime (800mg for one dose instead of 400mg) as well as intramuscular gentamicin 240mg for one dose combined with a single dose of oral azithromycin 2g. These alternative regimens are not considered reliable for pharyngeal gonorrhea.
A new development for M. genitalium is the presence of an FDA approved nucleic acid amplification test for multiple specimen types. Testing for M. genitalium should be performed in men with recurrent non-gonoccocal urethritis and women with recurrent cervicitis or pelvic inflammatory disease (PID). Asymptomatic screening is not yet advised due to uncertain clinical benefit.
Treatment for M. genitalium has also changed since prior guidelines due to increasing azithromycin resistance. If resistance testing for macrolide susceptibility is available and performed, that should dictate the treatment regimen. If macrolide sensitive M. genitalium, then oral doxycycline 100mg twice per day for 7 days followed by oral azithromycin 1g first dose then 3 additional days of 500mg daily should be given. However, if macrolide resistant or if susceptibility testing cannot be performed, then a 7-day course of oral doxycycline 100mg twice daily should be followed by oral moxifloxacin 400mg once daily for 7 days.
Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187. Published 2021 Jul 23. doi:10.15585/mmwr.rr7004a1
Lau A, Kong FYS, Fairley CK, et al. Azithromycin or Doxycycline for Asymptomatic Rectal Chlamydia trachomatis. N Engl J Med. 2021;384(25):2418-2427. doi:10.1056/NEJMoa2031631
Dombrowski JC, Wierzbicki MR, Newman LM, et al. Doxycycline Versus Azithromycin for the Treatment of Rectal Chlamydia in Men Who Have Sex With Men: A Randomized Controlled Trial [published online ahead of print, 2021 Feb 19]. Clin Infect Dis. 2021;ciab153. doi:10.1093/cid/ciab153
Geisler WM, Uniyal A, Lee JY, et al. Azithromycin versus Doxycycline for Urogenital Chlamydia trachomatis Infection. N Engl J Med. 2015;373(26):2512-2521. doi:10.1056/NEJMoa1502599
St Cyr S, Barbee L, Workowski KA, et al. Update to CDC’s Treatment Guidelines for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(50):1911-1916. Published 2020 Dec 18. doi:10.15585/mmwr.mm6950a6
As antibiotic resistance threatens to return us to the pre-antibiotic era where mere skin infections were harbingers of death, we have only a few tools in our box to slow what seems to be inevitable. The 2019 CDC Antimicrobial Resistance Threat report demonstrated 18% fewer deaths from antibiotic resistance overall, and 28% fewer antibiotic-resistance related deaths among hospitalized people since 2013. Despite this, the CDC still reported almost 3 million deaths and over 35K deaths annually from antibiotic resistant infections. Addressing antibiotic resistance includes developing new treatments (hindered by a currently limited, slow pipeline), prevention of spread using infection control, and slowing development of resistance using antimicrobial stewardship. These approaches have been challenged by inconsistent adoption of best practices, emergence of new threats, and incomplete surveillance
The gut microbiota have been examined as organisms of interest in the quest against antimicrobial resistance because while they can be disrupted by systemic antimicrobial use, the gut microbiota themselves may prevent overgrowth and colonization by pathogenic bacteria. Thus the interest in probiotics, with multiple potential advantages including relative safety, low cost, ease of administration and diversity of activity. However, there is still much to learn about the potential benefit, including its use in immunocompromised patients, adequate dosing for efficacy, and which strains are actually useful (McFarland et al.). Prior studies have demonstrated lower rates of C. difficile infection in probiotic recipients compared with placebo recipients (Johnson et. al). Conversely, other studies have shown no benefit; for example in an RCT pilot of Lactobacillus rahmnosus in ICU patients there were no significant differences in acquisition or loss of any multi-drug resistant organisms compared with placebo (Kwon et. al.)
So this is what we end up telling patients when they ask us about probiotics to prevent C. difficile and antibiotic resistance:
Hence, the important aim of this study by Rauseo et al.: To determine whether Lactobacillus rhamnosus GG (LGG) can safely prevent intestinal colonization due to antimicrobial resistant organisms (AROs).
This was a single center double-blinded, randomized, placebo-controlled pilot trial conducted at Barnes-Jewish Hospital, St. Louis, MO from January 2014-September 2015 among hospitalized adults over 18yrs. Anyone who was immunocompromised, actively dying, or currently having diarrhea was excluded. Interestingly, they also excluded any non-English-speaking individuals. People randomized received either LGG or placebo by orally from enrollment until discharge, and stool/rectal swabs obtained on enrollment and every 3 days until discharge. Primary outcome was overall ARO acquisition, secondary outcomes focused on loss/acquisition of individual ARO, and they collected safety endpoints like mortality and development of Lactobacillus systemic infection.
The groups were pretty similar, and the pilot enrollment was small with only 44 patients in each arm. There were differences in proportion with infection as primary cause of admission and likelihood of previous FQ use. There was no difference in acquisition or loss of ARO for primary or secondary endpoints, and bonus was that it seemed safe overall, with no concerning safety signals.
So can Lactobacillus rhamnosus GG (LGG) can safely prevent intestinal colonization due to antimicrobial resistant organisms (AROs)? The answer based on this study is: NOPE. Unfortunately, there were no practice changing conclusions from this study, but negative studies are important and should be reported. While it is disappointing that we don’t have anything new to tell our patients based on this study, it is still important that we can tell them that there is still not data that probiotics will harm them if they choose to take them.
While the RCT design was desirable, some of the limitations of this study include small sample size; short duration on study drug; potential impact of missed doses and systemic antibiotics on the Lactobacillus effectiveness; and the use of a single organism probiotic instead of a cocktail. Perhaps with a larger, multicenter design based on this preliminary data, the authors may finally be able to help us find the answer to this important question.
With respect to its aim of evaluating the impact of probiotics on ARO, this study is not that controversial or groundbreaking. However, it is perplexing that the authors chose to lump individuals into White/Nonwhite categories only, because that assumes White is the default, when in fact, the Black and White populations of St. Louis are almost equal. Additionally, the “nonwhite category” only includes Black and Asian participants; the ethnicity category in the demographics is absent (despite the fact that the city of St. Louis includes about 4% Hispanic/Latino people); and the authors excluded non-English speaking people, without explanation or scientific justification in the article regarding these choices. These represent some missed opportunities by both the authors and the journal to ensure that equity is adequately addressed in research assessing the impact of therapeutics on clinical disease.
Check out a letter to the editor I submitted about these points in collaboration with Nada Fadul MD, Kelly Cawcutt MD, and Jacinda Abdul-Mutakabbir PharmD, with some suggestions on how researchers and journals can commit to equity even if the topic of scholarship is not health disparities.
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