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Updated Antibiotic Guidance for Skin and Soft Tissue Infections and Diabetes-Related Foot Infections

This post was researched and written by Dr. Jonathan Ryder, Assistant Professor and previous UNMC ID Fellow. Dr. Ryder is also Associate Medical Director of the Nebraska Medicine Antimicrobial Stewardship Program and Associate Hospital Epidemiologist. Here, Dr. Ryder shares key changes the Antimicrobial Stewardship Program has recently made in guidance on the treatment of SSTIs.

The Nebraska Medicine Antimicrobial Stewardship Program has published updated local guidance on the management of patients with skin and soft tissue infections (SSTI) and diabetes-related foot infections (DFI). This includes conditions such as non-purulent cellulitis, abscesses, necrotizing skin soft tissue infections, and bite wounds. These changes are due to new 2023 IDSA guidelines on the management of diabetes-related foot infections as well as updates in the microbiology for these infections since the 2014 IDSA guidelines for SSTI.

In this post, we highlight the key changes we have made to our guidance and the rationale behind these changes.

So Long to Clindamycin

Two of the most common pathogens for SSTI and DFI are beta-hemolytic Streptococci (including group A Streptococci [GAS] and group B Streptococci [GBS]) and Staphylococcus aureus. Unfortunately, resistance to clindamycin is rising significantly in these pathogens. Per surveillance data from the Centers for Disease Control, resistance to clindamycin was found in 34.4% of invasive GAS and 51.4% of invasive GBS.1 For Staphylococcus aureus, our 2024 antibiogram shows over 25% resistance to clindamycin.2 Given these high rates of resistance to clindamycin, clindamycin is no longer recommended for empiric treatment of SSTIs or DFI. 

However, there are other reasons why clindamycin has fallen out of favor. Clindamycin is associated with high rates of adverse effects, in particular gastrointestinal side effects in over 20%.3 Specifically, antibiotic-associated diarrhea is found in over 13% of patients.3 Clindamycin is also associated with the highest risk of Clostridioides difficile infection (CDI) compared to other antibiotics, with one study demonstrating 25 times higher odds of CDI when receiving clindamycin.4,5 Clindamycin is also dosed 3-4 times per day, which can make adherence challenging for patients. In a systematic review assessing adherence to therapy, 3-times-daily dosing was associated with only 65% adherence, while 4-times-daily was 51%.6 Thus, clindamycin is also a poor choice for SSTI and DFI given its high rate of adverse events and poor adherence to therapy. 

But What about Patients with Penicillin Allergies?

Clindamycin has frequently been used as an alternative choice in patients with penicillin allergies; however, a better understanding of antibiotic allergies provides more alternatives. New guidelines for management of antibiotic allergies were released in 2022.7 In collaboration with our allergy experts, local guidance for management of penicillin allergy and other beta-lactam allergy were developed. Within the new SSTI and DFI guidance, penicillin allergy guidance is provided for each scenario. Reference to these documents is helpful for finding alternative regimens. Generally speaking, even in the presence of a severe IgE-mediated penicillin allergy (e.g., anaphylaxis), first-line regimens for cellulitis, such as intravenous cefazolin, can still be used.

Alternative Options Exist with Increased Accessibility

Other options for patients with beta-lactam allergy include trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid. Historically, TMP-SMX has been avoided in non-purulent SSTI due to concerns about high rates of resistance to TMP-SMX in GAS. However, this concern about resistance has been found to be a myth .8 Older studies found high rates of resistance to TMP-SMX in vitro as a result of methodologic problems. After these problems were corrected, TMP-SMX susceptibility rates were very high for GAS. In clinical studies, TMP-SMX has performed well in the treatment of SSTI.9 TMP-SMX has been a preferred alternative when allergy precludes first-line regimens.

Linezolid has excellent Staphylococcal and Streptococcal activity, but concerns have existed regarding cost and serotonin syndrome. Fortunately, the price of linezolid has decreased substantially, although there can be variation between outpatient pharmacies on price (ensuring patients can access the drug at a lower price is key for prescribing linezolid outpatient).10 Regarding serotonin syndrome, the risk for this adverse event in patients receiving linezolid is exceedingly low, even in patients on selective serotonin reuptake inhibitors.8 In patients with serious infections, a careful weighing of risks/benefits is warranted. Regardless, linezolid remains a much safer and more effective option compared to clindamycin, especially as an alternative agent in patients with severe penicillin allergies.

Changes in Management of Necrotizing Soft Tissue Infection

Another common indication for clindamycin has been adjunctive antitoxin therapy for necrotizing soft tissue infections due to GAS or Clostridium species. However, there has been debate about whether clindamycin should be replaced by linezolid, which has similar in vitro antitoxin activity.11 The crux of this debate involves the increasing GAS resistance to clindamycin, a lower risk of CDI with linezolid, and replacing empiric vancomycin (and its associated risk of acute kidney injury) with linezolid. Since publishing this debate, two small retrospective studies have demonstrated linezolid and clindamycin have similar efficacy, but replacing clindamycin (and vancomycin) with linezolid reduced a composite risk of death, CDI, and acute kidney injury in one of these studies.12,13 Another study found a lower risk of acute kidney injury with this switch as well.14

Shorter is Better

The new guidance documents include updated antibiotic durations. For non-purulent cellulitis, antibiotic durations of 5-6 days are now the standard.15 For necrotizing soft tissue infections without concurrent bacteremia or cellulitis, antibiotic therapy can likely be stopped within 48 hours of the final debridement.16 Several changes in duration for DFI have also been incorporated from the 2023 IDSA guidance.

Conclusion

The management of patients with SSTI and DFI is changing due to increasing resistance, myth busting, and improved understanding of antibiotic allergies. Our updated guidance accounts for these changes by moving away from clindamycin, recommending more linezolid and TMP-SMX use, and shortening antibiotic durations.

References

  1. US Centers for Disease Control and Prevention. ABCs Bact Facts Interactive Data Dashboard. Accessed May 3, 2024, 2024. https://www.cdc.gov/abcs/bact-facts-interactive-dashboard.html
  2. Nebraska Medicine Antimicrobial Stewardship Program. Antibiograms. Accessed May 3, 2024, 2024. https://www.unmc.edu/intmed/divisions/id/asp/antibiograms.html
  3. Neu HC, Prince A, Neu CO, Garvey GJ. Incidence of diarrhea and colitis associated with clindamycin therapy. J Infect Dis. Mar 1977;135 Suppl:S120-5. doi:10.1093/infdis/135.supplement.s120
  4. Miller AC, Arakkal AT, Sewell DK, Segre AM, Tholany J, Polgreen PM. Comparison of Different Antibiotics and the Risk for Community-Associated Clostridioides difficile Infection: A Case-Control Study. Open Forum Infect Dis. Aug 2023;10(8):ofad413. doi:10.1093/ofid/ofad413
  5. Brown KA, Khanafer N, Daneman N, Fisman DN. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother. May 2013;57(5):2326-32. doi:10.1128/aac.02176-12
  6. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. Aug 2001;23(8):1296-310. doi:10.1016/s0149-2918(01)80109-0
  7. Khan DA, Banerji A, Blumenthal KG, et al. Drug allergy: A 2022 practice parameter update. J Allergy Clin Immunol. Dec 2022;150(6):1333-1393. doi:10.1016/j.jaci.2022.08.028
  8. McCreary EK, Johnson MD, Jones TM, et al. Antibiotic Myths for the Infectious Diseases Clinician. Clin Infect Dis. Oct 13 2023;77(8):1120-1125. doi:10.1093/cid/ciad357
  9. Bowen AC, Carapetis JR, Currie BJ, Fowler V, Jr., Chambers HF, Tong SYC. Sulfamethoxazole-Trimethoprim (Cotrimoxazole) for Skin and Soft Tissue Infections Including Impetigo, Cellulitis, and Abscess. Open Forum Infect Dis. Fall 2017;4(4):ofx232. doi:10.1093/ofid/ofx232
  10. Cheap Generic Drugs. NEJM Journal Watch. Accessed May 3, 2024, 2024. https://blogs.jwatch.org/hiv-id-observations/index.php/hey-insurance-companies-and-pharmacies-stop-messing-around-with-cheap-generic-drugs/2024/04/26/
  11. Cortés-Penfield N, Ryder JH. Should Linezolid Replace Clindamycin as the Adjunctive Antimicrobial of Choice in Group A Streptococcal Necrotizing Soft Tissue Infection and Toxic Shock Syndrome? A Focused Debate. Clin Infect Dis. Sep 3 2022;doi:10.1093/cid/ciac720
  12. Heil EL, Kaur H, Atalla A, et al. Comparison of Adjuvant Clindamycin vs Linezolid for Severe Invasive Group A Streptococcus Skin and Soft Tissue Infections. Open Forum Infect Dis. Dec 2023;10(12):ofad588. doi:10.1093/ofid/ofad588
  13. Dorazio J, Chiappelli AL, Shields RK, et al. Clindamycin Plus Vancomycin Versus Linezolid for Treatment of Necrotizing Soft Tissue Infection. Open Forum Infect Dis. Jun 2023;10(6):ofad258. doi:10.1093/ofid/ofad258
  14. Lehman A, Santevecchi BA, Maguigan KL, et al. Impact of Empiric Linezolid for Necrotizing Soft Tissue Infections on Duration of Methicillin-Resistant Staphylococcus aureus-Active Therapy. Surg Infect (Larchmt). Apr 2022;23(3):313-317. doi:10.1089/sur.2021.329
  15. Lee RA, Centor RM, Humphrey LL, et al. Appropriate Use of Short-Course Antibiotics in Common Infections: Best Practice Advice From the American College of Physicians. Ann Intern Med. Jun 2021;174(6):822-827. doi:10.7326/m20-7355
  16. Lyons NB, Cohen BL, O’Neil CF, Jr., et al. Short Versus Long Antibiotic Duration for Necrotizing Soft Tissue Infection: A Systematic Review and Meta-Analysis. Surg Infect (Larchmt). Jun 2023;24(5):425-432. doi:10.1089/sur.2023.037

Dr. Rupp Comments on COVID-19 and Avian Flu on Rural Heath Matters

A few weeks ago, we proudly shared that our Chief of Infectious Diseases, Dr. Mark Rupp, was honored with the 2024 Bartee Advocacy of Science Award, which is given to a UNMC scientist who exemplifies and lives out a commitment to community engagement. Illustrating this commitment to public science and medicine outreach, Dr. Rupp recently appeared on Rural Health Matters with the University of Nebraska President Dr. Jeffrey Gold to discuss the current state of COVID-19, avian influenza, and Lyme disease.

Rural Health Matters is a television show that features experts from UNMC discussing various health topics and their impact on farmers, ranchers, and rural Americans. The show is hosted on RFD-TV and features a live call-in segment where viewers can pose questions on a wide range of health-related topics that impact rural America.

Dr. Gold and Dr. Rupp are common features on the show, especially with increased infectious outbreaks in recent years. In this episode, Dr. Gold and Dr. Rupp were able to give actionable advice on how to avoid Lyme disease as we approach the summer months and commented on the current and future risks of avian influenza- which are especially important topics for rural Americans and all who work in agriculture or with animals which may contract or spread disease.

Both Dr. Rupp and Dr. Gold also received multiple comments from callers thanking them for their support on this show throughout the pandemic and continuing to today; a sentiment we would like to echo. Thank you, Dr. Rupp, for your outreach and commitment to ID education and awareness!

Watch the full episode on UNMC’s YouTube page here, and spread the word about Rural Health Matters on RFD-TV to all who may be interested.

Research Digest: New Findings on COVID-19

Research Digest is a periodic installment that recognizes the world-class clinical research performed right here at UNMC ID. Today, we review three articles covering new developments regarding COVID-19. As always, check out the linked full articles for more details.

Dr. Fadul, senior author on a publication exploring the COVID-19 vaccination status and opinions of Sudanese Americans.

In the first article, authored by graduating UNMC medical student Jonathan Freese, Dr. Nada Fadul, and others, the state of vaccine hesitancy and uptake was characterized among Sudanese Americans. Community-level inquiries on vaccine practices are crucial as the risk of infection is not constant across the population, and certain groups, including Sudanese Americans and other immigrant and refugee communities, have historically higher risk of COVID-19 exposure. With the help of community leaders, this study surveyed over 100 individuals. Vaccine hesitancy, when present, was found to be driven primarily by fears that it had not been studied enough. However, the authors found that the rate of COVID-19 vaccination exceeded the national average (93% vs 78% for the American public), a metric that covaried with educational attainment and belief in vaccine efficacy. Find the full article here.

The second article, co-authored by Dr. Andre Kalil, is an invited commentary that calls for a change in the way COVID-19 investigational drug trials are controlled. The authors point out that while some COVID-19 investigational compounds have been reported to cause cardiac complications, COVID-19 infection itself is known to cause many of these same complications. Without a sound control group and a carefully designed study, it is all too easy to falsely attribute adverse cardiac events to the drug being used to treat the infection when they may be the result of the infectious pathology itself. Randomized controlled trials have a long history of sound scientific and medical success in both ID and cardiology, but this hinges on meticulously designed studies. In short, an adverse event seen in those given the experimental treatment may be a sign of clinical efficacy if the rate that it is observed is actually higher in the untreated control group. However, if this factor is not examined in the control group, it would appear falsely to be caused by the treatment instead. Read the full commentary here.

Dr. Andre Kalil, co-author on two recent publications examining COVID-19 treatments and their risks.

In the last article, also co-authored by Dr. Kalil, the risk of immunomodulatory medications in COVID-19 was assessed, specifically in immunocompromised patients at higher risk of side effects from these treatments. Several immunomodulators have been shown to be beneficial in the treatment of COVID-19, as they can help restrict an overactive immune response and prevent collateral damage to the body during infection. However, by inhibiting certain aspects of the immune system, these drugs may also have the potential to increase the risk of secondary infections in those with an already compromised immune system. This study examined the existing literature, conducting a meta-analysis to determine whether evidence of outsized risk of these medications existed within immunocompromised populations, finding no statistically significant difference between patients randomized to immunomodulators vs control in terms of mortality or secondary infections. Read the full details of the analysis, including more detailed conclusions and considerations, here.

UNMC ID Recognizes STI Awareness Week

This week is Sexually Transmitted Infection (STI) Awareness Week, a week set aside to educate and raise awareness about sexually transmitted infections, or STIs, and how they impact our lives. It is also a time to work towards reducing STI-related stigma, fear, and discrimination and a time to ensure people have the tools and knowledge for prevention, testing, and treatment.

The CDC estimates that about 20 percent of the U.S. population – one in five people – had an STI on any given day in 2018. Left undiagnosed or untreated, many STIs can lead to serious health problems and permanent damage, both in the short and long term. ID and primary care providers are on the frontlines of this crisis, and we would like to take this opportunity to recognize their work in identifying, diagnosing, and treating STIs- as early diagnosis and treatment is key to preventing associated complications.

For more information and resources about STIs, see the CDC’s page on general resources for STI Awareness Week 2024 here, including resources designed for clinicians to help improve communication about and treatment of STIs.

Dr. Rupp to Receive Bartee Advocacy of Science Award

Dr. Mark Rupp, chief of the UNMC Division of Infectious Diseases, is set to be awarded the Bartee Advocacy of Science Award in recognition of his exceptional community engagement as a scientist.

Support Dr. Rupp and UNMC ID by attending the awards ceremony at 12pm on March 26th (Yanney Conference Room, Fred & Pamela Buffett Cancer Center)

We are proud to share that our division’s chief, Dr. Rupp, will be awarded the Bartee Advocacy of Science Award tomorrow at noon! The Bartee Advocacy of Science Award is given to a UNMC scientist who exemplifies and lives out a commitment to community engagement. Dr. Rupp was chosen for the inaugural honor by a process led by Chris Kratochvil, Bob Bartee’s successor as vice chancellor of external relations for UNMC.

First published in a UNMC Newsroom post, Dr. Rupp commented on the award earlier this month:

“I am very pleased and incredibly honored to receive the inaugural Bartee Family Award for promotion of science literacy and advocacy. I have long respected and admired Bob for his incredible contributions to UNMC over the course of his career – which makes this award even more meaningful to me. I believe the amplification of scientific misinformation and disinformation via social media is a pressing challenge and the promotion of scientific literacy may be one of our best strategies to preserve public health. I am honored to share the stage with Mary Woolley, the president of Research America, and I look forward to her presentation.”

Bartee, the award’s namesake, has commented in return:

“During the COVID-19 pandemic, many medical center professionals distinguished themselves in providing accurate and timely scientific information to the public. Dr. Rupp stood out among an impressive group for his willingness to engage the media, elected officials and members of the public, at times almost daily, to provide a calm and reasoned voice among a cacophony of misinformation. I am pleased and honored that he is the first recipient of the Bartee Award.”

Please join us in celebrating Dr. Rupp’s huge (and well-deserved) achievement by attending the inaugural Bob and Helen Bartee and Family Advocacy of Science Lectureship; info below:

When: March 26th, 2024 @ 12pm

Where: Fred & Pamela Buffett Cancer Center (BCC), Yanney Conference Room

Research Digest: Antimicrobial Strategies

Research Digest is a periodic installment that recognizes the world-class clinical research performed right here at UNMC ID. Today, we review two articles covering novel antimicrobial efforts or discoveries that may help us better treat different infectious pathologies. As always, check out the linked full articles for more details.

Dr. Cortes-Penfield, co-author of a recent review of the literature covering the switch between i.v. and oral antibiotics.

In the first article, Dr. Nicholas Cortes-Penfield and co-authors review evidence for the timing and process of switching from i.v. to oral antibiotic treatments during bone or joint infection. The authors explain that, for the past 50+ years, the medical community has been divided on the best time to transition from the standard post-surgical i.v. antibiotic regimen to a more accessible oral strategy, with regional and global differences in accepted standard of care. The team reviewed 8 randomized control trials and multiple retrospective studies and concluded that no data exists to definitively set a minimum i.v. antibiotic duration post-surgery. That said, a growing body of research supports an early switch to oral antibiotics, in most cases, within a few days following surgery. The authors caution, however, that this approach should be tailored for case-specific factors. Read the full article here.

Dr. Jonathan Ryder, 2nd year UNMC ID fellow
Dr. Ryder, a recent co-author of a paper on antiseptic catheter cap strategies.

The second article, co-authored by Dr. Jonathan Ryder, Dr. Daniel Brailita, Dr. Mark Rupp, and Dr. Richard Hankins, along with others from the UNMC community, tests whether additional sterilization of catheter connectors is beneficial in reducing the risk of microbial colonization of catheter equipment. Antiseptic-containing port-protecting caps are routinely used to help limit this possibility. However, the team aimed to determine whether additional manual disinfection with an alcohol wipe was further preventative of microbial colonization (the current standard of care at UNMC). 356 catheter connectors were cultured in this study, 165 in each group, with an additional 26 that did not have an antiseptic cap as a control group. The team found that the vast majority of positive cultures were from the non-antiseptic cap group (15 positive cultures), while both antiseptic cap treatments (with and without manual disinfection) performed similarly, with 1 and 2 positive cultures, respectively. The team concluded that antiseptic caps are an extremely useful tool for preventing bacterial colonization, but additional disinfection strategies (i.e. manual alcohol-based disinfection) do not further decrease the chance of colonization. Read the full article here.

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Sneak Peak: UNMC Specialty Care Center to Present Work at National Conference

A huge congrats to the Telehealth and Text to Improve Engagement in Care (i2TEC) initiative team, including Lance L. Burwell, LIMHP, PC– behavioral therapist at the UNMC SCC, who will be presenting work at the 2024 National Conference on Social Work and HIV/AIDS between May 22nd and 25th. 

Lance and co-presenters will be detailing progress with the i2TEFC initiative, which is funded by the Health Resources and Services Administration (HRSA) Special Projects of National Significance.  The intervention is meant to be a tool that supports people with HIV in achieving viral suppression and engaging in care.  It consists of 12 video-based counseling sessions delivered by a social worker or mental health professional, who uses motivational interviewing and problem-solving methods to support clients with HIV in addressing mental health, substance use, and other barriers to care engagement.  By delivering services from a telehealth platform, barriers related to HIV stigma and transportation access can be reduced thus allowing more people access to services which address barriers and encourage engagement in care to help people living with HIV achieve and maintain viral suppression. 

This intervention has been implemented at UNMC for one year and has included intervention learning sessions, site visits, and monthly monitoring calls, with the results of this project presented in May at a workshop titled Bridging HIV Care Gaps through Telehealth: An Evidence-Informed Intervention to Support Engagement in Care.

Congrats Lance! If you happen to be attending the conference in May, you don’t want to miss this exciting presentation! If not, we will also recap the highlights here on the UNMC ID blog.

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Happy 7th Birthday to our UNMC ID Blog!

We just turned 7!

As this month comes to a close, I want to share a brief look-back and a lot of gratitude to all those who have made this blog possible.

February 14, 2017 was our first UNMC ID blog post. It is amazing how much time has passed since then, and we are so grateful to all of our readers of our content, and for all of our UNMC colleagues and trainees who have contributed to this blog over the years. There are over 500 posts to-date filled with introductions, accolades, accomplishments and education! I encourage you to go back and review your favorite posts, those you may have missed, and please do continue to share the posts with others!

I want to specifically call out a special thanks to Dr. Rupp, our ID Division chief who has remained continually supportive of sharing the work, expertise and accomplishments of our Division through this platform. I would also like to thank my partner in crime in coordinating this blog, Dr. Marcelin, who has been a continued author, curator of content and social media disseminator and supporter of all these efforts. Finally, I also would like to thank our amazing student editor, Zachary VanRoy, who truly is invaluable in ensuring we have content to share.

Thank you again to everyone who has supported us, contributed to the blog, and who has read and shared our content. We are continually grateful!

Call for Applications: UNMC ID Division Chief

The University of Nebraska Medical Center and College of Medicine is conducting a national search for a dynamic and accomplished individual to assume the role of Division Chief of Infectious Diseases. If you or someone you know may be ready for an exciting opportunity at UNMC ID, please see the contact information below, share this post within your network, and nominate yourself or others for this position!

UNMC ID Fast Facts:

The Division of Infectious Diseases supports all infection control activities at Nebraska Medicine and operates 5 inpatient teams including the vibrant General and Community ID services, as well as dedicated Orthopedic, Oncology, and Solid Organ Transplant ID consult teams.  Existing areas of strength include: antimicrobial stewardship, global health security, biocontainment, HIV, infection prevention, oncology ID, solid organ transplant ID, and orthopedic ID. Of particular note at UNMC is the Global Center for Health Security.  This nationally recognized center encompasses the Nebraska Biocontainment Unit, the Nebraska Quarantine Unit, Emerging Pathogens Lab and Deployable Teams.  In addition, it is the home of the ASPR funded national Training, Simulation and Quarantine Center.

General Qualifications:

  • MD, MD/PhD or equivalent degree, with board certification in Infectious Diseases.
  • Eligibility for medical licensure in the State of Nebraska.
  • Scholarship, clinical and research accomplishments that would merit the rank of Associate Professor or Professor in the College of Medicine.
  • Demonstrated leadership experience in academic medicine, clinical practice, or professional societies.
  • National recognition in clinical, translational, and/or basic research.
  • Leadership qualities and experience to grow and sustain the division’s mission as well as foster a collaborative and collegial work environment.

Contact, Links and Resources:

Interested applicants should contact the Grant Cooper Team at rachel@grantcooper.com for inclusion in the ongoing application review.

Want to nominate a qualified candidate? Contact Rachel at the above email as well.

UNMC ID Webpage

Chief, Division of Infectious Diseases – Position Announcement

Research Digest: Clinical Trials for COVID-19

Research Digest is a periodic installment that recognizes the world-class clinical research performed right here at UNMC ID. Today, we review three articles covering clinical trials that evaluate new drugs for the treatment of COVID-19, using three different approaches. As always, check out the linked full articles for more details.

Diana Florescu, MD, co-author of a recent reanalysis of a phase 3 COVID-19 clinical trial

In the first article, published in the journal Infection and co-authored by the late Dr. Diana Florescu, the authors examine the data from a phase 3 randomized and placebo-controlled trial of the antiviral medication molnupiravir specifically in immunocompromised patients. This medication works by inhibiting the ability of the virus to replicate and infect other cells. The study found a large reduction in hospitalization, death, and adverse events in immunocompromized patients who recieved treatment with molnupiravir, along with enhanced clearance of infectious virus. The authors conclude that, while this study had a small sample size, this evidence suggests that molnupiravir is a safe and efficacious treatment for mild-to-moderate COVID-19 in non-hospitalized immunocompromized patients.

Dr. Andre Kalil, co-author of a recent clinical trial exploring a new type of COVID-19 treatment

The second article, co-authored by Dr. Andre Kalil, takes a different approach by targeting the immune response to SARS-CoV-2 infection instead. Severe COVID-19 pneumonia can cause elevated production of a human protein called IL-33 by the immune system. While meant to enhance immune function, this exaggerated response instead causes excessive damage to the body during severe infection, contributing to the development of Acute Respiratory Distress Syndrome (ARDS). This study examined the efficacy and safety of new drugs aimed at interfering with the IL-33 pathway, among other approaches. While these new medications were not associated with safety concerns, the authors report that there was no improvement in time-to-recovery in patients with severe COVID-19 pneumonia.

Dr. Hewlitt, a member of the ACTT-4 Study Group which investigated this new approach to immunomodulation during COVID-19

The last article, published in The Lancet: Respiratory Medicine also co-authored by Dr. Kalil along with LuAnn Larson, RN, and Dr. Angela Hewlitt, explores the efficacy of adjunct therapy with baricitinib or dexamethasone in addition to a standard COVID-19 medication, remdesivir. Both baricitinib and dexamethasone calm an overactive immune response, though through different means, and have evidence supporting their use during COVID-19. However, a study comparing their efficacy in conjunction with antiviral therapy has not previously been performed. To explore this regimen, the authors conducted a randomized, double-blind, double placebo-controlled trial with patients enrolled at 67 trial sites across the globe. The study found that the addition of baricitinib or dexamethasone to remdesivir resulted in similar rates of mechanical ventilation-free survival by the end of the study period. However, patients administered dexamethasone experienced significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events than those taking baricitinib. The authors conclude, “a more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered”.

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