Research Digest: Antimicrobial Advances (Part 2)

Research Digest is a periodic installment that recognizes the world-class clinical research performed right here at UNMC ID. Last time, we reviewed two articles covering advances in antibiotic and antimicrobial medications. This week, we feature three more articles from UNMC exploring the pharmaceutical treatment of different infectious diseases with wide-reaching implications. As always, check out the linked full articles for more details.

Dr. Kimberly Scarsi, one of the co-authors of this article

The first article, titled Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis and co-authored by UNMC College of Pharmacy’s Michelle Pham, Anthony Podany, and Kimberly Scarsi, explores the interaction of isoniazid, rifampin, and efavirenz on the effectiveness of levonorgestrel as an emergency contraceptive. Some of these drugs alter the activity of detoxifying enzymes in the liver, potentially reducing the plasma concentrations of hormonal contraceptives. While this effect is avoided by administering higher levonorgestrel dosages, certain genetic mutations common in the general population also affect these enzymes and may further complicate compensatory treatment regimens. Indeed, this study found that individuals who possess CYP2B6 poor metabolizer genotypes displayed exacerbated efavirenz-levonorgestrel interactions, making this effect more difficult to overcome. In contrast, NAT2 slow acetylator genotypes reduced the interaction, underscoring that genetic variability can profoundly alter the efficacy and effective treatment dosages of many medications. Read the full story here.

Dr. Molly Miller, lead author of this article in Open Forum Infectious Diseases

The second article, co-authored by many members of UNMC ID and Pharmacy, including Molly Miller,  Trevor Van Schooneveld,  Erica Stohs, Jasmine Marcelin,  Bryan Alexander,  Andrew Watkins,  Hannah Creager, and Scott Bergman, aimed to assess whether the implementation of multiplex PCR panels for pneumonia diagnosis impacted antibiotic de-escalation. This is crucial as earlier identification of causative organisms could result in a more rapid adjustment to the narrowest effective antibiotic regimen, potentially limiting the generation of antibiotic resistance to broad-spectrum antimicrobials. Conversely, the increased sensitivity of this technique to detect organisms could have the opposite effect, as clinicians treat PCR results which may not end up clinically significant. The group did not detect a difference in antibiotic use before or after implementation of the PCR pneumonia panel in this pilot study; however, this work lays the groundwork to further evaluate a significant real-world impact on antibiotic de-escalation in ICU patients treated for pneumonia. Read the article here.

Dr. Andre Kalil, author of this comment piece on antiviral therapy

The last article, written by Dr. Andre Kalil and published in The Lancet: Respiratory Medicine, reviews the effectiveness of Remdesivir in the treatment of patients hospitalized for COVID-19. Remdesivir is a viral RNA polymerase inhibitor with a complicated recommended treatment history throughout the pandemic. Kalil reviews the wealth of data supporting the use of this drug in hospitalized COVID patients, namely a faster time to recovery, shorter length of hospital stay, decreased progression to mechanical ventilation, and lower mortality. Nonetheless, many published guidelines over the past few years showed little agreement with each other, and none recommended expanded use of this treatment, a trend aided by shortages of drug production as well as research decisions that favored analysis of many different patient situations over a generalized analysis of efficacy among hospitalized patients, limiting the power of these studies. Dr. Kalil explores the history of Remdesivir use over the past few years, the potential missteps along the way, and lessons we can learn for future treatment of viral illnesses with life-saving antiviral medications. Read the whole story here.

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