Home — Division of Infectious Diseases

Division of Infectious Diseases

Welcoming our new Division Chief – Dr. David Warren

We are pleased to welcome our new UNMC ID Division Chief, Dr. David Warren. Dr. Warren succeeds Dr. Mark Rupp, who served as Division Chief since 2011.

Dr. Warren comes to us from Washington University School of Medicine in St. Louis, MO, where he was the director of the Clinical Research Training Center, director of the Master of Science in Clinical Investigation Program, and Hospital Epidemiologist for Barnes-Jewish Hospital. University leaders including Dean Bradley Britigan, immediate past IM Department Chair Dr. Debra Romberger, and interim Department Chair Dr. Mark Rupp all praise Dr. Warren’s reputation of leadership and excellence in clinical research, education and mentorship, and clinical expertise, which will support and enhance the strong reputation of our division as we move into this new era. He has a keen interest and wealth of experience in mentoring trainees and junior faculty as we grow the next generation of infectious diseases physicians and scholars. Read on to get to know more about Dr. Warren!


Tell us a little about your background.

I was born and raised in Pittsburgh. I was a molecular and cell biology major at Penn State. My original plan was to get a PhD, but after a summer internship at the NIH where, on my first day of work, I had to sacrifice about 100 rats for a gene therapy study, I re-evaluated my goals. I attended the University of Pittsburgh for medical school, before going to Washington University in St. Louis for internal medicine residency and infectious diseases fellowship. I have conducted clinical research in the epidemiology and prevention of healthcare-associated related infections, particularly device- and procedure-related infections. I have a clinical interest in orthopedic infectious diseases. On a personal note, my wife is an internist – we met during residency. I have two children – my daughter, who lives in Pheonix, and my son who is currently a sophomore at the University of Colorado.

Why did you choose UNMC?

I am very excited to join the Infectious Diseases Division. The faculty at UNMC excel in many areas of clinical care and research, including transplant ID, orthopedic ID, the care of individuals living with HIV, infection prevention, antimicrobial stewardship, and biopreparedness, just to name a few. They serve as experts and leaders on national and international committees and panels. But most importantly, there is a spirit of support and camaraderie in the division. I felt it when I was interviewing for my position, and when I met several faculty and fellows at ID Week in October.

What about ID makes you excited?

The field of infectious diseases is never dull. ID specialists think of the whole patient. To us, social history is a critical part of our assessment. We often work with vulnerable individuals, and see firsthand how social determinants of health impact the treatment and prevention of infectious diseases. Some of the accomplishments that I have been most proud of have been my work in healthcare epidemiology and the prevention of catheter-associated bloodstream infections. Since infections are often a consequence of system issues, ID specialists are in an ideal position to advocate for changes at a population level.

Tell us something interesting about yourself unrelated to medicine.

I enjoy the outdoors. One of my favorite vacations I have had was when my wife and I were residents and took a two-week trip to Colorado and Utah to go hiking in Rocky Mountain National Park, the Gunnison Wilderness Area, and Arches National Park. I have done winter hikes in the Rocky Mountains. I have taken several weekend bicycle trips on the KATY Trail in Missouri.


 

Dr. Rupp’s final End of Year Reflection as Division Chief

As we wind down 2024 and look forward to 2025, it is appropriate to spend some time in reflection.

I am immensely proud of the UNMC ID Division and our contributions and accomplishments in 2024 – truly a great team effort! UNMC ID faculty were recognized within the organization and community, as well as nationally and internationally, for our expertise and delivery of compassionate patient care, effective education, innovative research, and valuable service. The faculty could not have accomplished the mission without the tremendous assistance of our provider colleagues, research personnel, and administrative support. Again, UNMC ID was near the top of the list of internal medicine divisions in terms of publications, grants and contracts, and awards for teaching and service. Keep up the great work in 2025!

For me personally, 2025 will be bittersweet as I stepdown from the ID Division Chief position. It has been an incredible honor for me to serve as the Chief for nearly the past 14 years and to see the Division flourish and rise to such great heights. It gives me great comfort to know the Division is well-positioned to continue its upward trajectory and I have full faith that with the leadership of the new Chief, Dr. David Warren, the ID Division will continue to exceed expectations. One thing for sure, there will be a friendly presence in Chair’s office as I serve my stint as Interim Chair of the Department of Internal Medicine.

My warmest wishes to the UNMC ID Division family for a joyous holiday season and a healthy and prosperous 2025!


 

Dr. Mark Rupp: Celebrating a Legacy of Innovation and Impact

On December 31, our UNMC ID Division Chief Dr. Mark Rupp will step down from this role and assume a new position as interim Chair of the Department of Internal Medicine. We celebrate his legacy in our ID Division and look forward to his continued leadership of the department during this interim period. Many Thanks to our outstanding Division Administrator Libby Morgan, for writing this heartfelt tribute message on behalf of the UNMC ID Division.

For the last 14 years, Dr. Mark Rupp has been dedicated to leading the UNMC Infectious Diseases Division with unwavering commitment, unparalleled expertise, and a compassionate heart. Dr. Rupp has not only been a brilliant physician and leader but also a mentor, a guide, and a true inspiration to everyone fortunate enough to work alongside him

For over a decade and a half, Dr. Rupp has shaped the landscape of infectious disease care, and the culture of our entire team. Over the last 14 years, the Infectious Diseases division has grown, adapted, and thrived in the face of challenges, from local outbreaks to global pandemics. His steady hand, keen intellect, and profound dedication to both patient care and medical education have been the cornerstone of our success.

Dr. Rupp has a unique ability to make complex concepts clear, instill confidence in those around him, and bring out the best in everyone. Whether guiding a newly minted fellow through their first difficult case or offering wisdom to a seasoned colleague facing tough decisions, Dr. Rupp’s approach has always been one of patience, kindness, and unwavering support.

But it is not just his clinical expertise that sets Dr. Rupp apart. His unwavering compassion for patients, dedication to advancing research, and tireless work to improve public health outcomes makes him an irreplaceable force within our institution. Under his leadership, our division has been at the forefront of cutting-edge research, patient advocacy, and efforts to reduce health disparities, often in the most difficult and uncertain of times.

As we look back on 15 years of service, we are reminded of the countless lives touched by Dr. Rupp’s expertise and humanity. We are reminded of the long hours, the difficult cases, and the moments of triumph, both big and small, that have defined our shared journey. Dr. Rupp has been a steady source of inspiration for all of us, always pushing us to be better, to learn more, and to give our very best to our patients and to each other.

Thank you, Dr. Rupp, for your vision, your leadership, and your unwavering dedication to our division, our patients, and our profession. Your impact will be felt for many years to come, and we are privileged to have had the opportunity to work alongside you. You have truly set a standard of excellence that will continue to inspire and guide us for generations.

At our final division meeting of 2024, we had the opportunity to surprise Dr. Rupp with a little tribute! As we usher in the new year with Dr. Rupp as our new interim chair, those of us in our ID Division feel fortunate to have had the opportunity to learn from him as the fearless leader of the Division of Infectious Diseases, and others may have witnessed his influence and leadership more directly during the COVID-19 pandemic. We look expectantly towards 2025 with admiration for the past, anticipation for the future, and most importantly, appreciation for the present. Thank you, Dr. Rupp!


 

UNMC ID Ranks Highly in World Science Citations

From left to right: Dr. Diana Florescu, Dr. Alison Freifeld, Dr. Andre Kalil, Dr. Mark Rupp, and Dr. Susan Swindells

As we round out the year, the UNMC ID blog would like to take a moment to recognize the academic successes of those in our Division. We routinely feature ground-breaking research from UNMC ID faculty though our Research Digest post series (see these posts here), and we are very lucky to have such amazing, productive, and insightful researchers in our Division.

As recently reported in UNMC Today, updated analysis of paper citations using a standardized citation metric identified over 100 UNMC researchers as top-cited in the world. Among these were multiple current and former members of UNMC ID, including: Dr. Diana Florescu, Dr. Alison Freifeld, Dr. Andre Kalil, Dr. Mark Rupp, and Dr. Susan Swindells! These rankings identify the top 100,000 scientists (by citations and extrapolated impact) across all fields and institutions. Given that there is an estimated more than 8.8 million scientists in the world, this places these individuals near the top 1% of researchers- a huge achievement.

However, the authors of this analysis admit that, “If an author is not on the list it is simply because the composite indicator value was not high enough to appear on the list. It does not mean that the author does not do good work…Citation metrics have limitations.” Therefore, we celebrate all of the fantastic scientists and work out of UNMC ID this year and thank everyone for their dedication to the advancement of ID practice, science, and the field at large!

UNMC ID’s Dr. Fadul Recognized by the NIH Office of Research on Woman’s Health

A huge congratulations to Dr. Nada Fadul, who was recently featured in the the NIH Office of Research on Woman’s Health’s quarterly publication: Woman’s Heath In Focus at NIH. The article explores Dr. Fadul’s work advancing long-acting antiretroviral medications, especially for women living in rural areas. See below for a snapshot of the feature, and here to check out the full story (see page 5).

“So much attention is focused on racial disparities among men living with HIV that disparities among women are sometimes overlooked, says Nada Fadul, M.D., who serves as assistant dean and professor of medicine in the University of Nebraska Medical Center (UNMC) Department of Internal Medicine’s Division of Infectious Diseases and medical director of the UNMC Specialty Care Center. Yet, disparities among women are often stark. In Nebraska, for example, Black women are diagnosed with HIV at eight times the rate of White women. Although effective antiviral regimens are available, multiple social and structural factors can reduce women’s ability to adhere to therapy and maintain viral suppression, including substance use, lack of health insurance or health care access, and intimate partner violence. In addition, health care access can be particularly challenging for women living in rural areas.

Dr. Fadul is now testing a new program to facilitate access to long-acting antiviral injections, taken every 2 months, at rural clinics. Women living in rural areas often cannot drive for hours every 2 months to receive their injections, so this program is providing injectables to local clinics and then using telehealth to monitor for viral suppression and side effects. One area Dr. Fadul would like to see explored further is promoting a sense of self-efficacy among women living with HIV. Researchers have found that higher self-efficacy corresponds to better treatment adherence and viral suppression among women. She shared that clinicians and other health care workers should do more while “working with women living with HIV to improve their self- efficacy and to empower them to see themselves as still beautiful, still worthy, still effective, still contributing to the society in a positive way while living with HIV.”

Congrats Dr. Fadul! Understanding and correcting HIV woman’s health disparities is a critically important effort, and your work does not go unnoticed (by us or the NIH). Thank you for all you do for patients, HIV care, and the ID community!

UNMC ID Recognizes National Influenza Vaccination Week

This week (December 2nd-6th, 2024) is National Influenza Vaccination Week. It is a time to spread awareness about, and celebrate, one of the most successful public health interventions.  

As the CDC notes:

National Influenza Vaccination Week (NIVW) is a critical opportunity to remind everyone 6 months and older that there’s still time to protect themselves and their loved ones from flu this flu season by getting their annual flu vaccine if they have not already. CDC data shows that flu vaccination coverage was lower last season, especially among certain higher risk groups, including children. When you get a flu vaccine, you reduce your risk of illness, and flu-related hospitalization if you do get sick. This week is meant to remind people that there is still time to benefit from the first and most important action in preventing flu illness and potentially serious flu complications: get a flu vaccine today.

While vaccine coverage was lower last season, there are also many things to celebrate regarding vaccination efforts. By the numbers:

  • For the 2022–2023 flu season, the CDC estimated that flu vaccination prevented:
    • 6 million flu-related illnesses in the U.S.
    • 2.9 million medical visits
    • 65,000 hospitalizations
    • 3,700 deaths.
  • Added to the estimated 64,000 lives saved in the 12 years prior, the flu vaccine is clearly a critical and effective component of healthcare.
  • All vaccination efforts in sum have been estimated to save over 154 million lives in the past 50 years!

Here at UNMC ID, we recognize the importance and the success of the influenza vaccine. Influenza viruses are constantly shifting. Additionally, your protection from last years vaccine wanes over time. Getting a flu vaccine every year is the best way to reduce your risk from flu. Help prevent illness, hospitalization, and deaths- talk to your healthcare provider and get a flu vaccination today.

Research Digest: Equity and Antimicrobial Stewardship

This post is part of a series recognizing Antimicrobial Awareness Week 2024. Research Digest is a periodic installment that recognizes the world-class clinical research performed right here at UNMC ID. Today, we review four articles covering the intersection of health equity and antimicrobial resistance/stewardship. As always, check out the linked full articles for more details.

photo of Dr. Cichon smiling. her hair is long and blonde, and she is wearing a black blazer with a white blouse

In the first article, Dr. Catherine Cichon (prior UNMC ID fellow) and Dr. Jasmine R. Marcelin, among others at UNMC, have reviewed existing data on health inequities. Recent studies have shown variable antimicrobial prescribing patterns and adverse events across race/ethnicity, rural or urban locations, and socioeconomic status. While these determinants of health outcomes have been described with respect to antimicrobial stewardship, there has been little effort to identify the driving factors of these disparities, a topic on which the review provides context, suggested next steps, and a call to action within the research community to identify and directly address the root causes of inequity pertaining to antimicrobial medications. Read the full article here.

The second article, also co-authored by Dr. Marcelin, dives into this issue by performing a scoping review of articles between 2000 and 2022 to characterize antibiotic prescribing practices. The authors identified significant differences across patient’s race and ethnicity, sex, age, socioeconomic factors, geography, clinician’s age and specialty, and healthcare setting, with an emphasis on the outpatient setting. These disparities contribute to healthcare inequality in profound ways. The authors conclude that future research should include specific health equity-related objectives to improve our understanding of the causes, effects, and interventions that may successfully correct inequity in the future. There is much nuance surrounding these findings, which is addressed in detail in this article. Read here for the full story.

Given the evidence explored in the first two articles, there is a great need to address antimicrobial stewardship through the lens of health equity. The third and fourth articles, written by Dr. Marcelin as well, define the interaction between social determinants of health and infectious disease health disparities, including in regard to antimicrobial stewardship. Crucially, these articles also provide actionable advice and steps to address disparities. The first article addresses this from an individual, organizational, and public health system level, while the second provides ample examples of detailed priorities that are aimed at aiding the implementation of strategies to address inequity in infectious disease. This is a fantastic resource for ID professionals everywhere and narratively describes and advises on the topic of health equity and infectious disease outcomes. Read the full articles here and here.

For a comprehensive approach to this important topic, check out the Society for Healthcare Epidemiology of America (SHEA)/CDC Advancing Health Equity through Antimicrobial Stewardship Workshop.


 

Antimicrobial Awareness Week: Shorter is Better for Antimicrobial Stewardship

This post is part of a series recognizing Antimicrobial Awareness Week 2024. Today, we are sharing some examples of clinical situations where shorter antibiotic duration of treatment are recommended. This post was written by Jeremy Tigh, PharmD.

The duration of antibiotic therapy for bacterial infections historically reflected long-standing dogma and relied largely on expert opinion and tradition. In the setting of a lack of high-quality data, and early false concerns for the development of resistance with short durations, longer fixed durations of therapy were sought after knowing that overtreatment occurred but ensured that every patient was “maximally cured.”1-2 In 2010 Paul Sax, MD wrote a satirical piece in the New England Journal of Medicine’s blog highlighting the lore in figuring out the length of antibiotic therapy, using non-evidence-based multiples of 5 (fingers on a hand) or 7 (days of the week).3 Since that piece, there has been an ongoing push towards studying proper durations of therapy, a movement dubbed “Shorter is Better” by expert in the field Brad Spellberg, MD.4-7 This refers to shortening the number of days an antibiotic course is given, while not increasing risk for treatment failure. This leads to less risk of harm including decreased antibiotic resistance, fewer adverse effects, and less Clostridioides difficile infection. Newer evidence supports shorter durations for some common infections. It is the goal of this document to encourage translating this evidence into current practice. 

Key Points8-10: Since 2019, IDSA has endorsed 5 days of antibiotics for patients with CAP who are clinically improving on therapy. A recent randomized controlled trial found antibiotics could be safely stopped at 3 days in patients who met markers for clinical stability (afebrile 48-72 hours, spO2 >90%, etc.). In patients with an initially elevated procalcitonin, antimicrobials can be stopped when it returns to normal (<0.25 ng/mL) or decreases by ³80%. Extra-pulmonary infections or those with infections caused by Pseudomonas aeruginosa or Staphylococcus aureus may require longer courses of treatment.

Key Points11-14: For uncomplicated cystitis, evidence supports 3 days of TMP-SMX (Bactrim) or 5 days of nitrofurantoin. Alternate options include 3 days of fluoroquinolones or 5 days of a beta-lactam (e.g., amoxicillin-clavulanate, cephalexin, cefuroxime). For complicated cystitis (including catheterized patients and those with urologic abnormalities), evidence supports 7 days of treatment. For pyelonephritis, longer courses of 7 days (fluoroquinolone) to 10-14 (TMP/SMX, beta-lactams) days are appropriate. Bacteria in the urine without any urinary symptoms is considered asymptomatic bacteriuria and should NOT be treated (exceptions: pregnancy, impending urologic surgery).

Key Points15-18: Multiple studies have demonstrated that 7 days of total antibiotic therapy is noninferior to 14 days in clinically stable patients who have adequate source control. Conversion to oral antibiotics is appropriate in patients who demonstrate clinical improvement while on IV therapy. Should use an oral antibiotic with demonstrated susceptibility against causative pathogen and high bioavailability (TMP/SMX, levofloxacin, cephalexin, amoxicillin-clavulanate). Longer durations may be necessary for immunocompromised patients, those with inadequate source control, or for certain pathogens such as Pseudomonas aeruginosa.

Key Points19-21: Treatment for 5-7 days is appropriate for most patients if there has been improvement in symptoms. Longer courses may be required for severe infections or infections without source control (undrained abscess). Diabetes alone is not an indication for a longer course

Key Points22-23: More than 1 in 5 antibiotics prescribed in adults are for sinusitis. In adults, acute bacterial rhinosinusitis should only be diagnosed when symptoms persist without evidence of improvement for at least 10 days beyond the onset of symptoms or after double worsening. In adults, 5-7 days of therapy is appropriate if improvement after 3-5 days of treatment occurs: 7-10 days if delayed response or switch to alternative therapy due to lack of response (Augmentin). In children, longer treatment duration of 10-14 days is recommended.

Key Points24: 10 days for penicillin, amoxicillin, 1st generation oral cephalosporins, clindamycin. 5 days for azithromycin (not preferred due to increasing macrolide resistance)

Key Points25: Amoxicillin, amoxicillin-clavulanate (preferred if antibiotic exposure within 30 days, recurrent infection), or oral cephalosporins: For children <2 years and children (any age) with tympanic membrane perforation or history of recurrent infection: 10 days. For children >2 years with intact tympanic membrane and no history of recurrent AOM 5-7 days.

References:

Document adapted from Public Health Ontario: Shorter is Smarter Resources.

  1. Llewelyn M J, Fitzpatrick J M, Darwin E, Tonkin-Crine S, Gorton C, Paul J et al. The antibiotic course has had its day BMJ 2017; 358 :j3418 doi:10.1136/bmj.j3418
  2. Rice LB. The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and Clostridium difficile. Clin Infect Dis. 2008;46(4):491-496. doi:10.1086/526535
  3. https://blogs.jwatch.org/hiv-id-observations/index.php/how-to-figure-out-the-length-of-antibiotic-therapy/2010/10/22/
  4. Spellberg B, Rice LB. Duration of Antibiotic Therapy: Shorter Is Better. Ann Intern Med. 2019;171(3):210-211. doi:10.7326/M19-1509
  5. Spellberg B. The Maturing Antibiotic Mantra: “Shorter Is Still Better”. J Hosp Med. 2018;13(5):361.362. doi:10.12788/jhm.2904
  6. Spellberg, Brad. “The New Antibiotic Mantra-“Shorter Is Better”.” JAMA internal medicine vol. 176,9 (2016): 1254-5. doi:10.1001/jamainternmed.2016.3646
  7. Spellberg B, Srinivasan A, Chambers HF. New Societal Approaches to Empowering Antibiotic Stewardship. JAMA. 2016;315(12):1229-1230. doi:10.1001/jama.2016.1346
  8. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST
  9. Dinh A, Ropers J, Duran C, et al. Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial [published correction appears in Lancet. 2021 Jun 5;397(10290):2150]. Lancet. 2021;397(10280):1195-1203. doi:10.1016/S0140-6736(21)00313-5
  10. https://www.unmc.edu/intmed/divisions/id/asp/clinical-pathways/docs/CAP-Guidance-2020-Revision-Final-Updated.pdf
  11. Gupta K, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e103-20
  12. Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(5):625-663. doi:10.1086/650482
  13. Drekonja DM, Trautner B, Amundson C, Kuskowski M, Johnson JR. Effect of 7 vs 14 Days of Antibiotic Therapy on Resolution of Symptoms Among Afebrile Men With Urinary Tract Infection: A Randomized Clinical Trial. JAMA. 2021;326(4):324-331. doi:10.1001/jama.2021.9899
  14. https://www.unmc.edu/intmed/divisions/id/asp/clinical-pathways/docs/NM-Updated-UTI-Guidance_Final-1.pdf
  15. Heil EL, Bork JT, Abbo LM, et al. Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process. Open Forum Infect Dis. 2021;8(10):ofab434. Published 2021 Oct 11. doi:10.1093/ofid/ofab434
  16. Yahav D, Franceschini E, Koppel F, et al; Bacteremia Duration Study Group. Seven versus 14 days of antibiotic therapy for uncomplicated gram-negative bacteremia: a noninferiority randomized controlled trial. Clin Infect Dis. 2019;69(7):1091-1098. doi:10.1093/cid/ciy1054
  17. von Dach E, Albrich WC, Brunel AS, et al. Effect of C-reactive protein–guided antibiotic treatment duration, 7-day treatment, or 14-day treatment on 30-day clinical failure rate in patients with uncomplicated gram-negative bacteremia: a randomized clinical trial. JAMA. 2020;323(21):2160-2169. doi:10.1001/jama.2020.6348
  18. Molina J, Montero-Mateos E, Praena-Segovia J, et al; SHORTEN trial team. Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized, controlled trial. Clin Microbiol Infect. Published online September 9, 2021. doi:10.1016/j.cmi.2021.09.001
  19. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America [published correction appears in Clin Infect Dis. 2015 May 1;60(9):1448. Dosage error in article text]. Clin Infect Dis. 2014;59(2):e10-e52. doi:10.1093/cid/ciu444
  20. Hepburn MJ, Dooley DP, Skidmore PJ, Ellis MW, Starnes WF, Hasewinkle WC. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med. 2004;164(15):1669-74
  21. https://www.unmc.edu/intmed/divisions/id/asp/clinical-pathways/docs/ssti-guidelines-2018.pdf
  22. Chow AW, et al. IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults. Clin Infect Dis 2012;54:e72-112.
  23.  Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical Practice Guideline (Update): Adult Sinusitis. Otolaryngology–Head and Neck Surgery. 2015;152(2_suppl):S1-S39. doi:10.1177/0194599815572097
  24. Shulman ST, et al. Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America. Clin Infect Dis 2012;55:e86-102
  25. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media [published correction appears in Pediatrics. 2014 Feb;133(2):346. Dosage error in article text]. Pediatrics. 2013;131(3):e964-e999. doi:10.1542/peds.2012-3488


 

PharmtoExamTable- Do Prophylactic Antibiotics have a role in Preventing Ventilator-Associated Pneumonia? 

This post is part of a series recognizing Antimicrobial Awareness Week 2024. Today, we feature a PharmtoExamTable post written by PharmD Candidate Theodore Blum. Read on to learn more!

Ventilator-Associated Pneumonia (VAP) is a hospital-acquired infection that affects anywhere from 5-40% of patients mechanically ventilated for two days or longer.1-2 In addition to a mortality rate of around 10%, VAP is associated with an increase in duration of mechanical ventilation, intensive care unit (ICU) length of stay, antibiotic resistance, and overall healthcare costs.2 The 2016 Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) guidelines for the management of VAP and Hospital-acquired pneumonia include empiric recommendations for antibiotics with activity against Staphylococcus aureus, Pseudomonas aeruginosa, and other gram-negative bacilli.1 Recommended strategies for preventing VAP include avoiding intubation when possible, daily sedation vacations, elevating the head of the bed, maintaining physical conditioning, providing oral care with toothbrushing, utilizing endotracheal tubes with secretion draining ports, and selective decontamination of the oropharynx and digestive tract.3 However, the role of short-term antibiotics as a prophylactic measure remains unclear. Several studies have evaluated this question using either intravenous or inhaled routes of antibiotic administration, but the wide range antibiotic agents, dosing strategies, and patient populations studied make broad recommendations in support or against VAP prophylaxis difficult.4, 6-9 

Studies Utilizing Intravenous Antibiotics

A French study from 2019 including nearly 200 patients admitted to the ICU evaluated the use of a two-day course of intravenous amoxicillin-clavulanate (Augmentin) in patients mechanically ventilated after cardiac arrest. It was a randomized placebo-controlled trial with the primary outcome of early VAP, defined as VAP occurring within the first seven days of hospitalization. The study showed amoxicillin-clavulanate significantly lowered the incidence of early VAP compared to placebo (19% vs. 34% respectively, HR 0.53; 95% CI 0.31-0.92; P=0.03). However, there were no differences in late VAP and other clinical endpoints like ICU length of stay, ventilator-free days, or 28-day mortality.4 In addition,  amoxicillin-clavulanate is not available in the United States as an intravenous product, preventing potential implementations of the dosing regimen used in the study.5 Most recently in 2024, another study in France including nearly 350 patients assessed the use of a single 2-gram dose of intravenous ceftriaxone to prevent early VAP in mechanically ventilated patients following acute brain injury. This was also a randomized, placebo-controlled trial that showed ceftriaxone reduced early VAP compared to placebo (14% vs. 32% respectively; HR 0.60; 95% CI 0.38-0.95; P=0.03). In contrast to the first trial discussed, a reduction in 28-day mortality and an increase in ventilator-free days were seen. However, there was still no difference in occurrence of late VAP. Also, 60-day mortality was not statistically different between the two groups.6

Studies Utilizing Inhaled Antibiotics

Inhaled antibiotics in VAP allow for delivery of high drug concentrations to the site of infection.  A meta-analysis published in 2018 suggested that antibiotics administered via nebulizer reduced the incidence of VAP but saw no reductions in ICU mortality.8 Some of the antibiotics used in the studies included ceftazidime, colistin, and gentamicin. There were some key limitations to the study, which highlight the difficulties of conducting clinically useful meta-analyses on the topic of prophylactic antibiotics to prevent VAP. First, there was significant heterogeneity identified between the studies with the use of different antibiotics, dosing regimens, and patient populations. Second, negative studies may be less likely to be published in medical literature, creating publication bias that may have affected the meta-analysis’ results.8 Lastly, most trials were conducted at a single center which limit repeatability and external validity. 

A multicenter randomized, placebo-controlled trial published in October 2023 added more literature to the use of inhaled antibiotics in VAP prevention.9 The study included nearly 850 patients, assessing the use of a 3-day course of 20mg/kg inhaled amikacin to reduce the incidence of VAP at 28 days. It showed the development of VAP was lower in the amikacin group compared to placebo (15% vs. 22% respectively, P=0.004), but as other trials found, there was no difference in mortality.9

Summary of Studies and Discussion

Many studies to date exploring antibiotic use for prevention of VAP have found significant reductions in the incidence of early VAP (within 7 days of mechanical ventilation), but no differences in late VAP or mortality. Some of the studies also show a reduction in ICU length of stay and increased ventilator-free days. Diagnosis of VAP is an important consideration when evaluating literature in this area. The IDSA/ATS Guidelines note VAP diagnosis is not straightforward. It involves using clinical criteria, identifying lung infiltrates correlating with physical examination findings suggestive of an infectious cause.1 However, some of the clinical criteria have low sensitivity and/or specificity for VAP, leading to overdiagnosis and overuse of antibiotics. For example, a meta-analysis found that fever only had a sensitivity of 66.4% and a specificity of 53.9% for VAP.10Misdiagnosis of VAP would affect the primary outcomes of the discussed studies.

Conclusion

There is not a short-term antibiotic prophylaxis regimen that shows consistent reductions in VAP, ICU length of stay, and mortality. Unnecessary antibiotic use will contribute to resistance. While overall antibiotic use may decrease by preventing VAP, the inconsistencies in VAP diagnoses and mortality reduction make it difficult to determine the benefit.  Therefore, the routine use of short-term antibiotics solely for the purpose of preventing VAP is not recommended. Further multicenter, randomized placebo-controlled trials should be conducted to better understand antibiotics’ role in VAP prevention.

Reviewed by: Jenna Preusker, PharmD, BCPS, BCIDP

Supervised by: Scott Bergman PharmD, BCIDP, FIDSA 

and Jillian Mack, PharmD

Sources:

  1. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111.
  2. Papazian L, Klompas M, Luyt CE. Ventilator-associated pneumonia in adults: a narrative review. Intensive Care Med. 2020;46(5):888-906.
  3. Klompas M, Branson R, Cawcutt K, Crist M, Eichenwald EC, Greene LR, et al. Strategies to prevent ventilator-associated pneumonia, ventilator-associated events, and nonventilator hospital-acquired pneumonia in acute-care hospitals: 2022 Update. Infect Control Hosp Epidemiol. 2022 Jun;43(6):687-713.
  4. François B, Cariou A, Clere-Jehl R, et al. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019;381(19):1831-1842.
  5. Amoxicillin and Clavulanate. Lexi-Drugs. UpToDate Lexidrug. UpToDate Inc. https://online.lexi.com. Accessed Oct. 17, 2024.
  6. Dahyot-Fizelier C, Lasocki S, Kerforne T, et al. Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial. Lancet Respir Med. 2024;12(5):375-385. 
  7. Zha S, Niu J, He Z, et al. Prophylactic antibiotics for preventing ventilator-associated pneumonia: a pairwise and Bayesian network meta-analysis. Eur J Med Res. 2023;28(1):348.
  8. Póvoa FCC, Cardinal-Fernandez P, Maia IS, Reboredo MM, Pinheiro BV. Effect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: A systematic review and meta-analysis. J Crit Care. 2018;43:240-245.
  9. Bellissimo-Rodrigues WT, Bellissimo-Rodrigues F. Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia. N Engl J Med. 2024;390(8):769-770.
  10. Fernando SM, Tran A, Cheng W, et al. Diagnosis of ventilator‑associated pneumonia in critically ill adult patients—a systematic review and meta‑analysis. Intensive Care Med. 2020;46:1170-9.


 

Antimicrobial Awareness Week: Equity and Stewardship

This post is part of a series recognizing Antimicrobial Awareness Week 2024. Today, we feature past and future seminars examining the intersection between health equity and antimicrobial stewardship. Read on to learn more!

In the first seminar, recorded on May 22nd as part of the US 2024 Department of Health and Human Services Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (PACCARB) public meeting, UNMC ID’s Dr. Jasmine Marcelin discusses pharmacoequity and how minoritized populations are uniquely impacted by antimicrobial resistance. Particularly, clinical trials testing antibiotics have historically been racially and ethnically imbalanced, without adequate representation of minoritized participants. Additionally, pharmacy deserts and structural differences in how individuals obtain and use antimicrobial medications have broad implications for the health of these communities. Dr. Marcelin also covers steps the field can take to address these inequities and ensure all individuals are protected from antimicrobial resistance. Check out the talk here.

Health equity is a critically important aspect of antimicrobial stewardship; later this week, Dr. Marcelin will speak again on this topic as part of the DPH initiative Health Equity Institute of Delaware’s Working4equity Series. Details and registration link below.

  • Title: How Antimicrobial Stewardship can Influence Health Equity
  • Date: Thursday, November 21, 2024; 5:00 pm Central (6pm Eastern)
  • Location: Virtual
  • Registration: Register Here! (Note that registration is free for those not seeking CME credit)

Please join us in attending this important and timely seminar!

Additionally, for additional important content on antimicrobial stewardship, Nebraska ICAP & ASAP have uploaded recordings from the 2024 Nebraska Antimicrobial Stewardship Summit, including updates and information on antibiotic resistance in Nebraska, antibiotic myths, tips on how to approach the administration for antimicrobial stewardship resources, and much, much more. Find all these seminars and more here.


 

Subscribe

Work at UNMC
Get Directions
Apply