Fighting serious bacterial infections in immunocompromised patients is a major theme in the medical career of Kari Neemann, MD, Assistant Professor in the Divisions of Adult and Pediatric Infectious Diseases (ID). She is motivated by the dual mission of tackling infection cases very directly as a clinician and with a much broader view in her role as a researcher. “I knew going through my fellowship that I wanted to do more than just take care of patients. I wanted to contribute to knowledge and make changes not just impacting my own patients but impacting all the patients who are similar to them.”
Judicious use of antibiotics and of their intravenous delivery are of utmost concern for ID physicians. Dr. Neemann will soon begin an antibiotic de-escalation study in children with leukemia who have febrile neutropenia. She explained, “The standard of care for those kids right now is that when they develop febrile neutropenia they get blood cultures drawn and put on broad-spectrum IV antibiotic therapy and they stay on that therapy until their counts come back up. That could be a few days or that could be weeks. In my project I'm trying to see, in the event a patient is doing great and meeting the eligibility criteria (resolution of fever, hemodynamically stable, and no evidence of infection identified), can we step them down to an oral agent that they can stay on until they are ready to go home, with their count recovery?” If backed with data, this has the potential to shorten their hospital stays and decrease the time they are connected to an IV pole.
In the same febrile neutropenic patient population, if a bacterial source of infection is identified, guidelines allow replacement of the broad-spectrum antibiotics with a targeted, narrower spectrum antibiotic. Over the past two years, an M4 honor student under Dr. Neemann’s mentorship has conducted a chart review to analyze the clinicians’ adoption of this preferred practice, which would lower patients’ exposure to unnecessary antibiotics and minimize conditions where antibiotic resistance can emerge.
The initial study Dr. Neemann spearheaded and published as a Fellow at UNMC was a retrospective analysis of Clostridioides difficile (C. diff) incidence and treatment in oncology patients who received hematopoietic stem cell transplant, with a special focus on the association of C. diff-associated diarrhea with cancer-related transplant outcomes. The incidence of C. diff diarrhea was substantial in this population (16.5%). However, guideline-adherent antibiotic treatment, starting with metronidazole, was effective in resolving diarrhea episodes, and no associations of C. diff with tumor relapse or patient mortality were evident. Dr. Neemann and UNMC colleague Alison Freifeld, MD, also authored a 2017 review article, “Clostridium difficile-Associated Diarrhea in the Oncology Patient,” which explored nuances of C. diff diagnosis and management in immunocompromised oncology populations.
In addition, Dr. Neemann has teamed with Stephen Obaro, MD, PhD, Professor in Pediatric ID, to investigate agents of neonatal sepsis in Nigerian infants. The initial study was funded by Dr. Neemann’s Early Career Award from the Thrasher Research Fund and published earlier this year in Clinical Microbiology and Infection. It analyzed outcomes of mother and infant colonization during pregnancy and the perinatal period with extended-spectrum beta-lactamase-producing Enterobacteriaceae (EBSL-E). These bacteria, resistant to a wide range of antibiotics, are more common in neonatal sepsis patients in Nigeria, compared with the US, where Group B Streptococcus (GBS), E. coli, and Listeria species are most typical. “We wanted to look at vertical transmission from mom to baby at the time of delivery, doing rectovaginal cultures on Mom and then doing surface cultures on baby within the first 15 minutes of life. Then we followed those babies through the first month of life to look at their outcomes. We found out that babies whose moms were colonized were more likely to be colonized, and babies who were colonized were more likely to have mortality.”
“What it leads to next is a whole host of questions,” remarked Dr. Neemann, including, “Does the timing of maternal ESBL-E rectovaginal colonization impact neonatal outcomes?” Experience with GBS in the US has shown that when a mother has a positive screening test at 37 weeks gestation, then maternal prophylaxis at the time of delivery will decrease the risk of early-onset GBS. “So, can we potentially do something similar with ESBL-E?" These organisms are also common agents of urinary tract infections (UTI). “We know that women with bacteriuria have increased risk of preterm birth and adverse pregnancy outcomes. Are these women experiencing bacteriuria and are they receiving appropriate therapy for diagnosed UTI? This raises important questions about mechanisms of transmission and pathogenesis of these infections. In our study, we noticed that moms who are colonized with ESBL-E have higher rates of stillbirths,” Dr. Neemann pointed out. “Is there some route for ascending infection, as has been observed with GBS? We need to start back when Mom approaches healthcare and follow her throughout pregnancy to the time of delivery and then the baby through that first month of life,” including the contribution of horizontal transmission between hospitalized infants.
Microbiome and genomic characterization of ESBL-E isolates from mothers and infants could answer a variety of critical questions about microflora and genetic determinants of transmission and neonatal sepsis. Dr. Neemann is developing an NIH mentored career development grant proposal that would support further investigations into selected questions like these. She looks forward to more opportunities to engage clinicians in Nigeria, both for research partnership and for the opportunity to exchange experiences and ideas with colleagues who practice medicine with the benefit of far fewer resources.
by Matthew Sandbulte, CHRI Grant Writer | September 18, 2019