Tag Archive for: urinary tract infection

kidneys with science images

PMA-based PCR amplifies DNA from only live bacteria in urine

kidneys with science images

The question of why urinary tract infection (UTI) symptoms can persist in some patients who have been seemingly appropriately treated with antibiotics and have negative post-antibiotic urine cultures is one that urologists have long sought to answer.

Experts at Children’s National Hospital have successfully developed propidium monoazide (PMA)-based polymerase chain reaction (PCR) methods that amplify DNA from only live bacteria in urine. The study’s results, published in Frontiers, suggest that non-PMA bound DNA from live bacteria can be present in urine, even after antibiotic treatment.

PMA has been shown to differentiate between non-viable and viable bacteria in various settings. However, its effectiveness in urine has not been previously studied.

The question of why urinary tract infection (UTI) symptoms can persist in some patients who have been seemingly appropriately treated with antibiotics and have negative post-antibiotic urine cultures is one that urologists have long sought to answer.

“One theory is that very low levels of bacteria that don’t show up on cultures may be the cause,” says Michael Hsieh, M.D., director of Transitional Urology at Children’s National and senior author of the study.

Although PCR has previously been used to try and confirm this theory, the use of this method has been criticized because PCR can amplify DNA from dead bacteria (which obviously don’t cause UTI).

The authors developed a PCR test that selectively detects DNA from live bacteria. In a preclinical setting, results show that with the use of antibiotics, cultures collected can be negative but urine can contain DNA from live bacteria, as detected using the PCR test.

“We think something similar can occur in patients and we show some data in the paper confirming the PCR test can work with patient samples,” Dr. Hsieh adds. “I’m excited that we might finally have an explanation as to why some patients have persistent UTI symptoms after antibiotic treatment.”

Namely, he adds, that these patients still have a UTI. This may lead to better follow-up management of patients with UTI. The next step is to confirm the theory in patients.

Hans Pohl

Q&A with Hans Pohl, M.D., on the future of pediatric urology

Hans Pohl

Hans Pohl, Division Chief, Urology

The Urology team at Children’s National Hospital is led by Hans Pohl, M.D., and includes seven other fellowship-trained pediatric urologists and three nurse practitioners. Dr. Pohl has experience in treating patients with spina bifida and bladder exstrophy, in addition to the other more common diagnoses and in using laparoscopy to perform surgery through minimally invasive techniques.

Here, Dr. Pohl tells us more about the department he is leading and what it means for the future of pediatric urology patients at Children’s National.

What excites you most about current research in the field of urology?

The most cutting-edge research these days pertains to understanding the complex and diverse role played by bacteria in the urinary tract. We previously thought the urinary tract is sterile but that turns out to not be the case. Just like the friendly bacteria living in our bodies, there are bacteria that live within our urinary tracts. It is thought that when the normal function of the urinary tract is disrupted, the balance of healthy to unhealthy bacteria is disrupted. Our faculty at the Children’s National Urology Division are looking at urinary tract infection (UTI) from various aspects. Michael Hsieh, M.D., is investigating the role of bacteria in causing inflammation; Daniel Casella, M.D., has investigated how a drug called varenicline might reduce inflammation in infected kidneys; and Briony Varda, M.D., will be investigating the socioeconomic factors affecting how people living with spina bifida manage their urinary tracts and UTIs. By looking at UTIs at all levels from bacteria factors to host factors to treatment we will understand better how to reduce the impact of a very common problem on human beings.

What are some of the most valuable changes or advancements for the program you hope to see in the next couple of years?

I believe that our next step in program evolution will focus on improving the quality of life of children with urination abnormalities and UTIs. Everyone has experienced that their child has urinary symptoms at some point during childhood, some also have UTIs. Pediatric urologists have learned that normal lower urinary tract function is critically important in reducing a child’s risk for a UTI. Even if a child does not have UTIs, there can be significant social stigma amongst a child’s peers when loss of urine control happens.

What makes the Urology Division at Children’s National unique from other programs in the country?

We have grown considerably over the past several years, adding to our faculty surgeons with complimentary skills outside of the operating room. For instance, we have pediatric urologists who are also basic scientists, translational scientists, systems scientists, a clinical informaticist and minimally invasive surgeons. These varied qualities create a dynamic group of people who bring diverse perspectives to treating patients’ problems and generating creative solutions. We believe that our democratic process of complex care management where all surgeons can openly think about how to optimize patient management is unique. Patients don’t get one opinion from their surgeon, they get ten.

Illustration of Bifidobacterium

Probiotic use in pediatric medicine

Illustration of Bifidobacterium

Probiotics have received significant attention within both the scientific and lay communities for their potential health-promoting properties, including the treatment or prevention of various conditions in children.

In a recent article published by Pediatric Research, Michael Hsieh, M.D., Ph.D., director of Transitional Urology at Children’s National Hospital, and other experts review the published data on use of specific probiotic strains for three common pediatric conditions: the prevention of urinary tract infections and antibiotic-associated diarrhea and the treatment of atopic dermatitis.

schistosome

Parasite-derived molecule could accelerate recovery from UTI

schistosome

Eggs from S. haematobium may produce the molecule IPSE to reduce the immune response against them, which happens to dampen UTI-induced bladder inflammation.

IPSE, a urogenital parasite-derived immunomodulatory molecule, can suppress bladder pathogenesis and anti-microbial peptide gene expression in bacterial urinary tract infection (UTI) according to a new study led by Michael Hsieh, Ph.D., director of Transitional Urology at Children’s National Hospital.

Half of all girls and women, and about 5% of boys and men, will have at least one urinary tract infection (UTI) in their lifetimes.

“Although antibiotics are very helpful for these infections, there are concerns that overuse of antibiotics may contribute to antibiotic-resistant infections,” Dr. Hsieh said. “There are also concerns that antibiotic therapy for UTI does not uniformly resolve infection-induced or inflammation-associated symptoms quickly.”

Parasitic infections are often associated with bacterial co-infections for unclear reasons. This may be true for urogenital schistosomiasis (caused by Schistosoma haematobium infection) and bacterial urinary tract co-infection (UTI), the study noted. Dr. Hsieh and other leading experts previously reported that this co-infection is facilitated by S. haematobium eggs triggering interleukin-4 (IL-4) production and sought to dissect the underlying mechanisms.

“Despite S. haematobium’s ability to make hosts more susceptible to UTI, we have identified IPSE, a bladder parasite protein, as a potential anti-inflammatory agent to accelerate recovery from UTI,” Dr. Hsieh explained. “S. haematobium eggs may produce IPSE to reduce the immune response against them, which happens to dampen UTI-induced bladder inflammation. It may be possible to develop IPSE as novel therapeutic to accelerate recovery from UTI.”

The study’s data showed that IPSE may play a major role in S. haematobium-associated urinary tract co-infection, although in an unexpected way. The study’s findings also indicated that IPSE either works in concert with other IL-4 -inducing factors to increase susceptibility of S. haematobium-infected hosts to bacterial co-infection or does not contribute to enchaining vulnerability to this co-infection.

You can find the full study published in Parasites and Vectors. Learn more about the Children’s National Department of Urology.

Billie Lou Short and Kurt Newman at Research and Education Week

Research and Education Week honors innovative science

Billie Lou Short and Kurt Newman at Research and Education Week

Billie Lou Short, M.D., received the Ninth Annual Mentorship Award in Clinical Science.

People joke that Billie Lou Short, M.D., chief of Children’s Division of Neonatology, invented extracorporeal membrane oxygenation, known as ECMO for short. While Dr. Short did not invent ECMO, under her leadership Children’s National was the first pediatric hospital to use it. And over decades Children’s staff have perfected its use to save the lives of tiny, vulnerable newborns by temporarily taking over for their struggling hearts and lungs. For two consecutive years, Children’s neonatal intensive care unit has been named the nation’s No. 1 for newborns by U.S. News & World Report. “Despite all of these accomplishments, Dr. Short’s best legacy is what she has done as a mentor to countless trainees, nurses and faculty she’s touched during their careers. She touches every type of clinical staff member who has come through our neonatal intensive care unit,” says An Massaro, M.D., director of residency research.

For these achievements, Dr. Short received the Ninth Annual Mentorship Award in Clinical Science.

Anna Penn, M.D., Ph.D., has provided new insights into the central role that the placental hormone allopregnanolone plays in orderly fetal brain development, and her research team has created novel experimental models that mimic some of the brain injuries often seen in very preterm babies – an essential step that informs future neuroprotective strategies. Dr. Penn, a clinical neonatologist and developmental neuroscientist, “has been a primary adviser for 40 mentees throughout their careers and embodies Children’s core values of Compassion, Commitment and Connection,” says Claire-Marie Vacher, Ph.D.

For these achievements, Dr. Penn was selected to receive the Ninth Annual Mentorship Award in Basic and Translational Science.

The mentorship awards for Drs. Short and Penn were among dozens of honors given in conjunction with “Frontiers in Innovation,” the Ninth Annual Research and Education Week (REW) at Children’s National. In addition to seven keynote lectures, more than 350 posters were submitted from researchers – from high-school students to full-time faculty – about basic and translational science, clinical research, community-based research, education, training and quality improvement; five poster presenters were showcased via Facebook Live events hosted by Children’s Hospital Foundation.

Two faculty members won twice: Vicki Freedenberg, Ph.D., APRN, for research about mindfulness-based stress reduction and Adeline (Wei Li) Koay, MBBS, MSc, for research related to HIV. So many women at every stage of their research careers took to the stage to accept honors that Naomi L.C. Luban, M.D., Vice Chair of Academic Affairs, quipped that “this day is power to women.”

Here are the 2019 REW award winners:

2019 Elda Y. Arce Teaching Scholars Award
Barbara Jantausch, M.D.
Lowell Frank, M.D.

Suzanne Feetham, Ph.D., FAA, Nursing Research Support Award
Vicki Freedenberg, Ph.D., APRN, for “Psychosocial and biological effects of mindfulness-based stress reduction intervention in adolescents with CHD/CIEDs: a randomized control trial”
Renee’ Roberts Turner for “Peak and nadir experiences of mid-level nurse leaders”

2019-2020 Global Health Initiative Exploration in Global Health Awards
Nathalie Quion, M.D., for “Latino youth and families need assessment,” conducted in Washington
Sonia Voleti for “Handheld ultrasound machine task shifting,” conducted in Micronesia
Tania Ahluwalia, M.D., for “Simulation curriculum for emergency medicine,” conducted in India
Yvonne Yui for “Designated resuscitation teams in NICUs,” conducted in Ghana
Xiaoyan Song, Ph.D., MBBS, MSc, “Prevention of hospital-onset infections in PICUs,” conducted in China

Ninth Annual Research and Education Week Poster Session Awards

Basic and Translational Science
Faculty: Adeline (Wei Li) Koay, MBBS, MSc, for “Differences in the gut microbiome of HIV-infected versus HIV-exposed, uninfected infants”
Faculty: Hayk Barseghyan, Ph.D., for “Composite de novo Armenian human genome assembly and haplotyping via optical mapping and ultra-long read sequencing”
Staff: Damon K. McCullough, BS, for “Brain slicer: 3D-printed tissue processing tool for pediatric neuroscience research”
Staff: Antonio R. Porras, Ph.D., for “Integrated deep-learning method for genetic syndrome screening using facial photographs”
Post docs/fellows/residents: Lung Lau, M.D., for “A novel, sprayable and bio-absorbable sealant for wound dressings”
Post docs/fellows/residents: Kelsey F. Sugrue, Ph.D., for “HECTD1 is required for growth of the myocardium secondary to placental insufficiency”
Graduate students: Erin R. Bonner, BA, for “Comprehensive mutation profiling of pediatric diffuse midline gliomas using liquid biopsy”
High school/undergraduate students: Ali Sarhan for “Parental somato-gonadal mosaic genetic variants are a source of recurrent risk for de novo disorders and parental health concerns: a systematic review of the literature and meta-analysis”

Clinical Research
Faculty: Amy Hont, M.D., for “Ex vivo expanded multi-tumor antigen specific T-cells for the treatment of solid tumors”
Faculty: Lauren McLaughlin, M.D., for “EBV/LMP-specific T-cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation”

Staff: Iman A. Abdikarim, BA, for “Timing of allergenic food introduction among African American and Caucasian children with food allergy in the FORWARD study”
Staff: Gelina M. Sani, BS, for “Quantifying hematopoietic stem cells towards in utero gene therapy for treatment of sickle cell disease in fetal cord blood”
Post docs/fellows/residents: Amy H. Jones, M.D., for “To trach or not trach: exploration of parental conflict, regret and impacts on quality of life in tracheostomy decision-making”
Graduate students: Alyssa Dewyer, BS, for “Telemedicine support of cardiac care in Northern Uganda: leveraging hand-held echocardiography and task-shifting”
Graduate students: Natalie Pudalov, BA, “Cortical thickness asymmetries in MRI-abnormal pediatric epilepsy patients: a potential metric for surgery outcome”
High school/undergraduate students: Kia Yoshinaga for “Time to rhythm detection during pediatric cardiac arrest in a pediatric emergency department”

Community-Based Research
Faculty: Adeline (Wei Li) Koay, MBBS, MSc, for “Recent trends in the prevention of mother-to-child transmission (PMTCT) of HIV in the Washington, D.C., metropolitan area”
Staff: Gia M. Badolato, MPH, for “STI screening in an urban ED based on chief complaint”
Post docs/fellows/residents: Christina P. Ho, M.D., for “Pediatric urinary tract infection resistance patterns in the Washington, D.C., metropolitan area”
Graduate students: Noushine Sadeghi, BS, “Racial/ethnic disparities in receipt of sexual health services among adolescent females”

Education, Training and Program Development
Faculty: Cara Lichtenstein, M.D., MPH, for “Using a community bus trip to increase knowledge of health disparities”
Staff: Iana Y. Clarence, MPH, for “TEACHing residents to address child poverty: an innovative multimodal curriculum”
Post docs/fellows/residents: Johanna Kaufman, M.D., for “Inpatient consultation in pediatrics: a learning tool to improve communication”
High school/undergraduate students: Brett E. Pearson for “Analysis of unanticipated problems in CNMC human subjects research studies and implications for process improvement”

Quality and Performance Improvement
Faculty: Vicki Freedenberg, Ph.D., APRN, for “Implementing a mindfulness-based stress reduction curriculum in a congenital heart disease program”
Staff: Caleb Griffith, MPH, for “Assessing the sustainability of point-of-care HIV screening of adolescents in pediatric emergency departments”
Post docs/fellows/residents: Rebecca S. Zee, M.D., Ph.D., for “Implementation of the Accelerated Care of Torsion (ACT) pathway: a quality improvement initiative for testicular torsion”
Graduate students: Alysia Wiener, BS, for “Latency period in image-guided needle bone biopsy in children: a single center experience”

View images from the REW2019 award ceremony.

Staphylococcus

How our bladder’s microbiota affect health

Staphylococcus

The presence of bacteria such as Staphylococcus in the urine is linked to the incidence and severity of urge urinary incontinence as well as treatment success.

About half of the cells in our bodies aren’t really “ours” at all. They’re the microbiota: The vast array of microorganisms that live in our gut, skin, oral cavity and other places. Decades ago, researchers thought that these organisms simply happened to colonize these areas, playing only a tangential role in health, for example, helping to break down food in the intestines or causing cavities. More recent work has revealed the incredibly complex role they play in diseases ranging from diabetes and schizophrenia.

The bladder is no exception. Just a single decade ago, the bladder was thought to be a sterile environment. But that view has shifted radically, with more sensitive cultivation methods and precise 16S rRNA gene-sequencing techniques revealing a significant bladder microbiome that could have an enormous impact on pediatric urologic diseases. These findings have opened brand new fields of research aimed at clarifying the role that the bladder’s microbiome plays in common urological diseases that affect children, according to a review article published online Feb. 22, 2018, by Current Urology Reports.

“There is a growing appreciation for the role of diverse bacteria in contributing to improved health as well as triggering disease processes or exacerbating illness,” says Michael H. Hsieh, M.D., Ph.D., director of the Clinic for Adolescent and Adult Pediatric Onset Urology (CAPITUL) at Children’s National Health System and study senior author. “Already, we know that probiotics and dietary modifications have the potential to play powerful roles in preventing urinary diseases that commonly occur among pediatric patients,” Dr. Hsieh says. This underscores the importance of conducting even more studies to improve our understanding and to identify new therapies for health conditions that resist current treatment options.”

The review conducted by Dr. Hsieh and co-authors highlights the effects of the microbiome on a number of urologic diseases that affect children, including:

  • Urinary tract infection A number of studies point to the association between decreased microbial diversity and the incidence of what is commonly called urinary tract infection (UTI) or “dysbiosis.” This relationship suggests that using probiotics to replace or supplement antibiotics could favorably alter the urinary microbiome. Future research will focus on the pathophysiological role of the microbiome to determine whether it can be manipulated to prevent or treat UTIs.
  • Urge urinary incontinence While data vary by study, the presence of bacteria in the urine, especially certain bacterial species – such as Gardnerella, Staphylococcus, Streptococcus, Actinomyces, Aerococcus, Corynebacterium and Oligella – are linked to the incidence and severity of urge urinary incontinence (UUI) as well as treatment success. Most studies find an association between greater genitourinary biodiversity and reduced incidence and lessened severity of UUI as well as improved treatment response. Future research will focus on further clarifying this relationship.
  • Urolithiasis Calcium oxalate stones, the most common type of kidney stone, have a microbiome that differs from the urinary microbiome leading researchers to question whether the stone’s own bacterial makeup could help to predict recurrence of future kidney stones. What’s more, Oxalobacter formigenes, a gram-negative bacterium, lowers oxalate levels in the blood and are associated with a 70 percent reduction in the risk of kidney stones forming. In an experimental model, fecal transplants with the full microbiome represented had a pronounced and persistent effect on oxalate production. Patients who receive some antibiotics often have reduced rates of formigenes colonization. However, the bacteria are resistant to amoxicillin, augmentin, ceftriaxone and vancomycin, which could point to preferential use of these antibiotics to stave off disease and ward off kidney stone formation.

Additional authors include Daniel Gerber, study lead author, The Georgetown University School of Medicine and Health Sciences; and Catherine Forster, M.D., study co-author, Children’s National.