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Neisseria meningitidis bacteria

Case report highlights importance of antibiotic stewardship

Neisseria meningitidis bacteria

Neisseria meningitidis is the leading cause of bacterial meningitis in adolescents and an important cause of disease in younger children as well.

A recent meningitis case treated at Children’s National Hospital raises serious concerns about a rise in antibiotic resistance in the common bacterium that caused it, researchers from the hospital write in a case report. Their findings, published online August 3 in the Journal of the Pediatric Infectious Disease Society, could change laboratory and clinical practice across the U.S. and potentially around the globe.

Neisseria meningitidis is the leading cause of bacterial meningitis in adolescents and an important cause of disease in younger children as well, say case report authors Gillian Taormina, D.O., a third year fellow in Pediatric Infectious Diseases at Children’s National, who was on service for this recent case, and Joseph Campos, Ph.D., D(ABMM), FAAM, director of the Microbiology Laboratory and the Infectious Diseases Molecular Diagnostics Laboratory at Children’s National. As standard clinical practice in the U.S., they explain, patients who are thought to have this infection are typically treated first with the broad spectrum antibiotic ceftriaxone while they wait for a microbiology lab to identify the causative organism from blood or cerebrospinal fluid samples. Once the organism is identified as N. meningitidis, patients are typically treated with penicillin or ampicillin, antibiotics with a narrower spectrum of activity that’s less likely to lead to ceftriaxone resistance. Family members and other close contacts are often prophylactically treated with an antibiotic called ciprofloxacin.

Because N. meningitidis has historically been sensitive to these antibiotics, most laboratories do not perform tests to confirm drug susceptibility, Dr. Campos says. But the protocol at Children’s National is to screen these isolates for penicillin and ampicillin resistance with a rapid 5-minute test. The isolate from Dr. Taormina’s five-month-old patient – a previously healthy infant from Maryland who came to the Children’s National emergency room after six days of fever and congestion – yielded surprising results: N. meningitidis grown from the patient’s blood was positive for beta-lactamase, an enzyme that destroys the active component in the family of antibiotics that includes penicillin and ampicillin. This isolate was also found resistant to ciprofloxacin.

“The lab used a rapid test, and after just a few minutes, it was positive,” Dr. Campos says. “We did it again to make sure it was accurate, and the results were reproducible. That’s when we knew we needed to share this finding with the public health authorities.”

Dr. Campos, Dr. Taormina and their colleagues sent samples of the antibiotic-resistant bacteria first to the Washington, D.C. Public Health Laboratory and the Maryland Department of Health, and later to the Centers for Disease Control and Prevention (CDC). When the CDC asked other state laboratories to send their own N. meningitidis samples to be tested, 33 were positive for beta-lactamase. And like the bacterium isolated from Dr. Taormina’s patient, 11 of these were also resistant to ciprofloxacin.

“These bacteria wouldn’t have been susceptible to the common antibiotics that we would normally use for this infection,” Dr. Taormina says, “so it’s entirely possible that the infections caused by these bacteria could have been treated inappropriately if doctors used the standard protocol.”

Dr. Taormina says that her patient cleared his infection after staying on ceftriaxone, the original antibiotic he’d been prescribed, for the recommended seven days. His six family members and close contacts were prophylactically treated with rifampin instead of ciprofloxacin.

Although this case had a positive outcome, Dr. Campos says it raises the alarm for other N. meningitidis infections in the U.S., where antibiotic resistance is a growing concern. The danger is even higher in other countries, where the vaccine that children in the U.S. commonly receive for N. meningitidis at age 11 isn’t available.

In the meantime, Drs. Taormina and Campos say their case highlights the need for the appropriate use of antibiotics, known as antibiotic stewardship, which is only possible with close partnerships between infectious disease doctors and microbiology laboratories.

“Our lab and the infectious diseases service at Children’s National interact every day on cases like this to make sure we’re doing the best job we can in diagnosing and managing infections,” says Dr. Campos. “We’re a team.”

Other Children’s National authors who contributed to this case report include infectious disease specialist Benjamin Hanisch, M.D.

coronavirus

Study finds children can become seriously ill with COVID-19

coronavirus

Despite early reports suggesting COVID-19 does not seriously impact children, a new study shows that children who contract COVID-19 can become very ill.

In contrast to the prevailing view that the novel coronavirus known as COVID-19 does not seriously impact children, a new study finds that children who contract the virus can become very ill—many of them critically so, according to physician researchers at Children’s National Hospital. Their results, published in the Journal of Pediatrics and among the first reports from a U.S. institution caring for children and young adults, shows differences in the characteristics of children who recovered at home, were hospitalized, or who required life support measures. These findings highlight the spectrum of illness in children, and could help doctors and parents better predict which pediatric patients are more likely to become severely ill as a consequence of the virus.

In late 2019, researchers identified a new coronavirus, known as SARS-CoV-2, which causes COVID-19. As the disease spread around the world, the vast majority of reports suggested that elderly patients bear the vast majority of the disease burden and that children are at less risk for either infection or severe disease. However, study leader Roberta DeBiasi, M.D., M.S., chief of the Division of Infectious Diseases at Children’s National, states that she and her colleagues began noticing an influx of children coming to the hospital for evaluation of a range of symptoms starting in mid-March 2020, who were tested and determined to be infected with COVID-19. One quarter of these children required hospitalization or life support.

“It was very apparent to us within the first several weeks of the epidemic that this was a very different situation than our colleagues on the West Coast of the US had described as their experience just weeks before,” DeBiasi says. “Right away, we knew that it was important for us to not only care for these sick children, but to examine the factors causing severe disease, and warn others who provide medical care to children.”

To better understand this phenomenon, she and her colleagues examined the medical records of symptomatic children and young adults who sought treatment at Children’s National for COVID-19 between March 15 and April 30, 2020. Each of these 177 children tested positive using a rapid assay to detect SARS-CoV-2 performed at the hospital. The researchers gathered data on each patient, including demographic details such as age and sex; their symptoms; whether they had any underlying medical conditions; and whether these patients were non-hospitalized, hospitalized, or required critical care.

The results of their analysis show that there was about an even split of male and female patients who tested positive for COVID-19 at Children’s National during this time period. About 25% of these patients required hospitalization. Of those hospitalized, about 75% weren’t considered critically ill and about 25% required life support measures. These included supplemental oxygen delivered by intubation and mechanical ventilation, BiPAP, or high-flow nasal cannula – all treatments that support breathing – as well as other support measures such as dialysis, blood pressure support and medications to treat infection as well as inflammation.

Although patients who were hospitalized spanned the entire age range, more than half of them were either under a year old or more than 15 years old. The children and young adults over 15 years of age, Dr. DeBiasi explains, were more likely to require critical care.

About 39% of all COVID-19 patients had underlying medical conditions, including asthma, which has been highlighted as a risk factor for worse outcomes with this infection. However, DeBiasi says, although underlying conditions were more common as a whole in hospitalized patients – present in about two thirds of hospitalized and 80% of critically ill – asthma didn’t increase the risk of hospitalization or critical illness. On the other hand, children with underlying neurological conditions, such as cerebral palsy, microcephaly, or global developmental delay, as well as those with underlying cardiac, hematologic, or oncologic conditions were significantly more likely to require hospitalization.

In addition, although early reports of COVID-19 suggested that fever and respiratory symptoms are hallmarks of this infection, Dr. DeBiasi and her colleagues found that fewer than half of patients had both concurrently. Those with mild, upper respiratory symptoms, such as runny nose, congestion, and cough were less likely to end up hospitalized than those with more severe respiratory symptoms, such as shortness of breath. The frequency of other symptoms including diarrhea, chest pain and loss of sense of smell or taste was similar among hospitalized and non-hospitalized patients.

Dr. DeBiasi notes that although other East Coast hospitals are anecdotally reporting similar upticks in pediatric COVID-19 patients who become seriously ill, it’s currently unclear what factors might account for differences from the less frequent and milder pediatric illness on the West Coast. Some factors might include a higher East Coast population density, differences between the genetic, racial and ethnic makeup of the two populations, or differences between the viral strains circulating in both regions (an Asian strain on the West Coast, and a European strain on the East Coast).

Regardless, she says, the good news is that the more researchers learn about this viral illness, the better prepared parents, medical personnel and hospitals will be to deal with this ongoing threat.

Other researchers from Children’s National who participated in this study include Xiaoyan Song, Ph.D., M.Sc.Meghan Delaney, D.O., M.P.H.Michael Bell, M.D. Karen Smith, M.D.Jay Pershad, M.D., Emily Ansusinha, Andrea Hahn, M.D., M.S., Rana Hamdy, M.D., M.P.H., MSCE, Nada Harik, M.D.Benjamin Hanisch, M.D.Barbara Jantausch, M.D.Adeline Koay, MBBS, MS.c., Robin Steinhorn, Kurt Newman, M.D. and David Wessel, M.D.