C . diff epidemic strikes pediatric population, greatly increasing risk of death in children

Infections more than double in a decade

By Gary Evans, Senior Managing Editor

The national epidemic of Clostridium difficile is moving into the pediatric population, causing infections in children that prolong hospitalizations, increase morbidity and spell a striking increase in the risk of death.

Cade Nylund"If kids get C. diff they are more likely to die," says Cade Nylund, MD, an assistant professor of pediatrics at the Uniformed Services University of the Health Sciences in Bethesda, MD. "They are more likely to require surgery. They are going to be having more complicated courses and stay longer in the hospital."

Nylund and colleagues analyzed national hospital discharge data using the national Healthcare Cost and Utilization Project Kids' Inpatient Database for the years 1997, 2000, 2003, and 2006.1 The researchers reviewed records of more than 10.5 million patients, of whom 21,274 (0.2%) had C. diff infection (CDI).

They found that the number of cases of CDI in children increased by 15% each year, from 3,565 in 1997 to 7,779 in 2006 — which means incidence more than doubled in a decade. Some children appeared more likely to become infected, including those with inflammatory bowel disease, organ transplant or cancer. The risk of infection was also higher among those who were white, lived in the West or in urban areas, or had private insurance. That suggests exposure to antibiotics — a classic trigger for CDI — could be driving the trend, though emerging virulent strains of the spore-forming bacteria may be a bigger factor.

In particular, emerging CDI in kids is increasing in part due to the continuing spread of the same highly virulent bug that is vexing adult patients: the North American Pulse Field type 1 (NAP1) strain.

"I think personally it is coming into play," Nylund says, though noting his study did not include strain typing. "There was a different study that showed the prevalence of NAP1 in children [with CDI] is actually relatively high — almost 20%.2 I do think that is part of the reason we are seeing an increase in C. diff in children."

The NAP1 strain secretes toxins and is resistant to both fluoroquinolones and third-generation cephalosporins, factors that add to virulence in any given infection and may enhance transmissibility. Making matters worse, there actually may be several other hyper-virulent strains of C. diff.

CDC verifies increase

"We analyzed some of the same data ourselves and saw a similar type of increase [in pediatric patients]," says L. Clifford McDonald, MD, FACP, a leading C. diff expert in the CDC's division of healthcare quality promotion. "The NAP1 strain is certainly one thing, but there may also be several more virulent strains. The other possibility is a change in antibiotic prescriptions, which is certainly a major risk factor in adults."

L. Clifford McDonaldIn Nylund's study, the risk of infection was lower among black or Hispanic children, those who lived in the South, those admitted to rural hospitals, those with Medicaid/Medicare insurance and those who had self-pay or no-pay insurance status. Asked if those findings could be surrogate markers for limited access to antibiotics, Nylund says: "That would be my hypothesis. I can't prove that in my study, but that is exactly what my thinking would be."

In terms of transmission, the longstanding view that CDI is predominantly a hospital phenomenon is being rethought as more cases arise in the community.

"It could have been acquired outpatient or inpatient in the hospital," Nylund says. "It's actually increasing in the community. It's possible that some of these patients acquired it as outpatients. There are several patients I see clinically who have never been in the hospital but have C. diff."

Overall, children with CDI had a greater likelihood of death, colectomy, longer length of hospital stay, and higher hospitalization charges than those without CDI.

"When pediatric patients are finally hospitalized they tend to be more complex and more susceptible to infections like C. diff," Nylund says. "At the same time, the patients, especially hospitalized children, are less able to fend off the serious effects of these infections, making them more likely to die."

The findings remained statistically significant even after controlling for CDI comorbid conditions associated with the severity outcomes, patient-level demographic variables, and a high-dimensional propensity score associated with acquiring CDI.

"So when we controlled for other diagnoses associated with death we still had an increase risk of death," he says. "Among those without C. diff it ranges from 2.9% to 3.7% and those with C. diff the mortality rate is 16.8% to 23.6%. It's a drastic increase."

Mild disease may be missed

Though the data underscore that CDI can be fatal in pediatrics, there is also a broad spectrum of disease so mild it may go undiagnosed in children, he noted. While the overall increase to some extent mirrors the well-documented upsurge of CDI in the adult population, there are distinct challenges presented by CDI in children.

"One thing in particular is that children don't tend to have as severe disease as adults," he says. "They can just have a little bit of non-bloody diarrhea, but it can be C. diff. In adults you have severe colitis, fevers, bloody stools. In children, you have milder symptoms, but it's still C. diff. In my opinion, it's under-recognized. "

That may be the case because pediatric clinicians have not typically dealt with CDI at this level.

"I think what's happening is that because C. diff is increasing overall in everyone, now pediatricians are seeing more," McDonald says. "Pediatricians who used to never see C. diff — never had any experience with it — now are seeing it. And that can be a challenge for them."

In general, the infection control principles are the same in the pediatric and adult patient populations, he adds. "The two big principles are to reduce unnecessary antibiotic use and prevent transmission," McDonald says. "But how those principals are applied may be different because the settings where these antibiotic exposures and transmissions are occurring are a little different."

Two of Nylund's major take-home points are to heighten suspicion for CDI in pediatric patients and not to rely on alcohol hand gels to interrupt transmission.

"We should absolutely increase our awareness and testing of it," Nylund says. "Also, in my opinion, if [any] patient has diarrhea, you should be washing your hands with soap and water. The alcohol rubs don't kill the C. diff spores."

Though many hospitals have long since switched over from soap to alcohol for most patient encounters, the Centers for Disease Control and Prevention endorsed the 2008 compendium guidelines that in an outbreak situation or in dealing with continuing C. diff transmission, health care workers should "perform hand hygiene with soap and water preferentially, instead of alcohol hand hygiene products."3 More to Nylund's point, however, some hospitals are going to soap and water for even a single CDI case.

Donna Peace Indeed, several pediatric hospitals in Atlanta have devised new isolation signs to cue workers to use soap and water with C. diff — while preserving patient privacy about the diagnosis, says Donna Peace, RN, CPHQ, CIC, an epidemiologist at Children's Healthcare of Atlanta.

"We created a sign that says: 'Contact Precautions: Hand washing is required,'" she says. "That is just a visual cue for our staff to know they can't use the alcohol."

The hand washing reminder is not included in other isolation signs, meaning, for example, that staff know it is safe to use the alcohol hand rubs with a patient with MRSA. Failure to wash hands with soap and water may have contributed to transmission of C. diff in one instance, she tells Hospital Infection Control and Prevention.

"We found an individual who did not realize that they could not use the alcohol foam with a C. diff [patient]," she says. "They were foaming, but for whatever reason did not put two and two together [to use soap and water]. We were able to do some education and some targeted cleaning and prevented a potentially huge problem. I think the biggest thing we do on any thing like this is education."

Though she emphasizes that her program is preventing CDI successfully, Peace dreads the thought of a single hospital-associated case. "The ones that really scare me are when we know it's health care acquired," she says. "The child is a week into the visit and they develop C. diff. And I know it occurred because of something we did or didn't do."

'Kids need to socialize'

In general, infection control in pediatrics presents some unique challenges, whether the pathogen is C. diff or some other bug.

"Kids need to socialize, so we have a mechanism in place — with certain ground rules — to allow children with various types of isolation including C. diff to get out and about," Peace says. "Adults can talk on the phone. With kids, their socialization is through play. It does make it a little bit more difficult for children to stay in isolation."

Children that come out of isolation are confined to a wagon which is covered with a sheet or blanket so they can be wheeled out to the hospital Koi ponds and see the elaborate entrance-way murals, she says. The wagons are then thoroughly cleaned and the covering material laundered.

"If a kid who has C. diff is not having profusive diarrhea we might let them go into a specific play area — by themselves or with their siblings — then clean very thoroughly after that," she says. "The bottom line is that most of the time the siblings either have the C. diff or the MRSA or whatever else. They have already been exposed at home, but they are not sick and more than likely it will not make them ill. But again, we have to tailor things for children considerably different than we do for an adult population."

In that regard, environmental services does not use bleach to clean rooms of patients because it may cause respiratory problems for children with asthma. The hospital uses alternative non-bleach products and is not having any problems with environmental contamination, says Peace, chair of the pediatric committee at the Association for Professionals in Infection Control and Epidemiology.

"The CDC recommends using bleach only in an outbreak situation," she says. "Bleach is very hard on equipment, it pits surfaces. And on top of that, from a pediatric standpoint, there are a lot of kids with asthma. If you use a lot of bleach it is very difficult — it's a very strong bleach smell. Our numbers support the fact that what we are doing is efficacious."

References

  1. Nylund CM, Goudie A, Garza JM, et al. Clostridium difficile Infection in Hospitalized Children in the United States. Arch Pediatr Adolesc Med. Published online January 3, 2011. doi:10.1001/archpediatrics.2010.282
  2. Toltzis P, Kim J, Dul M, et al. Presence of the epidemic North American Pulsed Field type 1 Clostridium difficile strain in hospitalized children. Jrl Pediatr. 2009;154:607-608.
  3. Society for Healthcare Epidemiology of America. Infectious Disease Society of America. Compendium of Strategies to Prevent Healthcare Associated Infections in Acute Care Hospitals. Infect Control Hosp Epidemiol. 2008;29:S81–S92.