MRSA infections kill six children with flu

Invasive infections with community strains

At least six children have died this year of invasive infections with community strains of methicillin-resistant Staphylococcus aureus (MRSA) after acquiring influenza, Hospital Infection Control has learned.

The finding surfaced after the Centers for Disease Control and Prevention (CDC) began investigating flu deaths in children. The reports are incomplete because there is no formal surveillance system for either flu deaths in children or community-acquired MRSA. However, HIC was able to confirm the six MRSA deaths and the fact that none were related to nosocomial strains of the pathogen.

"These were invasive infections that were community-associated," says Tim Ueki, MD, medical epidemiologist in the CDC influenza branch.

"Some children and adults are colonized with [MRSA], and they are carriers. It may not have any health implications for them until there is some invasive infection. I have actually heard about a few adult cases as well. You get influenza infection, and it facilitates the invasive staphylococcal bacterial infection. Primarily, that is going to [result in] pneumonia," he adds.

As of Jan. 6, 2004, the CDC had received reports of 93 fatal flu infections in children younger than 18. A total of 35 (38%) of the 93 children were reported to have had underlying chronic medical conditions. However, 41 (44%) were otherwise healthy. The medical history was unknown for 17 (18%) children.

Of the 55 children for whom the location of death was reported, 15 (27%) died at home, 12 (22%) died in emergency departments, 25 (45%) died as inpatients, and three (5%) died in transport to hospitals. Pneumonia was a reported complication in 25 of the 93 children. In addition to the aforementioned six children, invasive bacterial coinfections were reported in nine children with pathogens that include Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus sp., Haemophilus influenzae (type b and non-typable), Neisseria meningitidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Serratia marcescens.

"Secondary invasive bacterial infections [previously] have been associated with influenza virus infections," Ueki says. "But what is new is the increasing prevalence of community-acquired MRSA. We are starting to hear about more of these MRSA cases associated with influenza. [These infections] may have very bad outcomes, and can certainly result in critical illness or death."

In what proved to be a sentinel public health event in 1999, four fatal community-acquired MRSA infections occurred in otherwise healthy children with no history of previous hospitalization or other traditional risk factors for the pathogen.

While those cases were not linked to flu, they heralded the emergence of community-acquired strains of MRSA. Rather than "escaping" from their traditional hospital stronghold, the continuing cases of MRSA involve strains that have genetically acquired antibiotic resistance due to massive and often injudicious prescribing trends in the community. While little data are available regarding the flu death cases, the CDC reports that some of the recently recognized outbreaks of MRSA in communities are associated with different drug-resistance patterns and possibly increased virulence compared to hospital-based MRSA strains.

The problem is that clinicians may not suspect MRSA in the community, thereby choosing the wrong empiric antibiotic therapy and setting the patient up for treatment failure. Though that occurred in at least some of the 1999 cases, it is not known whether treatment failures led to death in the six 2003 MRSA/flu cases.

"It is always a concern, [but] we are not privy to all of the clinical details," he says. "We don’t have that information."

The CDC must rely on voluntary state and local reporting of such incidents and, in that regard, is requesting more reports of any flu deaths in children. The agency is developing studies in collaboration with health departments and other partners to estimate the rates of influenza-associated hospitalization and serious complications and to identify risk factors for severe illness and complications during the current season.

Additional studies are planned to assess the relative severity of this season compared to influenza-associated hospitalizations and mortality among children with those in previous seasons.

Such information might lead to revised pediatric influenza vaccination recommendations.

Of the 45 children whose influenza vaccination status was reported, only one child had evidence of adequate vaccination. In contrast, 33 (73%) were not vaccinated, and six children were only partially vaccinated (i.e., they had received one of two doses). Five children were reported as vaccinated, but the interval between vaccination and onset of illness was not documented.

Because young, otherwise healthy children are at increased risk for influenza-related hospitalization, influenza vaccination of healthy children ages 6-23 months continues to be encouraged when feasible. However, vaccination of children ages 6 months or older usually is more strongly recommended primarily for those with underlying medical conditions.

Clinicians should consider influenza testing in children who have severe febrile illness, when flu viruses are circulating in their local community. Clinicians should recognize that secondary conditions such as bacterial infection can complicate some cases of influenza. Susceptibility testing of bacterial isolates is important to guide appropriate antibiotic therapy, the CDC advises.

"Ninety-three children have died of flu so far this year, and that’s a very, very sad and sobering figure," said Julie Gerberding, MD, CDC director, at a recent press conference. "Because some of the children have died from complicating bacterial pneumonia, [we advise clinicians] to think about bacterial pneumonia, to test the child to make sure that the infection is sensitive to the antibiotics that would be indicated if there was a complicating pneumonia, and to be alert for drug-resistant bacteria because that has been a problem in some of the children with complicating illnesses," she added.

In addition, the CDC is emphasizing that children with chronic medical conditions are at increased risk for hospitalization and death with flu infection. "[Clinicians should] have a very low threshold of suspicion for thinking about flu in children with underlying medical conditions," Gerberding said.

The CDC is trying to stop transmission among children in schools and other public settings by launching the "Germ Stopper" campaign. (To obtain educational materials for the campaign, go to: www.cdc.gov/flu/.) The campaign urges hand hygiene and other common-sense measures to limit the spread of flu and colds in public gathering places.

"These materials are available for schools, for churches, for any venue where children gather or parents gather," Gerberding explained.

"This campaign is based on the concept that flu and colds are mainly spread through close contact, through coughing and sneezing, and through transmitting the germs on hands. So there’s a strong emphasis on that old-fashioned intervention, good hand hygiene. We’re hoping that this will just be a reminder, in schools and other public places, to take the simple steps that really do make a difference in preventing transmission of these infectious diseases," she said.

[Editor’s note: As this issue goes to press, the CDC received reports of 18 additional pediatric flu deaths, bringing the total to 111 as of Jan. 20, 2004. Possible coinfection with MRSA in any of the additional cases could not be determined at press time. In light of the cases, the CDC is asking for any clinical reports of pediatric flu deaths. To report the influenza-associated death of a child, state health departments should contact the CDC’s Influenza Branch at (800) 232-4636. E-mail: eocinfluenza@cdc.gov. Case-reporting and specimen- collection forms will be made available to state health departments and medical examiners via the Epidemic Information Exchange at www.cdc.gov/mmwr/epix/epix.html. When completed, the forms should be sent with a cover sheet headed ATTN: Fatal Case Reporting to the CDC via fax at (888) 232-1322.]