Fatal infections signal drug-resistant staph is now a threat in communities

The era of antibiotic resistance being just a nosocomial problem is over’

Methicillin-resistant Staphylococcus aureus — a pathogen that has bedeviled infection control professionals for decades while rarely posing a public health threat beyond the hospital — is now emerging in distinctly different community-acquired strains that are susceptible to more antibiotics but may be more efficiently transmitted than their nosocomial counterparts. Four fatal cases and hundreds of less severe infections have been reported in the upper Midwest over the past two years, signaling that community-acquired MRSA may well be on the rise nationally, investigators tell Hospital Infection Control.

In what may prove to be a sentinel public health event, the Centers for Disease Control and Prevention and state investigators in Minnesota and North Dakota recently reported the four fatal community-acquired infections occurred in otherwise healthy children with no history of previous hospitalization or other traditional risk factors for MRSA.¹ (See case reports, p. 127.) Rather than "escaping" from their traditional hospital stronghold, the new community strains of MRSA are likely caused by person-to-person transmission of staph strains that have genetically acquired antibiotic resistance due to massive and often injudicious prescribing trends among pediatric outpatients, investigators theorize. (See related story, p. 130.)

"The era of antibiotic resistance being just a nosocomial problem is over," says Michael Osterholm, PhD, MPH, a senior investigator in the case and the former state epidemiologist at the Minnesota Department of Health in Minneapolis. "This is, in my mind, the final nail in the coffin. We are all starting to realize that there is significant antibiotic pressure out there to make this happen. Outpatient antibiotic use today is so substantial that it is not surprising that we are seeing this."

In addition, the diverse demographics of the four fatal cases, coupled with the number of less severe cases, suggest that MRSA is getting widely established in the upper Midwest and may be emerging in other communities, says Osterholm, now CEO of the Infection Control Advisory Network, Inc., in Eden Prairie, MN.

"While there were four deaths, we now have over 300 cases in Minnesota of MRSA that clearly are community-acquired," says Osterholm. "One of the reasons that the four deaths themselves are important is because they represent white, black, and Native American children. They represent urban and rural and different areas in the upper Midwest. This is apparently throughout much of the upper Midwest right now. It very well may be present throughout much of the country, but it is just not recognized."

Investigators find the lines of evidence compelling for true community-acquired MRSA, citing such factors as the distinct antibiotic susceptibility profile of the pathogen when compared to nosocomial strains. Particularly concerning in the four deaths was the absence of risk factors for MRSA infection (i.e., recent hospitalization, recent surgery, residence in a long-term-care facility, or injecting drug use).

"To my knowledge, there isn’t anything in the medical literature that describes cases like these," says J. Todd Weber, MD, a senior medical officer in the CDC’s center for infectious diseases. "These were kids that just had no risk factors for these infections."

In addition to the four fatal pediatric infections, the less severe cases are also primarily occurring in children and young adults — the same group typically infected with methicillin-susceptible community staph strains, adds Timothy Naimi, MD, lead investigator in the case and a CDC epidemic intelligence service officer at the Minnesota Department of Health.

"They tend to mostly cause skin infections in healthy young kids and young adults," he says. "Hospital strains — even in pediatric hospitals — don’t tend to cause those types of infections."

Strains appear more easily transmitted

There also is concern that the novel MRSA strains may be more efficiently transmitted in the community than nosocomial strains, which have been infecting hospital patients for some 30 years without emerging as a threat to the public.

"It appears, at least circumstantially anyway, that these community organisms, while they are not multiresistant like some of these hospital strains, may be more transmissible," Naimi says. "But that remains to be seen."

While nosocomial MRSA strains certainly pose a threat to sick patients, it is possible they lose some aspect of transmissibility in the community because they are struggling to develop resistance to the wide array of antibiotics used in a hospital, he theorizes. "Bacteria have a certain amount of genetic potential, and if you are putting all of your effort into carrying every antibiotic resistance gene under the sun, you may lose something in terms of adherence and virulence," he says. "We need to characterize whether these [community] strains are more sticky,’ if you will."

While the investigation noted that no family members of the four cases worked in health care facilities, the traumatized relatives of the deceased patients were not sought out for culturing as part of the investigation, Naimi confirms. Thus, clear lines of transmission were not established, though the sibling of case No. 4 had a previous culture-confirmed MRSA infection with the same antibiotic susceptibility profile. "The traditional MRSA risk factors did not apply in these cases," he says. "Personally, we feel it is not whether you have been in the hospital or not, but what is your mom and dad and brother and sister colonized with?"

In addition, a continuing aspect of the CDC investigation in the upper Midwest is assessing whether children in day care centers are at increased risk for community-acquired MRSA, Naimi says. In that regard, a case of day care transmission of community MRSA was recently reported by Canadian investigators in Toronto.²

Given such concerns, it is important to remember that the community staph strains — while they are resistant to the beta-lactam class of antibiotics for which methicillin has become the common marker — are still treatable by a wide range of other commonly used antibiotics, Naimi adds. (See chart, p. 127.) "I think the main issues are for the practicing primary care physicians," he says. "I am concerned that over time, MRSA will become an increasing percentage of all staph infections among healthy outpatients. And that will have a lot of practical implications for treatment of outpatient infections."

Indeed, the cases raise important diagnostic and antibiotic treatment questions because clinicians who do not suspect community-acquired MRSA may prescribe ineffective empiric regimens, a factor that likely contributed to at least some of the fatal infections, investigators report. By the same token, officials also are concerned that the cases may now spur inappropriate use of vancomycin, contributing to emerging staph resistance to the most steadfast weapon against MRSA of any variety. (See related story, p. 131.)

"We need to have better diagnostic tests — things that can come back more rapidly than a culture test, which takes two days — so the physician can be armed with the information at the bedside," Naimi says. "That will not only allow him to use the proper antibiotic before the culture results come back, but will enable him to use the antibiotic with the smallest possible spectrum. So you don’t end up using a howitzer on a field mouse."

Out there and circulating

If the origin of the Midwest community MRSA strains is linked to antibiotic use in outpatients, it would certainly follow that other strains could be arising in other regions under similar antimicrobial pressures. Indeed, community-acquired MRSA is certainly not unheard of. Other studies have noted apparent increases in community-acquired MRSA in children, but skeptics have questioned whether some of the cases were actually nosocomial in origin, given that MRSA colonization has been shown to last up to three years.^3,4

Historically, community-acquired cases primarily have been restricted to intravenous drug users and residents of long-term care facilities, the CDC reports. However, both of those groups have extensive exposure to hospitals, and their infections generally are ascribed to nosocomial MRSA strains. More recently, however, community-acquired MRSA infections have also been identified in day care centers — in addition to the aforementioned case — and among minority communities in other countries.^5-7

While such reports point to an emerging pathogen, the CDC has no national surveillance system for community-acquired MRSA, and the most recent cases were primarily found because Minnesota and North Dakota have stepped up efforts to document them since 1996. "I’m not sure it is confined there; I think they have looked harder," Weber says. "Other states, now that they are seeing these reports, may also start to look hard for some of these cases. I would be very surprised if it wasn’t elsewhere in the country. Further studies will show us how widespread it is."

Rather than a national system, the CDC is emphasizing that local and state-based surveillance is needed to characterize and monitor community-acquired MRSA infections. CDC funding also has been requested to establish a sentinel surveillance network in Minnesota to better define the prevalence and epidemiology of the new strains, Naimi says. In addition to the two states reported, health officials have been apprised of similar cases in Nebraska and Illinois, he adds.

William Schaffner, MD, chairman of the department of preventive medicine at Vanderbilt University School of Medicine in Nashville, says clinicians are reporting some community-acquired MRSA cases in his area, though more often in adults than in pediatric patients. Schaffner says he also is hearing anecdotal reports of community-acquired cases from colleagues and via e-mail postings on infectious disease Web sites.

"Folks are seeing these around the country, but you might well ask, how carefully have these [patients] really been investigated to make sure that they don’t have some indirect association with the health care system or hospitalization?" he says. However, the lack of such risk factors in the recent Midwest cases suggests that in certain communities, MRSA is now slowly becoming part of the normal pathogenic flora, he adds. "It is being passed around — transmitted from person to person — and it can cause community-acquired infections in people who have had no direct contact with the health care system," Schaffner says. "That’s got to mean that it is out there and circulating."

In addition to case surveillance, ICPs experienced with MRSA can play important roles in educating the public. (See handout, p. 132.) In particular, heightened public education about basic infection control measures (i.e., hand washing) that have long proven effective against antibiotic-resistant pathogens may be one of the most important aspects to come out of the case, says Fran Slater, RN, MBA, CIC, CPHQ, manager of infection prevention and control at Methodist Hospital in Houston and an expert consultant to a recently formed federal task force on antibiotic resistance.

"The [public] needs to follow the fundamentals as far as infection control practices are concerned, particularly if they are going to be taking care of a family member who may be immunocompromised," Slater says. "This is bringing to the forefront something we have suspected would occur all along. We have an opportunity here to teach the public, to make them understand that MRSA is not confined to the hospital. It is a wake-up call for us. We need to get beyond these walls and get out there where the bugs are."

Indeed, if community-acquired MRSA begins emerging nationally, it will be important for ICPs, physicians, and public health officials to work together across the health care continuum to reduce inappropriate antibiotic use and reinforce infection control measures to prevent the pathogen from establishing a persistent presence in communities similar to the endemic foothold it has gained in many of the nation’s hospitals.

"That’s what has us all nervous, that very pros pect," Schaffner says. "It has everything to do with how we approach the patient who is initially sick. And there is an ominous sense that if yet another resistant organism is getting a foothold in the community, it reduces your therapeutic options."

References

1. Centers for Disease Control and Prevention. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus — Minnesota and North Dakota, 1997-1999. MMWR 1999; 48:707-710.

2. Shanin R, Johnson IL, Jamieson F, et al. Methicillin-resistant Staphylococcus aureus carriage in a child care center following a case of disease. Arch Pediatr Adolesc Med 1999; 153:864-868.

3. Herold BC, Immergluck LC, Maranan MC, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA 1998; 279:593-598.

4. Boyce JM. Are the epidemiology and microbiology of methicillin-resistant Staphylococcus aureus changing? JAMA 1998; 279:623-624.

5. Adcock PM, Pastor P, Medley F, et al. Methicillin-resistant Staphylococcus aureus in two child-care centers. J Infect Dis 1998; 78:577-580.

6. Embil J, Ramotar K, Romance L, et al. Methicillin-resistant Staphylococcus aureus in tertiary care institutions on the Canadian prairies, 1990-1992. Infect Control Hosp Epidemiol 1994; 15:646-651.

7. Maguire GP, Arthur AD, Boustead PJ, et al. Clinical experience and outcomes of community-acquired and nosocomial methicillin-resistant Staphylococcus aureus in a northern Australian hospital. J Hosp Infect 1998; 38:273-281.