'Not your father's MRSA': What you need to know -- and do -- about community-associated MRSA

If there was any lingering doubt about the scope or severity of methicillin-resistant S. aureus (MRSA) in the United States, it was dispelled by two developments last month. The first: a report in the Oct. 17 Journal of the American Medical Association, in which CDC researchers identified 5,287 cases of invasive MRSA infection and 988 deaths in 2005. Based on their data, collected from 9 locations through the CDC's Active Bacterial Core laboratory surveillance system from July 2004 through December 2005, the incidence of invasive MRSA infections in 2005 was 31.8 per 100,000 people -- nearly 3 times as high as the CDC's previous estimates. The researchers projected that 94,360 patients developed invasive MRSA infections in 2005, and that 18,650 of them -- nearly 20% -- died. If the study's projections are correct, the number of deaths annually from MRSA would exceed those from HIV/AIDS, emphysema or homicide. The second development -- presented in more personal rather than statistical terms -- was the news reports of a string of community-associated MRSA infections in schools in several states, including Virginia, West Virginia, Maryland, Georgia and New York. Among the cases, CA-MRSA was deemed the likely cause of death for 2 previously healthy teenagers. The developments prompted sobering assessments by infectious-disease specialists, who used words like "astounding" and "we should be very worried" to characterize the public-health problem.

MRSA goes outpatient

The overall burden of MRSA infections still falls disproportionately on hospitals and nursing homes. The JAMA report -- the first comprehensive, national estimate of invasive MRSA infections -- confirmed that the majority of invasive MRSA infections (85%) are healthcare-associated (originating in inpatient settings). Furthermore, the majority of all MRSA infections, whether community-associated or healthcare-associated, are noninvasive. Still, the report's findings and the highly publicized recent cases make clear that MRSA isn't just a hospital problem anymore. Because the JAMA study tracked only invasive MRSA infections, its estimates are "only the tip of the drug-resistance iceberg," according to the accompanying editorial by Elizabeth Bancroft, MD. There is no single reliable estimate for the prevalence of all MRSA infections nationally, as the CDC does not do comprehensive surveillance of CA-MRSA infections. But an April 2005 study from the CDC's Emerging Infections Program Network, based on surveillance in Baltimore, Atlanta and in 12 Minnesota hospitals, reported that the annual incidence of community-associated MRSA was 25.7 cases per 100,000 in Atlanta and 18.0 per 100,000 in Baltimore. And the rates have undoubtedly increased since then. "MRSA is everywhere. Most doctors know about it, but they may not have known know how big the problem is," says Henry F. Chambers, MD, professor of medicine and chief of infectious diseases at the University of California, San Francisco, who studies the prevalence of and treatments for community-associated MRSA. "The hospital isn't the epicenter of the problem anymore -- now it's the community," adds Robert S. Daum, MD, professor of pediatrics at the University of Chicago, who has done extensive research on the topic. "The whole paradigm has changed, but some doctors are still working under the old paradigm."

CA-MRSA brings new risk factors

While MRSA infections were once limited almost exclusively to patients with recent healthcare exposure, the rise of CA-MRSA has brought new risk factors. The following populations are especially vulnerable to CA-MRSA infections:

• children under 2 years and elderly patients
• athletes, particularly those playing contact sports
• military recruits
• children in daycare centers
• those living in households with poor hygiene and close contact
• black Americans
• Native Americans
• men who have sex with men

Perhaps the most striking feature of CA-MRSA is that it now routinely infects healthy children and adults with no recent healthcare exposure and none of the above-listed risk factors. "This isn't your father's MRSA," says Loren Miller, MD, associate professor of medicine in the Division of Infectious Diseases at Harbor-UCLA Medical Center. "A decade ago, if you had told us [doctors] that a healthy person who hadn't been in the hospital had MRSA, we wouldn't believe you -- it was unheard of. The scary thing is that now anyone can get it."

Heightened vigilance required For physicians, this new era calls for heightened vigilance and a stronger clinical suspicion that any skin or soft-tissue infection (SSTI), or any systemic infection consistent with a staph infection, could be caused by MRSA. Listed below are the clinical conditions most commonly associated with invasive MRSA infection, according to the JAMA report, including each condition's prevalence among all the invasive MRSA infections classified in the study, and the crude mortality rate. Other manifestations of invasive MRSA infection include pyomyositis, empyema, necrotizing fasciitis, and purpura fulminans.

Most patients with invasive MRSA infections have severe enough symptoms that they will go directly to the emergency department. For patients with suspected MRSA infections who present in outpatient settings, cultures should be taken from appropriate tissues and antibiotic susceptibility testing performed. Physicians should be particularly alert for cases of pneumonia following the flu, as these could be MRSA-caused, and for sudden-onset joint or bone pain -- including a limp in children -- accompanied by fever, as these could be signs of MRSA-caused osteomyelitis. The decision to hospitalize a patient with a MRSA infection will depend on the physician's judgment about the patient's health and the severity of the illness, though detailed guidance on the subject is beyond the scope of this article.

Biggest impact on management of SSTIs In terms of day-to-day clinical practice, CA-MRSA has the biggest implications for management of skin and soft-tissue infections, since they constitute 80-90% of all CA-MRSA infections. SSTIs are the 3rd-most-common type of infection seen in primary-care practice, after upper respiratory infections and urinary tract infections. In 2003, there were close to 12 million outpatient visits for skin infections typical of S. aureus, according to a 2006 study by CDC researchers. According to another 2006 study, from the EMERGEncy ID Net surveillance network, MRSA was the most common identifiable cause of skin and soft-tissue infections among patients presenting to emergency departments in 11 U.S. cities, representing 60% of all cases in the study. Based on these findings, there are several million cases of CA-MRSA-caused skin and soft-tissue infections each year in the United States. "The take-home message is that that skin infections nowadays should be assumed to be MRSA until proven otherwise," Miller says. "I've told this to primary-care physicians and a lot of them have had trouble believing it, because it's such a radical change from what they're used to treating."

Figure 1 

Among patients with uncomplicated SSTIs caused by CA-MRSA, the vast majority recover without complications if they receive proper treatment -- incision and drainage alone or with a systemic antibiotic (see latest guidance below). A small minority of these patients, however -- an estimated 1-3% -- develop more serious, invasive infections, underscoring the need for early detection, prompt treatment and follow-up.

Figure 2

Culturing lesions recommended as standard practice

Skin and soft-tissue infections caused by CA-MRSA typically appear as raised, red clusters of purulent abscesses, boils or lesions, and are often confused with spider bites (see images at left). They most commonly appear on the extremities, but can appear anywhere on the body.

Figure 3 

Because a lesion's clinical features won't indicate whether it's caused by MRSA or methicillin-suspeptible S. aureus, obtaining samples for culture and susceptibility testing is the only sure way to identify the cause. While culturing skin infections wasn't the standard of care in the past, the CDC is now strongly encouraging the practice for all abscesses or purulent skin lesions.

Culturing and testing lesions is important not only to guide the choice of treatment, but to provide information on the prevalence of MRSA in the physician's practice and the local community, as prevalence varies widely by geography. (MRSA is most common in urban areas but is now increasingly seen in rural areas as well.) Infectious disease specialists have suggested that once the prevalence of MRSA among all S. aureus isolates in a community reaches 10%, empiric treatment of SSTIs should include antibiotics that are reliably active against MRSA.

Latest guidance for outpatient management of SSTIs Routine culturing of infected tissues is just one of several changes clinicians may need to make in managing skin and soft-tissue infections in the age of CA-MRSA. The following guidance comes from the CDC's Strategies for Clinical Management of MRSA in the Community (March 2006), and from infectious-disease specialists who study and treat CA-MRSA infections.

• Incision and drainage should be performed on all purulent skin and soft-tissue lesions, regardless of whether or not antibiotics are also to be given.
• I&D alone is sufficient and is the recommended treatment for most uncomplicated lesions in healthy patients. A randomized, placebo-controlled trial by researchers at UC-San Francisco (published November 2007), found that for adult patients with deep skin abscesses and surrounding cellulitis -- of which 87% were caused by MRSA -- treatment success rates were over 90% for patients treated with incision and drainage alone. According to infectious-disease experts, I&D alone is usually sufficient if:
  
• the lesion is less than 5 cm
   
• it is not overly purulent
   
• the lesion is not on the hands, face or genitalia
   
• the patient is healthy, is not immunosuppressed and does not have a chronic disease
   
• the patient does not have signs of systemic infection
• Schedule a follow up visit for 24-48 hours after the patient's initial consultation, to determine whether further intervention is necessary.
• Instruct patients to call the doctor's office immediately, or go to the emergency department, if they develop a fever, feel suddenly worse, have trouble breathing, or notice other signs of worsening infection such as a large amount of pus, or increased pain or redness of the lesion.
• Give antibiotics only when necessary -- doing otherwise only exacerbates the problem. "There's been a tendency to overtreat these infections with antibiotics, because it's easy and the patient has an expectation of getting it," Chambers says. "But throwing antibiotics at minor infections won't do us any good." The CDC does not have specific recommendations for when antibiotics should be prescribed for SSTIs, but it notes that physicians should use their clinical judgment and should consider antibiotics if:
  
• the patient's condition has not improved 24-48 hours after the initial visit
   
• the lesion is 5 cm or larger
   
• the patient is very young or very old
   
• the patient is immunosuppressed or has a chronic illness
• Choose antibiotics carefully. If antibiotics are called for, choose one indicated by the culture results. Don't assume that the proven drugs of the past will work. "When we used to see skin infections, we we'd give Keflex [cephalexin] all the time, and it worked great until 6 or 8 years ago," Miller says. "Now cephalosporins and penicillins aren’t reliable for skin infections anymore. The era of Keflex is over." CA-MRSA is resistant to all currently available beta-lactam antibiotics, including penicillins and cephalosporins, as well as macrolides/azalides (erythromycin, clarithromycin and azithromycin). Resistance to other classes of antibiotics, such as fluoroquinolones and tetracyclines, has been observed and may be increasing. So which antibiotics are most effective for treating SSTIs caused by CA-MRSA? Unfortunately, few randomized, controlled clinical trials have been completed, so there's insufficient evidence to establish optimal therapy. Two multicenter studies now underway are evaluating the effectiveness of older off-patent antibiotics, including clindamycin and trimethoprim/sulfamethoxazole (TMP/SMX), in treating uncomplicated SSTIs caused by CA-MRSA. The trials will enroll 2,400 participants and will run through 2012. In the meantime, based on clinical experience and the results of susceptibility testing, the CDC suggests the following antibiotics as the best available options for treating SSTIs caused by MRSA (see bottom of page 3 for details and cautions):
  
• Clindamycin
   
• Tetracyclines (tetracycline, doxycycline, minocycline)
   
• Trimethoprim–sulfamethoxazole (TMP-SMX)
   
• Rifampin
   
• Linezolid
• Emphasize good hygiene. For all patients with CA-MRSA infections, physicians should discuss the importance of good hygiene in preventing transmission and guarding against recurrent infections. Key hygiene practices include:
  
• Proper hand hygiene. Hands should be washed often during the day, for 15-20 seconds with warm water. Clean hands immediately after touching infected skin or any item that has come in contact with a draining wound. Since antibacterial soap has not been shown to be more effective than regular soap, any soap can be used. All parts of the hand must be cleaned, including under the fingernails. Alcohol-based hand rubs that contain at least 60% alcohol are also effective, but their use cannot replace hand washing entirely. Depending on the product, alcohol-based hand rubs can be used up to a specified number of times (often 6-8 times) before hands must again be washed. When hands are visibly soiled, hand washing must be used, not alcohol rubs.
   
• Keep draining wounds covered with clean, dry bandages at all times.
   
• Don't share clothing, towels or personal items such as razors, combs, bar soap, etc.
   
• Wash the patient's clothes and linens separately; dry them thoroughly in a dryer
   
• Take showers immediately after playing sports
   
• Until the wound has healed, patients should avoid sex, kissing, and other forms of close contact. (Note: This guidance comes from some infectious-disease specialists, but is not a CDC recommendation.)
   
• If the wound cannot be kept covered with clean, dry bandages, patients should avoid settings such as daycare, gyms and sports participation

Recurrent infections should prompt questions, discussions of hygiene

Recurrent infections -- defined as 2 or more infections within 3 months -- are common with CA-MRSA. The recurrence rate, though not well-documented, is believed to be 10-30%. "Recurrence is one of our biggest concerns with MRSA -- it's a major, major problem," Daum says. Recurrent infections most often occur in patients who live in crowded, unsanitary conditions (such as in prison or housing projects), as well as among black Americans, Native Americans, intravenous drug users and men who have sex with men. If a patient presents with a second suspected MRSA infection, the physician should ask about his/her environment and risk factors, including whether anyone else in the household has recently had a skin infection. Such questions aren't easy to discuss, Daum acknowledges, but they're important to help identify the origins of the infection. "I can't overstate the impact of jail -- it's a perfect breeding ground for MRSA," he says. He advises raising the issue tactfully but directly. "I would say, 'We're trying to figure out how these infections are happening, and we know that jail is a real reservoir for them. Has anyone in your family been in jail?'" For patients with recurrent infections, physicians should emphasize the good hygiene practices outlined above, explaining that improvements in hygiene have been shown to reduce transmission and recurrence of CA-MRSA infections..

RELATED LINKS

Recent articles from Consultant

Emerging Infections: What You Need to Know, Part I

October 2007

Methicillin-Resistant Staph on the Rise, and on the Loose

May 2007

What to do When One Bacterial Scourge Begets Another

January 2007

Information & practice guidelines from the CDC

Community-Associated MRSA Information for Clinicians

Strategies for Clinical Management of MRSA in the Community: Summary of an Experts’ Meeting Convened by the Centers for Disease Control and Prevention

(March 2006)

Management of Multidrug-Resistant Organisms in Healthcare Settings

(2006)

Guideline for Hand Hygiene in Health-Care Settings

(2002)

Recent news on MRSA

Scientists Identify Factor Key to Severity of Community-Associated Methicillin-Resistant Staph Infections

National Institute of Allergy and Infectious Diseases, Nov. 11, 2007

Staph Germ Attacks Immune Cells

Associated Press via the Washington Post, Nov. 11, 2007

Invasive MRSA More Pervasive than Suspected

MedPage Today via ConsultantLive, Oct. 17, 2007

Journal articles

Invasive Methicillin-Resistant Staphylococcus aureus Infections in the United States

Journal of the American Medical Association, Oct. 17, 2007

Antimicrobial Resistance: It's Not Just for Hospitals

Journal of the American Medical Association, Oct. 17, 2007

Skin and Soft-Tissue Infections Caused by Methicillin-Resistant Staphylococcus aureus

New England Journal of Medicine, July 26, 2007

Treatment of Community-associated Methicillin-resistant Staphylococcus aureus

Current Infectious Disease Reports, September 2007

• Questions linger around decolonization For patients who develop recurrent infections even after making the recommended hygiene improvements, physicians can consider decolonization to rid the body of the bacteria. Suggested decolonization practices involve a 1-to-2-week regimen of intranasal mupirocin (Bactroban) along with antiseptic body washes (topical chlorhexidine gluconate used in the shower, or 1 tsp of bleach diluted in 1 gallon of bath water), possibly in addition to a systemic antibiotic. Decolonization is a grey area, however, as there has been no rigorous scientific evaluation regarding what regimens are most effective, which patients should undergo decolonization, or whether the strategy is effective at preventing subsequent infections. A July 2007 article by Daum in the New England Journal of Medicine, "Skin and Soft-Tissue Infections Caused by Methicillin-Resistant Staphylococcus aureus", notes that "The optimal strength of the chlorhexidine solution is not known, nor is it clear whether it is more effective if the solution is permitted to remain on the skin before rinsing." The article also notes that "eradication of nasal colonization appears to be transient, and the use of [intranasal mupirocin for this purpose] remains controversial." Although some decolonization efforts seem to be successful at minimizing recurrent MRSA infections, there is evidence of patients becoming recolonized and reinfected after undergoing decolonization. Compliance with decolonization regimens has been poor in some community settings. And there are reported cases of CA-MRSA developing resistance to the agents used for decolonization, raising concerns about widespread use of the practice. "We're lacking data on this -- it's all expert opinion at this point," Miller says. He calls the use of decolonization "somewhat controversial." To provide guidance on the issue, randomized controlled trials are now underway to evaluate the efficacy of decolonization strategies vs. usual care (patient education on hygiene improvements and recognizing skin infections) in minimizing the risk of recurrent CA-MRSA infection. Results won't be available for 3-5 years, however. Guidance on decolonization For now, the CDC offers the following guidance on decolonization:
• Decolonization may be a reasonable option when a patient has had several recurrences of MRSA infection, and/or if
• ongoing MRSA transmission is occurring in a well-defined closely associated area, such as a household.
• Decolonization should be considered only after improved hygiene measures have been unsuccessful.
• Consult with an infectious-disease specialist before prescribing a decolonization regimen.
• Regimens should be limited to short courses, to decrease the emergence of resistance.

In addition,

Jane D. Siegel

, MD -- professor of pediatrics at the University of Texas Southwestern Medical Center, and lead member of the CDC's guideline taskforce on

Management of Multidrug-Resistant Organisms in Healthcare Settings

-- advises that decolonization should be reserved for patients who are

• elderly
• about to have surgery
• on dialysis
• have a chronic disease, or
• or when such a patient lives in the household with the affected patient.

Infection control practices are key

Recent concern over MRSA outbreaks has prompted some hospitals to begin taking nasal swabs of all intensive-care patients to identify those colonized with the pathogen. In August, Illinois became the first state to mandate testing for all high-risk hospital patients and isolation of those colonized with MRSA. Pennsylvania and New Jersey have passed similar laws. Such measures aren't recommended for outpatient settings, however, given that MRSA colonization in the general population is so widespread (and usually harmless), and that screening for merely colonized (not infected) patients is unlikely to significantly reduce CA-MRSA infections. For primary-care physicians and their staffs, the biggest payoff will come from following standard infection-control practices:

• proper hand hygiene (see CDC's hand-hygiene guidelines)
• cleaning and disinfecting medical equipment and surfaces between patients
• changing and washing lab coats regularly
• wearing gloves when treating wounds
• wearing gowns and eye protection for procedures that could produce splashes or sprays of bodily fluids
• isolating patients with active MRSA infections by moving them to a separate waiting area.

Such measures are crucial to contain the spread of the notoriously sophisticated, adaptable bacteria. "Staph is smart and it likes challenges -- it keeps finding ways to outsmart us," Daum observes. That reality means physicians had better get accustomed to dealing with MRSA, he says. "One thing is true: Every place where this bacteria has arrived, it hasn't left."

Have comments or questions on this article? Please e-mail the author, Sara Selis, at sselis@cmp.com