CA-MRSA: preventing, managing leading culprit in skin, soft tissue infections

Good hand hygiene, keeping fingernails cut short, not sharing towels or washcloths remain the best prevention strategies.

If antibiotics are a physician’s weapon of choice, then methicillin-resistant Staphylococcus aureus is a moving target. For years, MRSA has been a hospital problem, but this bug’s movement into the community is confounding health officials and complicating treatment options.

MRSA USA300, the most common clone among the community-associated isolates, has become the leading cause of skin and soft tissue infections among otherwise healthy individuals since its identification in the late 1990s, with the most common patient presentations including furuncles, carbuncles and abscesses.

“Skin and soft tissue infections are by far what we see the most,” said James H. Brien, DO, chief of the section of pediatric infectious diseases at Scott and White Memorial Hospital in Temple, Texas. “Several times a week we admit patients with MRSA infections.”

Recurrent skin infections are typical and often require multiple doctor visits, placing additional burdens on an already strained health care system and heightening existing concerns regarding drug resistance.

“We don’t really know the optimal method of managing these recurrent infections,” said Rachel Gorwitz, MD, MPH, medical epidemiologist in the division of health care quality promotion at the CDC.

Necrotizing pneumonia, empyema, sepsis syndrome, necrotizing fasciitis and purpura fulminans have all been associated with CA-MRSA. Musculoskeletal infections such as pyomyositis and osteomyelitis are also increasing in prevalence.

“The USA300 clone has properties that we just don’t understand,” said Sheldon L. Kaplan, MD, professor and head of the section of pediatric infectious diseases, Baylor College of Medicine and chief of infectious diseases services at Texas Children’s Hospital in Houston.

In addition to its spread in the community, USA300 is beginning to eclipse traditional hospital-associated MRSA clones as a significant cause of nosocomial infections among patients in intensive care units, including pediatric intensive care units.

“In many cases, the MRSA strains that are being isolated in children’s hospitals and in the neonatal intensive care unit are of the community-associated type,” said Pablo J. Sánchez, MD, professor of pediatrics at the University of Texas Southwestern Medical Center in Dallas. “Where they are coming from is still a big issue.”

Who is at risk?

Tight living quarters, such as those found among prison inmates and military recruits, as well as crowded conditions, such as those found at some day care centers, put people at risk for infections with CA-MRSA. Children who have dermatitis and those who have other underlying medical conditions continue to be at risk, according to Kaplan. But knowing who may be at heightened risk has not helped quell the spread of this disease.

“The vast majority of children that we see have absolutely no risk factors,” Kaplan said.

Determining which patients will have more complicated courses of infection ahead of time is nearly impossible.

Bala Hota, MD, MPH, assistant professor in the section of infectious diseases at Stroger Hospital and Rush University Medical Center, said that CA-MRSA often leads to prolonged hospital stays. An optimal strategy for identifying and managing these infections has yet to be determined, Hota said.

Tailoring antibiotic therapies, improving cleaning regimens, establishing screening protocols and developing targeted decolonization strategies are among the most commonly debated.

Initial therapies

Since the emergence of CA-MRSA, treatment paradigms for managing S. aureus skin and soft tissue infections have changed, and it is important that physicians remember the basics. Incision and drainage and obtaining cultures to determine if the strains are methicillin-resistant are the first steps when a patient presents with uncomplicated abscesses or cellulitis.

It is common to start patients who present with simple soft tissue infections or bone and joint infection with an antibiotic that provides coverage against MRSA even before incision and drainage are performed, because there is no way to discern what is causing the infection before culture results come back, according to Brien.

While vancomycin may be first-line treatment for HA-MRSA due to typical resistance among these strains to multiple classes of antimicrobial agents, this regimen may not be best for CA-MRSA.

“We assume that there is probably going to be MRSA, so we start with clindamycin, mainly because here in this part of Texas, the vast majority of MRSA strains that we isolate are clindamycin-sensitive with no inducible resistance,” Brien said. “Anytime we think the patient has got bacteremia, sepsis, meningitis or something related to the brain or central nervous system, we’ll use vancomycin as our empiric therapy until we get culture results back with sensitivities.”

Sánchez said that vancomycin is not used as initial therapy in his center’s nursery. “We use oxacillin, in combination with gentamicin, for empiric therapy of possible late-onset sepsis, and that is a major issue because we want to prevent the development of vancomycin resistance,” Sánchez said.

Daptomycin (Cubicin, Cubist), tigecycline (Tygacil, Wyeth) and linezolid (Zyvox, Pharmacia & Upjohn) are among several FDA-approved antibiotic options discussed by Pradhan and Johnson in a treatment review article recently published in the Expert Review of Anti-Infective Therapy. Other therapies such as doxycycline, minocycline and trimethoprim-sulfamethoxazole (TMP/SMX) have been successful in case reports but are not FDA-approved for MRSA.

“If it’s an abscess, drainage is really almost a definitive cure,” Brien said. “In most cases involving soft tissue infections, getting the abscess drained is more important than which antibiotic you pick.”

Results of a 2004 study in the Pediatric Infectious Disease Journal by Lee and colleagues at the University of Texas Southwestern Medical Center compared treatment outcomes among 69 children with culture-proven CA-MRSA infection who received either incision and drainage with or without an antibiotic. Their data found no significant differences in response between the two groups.

Two trials are exploring these issues — Strategies Using Off-Patent Antibiotics for MRSA (STOP MRSA) and Uncomplicated Skin and Soft Tissue Infections caused by CA-MRSA — and should be complete by July 2012.

Infection control and prevention

Various screening and decolonization strategies have been proposed to prevent transmission and recurrent infections caused by CA-MRSA isolates among at-risk patients in hospital and community settings.

Several European countries, including Denmark and the Netherlands, have taken a “search-and-destroy” approach, nearly eradicating HA-MRSA by coordinating targeted active surveillance cultures, aggressive decolonization regimens and comprehensive cleaning programs. However, these are hospital-based strategies and do not address MRSA infections in the community.

Based on the success of these programs, several states, including Illinois, Maryland and Pennsylvania, have passed legislation mandating that hospitals perform universal active screening for MRSA. However, national organizations including the Society for Healthcare Epidemiology of America, the Association of Professionals in Infection Control and Epidemiology, the Infectious Diseases Society of America and the CDC oppose such action because of unresolved questions related to implementing such widespread screening and whether such a strategy would work in the United States, where CA-MRSA isolates are more prevalent than HA-MRSA.

“In general, none of these things are a one-size-fits-all approach,” Alexander Kallen, MD, MPH, a medical officer in the CDC’s Division of Healthcare Quality Promotion, said in an interview. “Different hospitals have different characteristics, so in our guidelines we try and present the potential options that hospitals can consider rather than insisting on what they should follow.”

Logistical questions include whether a given hospital has available staff to perform the tests and whether hospitals have enough rooms to provide necessary isolation precautions. Culture results take at least 48 hours to process and patients may spread the bacteria anyway if isolation precautions are not taken immediately. Performing rapid polymerase chain reaction-based surveillance on a large scale presents its own challenges as these tests are often more expensive and require a certain degree of skill to complete.

“Universal active-surveillance testing is really complicated, and that’s why at this point it’s not considered a first-line control measure,” Kallen said.

Screening, decolonization

One hospital population in which active surveillance is particularly useful is NICU patients, where invasive MRSA infections may be more likely among colonized infants because of a patient’s immature immune system and the presence of invasive medical devices.

“Some form of screening is important to identify these babies so that appropriate isolation precautions can be instituted to prevent the spread within the NICU [and also] to help guide empiric antibiotic coverage,” Sánchez said. “If you’re seeing CA-MRSA in your community … there should be some form of MRSA screening in the NICU.”

CA-MRSA is particularly worrisome in the neonatal population because skin-to-skin contact between the mother and child is encouraged as a vital part of development, and mothers who are colonized could easily spread the bacteria to these vulnerable infants.

“We encourage the mothers and fathers to hold and care for these babies. We want these babies to go to breast, we want to encourage skin-to-skin contact, and parents may be colonized as a lot of the community is,” Sánchez said.

At Parkland Memorial Hospital in Dallas where Sánchez practices, screening is performed monthly on all babies. Any child who is moved from the main nursery to the discharge nursery and any child who is transferred in from another hospital must also be screened. If a child has cultures that are positive for MRSA, isolation precautions are taken.

Many advocate using topical intranasal mupirocin twice a day for five days to eradicate nasal colonization in outbreak situations. Some have suggested using this decolonization strategy for babies in the NICU. Sanchez disagrees.

During an HA-MRSA outbreak during the early 1990s in which half of the patients in the NICU developed MRSA infections, Sánchez and colleagues used twice-daily mupirocin in the anterior nares and umbilicus of colonized patients. “When we cultured them later, 50% became colonized again,” Sánchez said. He attributes these high rates to multiple sites of colonization.

The option of decolonizing otherwise healthy children who experience recurring MRSA infections is another often discussed yet tricky area. “We rarely go into a staph-eradicating program with mupirocin or anything else because it is so hard to do and most parents just won’t stick with it,” Brien said.

Intranasal mupirocin for the patient alone is often insufficient. Combining this therapy with daily bleach baths may be a useful way to kill staphylococcal bacteria on the skin and is recommended for all family members and close contacts. Parents should also wash all clothes, sheets and pillowcases using hot water and color-safe bleach.

At the joint meeting of the IDSA and ICAAC in October, researchers from the University of Minnesota in Burnsville presented data indicating that proactive surveillance and decolonization helped reduce the number of CA-MRSA infections at a 28-day high school wrestling camp. After observing high rates of bacterial skin infections in 2006 (24.2% of 330 wrestlers), nasal cultures were obtained the following year from all camp counselors, coaches and athletic trainers.

Thirteen of 26 study participants had cultures positive for CA-MRSA. After culture-positive members of the training staff were decolonized, rates of bacterial skin infection dropped 57.8% from the previous year.

But while mupirocin is generally effective at eradicating S. aureus colonization short term, long-term recolonization is likely. Also, emerging resistance among some strains makes many cautious about routine use of the drug.

“Mupirocin resistance is something that people are concerned about,” Kaplan said. “About 15% of isolates around the country seem to have some mupirocin resistance — either high level or low level. But certainly in kids with recurrences, it’s something that we’re going to do.”

Other decolonization options include combining topical mupirocin with systemic antimicrobial agents and antiseptic body washes such as chlorahexidine, but further research is needed. “There are several different oral regimens like giving a quinolone such as ciprofloxacin plus rifampin, or tetracycline or doxycycline plus rifampin,” Hota said. “So combination oral therapy for three to five days can eradicate the organism from nasal sites.”

But Gorwitz warns that decolonization therapies may distract from more basic, common-sense strategies, like promoting hygiene and wound care, which have shown success at controlling community MRSA outbreaks.

Hand, surface hygiene best defense

“The main precaution that we urge for everyone is excellent hand hygiene: hand washing or alcohol disinfection before and after every patient contact,” Sánchez said. “That in and of itself will prevent transmission.”

Hota said that in a lot of the outbreaks in prisons and within football teams, there typically is some environmental site where MRSA is found. “So if you really emphasize cleaning of the environment, that can help to prevent further spread.”

Good hand hygiene, keeping fingernails cut short, and not sharing towels or washcloths remain the best prevention strategies, according to Kaplan. “Hopefully down the road we’ll have other agents and perhaps a vaccine that might be important in preventing more invasive infections.” – by Nicole Blazek

Is development of a S. aureus vaccine a realistic goal?

For more information:

• Anderson B. #G2-1313. Presented at: IDSA/ICAAC joint meeting. Washington:Oct. 25-28, 2008.
• Kale Pradhan K, Johnson LB. Treatment and recurrence management of staphylococcal infections: community-aquired MRSA. Expert Rev Anti Infect Ther. 2008 Dec;6(6):909-915.
• Lee MC, Rios AM, Aten MF et al. Management and outcome of children with skin and soft tissue abscesses caused by community-aquired methiciliin resistant Staphylococcus aureus. Pediatr Infect Dis J. 2004;23:123-127.
• Miller LG, Diep BA. Colonization, fomites and virulence: Rethinking the pathogenesis of community-associated methicillin-resistant Staphylococcus aureus infection. Clin Infect Dis. 2008;doi:10.1086/526773.
• Schaffer AC, Lee JC. Staphylococcal vaccines and immunotherapies. Infect Dis Clin N Am. 2009;doi:10.1016/j.idc.2008.10.2005.
• Weber SG, Huang SS, Oriola S, et al. Legislative mandates for the use of active surveillance cultures to screen for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: Position Statement from the joint SHEA and APIC Task Force. Infect Control Hosp Epidemiol. 2007;28.249-260.