MRSA

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CME/CE Released: 03/17/2011; Valid for credit through 03/17/2012

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This activity is intended for infectious disease specialists, emergency medicine clinicians, hospitalists, internists, primary care and family medicine physicians, nurses/advanced practice nurses, and physician assistants.

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The goal of this activity is to address the educational needs related to the evolving epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and increase clinical competency related to early and accurate identification and differential diagnosis of MRSA infections, treatment options including appropriate antimicrobial utilization, and emerging clinical controversies. In turn, patients will receive optimal care, and patient outcomes will be improved.

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Upon completion of this activity, participants will be able to:

1.Select evidence-based interventions for containing MRSA infections in the community and hospital
2.Identify clinical challenges resulting from the changing epidemiology of MRSA
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Author(s)Robert A. Weinstein, MD Chairman, Department of Medicine, Cook County Health and Hospitals System; Chief Operating Officer, Ruth M. Rothstein CORE Center, C. Anderson Hedberg, MD, Professor of Internal Medicine, Rush University Medical Center, Chicago, Illinois

Disclosure: Robert A. Weinstein, MD, has disclosed the following relevant financial relationships:
Received grants for clinical research from: US Centers for Disease Control and Prevention
Owns stock, stock options, or bonds from: Merck & Co., Inc.; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.; GlaxoSmithKline

Dr. Weinstein does intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics not approved by the US Food and Drug Administration (FDA) for use in the United States.

Dr. Weinstein does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.

Editor and Nurse PlannerSusan L. Smith, MN, PhDScientific Director, Medscape LLC

Susan L. Smith, MN, PhD, has disclosed no relevant financial relationships.
CME ReviewerNafeez Zawahir, MDCME Clinical Director, Medscape, LLC

Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

From Medscape Education Infectious Diseases
Containing the Superbug CME/CE
Robert A. Weinstein, MD


CME/CE Released: 03/17/2011; Valid for credit through 03/17/2012

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Editor's note: Staphylococcus aureus is the most commonly isolated human bacterial pathogen and is an important cause of several potentially serious and fatal infections, including bacteremia and sepsis, endocarditis, endovascular infections, foreign-body infections, osteomyelitis, pneumonia, skin and soft-tissue infections (SSTIs), and septic arthritis. The disease burden of methicillin-resistant S aureus (MRSA) (strains that are resistant to all available penicillins and other beta-lactam antimicrobial agents) in the United States has not only increased considerably, but the epidemiology of MRSA has changed. Historically, MRSA infections occurred in individuals considered at risk due to healthcare exposure; primarily patients admitted to inpatient healthcare facilities and/or those who frequented other healthcare environments.[1] Beginning in the mid-1990s, infections caused by new strains of MRSA began to be reported in individuals in the community without risk factors and are responsible for a significant proportion of the increased disease burden of MRSA in the last decade.

Delorme and colleagues conducted a retrospective survey of all staphylococcal infections diagnosed by a single medical center in Northeastern Ohio during 2006 and 2007.[2] The incidence of MRSA increased 77% overall, 58% in outpatients, 43% in hospitalized patients, and 183% in residents of long-term care facilities. Sixty-six percent of individuals diagnosed with MRSA had no risk factors for staphylococcal infection. SSTIs are especially burdensome, especially complicated SSTIs, which by definition are those requiring surgical intervention.[3] SSTIs are caused by a variety of pathogens, including aerobic gram-positive or gram-negative organisms, and in some settings other unique pathogens. Overall, S aureus is the pathogen most frequently isolated from complicated SSTIs. SSTIs in patients in healthcare settings are more likely due to MRSA, methicillin-resistant Staphylococcus epidermidis, vancomycin-resistant Enterococcus, and resistant gram-negative pathogens. Community-acquired or community-associated MRSA (CA-MRSA) is the single most frequent pathogen responsible for SSTIs.[3]

Infection control and prevention are responsibilities of all healthcare workers, whether caring for hospitalized patients or caring for and educating patients on preventive practices in community settings, including the home. MRSA in the community is widespread and therefore anyone is at risk. Nurses in particular, and especially those who practice in community health settings, schools, and correctional facilities, are more likely to provide this education. Because the majority of MRSA infections in the community are SSTIs, this should be the focus of education: to prevent the occurrence and spread of CA-MRSA. Individuals at highest risk for SSTIs are those in close skin-to-skin contact with others (eg, athletes, children in day care centers, and living in crowded conditions such as in dormitories, military barracks, or correctional facilities), with openings in the skin such as cuts or abrasions, likely to be in contact with contaminated items and surfaces, and with poor hygiene. The Centers for Disease Control and Prevention (CDC) provides special information and advice for family caregivers, athletes, coaches and athletic directors, school officials, and others. In particular, downloadable fact sheets for these groups are available at no charge on the CDC's Website. Examples are shown in Figure 1 and Figure 2.

(Download PDF) Figure 1. MRSA fact sheet for athletes, coaches, and athletic directors.

(Download PDF) Figure 2. MRSA fact sheet for early childhood care and education professionals.


Robert A. Weinstein, MD, Chairman of the Department of Medicine for the Cook County Health and Hospitals System, the Chief Operating Officer of the Ruth M. Rothstein CORE Center, and the C. Anderson Hedberg, MD, Professor of Internal Medicine at Rush University Medical Center, in Chicago, Illinois, discusses implications of the changes observed with MRSA over the last 2 decades and selected recommendations from recently published clinical practice guidelines from the Infectious Diseases Society of America (IDSA).[4]

Introduction


The epidemiologic landscape of MRSA has changed dramatically over time. In the 1990s, we saw MRSA infections only in hospitals. At the end of that decade and the beginning of the next, MRSA infections began to emerge in the community in individuals who had not been exposed to the hospital in the past year, did not have any indwelling catheters, were not on hemodialysis therapy, had not had surgery in the past 12 months, and did not have family members who worked in hospitals. In essence, MRSA infections occurring in the community were not due to feral nosocomial strains, and patients infected or colonized by these strains did not acquire them through direct or even indirect healthcare contacts. In light of this lack of connection to hospitals, these newly recognized antibiotic-resistant staphylococci became known as CA-MRSA.

CA-MRSA on the Move
MRSA strains are classified by phenotype and genotype (Table 1). Historically, certain MRSA phenotypes occurred in the community (CA-MRSA) and were distinct from MRSA phenotypes that occurred in hospitals (healthcare-associated MRSA [HA-MRSA]). CA-MRSA has slightly different antibiograms compared with HA-MRSA. CA-MRSA is more likely to be susceptible to nonbeta-lactam antibiotics, specifically trimethoprim-sulfamethoxazole (TMP-SMZ)*, the tetracyclines, and in some cases, clindamycin, whereas nosocomial HA-MRSA is more often broadly resistant with limited susceptibility to nonbeta-lactam antibiotics. From a genotypic perspective, CA-MRSA (vs HA-MRSA) has a slightly different genetic element that encodes for cell wall changes that make the bacteria methicillin resistant.

From an epidemiologic perspective, over the last 5-7 years, the differences between CA-MRSA and HA-MRSA have become blurred. In other words, the incidence of nosocomial infections caused by MRSA isolates phenotypically and genotypically consistent with CA-MRSA strains has increased.[5] Thus, CA-MRSA strains are now considered part of the epidemiologic continuum of HA-MRSA strains.

Table 1. Phenotypic and Genotypic Distinctions Between CA-MRSA and HA-MRSA

MRSA Isolates Phenotypea Genotypeb
CA-MRSA Often susceptible to nonbeta-lactam antibiotics. In addition to susceptibility to vancomycin, often susceptible to TMP-SMZ, doxycycline, minocycline, clindamycin, daptomycin, and linezolid. USA300,cUSA400c are the most common genotypes based on PFGE.

SCCmec type IV is the most common genetic element that encodes methicillin resistance.
HA-MRSA Resistant to more classes of antibiotics than are CA-MRSA. Usually susceptible to at least vancomycin, daptomycin, and linezolid. USA100, USA200, and USA600 are the most common genotypes based on PFGE.

SCCmec type II-III are the most common genetic elements that encode for methicillin resistance.

CA-MRSA = community-associated methicillin-resistant Staphylococcus aureus; HA-MRSA = healthcare-associated methicillin-resistant Staphylococcus aureus; TMP-SMZ = trimethoprim-sulfamethoxazole; PFGE = pulsed-field gel electrophoresis; SCCmec = staphylococcal cassette chromosome mec
a. Based on antimicrobial drug susceptibilities.
b. MRSA clones most closely associated with CA-MRSA and HA-MRSA in the United States.
c. Often contain Panton-Valentine leukocidin genes and are more frequently associated with skin and soft-tissue infections.
Management of SSTIs
The most common CA-MRSA infections are SSTIs[6];I'm going to focus on outpatient treatment of SSTI. In 2008, the New England Journal of Medicine polled its readers about how they would treat a college athlete who presented with a tender 5- by 3-cm area of erythema with an abscess in the center.[6,7] The poll included 11,205 participants from 124 countries. Readers were asked to choose 1 of the following 3 treatment options:

1.Incision and drainage alone with no antimicrobial therapy;
2.Incision and drainage plus antimicrobial therapy active against methicillin-susceptible S aureus (MSSA); the patient had not had a culture taken so it was a clinical scenario, not a known bacteria, that was being treated; or
3.Incision and drainage plus antibacterial therapy that would be active against MRSA, presuming that MRSA would be the most common cause of infection.
The results were interesting (Figure 3).[7] The majority of North American readers (53%) selected option 3, incision and drainage plus antibacterial therapy for MRSA. This probably reflects the fact that in the United States, if a patient goes to an emergency room with an abscess that is incised and drained, a culture of the drainage will be positive for MRSA more than 50% of the time if S aureus is the offending pathogen, even in individuals without exposure to hospitals. In Europe, where MRSA is far less common in the community, the highest percentage (45%) of respondents selected option 1, incision and drainage alone. Option 2, incision and drainage plus antibacterial therapy for MSSA, was selected by 18% of respondents in the United States and 34% of respondents in Europe.



Figure 3. Percentage of North American vs European participants choosing each treatment option for the management of skin and soft-tissue infection in an Internet poll.A discussion of participant feedback regarding their choices is included in the publication.
I&D = incision and drainage; MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-susceptible Staphylococcus aureus
From Diep BA, et al. Ann Intern Med. 2008;148:249-257.[8]

The IDSA recently published clinical practice guidelines for the treatment of MRSA infections in adults and children with recommendations for several different clinical scenarios in addition to SSTI, including uncomplicated and complicated bacteremia and severe community-associated pneumonia in the hospitalized patient.[4] Vancomycin and daptomycin are the recommended agents for bacteremia and vancomycin, linezolid, and clindamycin are the recommended agents for pneumonia. The new recommendations for management of SSTI are listed in Table 2.

Table 2. Recommendations for Management of Skin and Soft-Tissue Infections

Clinical Presentation Recommended Treatment
Simple cutaneous abscess Incision and drainage (I&D)
Abscess associated with severe disease, rapid progression with cellulitis, systemic comorbidities, difficult-to-drain areas I&D and antibiotic therapy
Purulent cellulitis in outpatient setting Empiric antibiotic therapy for MRSA: most often either clindamycin, TMP-SMZ*, doxycycline, or minocycline, with choice guided by local susceptibility pattern
Nonpurulent cellulitis in outpatient setting Empiric antibiotic therapy for beta-hemolytic Streptococcus: penicillin V or amoxicillin (with the caveat that beta-hemolytic streptococcal resistance to clindamycin is emerging in some communities), or if TMP-SMZ* or a tetracycline (doxycycline or minocycline) is used because of concern about potential CA-MRSA, add a beta-lactam (eg, amoxicillin) with activity against beta-hemolytic Streptococcus.

CA-MRSA = community-associated methicillin-resistant Staphylococcus aureus; MRSA = methicillin-resistant Staphylococcus aureus; TMP-SMZ = trimethoprim/sulfamethoxazole
From Liu C, et al. Clin Infect Dis. 2011;52:1-38.[4]


If, in addition to incision and drainage, you decide to treat MRSA with an antibiotic in the United States, of the options in Table 2, TMP-SMZ* tends to be the most active in vitro. However, in my experience, the agent chosen may depend on the individual providing the treatment. Infectious disease physicians who use a lot of TMP-SMZ* for a variety of infections tend to use TMP-SMZ*, most commonly for treatment of CA-MRSA-related SSTI; dermatologists who typically treat acne with tetracycline are more likely to use doxycycline or minocycline, and emergency medicine physicians tend to use clindamycin because they may not see the patient again and are concerned about covering for a potential group A Streptococcus infection.

In addition to the traditional first-line agents, the newer antimicrobials (telavancin and ceftaroline) also have in vitro activity against MRSA. Telavancin is approved by the US Food and Drug Administration (FDA) for treatment of MRSA-related complicated SSTI, and ceftaroline is FDA approved for treatment of acute bacterial SSTI, including those due to MRSA.

As implied in Table 2, the likelihood of S aureus is higher in an abscess or lesion with draining pus; treatment with TMP-SMZ*, doxycycline, minocycline, or clindamycin if these agents are active against CA-MRSA in your part of the country is a reasonable approach. If the infection is a cellulitis and there is no drainable pus, then a group A streptococcal infection is more likely. TMP-SMZ*, doxycycline, and minocycline are not as active against group A Streptococcus, so you would have to combine one of those agents with amoxicillin, ampicillin, or penicillin, whereas clindamycin may cover both MRSA and group A Streptococcus.

One must keep in mind that the epidemiologic MRSA landscape is ever-changing. For example, a new multidrug-resistant clone of MRSA has been reported in San Francisco and Boston in men who have sex with men.[8] This particular strain is resistant to clindamycin and tetracycline and has increased resistance to mupirocin, a topical agent used for staphylococcal nasal decolonization. If you are treating a soft tissue abscess and suspect MRSA in men who have sex with men in San Francisco or Boston and do not have susceptibility results, you might shy away from clindamycin, doxycycline, and tetracycline, and focus more on TMP-SMZ*.

Managing Recurrent MRSA-Related SSTI
Some individuals have recurrent MRSA-related SSTI and some of these individuals carry MRSA in the nares, the main reservoir of S aureus in the body, and in other body sites. Should these patients be decolonized in an effort to prevent recurrence, and if so when and how?

Recent clinical practice guidelines from the IDSA include recommendations for decolonization of patients with recurrent MRSA infections (Table 3).[4] The level of evidence for all of the recommendations for interventions is C-III, meaning that they have the least data to support them and are mostly based on expert opinion. In the United States, management is most often with nasal decolonization with mupirocin alone or in combination with chlorhexidine bathing, but usually not with oral antibiotics unless repeated MRSA infections occur despite use of a nasal and skin decolonization regimen. In Europe, particularly in The Netherlands where there has been pioneering work in control of MRSA, decolonization management with a combination of all 3 approaches (nasal mupirocin, chlorhexidine bathing, and oral antibiotic) is more likely to be done than in the United States.

Table 3. Recommendations for the Use of Decolonization in the Management of Recurrent Skin and Soft-Tissue Infections

Decolonization may be considered in selected cases if:

•A patient develops a recurrent SSTI despite optimizing wound care and hygiene measures (C-III*)
•Ongoing transmission is occurring among household members or other close contacts despite optimizing wound care and hygiene measures (C-III*)

Decolonization strategies should be offered in conjunction with ongoing reinforcement of hygiene measures and may include the following:
•Nasal decolonization with mupirocin twice daily for 5-10 days (C-III*)
•Nasal decolonization with mupirocin twice daily for 5-10 days and topical body decolonization regimens with a skin antiseptic solution (eg, chlorhexidine) for 5-14 days or dilute bleach baths. (For dilute bleach baths, 1 teaspoon per gallon of water [or one quarter cup per one quarter tub or 13 gallons of water] used for 15 min twice weekly for ~ 3 months can be considered) (C-III)*
Oral antimicrobial therapy is recommended for the treatment of active infection only and is not routinely recommended for decolonization (A-III**). An oral agent in combination with rifampin, if the strain is susceptible, may be considered for decolonization if infections recur despite the above measures (C-III*).

SSTI = skin and soft-tissue infection
*Indicates strength of recommendation and quality of evidence: C = poor evidence to support a recommendation; III = evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
**Indicates strength of recommendation and quality of evidence: A = good evidence to support a recommendation for or against use; III = evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
From Delorme T, et al. Am J Clin Pathol. 2009;132:668-677.[2]
What do you do at the institutional level? At an institutional level there is the issue of preoperative decolonization. In some hospitals, it is policy that patients who are having elective surgery (particularly cardiac surgery or placement of prosthetic devices) be treated with mupirocin for 5 days before surgery for nasal decolonization, particularly if the patient is known to be colonized with MRSA. This is somewhat controversial, but even more controversial is the use of active surveillance to prevent transmission of MRSA within hospitals.

Search and Destroy
The Dutch have eliminated the spread of MRSA by active surveillance or the so-called "search and destroy" approach to outbreak control, which consists of the use of active surveillance cultures for persons at risk, pre-emptive isolation of patients at risk, and strict isolation of known MRSA carriers and the eradication of MRSA carriage.[9] The Dutch culture the nares of patients who are admitted to hospitals if they're from other countries, being transferred from another hospital, or if there is reason to believe that the patient is colonized with MRSA. Through the initiation of contact precautions (gown and gloves before contact with the patient or patient's room environment) in these patients, MRSA has been eliminated from hospitals in The Netherlands and a number of Scandinavian countries.

In the United States, a number of states have adopted this approach and mandated that patients who are admitted from the community to intensive care units (ICUs) or who are admitted to the hospital from nursing homes or other potential high-risk areas undergo nasal screening for MRSA.[10] If positive, they are placed on contact precautions. In my view, whether that mandate will make a difference in terms of the spread of MRSA is controversial. My approach is to focus on device-related infections. For example, CDC published their experience recently and showed that from 2002 (when new central line-associated bloodstream infection [CLABSI] guidelines were introduced) to 2007 there was a marked decrease (46%) in the number of MRSA-related CLABSI in ICUs in hospitals monitored by the CDC, even though the percentage of S aureus that is MRSA has remained the same in those hospitals.[11] My view is that focusing on prevention of device-related infections will give more bang for the buck and prevent not only MRSA but other infections as well.

Back to the Basics: Hygiene
Prevention is also an issue in community settings where people are in close contact. For example, outbreaks of CA-MRSA have been documented among both professional and amateur athletic teams, military recruits, and men who have sex with men, and also in correctional facilities, schools, and newborn nurseries.[5] The major message here is hygiene. Individuals on sports teams should not share equipment unless it's cleaned between uses, and they should not share towels. Aggressive cleaning should be done in schools. Some schools have approached this by closing the school for 1 day or 2 to try to get rid of environmental contamination, but there are no data to support that approach and the benefit of this is unknown. Finally, communication needs to be better between nursing homes and hospitals. As patients move from hospitals to long-term acute care facilities or nursing homes, we need to do a better job of communicating if these patients may be colonized with MRSA and therefore, may need to be placed on contact precautions.

*TMP-SMX is not FDA-approved for the treatment of any staphylococcal infections. However, because 95%-100% of CA-MRSA strains are susceptible in vitro, it has become an important option for the outpatient treatment of SSTI.[2]

Supported independent educational grants from Cubist Pharmaceuticals, Inc.; Astellas Pharma, Inc.; and Pfizer Inc.

This article is a CME/CE certified activity. To earn credit for this activity visit:
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References
1.David MZ, Daum RS. Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev. 2010;23:616-687. Abstract
2.Delorme T, Rose S, Senita J, Callahan C, Nasr P. Epidemiology and susceptibilities of methicillin-resistant Staphylococcus aureus in northeastern Ohio. Am J Clin Pathol. 2009;132:668-677. Abstract
3.May AK, Stafford RE, Bulger EM, et al. Treatment of complicated skin and soft tissue infections. Surgical Infections. 2009;10:467-499. Abstract
4.Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38. Abstract
5.Maree CL, Daum RS, Boyle-Vavra, Matayoshi K, Miller LG. Community-associated methicillin-resistant Staphylococcus aureus isolates causing healthcare-associated infections. Emerg Infect Dis. 2007;13:236-242. Abstract
6.Chambers HF, Moellering RC Jr, Kamitsuka P. Management of skin and soft-tissue infections. N Engl J Med. 2008;359:1063-1067. Abstract
7.Hammond SP, Baden LR. Management of skin and soft-tissue infection - polling results. N Engl J Med. 2008;359:e20.
8.Diep BA, Chambers HF, Graber CJ, et al. Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men. Ann Intern Med. 2008;148:249-257. Abstract
9.Vos MC, Behrendt MD, Melles DC, et al. 5 years of experience implementing a methicillin-resistant Staphylococcus aureus search and destroy policy at the largest university medical center in the Netherlands. Infect Control Hosp Epidemiol. 2009;30:977-984. Abstract
10.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. Abstract
11.Burton DC, Edwards JR, Horan TC, et al. Methicillin-resistant Staphylococcus aureus central line-associated bloodstream infections in US intensive care units, 1997-2007. JAMA. 2009;301:727-736. Abstract
Sponsored by the National Foundation for Infectious Diseases.

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This article is a CME/CE certified activity. To earn credit for this activity visit:
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