C. BUDDY CREECH, MD Fellow, Infectious Diseases, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn.
LOUIS D. SARAVOLATZ, MD Chief, Department of Medicine, St. John Hospital and Medical Center; and Professor of Medicine, Wayne State University School
of Medicine,
Detroit, Mich.
WILLIAM SCHAFFNER, MD Chairman, Department of Preventive Medicine; Professor of Medicine, Division of Infectious Diseases, Vanderbilt University
School of Medicine, Nashville, Tenn; and member of the Patient Care Subspeciality Advisory Board.
In the emergency department at a university-associated children's hospital in Nashville, Tenn, investigators recently determined
that 60% of all cutaneous Staphylococcus aureus infections treated there in 2003 were caused by community-acquired methicillin-resistant S aureus (CA-MRSA). In addition, investigators also found a 9.2% prevalence of CA-MRSA nasal carriage among 500 healthy children seen
for well-child visits at 2 large Nashville pediatric outpatient clinics. A similar survey had been conducted only 3 years
earlier and turned up a CA-MRSA prevalence of just 1%.1 And although most infections caused by this organism are readily treated, a recent report by physicians at a Texas hospital
describes 14 previously healthy adolescents with CA-MRSA infections who developed sepsis and required treatment in the pediatric
intensive care unit; 3 died.2
Table 1 Traditional MRSA versus community-acquired MRSA
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Within the past 2 to 3 years, CA-MRSA has emerged and become widely disseminated within the United States and overseas (see
"Who has community-acquired MRSA?"). The strain differs in many significant ways from more familiar MRSA strains that are
nosocomial pathogens and affect primarily patients with significant comorbid illnesses (see Table 1). EPIDEMIOLOGY AND PATHOGEN CHARACTERISTICS
Risk factors for nosocomial MRSA include older age, nursing home residence, recent hospitalization, comorbid illness (especially
diabetes), indwelling catheters, dialysis, and prior antimicrobial exposure. In contrast, CA-MRSA affects patients who usually
have no significant risk factors. In fact, patients with CA-MRSA are often considered to be unlikely targets because of their
good health and robust athleticism. During the 2 to 3 years that this infection has been observed, most of the infected patients
have been young with no history of recent hospitalization or antibiotic exposure and no underlying medical illness.
Risk factors
Close contact with someone who is colonized or infected with CA-MRSA or with sports equipment, towels, or surfaces such as
benches or shower floors is the most important risk factor identified to date. A common scenario might start with a turf burn
on a player's exposed skin followed by direct contact with another player's site of infection during a tackle or by the sharing
of towels, uniforms, athletic supporters, or protective padding. Participants in sports with the potential for personal contact,
such as wrestling and football, are at highest risk. The infection has been observed spreading in families. Outbreaks have
also occurred in prisons, among military recruits, and in men who have sex with men. Although crowding and less-than-ideal
hygiene seem to foster outbreaks, CA-MRSA has not appeared to any great extent in hospitals or skilled nursing facilities.
Clinical characteristics
Most CA-MRSA infections have involved cutaneous and soft tissue in the form of boils and abscesses. Many cases are mistaken
for spider bites. With progression, contiguous bone infections have occurred. Necrotizing pneumonia has been reported in children
and adults. Bacteremia has also occurred, though sepsis seems to be less common. Few cases are life-threatening if treated
promptly; however, children and adolescents from rural and urban areas have died of CA-MRSA infections reported from 1997
to 1999.3,4
Organism susceptibilities
Several distinct strains of S aureus that cause CA-MRSA infections are circulating in the United States, according to the CDC.5 Some outbreaks have been associated with more than one strain.6 Several lines of evidence suggest that CA-MRSA strains have adaptations that facilitate its spread in the community.3
Most CA-MRSA strains are resistant to erythromycin. In the laboratory, CA-MRSA erythromycin-sensitive strains sometimes exhibit
inducible resistance to clindamycin, but this agent continues to work well in most clinical situations. Most CA-MRSA isolates
remain susceptible to ciprofloxacin, but data are limited for other fluoroquinolones. More than 95% of CA-MRSA isolates are
susceptible to trimethoprim-sulfamethoxazole (TMP-SMX).
Other agents to which CA-MRSA is susceptible include daptomycin, vancomycin, linezolid, quinupristin-dalfopristin, and possibly,
tetracycline and imipenem-cilastatin. The selection of an agent for empiric and definitive therapy of CA-MRSA infections is
discussed later in this article.7
SUSPICION AND DIAGNOSIS
Many skin infections caused by CA-MRSA resemble insect or spider bites, and physicians are urged to carefully assess these,
along with furuncles and cellulitis, for possible CA-MRSA infection. Be alert to symptoms such as pain or erythema that seem
out of proportion to the severity of the cutaneous findings. Areas of necrosis are a particularly strong clue to infection
with CA-MRSA.
Your index of suspicion for CA-MRSA should be quite high when a patient who plays a contact sport has a skin infection. The
threshold for performing a skin culture is low in this situation. Ask if the patient had an abrasion at the site before the
infection and if team members have had similar soft tissue infections.
In areas where CA-MRSA infections have been documented, physicians tend to obtain material for culture from furuncles and
abscesses on a routine basis, and experts advise this course of action, if possible. It not only helps tailor the therapy
for an individual patient, but it also contributes to local and national databases for this infection. In general, a culture
should be obtained from the infection site and sent to the microbiology laboratory for identification of the infecting organism
and determination of antibiotic susceptibilities. From cutaneous sites, a small biopsy of skin or a sample of draining material
will be sufficient.
Ask the patient to report back to you promptly if the pain worsens or if the infection site enlarges or becomes more purulent,
reddened, or necrotic. Consider having a staff member call the patient in 24 hours to check that the infection is improving.
Be wary of progressive infections, and ask patients (or parents) to call immediately if fever or chills set in. In a series
reported in 2004 from a Texas medical center, a significant predictor of eventual hospital admission for treatment of CA-MRSA
infection was a cutaneous lesion that exceeded 5 cm at presentation.8
Transient bacteremia may occur. Sepsis may lead to a necrotizing pneumonia, and children and adolescents may be more susceptible
than other patients. Most of the deaths attributed to CA-MRSA infection have occurred in patients who presented with necrotizing
pneumonia.7
TREATMENT
A report published last year from the University of Texas Southwestern Medical Center suggested that incision and drainage
without adjunctive antibiotics was sufficient treatment for children with skin and soft tissue abscesses that were less than
5 cm at presentation.8 This study included 65 children and was conducted at a single site. Most specialists prefer to drain and culture the abscess
and then treat with an antibiotic.
Empiric therapy
The choice of an antibiotic for a soft tissue infection is usually made before the causative organism is identified. In places
where CA-MRSA has not been reported or causes less than 10% to 20% of S aureus soft tissue infections, cephalexin is still preferred. Treatment can be adjusted if the infection worsens or does not respond
to treatment, or if culture results reveal CA-MRSA. If methicillin-susceptible S aureus is the causative agent, cephalexin or another beta-lactam antibiotic can be continued.
Therapy of culture-confirmed cases
Definitive therapy for CA-MRSA is recommended in areas such as Dallas, Houston, Nashville, San Francisco, and other communities
where this organism is thought to be the predominant form of S aureus, causing soft tissue infections. Switching to definitive therapy is also necessary if CA-MRSA is identified in culture or
if the patient's condition worsens on empiric therapy. The more you know about CA-MRSA in your area, the more on-target your
treatment decisions will be. Local emergency medicine physicians may be your best source of information.9
TMP-SMX is the agent used most often for definitive therapy because it has excellent in vitro activity against CA-MRSA. Though
studies proving its effectiveness in CA-MRSA are lacking, a 10- to 14-day course is typically recommended. To preserve efficacy,
experts urge their colleagues not to use TMP-SMX routinely for empiric therapy of possible CA-MRSA infections unless they
practice in an area where the agent predominates or CA-MRSA is identified in culture.
Clindamycin is an alternative because it is inexpensive, penetrates tissues well, and usually is highly effective. One caution
applies to clindamycin, however. Resistance of CA-MRSA to clindamycin is inducible in the laboratory, and the clinical implications
are poorly understood. The so-called D-test is performed in many laboratories to help determine whether an isolate is susceptible
to clindamycin.10 Resistance to this drug seems to occur in geographically circumscribed areas.
Doxycycline is another alternative to TMP-SMX for definitive therapy in patients who are intolerant of sulfa drugs. Rifampin
can be added to doxycycline, TMP-SMX, or clindamycin regimen to enhance its efficacy, but rifampin is never used alone to
treat CA-MRSA because of the risk of developing resistance. A major purported advantage of rifampin in this situation is the
eradication of nasal carriage.11
Some evidence suggests that ciprofloxacin is useful against CA-MRSA, and other fluoroquinolones may also be effective. Nonetheless,
other infectious agents, including nosocomial MRSA, have developed fluoroquinolone resistance quite rapidly, and experts fear
the same thing with CA-MRSA. Fluoroquinolones should probably be reserved for situations in which few alternatives exist.
Linezolid is highly effective against CA-MRSA. It is used infrequently to treat this infection because of its very high cost.
The next therapeutic step for hospitalized patients is vancomycin IV.
After treatment is complete
Most infectious disease specialists agree that it is unnecessary to repeat cultures after the infection has been successfully
treated. Further, the infection does not have a strong tendency to recur. Carriage is dynamic: For staphylococcal infections,
in general, one third of patients lose the strain within a few months of being infected, one third retain it, and one third
acquire a new strain. Some patients become persistent carriers, but these are believed to be the minority. Others may be transient
carriers. Immunity to S aureus remains a conundrum, however. One infection does not provide absolute protection against a future infection.
This consensus article was written by Mary Desmond Pinkowish, MPH, in consultation with Drs Creech, Saravolatz, and Schaffner.
Drs Creech and Schaffner disclose that they have no financial relationship with any manufacturer in this area of medicine.
Dr Saravolatz discloses that he has been a consultant to Pfizer Pharmaceuticals and receives grant support from Pfizer and
Theravance, Inc.
REFERENCES
1. Nakamura MM, Rohling KL, Shashaty M, et al. Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage in the community pediatric population. Pediatr Infect Dis J. 2002;21:917-922.
2. Gonzalez BE, Martinez-Aguilar G, Hulten KG, et al. Severe Staphylococcal sepsis in adolescents in the era of community-acquired
methicillin-resistant Staphylococcus aureus.Pediatrics. 2005;115:642-648.
3. Carleton HA, Diep BA, Charlebois ED, et al. Community-adapted methicillin-resistant Staphylococcus aureus (MRSA): population dynamics of an expanding community reservoir of MRSA. J Infect Dis. 2004;190:1730-1738. Epub 2004 Oct 18.
4. CDC. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus—Minnesota and North Dakota, 1997-1999. MMWR Morb Mortal Wkly Rep. 1999;48:707-710.
5. CDC. Division of Healthcare Quality Promotion. Community-associated MRSA (CA-MRSA). Available at: http://www.cdc.gov/ncidod/hip/ARESIST/ca_mrsa.htm. Accessed June 8, 2005.
6. 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.
7. Johnson LB, Saravolatz LD. Community-acquired MRSA: current epidemiology and management issues. Infect Med. 2005;22:16-20.
8. Lee MC, Rios AM, Aten MF, et al. Management and outcome of children with skin and soft tissue abscesses caused by community-acquired
methicillin-resistant Staphylococcus aureus.Pediatr Infect Dis J. 2004; 23:123-127.
9. Frazee BW, Lynn J, Charlebois ED, et al. High prevalence of methicillin-resistant Staphylococcus aureus in emergency department skin and soft tissue infections. Ann Emerg Med. 2005;45:311-320.
10. Lewis JS 2nd, Jorgensen JH. Inducible clindamycin resistance in Staphylococci: should clinicians and microbiologists
be concerned? Clin Infect Dis. 2005;40:280-5. Epub 2004 Dec 21.
11. Moran GJ, Talan DA. Community-associated methicillin-resistant Staphylococcus aureus: is it in your community and should it change practice? Ann Emerg Med. 2005; 45:321-322.
Who has community-acquired MRSA? Persons with methicillin-resistant Staphylococcus aureus (MRSA) infections that meet all of the following criteria likely to be infected with one of the community-acquired MRSA strains
(CA-MRSA):
- Diagnosis of MRSA was made in the outpatient setting or by a culture positive for MRSA within the first 48 hours after admission
to the hospital.
- No medical history of MRSA infection or colonization.
- No medical history in the past year of hospitalization; admission to a nursing home, skilled nursing facility, or hospice;
dialysis; or surgery.
- No permanent indwelling catheters or medical devices that pass through the skin into the body.
1. CDC. Division of Healthcare Quality Promotion. Community-associated MRSA (CA-MRSA). Available at: http://www.cdc.gov/ncidod/hip/ARESIST/ca_mrsa.htm. Accessed June 8, 2005.
Drugs mentioned in this articleCefadroxil (Duricef)
Cephalexin (Biocef, Keflex)
Ciprofloxacin (Cipro)
Clindamycin (Cleocin)
Daptomycin (Cubicin)
Doxycycline
Erythromycin
Imipenem-cilastatin (Primaxin)
Linezolid (Zyvox)
Rifampin
Tetracycline
Trimethoprim-sulfamethoxazole
Vancomycin (Vancocin)
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