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Community-Acquired MRSA: Current Epidemiology
and Management Issues
Leonard B. Johnson, MD; Louis D.
Saravolatz, MD
Infect Med. 2005; 22 (1): 16-20. ©2005 Cliggott Publishing, Division
of CMP Healthcare Media
Abstract and Introduction
Abstract
While current rates of methicillin-resistant Staphylococcus aureus (MRSA)
colonization among the general population remain low, large clusters
of infections have been reported in numerous locations worldwide. The
primary risk factors for community-acquired (CA) MRSA colonization and
infection are younger age, belonging to a minority group, and low
socioeconomic status. Most patients presenting with CA-MRSA infections
will have skin and soft tissue infections; a smaller number may
present with severe pneumonia that appears to be related to the Panton-Valentine
leukocidin toxin. Therapy for soft tissue infections, with incision
and drainage when necessary followed by adjuvant antibiotics, is
usually curative.
Introduction
The first reports of methicillin-resistant Staphylococcus aureus (MRSA)
occurred in the 1960s among hospitalized patients.[1,2] Within 20
years, MRSA was reported in infections originating in the
community.[3,4] Risk factors among initial reports included injection
drug use, previous antibiotic therapy, and recent hospitalization.
These initial reports likely represented dissemination in the
community of a single hospital-acquired strain of MRSA.[5]
By the late 1990s, community-acquired (CA) MRSA infections in patients
without traditional risk factors were being described in the United
States and Australia.[6-8] While the early US cases occurred among
children, subsequent outbreaks in other populations demonstrated the
increased prevalence of CA-MRSA.[8-10] The most recent outbreaks vary
geographically, yet share similar clinical and laboratory
features.[9,10]
Terminology
It is important to distinguish CA-MRSA infections, which occur in
persons with no significant exposure to health care, from
community-onset MRSA infections, which occur in persons with
significant exposure to health care (such as hemodialysis and oncology
patients). This review will focus on clinical and laboratory features
of CA-MRSA infection in patients without risk factors, in order to
assist the clinician with diagnosis and treatment of these infections.
Colonization
S aureus can colonize the nasopharynx, perineum, or skin. Screening
for colonization traditionally is performed by culture of specimens
from the nasopharynx. Although most colonized persons remain
asymptomatic, S aureus can cause localized or invasive infection
through both disrupted and intact skin. One third of the general
population and up to 50% of those with chronic medical conditions,
such as renal failure or diabetes mellitus, may be colonized with S
aureus .[11] Among healthy persons, rates of MRSA colonization remain
low. Rates of carriage among children with no risk factors for MRSA
colonization have ranged from 0.8% to 3.0%[12,13]; those among adults
have generally been lower.
In a study of 225 healthy adults in New York City, none were
colonized,[14] while only 2 (0.24%) of 833 urban poor adults in San
Francisco were found to carry MRSA in the nasopharynx.[15] A
prevalence of 1% was found among 469 rural American Indians and was
associated with recent antimicrobial use and larger households.[16] A
higher prevalence may be observed in settings that facilitate
cross-transmission of bacteria, such as day-care centers and
correctional facilities.[17,18]
Infection
While rates of colonization in the general population remain low, the
proportion of S aureus infections from the community that are caused
by MRSA is increasing. From 1990 to 1997, the rate of CA-MRSA isolates
among children increased from 1% to 8% in a Chicago tertiary care
facility.[19] A recent study of CA-MRSA infection in children in Texas
reported a 14-fold increase in cases from 1999 to 2001.[20] In both
these reports, isolates from children without risk factors for
colonization had high rates of susceptibility to clindamy cin;
susceptibility is typically lower in nosocomial isolates.
Among adults, rates of CA-MRSA infection have only recently increased
significantly. In a review of community-onset S aureus bacteremias
during 1998 in Connecticut, 15% were caused by MRSA but none occurred
among patients without risk factors.[21] In contrast, the rate of
resistance to methicillin among S aureus infections in persons in the
San Francisco County jail system was 74% in 2002.[18] Because of
underreporting and the episodic nature of cases, the true incidence of
CA-MRSA is difficult to estimate.
Risk factors for CA-MRSA infections appear to differ from those that
were initially observed in early community outbreaks (injection drug
use, previous antibiotic use, and hospitalization). A high prevalence
has been noted among minority populations, including African
Americans, American Indians, and Australian aborigines.[6,9,10,22-24]
Most reports of CA-MRSA infections concern poor populations, which
suggests economic status as a second factor.[6,9,10,22,24] A third
risk factor is age, with a higher prevalence of infection in younger
age groups.
A study that compared community-associated and health care–associated
MRSA infections in Minnesota found that the median age of patients
with community-associated infection was 23 years, versus 68 years for
patients with health care– associated infection.[24] The authors
considered health care–associated cases as those that occur in persons
after 48 hours in the hospital or in persons who have recently been
hospitalized; in residents of long-term– care facilities; or in
patients who have received chemotherapy, recent surgery, or
hemodialysis. Underlying medical conditions do not appear to be a
major risk factor.[6,10,23,24] The presence of a household contact who
is a health care worker also does not appear to increase the risk of
carriage or infection.[17,23]
The proportion and outcomes of adult and pediatric patients with CA-MRSA
infections, as well as the site of their MRSA infections in 8
different studies that provided clinical data are listed in the Table
1 . A high proportion of pediatric cases is noted in these studies,
but there also are increased published reports of adult cases.[25-28]
In most cases, patients present with skin and soft tissue infections,
including cellulitis, abscesses, and furuncles. Nosocomial spread of a
single CA-MRSA strain among postpartum women resulted in 4 cases of
mastitis, which indicates the wide range of soft tissue infections
that may be seen.[28] The next most frequently reported illness is
pneumonia, which appears more frequently in children.
Microbiology
Antimicrobial Susceptibility
CA-MRSA isolates are uniformly _-lactamase–positive
and are assumed to be resistant to all _-lactam agents. These isolates
tend to be more susceptible to other potential antistaph ylococcal
agents than are hospital-acquired or health care–associated MRSA.[29]
CA-MRSA isolates possess a shorter mec A gene than health
care–associated MRSA isolates do, which results in the inability of
CA-MRSA isolates to encode for resistance to other agents.
Among CA-MRSA isolates, susceptibility to erythromycin ranges from 10%
to 100%, with larger series generally reporting susceptibility rates
of more than 50%.[29] Resistance to erythromycin may be encoded by
inducible erm genes. Inducible resistance to clindamycin is seen when
isolates are exposed to erythromycin.[30] The clinical response of CA-MRSA
to clindamycin has been variable. Although most isolates (80% to 90%)
of CA-MRSA are reported as susceptible, the durability of clindamycin
as an antistaphylococcal agent is questionable in view of the
emergence of resistance to clindamycin reported in some areas.[30]
Susceptibilities to fluoroquino lones have been reported in a limited
number of series. More than 90% of CA-MRSA isolates are
ciprofloxacin-susceptible.[29] Susceptibilities to the new
fluoroquinolones, such as moxifloxacin, gatifloxacin, and gemifloxacin,
have not been well studied. Within a short time after the introduction
of ciprofloxacin, MRSA isolates that were resistant to that drug
emerged.[31] Based on this, there is concern that use of the
fluoroquinolone class in cases of MRSA infection may be limited by the
rapid emergence of resistance.
Trimethoprim-sulfamethoxazole (TMP-SMX) has maintained good in vitro
activity in most settings with MRSA. In CA-MRSA infection, generally
more than 95% of isolates remain susceptible to TMP-SMX. This agent
demonstrates an excellent safety profile, and limited clinical
experience suggests that it is an effective agent for MRSA infection,
even in patients with deep-seated infections.[32] Fortunately, CA-MRSA
isolates have also been uniformly susceptible to vancomycin,
daptomycin, linezolid, and quinupristin-dalfopristin. Limited data
suggest that these isolates also may be susceptible to tetracycline
and imipenem.
Genetic Background
Molecular technology has facilitated our ability to better clarify the
epidemiology of CA-MRSA infection. The most commonly described method
of identifying strains of MRSA is pulsed-field gel electrophoresis (PFGE),
in which chromosomal DNA is cut into pieces with an enzyme, SMA-1, and
run on a gel to separate the fragments, which are referred to as
bands.[33] Isolates of S aureus with the same band pattern are
considered the same strain; those with differences of 1 to 3 bands are
considered related strains; and those with differences of 4 to 6 bands
are possibly related.[34]
While early MRSA outbreaks in the community tended to represent a
single strain,[5] more recent CA-MRSA isolates have frequently
demonstrated more diverse genetic backgrounds.[6,9,18] When PFGE was
performed on small numbers of isolates in an early outbreak, 4
different strains among 7 isolates were found in children in the
Chicago area.[6] Subsequent larger studies have shown that most
isolates belong to several different genetically distinct clonal
groups.[9,18]
MRSA isolates possess a penicillin-binding protein 2a that has reduced
affinity for binding to _-lactam agents. This protein is encoded by
the mec A gene, which is carried by a large mobile element referred to
as staphylococcal chromosome cassette (SCC) mec .[35,36] The SCC mec
gene has been sequenced, and 5 types have been identified, designated
as I, II, III, IVa, and IVb. The novel element designated type IV SCC
mec is much smaller (21 to 24 kb) than other SCC mec elements (34 to
67 kb). The sequence of SCC mec type IV lacks non–_-lactam antibiotic
resistance determinants carried on this genetic element.
In one study, 11 of 12 CA-MRSA isolates contained this novel SCC mec
type IV element.[37] This common element has been found in isolates
that possess diverse genetic backgrounds (based on PFGE typing). This
novel type IV SCC mec element is smaller than the mec elements that
are found in health care–associated MRSA. It has been speculated that
the SCC mec type IV element possesses greater mobility and a greater
propensity toward transferring to S aureus strains with diverse
genetic backgrounds via plasmids or, possibly, bacteriophages.
Investigators recently suggested that the insertion of this element
into a virulent strain of methicillin-susceptible S aureus resulted in
a strain of CA-MRSA that was responsible for 2 pediatric cases of
severe pneumonia.[38]
Virulence Factors
The virulence characteristics of CA-MRSA appear distinct in that they
carry the Panton-Valentine leukocidin (PVL) genes that may lead to
serious necrotizing soft tissue infections. Among 117 CA-MRSA strains
from the United States, France, Switzerland, Australia, New Zealand,
and Western Samoa, all contained the PVL gene and type IV SCC mec
gene, whereas the presence of other enterotoxins varied widely.[39]
The frequency of PVL genes may explain the frequency of skin
infections, as well as the occasional necrotizing pneumonia, seen with
CA-MRSA infections. These clinical manifestations are distinct from
those seen in health care–associated MRSA infections.
Treatment Considerations
Despite resistance to most first-line antimicrobials, mortality rates
for patients with CA-MRSA infection are low. Most deaths occur in
patients who present with necrotizing pneumonia. Data concerning which
specific antimicrobial therapies were used are limited in most series.
A number of infections were cured with incision and drainage alone.
Since most isolates had retained susceptibility to non–_-lactam
antibiotics, a variety of agents, including vancomycin, TMP-SMX, and
ciprofloxacin, were used successfully.
Initial therapy for CA-MRSA infection should be with vancomycin;
TMP-SMX, daptomycin, linezolid, and quinupristin-dalfopristin are
alternative agents. Among these, TMP-SMX is the least expensive and is
useful in patients who have completed parenteral vancomycin therapy
and who need oral therapy for discharge.
Empiric coverage for MRSA is not currently indicated for all patients
with soft tissue infections, since the potential for increasing
antibiotic resistance outweighs the risk of delaying therapy pending
culture results. However, seriously ill patients with presumed
staphylococcal infections should probably be treated with drugs
effective against MRSA.
Patients presenting from the community in whom there is a high
suspicion of staphylococcal pneumonia should receive coverage for MRSA
pending culture results. Those with mild skin and soft tissue
infections should be treated with _-lactam agents (except for those
with _-lactam allergies). Physicians should continue to monitor local
trends in rates of CA-MRSA infection and should send appropriate
specimens for culture to evaluate for increasing resistance in their
communities.
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Leonard B. Johnson, MD , Louis D. Saravolatz, MD , Wayne State
University School of Medicine, DetroitSt John Hospital and Medical
Center, Detroit
Dr Johnson is assistant professor of medicine at Wayne State
University and assistant program director, division of infectious
diseases, St John Hospital and Medical Center, Detroit. Dr Saravolatz
is professor of medicine at Wayne State University and chief,
department of medicine, St John Hospital and Medical Center
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