Sludge Watch ==> Community Acquired MRSA - causing hospital associated infections

[Maureen Reilly]

Sludgewatch Admin:

People are getting, and dying of, antibiotic resistant infections at a 
staggering rate.
More than auto accidents breast cancer, and AIDs combined.

These diseases are increasingly acquired in the community - not just in 
healthcare settings among the old, sick, or immunocompromised.  So hospitals 
are worried about people tracking these infections into hospital and 
healthcare settings.

But under heavy pressure from the wastewater industry, healthcare 
professionals are quiet about the role of hospitals in sending those 
diseases out into the community in hospital sewage.  These antibiotic 
resistance bacteria end up in sewage - sewage sludge, effluents, and into 
the 'reclaimed water' that is increasingly irrigating our urban parks and 
private lawns and gardens.

And irrigating our fresh spinach fields in Monterey County, Salinas Valley.

We should not allow these diseases out into the community and into the rural 
environment and agricultural lands.  Better disinfection through thermal 
treatment of all hospital sewage may be a start.  But with community 
acquired infections and rampant antibiotic resistance, we have to find 
better ways to contain and manage the sewage we produce every day.  This is 
a sanitation crisis.


..............................................
www.medscape.com


NOTE: To view the article with Web enhancements, go to:
http://www.medscape.com/viewarticle/551380


--------------------------------------------------------------------------------


Community-Associated Methicillin-Resistant Staphylococcus Aureus Isolates 
Causing Healthcare-Associated Infections


Cynthia L. Maree; Robert S. Daum; Susan Boyle-Vavra; Kelli Matayoshi; Loren 
G. Miller

Emerg Infect Dis.  2007;13(2):236-242.  ©2007 Centers for Disease Control 
and Prevention (CDC)
Posted 02/26/2007

Abstract and Introduction
Abstract
We noted a marked increase in healthcare-associated (HA) 
methicillin-resistant Staphylococcus aureus (MRSA) infections caused by 
isolates phenotypically consistent with community-associated (CA)-MRSA 
strains. To study this trend, we retrospectively examined all HA-MRSA 
isolates from patients in our institution during 1999-2004. An isolate was 
considered an SCCmecIV phenotype if it had antimicrobial drug 
susceptibilities consistent with typical CA-MRSA isolates. Our phenotypic 
definition was validated in a limited subset of isolates by SCCmec genotype, 
pulsed-field gel electrophoresis, and multilocus sequence typing. Among 352 
patients with HA-MRSA isolates, SCCmecIV phenotype increased from 17% in 
1999 to 56% in 2003 (p<0.0001). Antimicrobial drug-susceptibility phenotype 
and genotype were consistent in 21 (91%) of 23 isolates. In a multivariate 
model, the SCCmec type IV phenotype was independently associated with wound 
culture source, later year of collection, and MRSA isolated earlier during 
hospitalization. In conclusion, MRSA isolates phenotypically similar to CA 
strains have become the predominant isolates associated with HA-MRSA in our 
hospital.

Introduction
Methicillin-resistant Staphylococcus aureus (MRSA) is the most frequently 
identified antimicrobial drug-resistant pathogen in US hospitals.[1] The 
epidemiology of infections caused by MRSA is rapidly changing. In the past 
10 years, infections caused by this organism have emerged in the community. 
The 2 MRSA clones in the United States most closely associated with 
community outbreaks, USA400 (MW2 strain, ST1 lineage) and USA300, often 
contain pvl genes and, more frequently, have been associated with skin and 
soft tissue infections.[2,3] Outbreaks of community-associated (CA)-MRSA 
infections have been reported in correctional facilities, among athletic 
teams, among military recruits, in newborn nurseries, and among men who have 
sex with men.[4-7] CA-MRSA infections now appear to be endemic in many urban 
regions and cause most CA-S. aureus infections.[5,6,8-10]

CA-MRSA isolates were first recognized by distinct resistance profiles of 
antimicrobial drugs that lacked resistance to older antimicrobial 
drugs.[11-13] Several groups have noted these distinct susceptibility 
patterns appearing in isolates from hospitalized patients. Denis et al. 
noted that since 1995, MRSA isolates in Belgian hospitals were losing 
resistance to older antimicrobial drugs such as gentamicin and 
clindamycin.[14] A Spanish hospital experienced a decrease in 
gentamicin-resistant MRSA isolates (from 97% in 1998 to 20% in 2002) and a 
simultaneous increase in MRSA isolates carrying the SCCmec type IV cassette 
(from 0% prevalence in 2000 to 23% prevalence in 2002).[15] A French group 
noted a similar finding in their hospitals over an 11-year period and found 
a correlation between isolates that contained SCCmec type IV and 
susceptibility profiles to &#8805;3 antimicrobial drugs.[16] However, these 
investigations did not distinguish between cultures obtained from patients 
hospitalized with CA infection and those with hospital-associated (HA) 
infections. Thus, it is unclear whether these trends in decreased 
antimicrobial drug resistance and increased number of MRSA isolates that 
contained SCCmec type IV were due to increased hospitalization of patients 
with CA-MRSA infections or to an increased prevalence of isolates containing 
SCCmec type IV among HA-MRSA isolates.

Some MRSA strains associated with CA infection have been noted to cause HA 
infections. Outbreaks of HA infections caused by isolates containing SCCmec 
type IV have been reported from Australia and the United States. Affected 
populations have included postpartum women and patients undergoing 
prosthetic joint replacement.[17-19] Another recent report demonstrated that 
CA strains had emerged as a substantial cause of HA bloodstream 
infections.[20] However, these reports are anecdotal, and data examining 
temporal trends are lacking.

At our institution, which is located in an area in which CA-MRSA infections 
are endemic, we have noted a large increase in HA infections caused by MRSA 
isolates that, by assessment of antibiotic susceptibility patterns, appear 
to carry the SCCmec type IV element (e.g., susceptible to gentamicin, 
clindamycin, and trimethoprim-sulfamethoxazole).[6,10,21] The aim of this 
study was to quantify this trend over a 6-year period.

Methods
Population
To find patients with HA-MRSA infections, we identified all cultures 
obtained &#8805;72 hours after hospitalization that grew MRSA, from January 
1, 1999, through December 31, 2004, at Harbor-UCLA Medical Center, a 
tertiary-care, urban, county hospital in Los Angeles County. At this 
hospital, surveillance cultures for MRSA colonization are not routinely 
performed; therefore, cultures positive for MRSA are likely to reflect 
infection rather than colonization. For a given patient, we examined only 
data from the first positive culture and excluded patients who had positive 
cultures both &#8805;72 hours and <72 hours after admission. If a patient 
had been hospitalized more than once during the study period, only data from 
the first hospitalization were retained. A standardized instrument was used 
to abstract data from the medical record of each patient. Information 
obtained included demographics, admission date and time, hospital location, 
antimicrobial drug susceptibility of the MRSA isolate, and time, date, and 
source of the MRSA culture.

We obtained only MRSA blood isolates for molecular typing because the 
clinical microbiology laboratory discards all other types of isolates after 
identification is complete. In vitro susceptibilities were reported as 
minimal inhibitory concentrations and performed with the VITEK system 
(bioMérieux, Durham, NC, USA), according to the protocols of the Clinical 
and Laboratory Standards Institute (CLSI). The investigation protocol was 
reviewed and approved by the Institutional Review Board of Harbor-UCLA 
Medical Center.

Molecular Characterization of Strains
Molecular typing was performed at the University of Chicago by investigators 
who were blinded to the clinical details and antibiograms of the isolates.

SCCmec Typing
PCR was performed to detect mecA by using the primer pair mecAF/mecAR.[22] 
SCCmec elements were distinguished by the molecular architecture of the ccr 
and mecA complexes.[21,23,24] PCR typing of SCCmec types I-IV was performed 
under the conditions previously described.[24,25] SCCmec type II (ccrAB 
complex type 2 and mec complex class A), SCCmec type III (ccrAB complex type 
3 and mec complex class A), and SCCmec type IV (ccrAB complex type 2 and mec 
complex class B) were assigned according to published criteria.[25] PCR 
primers used to detect mecI (primers mI3/mI4), the mecR1 membrane spanning 
region (MS) (primers mcR3/mcR4), and the mecR1 penicillin-binding region 
(PB) (primers mcR1/mcR5) were originally reported by Suzuki et al..[26] 
Screening for ccrAB complex types 1, 2, and 3 (ccrAB 1, 2 and 3) was 
accomplished with a multiplex PCR assay that uses a mixture of 4 primers 
designed by Ito et al., consisting of a common forward primer (ß2) and 
reverse primers, &#945;2, &#945;3, and &#945;4 specific for ccrAB complexes 
1, 2, and 3. Thermocycler conditions used have been described.[27] The 
presence of the ccrAB gene complex allotype 4 (ccr complex 4) was assessed 
in a separate reaction that used the primer pair ccrA4F and ccrB4R.[27] 
Screening for the ccrC gene (ccr complex 5) was performed with a forward 
primer (&#947;F) in combination with the reverse primer &#947;R described by 
Ito et al..[28] Prototype strains used for SCCmec typing were NCTC10442 
(SCCmec I), N315 (SCCmec II), 85/2082 (SCCmec III), MW2 (SCCmec IV), and WIS 
(SCCmec V). The control strain used for detection of ccrAB4 was S. 
epidermidis strain ATCC 12228, which contains ccrAB4 in the 
non-mec-containing SCCcomposite island.[24]

MLST
MLST was performed by PCR amplification and sequencing of 7 housekeeping 
genes by using the primer pairs designed by Enright et al.[29] Denville 
Taq-Pro Complete (Denville Scientific, Metuchen, NJ, USA) or the Taq DNA 
Polymerase (Promega, Madison, WI, USA) was used for the PCR reactions. PCR 
products were evaluated on an agarose gel and purified by using Millipore 
96-well Montage (Billerica, MA, USA) plates according to manufacturer's 
instructions. The purified templates were sequenced at the University of 
Chicago Core Sequencing Facility and evaluated with the use of Vector NTI 
software (Invitrogen, Carlsbad, CA, USA). Each sequence was submitted to the 
MLST database website (www.mlst.net) for assignment of the allelic profile 
and sequence type (ST).

Screening for pvl Genes
Isolates were screened for the lukF-PV and lukS-PV genes encoding the 
components of the PVL toxin by PCR amplification of a 433-bp product that 
includes a portion of both the lukS-PV and lukF-PV ORFs by using the primer 
pair luk-PV-1/ luk-PV-2 (final concentration 0.2 µM) designed by Lina et 
al..[30] The thermocycler conditions have been described.[27]

Case Definition and Data Analysis
A standardized definition of CA-MRSA infection was created by the Centers 
for Disease Control and Prevention (CDC) Active Bacterial Core Surveillance 
sites.[31] Using this definition, we defined HA-MRSA infections as those 
MRSA infections that did not meet the definition of CA-MRSA infections. 
Specifically, we defined an MRSA isolate as HA associated if the original 
entry criteria of hospitalization for &#8805;72 hours before culture 
acquisition was met and if in the year before the present hospitalization, 
the patient had had any 1 of the following: hospitalization, surgery, 
residency in a long-term care facility, and hemodialysis or peritoneal 
dialysis, or at the present admission had indwelling percutaneous devices or 
catheters. A CA infection was defined as a culture-confirmed MRSA infection 
without any of the above criteria. However, if the patient did not meet any 
of the above criteria, had an infection at the time of admission, and the 
culture of the infection on admission was taken &#8805;72 hours after 
admission, then the infection was considered CA. An example of this 
situation would be a deep tissue infection microbiologically diagnosed from 
a surgical biopsy specimen 4 days after the patient's admission.

To validate our definition of HA-associated infection, we reviewed 105 (30%) 
randomly selected charts of the patients with MRSA infections identified 
&#8805;72 hours after hospitalization. The purpose of this validation was to 
confirm that these cultures did not reflect CA infections that were 
diagnosed late (>72 hours) in the hospital course. Of note, in the CDC 
definition, an infection is considered HA if it occurs >48 hours after 
admission. Yet, we chose &#8805;72 hours as a cut-off to more conservatively 
capture HA infections, i.e., to minimize the miscategorization of CA 
infections as HA infections.

We then defined MRSA strains as having the SCCmec type IV phenotype if the 
isolates were resistant to oxacillin and susceptible to gentamicin, 
clindamycin, and trimethoprim-sulfamethoxazole. All other isolates were 
considered to be phenotypically non-SCCmec type IV.

Characteristics were compared between patients infected with the non-SCCmec 
type IV phenotype isolates and those infected with SCCmec type IV phenotype 
isolates by using a X2 or t test, as appropriate. No adjustments were made 
for multiple comparisons. Temporal trends in the proportion of the SCCmec 
type IV phenotype were compared with the Cochran-Armitage test of trends. A 
multivariate analysis that predicted phenotypically SCCmec type IV isolates 
was performed by using an unconditional logistic regression model and a 
backward model selection method. A p value of &#8804;0.05 was defined as 
statistically significant. Data analysis was done with SAS software version 
8.2 (SAS Institute Inc., Cary, NC, USA).

Results
Population Characteristics
We identified 352 patients who had HA-MRSA cultures; 229 (65%) were men, and 
the median age was 50 years (mean 49.5 years). In the subset of medical 
records reviewed for validation of HA or CA status, none of the patients' 
infections (0/105) fit our definition of a CA infection. The SCCmec type IV 
phenotype was identified in 128 (36%) of these 352 patients. Compared with 
the non-SCCmec type IV phenotype, patients with the SCCmec type IV phenotype 
were younger (median age 48 vs. 54 years, p = 0.02) and had the defining 
culture taken earlier in the hospitalization (median 8 vs. 15 days, p = 
0.01). Finding an isolate with the SCCmec type IV phenotype was more likely 
if the culture source was from a wound, blood, or source other than sputum 
(odds ratio [OR] 2.9, 95% confidence interval [CI] 1.7-5.0, p<0.0001; OR 
2.6, 95% CI 1.2-5.7, p = 0.02; and OR 1.2, 95% CI 0.6-2.3, p = 0.69) ( Table 
1 ).

Validation of the SCCmec Phenotype Definition
Of the 352 cultures, 35 were recovered from blood and were potentially 
available for genetic analysis. We were able to subculture 24 of the blood 
isolates. We could not perform SCCmec typing on 1 of the 24 growing 
isolates. The 23 remaining isolates were representative of each year of the 
6-year period except 1999, when no isolates could be recovered.

Twelve isolates carried the SCCmec type IV element, and 9 also carried the 
pvl genes ( Table 2 ). Eleven isolates carried the SCCmec type II element; 
none carried pvl. The clinical definition of the SCCmec IV phenotype was 
fulfilled by 11 (92%) of the 12 isolates that carried the SCCmec IV element. 
The exception was an isolate that contained SCCmec IV that was resistant to 
gentamicin, clindamycin, and trimethoprim-sulfamethoxozole. The definition 
of the non-SCCmec IV phenotype was fulfilled by 10 (91%) of 11 isolates 
carrying the SCCmec II element. Phenotypic case definition of SCCmec type 
was highly correlated with the genotype confirmation of the SCCmec type 
phenotype (p<0.0001 by Fisher exact test).

Trend and Multivariate Analysis of the SCCmec type IV Phenotype
The proportion of MRSA isolates with the SCCmec type IV phenotype increased 
from 17% in 1999 to 56% in 2003 (p<0.0001, Figure 1). The proportion of 
isolates that were of the SCCmec type IV phenotype in 2004 (52%) was little 
changed from 2003 (Figure 1). In the multivariate model, independent 
predictors for having an SCCmec type IV phenotype isolate were wound source 
of culture (referent group was sputum source, OR 2.6, 95% CI 1.5-4.6, p = 
0.001), culture obtained in less time after admission, (OR 0.88 per week, 
95% CI 0.8-0.98, p = 0.02), and year of culture acquisition (p<0.0001) ( 
Table 1 ).



Figure 1.
Percentage of methicillin-resistant Staphylococcus aureus (MRSA) isolates 
among healthcare-associated MRSA isolates that are SCCmec type IV phenotype, 
1999-2004.



Discussion
In many urban centers worldwide, infections due to MRSA account for a large 
proportion of CA-S. aureus infections; in some communities MRSA accounts for 
more than half of CA-S. aureus infections.[6,8-10,32] There have been 
reports of strains frequently associated with community outbreaks causing HA 
infections, but they have been mostly limited to case reports or case 
series.[17-19] To our knowledge, ours is the first investigation quantifying 
the rise of MRSA isolates typical of CA disease to become the predominant 
strain of HA-MRSA (i.e., accounting for >50% of MRSA strains) within the 
hospital setting. Remarkably, at our institution the number of HA-MRSA 
isolates that have a CA phenotype, which previously was uncommon, now is 
 >50%.

Our analysis found 3 significant risk factors for an SCCmec type IV 
phenotype MRSA culture. First, patients with MRSA cultures from a wound 
source were more likely to have the SCCmec type IV phenotype. This finding 
may be understandable, given that the most common clinical syndrome 
described with CA-MRSA infections has been skin and soft tissue 
infections.[10,33] In addition, 75% of CA-MRSA isolates that were genotyped 
carried the pvl gene, which has a strong association with skin and soft 
tissue infections.[33] A second risk factor for the SCCmec type IV phenotype 
was a shorter length of hospital stay before MRSA culture. This association 
may be due to the increased severity of illness and coexisting conditions in 
patients with a longer hospital stay, factors that have been commonly 
associated with the traditional (non-SCCmec type IV) HA-MRSA infections. 
However, measures of severity of illness and coexisting conditions were not 
captured in this investigation. A third risk factor was a later year of 
culture collection; the likelihood of SCCmec type IV phenotype peaked in 
2003. The rise of these isolates in our hospital may be from CA-MRSA 
isolates brought in from colonized persons from the community. CA-MRSA 
infections in Los Angeles County have rapidly become common and now exceed 
the frequency of those caused by CA-methicillin-susceptible S. aureus.[34] 
Alternatively, the rise of SCCmec type IV isolates may be a result of spread 
throughout our hospital by the usual means of dissemination in a healthcare 
setting (e.g., hands of healthcare workers, contaminated environment)[35] or 
possibly by a combination of factors.

Exactly why the SCCmec type IV strains are successful in hospital settings 
such as ours and others[20] is unknown. Some evidence indicates that SCCmec 
type IV strains may be more "fit" than SCCmec types II/III that contain 
HA-MRSA isolates. Compared with methicillin-susceptible S. aureus, isolates 
containing SCCmec type II/III replicate more slowly in vitro.[36] Okuma et 
al. found that CA-MRSA isolates that contain SCCmec type IV replicate more 
rapidly than these traditional HA-MRSA strains and argued that CA-MRSA may 
have enhanced ecologic fitness compared with SCCmec type II/III isolates, 
perhaps due simply to a shorter doubling time.[37] Given the vulnerable 
population within the hospital setting, it is unclear how infections with 
isolates that contain SCCmec type IV will differ in symptoms and severity 
from those caused by traditional HA-MRSA isolates. On the basis of our study 
and other somewhat similar reports,[20] concern is rising that USA300 
strains may overtake the traditional HA-MRSA strains in many hospital and 
healthcare settings.

Our investigation had some limitations. First, the analysis was 
retrospective and thus it was not possible to prospectively identify 
patients with HA infections and compare them with patients with CA 
infections. Although, by means of a chart review of a subset of patients who 
were selected by the criteria of a MRSA culture obtained &#8805;72 hrs after 
admission, none of these infections fulfilled the CDC definition of a 
CA-MRSA infection.[31]

A second limitation was that our case definition was based on phenotypic 
criteria because nonbloodstream isolates had been discarded and the SCCmec 
type could not be validated. Traditionally, most HA-MRSA isolates in the 
United States carry SCCmec type II (and to a lesser extent, SCCmec type III) 
that encodes resistance to ß-lactam antimicrobial agents bleomycin, 
macrolide-lincosamide-streptogamin B, aminoglycosides, and 
spectinomycin.[38] Gentamicin resistance occurs in most strains that carry 
the SCCmec type II element but is conferred by the aac6´-aph2´´ gene 
elsewhere on the chromosome and is frequently carried by transposon 
Tn4001.[11,16] Therefore, to select for isolates that did not confer a 
phenotype typical of healthcare-associated or non-SCCmec type IV-containing 
isolates, the SCCmec type IV phenotype was defined as isolates that were 
resistant to oxacillin and susceptible to gentamicin, clindamycin, and 
trimethoprim-sulfamethoxazole.

Some banked isolates did not grow, and in 1 isolate we could not detect an 
SCCmec element. Of note, stored isolates may lose their SCCmec elements over 
time,[39] which may explain our findings. Nevertheless, over the 6-year 
observation period of our investigation, among isolates, the phenotype and 
genotype definition of SCCmec type were in agreement for >90% of isolates. 
Thus, we were able to validate our case definition of an HA-MRSA isolate 
with SCCmec type IV phenotype using both chart review and SCCmec typing.

A third limitation of our investigation was that we were able to recover 
only bloodstream isolates, a subset of strains that are small and 
potentially nonrepresentattive. Whether the relationship of phenotype to 
genotype is similar for bloodstream and nonbloodstream infections is 
unclear. A fourth limitation is that all of the patients were from 1 
institution and, therefore, may only reflect local trends. However, as 
previously mentioned, reports of isolates associated with the CA-MRSA 
infections causing HA infections are growing.[17-20]

In summary, we found that over a 5-year span, MRSA with a CA-MRSA phenotype 
has become the most common cause of HA-MRSA infections in our institution. 
This finding has important implications for MRSA epidemiology, infection 
control practices, and empiric antimicrobial drug selection.

Findings from this investigation were presented in part at the 45th Annual 
International Conference on Antimicrobial Agents and Chemotherapy, 
Washington, DC, USA, December 2005.



Table 1. Patients With Healthcare-Associated MRSA Isolates, 1999-2004, and 
Predictors of SCCmec Type IV Phenotype*



Characteristic Patients with HA-MRSA, isolates, % (no.) SCCmec phenotype,% 
(no.) Predictors of SCCmec type IV phenotype
Type IV Type II/III Bivariate anaylsis Multivariate analysis
Odds ratio
(95% CI) p value Odds ratio
(95% CI) p value
Total (352) 36 (128) 64 (224)
Sex
   F 35 (123) 36 (44) 64 (79)   0.87   >0.05
   M 65 (229) 37 (84) 63 (145)
Age, y
   Mean 50±19 SD 47±1.7 SE 51±1.3 SE   0.02   >0.05
   Median (range) 50 (<1-97) 48 (<1-87) 54 (<1-97)
Time from admission to specimen collection, d
   Mean 19±21 SD 15±1.9 SE 21±1.4 SE   0.01 0.88 (0.8-0.98)† 0.02
   Median (range) 12 (4-184) 8 (4-174) 15 (4-184)
Culture specimen source
   Blood 10 (35) 46 (16) 54 (19) 2.6 (1.2-5.7) 0.02 2.2 (0.97-5.0) 0.058
   Sputum 34 (188) 25 (29) 75 (89) Reference   Reference
   Wound 38 (133) 49 (65) 51 (68) 2.9 (1.7-5.0) <0.0001 2.6 (1.5-4.6) 0.001
   Other 19 (66) 27 (18) 73 (48) 1.2 (0.6-2.3) 0.69 1.1 (0.5-2.2) 0.82
Year culture specimen collected
   1999 52 (15) 17 (9) 83 (43) Reference <0.0001‡ Reference <0.0001
   2000 57 (16) 19 (11) 81 (46) 1.1 (0.4-3.0)   NS§
   2001 65 (19) 28 (18) 72 (47) 1.8 (0.7-4.5) 1.8 (0.9-3.7)
   2002 47 (13) 43 (20) 57 (27) 3.5 (1.4-8.9] 3.2 (1.5-6.9)
   2003 63 (18) 56 (35) 44 (28) 6.0 (2.4-14.3) 5.2 (2.5-10.5)
   2004 68 (19) 52 (35) 48(33) 5.1 (2.1-12)   4.4 (2.2-8.8)

*MRSA, methicillin-resistant Staphylococcus aureus; HA, healthcare 
associated; CI, confidence interval; SD, standard deviation; SE, standard 
error; NS, not significant; boldface indicates significance.
†Multivariate analysis results reflect time in weeks.
‡Measured with the Cochran-Armitage test of trends.
§Was not a significant predictor in the multivariate model.



Table 2. Summary of Genetic Testing for 24 Healthcare-Associated MRSA Blood 
Isolates*†



No. isolates SCCmec mecI mecR1(PB) pvl MLST Clindamycin Gentamicin TMP-SMX 
SCCmec type phenotype‡
8 IV - - + 8 S S S IV
1 IV - - + 1 S S S IV
2 IV - - - 8 S S S IV
1* IV - - - 8 R R R II
5 II + + - 5 R R S II
4 II + + - 5 R S S II
1 II + + - 8 R S S II
1§ II + + - 5 S S S IV
1¶ - - - - 5 R S S II

*MRSA, methicillin-resistant Staphylococcus aureus; PB, penicillin-binding 
region; MLST, multilocus sequence typing; R, resistant; S, susceptible; 
TMP-SMX, trimethoprim-sulfamethoxazole.
†All isolates were associated with mecA and ccr2 genes.
‡Phenotype: as defined by the study case definition, according to 
antimicrobial drug susceptibilities (see Methods).
§SCCmec phenotype did not match genotype.
¶SCCmec was not located for this isolate.






References
Centers for Disease Control and Prevention. National Nosocomial Infections 
Surveillance System (NNIS) report, data summary from January 1992 through 
June 2003, issued August 2003. Am J Infect Control. 2003;31:481-98.
Deresinski S. Methicillin-resistant Staphylococcus aureus: an evolutionary, 
epidemiologic, and therapeutic odyssey. Clin Infect Dis. 2005;40:562-73.
Chambers HF. Community-associated MRSA -- resistance and virulence converge. 
N Engl J Med. 2005;352:1485-7.
Chambers HF. The changing epidemiology of Staphylococcus aureus? Emerg 
Infect Dis. 2001;7:178-82.
Centers for Disease Control and Prevention. Outbreaks of 
community-associated methicillin-resistant Staphylococcus aureus skin 
infections -- Los Angeles County, California, 2002-2003. MMWR Morb Mortal 
Wkly Rep. 2003;52:88.
Bancroft E, Kilgore G, Jones A, Yasuda L, Lee NE, Ruane P, et al. Four 
outbreaks of community-associated methicillin-resistant Staphylococcus 
aureus in Los Angeles County. Presented at the 41st Annual Meeting of the 
Infectious Diseases Society of America; 2003 Oct 9-13; San Diego, 
California. Alexandria (VA): Infectious Diseases Society of America; 2003.
Ellis MW, Hospenthal DR, Dooley DP, Gray PJ, Murray CK. Natural history of 
community-acquired methicillin-resistant Staphylococcus aureus colonization 
and infection in soldiers. Clin Infect Dis. 2004;39:971-9.
Eady EA, Cove JH. Staphylococcal resistance revisited: community-acquired 
methicillin resistant Staphylococcus aureus -- an emerging problem for the 
management of skin and soft tissue infections. Curr Opin Infect Dis. 
2003;16:103-24.
Kaplan SL, Hulten KG, Gonzalez BE, Hammerman WA, Lamberth L, Versalovic J, 
et al. Three-year surveillance of community-acquired Staphylococcus aureus 
infections in children. Clin Infect Dis. 2005;40:1785-91.
Moran GJ, Amii RN, Abrahamian FM, Talan DA. Methicillin-resistant 
Staphylococcus aureus in community-acquired skin infections. Emerg Infect 
Dis. 2005;11:928-30.
Lelievre H, Lina G, Jones ME, Olive C, Forey F, Koussel-Delvallez M, et al. 
Emergence and spread in French hospitals of methicillin-resistant 
Staphylococcus aureus with increasing susceptibility to gentamicin and other 
antibiotics. J Clin Microbiol. 1999;37:3452-7.
Seal JB, Moreira B, Bethel CD, Daum RS. Antimicrobial resistance in 
Staphylococcus aureus at the University of Chicago Hospitals: a 15-year 
longitudinal assessment in a large university-based hospital. Infect Control 
Hosp Epidemiol. 2003;24:403-8.
Weber JT. Community-associated methicillin-resistant Staphylococcus aureus. 
Clin Infect Dis. 2005;41(Suppl 4):S269-72.
Denis O, Deplano A, Nonhoff C, De Ryck R, de Mendonca R, Roltiers S, et al. 
National surveillance of methicillin-resistant Staphylococcus aureus in 
Belgian hospitals indicates rapid diversification of epidemic clones. 
Antimicrob Agents Chemother. 2004;48:3625-9.
Perez-Roth E, Lorenzo-Diaz F, Batista N, Moreno A, Mendez-Alvarez S. 
Tracking methicillin-resistant Staphylococcus aureus clones during a 5-year 
period (1998 to 2002) in a Spanish hospital. J Clin Microbiol. 
2004;42:4649-56.
Donnio PY, Preney L, Gautier-Lerestif AL, Avril JL, Lafforgue N. Changes in 
staphylococcal cassette chromosome type and antibiotic resistance profile in 
methicillin-resistant Staphylococcus aureus isolates from a French hospital 
over an 11 year period. J Antimicrob Chemother. 2004;53:808-13.
Kourbatova EV, Halvosa JS, King MD, Ray SM, White N, Blumberg HM. Emergence 
of community-associated methicillin-resistant Staphylococcus aureus USA 300 
clone as a cause of health care-associated infections among patients with 
prosthetic joint infections. Am J Infect Control. 2005;33:385-91.
O'Brien FG, Pearman JW, Gracey M, Riley TV, Grubb WB. Community strain of 
methicillin-resistant Staphylococcus aureus involved in a hospital outbreak. 
J Clin Microbiol. 1999;37:2858-62.
Saiman L, O'Keefe M, Graham PL III, Wu F, Said-Salim B, Kreiswirth B, et al. 
Hospital transmission of community-acquired methicillin-resistant 
Staphylococcus aureus among postpartum women. Clin Infect Dis. 
2003;37:1313-9.
Seybold U, Kourbatova EV, Johnson JG, Halvosa SJ, Wang YF, King MD,. et al. 
Emergence of community-associated methicillin-resistant Staphylococcus 
aureus USA300 genotype as a major cause of health care-associated blood 
stream infections. Clin Infect Dis. 2006;42:647-56.
Ito T, Katayama Y, Asada K, Mori N, Tsutsumimoto K, Tiensasitorn C, et al. 
Structural comparison of three types of staphylococcal cassette chromosome 
mec integrated in the chromosome in methicillin-resistant Staphylococcus 
aureus. Antimicrob Agents Chemother. 2001;45:1323-36.
Herold BC, Immergluck LC, Maranan MC, Lauderdale DS, Gaskin RE, Boyle-Vavra 
S, et al. Community-acquired methicillin-resistant Staphylococcus aureus in 
children with no identified predisposing risk. JAMA. 1998;279:593-8.
Mongkolrattanothai K, Boyle S, Kahana MD, Daum RS. Severe Staphylococcus 
aureus infections caused by clonally related community-acquired 
methicillin-susceptible and methicillin-resistant isolates. Clin Infect Dis. 
2003;37:1050-8.
Mongkolrattanothai K, Boyle S, Murphy TV, Daum RS. Novel non-mecA-containing 
staphylococcal chromosomal cassette composite island containing pbp4 and 
tagF genes in a commensal staphylococcal species: a possible reservoir for 
antibiotic resistance islands in Staphylococcus aureus. Antimicrob Agents 
Chemother. 2004;48:1823-36.
Ma XX, Ito T, Tiensasitorn C, Jamklang M, Chongtrakool P, Boyle-Vavra S, et 
al. Novel type of staphylococcal cassette chromosome mec identified in 
community-acquired methicillin-resistant Staphylococcus aureus strains. 
Antimicrob Agents Chemother. 2002;46:1147-52.
Suzuki E, Kuwahara-Arai K, Richardson JF, Hiramatsu K. Distribution of mec 
regulator genes in methicillin-resistant Staphylococcus clinical strains. 
Antimicrob Agents Chemother. 1993;37:1219-26.
Boyle-Vavra S, Ereshefsky B, Wang CC, Daum RS. Successful multiresistant 
community-associated methicillin-resistant Staphylococcus aureus lineage 
from Taipei, Taiwan, that carries either the novel staphylococcal chromosome 
cassette mec (SCCmec) type VT or SCCmec type IV. J Clin Microbiol. 
2005;43:4719-30.
Ito T, Ma XX, Takeuchi F, Okuma K, Yuzawa H, Hiramatsu K. Novel type V 
staphylococcal cassette chromosome mec driven by a novel cassette chromosome 
recombinase, ccrC. Antimicrob Agents Chemother. 2004;48:2637-51.
Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG. Multilocus sequence 
typing for characterization of methicillin-resistant and 
methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol. 
2000;38:1008-15.
Lina G, Piemont Y, Godail-Gamot F, Bes M, Peter MO, Gauduchon V, et al. 
Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus 
in primary skin infections and pneumonia. Clin Infect Dis. 1999;29:1128-32.
Minnesota Department of Health. Community-associated methicillin-resistant 
Staphylococcus aureus in Minnesota. Disease Control Newsletter. 
2004;32:61-72.
Centers for Disease Control and Prevention. Four pediatric deaths from 
community-acquired methicillin-resistant -- Minnesota and North Dakota, 
1997-1999. JAMA. 1999;282:1123-5.
Diep BA, Sensabaugh GF, Somboona NS, Carleton HA, Perdreau-Remington F. 
Widespread skin and soft-tissue infections due to two methicillin-resistant 
Staphylococcus aureus strains harboring the genes for Panton-Valentine 
leucocidin. J Clin Microbiol. 2004;42:2080-4.
Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB, et 
al. Methicillin-resistant S. aureus infections among patients in the 
emergency department. N Engl J Med. 2006;355:666-74.
Mulligan ME, Murray-Leisure KA, Ribner BS, Standiford HC, John JF, Korvick 
JA, et al. Methicillin-resistant Staphylococcus aureus: a consensus review 
of the microbiology, pathogenesis, and epidemiology with implications for 
prevention and management. Am J Med. 1993;94:313-28.
Cribier B, Prevost G, Couppie P, Finck-Barbancon V, Grosshans E, Piemont Y. 
Staphylococcus aureus leukocidin: a new virulence factor in cutaneous 
infections? An epidemiological and experimental study. Dermatology. 
1992;185:175-80.
Okuma K, Iwakawa K, Turnidge JD, Grubb WB, Bell JM, O'Brien FG, et al. 
Dissemination of new methicillin-resistant Staphylococcus aureus clones in 
the community. J Clin Microbiol. 2002;40:4289-94.
Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H, Kobayashi I, et al. Whole 
genome sequencing of methicillin-resistant Staphylococcus aureus. Lancet. 
2001;357:1225-40.
van Griethuysen A, van Loo I, van Belkum A, Vandenbroucke-Grauls C, Wannet 
W, van Keulen P, et al. Loss of the mecA gene during storage of 
methicillin-resistant Staphylococcus aureus strains. J Clin Microbiol. 
2005;43:1361-5.


Reprint Address

Loren G. Miller, Harbor-UCLA Medical Center, Division of Infectious Disease, 
1000 W Carson St, Box 466, Torrance, CA 90509, USA: Email: lgmiller at ucla.edu 
.



Cynthia L. Maree,* Robert S. Daum,† Susan Boyle-Vavra,† Kelli Matayoshi,‡,1 
Loren G. Miller*‡

*David Geffen School of Medicine at the University of California, Los 
Angeles, California
†University of Chicago, Chicago, Illinois
‡Los Angeles Biomedical Institute at Harbor-UCLA Medical Center, Torrance, 
California
1Current affiliation: University of Southern California School of Pharmacy, 
Los Angeles, California


Disclosure: C.L.M. reports having received grant support from Pfizer 
Pharmaceuticals. L.G.M. reports having received lecture and consulting fees 
from Pfizer Pharmaceuticals. C.L.M.'s effort was supported by a grant from 
the National Institute of Allergy and Infectious Diseases (NIAID) (T32 
AI07481-09). R.S.D.'s and S.B.V's efforts were supported by a grant from 
NIAID (AI40481-01A1), the Centers for Disease Control and Prevention (CDC) 
(RO1 CCR523379), and the Grant Health Care Foundation. L.G.M.'s effort was 
supported by grants from CDC (RO1/CCR923419) and the National Institutes of 
Health (K23AI0183).

--------------------------------------------------------------------------------