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Community-associated methicillin-resistant Staphylococcus aureus, Minnesota, 2000-2003.


We compared characteristics of community-associated methicillin-resistant Staphylococcus aureus methicillin-resistant Staphylococcus aureus Methicillin-aminoglycoside resistant Staphylococcus aureus, MRSA An organism with multiple antibiotic resistances–eg, aminoglycosides, chloramphenicol, clindamycin, erythromycin, rifampin, tetracycline,  (CA-MRSA CA-MRSA Community Acquired Methicillin-Resistant Staphylococcus Aureus ) skin and soft tissue infections (SSTIs) and CA-MRSA invasive disease identified in Minnesota from 2000 through 2003. A total of 586 patients with SSTIs and 65 patients with invasive disease were identified. Patients with invasive disease were more likely to be smokers (p = 0.03), and report a history of immunosuppressive therapy Immunosuppressive therapy
Medical treatment in which the immune system is purposefully thwarted. Such treatment is necessary, for example, to prevent organ rejection in transplant cases.
 (p = 0.03), emphysema emphysema (ĕmfĭsē`mə), pathological or physiological enlargement or overdistention of the air sacs of the lungs. A major cause of pulmonary insufficiency in chronic cigarette smokers, emphysema is a progressive disease that commonly  (p = 0.011), or injection drug use (p = 0.020) than were SSTI SSTI State Science & Technology Institute (Westerville, OH)
SSTI Skin and Soft Tissue Infection
SSTI Small Spacecraft Technology Initiative
SSTI Skin and Skin Structure Infection
SSTI Six Sigma Technical Institute
 patients. Invasive disease isolates were less likely to be susceptible to ciprofloxacin ciprofloxacin /cip·ro·flox·a·cin/ (sip?ro-flok´sah-sin) a synthetic antibacterial effective against many gram-positive and gram-negative bacteria; used as the hydrochloride salt.

cip·ro·flox·a·cin
n.
 (p = 0.002) and clindamycin (p = 0.001) and more likely to have healthcare-associated pulsed-field gel electrophoresis gel electrophoresis
n.
Electrophoresis performed in a gel composed of agarose, polyacrylamide, or starch.
 subtypes than SSTI isolates (p<0.001). Patients with invasive disease may have had healthcare exposures that put them at risk of acquiring healthcare-associated MRSA MRSA Methicillin-resistant Staphylococcus aureus. See MARSA. , and which were not exclusion criteria exclusion criteria AIDS Donor exclusion criteria, see there  in the CA-MRSA case definition. Continued surveillance of MRSA is needed to better characterize CA-MRSA infections.

**********

Methicillin-resistant Staphylococcus aureus (MRSA) was first reported in 1961 and was recognized as a nosocomial nosocomial /noso·co·mi·al/ (nos?o-ko´me-il) pertaining to or originating in a hospital.

nos·o·co·mi·al
adj.
1. Of or relating to a hospital.

2.
 pathogen by the late 1960s (1,2). Known MRSA risk factors include recent surgery or hospitalization, residence in a long-term care facility long-term care facility
n.
See skilled nursing facility.
, presence of a percutaneous device or indwelling catheter indwelling catheter Any catheter, usually understood to be for the urinary bladder–eg, a 'Foley' left in place for a prolonged period of time , or recent dialysis (3).

In the 1980s, MRSA infections were reported in persons who lacked traditional MRSA risk factors. These infections appeared to be acquired in the community and are now known as community-associated (CA) MRSA infections. These infections have been reported worldwide (4-18). Outbreaks have occurred in many settings and among different populations (10,16,19-23).

Previous studies have demonstrated significant differences between MRSA isolates from persons with health care exposures and persons without these exposures in both antimicrobial susceptibility results and pulsed-field gel electrophoresis (PFGE PFGE Pulsed-Field Gel Electrophoresis ) subtypes (5,7). Studies have also demonstrated demographic differences between CA-MRSA cases and healthcare-associated (HA) MRSA cases regarding age, race, and income (5,7).

The most common clinical manifestations of CA-MRSA are skin and soft tissue infections (SSTIs) such as abscesses or cellulitis Cellulitis Definition

Cellulitis is a spreading bacterial infection just below the skin surface. It is most commonly caused by Streptococcus pyogenes or Staphylococcus aureus.
 (5,7,9,24). Less commonly, CA-MRSA can cause severe diseases such as necrotizing pneumonia Necrotizing pneumonia
Pneumonia that causes the death of lung tissue. It often precedes the development of lung abscess.

Mentioned in: Lung Abscess

necrotizing pneumonia Pulmonology 1 Aspiration pneumonia, see there 2.
, osteomyelitis osteomyelitis (ŏs'tēōmī'əlī`tĭs), infection of the bone and bone marrow. Direct infection of bone usually occurs through open fractures, penetrating wounds, or surgical operations. , and septicemia septicemia (sĕptĭsē`mēə), invasion of the bloodstream by virulent bacteria that multiply and discharge their toxic products. The disorder, which is serious and sometimes fatal, is commonly known as blood poisoning.  (6 9). Most CA-MRSA infections resolve, but deaths from invasive CA-MRSA disease have been reported (8).

Although invasive disease caused by CA-MRSA has been described in the literature, no research has been published that evaluates possible patient and isolate differences between CA-MRSA SSTIs and CA-MRSA invasive disease. A subanalysis of CA-MRSA invasive disease patients and SSTI patients and isolates was conducted by using data collected from CA-MRSA prospective sentinel surveillance in Minnesota from 2000 through 2003.

Methods

Facility Enrollment

In 2000, 12 sentinel hospitals in Minnesota List of hospitals in Minnesota (U.S. state), sorted by location.
  • Brainerd
  • St. Joseph's Medical Center (Brainerd, Minnesota)
  • Buffalo
  • Buffalo Hospital
 (6 in the 7-county Minneapolis-St. Paul metropolitan area and 6 in greater Minnesota) began reporting all cases of MRSA isolated in their respective microbiology laboratories to the Minnesota Department of Health (MDH MDH Minnesota Department of Health
MDH Mälardalens Högskola (Swedish)
MDH Malate Dehydrogenase
MDH Manila Doctors' Hospital
MDH Carbondale, IL, USA - Southern Illinois Airport (Airport Code) 
). Characteristics of these sentinel sites have been described elsewhere (7).

Case Enrollment

Infection control practitioners from each hospital completed a case report form for patients with a positive MRSA culture obtained during 2000-2003. Patient medical records were reviewed to determine the type of infection, history of underlying illness (injection drug use, diabetes, malignancy, chronic heart or lung conditions, chronic skin conditions), or immunosuppressive therapy (defined as long-term systemic steroid use, excluding topical creams, steroids used only for short-course treatment, and inhaled steroids used for asthma) and any history of patient healthcare exposures as defined in the CA-MRSA case definition. The hospital laboratories submitted CA-MRSA isolates to MDH.

All patients with cultures obtained during 2000 2002 who met the CA-MRSA case definition based on medical record review were interviewed to confirm their classification (patient culture dates 2000-2002) and to assess possible CA-MRSA risk factors (patient culture dates 2001-2002). Patients identified at 4 of the 12 sentinel sites during 2003 who had no exclusionary healthcare exposures noted on medical record review were contacted to confirm CA-MRSA classification and conduct risk factor interviews. In addition, a random sample of 2003 patients from the remaining 8 sentinel sites were interviewed to confirm CA-MRSA classification. Informed consent was obtained from all patients before telephone interview.

US Census data from 2000 were used to provide median income by zip code zip code

System of postal-zone codes (zip stands for “zone improvement plan”) introduced in the U.S. in 1963 to improve mail delivery and exploit electronic reading and sorting capabilities.
 (25) as a proxy for case household income. The University of Minnesota (body, education) University of Minnesota - The home of Gopher.

http://umn.edu/.

Address: Minneapolis, Minnesota, USA.
 and MDH Institutional Review Boards reviewed and approved the study.

CA-MRSA Case Definition

The Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center.  (CDC See Control Data, century date change and Back Orifice.

CDC - Control Data Corporation
) Active Bacterial Core Surveillance Program defined a CA-MRSA case as a patient with an MRSA infection and no history of the following: surgery, hospitalization, or residence in a long-term care facility within the year before infection, presence of a percutaneous device or indwelling catheter, dialysis within the previous year, hospitalization >48 h before MRSA culture, or previous MRSA infection or colonization.

Patients were classified as confirmed CA-MRSA case-patients if the medical record review and interview did not show any of the above healthcare risk factors. Patients were classified as probable CA-MRSA case-patients if the medical record review did not show any healthcare risk factors, but the interview was not completed (because of patient refusal, inability to locate, or language barriers).

Subanalysis Inclusion

CA-MRSA patients identified from prospective sentinel surveillance with culture dates in 2000 and 2003 were included in this subanalysis if they had an SSTI (e.g., abscess abscess, localized inflamation associated with tissue necrosis. Abscesses are characterized by inflamation, which is due to the accumulation of pus in the local tissues, and often painful swelling. , cellulitis, folliculitis Folliculitis Definition

Folliculitis is inflammation or infection of one or more hair follicles (openings in the skin that enclose hair).
Description

Folliculitis can affect both women and men at any age.
, wound infection [nonsurgicall) or infection in a normally sterile site caused by CA-MRSA. CDC's Active Bacterial Core Surveillance Program definition of sterile site infections was used to define cases of invasive CA-MRSA disease. This definition defines a normally sterile site as a portion of the body in a healthy state in which no microorganisms are found and includes the following: blood, cerebrospinal fluid cerebrospinal fluid (CSF)

Clear, colourless liquid that surrounds the brain and spinal cord and fills the spaces in them. It helps support the brain, acts as a lubricant, maintains pressure in the skull, and cushions shocks.
, pleural fluid pleural fluid
n.
The thin film of serous fluid between the visceral and parietal pleurae.
, peritoneal peritoneal /peri·to·ne·al/ (per?i-to-ne´al) pertaining to the peritoneum.

peritoneal

pertaining to the peritoneum.
 fluid, pericardial fluid (Physiol.) a serous fluid of a pale yellow color contained in the pericardium.

See also: Pericardiac
, bone, joint fluid, internal body site (lymph node lymph node

Small, rounded mass of lymphoid tissue contained in connective tissue. They occur all along lymphatic vessels, with clusters in certain areas (e.g., neck, groin, armpits).
, brain, heart, liver, spleen, vitreous vitreous /vit·re·ous/ (vit´re-us)
1. glasslike or hyaline.

2. vitreous body.


primary persistent hyperplastic vitreous
 fluid, kidney, pancreas, or ovary ovary, ductless gland of the female in which the ova (female reproductive cells) are produced. In vertebrate animals the ovary also secretes the sex hormones estrogen and progesterone, which control the development of the sexual organs and the secondary sexual ), or other normally sterile site. Although cases of necrotizing pneumonia caused by CA-MRSA have been reported (26), CA-MRSA specimens isolated only from sputum sputum /spu·tum/ (spu´tum) [L.] expectoration; matter ejected from the trachea, bronchi, and lungs through the mouth.

sputum cruen´tum  bloody sputum.
 were not included in our subanalysis because sputum was not defined as a sterile site.

Isolate Characterization

All MRSA isolates submitted to MDH were tested to confirm Staphylococcus aureus Staphylococcus au·re·us
n.
A bacterium that causes furunculosis, pyemia, osteomyelitis, suppuration of wounds, and food poisoning.


Staphylococcus aureus Staphylococcus pyogenes
 identification by using a tube coagulase coagulase /co·ag·u·lase/ (-las) an antigenic substance of bacterial origin, produced by staphylococci, which may be causally related to thrombus formation.

co·ag·u·lase
n.
 test (27) (Difco Laboratories, Detroit, MI, USA). Testing for antimicrobial susceptibility was performed by using a broth microdilution panel (PML PML - Parallel ML.

["Synchronous Operations as First-Class Values", J.H. Reppy <jhr@research.att.com>, Proc SIGPLAN 88 Conf Prog Lang Design and Impl, June 1988, pp. 250-259].
 Microbiologicals, Wilsonville, OR, USA) containing the following 11 antimicrobial agents Antimicrobial agents

Chemical compounds biosynthetically or synthetically produced which either destroy or usefully suppress the growth or metabolism of a variety of microscopic or submicroscopic forms of life.
: ciprofloxacin, gentamicin gentamicin /gen·ta·mi·cin/ (jen?tah-mi´sin) an aminoglycoside antibiotic complex isolated from bacteria of the genus Micromonospora, , trimethoprim/sulfamethoxazole, clindamycin, tetracycline tetracycline (tĕ'trəsī`klēn), any of a group of antibiotics produced by bacteria of the genus Streptomyces. They are effective against a wide range of Gram positive and Gram negative bacteria, interfering with protein , erythromycin erythromycin (ĭrĭth'rōmī`sĭn), any of several related antibiotic drugs produced by bacteria of the genus Streptomyces (see antibiotic). , rifampin rifampin (rĭfăm`pĭn), antibiotic used in the treatment of tuberculosis. It is also used to eliminate the meningococcus microorganism from carriers and to treat leprosy, or Hansen's disease. , linezolid, mupirocin, vancomycin vancomycin (văn'kōmī`sĭn), antibiotic resembling penicillin in the way it acts. It is derived from the bacterium Streptomyces orientalis, which was isolated from soil of India and Indonesia. , and oxacillin oxacillin /ox·a·cil·lin/ (ok?sah-sil´in) a semisynthetic penicillinase-resistant penicillin used as the sodium salt in infections due to penicillin-resistant, gram-positive organisms. . Clinical and Laboratory Standards Institute (CLSI CLSI Clinical and Laboratory Standards Institute (Wayne, PA)
CLSI Cisco Link Services Interface
, formerly National Committee for Clinical Laboratory Standards) breakpoints were used to determine levels of resistance for all antimicrobial agents except mupirocin, for which no CLSI breakpoints exist (28). A standard of <4 [micro]g/mL was used as a breakpoint The location in a program used to temporarily halt the program for testing and debugging. Lines of code in a source program are marked for breakpoints. When those instructions are about to be executed, the program stops, allowing the programmer to examine the status of the program  for susceptibility to mupirocin (29).

Molecular Characterization

Molecular subtyping of MRSA isolates was performed by PFGE and digestion with the restriction endonuclease restriction endonuclease

one of over 200 enzymes isolated from bacteria that cleave any DNA molecule at specific sites which are usually palindromes of 4 to 10 or so nucleotides to yield a collection of restriction DNA fragments that can be separated, usually by electrophoresis in
 SmaI (30). Patterns were evaluated both visually and with BioNumerics software (Applied Maths, Kortrijk, Belgium) by using the dice coefficient. Indistinguishable patterns must visually appear identical, and the DNA DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 patterns must differ by <1.5% with respect to molecular weight. MRSA isolates were considered part of a CA-MRSA pulsed-field type (PFT PFT
abbr.
pulmonary function test
) if they were [greater than or equal to] 80% similar to the USA300 or USA400 reference strains based on Dice coefficients. MRSA isolates were considered part of an HA-MRSA PFT if they were [greater than or equal to] 80% similar to USA100, USA200, or USA500-800 reference strains (30).

Statistical Analysis

The Yates continuity corrected chi-square test chi-square test: see statistics.  was used to test for trends with EpiInfo version 6.2 (CDC, Atlanta, GA, USA), and univariate analysis of the data was performed with EpiInfo 2000 (CDC). Multivariate logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors.  was used to evaluate the association of the type of MRSA infection (SSTI versus invasive disease) with microbiologic and molecular features of the MRSA isolates. Demographic characteristics associated with the type of infection in the univariate analysis were controlled for in the multivariate analysis multivariate analysis,
n a statistical approach used to evaluate multiple variables.

multivariate analysis,
n a set of techniques used when variation in several variables has to be studied simultaneously.
 model. An [alpha] [less than or equal to] 0.05 significance level was required for predictors to remain in the model. Multivariate analysis was accomplished by using SAS (1) (SAS Institute Inc., Cary, NC, www.sas.com) A software company that specializes in data warehousing and decision support software based on the SAS System. Founded in 1976, SAS is one of the world's largest privately held software companies. See SAS System.  version 8.0 for Windows (SAS Institute SAS Institute Inc., headquartered in Cary, North Carolina, USA, has been a major producer of software since it was founded in 1976 by Anthony Barr, James Goodnight, John Sall and Jane Helwig. , Cary, NC, USA).

Results

A total of 738 CA-MRSA infections were identified from January 1, 2000, to December 31, 2003. SSTIs accounted for 79% (586/738) of all infections reported, and invasive disease accounted for 9% (65/738) of all CAMRSA infections reported. The proportion of CA-MRSA infections that were invasive did not differ significantly over the study period. The most common site of invasive disease was the bloodstream (50%), followed by joint or bone (32%). Clinical information was available for 511 (87%) of 586 SSTI patients. The most common clinical conditions reported for SSTIs were abscesses (49%) and cellulitis (33%) (Table 1).

Case Demographics

Invasive disease patients were more likely to be male than SSTI patients (66% vs. 51%, odds ratio [OR] 1.89, 95% confidence interval confidence interval,
n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%.
 [CI] 1.10-3.24). No difference in median age was found between the 2 groups. Race information was available for 54 (83%) of 65 invasive disease patients and 477 (81%) of 586 SSTI patients. No difference was shown between the 2 groups when race was analyzed in terms of white and nonwhite non·white  
n.
A person who is not white.



nonwhite adj.
 race categories (Table 2).

Patient hospitalization status was available for all of the invasive disease CA-MRSA patients and 562 (96%) of 586 SSTI patients. As expected, invasive disease patients were more likely to be hospitalized for their infection than were SSTI patients (OR 6.89, 95% CI 3.81-12.4). Results remained significant after controlling for age and sex (p<0.001). No differences were observed between median income of CA-MRSA invasive disease patients and SSTI patients (Table 2).

History of underlying medical conditions See carpal tunnel syndrome, computer vision syndrome, dry eyes and deep vein thrombosis.  was obtained for 58 (89%) of 65 invasive disease patients and 515 (88%) of 586 SSTI patients. Invasive disease patients were more likely to report a history of underlying illness than were SSTI patients (OR 2.08, 95% CI 1.05-4.20). Invasive disease CA-MRSA patients were more likely to have a history of immunosuppressive therapy (OR 9.31, 95% CI 1.87-47.2), solid organ malignancy (OR 9.16, 95% CI 1.27-66.3), or emphysema/chronic obstructive pulmonary disease (COPD COPD chronic obstructive pulmonary disease.

COPD
abbr.
chronic obstructive pulmonary disease


Chronic obstructive pulmonary disease (COPD) 
) (OR 13.9, 95% CI 2.29-85.5) than SSTI patients. Invasive disease CA-MRSA patients were also more likely to be current smokers (OR 2.18, 95% CI 1.09-4.67) or injection drug users (OR 5.56, 95% CI 1.29-23.9) than SSTI patients. History of underlying illness (p = 0.007), immunosuppressive therapy (p = 0.003), emphysema/COPD (p = 0.012), current smoking (p = 0.028), and injection drug use (p = 0.021) remained significant in a multivariate model that controlled for age and sex (Table 2).

Isolate Characteristics

We received isolates from 60 (92%) of 65 invasive disease patients and 525 (90%) of 586 SSTI patients. Tests for antimicrobial drug susceptibility were completed on 57 (95%) of 60 invasive disease isolates and 517 (98%) of 525 SSTI isolates. All isolates were susceptible to linezolid and vancomycin. Compared with SSTI isolates, those from invasive infections were less likely to be susceptible to ciprofloxacin (OR 2.79, 95% CI 1.54-5.04) and clindamycin (OR 3.34, 95% CI 1.67-6.69). When ciprofloxacin and clindamycin susceptibilities were analyzed in a model that controlled for sex and age, the results remained significant (p = 0.002 and p = 0.001, respectively) (Table 3).

Initial antimicrobial therapy information was documented for 41 (63%) of 65 patients with invasive disease whose isolates were available and for 415 (71%) of 586 patients with SSTI whose isolates were available. For 27 (66%) of 41 invasive disease patients and 333 (80%) of 415 SSTI patients, the initial antimicrobial agent prescribed was of a class to which the organism was resistant. Invasive disease patients were more likely to be empirically treated with an antimicrobial drug to which their MRSA isolate was susceptible than were SSTI patients (OR 2.10, 95% CI 1.05-4.20). Results remained significant after controlling for age and sex (p = 0.015).

All available isolates received were characterized by PFGE. Fifty-three (88%) of 60 invasive disease isolates and 501 (95%) of 525 SSTI isolates had PFGE subtypes that could be categorized into PFTs that have been associated with HA-MRSA disease (USA100, USA200, USA500-800) or CA-MRSA (USA300 and USA400) (30). Compared with PFGE subtypes from SSTI isolates, PFGE subtypes from invasive disease isolates were more likely to be associated with HA-MRSA PFTs (OR 3.63, 95% CI 2.03-6.50). This result remained significant after controlling for age and sex (p<0.001) (Table 4). When invasive disease and SSTI case isolate susceptibility to ciprofloxacin and clindamycin were analyzed in a multivariate model that controlled for CA or HA-MRSA PFT and sex, no difference in susceptibility patterns was found between the 2 groups (Table 3).

Confirmed CA-MRSA Analysis

Three hundred two (52%) of 586 SSTI patients and 36 (55%) of 65 invasive disease patients were confirmed (through patient interview and medical record review, as opposed to medical record review alone) to meet the CA-MRSA case definition. Confirmed CA-MRSA patients and isolates underwent the previously described analysis regarding differences in underlying conditions and isolate antimicrobial susceptibility. Underlying condition information was available for 30 (83%) of 36 invasive disease patients and 273 (90%) of 302 SSTI patients. Confirmed invasive disease CA-MRSA patients were more likely than confirmed SSTI patients to report a history of underlying illness (OR 2.36, 95% CI 1.09-5.10), history of immunosuppressive therapy (OR 10.0, 95% CI 1.92-52.0), solid organ malignancy (OR 19.4, 95% CI 1.71-221), or to be a current smoker (OR 3.06, 95% CI 1.25-7.50). Hospitalization information was available for all invasive disease patients and 299 (99%) of 302 SSTI patients. Confirmed invasive disease patients were more likely to be hospitalized for their infection than were confirmed SSTI patients (OR 5.94, 95% CI 2.75-12.8). Isolates were available for 30 (83%) of 36 invasive disease patients and 265 (88%) of 302 SSTI patients. Confirmed CA-MRSA invasive disease isolates were less likely to be susceptible to ciprofloxacin (OR 5.02, 95% CI 2.11-12.0) and clindamycin (OR 5.75, 95% CI 2.58-12.8). Twenty-eight (93%) of 30 invasive disease isolates and 257 (85%) of 302 SSTI isolates could be categorized into PFTs that have been associated with HA-MRSA or CA-MRSA. Invasive disease isolates were more likely to have HA-MRSA PFTs than were SSTI isolates (OR 4.24, 95% CI 1.90-9.43). When invasive disease and SSTI isolate susceptibility to ciprofloxacin and clindamycin were analyzed in a multivariate model that controlled for CA- or HA-MRSA PFT and sex, invasive disease isolates were still more likely to be resistant to ciprofloxacin than were SSTI isolates (p = 0.04).

Discussion

This report compares CA-MRSA invasive disease patients and their isolates with those of SSTI patients. Invasive disease patients were more likely to be male and more likely to have a history of underlying conditions (immunosuppressive therapy, emphysema/COPD, injection drug use, and smoking) than were SSTI patients. Invasive disease isolates were similar to HA-MRSA isolates in that they were resistant to additional antimicrobial drugs (clindamycin and ciprofloxacin) and were more likely to belong to a PFT usually associated with HA-MRSA (7). These similarities suggest that invasive CA-MRSA patients may have had healthcare exposures that put them at risk of acquiring HA-MRSA, even though they are classified as CA-MRSA by the current CDC case definition.

The results of the ciprofloxacin and clindamycin multivariate analysis, including PFT association with both confirmed and probable CA- or HA-MRSA, showed no difference in susceptibility patterns between invasive disease and SSTI isolates. This suggests that the initial differences in susceptibility were not due to more resistant CA-MRSA strains causing invasive disease, but rather that more of the invasive disease isolates classified as CAMRSA were actually HA-MRSA strains, which are typically resistant to more antimicrobial agents. However, when this same analysis was conducted by using confirmed CA-MRSA cases only, invasive disease isolates were still more likely to be resistant to ciprofloxacin. More research is needed to determine whether invasive disease CA-MRSA isolates are more resistant to antimicrobial drugs than CA-MRSA isolates that cause SSTI.

Invasive disease patient characteristics identified in this analysis were similar to results from other studies, which found that CA invasive disease patients had underlying conditions such as diabetes, smoking, and cardiovascular disease Cardiovascular disease
Disease that affects the heart and blood vessels.

Mentioned in: Lipoproteins Test

cardiovascular disease 
 (31,32). The underlying conditions identified in the S. aureus The aureus (pl. aurei) was a gold coin of ancient Rome valued at 25 silver denarii. The aureus was regularly issued from the 1st century BC to the beginning of the 4th century AD, when it was replaced by the solidus.  and MRSA patients in these studies do not disqualify To deprive of eligibility or render unfit; to disable or incapacitate.

To be disqualified is to be stripped of legal capacity. A wife would be disqualified as a juror in her husband's trial for murder due to the nature of their relationship.
 them from meeting the current CDC CA-MRSA case definition, yet these conditions may have put them at risk of acquiring HA-MRSA.

One possible explanation for some of the results of this analysis could be the likelihood that invasive disease patients had more healthcare exposures than did SSTI patients. This hypothesis is supported by the fact that invasive disease patients reported serious underlying illnesses that would imply a history of extensive healthcare contacts. During these healthcare contacts, invasive disease patients may have been colonized Colonized
This occurs when a microorganism is found on or in a person without causing a disease.

Mentioned in: Isolation
 by HA-MRSA strains. A recent study found that in 50% of patients nasally colonized with MRSA subsequent infection developed over the next 18 months (33). Although we were unable to determine the colonization status of our patients for this analysis, patients have been found colonized with MRSA for up to 40 months (34).

This study has several limitations. Although the hospital laboratories were selected to reflect state population demographics, the study was not population based. Therefore, generalizing the findings to entire state population is not possible. Also, some HA-MRSA patients may have been misclassified as CA-MRSA patients because of incomplete ascertainment of HA risk factors. However, since no major differences were found in results when analysis was restricted to confirmed CA-MRSA patients, misclassification bias as a result of incomplete ascertainment of HA risk factors that are exclusion criteria for the current CA-MRSA case definition is unlikely to be a large factor. In addition, the sample size, particularly of invasive disease cases, limited the ability to detect small statistical differences between the 2 groups. Finally, complete data on all cases were not available for all factors analyzed in this report. These missing data could have biased the results of this analysis.

Underlying conditions or healthcare exposures not currently included as exclusion criteria in the CA-MRSA case definition may put patients at risk of HA-MRSA colonization and infection. In addition, persons with underlying conditions may also be at greater risk of invasive disease caused by MRSA. Clinicians should be aware of possible serious MRSA infections in persons without previously recognized HA-MRSA risk factors. Continued surveillance of CA-MRSA is needed to further define the epidemiology of invasive disease and SSTI and to develop recommendations for the prevention and control of this emerging public health threat.

Acknowledgments

We thank Harry Hull, Joanne Bartkus, John Besser, Stephanie Borchardt, Karen Hilts, Billie Juni, Summer Martins, Jennifer Sweeney, Jessica West, Scott Fridkin, Jeff Hageman, Patricia Ackerman, Jeanne Anderson, Dorothy Berg, Jeanette Biorn, Becky Carlson, Charles Cartwright, John Cartwright, John, 1740–1824, English reformer and pamphleteer; brother of Edmund Cartwright. He had an early career in the navy. He declined to fight the American colonists and wrote American Independence: the Interest and Glory of Great Britain (1774).  Cota, Kathy Gray, Ann Endy, Charleen Hansen, Ron Jadwin, Jackie Koranda, Barbara Kotts, Richard Lally, Karen Margolis, Michael Olesen, Lucille Owen, Sally Petrowski, Barbara Piasecki, Joni Sherin, Kathleen Steinmann, Mary Thompson Mary Thompson (d. 1893) was one of Seattle, Washington's richest early African Americans. She owned the Minnehaha Saloon, which had a brothel upstairs. At the time of her death she had real estate in Seattle and in Butte, Montana. , Dean Tsukyama, Lianne Walker, Cindi Welch, Deb Westerberg, and Ann Zierden for contributing to this research and helping prepare this article.

This work was supported by a cooperative agreement (U50/CCU511190) with the CDC as part of the Emerging Infections Program. This work was presented, in part, at the 2004 International Conference on Emerging Infectious Diseases The ICEID or International Conference on Emerging Infectious Diseases is a conference for public health professionals on the subject of emerging infectious diseases. , Atlanta, Georgia.

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adj.
Of or relating to pediatrics.
 deaths from community-acquired methicillin-resistant Staphylococcus staphylococcus (stăf'ələkŏk`əs), any of the pathogenic bacteria, parasitic to humans, that belong to the genus Staphylococcus. The spherical bacterial cells (cocci) typically occur in irregular clusters [Gr.  aureus--Minnesota and North Dakota, 1997 1999. MMWR MMWR Morbidity & Mortality Weekly Report Epidemiology A news bulletin published by the CDC, which provides epidemiologic data–eg, statistics on the incidence of AIDS, rabies, rubella, STDs and other communicable diseases, causes of mortality–eg,  Morb Mortal Wkly Rep. 1999;48:707-10.

(9.) Herold BC, Immergluck LC, Maranan MC, Lauderdale DS, Gaskin gaskin

the muscular portion of the hindleg between the stifle and hock, corresponding to the human calf. The term is used in horses and sometimes dogs.
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a nonhemolytic toxin produced by Staphylococcus aureus which kills segmented neutrophils and macrophages.
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1. One that greets, acclaims, or catches someone's attention.

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Jessica M. Buck, * Kathryn Como-Sabetti, * Kathleen H. Harriman, * Richard N. Danila, * David J. Boxrud, * Anita Glennen, * and Ruth Lynfield *

* Minnesota Department of Health, Minneapolis, Minnesota, USA

Ms Buck is an epidemiologist with the Minnesota Department of Health Acute Disease Investigation and Control Unit. Her primary research interests are methicillin-resistant Staphylococcus aureus and infection control issues.

Address for correspondence: Jessica M. Buck, Acute Disease Investigation and Control, Infection Control and Antimicrobial Resistance Unit, Infectious Disease Infectious disease

A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions.
 Epidemiology, Prevention and Control, PO Box 9441, Minneapolis, MN 55440-9441, USA; fax: 612-676-5743; email: Jessica.Buck@health.state.nm.us
Table 1. Community-associated methicillin-resistant
Staphylococcus aureus invasive infection sites and skin
and soft tissue infection clinical manifestations

Site or manifestation                     No. (%)

Invasive infection site (n = 65)
  Bloodstream infection
    Without focus                         25 (38)
    With skin focus                        6 (9)
    With respiratory focus                 2 (3)
  Pleural fluid                            3 (5)
  Peritoneal fluid                         2 (3)
  Joint/bone                              21 (32)
    Other *                                6 (9)
Skin and soft tissue clinical
    manifestation (n = 511 ([dagger]))
  Abscess                                251 (49)
  Cellulitis                             171 (33)
  Folliculitis                            28 (5)
  Wound infection                         27 (5)
  Impetigo                                11 (2)
  Other ([double dagger])                 62 (12)

* Other invasive isolate sources included
brain tissue (1), lymph nodes (2), pancreatic
aspirate (1), kidney abscess aspirate (1), and
internal tissue (1).

([dagger]) A total of 411 skin and soft
tissue infection patients had clinical
manifestations reported. Results include
multiple clinical manifestations per patient.

([double dagger]) Other skin clinical manifestations
included psoriasis, mastitis, cystic acne, furuncles,
carbuncles, insect/spider bites, and eczema.

Table 2. Community-associated methicillin-resistant
Staphylococcus aureus invasive disease and skin
and soft tissue infection (SSTI) patient demographics *

                                  Invasive disease   SSTI patient
Characteristic                    patient (n = 65)     (n = 586)

Median age, y                            28               24
Sex (male), no. (%)                   43 (66)          296 (51)
Race, no. (%)
  White ([dagger])                    33 (51)          254 (43)
  Unknown                             10 (15)          105 (18)
  Nonwhite ([dagger])                 21 (32)          223 (38)
  Black                               14 (21)          125 (21)
  Native American                      6 (9)            82 (14)
  Asian                                1 (0.5)           4 (0.7)
  Other                                1 (0.5)          12 (0.2)
Median income (US)                    $38,237           $38,237
  ([double dagger])
Patients hospitalized,                49 (75)          173 (31)
  no. (%) ([section])

                                      (n = 58)         (n = 515)

Presence of underlying                31 (53)          183 (36)
  condition, no. (%)
Immunosuppressive therapy,             3 (5)            3 (0.6)
  ([paragraph]) no. (%)
Solid organ malignancy, no. (%)        2 (4)            2 (0.4)
Diabetes, no. (%)                      9 (16)          41 (8)
Current smoker, no. (%)               12 (21)          55 (11)
Emphysema/COPD, no. (%)                3 (5)            2 (0.4)
Injection drug use, no. (%)            3 (5%)           5 (1)

Characteristic                      OR (95% CI)

Median age, y                            NS
Sex (male), no. (%)               1.89 (1.10-3.24)
Race, no. (%)
  White ([dagger])                       NS
  Unknown
  Nonwhite ([dagger])                    NS
  Black
  Native American
  Asian
  Other
Median income (US)                       NS
  ([double dagger])
Patients hospitalized,            6.89 (3.81-12.4)
  no. (%) ([section])

Presence of underlying            2.08 (1.21-3.60)
  condition, no. (%)
Immunosuppressive therapy,        9.31 (1.83-47.2)
  ([paragraph]) no. (%)
Solid organ malignancy, no. (%)   9.16 (1.27-66.3)
Diabetes, no. (%)                        NS
Current smoker, no. (%)           2.18 (1.09-4.37)
Emphysema/COPD, no. (%)           13.9 (2.29-85.5)
Injection drug use, no. (%)       5.56 (1.29-23.9)

* OR, odds ratio, CI, confidence interval;
NS, not significant; COPD, chronic
obstructive pulmonary disease.

([dagger]) Race was calculated by using
the number of cases with known race
as the denominator.

([double dagger]) Based on the mean household income
in the zip code of each case-patient (source: 2000 US C

([section]) Calculated by using the number of cases
with known hospitalization status. Twenty-four SSTI
patients had unknown hospitalization status.

([paragraph]) Defined as long-term systemic steroid
use, excluding topical creams, steroids used only for s
treatment, and inhaled steroids used for asthma.

Table 3. Community-associated methicillin-resistant
Staphylococcus aureus (CA-MRSA) invasive disease patient
and skin and soft tissue infection (SSTI) patient
isolate characteristics *

                           Invasive disease       SSTI isolates
                           isolates (n = 57)        (n = 517)
Antimicrobial agent       No. (% susceptible)   No. (% susceptible)

Oxacillin (methicillin)            0                     0
Ciprofloxacin                   37 (65)              433 (84)
Clindamycin                     44 (77)              475 (92)
Erythromycin                    21 (37)              201 (39)
Gentamicin                      56 (98)              509 (98)
Linezolid                       57 (100)             517 (100)
Mupirocin                       56 (98)              508 (98)
Rifampin                        56 (98)              515 (99)
Tetracyline                     52 (91)              469 (91)
Trimethoprim-                   56 (98)              514 (99)
  sulfamethoxazole
Vancomycin                     57 (100)              517 (100)

                                                          p value
                                              p value     ([double
Antimicrobial agent         OR (95% CI)      ([dagger])   dagger])

Oxacillin (methicillin)          NA
Ciprofloxacin             3.34 (1.67-6.69)     0.002        0.23
Clindamycin               2.79 (1.54-5.04)     0.001        0.20
Erythromycin              1.09 (0.62-1.92)
Gentamicin                1.14 (0.14-9.25)
Linezolid                        NA
Mupirocin                 1.14 (0.14-9.23)
Rifampin                  4.60 (0.41-51.5)
Tetracyline               0.94 (0.36-2.46)
Trimethoprim-             3.06 (0.31-2.99)
  sulfamethoxazol
Vancomycin                       NA

* OR, odds ratio; CI, confidence interval;
NA, not applicable.

([dagger]) Refers to the probablility that
the percentage susceptible for invasive CA-MRSA
isolates differed from SSTI CA-MRSA isolates
after controlling for sex and age.

* Refers to the probability that the percentage
susceptible for invasive CA-MRSA isolates differed from
SSTI CA-MRSA isolates after controlling for sex
and pulsed-field type associated with
healthcare-associated MRSA or CA-MRSA.

Table 4. Distribution of HA-MRSA PFTs among invasive
disease and SSTI community-associated MRSA isolates *

                    Invasive disease    SSTI isolates
                   isolates (n = 25),     (n = 99),
HA-MRSA PFTs            no. (%)            no. (%)

USA100                   17 (28)            43 (8)
USA200                    3 (5)              4 (0.8)
USA500                    5 (8)             40 (7.6)
USA600                      0                1 (0.2)
USA700                      0                1 (0.2)
USA800                      0               10 (2)
Total ([dagger])         25 (42)            99 (19)

* HA, healthcare-associated; MRSA, methicillin-resistant
Staphylococcus aureus; PFTs pulsed-field types; SSTI,
skin and soft tissue infection.

([dagger]) Odds ratio 3.63, 95% confidence interval
2.03-6.50, p<0.001.
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Author:Lynfield, Ruth
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Date:Oct 1, 2005
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