Community-Acquired
Methicillin-Resistant Staphylococcus aureus
in a Rural American Indian Community
JAMA. 2001;286:1201-1205
Amy V. Groom, MPH; Darcy H. Wolsey, MPH; Timothy S. Naimi, MD, MPH;
Kirk Smith, DVM, PhD; Sue Johnson, MS; Dave Boxrud, MS; Kristine A. Moore, MD,
MPH; James E. Cheek, MD, MPH
Context Until recently, methicillin-resistant Staphylococcus aureus (MRSA) infections have been acquired
primarily in nosocomial settings. Four recent deaths due to MRSA infection in
previously healthy children in the Midwest suggest that serious MRSA infections
can be acquired in the community in rural as well as urban locations.
Objectives To document the occurrence of community-acquired MRSA infections
and evaluate risk factors for community-acquired MRSA infection compared with
methicillin-susceptible S aureus
(MSSA) infection.
Design Retrospective cohort study with medical record review.
Setting Indian Health Service facility in a rural midwestern American
Indian community.
Patients Patients whose medical records indicated laboratory-confirmed S aureus infection diagnosed during 1997.
Main Outcome
Measures Proportion of MRSA
infections classified as community acquired based on standardized criteria;
risk factors for community-acquired MRSA infection compared with those for
community-acquired MSSA infection; and relatedness of MRSA strains, determined
by pulsed-field gel electrophoresis (PFGE).
Results Of 112 S aureus
isolates, 62 (55%) were MRSA and 50 (45%) were MSSA. Forty-six (74%) of the 62
MRSA infections were classified as community acquired. Risk factors for
community-acquired MRSA infections were not significantly different from those
for community-acquired MSSA. Pulsed-field gel electrophoresis subtyping
indicated that 34 (89%) of 38 community-acquired MRSA isolates were clonally
related and distinct from nosocomial MRSA isolates found in the region.
Conclusions Community-acquired MRSA may have replaced community-acquired MSSA
as the dominant strain in this community. Antimicrobial susceptibility patterns
and PFGE subtyping support the finding that MRSA is circulating beyond
nosocomial settings in this and possibly other rural US communities.
JAMA. 2001;286:1201-1205
Methicillin-resistant Staphylococcus aureus (MRSA) first emerged as a nosocomial
pathogen in the early 1960s.1 Since then, data from
the Centers for Disease Control and Prevention's National Nosocomial Infection
Surveillance system indicate that the occurrence of MRSA infection in US
hospitals has been increasing steadily and that MRSA accounted for more than
40% of S aureus isolates in 1998.2 Established risk
factors for MRSA infection include recent hospitalization, recent surgery,
residence in a long-term care facility, and injection drug use.3
Methicillin-resistant strains of S aureus are resistant to all -lactam antibiotics
and, frequently, to many other antibiotic classes.1 -Lactam resistance is due to an alteration of the penicillin-binding
protein PBP 2a, which is encoded by the chromosomal gene mecA.4, 5 Most circulating
strains of MRSA appear to be derived from only 2 or 3 clones.6, 7 Once introduced into a
microbial population, mecA may be
transferred horizontally and recombined among methicillin-susceptible S aureus (MSSA) cells.7 This has led to the
global spread of MRSA in association with increasing geographic mobility of
infected patients and carriers of the organism.8-10
Despite the increased incidence of MRSA
infection in nosocomial settings, reports of infection acquired in the
community have been relatively rare until recently. In the 1990s, studies of
MRSA in Western Australia,11, 12 the Canadian
prairies,13 Illinois,3, 14, 15 southern Texas,16 Hawaii,17 and California18 suggested the
emergence of MRSA as a community-acquired pathogen. Medical record reviews
documented that most patients had no established risk factor for MRSA
infection.3, 11, 14-18 Furthermore,
antimicrobial susceptibility patterns showed that, unlike many nosocomial
strains of MRSA, community-acquired MRSA isolates tended to remain susceptible
to most non–-lactam
antibiotics.3, 11, 12, 14, 15, 17, 18 All studies from the
United States and Canada, however, were conducted in large hospitals in urban
areas, where patients are more likely to have exposure to tertiary care
facilities.3, 13-18 The only studies
that examined community-acquired MRSA among patients from nonurban areas were
those conducted in Australia.11, 12
A 1996 national survey of Indian Health Service
(IHS) facilities, many of which provide few or no inpatient services, found
that, overall, 40% (600/1490) of S aureus
isolates tested from the Midwest and Northern Plains were MRSA (IHS,
unpublished data, 1996). Subsequently in 1999, 4 deaths among children in
Minnesota and North Dakota, 1 of which occurred in an American Indian, were
attributed to community-acquired MRSA infection.19 These findings
suggested that MRSA was being acquired outside nosocomial settings. We
therefore sought to examine the prevalence of community-acquired MRSA and to
evaluate risk factors for community-acquired MRSA infection compared with those
for community-acquired MSSA infection in a rural American Indian community.
The study was conducted at a small IHS hospital
with a busy outpatient clinic located in a rural midwestern community. The
annual catchment population was 8311. All laboratory-confirmed S aureus infections among patients treated
at this facility between January 1 and December 31, 1997, were evaluated using
a retrospective cohort study design and medical record review. Cases of
laboratory-confirmed MRSA infection were compared with those of
laboratory-confirmed MSSA infection. The research proposal for this study was
approved by the IHS National Institutional Review Board and the local tribal
council.
Laboratory Methods
Initial antimicrobial susceptibilities were determined locally using MicroScan
panels (Dade Behring MicroScan Inc, West Sacramento, Calif). Confirmatory
antimicrobial susceptibility testing of 50 MRSA isolates (81%) was conducted at
the Minnesota Department of Health using Etest (AB Biodisk, Solna, Sweden).20-22 Oxacillin agar
screen testing and pulsed-field gel electrophoresis (PFGE)23-25 were performed on
a sample of MRSA isolates. Pulsed-field gel electrophoresis was performed using
a previously published method26 with slight
modifications (100 U of mutanolysin were added to the lysis solution; run
conditions were 2.2 seconds for the initial switch time and 37.3 seconds for
the final switch time, with linear ramping for 18 hours; and SeaKem Gold
agarose [BioWhittaker Molecular Applications, Rockland, Me] was used in place
of PFGE-certified agarose). The control strain, NCTC 8325, was run 3 times on a
10-well gel and 4 times on a 15-well gel. Restriction-fragment patterns derived
using the enzyme SmaI (ProMega,
Madison, Wis) were compared using Molecular Analyst Fingerprinting Data Sharing
Tools, version 1.6 (Bio-Rad, Hercules, Calif) set to a 1% molecular weight
position tolerance. Pulsed-field gel electrophoresis types were defined as
having indistinguishable band patterns in the 30- to 600-kilobase range and
were considered clonally related when patterns differed from a reference strain
by 3 or fewer bands.27 Five MRSA isolates
representing different PFGE subtypes underwent polymerase chain reaction
amplification for detection of the mecA
gene.28
Data Collection
Laboratory records from the on-site laboratory for 1989-1997 were reviewed. We
gathered information from patients' medical records using a standardized data
abstraction instrument. Abstracted data included basic demographic information,
anatomical site of infection, clinical symptoms, and treatment of S aureus infection. Information on
exposure to established risk factors for MRSA infection in the year before
infection was also obtained. No patients were contacted directly.
Infections were classified as community acquired
if isolates were obtained in an outpatient setting or less than 48 hours after
hospital admission and if patients had no history of hospitalization, renal
dialysis, or residence in a long-term care facility during the year before
infection and no documented history of injection drug use. Risk factor analyses
were limited to cohort members who met the criteria for a community-acquired
infection.
Statistical Analysis
Adjusted 2 or
2-tailed Fisher exact tests were performed for comparisons of categorical data
using Epi Info, version 6.04c,29 and StatXact 3.30 Risk ratios (RRs) and
exact 95% confidence intervals (CIs) were also calculated for all categorical
data in evaluating exposures among cohort members. Kruskal-Wallis tests were
used to evaluate non–normally distributed continuous data.
Demographics
From 1989 to 1997, MRSA infections increased dramatically in this community (Figure 1).
Our cohort contained 112 patients with S
aureus infections during 1997, of whom 62 (55%) had an MRSA
infection and 50 (45%) had an MSSA infection. All study patients were American
Indians. Infections occurred year-round, and there were no significant
differences between patients with MRSA and patients with MSSA with regard to
sex or age (median age for MRSA patients, 20.5 [range, 0.1-91.4] years and for
MSSA patients, 19 [range, 0.03-79.4] years).
Community-Acquired vs
Non–Community-Acquired Infections
Most MRSA infections (46 [74%]) were classified as community acquired. A
similar proportion of MSSA infections (32 [64%]) could also be classified as
community acquired.
Antimicrobial susceptibility patterns of MRSA
isolates demonstrated uniform resistance to -lactam
antibiotics. Most community-acquired MRSA isolates, however, were susceptible
to many other non–-lactam antibiotics
(Table 1).
Community-acquired MRSA isolates were significantly more likely than
non–community-acquired MRSA isolates to be susceptible to ciprofloxacin (P = .01), although other differences were
not significant. All 5 tested MRSA isolates demonstrated presence of the mecA gene.
Fifty (81%) of 62 MRSA isolates were available
for PFGE subtyping. Thirty-eight isolates (76%) were from community-acquired
MRSA infections and 12 isolates (24%) were from non–community-acquired
infections. One clonal group, designated as group A, accounted for 80% of all
isolates tested. Group A subtypes were significantly more likely among
community-acquired isolates (34/38 [89%]) than non–community-acquired isolates
(6/12 [50%]) (P = .007). The 3
most commonly identified PFGE group A subtype patterns, which accounted for 32
of the 34 community-acquired group A isolates, were distinct from non–group A
subtypes from residents of a long-term care facility in that community (Figure 2).
Among community-acquired infections, a similar
proportion of patients with community-acquired MRSA (89%) and
community-acquired MSSA (94%) presented with skin infection (P = .76). Six patients with
community-acquired MRSA (13%) and 1 patient with community-acquired MSSA (3%)
were hospitalized because of their infection (P
= .31). No deaths were attributed to S
aureus infection in either group.
Prior Health Care Exposures and
Underlying Medical Conditions
Among patients treated at either the outpatient clinic or the emergency
department during the year before their infection, 45 (60%) of 75 developed a
community-acquired MRSA infection compared with 1 (33%) of 3 patients who were
not treated at the clinic/emergency department (RR, 1.80; 95% CI, 0.56-59.76).
The median of 7 clinic/emergency department visits (range, 1-22 visits) among
patients with community-acquired MRSA was not significantly different from the
median of 6 visits (range, 1-34 visits) among patients with community-acquired
MSSA (P = .19). Among patients
with underlying chronic health conditions, 12 (50%) of 24 developed a
community-acquired MRSA infection compared with 34 (63%) of 54 patients with no
underlying chronic condition (RR, 0.79; 95% CI, 0.34-1.36).
In regard to exposure to antibiotics, we found
no significant difference between patients with community-acquired MRSA and
community-acquired MSSA. Among patients prescribed at least 1 course of
antibiotics during the year before infection, 31 (61%) of 51 developed
community-acquired MRSA compared with 15 (56%) of 27 who were not prescribed
antibiotics (RR, 1.09; 95% CI, 0.65-2.11). Of those who received an antibiotic
course, the median number of antibiotic courses for patients with
community-acquired MRSA was 3.0 vs 2.0 for those with community-acquired MSSA;
the difference was not significant (P
= .32).
The proportion of MRSA isolates in this
community increased substantially from 1989 to 1997, suggesting that
community-acquired MRSA has emerged only recently. Low socioeconomic status,
crowded housing conditions, and limited access to health care, which contribute
to the high background rate of skin infections in this population,31-34 may have enhanced
our ability to detect the emergence of community-acquired MRSA. These
characteristics, however, are not unique to this rural American Indian
population, and our findings suggest that over time, community-acquired MRSA
may be found in ever-increasing numbers in other communities of low
socioeconomic status.
There are multiple lines of evidence suggesting
that most MRSA infections in our study were acquired in the community rather
than nosocomially. Although recent studies suggest that exposure to hospitals
is a risk factor for many putative community-acquired MRSA infections,35, 36 we found no evidence
of such exposures. Although the term community
acquired is not clearly or consistently defined in current MRSA
literature,37 our criteria
for community acquisition were among the most conservative, requiring a full
year with no exposure to established nosocomial risk factors.38 Furthermore,
antimicrobial susceptibility patterns found among community-acquired MRSA
isolates in this community showed susceptibility to most classes of
antimicrobial agents other than -lactam
antibiotics, consistent with other studies of community-acquired MRSA.3, 11, 12, 14, 15, 17 Additional evidence
supporting community acquisition is found in the PFGE patterns of these
community-acquired MRSA isolates, which were distinct from the PFGE patterns of
circulating nosocomial MRSA strains. Subtyping by PFGE revealed that most
community-acquired MRSA infections were caused by clonally related MRSA
subtypes27 that were
either indistinguishable from or clonally related to the community-acquired
MRSA subtypes associated with the previously reported pediatric fatalities in
the Midwest.19 We found no
epidemiologic links between patients in this community and any of the 4 fatal
cases of community-acquired MRSA. The lack of any connections other than
geographic proximity in the Midwest suggests that community-acquired MRSA may
be emerging throughout this region and that this American Indian community can
be regarded as a sentinel for emerging community-acquired MRSA.
Community-acquired MRSA may be replacing
community-acquired MSSA in our study community. Although we would expect exposure
to established risk factors for MRSA to have resulted in more MRSA infections
than MSSA infections, this did not occur. Because there is apparently no
significant evolutionary "cost" in fitness for strains of MRSA
relative to MSSA, even slight selective pressure from antimicrobial drug use
may cause MRSA to overtake MSSA strains in a microbial population. This has
been a common pattern for the establishment of MRSA in nosocomial settings.39, 40 A similar pattern may
be observed in community settings.
Misclassification bias is a potential limitation
of this study. Our stringent definition of community-acquired infection could
have caused us to underestimate the true proportion of these infections. In
addition, undocumented nosocomial exposures and antibiotic use could have
occurred, such as when study participants sought health care at other
facilities. Because the IHS is essentially a form of managed care, however,
care received outside the system is usually documented, decreasing the
likelihood that there were unidentified nosocomial exposures. Finally, patients
with MRSA could have had a close contact who was exposed to a nosocomial
setting, thereby providing an indirect nosocomial source of infection.
Based on our findings, health care practitioners
in rural communities in the Midwest should consider the possibility of MRSA
infection among young, healthy patients without a history of nosocomial
exposure. Culturing suspected S aureus
infections and conducting antibiotic susceptibility testing, particularly in
communities with known high rates of MRSA infection, is important to ensure
that appropriate antibiotic therapy is provided. The report describing 4 deaths
in previously healthy young persons in the Midwest highlights the potentially
deadly consequences of community-acquired MRSA infection.19 Fortunately, most
community-acquired MRSA isolates in this study were susceptible to a variety of
antimicrobial agents in addition to vancomycin. Health care practitioners
should be particularly attentive to judicious use of antibiotics in outpatient
settings to avoid an expanding spectrum of antibiotic resistance among strains
of community-acquired MRSA.
Socioeconomic factors that may have facilitated
our recognition of the emergence of community-acquired MRSA in this rural
community are not unique to American Indian populations, and it is likely that
MRSA is becoming prevalent in other populations and locations. Patients who are
at risk of MSSA infection may also soon be at risk of MRSA infection. The deaths
attributed to strains of MRSA related to those found in our study occurred in
mostly rural, non–American Indian communities in Minnesota and North Dakota.19 This finding as well as
those of previous studies documenting community-acquired MRSA infection in
diverse populations3, 11-18 suggest that the
problem of MRSA is growing and that even rural communities are not sheltered.
Author/Article Information
Author Affiliations: National
Epidemiology Program, Indian Health Service Headquarters, Albuquerque, NM (Mss
Groom and Wolsey and Dr Cheek); Epidemiology Program Office, Centers for
Disease Control and Prevention, Atlanta, Ga (Dr Naimi); Acute Disease
Epidemiology Section (Drs Naimi and Smith) and Division of Public Health
Laboratories (Ms Johnson and Mr Boxrud), Minnesota Department of Health,
Minneapolis; and ICAN Inc, Eden Prairie, Minn (Dr Moore).
Corresponding Author and Reprints:
James E. Cheek, MD, MPH, Indian Health Service National Epidemiology Program,
5300 Homestead Rd NE, Albuquerque, NM 87110 (e-mail: [log in to unmask]).
Author Contributions: Study concept and design:
Wolsey, Smith, Moore, Cheek.
Acquisition of data: Groom, Wolsey, Naimi, Smith, Johnson, Boxrud.
Analysis and interpretation of
data: Groom, Naimi, Smith,
Boxrud, Moore, Cheek.
Drafting of the manuscript: Groom, Naimi, Smith, Moore, Cheek.
Critical revision of the
manuscript for important intellectual content: Groom, Wolsey, Naimi, Smith, Johnson, Boxrud, Moore, Cheek.
Statistical expertise: Groom, Naimi, Boxrud, Cheek.
Obtained funding: Smith, Cheek.
Administrative, technical, or
material support: Groom, Wolsey, Naimi,
Johnson, Moore, Cheek.
Study supervision: Wolsey, Smith, Moore, Cheek.
Funding/Support: This work was supported in part by cooperative agreement
U50/CCU511190 from the Centers for Disease Control and Prevention as part of
the Emerging Infections Program.
Acknowledgment: We thank Luella Brown, Linda Frizzell, PhD, Doris Jones, and
Steve Rith-Najarian, MD, for their support of this project; Robyn Anderson,
Teresa Chasteen, Jennifer Giroux, MD, Tammy Goodwin, and Greg Rozycki for their
assistance in data collection; Terri Carter for her work in the laboratory;
Douglas Thoroughman, PhD, for his assistance with the analysis; and Ralph
Bryan, MD, and Nathaniel Cobb, MD, for their critical review of an early
version of the manuscript.
1.
Jorgensen JH.
Laboratory and epidemiologic experience with methicillin-resistant Staphylococcus aureus in the USA.
Eur J Clin Microbiol.
1986;5:693-696.
MEDLINE
2.
Centers for Disease Control and Prevention.
National Nosocomial Infection Surveillance
System Data, 1989-1998.
Atlanta, Ga: Centers for Disease Control and Prevention; 1998.
3.
Herold BC, Immergluck LC, Maranan MC, et al.
Community-acquired methicillin-resistant Staphylococcus
aureus in children with no identified predisposing risk.
JAMA.
1998;279:593-598.
MEDLINE
4.
Hartman BJ, Tomasz A.
Low-affinity penicillin-binding protein associated with -lactam resistance in Staphylococcus
aureus.
J Bacteriol.
1984;158:513-516.
MEDLINE
5.
Wu S, Piscitelli C, de Lencastre H, Tomasz A.
Tracking the evolutionary origin of the methicillin resistance gene: cloning
and sequencing of a homologue of mecA
from a methicillin susceptible strain of Staphylococcus
sciuri.
Microb Drug Resist.
1996;2:435-441.
MEDLINE
6.
Kreiswirth B, Kornblum J, Arbeit RD, et al.
Evidence for a clonal origin of methicillin resistance in Staphylococcus aureus.
Science.
1993;259:227-230.
MEDLINE
7.
Musser JM, Kapur V.
Clonal analysis of methicillin-resistant Staphylococcus
aureus strains from intercontinental sources: association of the mec gene with divergent phylogenetic
lineages implies dissemination by horizontal transfer and recombination.
J Clin Microbiol.
1992;30:2058-2063.
MEDLINE
8.
Ayliffe GA.
The progressive intercontinental spread of methicillin-resistant Staphylococcus aureus.
Clin Infect Dis.
1997;24(suppl 1):S74-S79.
MEDLINE
9.
Aires de Sousa M, Santos Sanches I, Ferro ML, et al.
Intercontinental spread of a multidrug-resistant methicillin-resistant Staphylococcus aureus clone.
J Clin Microbiol.
1998;36:2590-2596.
MEDLINE
10.
Roberts RB, Tennenberg AM, Eisner W, et al.
Outbreak in a New York City teaching hospital burn center caused by the Iberian
epidemic clone of MRSA.
Microb Drug Resist.
1998;4:175-183.
MEDLINE
11.
Maguire GP, Arthur AD, Boustead PJ, Dwyer B, Currie BJ.
Emerging epidemic of community-acquired methicillin-resistant Staphylococcus aureus in the Northern
Territory.
Med J Aust.
1996;164:721-723.
MEDLINE
12.
O'Brien F, Pearman J, Gracey M, Riley T, Grubb W.
Community strain of methicillin-resistant Staphylococcus
aureus involved in a hospital outbreak.
J Clin Microbiol.
1999;37:2858-2862.
MEDLINE
13.
Embil J, Ramotar K, Romance L, et al.
Methicillin-resistant Staphylococcus aureus
in tertiary care institutions on the Canadian prairies, 1990-1992.
Infect Control Hosp Epidemiol.
1994;15:646-651.
MEDLINE
14.
Frank AL, Marcinak JF, Mangat PD, Schreckenberger PC.
Community-acquired and clindamycin-susceptible methicillin-resistant Staphylococcus aureus in children.
Pediatr Infect Dis J.
1999;18:993-1000.
MEDLINE
15.
Abi-Hanna P, Frank A, Quinn J, et al.
Clonal features of community-acquired methicillin-resistant Staphylococcus aureus in children.
Clin Infect Dis.
2000;30:630-631.
MEDLINE
16.
Moreno F, Crisp C, Jorgenson J, Patterson J.
Methicillin-resistant Staphylococcus aureus
as a community organism.
Clin Infect Dis.
1995;21:1308-1312.
MEDLINE
17.
Gorak E, Yamada S, Brown JD.
Community-acquired methicillin-resistant Staphylococcus
aureus in hospitalized adults and children without known risk
factors.
Clin Infect Dis.
1999;29:797-800.
MEDLINE
18.
Kallen A, Driscoll T, Thornton S, Olson P, Wallace M.
Increase in community-acquired methicillin-resistant Staphylococcus aureus at a naval medical center.
Infect Control Hosp Epidemiol.
2000;21:223-226.
MEDLINE
19.
Centers for Disease Control and Prevention.
Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureusMinnesota and North Dakota, 1997-1999.
MMWR Morb Mortal Wkly Rep.
1999;48:707-710.
20.
National Committee for Clinical Laboratory Standards.
Performance Standards for Antimicrobial Susceptibility
Testing; Ninth Informational Supplement.
Wayne, Pa: National Committee for Clinical Laboratory Standards; 1999.
Publication M100-S9.
21.
National Committee for Clinical Laboratory Standards.
Performance Standards for Antimicrobial Disk
Susceptibility Tests; Approved StandardSixth
Edition.
Wayne, Pa: National Committee for Clinical Laboratory Standards; 1997.
Publication M2-A6.
22.
National Committee for Clinical Laboratory Standards.
Methods for Dilution Antimicrobial
Susceptibility Tests for Bacteria That Grow Aerobically; Approved StandardFourth Edition.
Wayne, Pa: National Committee for Clinical Laboratory Standards; 1997.
Publication M7-A4.
23.
Bannerman TL, Hancock GA, Tenover FC, Miller JM.
Pulsed-field gel electrophoresis as a replacement for bacteriophage typing of Staphylococcus aureus.
J Clin Microbiol.
1995;33:551-555.
MEDLINE
24.
Roberts RB, de Lencastre A, Eisner W, et al.
Molecular epidemiology of methicillin-resistant Staphylococcus aureus in 12 New York Hospitals.
J Infect Dis.
1998;178:164-171.
MEDLINE
25.
Macfarlane L, Walker J, Borrow R, Oppenheim BA, Fox AJ.
Improved recognition of MRSA case clusters by the application of molecular
subtyping using pulsed-field gel electrophoresis.
J Hosp Infect.
1999;41:29-37.
MEDLINE
26.
Cockerill FR III, MacDonald KL, Thompson RL, et al.
An outbreak of invasive group A streptococcal disease associated with high
carriage rates of the invasive clone among school-aged children.
JAMA.
1997;277:38-43.
MEDLINE
27.
Tenover FC, Arbeit RD, Goering RV, et al.
Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel
electrophoresis: criteria for bacterial strain typing.
J Clin Microbiol.
1995;33:2233-2239.
MEDLINE
28.
Nishi J, Miyanohara H, Nakajima T, et al.
Molecular typing of the methicillin resistance determinant (mec) of clinical strains of Staphylococcus based on mec hypervariable region length
polymorphisms.
J Lab Clin Med.
1995;126:29-35.
MEDLINE
29.
Epi Info [computer program].
Version 6.04c.
Atlanta, Ga: Centers for Disease Control and Prevention; 1997.
30.
StatXact 3 [computer program].
Cambridge, Mass: Cytel Software Corp; 1997.
31.
Dajani AS, Ferrieri P, Wannamaker L.
Endemic superficial pyoderma in children.
Arch Dermatol.
1973;108:517-522.
MEDLINE
32.
Anthony BF, Perlman LV, Wannamaker LW.
Skin infections and acute nephritis in American Indian children.
Pediatrics.
1967;39:263-279.
MEDLINE
33.
Rhoades E, Hammond J, Welty T, et al.
The Indian burden of illness and future health interventions.
Public Health Rep.
1987;102:361-368.
MEDLINE
34.
Joe JR.
The health of American Indian and Alaska Native women.
J Am Med Womens Assoc.
1996;51:141-145.
MEDLINE
35.
Shopsin B, Mathema B, Martinez J, et al.
Prevalence of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in the community.
J Infect Dis.
2000;182:359-362.
MEDLINE
36.
Warshawsky B, Husain Z, Gregson D, et al.
Hospital and community-based surveillance of methicillin-resistant Staphylococcus aureus: previous
hospitalization is the major risk factor.
Infect Control Hosp Epidemiol.
2000;21:724-727.
MEDLINE
37.
Cookson B.
Methicillin-resistant Staphylococcus aureus
in the community: new battlefronts, or are the battles lost?
Infect Control Hosp Epidemiol.
2000;21:398-403.
MEDLINE
38.
Boyce J.
Are the epidemiology and microbiology of methicillin-resistant Staphylococcus aureus changing?
JAMA.
1998;279:623-624.
MEDLINE
39.
Monnet D.
Methicillin-resistant Staphylococcus aureus
and its relationship to antimicrobial use: possible implications for control.
Infect Control Hosp Epidemiol.
1998;19:552-559.
MEDLINE
40.
Tenover F, McGowan J.
The epidemiology of bacterial resistance to antimicrobial agents.
In: Evans A, Brachman P, eds. Bacterial
Infections in Humans. New York, NY: Plenum Medical Book Co;
1998:83-93.
Edward E.
Rylander, M.D.
Diplomat American
Board of Family Practice.
Diplomat American
Board of Palliative Medicine.