Clinical

Microbiology $88
Newsletter
Vol. 30, No. 23 www.cmnewsletter.com December 1, 2008

GeneXpert Testing: Applications for Clinical Microbiology, Part I*

Elizabeth M. Marlowe, Ph.D., D(ABMM),1 and Donna M. Wolk, Ph.D., D(ABMM),2 1Southern California Permanente Medical
Group, Regional Reference Laboratories, North Hollywood, California, 2Department of Pathology, University of Arizona, College
of Medicine, BIO5 Institute, Tucson, Arizona
Abstract
The impact of rapid polymerase chain reaction (PCR) technology on infectious disease testing is continuing to evolve outside
the realm of a centralized laboratory. The GeneXpert Dx system is the first unit dose, near-point-of-care molecular device com-
mercially available. To date, there are five FDA-cleared assays available for the GeneXpert System: group B Streptococcus (GBS)
from vaginal-rectal swabs, enterovirus from cerebrospinal fluid, methicillin-resistant Staphylococcus aureus (MRSA) from nares
swabs, MRSA and methicillin-susceptible S. aureus (MSSA) from skin and soft tissue infection swabs, and MRSA and MSSA
from positive blood cultures. Advantages of the GeneXpert assays include ease of use, random access, rapid results, and the ability
to run the assay without the need for pre- and post-analytical rooms. Limitations include a currently limited menu with few speci-
men types and potential delay of results due to indeterminate results. Part I of this article presents a review of this technology and
its application for the detection of GBS, enterovirus, and MRSA from various clinical specimens.

Introduction
When Kary Mullis first tested the
concept of polymerase chain reaction
(PCR), the initial experiments were per-
formed using water baths monitored by
a simple laboratory timer. This manual
cycling of temperatures quickly evolved
to automated cycling in thermocyclers,
followed by detection of PCR amplicons
with gel electrophoresis. Real-time PCR
is now used in many clinical laboratories
because it allows the rapid detection of
PCR products by the use of specific
fluorescent chemistries in a closed sys-
tem. It has become a mainstay of core
molecular laboratory technologies.
While molecular diagnostics has
revolutionized the way medicine is
*Editor’s Note: Part II of this article will
be published in the December 15, 2008
issue of CMN (Vol. 30, No. 24).
Mailing Address: Elizabeth M. Marlowe,
Ph.D., D(ABMM), Southern California
Permanente Medical Group, Regional Ref-
erence Laboratories, North Hollywood, CA
91605. Tel.: 818-503-7067. Fax: 818-503-
6713. E-mail: Elizabeth.M.Marlowe@kp.org
practiced, after 2 decades, the practice the cartridge. Once the sample and
of molecular diagnostics remains tied accompanying dispensable reagents are
to a highly skilled laboratory staff and added to the cartridge, no additional
batch processing. Emerging technology manual intervention is required. Controls
has the potential to change the reference include probe checks, pressure checks,
laboratory-centric model of molecular and specimen-processing controls. Inter-
diagnostics. The future of molecular nal controls are incorporated into each
diagnostics is changing and is focused run to ensure that the cartridge and
on producing rapid results in a general chemistry are functioning properly. The
hospital setting. The concept of point- cartridges are placed in an independently
of-care molecular diagnostics is evolv- controlled GeneXpert module, which
ing and is closer than was ever thought is a configuration of the independent
possible. heating and cooling optical reaction
The technology that has transformed (ICORE) module found in the Cepheid
molecular testing from “batch” to SmartCycler instrument. Accompany-
“STAT” is Cepheid’s GeneXpert system
(Sunnyvale, CA), which can offer near-
point-of-care results in 1 to 2.5 h. The
system consists of an instrument and a
personal computer with preloaded soft-
ware for running the tests and interpret-
ing the results. The assays are simple to
run and utilize a single-unit disposable
cartridge. The cartridge automates and
combines specimen processing, nucleic
acid extraction, amplification, and
detection. The PCR reagents are lyophi-
lized and held in various chambers in

Clinical Microbiology Newsletter 30:23,2008 © 2008 Elsevier 0196-4399/00 (see frontmatter) 175
ing software automates data interpreta-
tion. The GeneXpert instrument is avail-
able in random-access 1-bay, 4-bay, and
16-bay module, and more automated
48-bay configurations. A more auto-
mated 72-bay configuration is due to
be released soon.
Cepheid has received FDA clearance
for their GeneXpert device for a variety
of pathogens, including group B Strep-
tococcus (GBS) from vaginal-rectal
swabs (1,2), enterovirus (EV) from
cerebrospinal fluid (CSF) (3,4), and
methicillin-resistant Staphylococcus
aureus (MRSA) from nares swabs (5).
The Xpert methods are rapid and rela-
tively easy to perform; the GBS and
MRSA methods are rated as “moderate
complexity,” and the EV method is rated
as a “high complexity” test according
to Clinical Laboratory Improvement
Act (CLIA) categorization. Recently,
a GeneXpert assay that simultaneously
detects MRSA and S. aureus (SA) from
skin and soft tissue specimens was FDA
cleared. A similar MRSA-S. aureus
assay has also been FDA approved for
use in blood culture bottles.
Applications of the Technology
GBS
GBS emerged as a leading cause of
neonatal morbidity and mortality in the
1970s. As GBS is an inhabitant of the
gastrointestinal tract, transmission from
mother to infants can occur at the time
of delivery. Early-onset disease (EOD)
occurs within 7 days of birth and
accounts for about 80% of GBS infec-
tions in infants. Late-onset disease
appears after 7 days of age (6,7). Colo-
nization of pregnant women is approx-
imately 10 to 30% depending on the
patient population (8,9). Higher rates
of colonization have been noted among
African Americans, non-smokers, and
those with a high body mass index (10).
176 0196-4399/00 (see frontmatter)
In 2002, the CDC issued revised
guidelines in collaboration with the
American College of Obstetrics and
Gynecology and the American Academy
of Pediatrics recommending universal
prenatal screening of all pregnant women
between 35 and 37 weeks of gestations
to determine their vaginal-rectal GBS
colonization status. Since GBS is easily
treated with antibiotics, intrapartum
antibiotic prophylaxis (IAP) can be
provided during labor and delivery if
a woman is GBS positive (8). In 2005,
the CDC examined the impact of these
guidelines and found that overall EOD
had decreased more than 30% (11).
Despite these preventative measures,
disparities still remain among certain
ethnic groups and those with a lower
socioeconomic status (11). A 2007
report from the CDC highlighted that
among African Americans the incidence
of EOD had risen 70% to pre-recom-
mendation levels (12). Furthermore,
the majority of EOD cases arise from
women with negative GBS cultures
and no risk factors (13). Maternal GBS
colonization may be transient, chronic,
or intermittent (14). Thus, antepartum
screening may not provide the most
accurate determination of GBS colo-
nization status at the time of delivery
(15). Preterm deliveries can also miss
the 35- to 37-week GBS culture. These
births make up 7 to 11% of deliveries
but comprise 32 to 38% of EOD (13).
The solution to these problems would
be to screen these women at delivery,
since IAP given early enough (≥2 to
4 h) to GBS positive mothers at the
time of delivery significantly diminishes
GBS transmission to newborns (16).
The CDC recommends the use of
antepartum GBS screening, primarily
with culture from vaginal-rectal swabs.
Swabs are placed in selective media,
typically Todd-Hewitt or LIM broth,
© 2008 Elsevier
incubated for 18 to 24 h, and then plated
onto sheep blood agar. After 24 h, the
plates are examined for GBS; if nega-
tive, the plates are incubated another
24 h and re-examined. Suspicious colo-
nies can be confirmed as GBS by latex
agglutination methods (8).
For an assay to have maximum
impact when used for intrapartum test-
ing, the CDC suggested that it would
have to be rapid, sensitive, a minimum
of 85% accurate compared to culture,
and fit easily into the clinical labora-
tory’s routine (8). Routine PCR meets
some of these requirements; however,
the simplicity of the GeneXpert makes
it a good fit for around-the-clock testing
scenarios. GBS testing could potentially
occur in STAT laboratories to support
labor and delivery suites as testing is
needed.
PCR for GBS from vaginal-rectal
swabs is available. Only FDA-cleared
PCR methods will be discussed, since
full discussion of alternate PCR methods
is not within the scope of this review.
GBS-PCR has the ability to both
decrease turnaround time (TAT) and
increase sensitivity (17). The BD
GeneOhm Strep B PCR (BDGO) assay
(BD Diagnostics, San Diego, CA) was
the first FDA-cleared test on the market
for testing on the Cepheid SmartCycler
DX system (Cepheid, Sunnyvale, CA),
with results available within 2 h. A
multi-center study demonstrated that
the BDGO Strep B PCR had a sensi-
tivity and a specificity of 94% and
95.5%, respectively (17).
Cepheid also has two FDA-cleared
GBS assays: the Smart GBS, which is
run on their SmartCycler platform, and
the Xpert GBS assay that is run on the
GeneXpert Dx System. The Smart GBS
is FDA cleared for testing directly from
swabs or from LIM broth-enriched spec-
imens. The direct method demonstrated
Clinical Microbiology Newsletter 30:23,2008
a sensitivity of 85% and a specificity of
97% compared to culture among intra-
partum specimens tested in a clinical
trial, while the enriched method demon-
strated a sensitivity and specificity of
98.7% and 90.4%, respectively, com-
pared to culture among anetpartum spec-
imens (18). One limitation of the PCR
assays performed on the SmartCycler is
that they require a laboratory with suffi-
cient space to house the instrument and
a medical technologist to perform the
test. These tests are rated high com-
plexity by CLIA.
Clinical-trial data demonstrated that
the Xpert GBS assay has a sensitivity
and a specificity of 88.6% and 96.7%,
respectively, for both antepartum and
intrapartum specimens compared to cul-
ture (1). In the intrapartum arm of the
study, the sensitivity and specificity
were 91.3% and 95.6%, respectively.
The mean TAT was 1.84 h. During
the clinical trials, the FDA required
that nurses perform the testing on the
GeneXpert System. The assay was
FDA cleared in July 2006 as the first
molecular test given a moderate-com-
plexity rating by CLIA. In a prospective
study, Gavino and Wang (2) reported
the Xpert GBS assay to have a sensi-
tivity and a specificity of 95.5% and
64.5%, respectively.
Because of its sensitivity and perfor-
mance simplicity, the Xpert GBS assay
has the potential to decrease EOD, par-
ticularly among populations for which
there are marked disparities. However,
culture techniques will remain, as PCR-
based tests, as yet, do not provide
susceptibility results for the pencillin-
allergic populations. Antepartum cul-
tures would still need to be performed
to ensure GBS remains susceptible to
first line antibiotics. Another potential
limitation of the Xpert GBS assay is
that unresolved results, due to failed
controls or inhibition, require repeat
testing, thus delaying results and IAP,
as well as adding to the cost of testing.
Enterovirus
EV is composed of positive-sense,
single-stranded RNA viruses. The genus
is in the family Picornaviridae and cur-
rently consists of 68 distinct serotypes
(19). In the United States, an estimated
75,000 cases of aseptic meningitis
occur annually, and approximately 80
to 90% of these are caused by EVs (20-
22). Typically, most infants and young
Clinical Microbiology Newsletter 30:23,2008
children recover from EV meningitis
without sequelae. However, the clinical
diagnosis of EV is often one of exclu-
sion, so that a bacterial etiology cannot
be excluded. Without actual EV diag-
nostic confirmation, patients may be
hospitalized for further diagnostic test-
ing and the administration of antibiotics.
This practice leads to extended length
of stay and increased hospital costs.
Isolation of EV from CSF in cell
culture requires multiple cell lines and
3 to 8 days of incubation before cyto-
pathic effect appears. This time frame
is typically not rapid enough to affect
therapy or the duration of hospitaliza-
tion. Additionally, the sensitivity of cell
culture for recovery of EVs from CSF is
approximately 50 to 75% depending on
the serotype causing infection and the
concentration of virus in the CSF
(23,24).
It is no surprise that nucleic acid
amplification methods have replaced
traditional culture-based methods as
the gold standard for detecting EV in
CSF, as PCR supports a considerable
increase in sensitivity and a shorter
time to result (23,25-31). Depending
on when results are available and how
they are used in the discharge plan,
significant health care-associated cost
savings have been coupled with PCR
diagnosis of EV meningitis (21,32-37).
While many laboratories have
employed laboratory-developed assays
(LDAs) for the detection of EV for
years, LDAs require that each labora-
tory independently verify its assays.
In 2001, a multi-center study found
only 66% of laboratories performed
adequately on EV proficiency testing,
highlighting the need for more
standardized testing (38).
The Xpert EV cartridge is currently
the only FDA-cleared molecular assay
for the detection of EV from CSF. The
Xpert EV assay is able to detect 63 dif-
ferent serotypes of EV with a limit of
detection range of 0.0002 to 200 tissue
culture infective doses/ml (3,39). A
multi-center beta trial study demon-
strated that the performance character-
istics of the Xpert EV assay were
comparable to those of assays currently
being used in clinical laboratories (3).
Marlowe et al. (4) compared it to real-
time NASBA and a Taq-Man reverse
transcription-PCR and found similar
results. Assays were evaluated using a
© 2008 Elsevier
12-member proficiency panel and up
to 138 CSF specimens. The Xpert EV,
NASBA, and TaqMan assays correctly
identified 10/12, 8/12, and 7/12 profi-
ciency panel members, respectively. For
detection of EV RNA in CSF, the sensi-
tivities of the Xpert EV, NASBA, and
TaqMan were 100%, 87.5%, and 96%,
respectively.
In a prospective, unblinded compara-
tive study of the Xpert EV to the Argene
EV consensus kit (Argene SA, Varilhes,
France) and an in-house real-time PCR,
the initial and resolved sensitivities of
the Xpert EV assay were 90.45% and
98.8%, respectively (40). QCMD pro-
ficiency panel results were comparable
to those of Marlowe et al. (4).
A limitation of the Xpert EV assay
is the ability to test alternative specimen
types, as the assay is FDA cleared only
for CSF. While customers are indepen-
dently examining the off-label ability
of the cartridge to detect EV from alter-
native specimens, data are limited and
have yet to be validated in multiple
laboratories (41).
The ease of use and software inter-
pretation make the Xpert EV assay a
very attractive alternative for molecular
EV testing from CSF. Random-access
testing makes it particularly useful for
a low-volume assay and a short-staffed
laboratory. Testing can be performed as
specimens are received with less than 5
minutes hands-on time. Random access
and decreased TAT, compared to the
batch mode of testing have the potential
to significantly decrease hospital costs.
A cost analysis study demonstrating the
use of the Xpert EV assay in emergency
rooms and laboratories would be of
interest.
MRSA
The spread of drug-resistant bacteria,
such as MRSA, is a major concern for
healthcare and communities in which
aggressive infections have caused deaths
in both hospitalized patients and other-
wise healthy individuals (42). A known
colonizer, MRSA is often harbored in the
human nares, skin, throat, and mucosa
of the vagina and rectum. Human “car-
riers” can spread MRSA to others in
health care settings, who can fall victim
to potential infections. Since 2003,
MRSA has accounted for more than 60%
of all S. aureus health care-associated
infections (HAIs) reported in U.S. hos-
pitals (43). At last report, the National
0196-4399/00 (see frontmatter) 177
Health and Safety Network estimated
that in the U.S., hospitalized patients
acquire 2 million HAIs each year, caus-
ing 90,000 deaths and $4.5 billion in
excess health care costs. A large per-
centage of HAIs are due to MRSA (44).
Specific guidance continues to accu-
mulate for MRSA-related practices in
health care and the community. In 2003,
active surveillance was recommended
by national guidelines put forth by the
Society for Healthcare Epidemiology
of America (45). In 2005 and 2006, the
CDC’s Healthcare Infection Control
Practices Advisory Committee issued
recommendations focused on reporting
and management of multidrug-resistant
organisms in health care settings
(46,47). These recommendations detail
approaches for the reduction of MRSA
infections in health care facilities (48).
As of September 2008, the Association
for Professionals in Infection Control
reported 35 states that require some
form of mandatory MRSA reporting or
had study laws in place; 2 additional
states had voluntary reporting. On 26
September 2008, the state of California
passed legislation that will require hos-
pitals to increase their infection preven-
tion efforts and to report their infection
rates for posting to the public by 2011.
Note: Part II of this article will
appear in the December 15, 2008
issue of CMN (Vol. 30, No. 24).
References
1. Edwards, R.K. et al. 2008. Rapid group
B streptococci screening using a real-
time polymerase chain reaction assay.
Obstet. Gynecol. 111:1335-1341.
2. Gavino, M. and E. Wang. 2007. A
comparison of a new rapid real-time
polymerase chain reaction system to
traditional culture in determining group
B streptococcus colonization. Am. J.
Obstet. Gynecol. 197:388-4.
3. Kost, C.B. et al. 2007. Multicenter
beta trial of the GeneXpert enterovirus
assay. J. Clin. Microbiol. 45:1081-1086.
4. Marlowe, E.M. et al. 2008. Performance
of the GeneXpert enterovirus assay for
detection of enteroviral RNA in cere-
brospinal fluid. J. Clin. Virol. 43:110-113.
5. Cepheid. 2007. Xpert MRSA package
insert. Cepheid, Sunnyvale, CA.
6. Bergeron, M.G. et al. 2000. Rapid
detection of group B streptococci in
pregnant women at delivery. N. Engl.
J. Med. 343:175-179.
7. Schrag, S.J. et al. 2002. A population-
178 0196-4399/00 (see frontmatter)
based comparison of strategies to pre-
vent early-onset group B streptococcal
disease in neonates. N. Engl. J. Med.
347:233-239.
8. Schrag, S. et al. 2002. Prevention of
perinatal group B streptococcal disease.
Revised guidelines from CDC. Morb.
Mortal. Wkly. Rep. Recomm. Rep.
51:1-22.
9. Schrag, S.J. et al. 2000. Group B strepto-
coccal disease in the era of intrapartum
antibiotic prophylaxis. N. Engl. J. Med.
342:15-20.
10. Stapleton, R.D. et al. 2005. Risk factors
for group B streptococcal genitourinary
tract colonization in pregnant women.
Obstet. Gynecol. 106:1246-1252.
11. Annonymous. 2005. Disparities in uni-
versal prenatal screening for group B
streptococcus —North Carolina, 2002-
2003. MMWR Morb. Mortal. Wkly.
Rep. 54:700-703.
12. Anonymous. 2007. Perinatal group B
streptococcal disease after universal
screening recommendations — United
States, 2003-2005. MMWR Morb.
Mortal. Wkly. Rep. 56:701-705.
13. Honest, H., S. Sharma, and K.S. Khan.
2006. Rapid tests for group B Strepto-
coccus colonization in laboring women:
a systematic review. Pediatrics
117:1055-1066.
15. Yancey, M.K. et al. 1996. The accuracy
of late antenatal screening cultures in
predicting genital group B streptococcal
colonization at delivery. Obstet.
Gynecol. 88:811-815.
16. De Cueto, M. et al. 1998. Timing of
intrapartum ampicillin and prevention
of vertical transmission of group B
streptococcus. Obstet. Gynecol. 91:97-
102.
17. Davies, H.D. et al. 2004. Multicenter
study of a rapid molecular-based assay
for the diagnosis of group B strepto-
coccus colonization in pregnant women.
Clin. Infect. Dis. 39:1129-1135.
18. Cepheid. 2007. Smart GBS assay pack-
age insert. Cepheid, Sunnyvale, CA.
19. Stanway, G.F. et al. 2005. Picornaviridae,
p. 757-778. In C.M. Fauquet et al. (ed.),
Virus taxonomy. 8th report of the Inter-
national Committee on the Taxonomy
of Viruses. Elsevier Academic Press,
London, United Kingdom.
20. Rotbart, H.A. 1995. Enteroviral infec-
tions of the central nervous system.
Clin. Infect. Dis. 20:971-981.
21. Rotbart, H.A. et al. 1999. Clinical sig-
nificance of enteroviruses in serious
summer febrile illnesses of children.
Pediatr. Infect. Dis. J. 18:869-874.
22. Strikas, R.A., L.J. Anderson, and R.A.
© 2008 Elsevier
Parker. 1986. Temporal and geographic
patterns of isolates of nonpolio enter-
ovirus in the United States, 1970-1983.
J. Infect. Dis. 153:346-351.
23. Ginocchio, C.C. et al. 2005. Develop-
ment, technical performance, and clini-
cal evaluation of a NucliSens basic kit
application for detection of enterovirus
RNA in cerebrospinal fluid. J. Clin.
Microbiol. 43:2616-2623.
24. Storch, G.A. 2000. Central nervous
System Infections, p. 37-58. In G.A.
Storch (ed.), Essentials of diagnostic
virology. Churchhill Livingstone,
New York.
25. Capaul, S.E. and M. Gorgievski-Hrisoho.
2005. Detection of enterovirus RNA in
cerebrospinal fluid (CSF) using NucliSens
EasyQ Enterovirus assay. J. Clin. Virol.
32:236-240.
26. Lai, K.K. et al. 2003. Evaluation of
real-time PCR versus PCR with liquid-
phase hybridization for detection of
enterovirus RNA in cerebrospinal fluid.
J. Clin. Microbiol. 41:3133-3141.
27. Landry, M.L., R. Garner, and D.
Ferguson. 2005. Real-time nucleic acid
sequence-based amplification using
molecular beacons for detection of
enterovirus RNA in clinical specimens.
J. Clin. Microbiol. 43:3136-3139.
28. Monpoeho, S. et al. 2002. Application
of a real-time polymerase chain reaction
with internal positive control for detec-
tion and quantification of enterovirus
in cerebrospinal fluid. Eur. J. Clin.
Microbiol. Infect. Dis. 21:532-536.
29. Petitjean, J. et al. 2006. Development
and evaluation of a real-time RT-PCR
assay on the LightCycler for the rapid
detection of enterovirus in cerebrospinal
fluid specimens. J. Clin. Virol. 35:278-
284.
30. Silekens, P. et al. Real time NASBA
for the detection of enterovirus RNA
in cerebrospinal fluid, abstr. S14. Pan
American Society for Clinical Virology
Meeting, Clearwater, FL.
31. Verstrepen, W.A. et al. 2001. Rapid
detection of enterovirus RNA in cere-
brospinal fluid specimens with a novel
single-tube real-time reverse transcrip-
tion-PCR assay. J. Clin. Microbiol.
39:4093-4096.
32. Nigrovic, L.E. and V.W. Chiang. 2000.
Cost analysis of enteroviral polymerase
chain reaction in infants with fever and
cerebrospinal fluid pleocytosis. Arch.
Pediatr. Adolesc. Med. 154:817-821.
33. Polage, C.R. and C.A. Petti. 2006.
Assessment of the utility of viral culture
of cerebrospinal fluid. Clin. Infect. Dis.
43:1578-1579.
Clinical Microbiology Newsletter 30:23,2008
34. Ramers, C. et al. 2000. Impact of a
diagnostic cerebrospinal fluid entero-
virus polymerase chain reaction test on
patient management. JAMA 283:2680-
2685.
35. Robinson, C.C. et al. 2002. Impact of
rapid polymerase chain reaction results
on management of pediatric patients
with enteroviral meningitis. Pediatr.
Infect. Dis. J. 21:283-286.
36. Stellrecht, K.A. et al. 2002. The impact
of an enteroviral RT-PCR assay on the
diagnosis of aseptic meningitis and
patient management. J. Clin. Virol.
25(Suppl.1):S19-S26.
37. Hamilton, M.S. et al. 1999. Clinical
utility of polymerase chain reaction test-
ing for enteroviral meningitis. Pediatr.
Infect. Dis. J. 18:533-537.
38. van Vliet, K.E. et al. 2001. Multicenter
proficiency testing of nucleic acid ampli-
fication methods for the detection of
enteroviruses. J. Clin. Microbiol.
39:3390-3392.
Clinical Microbiology Newsletter 30:23,2008
39. Cepheid. 2006. Xpert EV package
insert, Cepheid, Sunnyvale, CA.
40. Seme, K. et al. 2008. GeneXpert entero-
virus assay: one-year experience in a
routine laboratory setting and evaluation
on three proficiency panels. J. Clin.
Microbiol. 46:1510-1513.
41. Bernard, H.C., B. Starkley, and B.
Yen-Lieberman. 2007. Evaluation
of enterovirus detection using the
GeneXpert Dx system, abstr. C-085.
Abstr. 107th Gen. Meet. Am. Soc.
Microbiol., American Society for
Microbiology, Washington, DC.
42. Klevens, R.M. et al. 2007. Invasive
methicillin-resistant Staphylococcus
aureus infections in the United States.
JAMA 298:1763-1771.
43. Anonymous. 2003. National Nosoco-
mial Infections Surveillance (NNIS)
System Report, data summary from
January 1992 through June 2003, issued
August 2003. Am. J. Infect. Control
31:481-498.
© 2008 Elsevier
44. Edwards, J.R. et al. 2007. National
Healthcare Safety Network (NHSN)
Report, data summary for 2006, issued
June 2007. Am. J. Infect. Control
35:290-301.
45. Muto, C.A. et al. 2003. SHEA guideline
for preventing nosocomial transmission
of multidrug-resistant strains of Staphylo-
coccus aureus and enterococcus. Infect.
Contr. Hosp. Epidemiol. 24:362-386.
46. McKibben, L. et al. 2006. Ensuring
rational public reporting systems for
health care-associated infections: sys-
tematic literature review and evaluation
recommendations. Am. J. Infect.
Control 34:142-149.
47. McKibben, L. et al. 2005. Guidance on
public reporting of healthcare-associated
infections: recommendations of the
Healthcare Infection Control Practices
Advisory Committee. Am. J. Infect.
Control 33:217-226.
48. Siegel, J.D. et al. 2007. Management of
multidrug-resistant organisms in health
0196-4399/00 (see frontmatter) 179