Infection Control In Health Care Settings

Keck Graduate Institute, ALS 320: Medical Diagnostics Fall 2013 Industry Review
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Infection Control in Health Care Settings
Sagar Desai, Esther Chung, Harshal Lal, Emerald Yuan,
Josh Finley, Roma Panjwani, Hari Purushothaman
ABSTRACT
Healthcare-associated infections are a broad class of
preventable conditions that affect patients during clinical
treatment. These conditions cause a significant number of
illnesses and incur high costs to the healthcare system in the
United States. Current diagnostics attempt to identify HAIs in
order to improve patient treatment and prevent further spread
of pathogens. This report examines these diagnostic methods,
including cultures, immunoassays, and nucleic acid tests, to
determine their effectiveness. By analyzing current literature
and commercialized devices, this report explores
improvements to the existing diagnostic framework.
Preventative measures in the healthcare setting can
significantly reduce both the economic and medical impact of
HAIs.
CLINICAL UTILITY
Healthcare-associated infections (HAIs) are defined by the
Centers for Disease and Control (CDC) and the National
Healthcare Safety Network (NHSN) as adverse conditions
caused by infectious agent(s) that were not present or
incubating at the time of admission (1). HAIs represent a
major preventable threat to patients and include infections
acquired from healthcare settings outside of the hospital, such
as long term care facilities and rehabilitation centers (2).
HAIs are caused by patient exposure to a variety of
pathogens while undergoing care in the healthcare setting.
Most of these pathogens are introduced through invasive
procedures and devices, such as surgery, urinary catheters,
central lines, or mechanical ventilators. HAIs are responsible
for 1.7 million infections and 99,000 deaths per year (3). HAIs
also represent a significant financial burden on patients, care
providers, and payors for treatment.
Average per patient treatment costs are $11,285 to treat
Clostridium difficile related infection, $45,814 for central line
associated blood stream infections (CLABSI), $40,144 for
ventilator acquired pneumonia (VAP), and $20,785 for
surgical site infections (SSI) (2). These costs only account for
the in-hospital treatment, the loss of productivity and patient
wages are not accounted for.
Many HAIs can be prevented, prompting the Centers for
Medicare and Medicaid Services (CMS) to change its
reimbursement rules for HAIs. The CMS will no longer
provide reimbursement for treatment of HAIs, such as SSIs,
CLABSIs, and catheter associated urinary tract infections
(CAUTIs) (3).
An additional threat to patients is the emergence of HAIs
cause by antibiotic resistant pathogens such as Methicillin-
resistant Staphylococcus aureus (MRSA) and Vancomycin-
resistant Enterococci. As antibiotics continue to be readily
prescribed for patient well-being, even for viral pathogens,
many antibiotics have begun to lose their effectiveness as
pathogens become resistant, making it increasingly difficult
for caregivers to treat HAIs (4).
Figure 1. Calculation of estimates of health care-associated
infections in U.S. hospitals among adults and children outside of
intensive care units, 2002. BSI: bloodstream infections, UTI: urinary
tract infections, PNEU: pneumonia, SSI: surgical site infections.
There were 1,195,142 estimated cases of HAIs in the United States in
2002. Urinary tract infections are the most common HAI (5).
The majority of common HAIs are preventable by
implementing regulations requiring healthcare workers to
wash their hands prior to patient contact, re-assessing the
length of times patients should be placed on ventilators, or
how long a central line or catheter must be in place. Other
requirements dictated by the CMS include that every US
hospital must designate at least one infection preventionist
(IP) who is responsible for implementing recommended
policies and practices aimed at the prevention and control of
infectious communicable diseases (6). To help in
distinguishing HAIs from other causal diseases, reporting of
present on admission (POA) conditions is required for
hospitals. The CDC has identified methicillin-resistant
Staphylococcus aureus (MRSA) and vancomycin-resistant
enterococci (VRE) as the top priorities for screening of
incoming patients (3).
Ventilator Associated Pneumonia
Ventilator associated pneumonia (VAP) is caused by
pathogens that pass to the lungs of patients on mechanical
ventilator support. The endotracheal tube is inserted into the
airway of the patient facilitates pathogen entry into the lower
respiratory tract, either through colonization of the inside, or
leakage around the outside of the endotracheal tube. Many
different pathogens can give rise to VAP, with Pseudomonas
aeruginosa and S. aureus accounting for approximately 44% of
the observed cases (7). The main symptoms of VAP are fever,
purulent (pus containing) sputum, and hypoxemia (low
oxygen in blood) (7, 8). However, these symptoms are often
difficult to observe in patients on ventilators because they are
frequently sedated (9). VAP diagnosis based on clinical
symptoms and chest radiography has low sensitivity and
specificity. Culture based methods are the gold standard but
entail long turn-around times. The primary treatment for VAP
is broad spectrum antibiotics. Treatment is adjusted to more
effective targeted antibiotics once the causative pathogen is
identified.

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Central Line Associated Bloodstream Infections
Central line associated bloodstream infections (CLABSI)
have the highest morbidity and mortality of HAIs, while also
occurring in 3-5 per 100 cases of CL use. The primary
symptoms of CLABSIs are bacteremia (bacteria in the blood),
or fungemia (fungus in the blood) without a documented
source, a fever greater than 38 degrees Celsius, hypotension,
and oliguria (low urine output) (10). The pathophysiology of
CLABSIs includes 4 main pathways of infection. The major
pathways are internal and external colonization of the catheter
surface by a pathogen. A patient’s glycoproteins (fibrinogen,
fibronectin, collagen, and laminin) absorbed on the surface of
the CL may form a layer that enhances the adherence of
certain bacteria such as S. aureus. Additionally, bacteria that
colonize the interior of the CL as biofilm are inherently more
resistant to antimicrobial agents. Frequent opening of the CL
may also be conducive to bacterial colonization. Through
external colonization, bacteria may proliferate on the skin
surrounding the CL insertion site and move into the patient via
capillary action. Additionally, contamination of the fluids and
drugs administered by CL may allow pathogens to enter the
body (11).Once bacterial sepsis occurs in systemic circulation,
a CLABSI is increasingly difficult to treat and chances of
morbidity and mortality increase.
Catheter Associated Urinary Tract Infections
Catheter associated urinary tract infections (CAUTI) account
for nearly 40% of HAIs in the US (12). CAUTIs occur
primarily due to unnecessary or prolonged use of a catheter
(13). The catheter disrupts the patient’s innate defense
mechanisms and provides pathogens with a pathway into the
bladder and upper urinary tract, allowing for the spread of a
pathogen via the catheter-mucosa interface. Also, two-thirds
of uropathogens are acquired extraluminally of the catheter
(14). Additionally, CAUTIs are seen more in women than in
men. The primary symptoms of a CAUTI are burning
sensation during micturition, a frequent need to urinate, pain
while urinating, and fever, nausea, and vomiting may occur in
upper UTIs (15, 16).
Clostridium difficile
One of the most common HAIs is a gastrointestinal
infection due to the Gram positive bacterium Clostridium
difficile, which is an opportunistic pathogen that invades
patients on broad-spectrum antibiotics to treat diarrhea or
different infections. Broad-spectrum antibiotics eliminate
colonic bacteria, enabling C. difficile to overgrow in the
intestine. The C. difficile spores most likely enter the patient
via the hands of healthcare workers. Ingested C. difficile
spores germinate and can freely colonize the vacant colon (17,
18). The main symptoms of a C. difficile infection are flu-like
symptoms such as a high fever, chills, fatigue, and body aches,
as well as bloating, diarrhea and abdominal pain (19). A C.
difficile infection is diagnosed by detection of the binary toxin
genes, tcdB and tcdC, which are produced by the spores (20).
Left untreated, an infection can develop into
pseudomembranous colitis, which has a higher morbidity and
mortality than the original infection, and is also much more
difficult to treat.
Methicillin-resistant Staphylococcus aureus (MRSA)
MRSA is the most common infectious agent in HAIs and
is given priority by the CDC because of its prevalence in
healthcare settings. It is highly virulent due to its broad disease
spectrum and multi-drug resistance (21). Colonized patients
do not present signs or symptoms of infection with MRSA.
Therefore, asymptomatic patients need to be identified
through pre-admission screening.
Methicillin resistance is acquired through horizontal gene
transfer. The most common transferred element is the
SCCmec cassette, containing the mecA gene, which codes a
speciﬁc methicillin-resistant transpeptidase, known as
penicillin-binding protein 2a (PBP2a) (22). This
transpeptidase causes low-affinity binding of β-lactam
antibiotics resulting in resistance to methicillin (23).
Nowadays MRSA is more commonly acquired through
community infections. Nasal carriage is the main cause of
clinically significant infections, therefore patients are
identified by nasal or oropharyngeal swabs. Once samples are
obtained, they are either tested by culture or by polymerase
chain reaction (PCR) based methods (3).
Vancomycin-resistant Enterococci (VRE)
Enterococci are another key infectious agent causing
HAIs. Most carriers are healthy members within a community.
Most human enterococcal infections are cause by E. faecium
(95%) and E. faecalis (5%) (3). The antibiotic vancomycin is
used frequently to treat Enterococci with inherent high
resistance to β-lactams. Vancomycin acts by binding to
peptidoglycan chain precursors, preventing them from
growing and cross-linking. Vancomycin-resistant enterococcal
species can be classified into 5 van genotypes, with vanA and
vanB being the most pathogenic and responsible for HAIs
(24). The vanA gene (along with genes vanR, vanS, vanH,
vanX, and vanZ) is acquired through horizontal gene transfer
via the transposon Tn1546 (24). These genes collectively
result in the synthesis of abnormal peptidoglycan precursors
which vancomycin cannot bind (24). Enterococcal vanA-
strains have high-level resistance to vancomycin and
teicoplanin, while vanB strains have more modest levels of
resistance to vancomycin, but are susceptible to teicoplanin.
For VRE, the ratio of infected symptomatic patients to
colonized asymptomatic patients is 1:10 in most hospital
settings, making it critical that all patients are screened before
admission (3). One risk factor for VRE colonization is the use
of oral vancomycin, since it inhibits the growth of the normal
gram-positive bowel flora (24). To test for the presence of
VRE, a stool sample from a rectal swab is cultured. Most tests
look for the presence of the vanA gene, but to definitively test
for VRE an assay should also be able to detect for the
presence of enterococci and vanB (3).
Pre-admission Screening
Both MRSA and VRE do not present symptoms upon
colonization, making pre-admission screening critical to
prevent incidence of HAIs. Pre-admission screening is done
by microbiology labs, which serve as the gatekeepers against
further spread of the pathogen (25). Active surveillance
cultures are commonly used and are designed to identify all

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patients colonized with a given multi-drug resistant organism.
This method is mainly used to detect MRSA and VRE. Ideally
these active surveillance culture programs should have a fast
turnaround time of less than 24 hours. Standard cultures
require 48-72 hours, which requires isolating patients for up to
3 days due to contact precautions regardless of the test results.
Contact isolation and contact precautions require physicians to
wear gowns and gloves before examining patients (26), and it
has been shown that physicians are less likely to examine
these patients. Reducing HAI outbreaks improves overall
patient care and is economically beneficial for hospitals, but
unnecessary isolation places a burden on patients, families,
and care providers, and leads to logistical challenges for the
hospital. Furthermore, certain patients such as those
undergoing psychiatric treatment, are not placed under contact
isolation measures, which can exacerbate symptoms and
interfere with treatment of the patient (25). Hence there is a
need for faster methods that prevent the violation of the ethical
principle of nonmaleficence (25).
Preventative Measures
In a recent study, universal decolonization of all patients in
the intensive care unit (ICU) has been found to be more
effective at preventing hospital-acquired bloodstream
infections from any type of pathogen, compared to MRSA
screening and isolation, or to targeted decolonization of only
patients identified to be MRSA carriers (21). Decolonization
involves removing transmittable bacteria from a patient, which
is accomplished via bathing in chlorhexidine and intranasal
administration of mupirocin over the course of several days.
Chlorhexidine is an antiseptic agent that has activity against a
broad array of pathogens. In comparison to other antiseptics, it
has residual antibacterial activity, which prevents secondary
infections from the environment and reduces microbial burden
on the patient’s system (27). However, because chlorhexidine
is an antiseptic, there needs to be careful monitoring of
potentially resistant pathogens in the future (27). Mupirocin
Figure 2. Strength of evidence for general infection prevention
practices targeted against MRSA: A. Alcohol-based hand rub. B.
Antimicrobial stewardship program. C. Chlorhexidine gluconate
cleansing cloth. D. Active surveillance cultures for MRSA. E. Nose
and skin MRSA decolonization prior to surgery. The varying
amounts of evidence correspond to the number of hospitals that saw
an effect through implementing those programs (6).
specifically kills staphylococci and is available only for
topical application. It is used in treating nasal carriage of
MRSA. Combined use with chlorhexidine bathing is more
effective than using mupirocin alone. However, resistance to
this antimicrobial agent has been reported (22). Universal
decolonization therefore may not be a sustainable strategy.
Other effective methods used to prevent HAIs are
summarized in Figure 2 (6). The use of alcohol-based hand
rubs and implementation of antimicrobial stewardship
programs have the highest level of evidence, while active
surveillance cultures for MRSA had a lower level of evidence
for effectiveness. Another preventative measure that can be
implemented relatively easily, decontamination of all surfaces
and medical equipment, is often overlooked or inadequately
performed (28).
TECHNICAL PRODUCT ANALYSIS
Culture-based Testing for Healthcare Associated
Infections (HAIs)
Despite long turnaround times, culture-based pathogen
identification and antimicrobial susceptibility testing is still
considered to be the gold standard of HAI testing (29).
Upon suspicion of HAIs, cultures of the infected area,
blood, sputum, urine, or other bodily fluids/tissue are
performed on general or specific media to identify the
causative organism (30).
Vancomycin resistant Enterococci (VRE)
Enterococci grow under specific conditions, and can be
isolated, detected and enumerated on selective media. Rectal
swabs or stool samples are typically plated on mEnterococcus
agar or KF Streptococcus agar. Enterococci will grow on most
blood containing agar, forming colonies that are alpha-
hemolytic (green margins) or non-hemolytic (no margins).
Bile-esculin-azide agar is used as a confirmation test, since
Enterococci can hydrolyze esculin in the presence of bile (31).
mEnterococcus agar contains Triphenyl tetrazolium chloride
(TTC) dye, which is reduced to formazan in the bacterial cell
to give red/maroon colonies.
Enterococci are gram positive, meaning the bacteria
appear purple under the a microscope after gram staining due
to uptake and retention of crystal violet into the peptidoglycan
layer in the cell wall. Isolates are further characterized using
biochemical tests such as the catalase test. Enterococci are
catalase negative, meaning no bubbles are formed when a
dilute peroxide solution is added to a bacterial isolate, since
Enterococci do not produce the enzyme catalase which
converts hydrogen peroxide to water and oxygen gas.
However, Enterococci are PYR positive, meaning they
produce the enzyme pyrrolidonase, which converts a substrate
in the PYR reagent into a compound that undergoes a
secondary reaction, generating a red product. To determine if
an enterococcal isolate is vancomycin resistant, agar dilution
antimicrobial susceptibility testing (AST) is performed
according to Clinical and Laboratory Standards Institute
(CLSI) guidelines. The bacterium is plated on agar plates
containing different concentrations of vancomycin, enabling
the minimum inhibitory concentration to be determined (32).
Methicillin-resistant Staphylococcus aureus (MRSA)

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S. aureus can be identified using standard microbiological
methods such as growth characteristics, colony morphology,
Gram’s staining, catalase and coagulase tests. Similar to
Enterococci, Staphylococci are gram positive ball shaped
bacteria that give rise to partial hemolysis when grown on
blood agar. However, Staphylococci are catalase positive, as
opposed to Enterococci. S. aureus is also coagulase positive,
meaning it produces a coagulase enzyme that clots blood
plasma, acting as one of the virulence factors of S. aureus. The
formation of a clot around an infection caused by these
bacteria likely protects it from phagocytosis by the host cells.
The coagulase test makes it possible to differentiate S. aureus
from other less pathogenic coagulase negative Staphylococci
which are part of the normal human skin flora.
Methicillin resistance can be tested using a standard disk
diffusion assay (Figure 3A), such as the Kirby-Bauer disk
diffusion method, which is performed by plating bacterial
inoculum on the surface of an agar plate. A paper disk
containing a known concentration of the antibiotic oxacillin is
placed on the inoculated agar surface and the plates are
incubated for 16 to 24 hours at 35°C. The antibiotic leaches
into the surrounding agar by diffusion. If the inoculated
bacteria are susceptible to the antibiotic from the disk, a zone
of growth inhibition (halo) is formed around the disk where
the bacteria do not grow. The diameter of this zone enables
classification into susceptible, intermediate, or resistant, using
criteria published by the CLSI (33). MRSA is resistant to
oxacillin, hence no halo is observed in Figure 3A.
Alternatively, the bacteria can be grown directly on antibiotic
containing agar (Figure 3B), wherein growth indicates that the
bacteria are resistant (33).
Figure 3. (A) Oxacillin disk diffusion plate showing methicillin-
resistant Staphylococcus aureus(34). (B) Mannitol salt agar plate with
oxacillin showing methicillin-resistant S. aureus (34)
These manual methods are relatively time consuming and
can be prone to error. Newer automated testing technologies
such as the bioMérieux’s VITEK® 2 system, are aimed at
same day bacterial identification and AST using standardized
protocols.
Clostridium difficile
To detect C. difficile via culture, stool samples are treated
with heat shock or ethanol to kill off all bacteria except spores.
The spores are then inoculated and incubated on selective
media under anaerobic conditions (35). After incubation the
colonies exhibit characteristics unique to C. diffcile such as
fluorescence under Wood’s Lamp (which uses black light to
detect bacterial infections), and the production of a horse
manure-like odor.
The major virulence factors of C. difficile are toxins A and
B. Toxin B is ~1000 times more toxic than A because it has
100-fold higher enzymatic activity than toxin A (36).
Culture methods cannot distinguish between toxin-
producing and non-toxin producing isolates. Hence, positive
culture tests require additional toxin screening (37), for
example, via cell culture Cytotoxicity Neutralization Assays
(CCCNAs). C. difficile toxins can be identified using tissue
cultures. A monolayer of human or mammalian cells in culture
is inoculated with a filtrate of the stool sample and incubated.
The cytopathic effect (CPE) causes the cells to round up and
slough off the monolayer. The sample is positive for C.
difficile toxin B if the CPE is neutralized by an antiserum from
either C. sordellii or C. difficile. (38).
This test is very sensitive and specific and is considered
the gold standard in C. difficile testing (37).
Immunoassays
Enzyme linked immunosorbent assays (ELISAs) are use to
detect antigens produced by HAI pathogens, or antibodies
produced by the host in response to a pathogen, with
enzymatic signal amplification.
Figure 3. Interpretation of C. diff Quik Chek Complete results. (A)
positive result for non-toxigenic C.diff; (B) positive result for
toxigenic C.diff; (C) Negative result; (D)-(G) Invalid results; (H)
Indeterminate. Due to low bacterial load, the specimens may test
negative for antigen but positive for toxin. Adapted from (39).
One example, the C. diff Quik Chek Complete by Alere
tests for the presence of C. diff glutamate dehydrogenase
(E)
ToxAg
C
C
Tox
Tox Tox
Tox
Tox Tox
Tox
Ag
Ag
Ag
Ag
Ag
Ag
Ag
C
C
C
C
C
C
(A)
(F)
(C)
(D)
(G)
(H)
(B)

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(GDH) and for toxin A and B specific to C. diff (39). The
assay uses mouse monoclonal antibody specific for GDH and
goat polyclonal antibodies for toxins A and B. The detection
antibodies are coupled to HPR (39). The capture antibodies
are immobilized on a membrane with three lines (
Figure 3): the antigen line (Ag) contains the antibodies
against C. diff glutamate dehydrogenase, the dotted control
line (C) contains anti-horseradish peroxidase antibodies, and
the A and B test lines (Tox) contain the antibodies against C.
diff toxins A and B (39). The stool sample is diluted and added
to a solution containing the respective detection antibodies
(39). This solution is then added to the sample well on top of
the membrane and incubated for 15 minutes at room
temperature. This incubation process allows for formation of
the sandwich complex between the respective capture and
detection antibodies with their antigens GDH and toxins A and
B (39). Regardless of the presence of C.diff antigen, the anti-
HRP antibody on the control line should always bind to HRP
antibody conjugated detection antibodies in solution. The
reaction window is then washed with the wash buffer, to
remove unbound detection antibodies, and then a solution
containing the HRP substrate tetramethylbenzidine is added.
After another 10 minute incubation period, the test results are
interpreted as illustrated in Figure 4. The C. diff Quik Chek
Complete assay has sensitivity to GDH and toxins A and B of
92.4% and 93.9% and specificity of 83.5% and 99.3% (40).
This assay allows for quick results with diagnosis in less than
1 hour. It is less expensive and easier to use than PCR (40,
41). This immunoassay has lower biohazard risks than culture
method and no isolation of organisms is needed because the
test can be performed directly from the sample.
Immunoassays are also used for the identification of
MRSA. One study developed a novel screening test for MRSA
that detects penicillin-binding protein 2a (PBP2) with 94.4%
sensitivity and 100% specificity (42). The method uses anti-
PBP2 monoclonal IgM and anti-mouse IgG antibodies in
conjunction with standard ELISA or other immunoassay
methods to detect MRSA. Matsui et al. developed an
immunochromatographic test (ICT) for the detection of PBP2-
producing cells for use in clinical laboratories. Two
monoclonal antibodies, 10G2 and 1G12 were used to form an
antigen sandwich. The 10G2 antibody was combined with a
colloidal gold particle that served as a detector of PBP2. The
1G12 antibody was immobilized on a nitrocellulose membrane
that captured the 10G2-gold colloid-PBP2 complex. To
measure sensitivity, recombinant PBP2 (rPBP) was used.
Results showed that the test strip was able to detect purified
rPBP at concentrations as low as 1.0ng/50ul/test but was
unable to detect protein levels below 0.5ng/test. Such rapid
immunoassay tests may allow for better screening in hospital
settings. The Luminex xTAG multiplex system offers a way to
detect for at a sensitivity and specificity of 97.7% and 94.9%
respectively (43). Test results are delivered in under five
hours.
Nucleic Acid Testing
Nucleic Acid Testing (NAT) is one of the most rapidly
developing IVD market segments, and is used to diagnose
infectious diseases such as HAIs. While immunoassays can
typically be performed directly on clinical samples, nucleic
acid testing requires the nucleic acids to be separated and
purified due to the risk of nucleic acid degradation or
polymerase inhibition (44). NAT can reduce the time to
diagnose a patient to as little as 1-2 hours, compared to 24-48
hours required for current gold standard culture-based
methods. NAT therefore offers rapid and accurate detection
which is crucial in diagnosing HAIs to prevent transmission.
Cepheid GeneXpert
The GeneXpert system by Cepheid is a fully automated
platform that conducts sample preparation followed by target
amplification via the Polymerase Chain Reaction (PCR), with
real time fluorescence detection. The GeneXpert uses
disposable, single-use cartridges. Different cartridges are
available to test for MRSA, C. difficile, and VRE.
The GeneXpert MRSA test targets the staphylococcal
cassette chromosome mec (SCCmec), which contains the
mecA gene that is responsible for resistance to β-lactams such
as meticillin in S. aureus (45, 46). The cartridge contains
multiple chambers, which enable reagent storage, nucleic acid
extraction, PCR amplification, and real time detection. The
cartridge contains a piston and rotating valve to enable fluid
transfer between the 11 chambers. Within the chambers are
freeze-dried enzymes, DNA building, and other reagents
required for the reaction mixture. The system enables
ultrasonic lysis of the pathogen, and nucleic acid extraction.
Figure 4. (A) Cepheid GeneXpert Cartridge Parts (B) Cutaway of
Cartridge. The cartridge contains 11 chambers that hold sample,
diluents, and reagents. Reagents and samples are transferred between
the chambers using a plunger in the middle of the cartridge, in
conjunction with a rotating valve. Most of the cartridge is dedicated
to reagent storage and sample preparation, with PCR amplification
and detection performed in the small square chamber at the back of
the cartridge. Adapted from (49).
Once the sample is processed, it is mixed with the PCR
reagents and moved into the reaction tube. The reaction tube
allows for thermal cycling, optical excitation, and detection of
the generated amplicons (47). The assay is started after the
cartridge containing the patient stool sample and required
reagents are inserted into the GeneXpert system. Compared to
culture methods, the GeneXpert MRSA provides sensitivity
(A) (B)
Cover
Liquid
reservoirs
PCR
reaction
vessel
Syringe
Rotary valve
Ultrasonic interface
Base
Plunger
Bead retaining
material
Internal
control bead
Bead retaining
material
Primers &
Probes
Enzyme reagents

6
and specificity values of 95%-100% and 89.7%-97%,
respectively (45, 46, 48).
Along with MRSA, GeneXpert has a kit that tests for
Vancomycin-resistant enterococci (VRE). VRE grow
resistant due to possession of vanA and vanB genes from other
organisms (50, 51). GeneXpert vanA/vanB detects for these
genes in the sample through RT-PCR just like the assays for
MRSA and C. diff. Sensitivity and specificity for vanA and
vanB were reported to be 95.8%-100% and 83.2%-99.5%,
respectively compared to culture methods (50, 51).
GeneXpert also tests for C. difficile, which is the cause for
the majority of healthcare acquired infections leading to
antibiotic-associated diarrhea and pseudomembranous colitis
(52). C. difficile carry toxin A (tcdA) or B (tcdB) genes,
which are assay targets for diagnosis. There are two assays
offered by GeneXpert to test for C. difficile. GeneXpert C.
difficile PCR assay detects tcdB using RT-PCR. GeneXpert C.
difficile /Epi PCR assay is a multiplex RT-PCR that detects
binary toxin gene (cdt), tcdC gene, along with the tcdB
leading to the identification of the epidemic 027/NAP1/B1
strain (20).
Illumigene C. difficile
The Illumigene C. difficile assay by Meridian Bioscience
uses loop-mediated isothermal amplification (LAMP) to detect
a conserved 204-bp sequence within tcdA (20). Manual
sample extraction consists of stool collection using the sample
brush provided in the kit, placing the brush in diluent, and
vortexing for 10 seconds. Lyophilized S.aureus is added to the
sample, serving as the extraction and external amplification
control. The solution is squeezed into the extraction tube and
heated at 95° C for 10-minutes, then vortexed for an additional
10 seconds. The extracted solution is added to the reaction
buffer tube and vortexed for another 10 seconds. This solution
is then transferred into the test and control tubes, which
contain primers for C. difficile and S.aureus, respectively. The
reaction tubes are placed into the Illumipro-10 device where
the sample undergoes automated isothermal amplification and
detection (50). Along with the sample, the control consisting
of S. aureus DNA target is amplified and detected to
determine results read by the Incubator/Reader (51).
Compared to culture methods, Ilumigene C. diff showed a
sensitivity and specificity of 94%-95.2% and 95.3%,
respectively (20, 51). Unlike the Cepheid GeneXpert, the
Illumigene C. diff assay is not able to detect the hypervirulent
027/NAP1/BI strain (20).
Portrait Toxigenic C. difficile Assay
The Portrait Toxigenic C. diff. Assay by Great Basin
diagnoses the presence of C. diff. in stool samples. Similar to
the Cepheid GeneXpert system, extraction, amplification, and
detection occur in a single use test cartridge. The test is
initiated once the cartridge is inserted into the analyzer. The
assay uses isothermal helicase-dependent amplification (HDA)
to unwind the double-stranded DNA (52, 53) . In this process,
DNA helicase enzymes are used to separate the DNA strands
instead of heat. Single strand binding proteins present in the
mastermix keep the now single stranded DNA separated. In
the Portrait C.diff assay, the 78-nucleotide 3’ region of the
tcdB gene is amplified, and then detected using immobilized
capture probes on a slide array (54, 55). The addition of
tetramethylbenzidine (TMB) added to the bound conjugate
forming a colored precipate at the probe/target sequence
complex location. Results are based these colored spots which
form on the chip surface, which are then read by the optical
reader (52). The sensitivity and specificity of the assay has
been reported to be 97.6% and 96.4%, respectively (56).
Table 1. Nucleic Acid Tests to diagnose Healthcare-Associated
Infections
Company -
Platform
Pathogen Target
Molecular
method
Extraction Time
MRSA SCCmec PCR Automated <2h
Cepheid -
GeneXpert
C. diff tcdA PCR Automated 45min
C.
diff/EPI
tcdB/tcdC PCR Automated 45min
VRE vanA/vanB PCR Automated ~50min
Illumigene C. diff tcdA LAMP Manual 1h
Portrait C. diff tcdB HDA Automated 1.5h
MARKET / COMPETITOR ANALYSIS
Most hospitals have a policy of self-oversight regarding
decisions about HAIs. A group of professionals, called an
Infection Control Board or a similar name, is tasked with
oversight and decision-making regarding HAIs at the
particular hospital. The structure and organization of these
Infection Control Boards varies from hospital to hospital (57).
However, the professionals in these groups are expected to be
trained and certified in the safe handling of infectious
materials. The Certification Board of Infection Control and
Epidemiology, Inc., or CBIC, is one organization that offers
this certification (58). These certified professionals are then
tasked with making decisions regarding infection control
protocols, treatment, and diagnostics.
Poor infection control policies can impact a hospital’s
finances in a number of ways. Reimbursement schedules from
the CMS are tied to a hospital’s performance in controlling
HAIs. A policy, enacted in 2008, specifically denies payment
for readmissions attributable to certain preventable HAIs—
specifically, CAUTIs, SSIs and CLABSIs (59). Interestingly,
though, some evidence indicates that this has not actually
affected infection rates (60).
Another factor that plays into the financial motivation is
consumer (i.e. patient) satisfaction. Like any company, a
hospital must provide high-quality service to attract and retain
customers. In fact, evidence shows that increased patient
satisfaction, as measured by patient surveys, is tied to a
hospital’s financial performance (61, 62).
Significant direct costs are incurred as a result of HAIs in
the United States. Estimates place the nationwide costs of
HAIs between $28.4 and $33.8 billion for 2007, when
adjusted for inflation (63). Per patient, this equals between
$16,359 and $19,430 on average. These costs can be broken
down by infection site (Figure 5). The potential cost savings

7
through HAI prevention have been estimated between $5.7-6.8
billion (low estimate) and $25.0-31.5 billion (high estimate)
(63). The current analyses assume that 65%-70% of CLABSIs
and CAUTIs and 55% of VAP and SSIs are preventable.
CLABSI prevention has been singled out as having a higher
cost impact than the other infection types due to the high cost
combined with the high fatality rate and preventability (64).
As shown in Figures 6 and 7, CLABSI and VAP both have
high fatalities and average costs per patient, but low
prevalence, complicating the cost impact estimates.
Figure 5. Mean Cost of HAIs per Patient by Infection Site. SSI =
Surgical Site Infection; CLABSI = Central Line-Associated Blood
Stream Infection; VAP = Ventilator-Associated Pneumonia; CAUTI
= Catheter-Associated Urinary Tract Infection; CDI = Clostridium
difficile-associated Infection (63).
The patient as a consumer is beginning to play a more
important role in the HAI landscape, primarily through patient
satisfaction surveys. The only government-utilized satisfaction
survey is the HCAHPS, or Hospital Consumer Assessment of
Healthcare Providers and Systems (65).
Figure 6. Fatality Rate of HAIs by Infection Site. CDI (Clostridium
difficile-associated Infection) is omitted due to lack of reliable data.
Hospital adaption of this survey has been increasing
steadily, and has grown from 1.1 million completed surveys
from 2,421 hospitals to 3.1 million surveys from 3,928
hospitals (66).
Acute-care hospitals that participate in the IPPS (Inpatient
Prospective Payment System), a reimbursement system
created by CMS for Medicare-qualified acute hospital stays,
receive payments from CMS based on patient discharges (67).
As of 2006, CMS has levied percentage penalties to a
hospital’s payments if their HCAHPS performance is too low
(59).
Figure 7. Infection Prevalence of HAIs by Infection Site. Prevalence
measured as total number of infections per year (68).
Other surveys, such as the Leapfrog survey, exist but do
not affect a hospital’s reimbursement and are voluntary (69).
Furthermore, there is increasing confusion as a result of too
many disparate surveys being developed—a single hospital
can have a different rating for each survey (70). Further
complicating matters, at least one study has indicated that
patient satisfaction scores, on average, are not affected by the
patient getting a hospital-acquired condition (71).
Still, by completing these surveys, patients have a direct
role in pressuring hospitals to perform better HAI control. A
hospital’s HCAHPS score affects its reimbursements, and
evidence suggests the LeapFrog initiatives have had an overall
positive effect on the performance of participating institutions,
despite hurdles such as limited participation nationwide (72).
Another source of pressure from patients is the use of
social media, which is becoming increasingly important to
hospitals. Patients have indicated a desire for their health care
providers to engage in social media platforms (73). As a
marketing and surveying strategy, social media is more cost-
effective than current solutions (74). Finally, the widespread
visibility of social media-based information puts pressure on
health care providers in the face of a potentially large
audience, as opposed to patient survey data (75).
Regulations to control HAIs
To monitor and control HAIs, in 2005, the National
Healthcare Safety Network (NHSN) was established under the
Healthcare Quality Promotion Division at the CDC. The CDC
incorporated three former systems, the National Nosocomial
Infections Surveillance system, the Dialysis Surveillance
Network, and the National Surveillance System for Healthcare
Workers, into a common national database (77). The goals of
this consolidation were to estimate the magnitude of HAIs,
and to develop and evaluate strategies to prevent HAIs. The
NHSN also aids in improving quality by providing risk-
adjusted data for both inter-facility and intra-facility

8
Table 2. Prevalence of Healthcare-Associated Infections, based on pathogen type, accounted to the NHSN, by Type of HAI, 2009–2010
CLABSI - Central Line-Associated Blood Stream Infection; CAUTI - Catheter-Associated Urinary Tract Infection; VAP - Ventilator-Associated
Pneumonia; SSI - Surgical Site Infection (76).
comparisons. Healthcare facilities receive assistance in
developing surveillance and analysis methods to acknowledge
patient safety problems as well as prevent HAIs (77), (78).
According to the CDC, the NHSN is the gold standard for
HAI surveillance (79).
NHSN functions and workflow
In 2008, NHSN began enrolling all healthcare facilities in
the United States (80). Data is collected and reported by the
NHSN-trained healthcare facility personnel, on a monthly
Figure 8. Deaths due to Clostridium difficile infection between 1999
and 2010 (82).
basis using standardized methods. Information is either
manually entered into the NHSN database, or uploaded as xml
files. NHSN categorized these data into two modules. The
device-associated module includes CLABSIs, CAUTIs and
VAP. The procedure-associated module includes SSIs and
post procedure pneumonia (76). In addition to reporting based
on HAI types, HAIs are also reported based on the pathogen
causing infection (Table 2) (81). With C. difficile infections
causing increased mortality each year (Figure 9), the federal
government is mandating the reporting of C. diff infections
(82), to facilitate implementation of appropriate
epidemiological control strategies.
The reported infections are calculated based on the number
of patient-days and infection rate. These infections are also
categorized based on the nature of the healthcare facility and
based on the age of patients (76). To hold active status,
healthcare facilities must submit at least data for 6 months
each year per module (83).
Measures to overcome drawbacks
To incentivize the reduction of HAIs, the CMS terminated
reimbursing healthcare providers for treating SSIs, CAUTIs
and CLABSIs (84). Even with such policies, payment
reductions were negligible and healthcare providers do not
show much variation in the services they provide. The Federal
government is attempting to implement more stringent
mandates by means of the Affordable Care Act (ACA) to
overcome this problem (84). A claim is denied reimbursement
if the patient does not present with symptoms of the HAI at
the point of admission (POA) as well as 30 days from
discharge (85). This reimbursement change aims to alter staff
behavior with the top management insisting on preventive
measures. By modifying organizational structures, hospitals

9
can bring about changes in patient care methods and clinician
behavior, such as hand hygiene. By accepting the best HAI
measures, consumers, clinicians, administrators and policy
makers, can eliminate the preventable HAIs and identify
various other benefits such as better quality of life (86).
The ACA tries to prevent HAIs by introducing incentives
to improve measurement and reporting. It also ensures that
transparent information concerning HAI prevalence is
available online so that the public can better evaluate their
healthcare providers. Hospitals, with higher rates of HAI will
be imposed a penalty and with such mandates it is expected
that the cost of Medicare will reduce by $3.2 billion over the
next decade (87).
Table 3. Overview of Different Diagnostic Tests Used to Screen for HAIs
Assay Mol. Method Pathogen Target Time Sensitivity Specificity Ease of Use*
Bile-Esculin-
Azide Agar
Culture VRE Pathogen 24-48 hours 86% 92% 2
CCCNAs Culture C. diff Toxin B 24- 48 hours 98% 100% 2
Blood Agar Culture MRSA Pathogen 18 to 24 hours 99% 99% 2
Kirby-Bauer
Disk Diffusion
Method
Culture MRSA
Susceptibility of
organism to
Antibiotics
Depends on
growth of the
organism (18-
36 hours)
99% 100% 2
Vitek 2 Culture S.aureus
Pathogen and
AST
24 hours 97.5% 100% 1
aBCYE Culture Legionellosis NA ~ 5 days 80% 100% 2
C. diff
QuikChek
Immunoassays C. diff A and B Toxins <30m 94.40% 100% 2
Luminex xTAG Immunoassays C. diff PBP2 <5h 97.70% 94.90% 2
NAT MRSA SCCmec <2h 95% - 100% 89.7% - 97% 2
Cepheid
GeneXpert
NAT VRE VanA / VanB 45 min 95.8% - 100% 83.2% - 99.5% 2
NAT C. diff tcdA 45 min 93.50% 94.00% 2
NAT C. diff / EPI tcdB ~50 min 93.39% 94.02% 2
Illumigene NAT C. diff tcdA 1h 94% - 95.2% 95.30% 2
Portrait NAT C. diff tcdB 1.5h 97.60% 96.40% 2
*Ease of Use scoring: 1—requires extensive training and technical knowledge, 2—some training
and technical knowledge is necessary, 3—anyone can run the assay after reading instructions.
References
1. [Article] Horan, T. C., Andrus, M., and Dudeck, M. A.
(2008) CDC/NHSN Surveillance Definition of Health Care-
Associated Infection and Criteria for Specific Types of
Infections in the Acute Care Setting. Am. J. Infect. Control.
36, 309-332, http://dx.doi.org/10.1016/j.ajic.2008.03.002
2. [Article] Zimlichman, Eyal , Henderson, Daniel , Tamir,
Orly , Franz, Calvin, Song, Peter , Yamin Cyrus K., Keohane,
Carol , Denham, Charles R., Bates David W. ,. (2013) Health
Care–Associated Infections A Meta-Analysis of Costs and
Financial Impact on the US Health Care System. JAMA Intern
Med. Epub,
http://dx.doi.org/10.1001/jamainternmed.2013.9763
3. [Article] Dolinger, D. L., and and Jacobs, A. A. (2011)
Molecular Diagnostics and Active Screening for Health Care-
Associated Infections: Stepping-Up the Game. Labmedicine.
42, 267-272,
http://dx.doi.org/10.1309/LMH144ZOETKVQCJU
4. Prevention of Hospital-Acquired Infections: A Practical
Guide. (2002) 2nd ed., World Health Organization, Geneva
5. [Article] Klevens, R. M., Edwards, J. R., Richards, C. L.,
Jr., Horan, T. C., Gaynes, R. P., Pollock, D. A., and Cardo, D.
M. (2007) Estimating Health Care-Associated Infections and
Deaths in US Hospitals, 2002. Public Health Rep. 122, 160-
166
6. [Article] Saint, S., Greene, M. T., Olmsted, R. N., Chopra,
V., Meddings, J., Safdar, N., and Krein, S. L. (2013) Perceived
Strength of Evidence Supporting Practices to Prevent Health
Care-Associated Infection: Results from a National Survey of
Infection Prevention Personnel. Am. J. Infect. Control. 41,
100-106, http://dx.doi.org/10.1016/j.ajic.2012.10.007
7. [Article] Messika, J., Magdoud, F., Clermont, O., Margetis,
D., Gaudry, S., Roux, D., Branger, C., Dreyfuss, D., Denamur,
E., and Ricard, J. (2012) Pathophysiology of Escherichia Coli

10
Ventilator-Associated Pneumonia: Implication of Highly
Virulent Extraintestinal Pathogenic Strains. Intensive Care
Med. 38, 2007-2016, http://dx.doi.org/10.1007/s00134-012-
2699-5
8. [Article] Mietto, C., Pinciroli, R., Patel, N., and Berra, L.
(2013) Ventilator Associated Pneumonia: Evolving
Definitions and Preventive Strategies. Respir. Care. 58, 990-
1003, http://dx.doi.org/10.4187/respcare.02380
9. [Article] Grgurich, P. E., Hudcova, J., Lei, Y., Sarwar, A.,
and Craven, D. E. (2013) Diagnosis of Ventilator-Associated
Pneumonia: Controversies and Working Toward a Gold
Standard. Curr. Opin. Infect. Dis. 26, 140-150,
http://dx.doi.org/10.1097/QCO.0b013e32835ebbd0
10. Making Health Care Safer: Reducing Bloodstream
Infections. (2011) Centers for Disease Control and Prevention,
Atlanta
11. [Article] Wagner, J., Schilcher, G., Zollner-Schwetz, I.,
Hoenigl, M., Valentin, T., Ribitsch, W., Horina, J.,
Rosenkranz, A. R., Grisold, A., Unteregger, M., Troppan, K.,
Valentin, A., Neumeister, P., and Krause, R. (2013)
Microbiological Screening for Earlier Detection of Central
Venous Catheter-Related Bloodstream Infections. Eur. J. Clin.
Invest. 43, 964-969, http://dx.doi.org/10.1111/eci.12126
12. [Article] Tambyah, P., Knasinski, V., and Maki, D. (2002)
The Direct Costs of Nosocomial Catheter-Associated Urinary
Tract Infection in the Era of Managed Care. Infection Control
and Hospital Epidemiology. 23, 27-31,
http://dx.doi.org/10.1086/501964
13. [Article] Topal, J., Conklin, S., Camp, K., Morris, V.,
Balcezak, T., and Herbert, P. (2005) Prevention of
Nosocomial Catheter-Associated Urinary Tract Infections
through Computerized Feedback to Physicians and a Nurse-
Directed Protocol. American Journal of Medical Quality. 20,
121-126, http://dx.doi.org/10.1177/10628606052-76074
14. [Article] Hooton, T. M., Bradley, S. F., Cardenas, D. D.,
Colgan, R., Geerlings, S. E., Rice, J. C., Saint, S., Schaeffer,
A. J., Tambayh, P. A., Tenke, P., and Nicolle, L. E. (2010)
Diagnosis, Prevention, and Treatment of CatheterAssociated
Urinary Tract Infection in Adults:
2009 International Clinical Practice Guidelines
from the Infectious Diseases Society of America. Clinical
Infectious Diseases. 50, 625-663
15. [Article] Eggimann, P., and Pittet, D. (2003)
Pathophysiology and Prevention of Intravascular Catheter-
Related Infection. Med. Mal. Infect. 33, 554-563,
http://dx.doi.org/10.1016/S0399-077X(03)00238-5
16. [Article] Eggimann, P., and Pittet, D. (2002) Overview of
Catheter-Related Infections with Special Emphasis on
Prevention Based on Educational Programs. Clinical
Microbiology and Infection. 8, 295-309,
http://dx.doi.org/10.1046/j.1469-0691.2002.00467.x
17. [Webpage] Clostridium difficile excerpt: Guideline for
environmental infection control in health-care facilities,
2003Centers for Disease Control and Prevention2010.
Available from:
http://www.cdc.gov/HAI/organisms/cdiff/Cdiff_excerpt.html
18. [Article] Ochsner, U. A., Katilius, E., and Janjic, N. (2013)
Detection of Clostridium Difficile Toxins A, B and Binary
Toxin with Slow Off-Rate Modified Aptamers. Diagn.
Microbiol. Infect. Dis. 76, 278-285,
http://dx.doi.org/10.1016/j.diagmicrobio.2013.03.029
19. [Article] Lipp, Michael J, Nero, Damion C, Callahan,
Mark A. (2012) Impact of Hospital-Acquired Clostridium
Difficile. J Gastroenterol Hepatol. 27, 1733-1737
20. [Article] Pancholi, P., Kelly, C., Raczkowski, M., and
Balada-Llasat, B. (2012) Detection of Toxigenic Clostridium
Difficile: Comparison of the Cell Culture Neutralization,
Xpert C. Difficile, Xpert C. difficile/Epi, and Illumigene C.
Difficile Assays. Journal of Clinical Microbiology. 50, 1331-
1335, http://dx.doi.org/10.1128/JCM.06597-11
21. [Article] Huang, S. S., Septimus, E., Kleinman, K.,
Moody, J., Hickok, J., Avery, T. R., Lankiewicz, J.,
Gombosev, A., Terpstra, L., Hartford, F., Hayden, M. K.,
Jernigan, J. A., Weinstein, R. A., Fraser, V. J., Haffenreffer,
K., Cui, E., Kaganov, R. E., Lolans, K., Perlin, J. B., Platt, R.,
CDC Prevention Epictr Program, AHRQ DECIDE Network,
and and Healthcare-Associated Infections P. (2013) Targeted
Versus Universal Decolonization to Prevent ICU Infection. N.
Engl. J. Med. 368, 2255-2265,
http://dx.doi.org/10.1056/NEJMoa1207290
22. [Article] Chambers, H. (1997) Methicillin Resistance in
Staphylococci: Molecular and Biochemical Basis and Clinical
Implications. Clin. Microbiol. Rev. 10, 781
23. [Article] Belmekki, M., Mammeri, H., Hamdad, F.,
Rousseau, F., Canarelli, B., and Biendo, M. (2013)
Comparison of Xpert MRSA/SA Nasal and MRSA/SA ELITe
MGB Assays for Detection of the mecA Gene with
Susceptibility Testing Methods for Determination of
Methicillin Resistance in Staphylococcus Aureus Isolates. J.
Clin. Microbiol. 51, 3183-3191,
http://dx.doi.org/10.1128/JCM.00860-13
24. [Article] Cetinkaya, Y., Falk, P., and Mayhall, G. (2000)
Vancomycin-Resistant Enterococci. Clinical Microbiology
Reviews. 13, 686-707, http://dx.doi.org/0893-
8512/00/$04.0010
25. [Article] Diekema, D. J., and Edmond, M. B. (2007) Look
before You Leap: Active Surveillance for Multi-Drug
Resistant Organisms. Clinical Infectious Diseases. 44, 1101-
1107, http://dx.doi.org/10.1086/512820
26. [Article] Saint, S., Higgins, L., Nallamothu, B., and
Chenoweth, C. (2003) Do Physicians Examine Patients in
Contact Isolation Less Frequently? A Brief Report. Am. J.
Infect. Control. 31, 354-356,
http://dx.doi.org/10.1067/mic.2003.50
27. [Article] Climo, M., Yokoe, D., Warren, D., Perl, T.,
Bolon, M., Herwaldt, L., Weinstein R., Sepkowitz, K.,
Jernigan J., Sanogo, K., and Wong, E. (2013) Effect of Daily
Chlorhexidine Bathing on Hospital-Acquired Infection
. N Engl J Med. 368, 533-542,
http://dx.doi.org/10.1056/NEJMoa1113849

11
28. [Article] Weber, D. J., and Rutala, W. A. (2013)
Understanding and Preventing Transmission of Healthcare-
Associated Pathogens due to the Contaminated Hospital
Environment INTRODUCTION. Infection Control and
Hospital Epidemiology. 34, 449-452,
http://dx.doi.org/10.1086/670223
29. [Chapter] Moore, V. L. (2011) APIC Textbook - Chapter
16 -
Microbiology Basics, in APIC textbook
30. [Article] EMORI, T., and GAYNES, R. (1993) An
Overview of Nosocomial Infections, Including the Role of the
Microbiology Laboratory. Clin. Microbiol. Rev. 6, 428-442
31. [Article] Drews, S., Johnson, G., Gharabaghi, F., Roscoe,
M., Matlow, A., Tellier, R., and Richardson, S. (2006) A 24-
Hour Screening Protocol for Identification of Vancomycin-
Resistant Enterococcus Faecium. J. Clin. Microbiol. 44, 1578-
1580, http://dx.doi.org/10.1128/JCM.44.4.1578-1580.2006
32. [Article] Manero, A., and Blanch, A. (1999) Identification
of Enterococcus Spp. with a Biochemical Key. Appl. Environ.
Microbiol. 65, 4425-4430
33. [Article] Jorgensen, J. H., and Ferraro, M. J. (2009)
Antimicrobial Susceptibility Testing: A Review of General
Principles and Contemporary Practices. Clinical Infectious
Diseases. 49, 1749-1755, http://dx.doi.org/10.1086/647952
34. [Article] Pillai, M. M., Latha, R., and Sarkar, G. (2012)
Detection of Methicillin Resistance in Staphylococcus
Aureus by Polymerase Chain Reaction and Conventional
Methods: A Comparative Study. Journal of Laboratory
Physicians. 4, 83-83-88, http://dx.doi.org/10.4103/0974-
2727.105587
35. [Article] Eckert, C., Burghoffer, B., Lalande, V., and
Barbut, F. (2013) Evaluation of the Chromogenic Agar
chromID C. Difficile. J. Clin. Microbiol. 51, 1002-1004,
36. [Article] ChavesOlarte, E., Weidmann, M.,
vonEichelStreiber, C., and Thelestam, M. (1997) Toxins A
and B from Clostridium Difficile Differ with Respect to
Enzymatic Potencies, Cellular Substrate Specificities, and
Surface Binding to Cultured Cells. J. Clin. Invest. 100, 1734-
1741, http://dx.doi.org/10.1172/JCI119698
37. [Article] Bouza, E., Munoz, P., and Alonso, R. (2005)
Clinical Manifestations, Treatment and Control of Infections
Caused by Clostridium Difficile. Clinical Microbiology and
Infection. 11, 57-64, http://dx.doi.org/10.1111/j.1469-
0691.2005.01165.x
38. Burnham, C. D., Carroll, K. C., Carroll, K. C., and
Bartlett, J. G. (2013) Diagnosis of Clostridium Difficile
Infection: An Ongoing Conundrum for Clinicians and for
Clinical Laboratories; Biology of Clostridium Difficile:
Implications for Epidemiology and Diagnosis.
39. Alere North America, I. (2012) C. Diff Quik Chek
Complete. Alere North America, Inc., USA
40. [Article] Samra, Z., and et. al. (2013) Evaluation of a New
Immunochromatography Test for Rapid and Simultaneous
Detection of Clostridium Difficile Antigen and Toxins. Israel
Medical Associate Journal, IMAJ. 15, 373-376
41. [Article] Cockerill, F. (2003) Rapid Detection of
Pathogens and Antimicrobial Resistance in Intensive Care
Patients using Nucleic Acid-Based Techniques. Scandinavian
Journal of Clinical & Laboratory Investigation. 63, 34-46,
http://dx.doi.org/10.1080/00855910310002213
42. [Article] Swindells J, FAU - Brenwald, N., Brenwald N,
FAU - Reading, N., Reading N, FAU - Oppenheim, B., and
Oppenheim B. Evaluation of Diagnostic Tests for Clostridium
Difficile Infection. - J Clin Microbiol.2010 Feb;48(2):606-
8.doi: 10.1128/JCM.01579-09.Epub 2009 Dec 23.
43. [Webpage] xMAP technologyLuminex Corporation.
Retrieved on: 11/9/13. Available from:
http://www.luminexcorp.com/TechnologiesScience/xMAPTec
hnology/
44. Niemz, A. (2013) Medical Diagnostics Lecture #10:
Nucleic Acid Test. Claremont
45. [Article] Rossney, A., Herra, C., Brennan, G., Morgan, P.,
and O'Connell, B. (2008) Evaluation of the Xpert Methicillin-
Resistant Staphylococcus Aureus (MRSA) Assay using the
GeneXpert Real-Time PCR Platform for Rapid Detection of
MRSA from Screen Specimen. Journal of Clinical
Microbiology. 46, 3285-3290,
46. [Article] Oh, A., and et. al. (2013) Clinical Utility of the
Xpert MRSA Assay for Early Detection of Methicillin-
Resistant Staphylococcus Aureus. Molecular Medicine
Reports. 7, 11-15, http://dx.doi.org/10.3892/mmr.2012.1121
47. [Webpage] Genexpert faqCepheid2012. Retrieved on:
November 2, 2013. Available from:
http://www.cepheid.com/resources-and-
support/support/technical-faq/genexpert-faq
48. [Article] Cercenado, E., and et. al. (2012) Rapid Detection
of Staphylococcus Aureus in Lower Respiratory Tract
Secretions from Patients with Suspected Ventilator-Associated
Pneumonia: Evaluation of the Cepheid Xpert MRSA/SA SSTI
Assay. Journal of Clinical Microbiology. 50, 4095-2097,
49. [Webpage] Dealing with the complexity of a living
targetCepheid. Last Updated: 2011, 2011. Retrieved on:
November 7, 2013. Available from:
http://www.cepheidondemand.com/Fall-2010/cover-story.php
50. Meridian Bioscience, I. (2013) Illumigene Molecular
Diagnostic System. Meridian Bioscience, Inc., USA
51. Meridian Bioscience, I. (2013) Illumigene C Diff DNA
Amplifcation Assay for the Detection of Cytotoxigenic C.
Difficile in Stool Specimens. Meridian Bioscience, Inc., USA
52. Finch, L. S., and Duncan, C. M. (2013) Molecular Test to
Determine Toxigenic Capabilities in GDH-Positive, Toxgin
Negative Samples: Evaluation of the Portrait Toxigenic C.
Difficile Assay. British Journal of Biomedical Science, United
Kingdom
53. [Webpage] Isothermal amplificationGreat Basin2013.
Retrieved on: November 4, 2013. Available from:
http://www.gbscience.com/technology/iso-amp/
54. [Article] Buchan, B., Mackey, T., Daly, J., Alger, G.,
Denys, G., Peterson, L., Kehl, S., and Ledeboer, N. (2012)

12
Multicenter Clinical Evaluation of the Portrait Toxigenic C.
Difficile Assay for Detection of Toxigenic Clostridium
Difficile Strains in Clinical Stool Specimens Journal of
Clinical Microbiology. 50, 3932-3936,
55. [Article] Hicke, B., and et. al. (2012)
Automated Detection of Toxigenic Clostridium Difficile in
Clinical Samples: Isothermal tcdB Amplification Coupled to
Array-Based Detection Journal of Clinical Microbiology.
50, 2681-2687, http://dx.doi.org/10.1128/JCM.00621-12
56. BioCentury. (2012) Portrait Toxigenic Clostridium
Difficile Assay Diagnostic Data. BioCentury, Redwood City,
CA
57. [Article] Lin, M. Y., Hota, B., Khan, Y. M., Woeltje, K.
F., Borlawsky, T. B., Doherty, J. A., Stevenson, K. B.,
Weinstein, R. A., Trick, W. E., and CDC Prevention Epictr
Program. (2010) Quality of Traditional Surveillance for Public
Reporting of Nosocomial Bloodstream Infection Rates. Jama-
Journal of the American Medical Association. 304, 2035-
2041, http://dx.doi.org/10.1001/jama.2010.1637
58. [Article] Feltovich, F., and Fabrey, L. J. (2010) The
Current Practice of Infection Prevention as Demonstrated by
the Practice Analysis Survey of the Certification Board of
Infection Control and Epidemiology, Inc. Am. J. Infect.
Control. 38, 784-788,
http://dx.doi.org/10.1016/j.ajic.2010.05.020
59. Hospital-Acquired Conditions (HAC) in Acute Inpatient
Prospective Payment System (IPPS) Hospitals. (October 2012)
Centers for Medicare & Medicaid Services,
60. [Article] Lee, G. M., Kleinman, K., Soumerai, S. B., Tse,
A., Cole, D., Fridkin, S. K., Horan, T., Platt, R., Gay, C.,
Kassler, W., Goldmann, D. A., Jernigan, J., and Jha, A. K.
(2012) Effect of Nonpayment for Preventable Infections in
U.S. Hospitals. N. Engl. J. Med. 367, 1428-1437,
http://dx.doi.org/10.1056/NEJMsa1202419
61. [Article] Nelson, E. C., Rust, R. T., Zahorik, A., Rose, R.
L., Batalden, P., and Siemanski, B. A. (1992) Do Patient
Perceptions of Quality Relate to Hospital Financial
Performance? J. Health Care Mark. 12, 6-13
62. Gemme, E. M. (1997) Retaining Customers in a Managed
Care Market. Hospitals must Understand the Connection
between Patient Satisfaction, Loyalty, Retention, and Revenue.
UNITED STATES
63. Scott, R. (2007) The Direct Medical Costs of Healthcare-
Associated Infections in U.S. Hospitals and the Benefits of
Prevention. Centers for Disease Control and Prevention,
64. [Article] Umscheid, C. A., Mitchell, M. D., Doshi, J. A.,
Agarwal, R., Williams, K., and Brennan, P. J. (2011)
Estimating the Proportion of Healthcare-Associated Infections
that are Reasonably Preventable and the Related Mortality and
Costs. Infection Control and Hospital Epidemiology. 32, 101-
114, http://dx.doi.org/10.1086/657912
65. Giordano, L. A., Elliott, M. N., Goldstein, E., Lehrman,
W. G., and Spencer, P. A. (2010) Development,
Implementation, and Public Reporting of the HCAHPS Survey.
Sage Publications,
66. HCAHPS Fact Sheet. (August 2013) Centers for Medicare
& Medicaid Services (CMS), Baltimore, MD USA
67. Acute Care Hospital Inpatient Prospective Payment
System. (April 2013) Department of Health and Human
Services, Centers for Medicare & Medicaid Services,
68. [Article] Calfee, D. P. (2012) Crisis in Hospital-Acquired,
Healthcare-Associated Infections. Annual Review of Medicine,
Vol 63. 63, 359-371, http://dx.doi.org/10.1146/annurev-med-
081210-144458
69. [Article] Fairfield, C. (2000) Improving the Safety of
Health Care: The Leapfrog Initiative. Eff. Clin. Pract. 6, 313-
316
70. [Article] Rothberg, M. B., Morsi, E., Benjamin, E. M.,
Pekow, P. S., and Lindenauer, P. K. (2008) Choosing the Best
Hospital: The Limitations of Public Quality Reporting. Health
Aff. 27, 1680-1687
71. [Article] Day, M. S., Hutzler, L. H., Karia, R., Vangsness,
K., Setia, N., and Bosco, J. A. (2013) Hospital-‐Acquired
Conditions After Orthopedic Surgery do Not Affect Patient
Satisfaction Scores. Journal for Healthcare Quality.
72. [Article] Galvin, R., Delbanco, S., Milstein, A., and
Belden, G. (2005) Has the Leapfrog Group had an Impact on
the Health Care Market? Health Aff. 24, 228-233,
http://dx.doi.org/10.1377/hlthaff.24.1.228
73. [Article] Fisher, J., and Clayton, M. (2012) Who Gives a
Tweet: Assessing Patients’ Interest in the use of Social Media
for Health Care. Worldviews on Evidence-‐Based Nursing. 9,
100-108
74. [Article] Hawn, C. (2009) Take Two Aspirin and Tweet
Me in the Morning: How Twitter, Facebook, and Other Social
Media are Reshaping Health Care. Health Aff. 28, 361-368
75. Thielst, C. B. (2011) Social Media: Ubiquitous
Community and Patient Engagement. United States
76. [Article] Klevens, R. M., Edwards, J. R., Richards, C. L.,
Jr., Horan, T. C., Gaynes, R. P., Pollock, D. A., and Cardo, D.
M. (2007) Estimating Health Care-Associated Infections and
Deaths in US Hospitals, 2002. Public Health Rep. 122, 160-
166
77. [Article] Edwards, J. R., Peterson, K. D., Mu, Y.,
Banerjee, S., Allen-Bridson, K., Morrell, G., Dudeck, M. A.,
Pollock, D. A., and Horan, T. C. (2009) National Healthcare
Safety Network (NHSN) Report: Data Summary for 2006
through 2008, Issued December 2009. Am. J. Infect. Control.
37, 783-805,
http://dx.doi.org/http://dx.doi.org/10.1016/j.ajic.2009.10.001
78. [Article] EMORI, T., CULVER, D., HORAN, T.,
JARVIS, W., WHITE, J., OLSON, D., BANERJEE, S.,
EDWARDS, J., MARTONE, W., GAYNES, R., and
HUGHES, J. (1991) National Nosocomial Infections
Surveillance System (Nnis) - Description of Surveillance
Methods. Am. J. Infect. Control. 19, 19-35,
http://dx.doi.org/10.1016/0196-6553(91)90157-8
79. [Webpage] Tracking infections in long-term acute care
facilitiesCenters for Disease Control and PreventionMarch 15,
2013. Retrieved on: September 30, 2013. Available from:
http://www.cdc.gov/nhsn/LTACH/

13
80. [Webpage] National healthcare safety network
(NHSN)Healthy peopleMarch 28, 2013. Retrieved on:
September 28, 2013. Available from:
http://www.healthypeople.gov/2020/data/datasource.aspx?id=
206
81. [Article] Sievert, D. M., Ricks, P., Edwards, J. R.,
Schneider, A., Patel, J., Srinivasan, A., Kallen, A., Limbago,
B., Fridkin, S., Natl Healthcare Safety Network, and
Participating NHSN Facilities. (2013) Antimicrobial-Resistant
Pathogens Associated with Healthcare-Associated Infections:
Summary of Data Reported to the National Healthcare Safety
Network at the Centers for Disease Control and Prevention,
2009-2010. Infection Control and Hospital Epidemiology. 34,
1-14, http://dx.doi.org/10.1086/668770
82. CDC Vital Signs. (Retrieved on: December 9, 2013)
Centers for Disease Control and Prevention,
83. Operational Guidance for Acute Care Hospitals to Report
Central LineAssociated BloodstreamInfection (CLABSI) Data
to CDC’s NHSN for the Purpose of Fulfilling CMS’s
Hospital Inpatient Quality Reporting (IQR) Requirements.
(September 26, 2013) Centers for Disease Control and
Prevention,
84. [Article] McNair PD, FAU - Luft, H. S., Luft HS, FAU -
Bindman, A. B., and Bindman AB. Medicare's Policy Not to
Pay for Treating Hospital-Acquired Conditions: The Impact. -
Health Aff (Millwood).2009 Sep-Oct;28(5):1485-93.doi:
10.1377/hlthaff.28.5.1485.
85. [Webpage] Readmissions reduction programThe Centers
for Medicare & Medicaid Services. Last Updated: August 2,
2013, . Retrieved on: December 9, 2013. Available from:
http://www.cms.gov/Medicare/Medicare-Fee-for-Service-
Payment/AcuteInpatientPPS/Readmissions-Reduction-
Program.html
86. [Article] Stone, P. W., Glied, S. A., McNair, P. D.,
Matthes, N., Cohen, B., Landers, T. F., and Larson, E. L.
(2010) CMS Changes in Reimbursement for HAIs Setting A
Research Agenda. Med. Care. 48, 433-439,
http://dx.doi.org/10.1097/MLR.0b013e3181d5fb3f
87. Affordable Care Act Update: Implementing Medicare Cost
Savings. (Retrieved on: December 9, 2013) Centers for
Medicare & Medicaid Services,
88. [Article] Jenkins, S. G., Raskoshina, L., and Schuetz, A.
N. (2011) Comparison of Performance of the Novel
Chromogenic Spectra VRE Agar to that of Bile Esculin Azide
and Campylobacter Agars for Detection of Vancomycin-
Resistant Enterococci in Fecal Samples. J. Clin. Microbiol. 49,
3947-3949, http://dx.doi.org/10.1128/JCM.00180-11
89. [Webpage] Legionella - diagnostic testingCentre for
Disease Control and Prevention. Last Updated: February 5,
2013, 2013. Retrieved on: 12/10/2013. Available from:
http://www.cdc.gov/legionella/diagnostic-testing.html

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