Download A New Paradigm for the Management of Skin and Soft Tissue

CEPHEID
ON-DEMAND
REPORT
A Quarterly Publication by Cepheid
Volume 1, Issue 3
IN THIS ISSUE…
Cover Story:
A New Paradigm for the Management
of Skin and Soft Tissue Infections
(SSTI) in the Era of MRSA
Inside:
Highlights from ICAAC/IDSA
a Summary of Selected
Presentations with a Focus on
Healthcare-Associated Infections
Online:
www.cepheidondemand.com
A New Paradigm for the Management of Skin and
Soft Tissue Infections (SSTI) in the Era of MRSA
How will rapid MRSA/SA test results affect treatment algorithms?
Ellen Jo Baron, Ph.D.
Director, Clinical
Microbiology Lab, SHC
Professor, Dept. of
Pathology,
Stanford Med School
Recently, Cepheid convened a panel of
experts in emergency medicine, surgery,
infectious disease, and epidemiology to
discuss how treatment algorithms might
change in response to having rapid test
results available. Doctors David Alland,
MD, Samir Awad, MD, Stanley Deresinski,
MD, FACP, and David Talan, MD, FACEP,
FIDSA expressed their perspectives on
being able to know whether a patient’s
infection was caused by MSSA or MRSA
while the patient is still in the emergency room.
Emergency department (ED) physicians thrive on action. Their practice
is exemplified by constant multiple
demands for their attention and their
decisions, and they like it that way. So
defining on-demand molecular diagnostics.
when patients show up with infected
lesions that the patients describe as
“spider bites,” if the patients are not
systemically ill and the lesions are not
considered severe, emergency department physicians instinctively want to
take action. “Drain and refrain” (from
See RAPID TESTING on next page
December – February 2008 – 2009
Rapid Testing, a New Paradigm Affecting
ON-DEMAND
CEPHEID
Executive Editor
David Persing, M.D., Ph.D.
Managing Editor
Stripe Demarest
Lead Author
Ellen Jo Baron, Ph.D.
Contributing Author
Fred Tenover, Ph.D
Production Manager
Gregory Birgfeld
Newsletter Design
Bijal Patel
Print/Web Design &
Production
Tori Muir
prescribing antimicrobials) has been at
least one publicized approach to such
situations.1 And in fact, in most cases
(90.5% in one study), the patient without other risk factors does well with
drainage alone.2
But wouldn’t it be helpful to know the
identity of the offending organism?
If infected patients knew that their
infection was caused by the infamous
methicillin-resistant Staphylococcus
aureus (MRSA), for example, they might
take precautions to avoid reinfection,
or they might modify their personal
hygiene practices to prevent spreading the infection to family members,
friends, or close contacts.
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Contents are ©2008 by Cepheid unless
otherwise indicated. Rights reserved on
all guest columns. The contents of this
publication may not be reproduced in
any form without written permission of
the editor. The mention of trade names,
commercial products, or organizations
does not imply endorsement by Cepheid.
physician who saw that patient is no
longer responsible for the care of that
patient. So either that physician must
attempt to contact the patient on his
day off, or an ED nurse, with many
other more pressing tasks, must spend
precious time trying to locate and
speak with the patient. If the lesion has
healed properly, the patient may not
appreciate the call.
What if the infection is severe enough
that the patient is admitted to the hospital? Of course cultures will be obtained.
If the cultures show the patient is
infected with MRSA, then the patient is
placed on contact precautions or moved
to a private room—but this information
isn’t available for at least two days.
53% of North American respondents
would treat a young athlete’s wound
infection with an anti-MRSA antibiotic after
incision and drainage— NEJM poll
MRSA patients have a dramatically
higher risk of reinfection. One study
showed that 29% of MRSA-colonized
or infected patients became reinfected,
often at a different site and sometimes
with very serious, even fatal, infections,
within 18 months of their initial infection.3 Colonized patients and healthcare
workers can also pass the organism to family members or other close
contacts.4-5
A recent New England Journal of
Medicine poll found that even without
culture results, 53% of North American respondents would treat a young
athlete with a wound infection with an
anti-MRSA antibiotic after incision and
drainage.6
A problem with those culture results
remains. The results are available
two days after the ED visit, and the
2
The patient and his or her family will
certainly wonder why they, the nurses,
and the doctors could go in and out of
the room freely for two days, and suddenly now they need to put on gowns
and gloves. Suddenly there are fewer
visits for patient care, and the sense of
worry and concern grows and grows.7
Understandably, everyone involved is
just a bit grumpier and the previously
non-colonized roommate possibly even
unhappier.
For nearly three decades, the Star Trek
Tricorder used by Dr. McCoy to get an
instantaneous diagnosis of a patient’s
malady with a single, non-invasive
pass over the patient’s body was the
best of medical science fiction. With
FDA clearance of Cepheid’s moderatecomplexity Xpert™ MRSA/SA Skin and
Soft Tissue Infection (SSTI) on-demand
Cepheid On-Demand Report
Patient Treatment Algorithms in the Era of MRSA
molecular test, we are one step closer
to real-time diagnosis —although
we still have to use a swab! A new
diagnostic paradigm is emerging, and
ED doctors will have to rethink their
practices. Starting now, the presence
of either Staphylococcus aureus (i.e.,
MSSA) or MRSA in a swab from a wound
lesion can be determined within one
hour of sample collection—right in the
ED, if desired.
This test offers an exciting new option
for diagnosing infections rapidly and
accurately. If surgeons knew that a
patient’s wound was infected with
MSSA and not MRSA, they could be
confident that their cephalosporin or
extended-spectrum penicillin therapy
would be effective. Alternatively, they
could avoid using vancomycin, which
is not as effective as beta-lactam
drugs for MSSA. If they knew that the
wound carried MRSA, they could opt
for vancomycin or one of several newer
antimicrobial agents that are highly
effective against MRSA. Recent studies
have shown that appropriate treatment
improves patient outcomes, which
is the major goal of all healthcare
institutions.8
The most widely used algorithm for
SSTIs today is the one developed by
Centers for Disease Control and Prevention (CDC), the American Medical
Association, and the Infectious Diseases
Society of America (Figure 1). Empiric
therapy options are listed in the algorithm for presumptive treatment of
MRSA. Figure 2 provides an often-used
algorithm for pediatric patients presents more details on the lesion size
and location.9 Using these references
as guidelines, our panel had a freeflowing discussion about how the use of
rapid results for MSSA and MRSA might
change their practices.
See RAPID TESTING on next page
In one institution, having MRSA/MSSA
information within one hour would prevent
the overutilization of anti-MRSA therapy in
approximately 30% of patients
Outpatient† management of skin and soft tissue infections in the era
of community-associated MRSA‡
Patient presents with signs/
symptoms of skin infection:
• Redness
• Swelling
• Warmth
• Pain/tenderness
• Complaint of “spider bite”
Is the lesion purulent (i.e., are any
of the following signs present)?
YES
• Fluctuance—palpable fluid-filled
cavity, movable, compressible
• Yellow or white center
• Central point or “head”
• Draining pus
• Possible to aspirate pus with
needle and syringe
Possible cellulitis without abscess:
NO
• Provide antimicrobial therapy
with coverage for Streptococcus
spp. and/or other suspected
pathogens
• Maintain close follow-up
• Consider adding coverage for
MRSA (if not provided initially),
if patient does not respond
YES
† For severe infections requiring
inpatient management, consider
consulting an infectious disease
specialist.
‡ Visit www.cdc.gov/mrsa
.for more information
1. Drain the lesion
2. Send wound drainage for culture
and susceptibility testing
3. Advise patient on wound care
and hygiene
4. Discuss follow-up plan with
patient
Abbreviations:
I&D—incision and drainage
MRSA—methicillin-resistant S. aureus
SSTI—skin and soft tissue infection
If systemic symptoms, severe local symptoms, immunosuppression, or failure to respond to I&D,
consider antimicrobial therapy with coverage for MRSA in addition to I&D (see below for options).
Options for empiric outpatient antimicrobial treatment of
SSTIs when MRSA is a consideration*
Drug Name
Considerations
Precautions**
Clindamycin
•FDA-approved to treat serious infections
due to S. aureus
•D-zone test should be performed to
identify inducible clindamycin resistance in
erythromycin-resistant isolates
•Clostridium difficile-associated disease, while uncommon,
may occur more frequently in association with clindamycin
compared to other agents.
Tetracyclines
•Doxycycline
•Minocycline
•Doxycycline is FDA-approved to treat S.
aureus skin infections.
•Not recommended during pregnancy.
•Not recommended for children under the age of 8.
•Activity against group A streptococcus, a common cause of
cellulitis, unknown.
TrimethoprimSulfamethoxazole
•Not FDA-approved to treat any staphylo‑
coccal infection
•May not provide coverage for group A streptococcus, a com‑
mon cause of cellulitis
•Not recommended for women in the third trimester of pregnancy.
•Not recommended for infants less than 2 months.
Rifampin
•Use only in combination with other agents.
•Drug-drug interactions are common.
Linezolid
•Consultation with an infectious disease
specialist is suggested.
•FDA-approved to treat complicated skin in‑
fections, including those caused by MRSA.
•Has been associated with myelosuppression, neuropathy and
lactic acidosis during prolonged therapy.
•MRSA is resistant to all currently available beta-lactam agents (penicillins and cephalosporins)
•Fluoroquinolones (e.g., ciprofloxacin, levofloxacin) and macrolides (erythromycin, clarithromycin, azithromycine) are not optimal
for treatment of MRSA SSTIs because resistance is common or may develop rapidly.
* Data from controlled clinical trials are needed to establish the comparative efficacy of these agents in treating MRSA SSTIs.
Patients with signs and symptoms of severe illness should be treated as inpatients.
** Consult product labeling for a complete list of potential adverse effects associated with each agent.
Role of decolonization
Regimens intended to eliminate MRSA colonization should not be used in patients with active infections. Decolonization regimens
may have a role in preventing recurrent infections, but more data are needed to establish their efficacy and to identify optimal
regimens for use in community settings. After treating active infections and reinforcing hygiene and appropriate wound care,
consider consultation with an infectious disease specialist regarding use of decolonization when there are recurrent infections in
an individual patient or members of a household.
Figure 1. Treatment algorithm flowchart based on CDC guidelines.
3
December – February 2008 – 2009
Rapid Testing, a New Paradigm Affecting Patient Treatment
Common Algorithm for Treatment of
Skin/Soft Tissue Infections in Children
OUTPATIENT
INPATIENT
Clindamycin 20–30
mg/kg/day PO
Clindamycin 30–40
mg/kg/day IV; if
life-threatening, add Vancomycin 40 mg/ kg/day IV
Penicillin
Penicillin + clindamycin in
severe soft-tissue
infections
Sensitive (MSSA)
Cephalexin or dicloxicillin
50–75 mg/kg/day
Nafcillin 150–200
mg/kg/day; D/C vancomycin and/or clindamycin
Resistant
Trimethoprimsulfamethoxazole or
linezolid, if susceptible
Vancomycin 40 mg/kg/day
IV; potential role for linezolid,
other agents
Susceptible
Continue clindamycin
Continue clindamycin and/or
vancomycin, depending on
site & severity of infection
Trimethoprimsulfamethoxazole or
linezolid, if susceptible
Vancomycin
40 mg/kg/day IV
Culture & susceptibility
(very important)
Empiric therapy
Positive culture
Staph or Strep?
Strep. pyogenes
(group A streptococcus)
Staph. aureus
Methicillin/oxacillin
susceptibility
Resistant (MRSA)
Clindamycin susceptibility
Susceptible
Erythromycin susceptibility
Resistant
(inducible resistance to
clindamycin is possible)
Negative
D Test
(measures inducible
resistance to clindamycin; this
may lead to clindamycin
treatment failures)
Positive
Please note that these are general
recommendations; therapy for children
with skin/soft tissue infections must be
individualized.
Figure 2. A standard pediatric treatment algorithm.
David Talan, MD,
FACEP, FIDSA
Professor, Medicine/
Emergency Medicine
Chair, Dept. of Emer‑
gency Medicine, Olive
View-UCLA Medical
Center
Dr. David Talan started the discussion
with his assertion that there are three
types of patients. First, there are those
who are critically ill, further characterized by Dr. Stanley Deresinski as patients
with immediate life- or limb-threatening
conditions, for whom physicians must
start antimicrobial therapy immediately.
There is no time to wait for the results
of a rapid microbiology diagnostic test,
no matter how quickly the results are
available. Empiric treatment must be
immediate to decrease mortality in this
very ill group of patients.
The second group of patients is one
for which an algorithm that includes a
rapid diagnostic arm makes sense. These
patients present with an SSTI but they are
not systemically ill and the infection is not
necrotizing or a bite wound. Dr. Deresinski agrees that this is the type of patient
for whom a rapid MRSA result would
impact therapy. A rapid result showing
the presence of MSSA and not MRSA, for
example, would indicate that treatment
with vancomycin or a newer, more expensive anti-MRSA agent, such as linezolid,
daptomycin, or tigecycline is unnecessary. Knowing up front that nafcillin or
cephalexin will be effective both simplifies
and lowers the cost of treatment.
Dr. Talan and Dr. Samir Awad noted that
a third type of patient presents with
an SSTI that is chronic (not necrotizing
Stanley Deresinski,
MD, FACP
Clinical Professor, Med.
in Infectious Diseases,
Stanford Medical School
Associate Chief, Infec‑
tious Diseases at Santa
Clara Valley Medical
Center
Senior Editor,Infectious
Disease Alert Newsletter
4
Samir Awad, MD
Associate Professor of
Surgery; Chief, Section
of Critical Care for the
Michael E. DeBakey
Dept. of Surgery
Associate Chief of
Surgery Medical Direc‑
tor, SICU MED VAMC
Houston, TX
fasciitis) and likely to be polymicrobial.
Such patients require debridement of
the wound and long-term antimicrobial
therapy. For these patients, a rapid result
showing the presence of MSSA or MRSA
will help the physician to target the antistaphylococcal therapy.
In Dr. Awad’s institution, having this information within one hour would prevent
the overutilization of anti-MRSA therapy
in approximately 30% of the patients. Dr.
David Alland concurred with this assessment. He pointed out that anti-MSSA
therapy is not only less expensive, but is
given for shorter duration. According to
Dr. Alland, the negative predictive value of
a rapid test has to be extremely good to
reap these benefits.
Cepheid On-Demand Report
Algorithms in the Era of MRSA
David Alland, MD
Director, Center for
Emerging & Re-Emerging
Pathogens
Professor, Department
of Medicine, Infectious
Diseases at the Univ. of
Medicine and Dentistry,
Newark, NJ
The panel also discussed how the use
of a rapid test would alter the management of hospitalized patients. One
obvious arena for immediate utilization
of the results is for the patient undergoing surgery. Vancomycin as a preemptive
prophylactic agent could be avoided,
with two positive consequences:
• Lessening the risk of driving up
the rate of vancomycin-resistant
Enterococcus species (in that patient
and in the hospital environment)
• Allowing the use of a potentially more
effective prophylactic agent
Another positive outcome would be
institution of appropriate infection
control measures before the patient was
placed in a room. Until all hospitals in
the United States have migrated to allprivate rooms, the problem of patient
placement and proper isolation will
remain a key infection control issue.10
A less-recognized benefit of knowing
that MRSA is the cause of an SSTI is that
an antimicrobial agent known to have
anti-toxin activity, such as linezolid or
clindamycin could be used to potentially
reduce the severity of the infection.11
Even before the organism is destroyed,
its toxin-producing abilities are inhibited by these ribosomal-active agents.
MRSA toxins, including Panton-Valentine leukocidin, alpha toxin, and toxic
shock toxin, contribute to virulence of
the organisms that carry them.
The findings of the Institute for Healthcare Improvement, new guidelines from
CDC and professional societies, and
the plethora of states enacting legislation mandating MRSA surveillance and
subsequent action have magnified the
need for cost-effective strategies in
healthcare settings. Cost-effectiveness
studies such as those of Forrest and
colleagues can be cited to mitigate the
perceived price barriers to enacting
the new molecular technology-based
tests.12 New antimicrobial agents that
are due to be released in the coming
year, such as ceftibiprole, dalbavancin,
televancin, and oritavancin, are highly
effective but are likely to be expensive,
emphasizing the need for such costbenefit studies.
on the need for vigilance with regard
to personal hygiene and the possibility
of chronic problems.
• Trimethoprim-sulfamethoxazole was
mentioned as a good choice for initial
therapy, but anti-MRSA therapy in
general should be used, with different
agents based on factors as indicated in
the table shown on page 6.
• Children in particular dislike the bad
taste of clindamycin, so although it is
an excellent drug for MRSA because of
its anti-toxic properties, it is not the
best choice for pediatric patients.
New requirements for MRSA surveillance
and subsequent action have magnified
the need for cost-effective strategies in
healthcare settings
Finally, the experts noted that they
could simplify a protocol for outpatient
treatment of SSTI if they knew up front
that MRSA was the etiological agent.
The following points were discussed:
• If diabetic foot ulcers were encountered,
they would require debridement and
scraping (no swabs) for complete
culture. Good studies have shown that
such infections involve only 14% S.
aureus and 4% MRSA.
• Similarly, abscesses rarely involve
streptococci, so testing for presence of
S. aureus or MRSA alone is appropriate.
• Even those patients presenting with
furuncles which previously would
have been incised and drained and not
treated should be seen in a new light.
Now, knowing the furuncle contained
MRSA, the patient could be educated
5
• Patients without pus (those with
lumps, bumps, or cellulitis) are difficult
to culture or test by PCR, as there is no
easily obtained sample to test. Cellulitis
is not likely to yield MRSA at any rate,
as most cellulitis is due to streptococci.
The current IDSA Guidelines state
“Therapy for the typical case of
erysipelas or cellulitis should include an
antibiotic active against streptococci.
Many clinicians choose an agent that
is also effective against S. aureus,
although this organism rarely causes
cellulitis unless associated with an
underlying abscess or penetrating
trauma. A large percentage of patients
can receive oral medications from
the start. Suitable agents include
dicloxacillin, cephalexin, clindamycin,
or erythromycin, unless streptococci or
staphylococci resistant to these agents
are common in the community (A-I).”
December – February 2008 – 2009
• Overall, the algorithms were
appropriate except that instead of
suspicion of MRSA triggering the use
of anti-MRSA therapy, the actual
presence of MRSA would do so. Given
the excellent predictive value of
negative results (as seen in beta trials),
presence of S. aureus would suggest
use of cephalexin, nafcillin, or other
anti-S. aureus antibiotics.
In summary, our panel of experts
expressed great enthusiasm for the
ability to quickly identify those patients
with skin and soft tissue infections
who harbored either S. aureus or MRSA.
These distinguished clinicians anticipate a new era in which more rapid
information will lead to better initial
treatment choices.
Anti-MRSA
Anti-MSSA
Choices in Antimicrobial Treatment (Based on CDC Algorithm)
Antimicrobial
Agent
Drug Class
Comments
Cephalexin
Cephalosporin - oral
Also has anti-streptococcal activity; should be considered when cellulitis is present
Dicloxacillin
Penicillin - oral
Nafcillin
Penicillin – IM orIV
Levofloxacin
Fluoroquinolone –
oral or IV
Not first-line drug; not recommended for children
TrimethoprimSulfamethoxazole
Folate pathway in‑
hibitors - oral or IV
Oral, usually active against MRSA but not FDA-cleared for use against MRSA; choice for
SSTI in otherwise healthy patients, not for pregnant women (i.e., >12 weeks) or babies; some
studies suggest less efficacy than clindamycin
Clindamycin
Lincosamide - oral,
IM, or IV
Has anti-toxin activity; requires special laboratory test to detect inducible resistance; bad
taste disliked by children
Linezolid
Oxazolidinone oral or IV
Has anti-toxin activity; more expensive than other agents; both oral and IV formulas available
Doxycycline
Tetracycline - oral
or IV
May have side-effects; not for use in children <5 years of age
Minocycline
Tetracycline - oral
or IV
Under-appreciated agent; similar to tetracycline
Vancomycin
Glycopeptide oral or IV
May be less effective than other agents, particularly for bloodstream infections; levels should
be monitored; overutilization can contribute to development of VRE; CDC recommends ef‑
forts to reduce use of vancomycin; recent studies suggest mean MRSA vancomycin MICs
are increasing
Daptomycin
Lipopeptide - IV
Effective against MRSA; not active in respiratory tract; more expensive than other agents
Oritavancin
Lipoglycopeptide - IV
New agent currently in clinical trials; appears to have excellent anti-MRSA activity
Ceftobiprole
Cephalosporin – IV
New extended spectrum cephalosporin that has anti-MRSA activity
References
1. Chambers, Moellering. Clinical Decisions: Management of Skin
and Soft-Tissue Infection. New England Journal of Medicine. 2008;
359(10):1063–1065.
2. Rajendran PM, Young D, Maurer T, et al. Randomized, double-blind,
placebo-controlled trial of cephalexin for treatment of uncomplicated
skin abscesses in a population at risk for community-acquired meth‑
icillin-resistant Staphylococcus aureus infection. Antimicrob Agents
Chemotherapy. 2007; 51:4044–8.
3. Huang SS, Platt R. Risk of Methicillin-Resistant Staphylococcus aureus
Infection after Previous Infection or Colonization. Clinical Infectious
Diseases. 2003; 36:281–5
4. Bonness S, Szekat C, Novak N, Bierbaum G. Pulsed-Field Gel Elec‑
trophoresis of Staphylococcus aureus Isolates from Atopic Patients
Revealing Presence of Similar Strains in Isolates from Children and
Their Parents. Journal of Clinical Microbiology. 2008; 46:456–461.
5. Lu P-L, Tsai J-C, Chiu Y-W, Chang F-Y, Chen Y-W, Hsiao C-F, Siu LK.
Methicillin-resistant Staphylococcus aureus carriage, infection and
transmission in dialysis patients, healthcare workers and their family
members Nephrol Dial Transplant. 2008; 23:1659–1665.
6. Hammond SP, Baden LR: Management of Skin and Soft-Tissue
Infection — Polling Results. New England Journal of Medicine. 2008;
359:e20.
7. Kirkland KB, Weinstein JM. Adverse effects of contact isolation. Lancet. 1999; 354(9185):1177–1178.
8. Ruhe JJ, Smith N, Bradsher RW, Menon A. Community-Onset
Methicillin-Resistant Staphylococcus aureus Skin and Soft-Tissue
Infections: Impact of Antimicrobial Therapy on Outcome. Clinical Infectious Diseases. 2007; 44:777–784.
9. Lee, MC, Rios AM, Aten MF, Mejias A, Cavuoti D, McCracken GH Jr,
Hardy RD. Management and outcome of children with skin and soft
tissue abscesses caused by community-acquired methicillin-resistant
Staphylococcus aureus. Pediatric Infectious Disease Journal. 2004;
23(2):123–7.
10.Huang SS, Datta R, Platt, R. Risk of Acquiring Antibiotic-Resistant
Bacteria From Prior Room Occupants. Archives of Internal Medicine.
2006; 166:1945–1951.
11.Stevens DL, Ma Y, Salmi DB, McIndoo E, Wallace RJ, Bryant AE.
Impact of antibiotics on expression of virulence-associated exotoxin
genes in methicillin-sensitive and methicillin-resistant Staphylococcus
aureus. Journal of Infectious Diseases. 2007; 195(2):202–11.
12.Forrest GN, Mehta S, Weekes E, Lincalis DP, Johnson JK, Venezia RA.
Impact of rapid in situ hybridization testing on coagulase-negative
staphylococci positive blood cultures. Journal of Antimicrobial Chemotherapy. 2006; 58:154–158.
6
Cepheid On-Demand Report
Highlights from ICAAC/IDSA
Focusing on Healthcare-Associated Infections
Ellen Jo Baron, Ph.D.
The American Society for Microbiology’s
Interscience Congress on Antimicrobial Agents and Chemotherapy and the
Infectious Diseases Society of America’s
annual meeting were combined and held
in Washington, DC this October. More
than 14,000 attendees acquired the
latest information on new diagnostics,
new therapies, microbial pathogenesis, and more. Here is a summary of a
few abstracts whose findings focus on
healthcare-associated infections.
The majority of recent studies are
proving that infection control based
on surveillance is cost-effective and
beneficial, even when surveillance is
restricted to limited inpatient units.
C2-106. Detection of Oxacillin/Methicillin
Resistant and Susceptible Staphylococcus
aureus by Culture and RT-PCR in Patients
Scheduled for Orthopedic Surgery
Halstead DC, Kirspel CE, Mckean KA, Meyer KS,
Boland BJ
Nasal swabs from 275 patients scheduled
for orthopedic surgery at Baptist Hospital
(Jacksonville, FL) were tested by CHROMagar
and BD GeneOhm MRSA in Phase I and another
137 patients by the Xpert™ MRSA test (using a
frozen swab obtained at the same time) during
Phase II. Rates of positivity more than doubled
with the Xpert MRSA test. Both molecular
systems usually agreed. The authors concluded
that molecular methods were more sensitive
than culture and that the GeneXpert® System
gave more rapid results with less hands-on
time than did the SmartCycler® System.
C2-1066. Real-Time PCR (RT-PCR) for
Methicillin-Resistant Staphylococcus aureus
(MRSA) Detection: Implications in a Neonatal
Intensive Care (NIC) Setting
Song X, Campos J, Short B, Singh N
In 2005, National Childrens’ Hospital in Washington DC tested for MRSA at admission and
weekly thereafter using cultures. After they
switched to rt-PCR (GeneXpert, Cepheid) in
2007 the incidence of MRSA increased from
6.9% to 10.8%. This enhanced detection
led to a statistically significant reduction
in hospital acquisitions of colonizing MRSA.
During the time of culture surveillance 30.4%
of MRSA-colonized patients developed an
MRSA infection, whereas during PCR-based
testing, only 9.1% of MRSA-positive patients
developed MRSA infection. They concluded
that PCR-based testing enhanced infection
control measures for MRSA.
K-3367. A Pilot Study of Active Surveillance
for MRSA by PCR on Admission to ICUs at a
Tertiary Care Center
Espinoza C, Fisher V, Jean W, Gaines B, Davis K,
Wanger A, Schaeffer M, Ostrosky-Zeichner L
Mem. Hermann TX Medical Ctr., Houston,
performed the BD GeneOhm assay once daily
on all patients admitted to the adult ICU.
Patients were initially all placed on modified
contact precautions and positive patients
were placed on full contact precautions and
flagged for future infection control actions.
During the 3-month intervention period,
11.6% of patients tested were MRSA positive.
There was a statistically significant decrease
in healthcare-associated ventilator-associated pneumonias and bloodstream infections
overall in the ICU, from 59 to 38 per 1000 admissions. MRSA infections dropped from 9%
to 5%. Importantly, the authors extrapolated
costs to one year. Even considering the cost
of testing and isolation, the cost avoidance
associated with preventing healthcare-associated infections by PCR screening and subsequent isolation was estimated at $567,000.
What’s good and what’s disappointing
about the various surveillance methods?
D-1137. Comparison of Direct Plating and
Broth Enhanced Culture for Recovery of
MRSA from PCR Positive Nasal Swabs
Vonrentzell JE, Schreckenberger PC
To resolve discrepancies between positive GeneXpert (Cepheid) MRSA results and negative
culture results, Loyola scientists evaluated enhanced culture methods for recovery of MRSA.
During Phase I, the second swab from
patients whose first swab yielded a positive
or inconclusive PCR was plated directly onto
blood agar, two types of MRSA selective
CHROMagars and then incubated in 1 mL
of 6.5% NaCl in trypticase-soy broth (TSB)
overnight. Broths from negative plate cultures
7
were plated to the same 3 agars. In Phase II,
the second swab was vortexed in sterile saline,
and inoculated onto the 3 agars and into 6.5%
and 3.25%NaCl TSBs. Broths were subcultured
if direct plating did not yield MRSA.
In Phase I, direct plating recovered 68% of
those with positive results in the Xpert MRSA
test. Seven more MRSA were recovered from
TSB subcultures (total 76% recovery). However,
13 of 21 MRSA culture negative samples grew
MSSA. In Phase II, cultures overall yielded 87%
on blood agar and 92-93% on CHROMagars. Of
20 MRSA-negative cultures , 13 grew MSSA. The
MSSA isolates were further characterized; 2/3
were found to have a deletion in the mecA region. The isolation of MRSA from PCR-positive
patients was increased 10% by vortexing swabs
in saline before plating and 7% by enriching
overnight in TSB. These results further support
the superior sensitivity of molecular methods
for detection of MRSA colonized patients.
D-1136. Surveillance Swabs for Detection of
Methicillin-Resistant Staphylococcus aureus
(MRSA): Diagnostic Yield of Different Anatomic Sites and Comparison of Provider and
Patient-Collected Samples
Lautenbach E, Fishman N, Nachamkin I, Hu B,
Tolomeo P, Prasad P, Bilker W, Zaoutis T
Using cultures, workers at the Univ. of
Pennsylvania (Philadelphia) compared swabs
from different sites collected by healthcare
workers and by the patients themselves. Axillae,
nares, throat, perineum, and groin swabs were
evaluated. Patient-collected swabs compared
favorably with professionally collected samples.
The best agreement between patient- and
provider-collected samples was 95% for the
groin. To achieve >90% detection of colonized
persons, >1 site had to be sampled. In this population, the best single sites were nares (84%
sensitive) and throat (65% sensitive). Groin and
perineum cultures were more likely to be positive in community-onset patients (81%) than
hospital-onset patients (41%). Nares, throat,
and groin together achieved 100% sensitivity
and either nares and throat or nares and groin
reached 91% sensitivity for recovery of MRSA.
K-3355. A Targeted Approach to MRSA Colonization Screening Using a PCR Assay and
Multi-Site Sampling Strategy
Metzger BS, Leung SS, Currie BP
Colleagues at Montefiore Medical Center
in the Bronx increased the sensitivity of
December – February 2008 – 2009
surveillance cultures almost 24% by collecting
swabs from axilla, nares, and groin vs. nares
alone. 268 patients, of whom 21.3% were positive from at least one site: 17.2% nares, 10.1%
axilla, and 13.4% groin, were evaluated. Targeting screening to those patients who had either
long-term care residence, a previous MRSA
isolate, or antibacterial use within the last 6
months, yielded a sensitivity of 80.7% and the
need to test 43.7% of admissions. By adding
the risk factor of hospitalization within the
last 6 months, sensitivity increased to 91.2%
with the need to screen 57.8% of admissions.
They concluded that a targeted approach to
surveillance and a two-swab (nares and skin)
sample could result in near-complete capture
of MRSA-colonized patients.
Use of PCR as a point-of-care test: at
this time, there is only one moderate
complexity PCR assay FDA-cleared for
use in the United States.
Admissions wards of two hospitals in Birmingham, UK. Double swabs were collected from
patients in the wards and one swab was used
for near-patient testing, the other was sent
to the central laboratory. Valid paired results
were available for 735 swabs, 62 of which were
MRSA positive. There was 97.1% agreement.
Sampling errors were thought to account
for all discrepancies. The results of tests
performed at the wards were available in ≤ 2
hours for 97.7% of the swabs collected. The
authors said that the use of the GeneXpert
System at the patient point of care dramatically reduced the time to result compared with
testing in the laboratory.
Late Breaker: First look at the new Xpert
MRSA/SA test for SSTI and blood culture broths.
D-1139. Potential Use of the Cepheid Xpert™
MRSA Test for Near-Patient Testing
Brenwald NP, Baker N, Oppenheim B
D-2250a. Automated PCR to Detect Methicillin-Resistant (MR) or -Susceptible (MS)
Staphylococcus aureus (SA) in Blood Cultures
(BC) and Wound Swabs (WS)
Musher DM, Goebel M, Matloobi M, Stager C,
Parta M
Computer-interfaced Cepheid GeneXpert®
Systems were installed in the Critical Care and
132 blood cultures yielding gram-positive cocci
in clusters were tested using the Xpert MRSA/SA
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test. All 25 MRSA and 7 MSSA were correctly identified by the Xpert test in 50 minutes. One blood
culture (negative for S. aureus) was identified as
MRSA by the Xpert test.
The sensitivities of the Xpert test for blood
cultures were 100% for MRSA and MSSA and
99% for no S. aureus. Specificities were 99%
for MRSA and 100% for MSSA. Sensitivity of
the Xpert test for wounds culture-positive for
MRSA was 99%. Sensitivities for wounds yielding MSSA and no S. aureus on culture were 91%
and 79%; and specificities were all >91%. Of 80
MRSA cultured from 235 wound swabs, the Xpert
test correctly identified 79. The Xpert MRSA/SA
test correctly identified 30 of 33 MSSA isolates
from wounds; 2 were incorrectly called MRSA,
and one was not detected.
From 122 wound cultures where no S. aureus
were isolated, the Xpert test detected MRSA
in 12 samples and MSSA in 14 samples. Because
resolving tests were not performed, the true
nature of the discrepant results is not known
yet. Dr. Musher suggested that previously
treated patients may account for some of the
inconsistencies.