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Objetivo de BD BD HAI: Tus socios en la prevención y el control de
la infección hospitalaria
www.bd.com/hais
ÍNDICE
1. MRSA: La amenaza oculta 2. MRSA: Situación actual 3. Control de
MRSA:Vigilancia
Activa 4. Vigilancia de MRSA en UCI 5. El impacto de utilizar
métodos
moleculares 6. BD GO. Rendimiento de la
prueba y publicaciones 7. Control de MRSA: Innovación:
RT-PCR + Tradición: cultivo
1. MRSA: La amenaza oculta
• Los pacientes infectados y colonizados constituyen un reservorio
por igual para la transmisión nosocomial del MRSA.
• Más del 70% del reservorio son pacientes colonizados, solo
detectados con sistemas de vigilancia activa.
• El 30-50% de los pacientes hospitalizados que sean portadores de
MRSA pueden desarrollar una infección por MRSA.
• Las infecciones por MRSA están asociadas a una alta
mortalidad.
Karchmer IDSA 2002, APIC 2005 Selgado SHEA 2003 Boyce et al., SHEA
1998 Perencevich APIC 2005
• La colonización por MRSA es asintomática.
• Los reservorios son normalmente la piel y las fosas
nasales.
• La transmisión se produce generalmente de un paciente colonizado
a otros, y a través de las manos del trabajador sanitario.
• Se transmite fácilmente y sin darnos cuenta. Colonizados
Pacientes asintomáticos
Boyce et al., SHEA 1998, Abstract S74. Zachary et al., ICHE (2001)
22:560-564. Boyce et al., ICHE (1997) 18:622.
Infecciones clínicas
MRSA: La amenaza oculta
• Se estima que aprox. 50.000 pacientes al año mueren por HAIs en
Europa. Esto representa más de 150 por día. (EC Health and Consumer
Directorate General)
• Una infección por MRSA prolonga la estancia en el hospital en una
media de entre 4 y 14 días y el coste del tratamiento asociado
oscila entre €10.000 y €36.000 por paciente. (Kim et al, 2001;
Stone et al, 2002)
• La colonización por MRSA después de la admisión del paciente
aumenta por diez el riesgo de sufrir una infección por MRSA durante
su estancia en el hospital. (Davis et al. 2004)
• Se producen aproximadamente 3 millones de HAIS al año en Europa,
afectando a 1 de cada 10 pacientes. (Cosgrove et al, 2003)
2. MRSA: situación actual
MRSA: proporción por países
MRSA en España
Los aislados de MRSA suponen un 48 % del total de S. aureus
causantes de infección nosocomial (EPINE, año 2007)
5
14
s
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
2003 2004 2005 2006 2007
Año
• Medidas higiénicas y de contención: lavado de manos, ventilación,
limpieza, aislamiento, barreras de precaución.
• Aislamiento de los pacientes colonizados o infectados por
MRSA.
• Vigilancia de MRSA.
Control de MRSA
Vigilancia activa en la prevención y control de Staphylococcus
aureus resistente a la meticilina (MRSA)
• Screening para la identificación de pacientes portadores:
• Cultivo • Mannitol Salt Agar + 2 % Oxacilina. • Medios
cromogénicos.
• Métodos moleculares • PCR en tiempo real a partir de
muestra
directa.
VIGILANCIA ACTIVA EN LA PREVENCIÓN Y CONTROL DE STAPHYLOCOCCUS
AUREUS
RESISTENTE A LA METICILINA (MRSA) La “vigilancia activa” es una de
las mejores formas documentadas para prevenir la transmisión de
MRSA
en hospitales. Este procedimiento implica un régimen de admisión en
el que se incluya una prueba de
pacientes para detectar la presencia de MRSA1. La vigilancia activa
también se puede llevar a cabo
periódicamente en ciertas áreas de riesgo, como la UCI.
La rápida identificación de MRSA en pacientes es primordial a la
hora de iniciar las intervenciones
adecuadas para prevenir infecciones asociadas a MRSA. Los
individuos infectados o colonizados pueden
ser aislados, tomando las precauciones de contagio necesarias,
descolonizados y tratados casi
inmediatamente para minimizar la oportunidad de una mayor
transmisión de MRSA e infección adicional de
pacientes.
RESUMEN DE VIGILANCIA ACTIVA
- Una vez que el test haya dado positivo, los pacientes deben ser
aislados, descolonizados y /o
tratados, estableciendo un estricto control sobre las debidas
precauciones a tomar y los protocolos
de higiene en manos.
- Las pruebas utilizadas en la vigilancia activa junto con otros
métodos de prevención de infecciones
vienen establecidos por las directrices facilitadas por los
siguientes organismos:
o La Sociedad Americana de Salud Epidemiológica (SHEA) 2
o La Asociación de Profesionales en Control de Infecciones y
Epidemiología (APIC)3
o La CDC Healthcare Infection Control Practices Advisory Committee
(HICPAC) 4
- Las directrices de la SHEA indican claramente: “Los cultivos de
vigilancia activa son esenciales
para identificar el reservorio de expansión de infecciones MRSA y
VRE (Enterococcus resistente a
la vancomicina) y posibilitar el control mediante las precauciones
anticontagio recomendadas por la
CDC 5.
- La vigilancia activa incluye testar a aquellos sujetos de alto
riesgo susceptibles de MRSA, lo cual
puede incluir variables basadas en anteriores exposiciones, estilos
de vida y factores sociales tales
como:
o Residencia en un centro de cuidados para mayores.
o Historial de diálisis y enfermedades renales, diabetes mellitas
y/o cirugía.
o Historial de uso de catéteres o cualquier otro instrumento médico
que vaya al cuerpo atra-
vesando la piel.
o Uso frecuente y/o reciente de antibióticos.
o Alta prevalencia de MRSA en la comunidad local o entre la
población de pacientes.
o Contacto cercano con alguien infectado o colonizado con
MRSA.
o Condiciones de vida de hacinamiento (por ej. Refugios para gente
sin hogar, cárceles…).
o Infecciones entre deportistas por contacto de piel, heridas ya
existentes o por compartir
ropa y/o equipación.
o Edad avanzada.
- En EEUU existen muchos hospitales que han implementado con éxito
la vigilancia activa para
controlar epidemiológicamente MRSA y eliminar las infecciones
asociadas. Ejemplos de programas
implementados con éxito incluyen: Evanston Northwestern Healthcare,
Evanston, IL; el University
of Pittsburg Medical Center, Pittsburg, PA; el Newark Beth Israel
Hospital en Newark, NJ; y el
University of Maryland Medical Center, Baltimore, MD.
- Los métodos más nuevos de test moleculares rápidos son la
tecnología ideal para implementar las
medidas de vigilancia activa. La obtención de resultados
definitivos para MRSA en dos horas, en vez de dos o tres días
siguiendo los métodos de cultivo tradicionales, permite tomar las
debidas precauciones y poner un tratamiento casi inmediatamente. La
rapidez del test ayuda
a minimizar el riesgo de complicaciones y transmisión, y evita la
necesidad de mantener el
aislamiento mientras se esperan los resultados.
OTROS TIPOS DE VIGILANCIA DE MRSA
Vigilancia Universal, también conocida como vigilancia en todas las
admisiones, incorpora el test a todos
los pacientes admitidos, no sólo a los pacientes de alto riesgo
(según se describe arriba). Un nuevo estudio
publicado en la Sociedad Americana de Microbiología durante la 46
Conferencia anual sobre Agentes
Antimicrobianos y Quimioterapia (ICAAC) demostró que la
implementación de la vigilancia universal es
mucho más efectiva a la hora de controlar MRSA que simplemente la
pasiva o la activa dirigida hacia un
diana específica.
“Búsqueda y destrucción” es otra forma de aproximación que se
utiliza con éxito en países como
Finlandia, Dinamarca y Holanda para mantener el MRSA en los más
bajos niveles posibles. Implica la
utilización de una vigilancia activa en pacientes y personal
sanitario, con una búsqueda de MRSA en el
momento de admisión y a ciertos intervalos en áreas de alto riesgo.
Va acompañado de estrictas
precauciones anticontagio. También se pone énfasis en un uso
juicioso de antibióticos de amplio espectro.
Vigilancia Pasiva implica testar solo aquellos en los que han
aparecido signos clínicos o síntomas de
infección por MRSA. Es el método más habitual para identificar MRSA
en pacientes hospitalarios en USA.
Consiste en una vigilancia no activa, que depende de cultivos
rutinarios para identificar pacientes con
MRSA, no identifica el 85% de los pacientes colonizados de MRSA en
admisión en el hospital. Los
pacientes identificados como portadores a través de una vigilancia
activa son tratados de forma mucho
más rápida estableciendo rigurosas precauciones anticontagio para
frenar la transmisión de la infección.
Los programas hospitalarios para controlar y prevenir la
transmisión de MRSA no pueden ser efectivos sin
una vigilancia activa en los pacientes de admisión con un resultado
de rápida implementación de medidas
anticontagio en aquellas personas identificadas como portadores de
MRSA;
Vigilancia de MRSA en UCI mediante cultivo tradicional (Huang et
al., 2006)
La vigilancia rutinaria de MRSA en UCI mediante cultivo permitió el
establecimiento temprano de precauciones de aislamiento y se asoció
con una reducción significativa de la incidencia de bacteriemia por
MRSA. No se pudo atribuir ninguna reducción similar debida a otros
métodos de control de la infección. Huang et al., 2006. Clin.
Infect. Dis. 43:971-978.
4. Vigilancia de MRSA en UCI
Prevalencia de SARM en el momento de la admisión Tasa de
transmisión mensual
Transmisión de MRSA en UCI durante las fases de screening mediante
cultivo o screening basado en PCR
Vigilancia de MRSA en UCI mediante RT-PCR: reducción de las
transmisiones (Cunningham et al., 2007)
0
5
10
15
20
25
PCR
Se considera factible la búsqueda mediante PCR de pacientes
portadores de MRSA durante la admisión a unidades de cuidados en el
marco de la rutina clínica; proporciona resultados más rápidamente
que el cultivo y se asocia con una reducción significativa en la
subsiguiente transmisión de MRSA.
Control de MRSA
www.elsevierhealth.com/journals/jhin
Effect on MRSA transmission of rapid PCR testing of patients
admitted to critical care
R. Cunningham a,*, P. Jenks a, J. Northwood a, M. Wallis a, S.
Ferguson b, S. Hunt b
a Department of Microbiology and Infection Control, Derriford
Hospital, Plymouth, UK b Critical Care Unit, Derriford Hospital,
Plymouth, UK
Received 31 May 2006; accepted 15 September 2006 Available online 4
December 2006
KEYWORDS MRSA; PCR; Screening; Critical care
Summary Wereporta significant reduction in the
rateofmeticillin-resistant Staphylococcus aureus (MRSA)
transmission on a critical care unit when admission screening by
culture was replaced with a same-day polymerase chain reaction
(PCR) test. This was an observational cohort study, set in a 19-bed
mixed medical and surgical adult critical care unit in southwest
England. We studied 1305 patients admitted between April 2005 and
Febru- ary 2006. Standard MRSA culture methods were used to screen
612 patients between April 2005 and August 2005, and the IDI MRSA
PCR test was used to screen 693 patients between September 2005 and
February 2006. Stan- dard infection control precautions were
instituted when positive results were obtained by either method.
Outcome measures included carriage rate, turnaround time for
results and rate of subsequent MRSA transmission on the unit. The
overall carriage rate on admission to the unit was 7.0%. Culture
re- sults were available in three working days, PCR results within
one working day. The mean incidence of MRSA transmission was
13.89/1000 patient days during the culture phase and 4.9/1000
patient days during the PCR phase (relative risk reduction 0.65,
95% CI 0.28e1.07). PCR screening for MRSA on admission to critical
care units is feasible in routine clinical practice, pro- vides
quicker results than culture-based screening and is associated with
a significant reduction in subsequent MRSA transmission. ª 2006 The
Hospital Infection Society. Published by Elsevier Ltd. All rights
reserved.
* Corresponding author. Address: Department of Microbiology and
Infection Control, Derriford Hospital, Plymouth, PL6 8DH, UK. Tel.:
þ44 1752 7923 87; fax: þ44 1752 5177 25.
E-mail address: richard.cunningham@phnt.swest.nhs.uk
0195-6701/$ - see front matter ª 2006 The Hospital Infection Soc
doi:10.1016/j.jhin.2006.09.019
Introduction
Meticillin-resistant Staphylococcus aureus (MRSA) is one of the
most important causes of hospital- acquired infection in the UK.
The spectrum of
iety. Published by Elsevier Ltd. All rights reserved.
infection ranges from asymptomatic colonization to bacteraemia and
death. Community-acquired MRSA is an increasing problem, but in the
UK most severe MRSA infection is still hospital associated.
Within hospital, critical care units (CCUs) are a crucial site for
MRSA control measures. Severe underlying illness, a high degree of
comorbidity, intravascular lines and endotracheal intubation all
contribute to high rates of MRSA transmission. Attempts have been
made to reduce this by screening on admission followed by
isolation, topical eradication therapy, and attention to hand
hygiene.1e4 The results have been inconclu- sive, possibly because
traditional culture methods for MRSA detection take at least two
days. This means that positive patients remain undetected and act
as a reservoir for transmission during the most intensive phase of
their CCU stay. A recent study in Geneva described a reduction in
MRSA in- fections on a medical intensive care unit (ICU), when a
rapid molecular screening test was com- bined with pre-emptive
isolation of all admissions until a negative result was obtained.5
They found no effect with screening alone, or when the strat- egy
was applied to a surgical ICU.
In the present study, the impact of a rapid PCR test on MRSA
transmission in a mixed medical and surgical CCU was compared with
the preceding control period when patients were screened using a
traditional culture method.
Methods
Setting and study population
Derriford Hospital is a 1200-bed teaching hospital in southwest
England. The general adult CCU comprises a four-bed neurosurgical
section, a six- bed high-dependancy unit, and a nine-bed ICU. The
units are adjacent and linked, and share staff and equipment. The
unit receives approxi- mately 1400 admissions each year, and the
average length of stay is four days. The three siderooms available
are not exclusively reserved for MRSA-positive patients, although
where pos- sible, such patients are nursed in these rooms.
Culture-based MRSA screening
Screening of all CCU admissions and discharges was introduced in
April 2005 as a quality improvement measure. Swabs were taken from
the nose, throat, axillae and groin, and wounds if present.
The
swabs were pooled in 7% sodium chloride broth and incubated
overnight at 30C. They were sub- cultured on mannitol salt agar
with oxacillin (2 mg/L) and incubated at 37C in air for 48 h. Sus-
pected MRSA colonies were confirmed by standard methods. CCU staff
were informed verbally of all positive results by an infection
control nurse or consultant microbiologist. Electronic and printed
results were issued the same working day. All pa- tients discharged
from CCU were screened using the same method on the day of
discharge.
PCR-based MRSA screening
From September 2005 culture-based admission screening was replaced
with the IDI-MRSA PCR assay, run on the Cepheid Smart Cycler
platform. The performance of the assay in the patient population
was assessed in a pilot phase, when swabs from 174 patients were
processed by culture and PCR in parallel. This showed a sensitivity
of 100% and specificity of 92%, consistent with pre- vious
experience of the test. A single nose swab was collected on
admission, and processed Monday to Friday on the same day according
to the manufacturer’s instructions. Weekend samples were processed
the following Monday. Positive and negative controls were included
in each run. Any samples unresolved due to PCR inhibitors were
repeated after a single freezeethaw cycle on the same DNA extract.
All positive and unresolved swabs were cultured and full
susceptibility testing of MRSA isolates performed using standard
methods. Positive results were transmitted to CCU staff in the same
way as for conventional culture, except that PCR results were
reported as provisional, pending the final results from
culture.
Infection control policies
A dedicated link nurse (S.H.) who is a senior sister on the CCU
liaised with the infection control team and laboratory throughout
both phases. Standard infection control procedures such as
educational sessions and ward audits continued unchanged
throughout. The National Patient Safety Agency ‘Clean your hands’
campaign began before screen- ing was introduced and continued
throughout. No changes in ward cleaning, disinfectant use, line
care or management of ventilators/endotracheal tubes occurred
during the study period. Pre- emptive isolation of new admissions
was not employed. Identified MRSA carriers were com- menced on
nasal mupirocin ointment thrice daily and topical triclosan for
five days. Patients with
26 R. Cunningham et al.
evidence of MRSA infection were treated with appropriate
antibiotics, mainly vancomycin, rifam- picin, gentamicin and
linezolid. Patient case notes and the computerized patient
information system were tagged with their MRSA status, and standard
infection control precautions were reinforced. Patients were nursed
in a sideroom if available, but shortage of siderooms meant this
was not always possible. Similar precautions were taken if MRSA was
isolated from a routine culture later in the patients ICU
stay.
Definitions
CCU acquired infection was defined as MRSA detection more than 48 h
after admission, in a pa- tient whose admission screen had been
negative. The transmission rate was defined as the number of CCU
acquired cases divided by the number of bed days at risk, expressed
as cases per 1000 bed days.
Statistical analysis
Data was analysed with the non-parametric Wil- coxon test. A
P-value of <0.05 was considered significant.
Results
Carriage rate
The overall pre-admission carriage rate throughout the period of
study was 7.0%. Monthly rates ranged
between 3.6 and 10.8%, but there was no signifi- cant trend or
difference between the culture and PCR phases. Rates are summarized
in Figure 1.
Turnaround time
The turnaround time was three working days during the culture phase
and less than one working day during the PCR phase.
Success rate of decolonization regimen
This was defined as MRSA culture negative at four weeks
post-decolonization. It was 36% in the culture phase and 33% in the
PCR phase (no significant difference).
MRSA transmission
Thirty-three out of 612 patients acquired MRSA on the CCU during
the culture phase, and 14 out of 693 patients during the PCR phase.
This gives a mean incidence of transmission of 13.89/1000 patient
days during the culture phase and 4.90/ 1000 patient days during
the PCR phase (P<0.05). The absolute reduction is 8.98
transmissions/1000 patient days (95% CI 8.56e9.42). The relative
risk reduction is 0.65 (95% CI 0.28e1.07).
These results are summarized in Figure 1.
Discussion
These results suggest that rapid PCR screening of patients admitted
to CCUs may reduce the rate of
0
5
10
15
20
25
Culture MRSA screening Mean transmission rate 13.9/1000 patient
days
PCR MRSA screening Mean transmission rate 4.9/1000 patient
days
Figure 1 MRSA transmission on CCU during culture and PCR-based
screening phases. Columns represent transmission rate each month
and the continuous line is the prevalence of MRSA at the time of
admission.
MRSA PCR testing on Critical Care 27
subsequent MRSA transmission more effectively than traditional
culture based methods. Possible explanations include earlier use of
decolonization regimens, earlier use of appropriate antibiotics,
earlier isolation, and better compliance with hand hygiene
procedures.
It is not possible to define which of these factors is most
important from the present data, but since the success rate of
decolonization was similar in both phases of the study, we suspect
that better compliance with hand hygiene and early use of topical
eradication agents might be the most important mechanisms.
The reduction in turnaround time gained using the PCR test is
substantial, since presumptive results are obtained early in the
CCU stay, when nursing and medical care is most intensive. It could
be reduced even further if the PCR test is made available at
weekends. Eight patients admitted at the weekend were MRSA
carriers, five during the culture phase and three during the PCR
phase. Availability is limited by financial rather than technical
constraints; the cost of the assay is approximately £25.00, but
this would be increased by the staffing costs of a weekend service.
PCR is clearly more expensive than bacterial culture, but should be
considered in the context of an average cost of over £10 000 for a
single CCU admission.
The PCR test is highly sensitive, but its speci- ficity is less
good. This is difficult to quantify in a retrospective study as
some patients with posi- tive PCR and negative cultures were
already on antimicrobials or antiseptics active against MRSA. Some
patients had been positive in the recent past, or were culture
positive from other anatom- ical sites. This did not present major
practical difficulties in the CCU population, since the main aim
was not to miss any MRSA carriers. PCR results were initially
reported as provisional and subject to confirmation. Patients with
a false-positive PCR result would have been started on topical
decolonization regimens unnecessarily, but we are not aware of any
serious adverse consequences arising from this.
There were a number of interesting differences between our findings
and those of Harbarth et al. in a Swiss ICU.5 First, despite a
comparable pre- admission prevalence of MRSA in their cohort, over-
all transmission rates on their ICUs were lower. This may be
because they did not carry out discharge screening throughout the
whole study period, which could potentially underestimate the
transmission rate. It may also reflect increased availability of
isolation rooms in the Swiss healthcare setting. Although their
report does not state how many single rooms were available, they
were able to isolate all
new admissions until MRSA screening results were available. This
suggests a relatively generous provi- sion compared with most UK
units.
Second, they did not observe any reduction in transmission until
pre-emptive isolation was in- troduced. The present results suggest
that benefit can be obtained from rapid results, even without the
ability to isolate all new admissions in this way.
Finally, they found that rapid testing had no impact when applied
on a purely surgical ICU. The present study included mixed medical
and surgical high-dependancy, intensive care and neurosurgical
intensive care patients. This is more representa- tive of routine
UK practice, and provides some reassurance that the present results
can be generalized to other similar units.
This is an observational study, and conse- quently has many
limitations. We cannot exclude the possibility that other changes
in MRSA epi- demiology or management influenced transmis- sion
rates. We cannot identify any changes in antibiotic susceptibility
or virulence over this period, neither can we identify any changes
in patient management or infection control policy. The ‘Clean your
hands’ campaign was most heavily promoted during the culture
screening phase, and there is no reason to believe it had a greater
impact when PCR screening began five months later. The PCR
screening phase spanned the winter period, when hospital activity
is highest. We have not performed a formal cost- effectiveness
analysis, though the business case used to obtain funding for this
initiative predicted significant overall savings with much smaller
reductions in MRSA transmission than we subsequently
observed.
The benefits of rapid MRSA PCR screening can only be determined by
large randomized, con- trolled trials, with robust health economic
anal- ysis. At least one such study is underway and will be vital
in defining the best use for this technol- ogy. Details are
available on the UK National Research Register Document,
http://www.nrr. nhs.uk/ViewDocument.asp?ID=N0046162252. The results
of this study suggest the possibility of sub- stantial benefits as
well as grounds for optimism in the struggle to control MRSA in
critical care.
References
1. Chaix C, Durand-Zaleski I, Alberti C, Brun-Buisson C. Control of
endemic methicillin-resistant Staphylococcus aureus: a costebenefit
analysis in an intensive care unit. JAMA 1999;282:1745e1751.
2. Cepeda JA, Whitehouse T, Cooper B, et al. Isolation of pa-
tients in single rooms or cohorts to reduce spread of MRSA
in intensive-care units: prospective two-centre study. Lancet
2005;365:295e304.
3. Rubinovitch B, Pittet D. Screening for methicillin-resistant
Staphylococcus aureus in the endemic hospital: what have we
learned? J Hosp Infect 2001;47:9e18.
4. Grundmann H, Hori S, Winter B, Tami A, Austin DJ. Risk factors
for the transmission of methicilln-resistant
Staphylococcus aureus in an adult intensive care unit: fitting a
model to the data. J Infect Dis 2002;185:481e488.
5. Harbarth S, Masuet-Aumatell C, Schrenzel J, et al. Evalua- tion
of rapid screening and pre-emptive contact isolation for detecting
and controlling methicillin-resistant Staphylo- coccus aureus in
critical care: an interventional cohort study. Critical Care 2006
Feb 6;10:R25 [Epub ahead of print].
El impacto al utilizar métodos moleculares
Metodología tradicional: cultivo
12 h 36 h 48 h 60 h 72 h 84 h24 h 96 h
Cultivo
2-3 días de transmisión potencial de MRSA
12 h 36 h 48 h 60 h 72 h 84 h24 h 96 h
PCR
Las medidas de aislamiento y/o descontaminación se establecen el
mismo día de la toma de muestra
Resultado en 2 horas
5. Control de MRSA: El impacto de utilizar métodos
moleculares
BD GeneOhm™ MRSA
definitivos
6. BD GO. Rendimiento de la prueba y publicaciones
BD GeneOhm™ MRSA
Huletsky et al, 2004. New real time PCR assay for rapid detection
of MRSA directly from specimen containing a mixture of
staphylococci. J. Clin. Microbiol. 42(5): 1875-1884. Sensibilidad:
98,7% Especificidad: 95,4%
Paule et al., 2007. Performance of the BD GeneOhm Methicillin-
Resistant Staphylococcus aureus Test before and during High- Volume
Clinical Use. J. Clin. Microbiol. 45(9): 2993-2998 Sensibilidad:
98% Especificidad: 96 % VPN: 99,7% VPP: 77 %
Sensibilidad: 93,1% Especificidad: 98,4%
Oberdorfer et al., 2006. Evaluation of a single-locus real-time
polymerase chain reaction as a screening test for specific
detection of methicillin-resistant Staphylococcus aureus in ICU
patients. Eu. J. Clin. Microbial. Infect. Dis. 25: 657-663.
Sensibilidad: 92,3% Especificidad: 98,6% VPN: 99,6% VPP: 75 %
Wren et al., 2006. Rapid Molecular Detection of
Methicillin-Resistant Staphylococcus aureus. J. Clin. Microbiol.
44(4): 1604-1605. Sensibilidad: 95,0% Especificidad: 98,8% VPN:
99,6% VPP: 84,4%
Vigilancia de MRSA en pabellones quirúrgicos mediante RT- PCR:
importancia de un diagnóstico rápido
Kesthgar et al., 2007 • El estudio demuestra una reducción
significativa de
las bacteriemias debidas a MRSA al introducir una técnica rápida de
screening, en comparación con el periodo donde no se realizaba
screening.
• También se observa una reducción de las infecciones de herida por
MRSA.
• El programa de screening es rentable, especialmente en años donde
hay un pico en la incidencia de MRSA, y supone una mejora
considerable en la calidad de vida de los pacientes.
Jog et al., 2007 • El screening mediante PCR combinado con la
supresión de MRSA en el momento de la cirugía cardiaca es viable
dentro de la práctica clínica rutinaria y se asocia con una
reducción significativa en las posteriores SSIs (Infecciones de
Herida Quirúrgica) debidas a MRSA.
Control de MRSA: Cirugía
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27 Nov 2007 Copyright © 2007 British Journal of Surgery Society
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Original Article
*Correspondence to M. R. S. Keshtgar, Department of Surgery, Royal
Free Hospital, Pond Street, London NW3 2QG, UK
The Editors are satisfied that all authors have contributed
significantly to this publication
Accepted: 12 November 2007
Introduction
The incidence of hospital-acquired meticillin-resistant
Staphylococcus aureus (MRSA) infection is rising worldwide, over
and above the increase in meticillin-sensitive S. aureus (MSSA)
infection. In the UK, the incidence of MRSA septicaemia increased
by 5·5 per cent between 2001 and 2003-2004[1] with a corresponding
rise in MRSA-related deaths[2]. Indeed, the UK is reported to have
one of
Impact of rapid molecular screening for meticillin-resistant
Staphylococcus aureus in
surgical wards
M. R. S. Keshtgar 1 *, A. Khalili 1, P. G. Coen 2, C. Carder 2, B.
Macrae 2, A. Jeanes 2, P. Folan 2, D. Baker 2, M. Wren 2, A. P. R.
Wilson 2
1Department of Surgery, Windeyer Institute of Medical Sciences,
University College London Hospitals Foundation Trust, London, UK
2Department of Microbiology, Windeyer Institute of Medical
Sciences, University College London Hospitals Foundation Trust,
London, UK
email: M. R. S. Keshtgar (m.keshtgar@ucl.ac.uk)
ABSTRACT
Background: This study aimed to establish the feasibility and
cost-effectiveness of rapid molecular screening for
hospital-acquired meticillin- resistant Staphylococcus aureus
(MRSA) in surgical patients within a teaching hospital.
Methods: In 2006, nasal swabs were obtained before surgery from all
patients undergoing elective and emergency procedures, and screened
for MRSA using a rapid molecular technique. MRSA-positive patients
were started on suppression therapy of mupirocin nasal ointment (2
per cent) and undiluted chlorhexidine gluconate bodywash.
Results: A total of 18 810 samples were processed, of which 850
(4·5 per cent) were MRSA positive. In comparison to the annual mean
for the preceding 6 years, MRSA bacteraemia fell by 38·5 per cent
(P < 0·001), and MRSA wound isolates fell by 12·7 per cent (P =
0·031). The reduction in MRSA bacteraemia and wound infection was
equivalent to a saving of 3·78 beds per year (£276 220), compared
with the annual mean for the preceding 6 years. The cost of
screening was £302 500, making a net loss of £26 280. Compared with
2005, however, there was a net saving of £545 486.
Conclusion: Rapid MRSA screening of all surgical admissions
resulted in a significant reduction in staphylococcal bacteraemia
during the screening period, although a causal link cannot be
established. Copyright © 2007 British Journal of Surgery Society
Ltd. Published by John Wiley & Sons, Ltd.
DIGITAL OBJECT IDENTIFIER (DOI)
the highest rates of MRSA infection in Europe[3].
MRSA-colonized patients may have acquired the bacterium from
previous hospital and nursing home admission, but others are truly
community acquired[3-5]. The identification of MRSA carriers on
admission and use of topical suppression may reduce the rates of
MRSA infection[6]. Previously, routine MRSA screening relied on
culture techniques with a turnaround time of up to 3 days.
Polymerase chain reaction (PCR) technology now enables results to
be reported within hours, so topical suppression protocols can
start immediately.
The aim of the present study was to establish the feasibility and
cost-effectiveness of rapid molecular screening for MRSA in
surgical patients within a teaching hospital, and to monitor the
effect of rapid screening and topical suppression therapy on the
rate of MRSA wound infection and bacteraemia.
Methods
After obtaining ethics committee approval, all patients admitted in
2006 (January to December inclusive) to the University College
London Hospitals (UCLH) Foundation Trust for critical care, routine
or emergency surgery (i.e. incision) were targeted for rapid MRSA
screening. In those scheduled for elective surgery, cotton swabs
(in Amies transport medium) from both nostrils were taken in the
preadmission clinic. In emergency patients, nasal swabs were
obtained on admission to the ward. Swabs were analysed in batches
of 30 to 46, two to three times daily during the working week.
Positive and negative controls were included in each run for
quality control.
PCR was performed using the GeneOhm® MRSA Test (Becton Dickinson,
Franklin Lakes, New Jersey, USA), which achieves detection of MRSA
in a nasal swab by target amplification with primers and probes
designed to detect the right-hand region of the mecA cassette and
neighbouring orfX gene. The amplified targets are detected by using
fluorescent beacon technology[7]. Inhibited samples (those in which
the internal control was not detected) were repeated after freezing
the lysate at - 20 °C for approximately 2 h. If there was still
inhibition on repeat, a further swab was requested and, if surgery
was anticipated within 3 days, the suppression protocol was
instigated.
When a patient was found to be MRSA positive, the appropriate
doctor or preadmission clinic was informed by telephone and asked
to contact the patient to prescribe the suppression protocol.
Outpatients were asked to visit the hospital pharmacy to collect a
prescription written by the microbiologist.
The suppression protocol was expected to start 5 days before
surgery, or the operation might be delayed. In more urgent cases,
the suppression protocol was commenced immediately. Mupirocin nasal
ointment (2 per cent) was applied to the inside of the nostrils
three times daily, and undiluted chlorhexidine gluconate 4 per cent
(Hibiscrub®; Moinlycke Health Care, Dunstable, UK) was used as a
bodywash. Patients were advised to use undiluted Hibiscrub® as a
shampoo to wash hair on days 1, 3 and 5, and to change their
clothing and bedlinen daily.
If antibiotic prophylaxis was required, existing practice was to
use a combination of teicoplanin and gentamicin. Patients who
required emergency surgery before the result of MRSA screening was
available were given mupirocin nasal ointment and chlorhexidine
wash. The suppressive measures were continued until the result of
MRSA screening was known. Blood cultures were obtained when the
temperature rose above 37·5 °C (either peripherally or from a
central or arterial catheter).
The hospital wound surveillance team has examined surgical wounds
in all specialties for at least 6 months every year since 2000 by a
combination of observation, questioning of staff, examination of
case notes, and telephone or postal contact with patients[8]. After
discharge, surveillance was performed at 1-2 months. Patients were
excluded from wound surveillance if they stayed in hospital for
fewer than two nights or if the procedure did not involve wounding
(for example, endoscopy alone).
Cost-effectiveness analysis The annual saving to the hospital
attributable to the MRSA screening programme was assessed by
comparing the numbers expected (E) in the absence of screening
(using incidence rates for 2000-2005 and for 2005 alone) with the
observed numbers (O) for 2006. The saving is given by the
expression (E - O) × C, where C is the cost per bacteraemia (or
wound). C was calculated from the mean treatment costs for MRSA
bacteraemia (£3500) and wound infection (£4018), primarily through
prolonged hospital stay[8][9]. The estimated daily labour costs
(all staff) of looking after an infected patient at UCLH was £314
in a general ward, £1002 in the high- dependency unit and £1390 in
the intensive care unit (ICU)[8]. Other costs, such as dressings,
drainage and antibiotics, accounted for only 2 per cent of costs.
The saving was then translated into bed-years using the benchmark
cost of an average medical/surgical bed (£200 above the estimated
trimpoint - the point after which a length of stay is determined to
be abnormally long).
The cost-effectiveness of the programme was calculated by comparing
the saving with the annual cost of screening (including reagents,
equipment and staffing).
Statistical analysis Most statistical tests were performed using
Stata
TM version 9.0 (StatCorp, College Station, Texas, USA). Incidence
rates were
compared with Fisher's exact test. The 2 test for trends was used
to assess monthly and quarterly changes in MRSA prevalence on
admission screening. Time to event data were collected for
inpatients with positive MRSA screening results and analysed by
means of survivorships between January and September 2006. Median
times to event and their 95 per cent confidence intervals (c.i.)
were calculated from the time to 50 per cent survival in
Kaplan-Meier survivorships. For estimates of screening compliance,
each surgical operation was considered compliant with the screening
protocol if the inpatient had been screened within 6 months before
and 2 weeks after surgery.
Results
Between 16 January and 31 December 2006, 20 447 screening samples
were received, of which 18 810 were processed. The remaining
samples were discarded as they were from inappropriate sites (n =
627), duplicate nares (n = 423) or patients found to be MRSA
positive on a previous screen (n = 587).
There were 850 MRSA-positive samples (4·5 per cent of all samples
processed). Patients admitted for emergency surgery were more
likely to be colonized (99 of 1854 patients; 5·3 per cent) than
those undergoing elective surgery (289 of 7938; 3·6 per cent; 2 =
10·9, P = 0·001), resulting in an overall prevalence of 4·0 per
cent for all surgical admissions. Table 1 shows MRSA isolates
stratified by surgical specialty and ICU admission. A continuous
audit of surgical prophylaxis (as part of the wound surveillance
programme) showed no policy changes in antibiotic prophylaxis
effective against MRSA between 2000 and 2006[8]. Tests for trend
failed to reveal statistically significant changes in the
prevalence of MRSA positivity on admission during 2006.
Processing of specimens A total of 215 positive admission episodes
were audited. Median time lags for the processing of positive
samples are shown in Table 2. The busiest days for laboratory
processing were Monday and Tuesday, as a result of the backlog of
unprocessed samples collected during the weekend.
MRSA bacteraemia Fifty-three patients developed MRSA bacteraemia
over the study interval, 41 in screened and 12 in non-surgical
patients. The annual
Table 1. Proportion of patients with meticillin-resistant
Staphylococcus aureus colonization on admission
Surgical specialty Elective surgery Emergency surgery Total
Anaesthetics 2 of 95 (2) 0 of 11 (0) 2 of 106 (1·9)
Cardiothoracic 25 of 1184 (2·1) 7 of 186 (3·8) 32 of 1370
(2·3)
General surgery 59 of 1459 (4·0) 21 of 279 (7·5) 80 of 1738 (4·5)
Maxillofacial 51 of 977 (5·2) 9 of 163 (5·5) 60 of 1140 (5·3)
Orthopaedics 40 of 1813 (2·2) 30 of 652 (4·6) 70 of 2465
(2·8)
Plastics 15 of 225 (6·7) 16 of 415 (3·9) 31 of 640 (4·8)
Urology 84 of 1929 (4·4) 9 of 81 (11) 93 of 2010 (4·7)
Vascular 13 of 254 (5·1) 2 of 38 (5) 15 of 292 (5·1) Unknown 0 of 2
(0) 5 of 29 (17) 5 of 31 (16)
All specialties 289 of 7938 (3·6) 99 of 1854 (5·3) 388 of 9792
(4·0)
ICU n.r. n.r. 235 of 2736 (8·6)
Values in parentheses are percentages. ICU, intensive care unit;
n.r., not recorded.
Table 2. Median time lag for events in the processing of positive
samples
Time lag
13·7 (9·78, 15·1) h
From receipt of sample in laboratory to obtaining result (n =
212)*
21·8 (21·0, 22·5) h
From obtaining result to telephone call (n = 215)* 1·03 (0·83,
1·41) h
From receipt of sample in laboratory to start of
surgery (n = 217)
days
From start of suppression to surgery (n = 200) § - 0·42 (-1·90 to
2·85)
days
median (interquartile range).
A negative value indicates that surgery took place before the
sample had been processed. § If less than 5 days to surgery, then
suppression continued into the postoperative period.
means and ranges for 2000-2005 were 67 (53-87) and 29 (17-45)
respectively in the equivalent patient populations.
The overall rate of MRSA bacteraemia per 1000 patient-days fell by
38·6 per cent compared with 2005 (P < 0·001; two-tailed Fisher's
exact test) and by 38·5 per cent compared with the annual mean for
2000-2005 (P < 0·001) (Table 3). In addition, there was a 32·1
per cent reduction in MSSA bacteraemia compared with 2005 (P <
0·001) and a 30·4 per cent reduction compared with the annual mean
for 2000-2005 (P < 0·001) (Table 3).
MRSA wound infection The rate of isolation of MRSA from wounds fell
by 27·9 per cent compared with 2005 (P < 0·001) but by only 12·7
per cent compared with the annual mean between 2000 and 2005 (P =
0·021) (Table 3). The 2006 MSSA isolation rates did not change
significantly compared with those for 2005 (4·4 per cent reduction;
P = 0·430), but increased by 12·7 per cent compared with 2000-2005
(P = 0·006) (Table 3). Although there was a reduction in wound
infection in seven of 11 specialties covered by wound surveillance,
the overall prevalence was unchanged because of a rise in wound
infection in general surgery (surveillance data available only for
January to July 2006).
MRSA isolates There were no significant differences in the
proportion of mupirocin resistance (predominantly low levels) in
wound and blood isolates between 2005 and 2006: 93 (13·9 per cent)
of 671 versus 74 (15·7 per cent) of 472 isolates (P = 0·396). In
surgical and critical care patients in 2000-2006, 11 (6·7 per cent)
of 163 isolates tested (281 not tested) were sensitive to
ciprofloxacin and 54 (12·3 per cent) of 438 (six not tested) were
sensitive to erythromycin.
Compliance with screening and treatment Compliance with screening
in different surgical specialties improved during 2006 (Fig. 1). Of
218 audited patients found to have MRSA at or before surgery, 92
either received no topical suppression or it was started only after
the procedure. In 30 (33 per cent) of these patients MRSA was later
isolated from the surgical wound. The other 126 patients received
suppression (at least one dose) before the procedure; in 26 (20·6
per cent) of these patients MRSA was later isolated from the wound
(P < 0·05, 2 test).
Costings Table 4 shows that the observed reduction in MRSA
bacteraemia and wound infection rates was equivalent to a saving of
3·78 beds per year (£276 220) compared to the annual mean for the
preceeding 5 years. The reduction in infection rates was observed
both in patients who were screened and in those who were not; in
many wards these patients were mixed, so separate costings have not
been attempted.
Table 3. Incidence rates for meticillin-resistant and
meticillin-sensitive Staphylococcus aureus bacteraemia and wound
infection
Year No. of patient-days
Bacteraemia Wound Bacteraemia Wound
2000-2005 1 469 399 0·39 (573) 1·44 (2110) 0·59 (860) 2·58 (3788)
2005 186 867 0·39 (73) 1·74 (325) 0·60 (112) 3·04 (568)
2006 221 027 0·24 (53) 1·25 (277) 0·41 (90) 2·90 (642)
Values in parentheses are numbers of patients. MRSA,
meticillin-resistant Staphylococcus aureus; MSSA,
meticillin-sensitive S. aureus.
Figure 1. Screening compliance stratified by elective and emergency
surgery. Compliance was measured as the percentage of surgical
episodes classified as screened. Dotted and dashed horizontal lines
indicate 80 and 70 per cent compliance respectively [Normal View
25K | Magnified View 36K]
Table 4. Cost-effectiveness of the rapid meticillin-resistant
Staphylococcus aureus test screening programme
MRSA MSSA
Based on 2000-2005 figures 86 317 129 570 Observed numbers
2006 53 277 90 642
The annual cost of screening was estimated at £302 500 (cost per
test: kit £11·59 including value added tax and cost of repeats, £1
for disposable tips, £1 for telephoning results and £3·01 per test
for labour; less previous annual spending of £9900), which is
equivalent to 4·1 beds for the year. The programme is therefore
cost-effective and demonstrates large cost savings when compared to
costs incurred during years of peak incidence (for example,
2005).
Discussion
In 2004, the UK Department of Health set a target of a 60 per cent
reduction in MRSA bacteraemia by 2008. In January 2006, UCLH became
the first National Health Service Trust (public sector corporation)
nationally to introduce a rapid molecular MRSA detection technique
for routine screening of most surgical patients. Before the start
of this project, validation of the technique against culture showed
a sensitivity of 95·0 per cent and a specificity of 98·8 per cent,
with a positive predictive value of 84·4 per cent and a negative
predictive value of 99·6 per cent[7].
Although more than 40 different decolonization regimens have been
tested during the past 60 years, topical intranasal application of
mupirocin ointment and bodywash with 4 per cent chlorhexidine has
proven to be the most effective measure[10]. However, showering of
all patients with chlorhexidine before surgery is not effective in
reducing surgical infection rates[11].
This study demonstrated a significant reduction in the MRSA
bacteraemia rate of 38·5 per cent compared with 2000-2005 figures
and 38·6 per cent compared with 2005. A possible explanation is the
reduction in the turnaround time for reporting of the MRSA
screening swab, such that the suppression protocol and appropriate
surgical prophylaxis can be started quickly. There was no other
change in the authors' practice, as careful attention to hand
hygiene and specific surgical prophylaxis for MRSA carriers had
been in place well before the start of this study. These results
need to be interpreted with caution, however, as in 2005, 4 months
before the commencement of screening, most inpatients had been
moved to a new building - this coincided with an increased
incidence of MRSA infection. Hence, comparison was made not only
with 2005 but also with the preceding 6 years.
The effect on wound infection was modest in comparison with that on
blood isolates. There is an appreciable recurrence of superficial
MRSA colonization following topical suppression. Unlike
bacteraemia, wound infection can be prolonged.
MRSA infection has a cost for the patient and healthcare providers
that includes prolonged hospital stay and treatment of
complications associated with the infection. Variations in MRSA
infection rate, such as the peak reported in 2005, can make it
difficult to assess the effect of a screening programme. Although
the screening programme is costly, the reduction in MRSA surgical
wound infection and bacteraemia produces nearly equivalent savings
and the improvements in quality of life for patients are
considerable.
Acknowledgements
The authors thank Elizabeth O'Donnell and the wound surveillance
team, microbiology laboratory staff, the UCLH infection control
nurses, the surgical preadmission clinic and UCLH ward and pharmacy
staff.
Becton Dickinson funded production of a video presentation of the
use of topical suppression for the benefit of patients and
staff.
Cost savings (£)
Versus 2005 figures £115 500 £429 926 £147 000 £120 540 £812
966
Bed-year equivalents 1·58 5·89 2·01 1·65 11·1
Versus 2000-2005 figures £115 500 £160 720 £136 500 - £289 296 £123
424 Bed-year equivalents 1·58 2·20 1·87 - 3·96 1·69
MRSA, meticillin-resistant Staphylococcus aureus; MSSA,
meticillin-sensitive S. aureus.
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Journal of Hospital Infection (2008) 69, 124e130
Available online at www.sciencedirect.com
Impact of preoperative screening for meticillin- resistant
Staphylococcus aureus by real-time polymerase chain reaction in
patients undergoing cardiac surgery
S. Jog a, R. Cunningham a, S. Cooper a, M. Wallis a, A. Marchbank
b, P. Vasco-Knight a, P.J. Jenks a,*
a Department of Microbiology and Infection Prevention and Control,
Derriford Hospital, Plymouth, UK b Department of Cardiothoracic
Surgery, Derriford Hospital, Plymouth, UK
Received 18 October 2007; accepted 20 February 2008 Available
online 2 April 2008
KEYWORDS MRSA; Polymerase chain reaction; Screening; Cardiac
surgery; Surgical site infection
* Corresponding author. Address: Dep UK. Tel.: þ44 01752 792366;
fax: þ44
E-mail address: Peter.Jenks@phnt.
0195-6701/$ - see front matter ª 200
doi:10.1016/j.jhin.2008.02.008
Summary We report a significant reduction in the number of surgical
site infections (SSIs) due to meticillin-resistant Staphylococcus
aureus (MRSA) in patients undergoing cardiac surgery after the
introduction of preopera- tive screening using a same-day
polymerase chain reaction (PCR) test. This was an observational
cohort study set in a cardiac surgery unit based in southwest
England. We studied 1462 patients admitted for cardiac surgery
between October 2004 and September 2006. The IDI MRSA PCR test was
used preoperatively to screen 765 patients between October 2005 and
Sep- tember 2006. Patients identified as carriers were treated with
nasal mupir- ocin ointment and topical triclosan for five days,
with single-dose teicoplanin instead of flucloxacillin as
perioperative antibiotic prophylaxis. The rate of SSI following
cardiac surgery in this group was compared to 697 patients who
underwent surgery without screening between October 2004 and
September 2005. After introduction of PCR screening, the overall
rate of SSI fell from 3.30% to 2.22% with a significant reduction
in the rate of MRSA infections (relative risk reduction: 0.77; 95%
confidence interval:
artment of Microbiology, Plymouth Hospitals NHS Trust, Derriford
Hospital, Plymouth PL6 8DH, 01752 517725. swest.nhs.uk
8 The Hospital Infection Society. Published by Elsevier Ltd. All
rights reserved.
MRSA PCR screening in cardiac surgery 125
0.056e0.95). PCR screening combined with suppression of MRSA at the
time of cardiac surgery is feasible in routine clinical practice
and is associ- ated with a significant reduction in subsequent MRSA
SSIs. ª 2008 The Hospital Infection Society. Published by Elsevier
Ltd. All rights reserved.
Introduction
Surgical site infections (SSIs) contribute substan- tially to
morbidity and mortality following cardiac surgery.1e4 Deep sternal
wound infections may ex- tend into the mediastinum, require
aggressive combined medical and surgical management, and have a
mortality as high as 47%.3,5e9 Meticillin- resistant Staphylococcus
aureus (MRSA) is a leading cause of SSI following cardiac surgery
and is inde- pendently associated with increased patient mor-
tality, prolonged length of stay and higher hospital costs.1,10
Prior to the study, MRSA was the major cause of SSIs following
cardiac surgery at our hospital, being responsible for more than
50% of cases. Nasal carriage of S. aureus has been identified as an
important risk factor for sternal wound infections.11 Elimination
of S. aureus nasal carriage using perioperative intranasal
mupirocin has been shown to be effective in reducing sternal wound
infections in patients undergoing cardiac surgery, as well as MRSA
SSIs following orthopaedic surgery.12e16 Since the widespread use
of mupiro- cin has the potential to increase the rate of resis-
tance, it may be prudent to restrict prophylaxis to those found to
be colonised.17 Identifying car- riers of MRSA would also highlight
the requirement for additional infection control precautions, in-
cluding isolation, as well as the need for a different systemic
antibiotic for perioperative prophylaxis. Rapid diagnostic testing
now allows MRSA screening in the immediate preoperative period with
suffi- ciently short turnaround time to allow the imple- mentation
of appropriate control measures before surgery. In the present
study, the impact of rapid preoperative detection of MRSA on the
develop- ment of SSIs in patients undergoing cardiac surgery was
compared with the preceding control period when patients were not
screened.
Methods
Setting and study population
Derriford Hospital is a 1200-bed teaching hospital in southwest
England. The Southwest Cardiac
Surgery Unit comprises a seven-bed intensive care unit, a six-bed
high-dependency unit and a 32-bed general ward. Each ward has its
own dedicated staff and equipment. The seven single rooms available
are not exclusively reserved for MRSA-positive patients, although
where possible, such patients are nursed in these rooms. Approx-
imately 750 patients undergo cardiac surgery each year and the
average length of stay is 7.2 days. Elective patients are admitted
the day before their operation. The study population comprised pa-
tients undergoing cardiac surgery at the Southwest Cardiac Surgery
Unit between October 2004 and September 2006.
The Plymouth cardiac care pathway
An assay for MRSA screening of all preoperative cardiac surgery
patients was introduced as a quality improvement measure in
September 2005. The lack of a pre-assessment clinic meant that
determining MRSA status in advance of admission was difficult.
Rapid diagnostic testing for MRSA by real-time polymerase chain
reaction (PCR) was therefore performed on patients admitted the day
before surgery. A single nose swab was collected in Stuart’s medium
from each patient on admission. Topical MRSA suppression therapy,
consisting of na- sal mupirocin 2% ointment thrice daily and
topical triclosan 2%, was then immediately commenced pending the
result of the PCR assay. If the MRSA screening result was negative,
mupirocin and tri- closan were discontinued and the patient
received standard, previously used perioperative antibiotic
prophylaxis of a single dose of gentamicin (3e 5 mg/kg depending on
renal function) and flucloxa- cillin (1 g every 6 h for 24 h). If
the PCR result was positive, mupirocin and triclosan were continued
for five days (as per national guidelines for suppres- sion of
MRSA) and the patient was given single doses of gentamicin (3e5
mg/kg) and teicoplanin (400 mg) as perioperative prophylaxis.18
This latter regimen was followed for patients previously colonised
with MRSA regardless of any subsequent screening results, patients
with unknown MRSA status and patients who have been on the ward for
more than 96 h since their last screen.
126 S. Jog et al.
PCR-based MRSA screening
MRSA screening was performed with the Gene Ohm
MRSA Test (Becton Dickinson, Franklin Lakes, New Jersey, USA), run
on the Cepheid Smart Cycler as previously described.19 Briefly, a
single nose swab was processed Monday to Friday on the same day
according to the manufacturer’s instructions. Weekend samples were
processed the following Monday. An internal control detected the
presence of substances inhibitory to PCR. Positive and nega- tive
samples were included in each run. Any samples unresolved due to
PCR inhibitors were repeated after a single freezeethaw cycle on
the same DNA extract. All positive and unresolved swabs were
cultured and full susceptibility testing of MRSA isolates performed
using standard methods. Positive PCR results were reported as
provisional, pending the final results from culture.
Nasal swab culture and performance of the assay
The same nasal swabs used for the PCR assay were also cultured at
two different steps of the assay procedure. Direct culture was
performed onto chromID MRSA agar (bioMerieux, Marcy l’Etoile,
France) and enrichment culture was performed after the assay
procedure. For the latter, the swabs were incubated overnight in
trypic soy broth containing 6.5% NaCl at 35 C before subculture
onto chromID MRSA and 5% sheep blood agar (Oxoid, Basingstoke, UK)
with a 1 mg oxacillin disc.
Positive results for MRSA by the real-time PCR assay were
designated as true or false positives on the basis of nasal swab
cultures and whether the patient had any other cultures positive
for MRSA during a 7-day period before or after the date on which
the PCR was performed. In order to de- termine the extent of
colonisation, a full culture screen of nose, groin and throat swabs
was performed on patients found to be MRSA carriers by the PCR
method.
Infection control policies
Standard infection control procedures, such as ward audits and
education, and a daily ward round on the cardiac surgery unit by a
microbiologist (P.J.) continued unchanged. The National Patient
Safety Agency ‘Cleanyourhands’ campaign was launched across the
Trust in February 2005 and was piloted on the Cardiac wards from
June 2004. No changes in ward cleaning, disinfectant use, line care
or management of ventilators/endotracheal
tubes occurred during the control or study periods. Similar
precautions were taken when MRSA was isolated on the preoperative
screen or from a later culture in the patient’s stay. Patient case
notes and the computerised patient information system were tagged
with their MRSA status and standard infection control precautions
were reinforced. Patients were nursed in a single room if
available, but shortage of single rooms meant that this was not
always possible. Patients with evidence of MRSA infection were
usually treated with vanco- mycin and rifampicin.
Surveillance of surgical site infection
The outcomes were the overall rate of SSI follow- ing cardiac
surgery and those due to individual micro-organisms. Prospective
surveillance of SSI was performed by a dedicated surveillance clerk
using the protocol established by the English Health Protection
Agency.20 The following vari- ables were recorded: age, sex, dates
of admission, surgery and discharge, duration of operation, sur-
geon, underlying disease, use of immunosuppres- sive drugs,
American Society of Anesthesiologists score, use of topical
antimicrobials and antibiotic prophylaxis. During admission, the
clinical records of all patients were studied for the development
of SSI. After discharge from hospital, follow-up reviews were
performed in outpatient clinics. All patients were checked to see
whether they were readmitted to the hospital and whether this read-
mission was due to a wound infection. For SSI, the date of onset,
site (sternal or donor), type (super- ficial, deep or organ space)
and pathogens in- volved were recorded.
Statistical analysis
Data were analysed using the Chi-squared test. P< 0.05 was
considered significant. Koopman’s likelihood-based approximation
was used to con- struct confidence for relative risk.21
Results
Between October 2005 and September 2006, 765 cardiac operations
were performed at our hospi- tal. In total, 681 (89%) of these
patients were screened for MRSA using the real-time PCR assay. The
assay primers were changed part-way through the study and the
sensitivity and specificity of the assay using these
second-generation primers was 84.6% and 100% respectively (Table
I). The positive
Table I Results for the performance of the IDI testa
IDI result Culture result
MRSA negative 407 2 MRSA positive 0 11
a Sensitivity, 84.6% [95% confidence interval (CI): 60.5e 97.1%];
specificity, 100% (95% CI: 99.3e100%); positive pre- dictive value,
100% (95% CI: 77.9e100%); negative predictive value, 99.5% (95% CI:
98.4e99.9%).
Table III Micro-organisms causing surgical site infection (SSI)
before and after screening for meticil- lin-resistant S. aureus by
polymerase chain reaction
Micro-organism No. of SSIs before
screening
Meticillin-susceptible S. aureus 0 1 Coagulase-negative
staphylococci 5 5 Coliforms/Pseudomonas spp. 7 6 Other 3 3
Total 23 17 a P< 0.05.
MRSA PCR screening in cardiac surgery 127
predictive value was 100% and positive and nega- tive predictive
value 99.5% (Table I). Nineteen pa- tients were positive for MRSA,
giving a prevalence of MRSA colonisation in patients who underwent
cardiac surgery at our hospital of 2.5%. Of the 19 MRSA-positive
patients, 18 were screened prior to the surgery and one after the
procedure (a proced- ural error that occurred shortly after the
screening protocol was introduced). Topical MRSA suppres- sion
therapy and appropriate perioperative pro- phylaxis were prescribed
in 17 patients.
In the 12-month period before screening was introduced, 697
procedures were performed with an overall SSI rate of 3.30%, with
eight infections due to MRSA (Tables II and III). During the
12-month period following the introduction of screening, al- though
the overall SSI rate fell to 2.22%, this did not reach statistical
significance. However, there was a significant reduction in the
rate of MRSA infection from 1.15% to 0.26% (P< 0.05; relative
risk reduction 0.77; 95% CI: 0.056e0.95), which was independent of
any underlying risk factors (as defined by Gaynes et al.22). There
was no asso- ciated increase in the proportion of infections due to
other micro-organisms (Table III).
None of the patients identified preoperatively as being MRSA
carriers developed SSI or other postoperative infections due to
MRSA. Of the two MRSA SSIs that occurred after the introduction of
screening, one was a deep MRSA sternal wound infection that
occurred in a patient who was not
Table II Surgical site infection (SSI) rates 12 months before and
after screening for meticillin-resistant S. aureus by polymerase
chain reaction
Type of infection
Sternal Leg Total Sternal Leg Total
Superficial 1.72 0.29 2.01 0.79 0.39 1.18 Deep 0.43 0.14 0.57 0.52
0 0.52 Organ space 0.72 0 0.72 0.52 0 0.52
Total 2.87 0.43 3.30 1.83 0.39 2.22
screened preoperatively and did not receive top- ical suppression
therapy or teicoplanin prophy- laxis. The second occurred in a
patient who was MRSA PCR-negative preoperatively and was re-
admitted from another hospital with a deep MRSA sternal wound
infection 20 days after surgery. During the study, two other
patients, who were both MRSA-negative preoperatively, developed
MRSA infection at other sites: one at a chest drain site 26 days
after surgery and another at a trache- ostomy site 40 days after
surgery.
Discussion
Our study shows that rapid PCR screening is an effective method of
identifying nasal colonisation with MRSA in preoperative cardiac
surgery pa- tients. Similar results may be seen when screening is
performed using conventional culture methods. However, the
reduction in turnaround time gained using the PCR test is
substantial. This is particu- larly useful in situations when
pre-admission as- sessment of MRSA carriage by conventional methods
is impracticable and when patients are admitted shortly before
their procedure. Rapid screening on admission is also useful for
emer- gency cases and will identify MRSA acquisition that occurs
during the period between pre-operative assessment and admission
for surgery. Our study also shows that the use of decolonisation
regimens and targeted surgical prophylaxis is effective at
preventing MRSA SSIs in individuals colonised with this bacterium.
The addition of teicoplanin to standard perioperative prophylaxis,
as well as the use of topical suppression therapy, may explain why
we observed a significant reduction in MRSA SSIs whereas other
studies that have examined intranasal mupirocin alone have
not.23e25
128 S. Jog et al.
Compliance with the screening was high and was achieved through
education and incorporating the protocol into the patient surgical
care plan. In particular, a prompt to perform screening was added
to the admission checklist for nursing staff and reminder to check
MRSA status added to the anaesthetic preoperative assessment. The
preva- lence of MRSA carriage in this cohort was compar- able to
that reported in similar cardiac centres, as well as other local
elective surgical popula- tions.26,27 The sensitivity of the assay
reported by us was lower than that reported in other stud-
ies.28e30 All three patients with false-negative na- sal PCR
screens grew MRSA from concurrent groin swab cultures. Currently
the IDIeMRSA PCR assay is only validated for nasal specimens and
although combined processing of nose and groin swabs would avoid
such false-negative results, the over- all sensitivity of the assay
may be compromised when used for extra-nasal samples.30,31
Previous studies have demonstrated that the use of mupirocin to
suppress nasal carriage of S. aureus reduces SSI and is
cost-effective in patients under- going cardiothoracic
surgery.12e15 However, the risk of selecting mupirocin-resistant
strains has led to recommendations that prophylaxis be limited to
those found to be colonised with MRSA.32,33 The finding that none
of the patients identified as being MRSA carriers by screening
developed surgical site or other postoperative infections due to
MRSA sup- ports both the targeted use of measures to suppress this
organism at the time of surgery and the practice not to delay
surgery pending attempted eradication of the organism.
A total of four MRSA infections, including two SSIs, were observed
in patients who were either not screened or found to be
MRSA-negative by PCR. One MRSA SSI occurred in the first month of
the screening programme in a patient who was in- advertently not
screened and did not receive MRSA suppression therapy or
teicoplanin prophylaxis. The other MRSA SSI and two MRSA infections
at non-surgical sites were observed in patients who were found
preoperatively to be MRSA-negative by PCR. One of these three cases
had a negative MRSA PCR as well as a negative three-site culture
screen, and it is likely that this infection was acquired during
the postoperative period. Another patient who was found to be
MRSA-negative prior to surgery had a repeat nasal MRSA PCR test 33
days following surgery. This test was positive and screening swabs
revealed extensive colonisation with MRSA; the patient subsequently
developed an infection of the tracheostomy site. The PCR results
probably reflected the colonisation status of the patient and the
fact that infection occurred after
the surgical procedure. These cases emphasise that maintaining high
infection control standards throughout the patient’s stay in
hospital are essential to prevent acquisition of infection in the
period following surgery. The final patient, who was re-admitted
from another hospital with SSI, first had MRSA isolated from the
sternal wound. Although this infection may also have been acquired
following surgery, it is also possible that MRSA colonisation was
present preoperatively at an extra-nasal site and was not detected
by the PCR test.
Although the fall in the number of cases of MRSA was associated
with a reduction in the overall SSI rate, this did not reach
statistical significance. However, our data support previous
studies show- ing that suppression of MRSA does not result in a
significant compensatory increase in the rate of infections due to
other species.25 Similar results have been observed in the three
quarters following the study period, with 557 procedures performed
with an infection rate of 1.6% and no postoperative SSIs due to
MRSA. Furthermore, the number of MRSA bacteraemias has fallen from
nine in the year prior to the introduction of screening to three in
the last 12-month period.
This is an observational study, and consequently has many
limitations. We cannot exclude the possibility that changes in MRSA
epidemiology or management influenced infection rates. We can- not
identify any changes in antibiotic susceptibility or virulence of
MRSA over this period. We have not identified any changes in
patient management or infection control policy, and there were no
signif- icant changes in surgical personnel during the study
period. The cost of the assay is about £25.00, but should be
considered in the context of the cost of a deep sternal infection,
which we estimate locally to be more than £10,000. Our data predict
that it is necessary to screen 113 patients, at a cost of about
£2825, in order to prevent one MRSA SSI. We have not performed a
formal cost- effectiveness analysis, though the business case used
to obtain funding for this initiative predicted significant overall
savings with much smaller re- ductions in MRSA SSIs than we
subsequently ob- served. The business model used predicted
significant savings from targeted rather than uni- versal use of
mupirocin and teicoplanin. Restrict- ing the use of the agents to
those proven to be carriers of MRSA would also be expected to
reduce the likelihood of toxicity or the risk of an overall
increase in resistance.
Ultimately the benefits of rapid MRSA screening can only be
determined by large randomised controlled trials, with robust
economic analysis.
MRSA PCR screening in cardiac surgery 129
However, the results of this study suggest that preoperative
screening by real-time PCR has a sub- stantial impact on
postoperative MRSA SSIs in patients undergoing cardiac
surgery.
Conflict of interest statement None declared.
Funding sources None.
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Vigilancia Universal de MRSA (Robisek et al., 2007) y RT-PCR
• Vigilancia universal en un complejo de tres hospitales.
• Reducción significativa de las tasas de infección de MRSA en un
70 % en menos de dos años, en todas las categorías medidas:
infecciones sanguíneas, del tracto urinario, de herida quirúrgica y
respiratorias.
Control de MRSA: Vigilancia Universal
Universal Surveillance for Methicillin-Resistant Staphylococcus
aureus in 3 Affiliated Hospitals Ari Robicsek, MD; Jennifer L.
Beaumont, MS; Suzanne M. Paule, BS; Donna M. Hacek, BS; Richard B.
Thomson Jr., PhD; Karen L. Kaul, MD, PhD; Peggy King, RN, MBA; and
Lance R. Peterson, MD
Background: The effect of large-scale expanded surveillance for
methicillin-resistant Staphylococcus aureus (MRSA) on health care–
associated MRSA disease is not known.
Objective: To examine the effect of 2 expanded surveillance inter-
ventions on MRSA disease.
Design: Observational study comparing rates of MRSA clinical dis-
ease during and after hospital admission in 3 consecutive periods:
baseline (12 months), MRSA surveillance for all admissions to the
intensive care unit (ICU) (12 months), and universal MRSA surveil-
lance for all hospital admissions (21 months).
Setting: A 3-hospital, 850-bed organization with approximately 40
000 annual admissions.
Intervention: Polymerase chain reaction–based nasal surveillance
for MRSA followed by topical decolonization therapy and contact
isolation of patients who tested positive for MRSA.
Measurements: Poisson and segmented regression models were used to
compare prevalence density of hospital-associated clinical MRSA
disease (bloodstream, respiratory, urinary tract, and surgical
site) in each period. Rates of bloodstream disease with
methicillin- susceptible S. aureus were used as a control.
Results: The prevalence density of aggregate hospital-associated
MRSA disease (all body sites) per 10 000 patient-days at
baseline,
during ICU surveillance, and during universal surveillance was 8.9
(95% CI, 7.6 to 10.4), 7.4 (CI, 6.1 to 9.0; P 0.15 compared with
baseline), and 3.9 (CI, 3.2 to 4.7; P 0.001 compared with base-
line and ICU surveillance), respectively. During universal surveil-
lance, the prevalence density of MRSA infection at each body site
had a statistically significant decrease compared with baseline.
The methicillin-susceptible S. aureus bacteremia rate did not
statistically significantly change during the 3 periods. In a
segmented regression model, the aggregate hospital-associated MRSA
disease prevalence density changed by 36.2% (CI, 65.4% to 9.8%; P
0.17) from baseline to ICU surveillance and by 69.6% (CI, 89.2% to
19.6%]; P 0.03) from baseline to universal surveillance. During
universal surveillance, the MRSA disease rate decreased during hos-
pitalization and in the 30 days after discharge; no further
reduction occurred thereafter. Surveillance with clinical cultures
would have identified 17.8% of actual MRSA patient-days, and
ICU-based sur- veillance with polymerase chain reaction would have
identified 33.3%.
Limitation: The findings rely on observational data.
Conclusion: The introduction of universal admission surveillance
for MRSA was associated with a large reduction in MRSA disease
during admission and 30 days after discharge.
Ann Intern Med. 2008;148:409-418. www.annals.org For author
affiliations, see end of text.
Methicillin-resistant Staphylococcus aureus (MRSA) is now endemic
in many U.S. hospitals (1, 2). Colo-
nization with this organism is a risk factor for eventual MRSA
clinical infection (3), which is associated with high cost (4) and
poor clinical outcomes (5). The burden of health care–associated
MRSA disease is high and may be increasing: In their multiregion
survey of invasive MRSA disease, investigators for the Centers for
Disease Control and Prevention noted substantial increases in both
com- munity- and health care–associated infections at several sites
when comparing data from 2001 to 2002 with data from 2004 to 2005
(6). Driven by the emerging concern that community-associated MRSA
has entered the hospital environment (7), the medical community and
the public are seeking to limit the spread of this organism with
in- creasing urgency (8). In the United Kingdom, the De- partment
of Health has instituted mandatory reporting of MRSA infections in
hospitals (9), and in the United States, state legislatures are
considering (or have passed bills) requiring active surveillance
for MRSA (10 –12). Consumer organizations (13) and the media (14)
also seek action. The Healthcare Infection Control Practices
Advisory Committee of the Centers for Disease Control and
Prevention (15) recently published guidelines rec-
ommending expanded surveillance of asymptomatic pa- tients in
settings in which multidrug-resistant organisms are poorly
controlled with other measures. However, the evidence supporting
this practice is limited to surveil- lance on circumscribed (for
example, intensive care only) populations in small, single-center
studies at large academic hospitals (16 –18).
Because rates of MRSA infection remained unaccept- ably high
despite conventional interventions, we imple- mented expanded
surveillance at our 3-hospital health care organization in 2 steps.
For 12 months, we implemented organization-wide, intensive care
unit (ICU)–based MRSA
See also:
Print Editors’ Notes . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . 410 Editorial comment. . . . . . . . . . . . . . . . .
. . . . . . . . . 474 Summary for Patients. . . . . . . . . . . . .
. . . . . . . . . . I-46
Web-Only Conversion of graphics into slides Audio summary
Annals of Internal Medicine Article
© 2008 American College of Physicians 409
surveillance. On 1 August 2005, we initiated the first pro- gram
(to our knowledge) of universal surveillance of all hospital
admissions in the United States. We aimed to determine whether
expanded surveillance was associated with changes in the rate of
MRSA clinical disease.
METHODS
We measured the utility of expanded surveillance for MRSA by using
a 3-period before-and-after design (Figure 1). Period 1 (no active
surveillance) was the baseline. In periods 2 and 3, we introduced
ICU-based surveillance and universal admission surveillance,
respectively. We com- pared MRSA disease rates during and after
hospitalization in the 3 periods.
Outcomes The primary outcome was aggregate hospital-associ-
ated MRSA infection rate, defined as the sum of all MRSA
bloodstream, respiratory, urinary tract, and surgical site clinical
infections occurring more than 48 hours after admission through day
30 after discharge. Secondary outcomes were rates of health
care–associated MRSA and methicillin-susceptible Staphylococcus
aureus (MSSA) bac- teremia, rates of aggregate MRSA infections
occurring up to 180 days after discharge, and adherence to MRSA
sur- veillance. We defined adherence as the percentage of ad-
missions (ICU or whole house, depending on the period) in which
surveillance testing was done.
Study Sites Evanston Northwestern Healthcare, Evanston,
Illinois,
is a 3-hospital organization with approximately 40 000 an- nual
admissions, 75 affiliated off-site offices, 450 staff phy- sicians,
and more than 1000 affiliated physicians. Hospital 1 is an academic
facility with several residency programs, 476 beds, and a high
proportion of surgical patients. Hos- pital 2 is a primary care
teaching hospital with 143 beds
Context
Contribution
After a baseline year, the authors screened all intensive care unit
admissions for MRSA colonization using polymer- ase chain reaction.
In year 3, they screened all hospital admissions. They placed
patients who tested positive for MRSA on contact precautions. The
prevalence density of MRSA clinical infection was 8.9, 7.4, and 3.9
per 10 000 patient-days in years 1, 2, and 3, respectively.
Methicillin- sensitive S. aureus infection rates did not
change.
Caution
Implication
Screening for MRSA colonization is associated with sub- stantially
reduced rates of MRSA clinical infection.
—The Editors
Routine Therapy for Colonization
Follow-up for MRSA Disease
Period 3
Aug 05
Apr 07
180 days after discharge (less if discharged in final 180 days of
period)
ICU intensive care unit; MRSA methicillin-resistant Staphylococcus
aureus.
Article Universal Surve