Superstar of Antibiotic Resistance
MRSA
Created for Advanced Pathology/Physiology
Alverno College
MSN 621, Spring 2008
Shelly Schwingle, RN, BSN, CAPA
sasquilter@yahoo.com
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Objectives
Identify the two types of MRSA
Identify the three ways MRSA is transmitted
Describe the role of the general stress response in
MRSA pathogenesis
Describe the role of the immune system in MRSA
pathogenesis
Discuss the potential role of genetics in the
treatment of MRSA
What is MRSA ?
MRSA is the acronym
for
Methicillin -resistant
Staphylococcus Aureus
Image from Microsoft Clip art
Photo by www.flickr.com/photos August 15, 2005
Lets examine the characteristics of
Staphylococcus aureas (S. aureas)
S. aureus is a bacteria commonly
found on the skin, in the nose, or
perineum of healthy individuals.
About 30% of healthy populations
persistently carry the bacteria in their
anterior nares.
If you are a healthy carrier of
staphylococcus bacteria, you are
considered “colonized”.
Banning, 2005, p. 548
Stirling, Littlejohn, & Willbond, 2004, p. 19
Gould & Chamberlaine, 1995, p. 5
Image from Microsoft Clip art
S. aureus can develop into two types of
MRSA
HA is hospital acquired
CA is community acquired
Images from Microsoft Clip art
Epidemiologic Classification of
Invasive MRSA
Classification
Health care associated
Community onset
Definition
Cases with at least 1 of the
following healthcare risk factors
1. Presence of an invasive device at
time of admission
2. History of MRSA infection or
colonization
3. History of surgery, dialysis,
hospitalization, or residence in a
long term care facility in previous
12 mo preceding culture date
Klevens, et al., 2007, JAMA, p. 1765
Epidemiologic Classification of
Invasive MRSA
Classification
Hospital onset
Community Associated
Definition
Cases with positive culture
result from a normally sterile
site obtained > 48 h after hospital
admission. These cases might also
have > 1 of the community onset risk
factors.
Cases with no documented community
onset health care risk factor
Klevens, et al., 2007, JAMA, p. 1765
Microbe Resistance
Regardless of the type of MRSA, HA or CA, the
antimicrobial resistance is related to two major
forces:
1. The outstanding genetic diversity of S. aureus
and the ability to transfer resistance among
bacteria.
2. The selective pressures of antibiotic use.
Trnobranski, 1998, p.395
4 Inpatient MRSA Case Examples 3/20/08
Identify what they have in common?
Gender
1.
F
Age
53
MRSA Location
Nares
on admit
to hospital
Health Hx
Hypertension / Diabetes
Dialysis / ↑ cholesterol / CHF
CAD / obesity / L BKA
2.
M
74
Nares
on admit
to hospital
CAD / Cancer esophagus
Renal failure / COPD
Diabetes / Hx DVT / Stroke
3.
M
87
Nares
on admit
to hospital
Diabetes / Nephrectomy
Hypertension / CAD / Stroke
Kidney disease / Cancer
4.
M
53
Nares
on admit
to hospital
CA-MRSA cellulitis L hand 2007
R facial cellulitis currently
Please move forward to next slide for answers
Inpatient MRSA Case Examples
Hover the mouse on these common features from
the case examples to learn more;
1. age
2. gender
3. location of MRSA
4. multiple co – morbidities
Kenner, et al., 2003, p. 440
HA-MRSA Prevalence
Click on each bar for information
Bacteremia
Pneumonia
Extremes of age
Intensive antibiotic therapy
Dialysis
Co-morbidities
Surgical wounds/incisions
Invasive medical devices
CA-MRSA Case Examples
Identify what they have in common?
Gender
Age
MRSA Location
1.
M
53
Nares
R facial cellulitis currently (3/08)
L hand cellulitis CA-MRSA (5/07)
2.
M
16
R hand cellulitis
Day Surg Tonsillectomy (3/21/08)
Hockey player
3.
F
54
Groin/buttock
Boils
Beaten/abrasions in groin (10/07)
cracked/abcessed tooth
↑ BP / ↑ cholesterol
4.
M
2yr-9mo
R middle ear
Nares Neg
6 weeks abx/no response (9/07)
2xs inpt for resp infection/distress
Bilat Ear tube placement (12/07)
Skin test positive TB (5/27/05)
In day care
Please move forward to next slide for answers
Health Hx
CA-MRSA Case Examples
Hover the mouse on common features from
the case examples;
1. Age
2. Nothing !
3. Location of MRSA
4. Co - morbidities
Incidence of CA-MRSA
Varies by age
Varies by race
6% of infections are invasive in nature
77% are skin & soft tissue
24% of CA-MRSA require hospitalization
Klevens, et al., JAMA, 2007, p. 1769
Kollef & Micek, 2006, p.163
Non MRSA
S. aureus skin infection
Note raised pustules, small
area erythema around pustules
No significant swelling present.
Please see next slide for
comparison to skin & soft
tissue infected with MRSA
Photo by www.flickr.com/photos December 19, 2007
Different sites of skin & soft tissue
CA-MRSA infection
Deep ruptured pustule, swelling,
erythema surrounding pustule.
Diffuse redness into surrounding
tissue. Usually are very painful.
Photos by www.flickr.com/photos September 23, 2007
Please select True or False on these
questions about MRSA
• T F
MRSA is the acronym for Methicillin resistant staphylococcus aureus.
• T F
There are two types of MRSA, hospital
acquired and community acquired.
• T F
Hospital acquired MRSA can lead to health
problems such as pneumonia, bacteremia,
and delayed wound healing.
• T F
Community acquired MRSA develops in skin
and soft tissue injuries.
S. aureus/ MRSA virulence
Infections caused by S. aureus range in severity from trivial to
life threatening and in any body part.
“All MRSA strains contain a mecA gene and regulatory
sequences that code for the production of penicillin
binding protein (PBP2a)” This is what makes S. aureus
resistant to β-lactam antibiotics.
Kollef & Scott, 2006, p.163
Genetic Identification of MRSA
A hospital & community acquired
MRSA study conducted in 7
urban areas in the United
States from July 2004 through
Dec 2005….
Identified
10 different genotypes of MRSA !
Klevens, et al., JAMA, 2007, p. 1769
Image from Microsoft Clip art
Genetic Identification and
MRSA virulence
CA-MRSA possess different exotoxin genes
than HA-MRSA
Identified as the PVL gene (panton-valentine
leukocidin) it is the “dermonecrotic cytotoxin”
– 77% CA MRSA contain the PVL gene
– 4% HA MRSA contain the PVL gene
Klevens, et. al., 2007, JAMA, p. 1764
Kollef & Micek, 2006
Role of Bacterial Genetics
Gaining an understanding of bacterial genetics is
providing small clues to assist in the treatment of
individuals colonized and infected with MRSA.
Image from Microsoft Clip art
S. aureus/ MRSA virulence
In conclusion; “any S. aureus genotype that is
carried by humans can transform into a lifethreatening human pathogen”
This transformation occurs by the natural population
dynamics and virulence of the staphylococcus
bacteria.
Kumar et al., 2006, p.423
The Environment
“MRSA lives on skin and survives on
objects and surfaces for more than
24 hours”
©1999-2006 Georgia Department of Human Resources,
Division of Public Health
http://health.state.ga.us/pdf/publications/factssheets/M
RSA_FactSheet.pdf accessed March 2, 2008.
Images from Microsoft Clip art
MRSA Methods of Transmission
Can you name 3 methods of transmission?
The picture provides the clue, click on the bacteria to learn more.
1.
2.
3.
Images from Microsoft Clip art
Please select True or False on these
questions about the environment
• T F
MRSA can live on environmental
surfaces for up to 24 hours.
• T F
The main method of transmission of
MRSA is through skin to skin contact.
• T F
Hand washing is the primary method to
interrupt transmission of MRSA.
Who is the
Host for
S. aureus?
Young or old
Any ethnicity
Any gender
Images from Microsoft Clip art
Who
is the
Host?
Outpatient
Healthy
Co-morbidities
Inpatient
Images from Microsoft Clip art
What allows S. aureus to invade
us, the host?
Image from Microsoft Clip art
What allows S. aureus to invade us?
“S. aureus is one of the most successful human
pathogens with the ability to colonize and
infect both hospitalized patients, with or
without compromised host defenses, and
healthy immunologically competent people in
the community”
Kumar, et at., 2006, p. 418
“
S. aureus can become invasive given the
appropriate circumstances”
van Belkum, 2006, p. 341
What allows S. aureus to invade us?
Homeostasis of the host’s external environment
does exist with S. aureas on our skin and
colonized MRSA in our nares.
Let’s explore the host’s internal cellular
environment.
Image from Microsoft Clip art
The General Stress Response
Hans Seyle described stress as;
“a state manifested by a specific syndrome of the
body developed in response to any stimuli that
made an intense systemic demand on it”
Porth, 2005 p. 189
The General Stress Response
Seyle identified
the hypothalamus/pituitary/adrenal axis (HPA)
as playing a major role in the cellular response to
stress that originated both externally and internally
Image from Microsoft Clip art
Long term stress due to chronic illnesses ultimately results in a
decrease in the immune response as illustrated by this graph
Stressor
(threatening homeostatsis)
Hypothalamus
↓
Release of Corticotrophin Releasing Hormone
Anterior Pituitary
↓
Secretion of Adrenocorticotrophic Hormone
Adrenal Cortex
Mineralocorticoids
salt & water retention
↑ blood volume
↑ blood pressure
Glucocorticoid
↑ blood glucose
↑catabolism of fat & protein
↓ inflammatory response
↓ immune response
Longer term response to stress
Adapted and used with permission, Payne, 2005, p. 7
The Role of the
General Stress Response
“Organ systems become progressively less capable of
maintaining homeostasis in the face of stresses imposed by the
environment, disease, or medical therapies”
Environmental influences
Social support
Smoking
Dietary habits
Physical activity
Alcohol consumption
Internal influences
Age
Gender
Genetics
Capezuti, et al., 2008, p. 431
The Role of the
General Stress Response
Let’s look back at the chronic diseases our inpatients from the
case studies had diagnosed.
CAD
Diabetes
COPD
Kidney disease
Dialysis
Obesity
Cancer
Stroke
“Chronicity and excessive activation of the stress response can
result from chronic illnesses as well as contribute to the
development of long-term health problems”
Porth, 2005, p. 196
Co-morbidities do place the patient at an↑ risk to develop MRSA,
but exactly why remains to be answered.
Cosgrove, 2005
The Role of the
General Stress Response
Let’s look back at the CA MRSA case examples and possible risk factors and/or
the role of the stress response.
1.
Facial cellulitis, previous MRSA cellulitis, probably a colonized carrier, was
Nare positive on admission. Patient had recently returned from vacation.
2.
Immunologically competent. Shared sports equipment, hockey glove.
3.
External stress from abusive relationship and soft tissue injury/abrasions.
4.
Extreme of age (2 yr old) immature immune system, multiple antibiotic
exposure, indwelling ear tubes, hospitalized twice in past 18 months, in
day care, TB skin positive.
don’t remember the cases ?
Click back to view slide on case examples
The Role of the
General Stress Response
“Disease manifestation is the culmination of complex
interactions between the pathogen, host and
environment, and a number of agent and host
factors”
Kumar, 2005, p. 419
“It is still not clearly understood what decides a
superficial/localized infection while in others the
pathogen disseminates to produce deep seated or
generalized infections”
Kumar, 2005, p.419
Please answer True or False to the role of the
stress response in the development of MRSA
• T F
Sustained external or internal stress
on our body can create an imbalance
in homeostasis of our bodies.
Role of the Immune System
“Surprisingly little is known about the
immune mechanisms that give rise
to neutral colonization or infection”
van Belkum, 2006, p. 342
“The current opinion, however, is that
too little is known about the impact
of virulence factors … on the
inflammatory response to S. aureus
infections let alone colonization”
van Belkum, 2006, p. 342
Image from Microsoft Clip art
Future Strategies
Current strategy involves interfering with nasal
carriage to prevent autoinfection.
Also combined research on human innate
immunity and bacterial virulence may be
useful in the development of treatment plans.
Exploration of the pathogen’s genetic structure
to aide in the development of a vaccine.
Hayney, 2002, p. 1626
Future Strategies
Pharmacogenomics
The use of genetics provides the
opportunity to identify new drug targets
in both the host and pathogen.
The interactions of genetics between the
host and pathogen adds another layer
of complexity to an already complex
epidemiology mixture of host,
pathogen, and the environment.
Hayney, 2002, p. 1626
Image from Microsoft Clip art
Please answer True or False to the questions on
the immune response and the role of genetics
and MRSA
• T F
The exact human immune
mechanisms involved with a MRSA
invasion are known.
• T F
Current research involves examining
the human innate immunity system as
well as the virulence of the S. aureus
bacteria.
• T F
The potential identification and role of
human genes in infectious disease may
provide new drug targets.
Thought to Ponder….
Theodosius Dobzhansky (1900 - 1975) helped lay
the intellectual foundation of modern evolutionary
theory states…
“Nothing in biology makes sense except in the light
of evolution”
Bacterial resistance is the product of natural
selection. Unfortunately for us, bacteria evolve
quicker than humans.
Fairclough, 2006, p. 72
Conclusion
click for answers
Host
Most significant action
to control the spread
of MRSA
Environment
Is anyone
S. aureus bacteria
Is anywhere
hospital or community
setting
Always adapting
and evolving
Image from Microsoft Clip art
References
• Banning, M. (2005). Transmission and epidemiology of MRSA: current
perspectives. British Journal of Nursing, 14(10), 458-554.
• Boyce, J., Havill, N., Kohan, C., Dumigan, D., & Ligi, C. (2004). Do
infection control measures work for methicillin-resistant
staphylococcusaureus? Infection Control and Hospital Epidemiology
25(5), 395-401.
• Capezuti, E., Zwicker, D., Mezey, M., Fulmer, T. (2008). Evidence-based
geriatric nursing protocols for best practice. 3rd ed., Springer Publishing
Company, New York.
• Cosgrove, S., Qi, Y., Kaye, K., Harbarth, S., Karchmer, A., Carmeli,Y.
(2005). The impact of methicillin resistance in staphylococcus aureus
bacteremia on patient outcomes: mortality, length of stay, and hospital
charges. Infection Control and Hospital Epidemiology, 26(2), 166-174.
• Dawes, J. (2007). Over prescribing of antibiotics continues. British Journal
Community Nursing, 12(8), 333.
• Fairclough, S. (2006). Why tackling MRSA needs a comprehensive
approach. British Journal of Nursing, 15(2), 72-75.
References
• Georgia Department of Human Resources, Division of Public Health
©1999-2006, accessed March 2, 2008.
http://health.state.ga.us/pdf/publications/factsheets/MRSA_FactSheet.pdf
•
Gould, D., Chamberlaine, A. (1995). Staphylococcus aureus: a review of the
literature. Journal of Clinical Nursing, 4(1), 5-12.
• Hayney, M. (2002). Pharmacogenomics and infectious diseases: impact on
drug response and applications to disease management. American
Journal of Health-System Pharmacy, 59(1), 1626-1631..
• http://www.flickr.com/photos/11873114@N03/2123391468
• Kenner, J., O’Connor, T., Piantanida, N., Fishbain, J., Eberly, B., et al.
(2003). Rates of carriage of methicillin-resistant and meticillinsusceptible staphylococcus aureus in an outpatient population.
Infection Control and Hospital Epidemiology, 24(6), 439-443.
• Klevens, R., Morrison, M., Nadle, J., Petit, S., Gershman, K., et al. (2007).
Invasive methicillin-resistant staphylococcus aureus infections in the
united states. Journal of the American Medical Association, 298(15),
1763-1771.
References
• Kollef, M., Micek, S. (2006). Methicillin-resistant staphylococcus
aureus: a new community-acquired pathogen? Current Opinion in
Infectious Diseases, 19, 161-168.
• Kumar, A., Ray, P., Kanwar, M., Sharma, M., Varma, S. (2006). Analysis
of genetic diversity among staphylococcus aureus isolates from
patients with deep-seated and superficial staphylococcal infections
using pulsed-field gel electrophoresis. Scandinavian Journal of
Infectious Diseases, 38, 418-426.
• Payne, R. (2005). Relaxation techniques: a practical handbook for the health
care professional. 3rd ed., Elsevier, London.
• Porth, C. (2005). Pathophysiology: concepts of altered health states.
Lippincott, Williams & Wilkins, Philadelphia, PA.
• Romero, D., Treston, J., Sullivan, A. (2006). Hand to hand; preventing
MRSA. The Nurse Practitioner, 31(3), 16-23
• Stirling, B., Littlejohn, P., Willbond, M. (2004). Nurses and the control of
infectious disease. Canadian Nurse 100(9), 17-20.
References
• Trnobranski, P. (1998). Are we facing a “post-antibiotic era”?-a review of the
literature regarding antimicrobial drug resistance. Journal of Clinical
Nursing, 7, 392-400.
• van Belkum, A. (2006). Staphylococcal colonization and infection:
homeostasis versus disbalance of human innate immunity and bacterial
virulence. Current Opinion in Infectious Diseases, 19, 339-344.
• Yao, Y., Vuong, C., Kocianova, S., Villaruz, A., Lai, Y., Sturdevant, D., Otto,
M. (2006). Characterization of the staphylococcus epidermidis
accessory-gene regulator response: quorum-sensing regulation of
resistance to human innate host defense. The Journal of Infectious
Diseases, 193(March 15), 841-848.
The End
Bacteremia
MRSA is the 2nd leading cause of bloodstream
infections in the United States
Mortality rate is 15 - 60% among patients with
MRSA bacteremia.
Chronic lung disease and renal disease are more
likely to exist in patients with MRSA bacteremia.
Cosgrove, et al., 2005
Pneumonia
HA-pneumonia is the 2nd most common cause of hospital
acquired infection.
HA-pneumonia has a mortality rate of 20-50%
People at greatest risk are
– Ventilator dependant
– Compromised immune system
– Chronic lung disease
Porth, 2005, p. 669
Surgical wounds/incisions
MRSA competes with damaged tissues for oxygen
and nutrients.
MRSA converts soluble fibrinogen to insoluble fibrin
which causes blood around the bacteria to clot,
thereby protecting it from phagocytosis.
MRSA produces extracellular proteins, toxins, and
enzymes which enhance its virulence and delays
wound healing.
Banning, 2005
Invasive medical devices
S. aureus is the most frequent cause of infections
due to indwelling medical devices.
S. aureus develops “sticky bacterial agglomerations”
on implants which decreases the effect of
antibiotics and the host’s immune defenses.
Yao, et al., 2006, p. 841
Intensive antibiotic therapy
Over prescribing of antibiotics is adding to the growing
resistance of micro-organisms.
Many people still believe that antibiotics are effective against
viral infections.
Many people do not take their antibiotics as prescribed or
finish the full course.
HA-MRSA is resistant to multiple antibiotics.
Vancomycin is first line therapy for infections caused by
MRSA. Therapy decisions based on culture sensitivity.
Dawes, 2007, p. 333
Co-morbidities
Co - morbidities place the patient at increased risk
to develop MRSA.
On average MRSA patients with bacteremia have
3 co - morbidities
–
–
–
–
–
–
–
–
Cancer
Cardiovascular disease
Chronic lung disease
Diabetes
Liver disease
Renal disease
Transplant
Dialysis patient
Cosgrove, 2005, p.168 &169
Extremes of age
Many older people have co - morbidities.
Elders are more susceptible to infections.
Elders have a decreased/slower immune response to
infections.
Infants have an immature immune system.
Infants are more prone to bacterial sepsis.
Porth, 2005, p. 35 & 384
Dialysis
The vascular access site is the most
common site for infection.
Pts with nasal carriage of MRSA have ↑ risk
of vascular access devise infection.
Arduino & Tokars, 2005
Transmission of Staphylococcus Bacteria
by direct contact from contaminated hands
hand hygiene is the single
most important behavior to
prevent cross infection
Hands should be washed
between patients
When moving from a
contaminated body site to a
clean site on the same
patient
Hover mouse over picture for more information
Image from Microsoft Clip art
Areas most frequently missed
when washing hands
British Journal of Nursing, 2005, p. 540
Transmission of
Staphylococcus Bacteria
microbial fallout (droplets) from colonized patients
sneezing or coughing places the microbe in a
perimeter on and around the patient.
“Studies with slit sampler to detect evidence of air
borne dissemination suggested that if airborne
spread occurred at all, it must operate over short
distances only, no more than a few feet”
Gould, 1995, p. 8
It is helpful for staff to realize the location of
contamination around the patient and on
equipment.
Image from Microsoft Clip art
Hospital Surfaces
Surfaces
“…patient bed linen and gowns, over - bed tables,
blood pressure cuffs, and bedside rails may
become contaminated with MRSA”
“Health care workers can contaminate their gloves,
and presumably their hands, by touching such
contaminated objects, even when there has been
no direct contact with patients”
Boyce, et al., 2004, p.397
Hospital Surfaces
X
X
X
X
X
X
X
X
used with permission; APells, 2008
ProHealthcare
Faucet Over bed table
Handles
Bed railings
Door handle
Call light
Light switches
Phone
Community Surfaces
“Skin to skin contact involving abrasions and indirect contact with
contaminated objects such as towels, sheets, and sports
equipment seem to represent a mode of transmission”
Banning, 2005, p.551
Images from Microsoft Clip art
Wear long sleeves and pants
wash surfaces before and after working out
Shared sports equipment
Image from Microsoft Clip art
Community Settings
Jails, Daycare, Schools
Images from Microsoft Clip art
CA-MRSA Case Examples
Identify what they have in common?
Gender
Age
MRSA Location
Health Hx
1.
M
53
Nares
R facial cellulitis currently (3/08)
L hand cellulitis CA-MRSA (5/08)
2.
M
16
R hand cellulitis
Day Surg Tonsillectomy (3/21/08)
Hockey player
3.
F
54
Groin/buttock
Boils
Beaten/abrasions in groin (10/07)
cracked/abcessed tooth
↑ BP / ↑ cholesterol
4.
M
2yr-9mo
R middle ear
Nares Neg
6 weeks abx/no response (9/07)
2xs inpt for resp infection/distress
Bilat Ear tube placement (12/07)
Skin test pos TB (5/05)
To return to The Stress Response Slide, click on