Transcript Methicillin Resistant Staphylococcal Aureus: An Emerging Threat

Methicillin Resistant Staphylococcal
Aureus: An Emerging Threat With
Increasing Pathogenicity and Antibiotic
Resistance
By: Cortney A. Stringer, PA-S
Mentor: Dr. Frank Romanelli
WHERE IT IS
Colonizes 1/3 US population
Salt and heat tolerant up to 140 degrees
Fahrenheit
S. aureus can be opportunistic to cause infection
dwelling on inanimate objects for up to 2 mos
(Bauman, 2004)
Prevalent in hospital settings, termed hospital
associated (HA)MRSA
Smaller incidence in community setting with
historically less pathogenicity and resistance, CAMRSA
HA-MRSA
Can spread via contaminated hands or garments
of healthcare workers to vulnerable patients
Secondary transmission from contaminated
objects and hospital equipment
Immunocompromised patients are a particular
target
Pts with HIV, CA, diabetes, pneumonia,
dermatological abrasions or psoriasis, and
dialysis pts; pts needing routine procedures with
catheters, post op pts introduced to prosthetics
CA-MRSA
Strains of MRSA that have arisen in community apart from
nosocomial strains
Becoming a more frequent occurrence
Among people having healthcare contact or no healthcare
contact
Babies coddled by healthcare parents, esp problem with
small immunities
School age children spreading bacteria to classmates
Locker rooms and athletic equipment in gyms and
organized sports leagues
Nursing homes, rehabilitation centers, prisons
CA-MRSA
Until recently, MRSA infections in community
have presented as skin infections perhaps
necessitating I&D and sometimes Abx
prophylaxis
These strains resembling HA counterparts
molecularly and in morbidity/mortality
consequence
Other infections are including diseases of
increased severity (e.g. sepsis, endocarditis,
pulmonary emboli, extensive soft tissue
infections, bone destruction)
Baba, et. al studies
CA-MRSA
41 strains typified using BURST technology
and are mutating to resemble HA strains
Strains including SCC type III and IV
Concluded that type IV SCC strains
exhibited increased mobility and thus
increased propensity for genetic diversity
CA-MRSA bigger
problem?
ALL type IV strains demonstrated
resistance to one additional Abx aside from
beta lactams and 3 of such strains
demonstrated multi dx resistance
In addition, such CA-MRSA strains were
differentiated from others with 19 more
genes for virulence
HOW DID WE GET TO THIS
POINT?
S. aureus
Evolutionary HX
Incidents of resistance to penicillin first reported
in 1920s
By 1940s nosocomial resistance approaching
25%
Methicillin introduced in 1959
By 1961 United Kingdom reports MRSA
By 1970s MRSA reported in 25% of
hospitalized pts (CDC 2001)
HX cont.
Staphylococcus aureus first evolutionary change
included a penicillinase enzyme to inactivate the beta
lactam ring, the bactericidal element of penicillin
Next change, mecA gene that encodes for altered
penicillin binding protein. This mecA gene resides
within a mobile cassette chromosome (SCC element),
allowing for easy evolutionary change. As a locus on
SCC, the mecA gene can code for resistance and
pathogenicity to transfer to descendent staph strains
Result, penicillin and other beta lactam ring Abx
useless (Enright, et al)
HX cont.
Some researchers think MRSA strains
originated from a single methicillin
susceptible s. aureus (MSSA) progenitor
Others hypothesize that these methicillin
resistant strains stem from many different
MSSA ancestors
Studying Lineage
Desirable because determining MRSA lineage
from MSSA with respect to mutations can enable
prediction of future strains can generate better tx
options
912 typified staphylococcus aureus strains
Results show that these strains have developed
genetic components allowing for easy
transmission into hospitals, and then acquisition
of mecA
Researchers (Enright, et. al) tell of “depressing
evolutionary resistance” if this mechanism occurs
with vancomycin
Another study reports 8 case studies of s. aureus
infections with vancomycin resistance (Chang et.
al)
Elements for
pathogenisis
Via enzymes and toxins
Hyaluronidases potentiate infection by attacking
ground membranes of connective tissue
Kinases activates plasmin, which prevents blood
clotting with fibrinolysis. bacterial diffusion can
occur in absence of clotting factors
Hemolysins lyse RBCs
Lipases digest lipids allowing for colonization on
skin surfaces and oil glands
PATHO elements
cont.
Staphylococcal coagulase perhaps
contribute to virulence by providing
antigenic disguise preventing the
recognition of bacterial antigen surfaces
Protein A molecule inhibits phagocytic
ingestion
Beta lactamase facilitates survival in face
of Abx
Toxins of
pathogenesis
Cytolytic toxins disrupt cell membranes by
lysing phagocytes and granules involved in
immunological defenses
Exfoliate toxins dissolute desmosomes that
bridge skin cells to one another resulting in skin
flaking and sloughing
TSS, toxic shock syndrome, toxin causing N/V
similar to food poisoning
Panton-Valentine Leukocidin ass. with extreme
virulence (e.g. necrotizing pneumonia)
Studying Pathology
A Rocky Mountain Lab group suggests that the
PVL toxin cannot be causative of extreme
virulence
Studies have shown s. aureus infections result in
similar presentations with or without the PVL gene
(Voyich, et. al, 2006)
Another thought, MSSA has same propensities
and molecular mechanisms to cause disease as
MRSA, and with developing Abx resistance
opportunism for infection occurs when tx fails
(Layer, et.al, 2006)
What it looks like
Clinical Significance
Skin infections include impetigo, folliculitis,
carbuncles, styes or boils
Other skin infections include furuncles and
abscesses can begin as painful red
papules with surrounding erythema and
can develop necrotic centers (Dale,
Federman 2007)
Clinical Significance
cont.
More serious problems include penetration
beyond cutaneous and soft tissue
manifestations
(e.g. pneumonia, deep abscesses,
osteomyelitis, endocarditis, phlebitis, mastitis,
and/or meningitis, Baron, et. al)
Atypicals include toxic shock syndrome,
bacteremia, endocarditis, pneumnoia,
osteomyelitis, necrotizing fasciitis
Such disease states are becoming
consequence of CA-MRSA infections, no
longer limited to hospital settings and very
sick populations representative of HAMRSA
In many of these cases, complications
arise with the absence of underlying
medical conditions and mortality rates are
approaching 64% (Crum, 2004)
Epidmiology
HA MRSA infections have increased from
2% in 1974 to 22% in 1995 (CDC, 2007)
and to 64% in 2004
Each year from the years 2001 to 2003 12
million people were treated for soft tissue
infections attributed to s. aureus (CDC,
2007)
Studying the Epi
94,000 acquire invasive MRSA ea year,
with a death toll of 19,000 (Klevins, et. al)
Media reports that MRSA kills more than
AIDS
9 metropolitan areas were followed for
more than a year concluding in a statement
that MRSA is a serious problem affecting
populations disproportionately
AMA says...
MRSA is no longer a problem confined to
intensive care units, but a problem affecting
31.8 per 100,000 people
During the course of surveillance 8987
cases of MRSA
58.4% HA, 26.6% CA, 1.3% undetermined
(Klevins, et. al)
How to treat
Trimethoprim sulfamethoxazole/Bactrim usually
a successful DOC
With more severe infections with debridgment
or necrosis of soft tissue increased chance of
systemic illness--signs to recognize are fever,
chills, fatigue, muscle aches, H/A, and/or rash
In such cases of threatened systemic illness,
determine the strain type and origin b/c tx is
different
TX
For more aggressive CA-MRSA infections tx
with Bactrim, doxycycline, minocycline,
rifampin,or Zylox for very resistant strains
Tx for active HA-MRSA infections include
paraenteral Abx, vancomycin, clindamycin,
linelozid, or combo dxs
Additional outpt tx should include keeping nails
short and clean, change sleepwear, linens,
towels, and wash cloths;
TX
Mupirocin/Bactroban ointment BID to eliminate
nasal carriage
Bleach/water solution for skin colonization BID,
twice a week for 15 min
Hibiclens soap
Oral Abx for ten days, followed by rifampin
10mg/kg/dose BID for two days
Tx family members and pets too
In England and
Wales
Things I don’t think
you’ve
heard
New treatments
with honey and maggots
Groups are questioning the benefit of
circumcision when s.aureus presence in hospitals
is increasing
Can MRSA be a sexually transmitted infection?
Streptococcus has historically been causative
organism for ‘flesh eating virus’ infections, yet
new research shows s.aureus cultured from such
wounds
MRSA strains responsible for outbreak type
In
Conclusion
MRSA publications on the rise
No doubt Abx resistance has been problem
for years
Now evidence of increased virulence
Evidence of increased incidence, though it
is difficult to ascertain true numbers without
cohesive federal tracking
No standard/law to report MRSA infections
in hospitals. It is not classified as a
In Conclusion
DO WE KNOW THE TRUTH?
To what degree is the severity? More
research needed.
Can we gage the problem accurately? (i.e.
hospitals not reporting or under reporting)
Despite varying incidence numbers among
population, AMA says it best, I think.
Affects populations disproportionately.
Nonetheless, a problem you will encounter.
•
2
•
8
•
•
Law suits in the UK
10
2002-03
•
3
•
15
•
24
•
42
•
2003-04
•
4
•
34
•
28
•
66
•
2004-05
•
10
•
47
•
15
•
72
•
2005-06
Unsure of need for frenzied plans of action.
Sure of need for Education
Otherwise...
Scary Media
Propaganda
•
•
•
Bauman, Robert W. Microbiology. San Francisco: Pearson, 2004.
References
Chambers, Henry F. (2001). The changing epidemiology of staphylococcus aureus?
CDC, 7.
Baba T, Takeuchi F, Kuroda M, Yuzawa H, Aoki K, Oguchi A, Nagai Y, Iwama N, Asano
•
Chang, Soju, Sievert, Dawn, Hageman, Jeffery C., Boulton, Matthew L., Tenover, Fred
•
C., Downes, Frances Pouch, et al. (2003). Infection with Vancomycin-Resistant
•
Staphylococcus aureus Containing the vanA Resistance Gene. The New England
•
Journal of Medicine, 348, 1342-47.
•
Crum, Nancy. (2005). The emergence of severe, community-acquired methicillin
•
resistant staphylococcus aureus infections. Scand J Infect Dis, 37, 651-6.
•
Dale, David C., Federman, Daniel D. ACP Medicine. 3rd Edition. New York:
•
WebMD, 2007.
•
Enright, Mark, Robinson, Ashley, Randle, Gaynor, Feil, Edward J., Grundmann, Hajo,
•
Spratt, Brian G. (2002). The evolutionary history of methicillin-resistant
•
•
•
Staphylococcus aureus in Los Angeles. New England
References
Journal of Medicine, 14, 1485-7: 4, 353: 5, 530-2. Retrieved October 26, 2007, from
PubMed.
•
•
Nelson, Chris. Comprehensive staphylococcal infection and colonization eradication
•
plan: MRSA. Division of Pediatric Infectious Disease, 2007.
•
•
Regev A, Weinberger M, Fishman M, Samra Z, Pitlik SD. (1998). Necrotizing fasciitis
•
caused by Staphylococcus aureus. Eur J Clin Microbiol Infect Dis, 2, 101-3.
•
Retrieved October 26, 2007, from PubMed.
•
The Centers for Disease Control and Prevention. 2007, Available at: http://
•
www.cdc.gov/ncidod/dhqp/ar_mrsa_surveillanceFS.html, Accessed on October 6,
•
2007.
•
Voyich JM, Otto M, Mathema B, Braughton KR, Whitney AR, Welty D, Long RD,
•
Dorward DW, Gardner DJ, Lina G, Kreiswirth BN, DeLeo FR. (2006). s Panton-