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Dr.T.V.Rao.MD
COMMUNITY ASSOCIATED- MRSA(CA-MRSA)
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Staphylococci: Gram positive cocci( from Greek staphyle, means bunch of
grapes ) that occur singly and in pairs,
short chains and irregular grape-likeclusters.
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MRSA Discovered in 1981 Found on skin and in the nose of 1 in 3
healthy people - symptomless carriers
Widespread in hospitals andcommunity
Resistant to most antibiotics
When fatal - often due to septicaemia
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METHICILLIN RESISTANT
STAPHYLOCOCCUS Methicillin-resistant Staphylococcus aureus
(MRSA) are identified as nosocomial pathogens
throughout the world . Established risk factors
for MRSA infection include recent hospitalizationor surgery, residence in a long-termcare facility,
dialysis, and indwelling percutaneous medical
devices and catheters. Recently, however, casesof MRSA have been documented in healthy
community-dwelling persons without established
risk factors for MRSA acquisition.DR.T.V.RAO MD 4
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Healthcare system is evolving to an increased use of outpatientprocedures and long-term care
Many long-term-care facilities now experience infection rates comparable to thosein acute hospital settings
Outbreaks are common
High rates of colonization with resistant strains
THE LANDSCAPE OF
HEALTHCARE-ASSOCIATED (HCA) INFECTIONS
Nicolle LE. Clin Infect Dis. 2000;31:752-756.
Hospital or
Acute care setting
Home careOutpatient facility
Long-term-care facility
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S. aureus
Penicillin
[1950s]
Penicillin-resistant
S. aureus
EVOLUTION OF DRUG RESISTANCE IN S. AUREUS
Methicillin
[1970s]
Methicillin-resistant
S. aureus(MRSA)
Vancomycin-resistant
enterococci (VRE)
Vancomycin
[1990s]
[1997]
Vancomycin
intermediate-resistantS. aureus(VISA)
[ 2002 ]
Vancomycin
-resistant S.aureus
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0
10
20
30
40
50
60
1989
1991
1993
1995
1997
1999
2001
2003
2005
PercentRe
sistance
Methicillin-ResistantStaphylococcus aureus (MRSA)
U.S. Non-Intensive Care
U.S. Intensive CareThe Nebraska Medical Center
Source: National Nosocomial InfectionsSurveillance (NNIS) System
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INFECTION CLASSIFICATION
Infections historically identified as community acquiredor hospital acquired, based on location and time of symptom
onset
Community-acquired (CA): hospitalization 48 hours
Hospital-acquired (HA): hospitalization > 48 hours
Associated with inherent assumptions:Hospital-acquired infectionsCommunity-acquired infections
Patients with compromised defenses
Environment with resistant microorganisms
Often associated with invasive devices or
medical procedures
Otherwise healthy patients
Environment with little selective pressure,
fewer resistant microorganisms
Develop spontaneously
Siegman-Igra Y, et al. Clin Infect Dis. 2002;34:1431-1439.
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They are apparently acquired in the
community, these infections are
referred to as community-acquired
(CA)-MRSA (. CA-MRSA infections
have been reported in North
America, Europe, Australia, and New
Zealand . The recent genomic
sequence of a CA-MRSA isolate
indicated the presence not only of a
novel smaller variant of the
methicillin-resistance locus(SCCmecIVa, according to Baba et
al. designation , but also that of the
locus for the Panton-Valentine
leukocidin (PVL).
COMMUNITY ACQUIRED MRSA
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TERMINOLOGY OF CA-MRSA
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Terminology has been inconsistent Community-Onset
(CO) MRSA: infection
diagnosed or index culture collected in community
Established risk factors (RFs): recent hospitalization,surgery, dialysis, long-tern care; indwelling catheter or
percutaneous medical device; history of MRSA
Community-Acquired MRSA: Used for CO infections or CO
infections in patients without established RFs, but difficultto establish with certainty where acquisition occurred
Community-Associated MRSA: CO infections in persons
without established RFs
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CA-MRSA: A COMPLEX ISSUE Epidemiologic and clinical risk factors cannot reliably
distinguish between MRSA and
MSSA in patients with community-acquired
S aureus infections
CA-MRSA strains are emerging with resistance to some
non--lactam classes of antibiotics
Strains resistant to fluoroquinolones and
aminoglycosides have been isolated
The distinction between CA- and HA-MRSA strains is
blurring
1. Miller LG, et al. Clin Infect Dis. 2007;44:471-482. 2. Del Giudice P, et al. Br J Dermatol. 2006;154:118-124. 3. Gonzalez BE, et al. Infect Control Hosp Epidemiol.
2006;27:1051-1056. 4. Klevens RM, et al. Emerg Infect Dis. 2006;12:1991-1993. 5. Maree CL, et al. Emerg Infect Dis. 2007;13:236-242.
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COMMUNITY-ASSOCIATED MRSA Methicillin-resistant S aureus strains are endemic in
many communities
Strains from the community may be referred to as either
community-associatedorcommunity-acquired(CA) MRSA
CA-MRSA is genetically different from the strains normally
associated with hospital-acquired infections
CA-MRSA first emerged in the 1990s
Outbreaks of CA-MRSA have been reported2
CA-MRSA infections most often involve skin
and soft tissue1-3
1. Zetola N, et al. Lancet Infect Dis. 2005;5:275-286. 2. McDonald LC. Clin Infect Dis. 2006;42:S65-S71. 3. Naimi TS, et al. JAMA. 2003;290:2976-2984.
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GROWING INCIDENCES OF CA-MRSA Patients with HCA infections have an increased risk
of infection with MRSA compared to patients with CAinfections
Identifying and treating patients in a timelymanneris critical
The prevalence of MRSA is increasing in the community and hospital
settings
Infection with MRSA is associated withnegative outcomes
MRSA is frequently associated with
inappropriate treatmentDR.T.V.RAO MD 13
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WHATS DIFFERENT ABOUTCA-MRSA?
SCCmec IV (V) is mobile and in variety ofbackground strains
Replicate more rapidly than HA-MRSA (23 minvs 46 min) More fit than HA-MRSA
MW2 sequence vs 5 HA-MRSA reveal 19putative virulence genes: 4 Enterotoxins, 11exotoxins (PVL), collagen adhesin, etc. Morevirulent?
LD is 5x less than HA-MRSA (no single geneappears responsible)
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Necrotizing cytotoxin
Associated withabscesses and severe
pneumonia Also found in some
methicillinsusceptible
S. aureus (MSSA)isolates
PANTON-VALENTINE LEUKOCIDIN
(PVL) TOXIN
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COMMON CLINICAL PRESENTATIONS OF CA-MRSA
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RECURRENT FURUNCULOSIS
Very little data indicating long-term benefit of decolonizationregimens. Toxicity/cost/resistance
Combination of topical, mucosal, and systemic antibiotics: Oral TMP-SMX, nasal mupirocin, chlorhexidine showers x 5d
Bleach baths (1 teaspoon of bleach per gallon of water) x 10minutes 2 times/wk
Environmental cleaning (bedclothes, towels, surfaces)
Close contacts? Pets? Environment?
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WHAT IS PVL (PANTON-VALENTINE
LEUKOCIDIN)?
1st described in 1932
Bicomponent synergistic membrane-tropic toxin
Encoded by lukS-PV and lukF-PV genes
Assembled as hetero-oligimers thatsynergistically act to form pores in cell
membranes (lysis) of pmns andmonocytes/macrophages
Associated with necrotizing skin and soft tissueinfections and pneumonia
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The PVL locus iscarried on a
bacteriophage and is
present in only a small
percentage ofS. aureus
isolates from France,
where this locus is
associated with skininfections, and
occasionally, severe
necrotizing pneumonia
LOCATION OF PANTON-VALENTINE LEUKOCIDIN (PVL).
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Nosocomial infection
Community-acquired infection
Methicillin-resistant S aureus
0
25
50
75
100
1970 1980 2000
Year
Resistantisolates(%)
1990
Nosocomial infection
Community-acquired infection
Methicillin-resistant S aureus
0
25
50
75
100
1970 1980 2000
Year
Resistantisolates(%)
1990
Nosocomial infection
Community-acquired infection
Methicillin-resistant S aureus
0
25
50
75
100
1970 1980 2000
Year
Resistantisolates(%)
1990
Prevalence of MRSA
increasing in hospitals
and in the community1
INFECTIONS DUE TO COMMUNITY- AND
HEALTHCARE-ASSOCIATED MRSA
1. McDonald LC. Clin Infect Dis. 2006;42:S65-S71. 2. Naimi TS, et al. JAMA. 2003;290:2976-2984.
Infections associatedwith CA-MRSA (n = 131)2
Infections associatedwith HA-MRSA (n = 937)2
Skin/Soft tissue 75%
Otitis media/externa7%
Respiratory tract 6%
Bloodstream 4%
Urinary tract 1%
Other 8%
Skin/Soft tissue 75%
Otitis media/externa7%
Respiratory tract 6%
Bloodstream 4%
Urinary tract 1%
Other 8%
Skin/Soft tissue 37%
Otitis media/externa 1%
Respiratory tract 22%
Bloodstream 9%
Urinary tract 20%
Other 12%
Skin/Soft tissue 37%
Otitis media/externa 1%
Respiratory tract 22%
Bloodstream 9%
Urinary tract 20%
Other 12%
Infections associatedwith CA-MRSA (n = 131)2
Infections associatedwith HA-MRSA (n = 937)2
Skin/Soft tissue 75%
Otitis media/externa7%
Respiratory tract 6%
Bloodstream 4%
Urinary tract 1%
Other 8%
Skin/Soft tissue 75%
Otitis media/externa7%
Respiratory tract 6%
Bloodstream 4%
Urinary tract 1%
Other 8%
Skin/Soft tissue 37%
Otitis media/externa 1%
Respiratory tract 22%
Bloodstream 9%
Urinary tract 20%
Other 12%
Skin/Soft tissue 37%
Otitis media/externa 1%
Respiratory tract 22%
Bloodstream 9%
Urinary tract 20%
Other 12%
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DECIPHERING MRSA STRAINS
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DECIPHERING MRSA STRAINS:HA-MRSA VS. CA-MRSA
HA-MRSA CA-MRSA
Genetic characteristics SCC mectype I, II, or III SCC mectypeIV
Commonresistance
-lactamsMacrolides
AminoglycosidesQuinolones
Lincosamides
-lactams
Macrolides
Panton-Valentine
leukocidin (PVL)exotoxinNot common Common
1. Carleton HA, et al. J InfectDis. 2004;190:1730-1738. 2. Drew RH. Pharmacotherapy. 2007;27:2027-249. 3. Zetola N, et al. Lancet Infect Dis. 2005;5:275-286. 4. Klevens RM, et al.
Emerg Infect Dis. 2006;12:1991-1993.
HA-MRSA = strains first isolated in the hospital (nosocomial pathogen);
CA-MRSA = strains first isolated in the community setting.
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PANTON-VALENTINE LEUKOCIDIN
Panton-Valentine leukocidin (PVL) is a cytotoxinone of the
-pore-forming toxins. The presence of PVL is associated with
increased virulence of certain strains (isolates) of
Staphylococcus aureus. It is present in the majority of
community-associated Methicillin-resistant Staphylococcusaureus (CA-MRSA) isolates studied] and is the cause of
necrotic lesions involving the skin or mucosa, including necrotic
hemorrhagic pneumonia. PVL creates pores in the membranes
of infected cells. PVL is produced from the genetic material of abacteriophage that infects Staphylococcus aureus, making it
more virulent.
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PANTON-VALENTINE LEUKOCIDIN (PVL)
Panton-Valentine leukocidin (PVL) is one of many
toxins associated with S. aureus infection. Because it
can be found in virtually all CA-MRSA strains that
cause soft-tissue infections, it was long described as akey virulence factor, allowing the bacteria to target and
kill specific white blood cells known as neutrophils. This
view was challenged, however, when it was shown that
removal of PVL from the two major epidemic CA-MRSAstrains resulted in no loss of infectivity or destruction of
neutrophils in a mouse model.[
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CA-MRSA: Whats Going On?
SCCmec I-V, mecIV is most commonly found in CA-MRSA; 25 KB,
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Patients with MRSA infection
(n = 100 isolates)
Infection
with typical
CA-MRSA
strain
Healthcare-related risk factors?
Yes
(n = 73)
No
(n = 27)
Infection
with typical
HA-MRSA
strain
Infection
with typical
CA-MRSA
strain
Infection
with typical
HA-MRSA
strain
22%
(16/73)
70%
(19/27)
77%
(56/73)
26%
(7/27)
Patients with MRSA infection
(n = 100 isolates)
Infection
with typical
CA-MRSA
strain
Healthcare-related risk factors?
Yes
(n = 73)
No
(n = 27)
Infection
with typical
HA-MRSA
strain
Infection
with typical
CA-MRSA
strain
Infection
with typical
HA-MRSA
strain
22%
(16/73)
70%
(19/27)
77%
(56/73)
26%
(7/27)
DISTINCTION BETWEEN CA-MRSA
AND HA-MRSA IS BLURRING
Klevens RM, et al. Emerg Infect Dis. 2006;12:1991-1993.
CA-MRSA strains are emerging in the healthcare setting, while
HA-MRSA strains are moving out into the community
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THE DISTINCTION BETWEEN CA AND HA
IS BLURRING!
Characterized 132 cases of MRSA BSI in Atlanta
34% of MRSA were USA 300
28% of pts with HA BSI factors
20% of pts with nosocomial BSI
0%
20%
40%
60%
80%
100%
Total (n=116) HA (n=107) Noso (n=49)
USA800
USA500
USA100USA300
Seybold U, et al. ClinInfect Dis, 2006
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1. In all pus forminglesions
Gram stain andculture of pus
2. In all systemicinfections
Blood culture
3. In infections of other
tissues Culture of relevant
tissue or exudate
DIAGNOSIS
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On isolating any MRSA strains
with clinical and epidemiological
suspicion of CA-MRSA, further
laboratory characterization
needs to be undertaken to
support the diagnosis. SCCmectyping is performed by
determining the combination of
two attributes: the class of the
mecgene complex, and with the
type of the ccr(chromosomalcassette recombinase) gene
complex
CA-MRSA DIAGNOSIS
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The mecgene complex,
comprises classes A to C,
and the latter comprises
types 1 to 3. The technique
employed is polymerasechain reaction (PCR), either
using individual reactions or
in a multiplex format.9-11 In
addition, the presence ofthe PVL gene is also
detected by PCR.
CA-MRSA DIAGNOSIS
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SENSITIVITY AND RESISTANCE PATTERNS
OF STAPHYLOCOCCUS AUREUS
MRSA
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Community-associated
methicillin-resistant
Staphylococcus aureus strain
(note golden colour) showing
resistance to -lactams and
susceptibility to multipleantimicrobials. Key: Resistant
to penicillin (P) and cefoxitin
(FOX); Susceptible to
erythromycin (E), clindamycin
(DA), gentamicin (CN),tetracycline (TE),
chloramphenicol
(C),ciprofloxacin (CIP),
rifampicin (RD) and
cotrimoxazole (SXT).
CA-MRSA DIAGNOSIS
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PLATE 1B: A MECA GENE NEGATIVE STAPHYLOCOCCUS AUREUSWITH HIGH B-LACTAMASE ACTIVITY SHOWING BORDERLINE RESISTANCE TO OXACILLIN
(BORSA) WHILST THERE IS AN INHIBITORY ZONE OF 7.5 MM AROUND THE CEFOXITIN
(FOX 10) DISC.DR.T.V.RAO MD 32
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NON-MULTIPLE RESISTANT MRSA SUSCEPTIBLE
TO COTRIMOXAZOLE
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: A MECA GENE POSITIVE STAPHYLOCOCCUS AUREUS(MRSA) BUT LACKING
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: A MECA GENE POSITIVE STAPHYLOCOCCUS AUREUS(MRSA) BUT LACKING B-LACTAMASE ACTIVITY. NOTE THE LARGE ZONES AROUND PENICILLIN (P 0.5) AND
OXACILLIN (OX 1) DISCS BUT THE REDUCED INHIBITORY ZONE AROUND CEFOXITIN
(FOX 10).
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: MRSA WITH INDUCIBLE CLINDAMYCIN RESISTANCE (ICR): NO INHIBITORY
ZONE AROUND ERYTHROMYCIN (E 5) AND A FLATTENED INHIBITORY ZONE
AROUND CLINDAMYCIN (DA 2) NEAR THE ERYTHROMYCIN DISC.
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: STAPHYLOCOCCUS AUREUS NCTC 6571 NOTE THE APPROXIMATE
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: STAPHYLOCOCCUS AUREUSNCTC 6571. NOTE THE APPROXIMATE
INHIBITORY ZONE SIZES AROUND PENICILLIN (P 0.5), CEFOXITIN (FOX
10) AND VANCOMYCIN (VA 5) DISCS ARE 12 MM, 10 MM AND 3 MM
RESPECTIVELY
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PLATE 4: MRSA WITH REDUCED SUSCEPTIBILITY TO VANCOMYCIN (VISA/GISA).
NOTE THE REDUCED ZONE AROUND VANCOMYCIN (VA 5) AND TEICOPLANIN (TEC
15) DISCS.DR.T.V.RAO MD 37
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Further typing ofCA-MRSAstrains is possible using various
methods, including pulsed-field
gel electrophoresis (PFGE),
multilocus sequence typing
(MLST) and S. aureus protein A
(spa) typing.5,12 These methods
are employed when it is
necessary to delineate
epidemiological relationships
among CA-MRSA strains isolatedfrom different sources, such as in
outbreak settings
EPIDEMIOLOGICAL TYPING
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OPTIMIZING INITIAL
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OPTIMIZING INITIAL
ANTIMICROBIAL THERAPY
Initial therapy is often empiric and should cover all pathogensthat may be present
Knowledge of underlying risk factors for antimicrobial
resistance and local Antibiogram contribute to correct
treatment choice
Appropriate antimicrobial therapy includes an agent or regimen
that is effective against the causative pathogen(s)
Broad-spectrum therapy is often recommended
Adequate empiric therapy should not be delayed
1. Kollef MH. Drugs 2003;63(20):2157-2168. 2. The American Thoracic Society and the Infectious Diseases Society of America.Am J Respir Crit Care Med. 2005;171:388-416.
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TREATING MRSA INFECTIONS
Agents with anti-MRSA activity include:
Limitations of some agents include:
Emerging resistance, changing susceptibilities
Bacteriostatic rather than bactericidal activity
Decreased penetration or inactivity in some tissues
(eg, lung)
Side effects/toxicity
Drew RH. Pharmacotherapy. 2007;27:227-249.
TMP-SMX = trimethoprim-sulfamethoxazole.
Vancomycin Linezolid Daptomycin
Tigecycline TMP-SMX Clindamycin
Vancomycin Linezolid Daptomycin
Tigecycline TMP-SMX Clindamycin
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TREATMENT OF CA-MRSA
Most disease is skin & soft tissue (75% - 80%)
Data suggests that many cases can be treated
with I&D without Abx
73% of pts in one study received antibiotics to
which the organisms was resistant. No difference
in number of follow-up visits, subsequent need forI&D, or change in antibiotic therapy (Fridkin, NEJM,
2005)
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TREATMENT ALGORITHM: DISTINGUISHING
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TREATMENT ALGORITHM: DISTINGUISHINGBETWEEN HCA AND CA INFECTIONS IS A CRITICAL
STEP
1. American Thoracic Society.Am J Respir Crit Care Med. 2005;171:388-416. 2. Mandell LA, et al. Clin Infect Dis. 2007;44:S27-S72.
Treat with: Extended spectrum antipseudomonal
cephalosporin, carbapenem,or -lactam/-lactamase inhibitor
+
Antipseudomonal fluoroquinoloneor aminoglycoside
+/- Anti-MRSA agent
Patient presents to hospital with suspected pneumonia
Underlying risk factors for healthcare-associated infection?
Recent hospitalization Residence in nursing home
Home infusion therapy Chronic dialysis
Home wound care Family member with resistant pathogen
Community-acquired
pneumonia suspected
Treat with (non-ICU treatment): Respiratory fluoroquinolone
or -lactam + macrolide
Healthcare-associated
pneumonia suspected
NoYes
Note: Local prevalence and susceptibilitypatterns should be used when choosing an
empiric antibiotic regimen
Treat with: Extended spectrum antipseudomonal
cephalosporin, carbapenem,or -lactam/-lactamase inhibitor
+
Antipseudomonal fluoroquinoloneor aminoglycoside
+/- Anti-MRSA agent
Patient presents to hospital with suspected pneumonia
Underlying risk factors for healthcare-associated infection?
Recent hospitalization Residence in nursing home
Home infusion therapy Chronic dialysis
Home wound care Family member with resistant pathogen
Community-acquired
pneumonia suspected
Treat with (non-ICU treatment): Respiratory fluoroquinolone
or -lactam + macrolide
Healthcare-associated
pneumonia suspected
NoYes
Note: Local prevalence and susceptibilitypatterns should be used when choosing an
empiric antibiotic regimen
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0 4 8 12 24 36 4810
2
103
104
105
106
107
108
109
1010
Bacteria[CFU/mL]
Time (hours)
LinezolidRifampin
SXT
SXT+Rifampin
Clindamycin
Minocycline
Control
Time-kill curves for all isolates of MethicillinResistant Staphylococcus Aureus (12)
Kaka, et al
IDSA, 2005
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DR.T.V.RAO MD 44
NEW DRUGS ON TRAILS FOR USE
IN STAPHYLOCOCCAL INFECTIONS
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INVESTIGATIONAL
ANTI-STAPHYLOCOCCAL ANTIBIOTICS
Glycopeptides
Ortivancin (Intermune)
Dalbovancin (Vicuron)
Telavancin (Theravance)
DHFR inhibitor
Iclaprim (Arpida)
Novel B-lactams Ceftobiprole
BMS-247243, RWJ 54428, CB-181963, BAL 5788, S-3578
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OTHER POTENTIALANTI-STAPHYLOCOCCAL AGENTS
Capsule 5/8 Vaccine (NABI): - FDA fast tracked announced 10/12/04;Halt in development 11/05
Staph capsule IG (NABI & Biosynexus) (Halt 11/05)
Lysostaphin (Biosynexus)
Aurexis (Inhibitex) anti-ClfA
Veronate (Inhibitex) Adhesin Ab (neonates)
Aurograb (NeuTec) Ab vs ABC transporter
Peptide deformylase inhibitors
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Cover all wounds
Train athletes in first aid for
wounds and signs of infection
Encourage good hygiene
Discourage sharing of items
Establish routine cleaning
schedules for shared
equipment
Encourage players to reportskin lesions
PREVENTION AND CONTROL
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Multi-component strategies
used (difficult to assess
individual contribution of
each)
Strategies focusing on
increased awareness, early
detection and appropriate
management, enhanced
hygiene, and maintenance ofa clean environment appear
to have been successful at
interrupting transmission
CA-MRSA OUTBREAK CONTROL
MEASURES
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UNIVERSAL INFECTION
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UNIVERSAL INFECTION
CONTROL PRECAUTIONS
Devised in US in the 1980s in response togrowing threat from HIV and hepatitis B
Not confined to HIV and hepatitis B Treat ALL patients as a potential bio-hazard
Adopt universal routine safe infectioncontrol practices to protect patients, selfand colleagues from infection
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UNIVERSAL PRECAUTIONS Hand washing
Personal protective equipment [PPE]
Preventing/managing sharps injuries
Aseptic technique
Isolation Staff health
Linen handling and disposal
Waste disposal
Spillages of body fluids
Environmental cleaning
Risk management/assessment
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HAND WASHING
Single most effective action to prevent HAI -resident/transient bacteria
Correct method - ensuring all surfaces are cleaned -more important than agent used or length of timetaken
No recommended frequency - should be determinedby intended/completed actions
Research indicates:
poor techniques - not all surfaces cleaned frequency diminishes with workload/distance
poor compliance with guidelines/training
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YOUR HABITS KEEP THE PEOPLE AT RISK
NASAL CAVITY A SOURCE OF INFECTION
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MAKE HAND WASHING A HABIT
SOME BODY WATCHING YOU
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Programme created by Dr.T.V.Rao MD
for Medical Professionals in theDeveloping World Email