Transcript TM TM Prepared for your next patient. Community-Acquired MRSA: Update on Epidemiology, Treatment, and Prevention John S.

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Prepared for your next patient.
Community-Acquired MRSA:
Update on Epidemiology,
Treatment, and Prevention
John S. Bradley, MD, FAAP
Infectious Diseases Division
University of California, San Diego
Rady Children’s Hospital San Diego
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CA-MRSA
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Epidemiology
Pathogenicity
Clinical Presentation
Treatment (New Guidelines)
Prevention
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Epidemiology:
Virulent CA-MRSA
• First clinical reports in the US appeared about
10 years ago
• Likely to have emerged several times in the past
(many different clones described, but only a
few have been successful over time)…still
evolving!
• May now be losing methicillin-resistance genes,
but still virulent!!
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CA-MRSA
• Differs in clinical disease compared with MSSA
and past hospital-acquired MRSA strains
– Uniformly resistant only to beta-lactam
antibiotics (penicillins, cephalosporins,
carbapenems)*
– Variably resistant to macrolides and to
lincosamides (clindamycin)
*Except ceftaroline, just approved by FDA for adults in October 2010.
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CA-MRSA:
Primary PFGE type: USA 300 (CDC)
• SCCmec types (Staphylococcal Chromosome Cassette)
Methicillin-resistance cassette associated with CA-MRSA
Deurenberg RH, Vink C, Kalenic S, et al. The molecular evolution of methicillin-resistant Staphylococus aureus. Clin Microbiol and
Infect. 2006;13(3):222-235.
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Increased virulence in
CA-MRSA USA 300
appears to be linked to
virulence factors OR
Alterations in gene
Regulation
• Phenol soluble modulins
• Panton-Valentine
leukocidin
• α-hemolysins
• Arginine catabolic
mobile element (ACME)
• agr (accessory gene
regulator)
Kobayashi SD, DeLeo FR. An update on community-associated MRSA virulence. Curr Opin
Pharmacol. 2009;9(5):545-551.
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CA-MRSA:
PMN Killing Following Phagocytosis
Kobayashi SD, DeLeo FR. An update on community-associated MRSA virulence. Curr Opin Pharmacol. 2009;9(5):545-551.
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CA-MRSA:
Mouse Lung Infection Model
Saline control in lungs
Staph without PVL
Staph with PVL
Subsequently found to be a dysregulated PVL hyperproducer.
Labandeira-Rey M, Couzon F, Boisset S, et al. Staphylococcus aureus Panton-Valentine leukocidin causes necrotizing pneumonia. Science.
2007;315(5815):1130-1133.
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CA-MRSA:
Necrotizing Pneumonia
PVL
PVL
Labandeira-Rey M, Couzon F, Boisset S, et al. Staphylococcus aureus Panton-Valentine leukocidin causes necrotizing pneumonia.
Science. 2007;315(5815):1130-1133.
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CA-MRSA: What it Does
• CA-MRSA appears to cause deeper, more invasive
infections than MSSA
• CA-MRSA appears to cause necrotizing fasciitis at a
greater rate than MSSA
• CA-MRSA does not appear to cause bacteremic
disease more frequently
• CA-MRSA appears to cause recurrent infections more
frequently
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CA-MRSA
• CA-MRSA appears to have a selective advantage in
the community, and represents an increasing
proportion of staph responsible for hospitalizations,
just like penicillin-resistant strains did over 30 years
ago
• In many regions of the USA, rates of MRSA have
stabilized at 40-90% (we don’t know why rates vary)
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All children with abscesses (n = 69)
Clinical
Characteristics
and Management
Dallas, Texas
The “spider bite”
Lee MC, Rios AM, Aten MF, et al. Management and
outcome of children with skin and soft tissue
abscesses caused by community-acquired
methicillin-resistant Staphylococcus aureus. Pediatr
Infect Dis J. 2004;23(2):123-127.
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Complicated MRSA Pneumonia
Enhanced Destruction of Lung with Influenza Co-infection
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Complicated MRSA Pneumonia
Late Fibrosis
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Necrotizing Fasciitis with MRSA
Cellulitis (short arrow)
Panniculitis (long arrow)
Fasciitis (arrowhead)
Gram-positive cocci in
clusters (arrow)
Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis
caused by community-associated methicillin-resistant Staphylococcus
aureus in Los Angeles. N Eng J Med. 2005;352(14):1445-1453.
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CA-MRSA in Pediatrics
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CA-MRSA in Pediatrics
2 weeks post skin grafting
[But no Necrotizing Fasciitis since in SD in 3 years]
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CA-MRSA: Complication Rates
• This is not the old Staph: all of the
information/publication/experience regarding the old
MSSA strains may not apply to CA-MRSA
• Complication rates are higher and response to
treatment is slower; inflammation and induration may
not be resolved by 10-14 days
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CA-MRSA: Diagnosis
• Cultures are important for all presumed staph
infections as many are still MSSA
• Rapid tests are now available
– From cultured organisms: latex particles coated with
monoclonal antibody to PBP 2a
– PCR from colonized anatomic sites, looking for the
mecA methicillin resistance genes
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IDSA Guidelines for CA-MRSA
Endorsed by the AAP
January 2011
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
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CA-MRSA:
Community-Acquired Pneumonia (CAP)
•
For children hospitalized with severe CAP empiric therapy
for MRSA is recommended (pending sputum and/or blood
culture results):
– Those requiring an intensive care unit (ICU) admission, OR
– Necrotizing or cavitary infiltrates, OR
– Empyema
•
Vancomycin recommended for children
– If the patient is stable without ongoing bacteremia
or intravascular infection, clindamycin can be used
as empirical therapy if the clindamycin resistance rate is low
(eg, 10%)
– Linezolid is an alternative [watch for more data on this issue]
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society
of America for the treatment of methicillin-resistant Staphylococcus aureus infections in
adults and children. Clin Infect Dis. 2011;52:1-38.
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CA-MRSA:
Adjunctive Therapy for MRSA
• Not routinely recommended: Protein synthesis
inhibitors (eg, clindamycin and linezolid) and
intravenous immunoglobulin (IVIG)
– Some experts may consider these agents in selected
scenarios (eg, necrotizing pneumonia or severe sepsis)
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
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CA-MRSA:
Vancomycin Dosing for Children
• Vancomycin 15 mg/kg/dose every 6 h (60 mg/kg/day) is
recommended for serious or invasive disease (data are limited to
guide vancomycin dosing in children).
• Trough concentrations of 15–20 mcg/mL should be considered
in those with serious infections, such as bacteremia, infective
endocarditis, osteomyelitis, meningitis, pneumonia, and severe
SSTI (eg, necrotizing fasciitis)
– The efficacy and safety of this dose requires additional study
• [AUC:MIC > 400]
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
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CA-MRSA:
Treatment for Skin / Skin Structure Infections (SSTI)
• Hospitalized children with complicated SSTI:
– Vancomycin
– Clindamycin is an option if the patient is stable, without
ongoing bacteremia or intravascular infection, and if the
clindamycin resistance rate is low (eg,10%); allows transition to
oral therapy
– Linezolid is an alternative
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
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CA-MRSA: Therapy
Invasive, Serious Disease
• Roles not well defined for pediatrics:
– Linezolid (Zyvox®): IV/PO, bacteriostatic in vitro (?not in
vivo?)
 Superior to vancomycin for treatment of adults with MRSA
pneumonia (IDSA 2010 abstract)
– Daptomycin (Cubicin®): rapidly bactericidal, but virtually
NO pediatric data and NOT EFFECTIVE for pneumonia
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CA-MRSA:
Treatment for Skin / Skin Structure Infections (SSTI)
• Oral antibiotics for Abscess/Cellulitis:
– Clindamycin (if local strains susceptible) Staph + Strep [tastes
bad]
– TMP-SMX (Septra/Bactrim) Staph + ?Strep [no prospective,
controlled studies vs clinda]
– Doxycycline [bacteriostatic, for children older than 7 years]
– Linezolid (Zyvox) Staph + Strep [expensive! Marrow toxicity for
courses beyond 10 days]
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
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All you need is drainage!
Lee MC, Rios AM, Aten MF, et al.
Management and outcome of
children with skin and soft tissue
abscesses caused by communityacquired methicillin-resistant
Staphylococcus aureus. Pediatr
Infect Dis J. 2004;23(2):123-127.
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CA-MRSA:
Therapy of Mild –
Moderate Infections
How solid are the data
supporting the use of
TMP-SMX?
…retrospective
Retrospective review of convalescent therapy of MRSA
infections (Baylor College of Medicine)
Hyun DY, Mason EO, Forbes A, et al. Trimethoprimsulfamethoxazole or clindamycin for treatment of communityacquired methicillin-resistant Staphylococcus aureus skin and
soft tissue infections. Pediatr Infect Dis J. 2009;28(1):57-29.
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CA-MRSA:
Therapy of Mild – Moderate Infections
A child with fever,
induration or abscess,
seen in the ED, has a
40% chance of failing
TMP-SMX with
infection presumed to
be caused by MSSA,
MRSA or Gp A strep
Retrospective review of non-cultured, non-drained skin infections
Elliott DJ, Zaoutis TE, Troxel AB, et al. Empiric antimicrobial therapy for pediatric skin and soft-tissue infections in the era of
methicillin-resistant Staphylococcus aureus. Pediatrics. 2009;123(6):e959-e966.
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CA-MRSA:
Treatment for Skin / Skin Structure Infections (SSTI)
• Minor skin infections (such as impetigo) and secondarily
infected skin lesions (eg, eczema, ulcers, or lacerations):
– Topical 2% mupirocin ointment
• Cutaneous abscess:
– Incision and drainage may be sufficient
– Consider oral antibiotics for more severe cases
• Cellulitis: Consider oral antibiotics
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
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CA-MRSA:
Bone and Joint Infections
• Surgical debridement and drainage of associated soft
tissue abscesses is the mainstay of therapy
– Antibiotics intravenously:
• Vancomycin
– Antibiotics intravenous and oral:
• Clindamycin
• TMP-SMX 4 mg/kg/dose in combination with rifampin
• Linezolid
– Some experts recommend the addition of rifampin to IV or
oral regimens
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
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CA-MRSA:
Bone and Joint Infections
• The optimal duration of therapy for MRSA
osteomyelitis is unknown:
– A minimum of 4-6 weeks
– An additional 1–3 months ( for chronic infection
or if debridement is not performed) may be
required
• CRP (and/or ESR) may be helpful to guide
response to therapy
• Magnetic resonance imaging (MRI) with
gadolinium is the imaging modality of choice
for osteomyelitis
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
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CA-MRSA:
Bacteremia / Endocarditis
• Vancomycin is recommended for the treatment of bacteremia and infective
endocarditis
– Duration of therapy may range from 2 to 6 weeks depending on source, presence
of endovascular infection, and metastatic foci
– Data regarding the safety and efficacy of alternative agents in children are limited;
daptomycin may be an option
• Clindamycin or linezolid may be considered in children whose bacteremia
rapidly clears and is not related to an endovascular focus
• Data are insufficient to support the routine use of combination therapy with
rifampin or gentamicin in children with bacteremia or infective endocarditis;
the decision to use combination therapy should be individualized
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
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CA-MRSA:
Decolonization for Recurrent SSTI
• Decolonization may be considered in selected cases if
– A patient develops a recurrent SSTI despite optimizing wound care and hygiene
measures
– Ongoing transmission is occurring despite optimizing wound care and hygiene
measures
• Decolonization strategies should be offered in conjunction with ongoing
hygiene measures:
– Nasal decolonization with mupirocin twice daily for 5–10 days with or without
concurrent topical body decolonization regimens with a skin antiseptic solution (eg,
chlorhexidine*) for 5–14 days or dilute bleach baths
• Oral antimicrobial therapy is not routinely recommended for decolonization
*In San Diego, we use chlorhexidine every other day, or 3x/wk to decrease rates of recurrence
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
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CA-MRSA in Sports
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Current CA-MRSA:
Pediatric Antibiotic Research
• NIH/NICHD-sponsored trials of oral therapy/I&D for
uncomplicated skin infections (clinda vs cephalexin
vs TMP-SMX vs I&D)
• Daptomycin is in pediatric clinical trials for
complicated skin infections
• Phase I PK studies ceftaroline, dalbavancin and
torezolid
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CA-MRSA:
Summary
• Respect CA-MRSA!
• Vancomycin is still the preferred drug for invasive infection in
children
– Many new options are appearing for adults, not yet tested
in children
– Optimal dosing in children is not well defined
• Clindamycin/TMP-SMX are reasonable options for mild/mod
disease (little prospective data exist)
• Whatever you use, do not automatically assume that the child
will respond!
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