Management of Suspected
Staphylococcal Infections in Children
in the Era of Community MRSA
Thursday, May 15, 2008
12:00 – 1:00 p.m. EDT
© American Academy of Pediatrics 2008
Moderator:
Marlene R. Miller, MD, MSc, FAAP
Vice President, Quality - NACHRI
Director of Quality and Safety & Associate Professor
Johns Hopkins Children’s Centers
Baltimore, Maryland
This activity was funded through an
educational grant from the
Physicians’ Foundation for Health
Systems Excellence.
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Speaker:
George K. Siberry, MD, MPH, FAAP
Assistant Professor of Pediatrics
Medical Director, Harriet Lane Clinic
Johns Hopkins Medical Institutions
Baltimore, Maryland
MRSA
George K Siberry, MD, MPH
Pediatric Infectious Diseases
General Pediatrics & Adolescent Medicine
Johns Hopkins Medical Institutions
May 15, 2008
Disclosure: Nothing to Disclose
Learning Objectives
• Understand the emergence and origin of
methicillin-resistant S. aureus (MRSA) strains
causing infections in healthy children
• Recognize the clinical presentations of
community staphylococcal infections
• Learn how to work with your local laboratory to
understand local antibiotic susceptibility
patterns
• Develop an approach to the management of
suspected staphylococcal infections in children
in the face of high rates of community MRSA
Vignette
• 2 year old with painful red swelling on thigh, T
102, otherwise well. August, 2002.
• Started as a “spider bite” (Baltimore!)
• Exam reveals fluctuant lesion, that yields
copious pus with lancing, leaving a “crater”
• Mother and 6 year old brother have had similar
skin infections in past 2 months
• Treated with cephalexin
• Culture grows MRSA
• 2 day follow-up: no fever; no drainage; lesion
healing
Learning Objectives
• Understand the emergence and origin of
methicillin-resistant S. aureus (MRSA) strains
causing infections in healthy children
• Recognize the clinical presentations of
community staphylococcal infections
• Learn how to work with your local laboratory to
understand local antibiotic susceptibility
patterns
• Develop an approach to the management of
suspected staphylococcal infections in children
in the face of high rates of community MRSA
MRSA: A Healthcare Associated Infection
•
•
•
•
•
•
•
•
•
Hospitalization (1 year)
Surgery (1 year)
Long-term care
Dialysis
Permanent indwelling catheters or percutaneous
medical devices
Recent antibiotic use (6 months)
Intravenous drug use
*History of MRSA
*close contact with risk factor
MRSA first appeared in 1960s
Emergence of MRSA in the Community
Community-Acquired Methicillin-Resistant
Staphylococcus aureus in Children With No
Identified Predisposing Risk
JAMA, February 25, 1998 – 279(8)
Betsy C. Herold, MD; Lilly C. Immergluck, MD; Melinda
C. Maranan, MD; Diane S. Lauderdale, PhD; Ryan E.
Gaskin; Susan Boyle-Vavra, PhD; Cindy D. Leitch;
Robert S. Daum, MD
Emergence of MRSA in the Community
Emergence of MRSA in the Community
A Clone of Methicillin-Resistant
Staphylococcus aureus among Professional
Football Players
N Engl J Med 2005; 352:468-75
Sophia V. Kazakova, MD, MPH, PhD; Jeffrey C.
Hageman, MHS, et al.
Strain Characteristics
• Worldwide, the genetic backgrounds of
MRSA strains that emerged in the
community vary, but these strains share
some features
–
–
–
–
–
Distinct from strains established in healthcare
Non-multi-resistant
SCCmec IV or V
Panton Valentine Leukocidin (PVL) toxin genes
Propensity to cause infection in healthy
persons
Dice (Opt:0.50%) (Tol 1.3%-1.3%) (H>0.0% S>0.0%) [0.0%-100.0%]
100
80
70
60
50
90
S. aureus
Pulsed-Field Types
Pfsma
Pfsma
PFT MLST SCCmec
2001005114 .IVa 8
USA300
USA300 IV8
pvl
.POS
POS
NE
2001005078 .IVa 72 USA700 IV72
USA700
.NEG
NEG
NE
2000018626 .I I 5
USA100
USA100 I I5
.NEG
NEG
NE
2001035045 .I V 5
USA800
USA800 IV5
NEG
NEG
NE
99045065 .IVa 1
USA400
USA400 IV 1
.
POS
95009938 .I V 8
USA500
USA500 IV,8 I I
94042318 .IV 59 USA1000IV59
USA1000
96023760 . 15 USA900 MSSA
15 / 13
USA900
.NEG
NEG
NE
NEG/POSNE
1.NEG
99034758 .I I 45 USA600 I .I
USA600
.
NEG
96028758 .I I 36 USA200 I I36
USA200
.
NEG
PO
AA0097 .IVa 30 USA1100IV30
USA1100
POS
NE
2004711282 .
USA1200
McDougal et al J Clin Micro 2003;41:5113-20
USA1200MSSA POS
Prevalence of MRSA Nasal Colonization
by Age, 2001-02 and 2003-04
NHANES Nasal Swab Survey*
Overall MRSA Prevalence:
2001-02: 0.8%
2003-04: 1.5%
3.5
3
2.5
Percent
2
MRSA
1.5
Colonized
1
0.5
0
1-5
6-11 12-19 20-29 30-39 40-49 50-59 60+
Age in years
2001-02
*Preliminary Results
2003-04
Courtesy: Dr Rachel Gorwitz, CDC
Possible Virulence Factors
• Panton-Valentine Leukocidin toxin (PVL)
– Associated with necrotizing pneumonia, skin disease,
↑d complications in S. aureus osteomyelitis
– Strongly linked to “community” MRSA strains
– Also in some MSSA strains
– Recent studies both support and refute role in
virulence
• Arginine catabolic mobile element (ACME)
–
–
–
–
Likely acquired from S. epidermidis
Encodes arginine deaminase pathway
Inhibits PMN function, enhances survival at low pH
USA300-0114 and related strains, some USA100
Learning Objectives
• Understand the emergence and origin of
methicillin-resistant S. aureus (MRSA) strains
causing infections in healthy children
• Recognize the clinical presentations of
community staphylococcal infections
• Learn how to work with your local laboratory to
understand local antibiotic susceptibility
patterns
• Develop an approach to the management of
suspected staphylococcal infections in children
in the face of high rates of community MRSA
Community Associated MRSA (CA-MRSA):
Predominance of Skin and Soft Tissue
Infections
• 48/53 (91%) of CA-MRSA (Fergie,
PIDJ2001)
• 2542/2659 (96%) CA-MRSA
(Kaplan, PIDJ 2005)
Gorwitz RJ, et al
CDC Strategies for
clinical
management of
MRSA in the
community:
Summary of an
experts’ meeting
convened by the
CDC 2006.
Available at
http://www.cdc.gov
/ncidod/dhqp/ar_m
rsa_ca.html.
Brown Recluse Spider: Be Skeptical!
http://spiders.ucr.edu/images/colorloxmap.gif By permission of Dr Rick Vetter
MRSA Was the Most Commonly Identified Cause
of Purulent SSTIs Among Adult ED Patients
(EMERGEncy ID Net), August 2004
54%
39%
15%
97% MRSA -> USA 300
55%
74%
51%
68%
60%
60%
72%
67%
Moran et al NEJM 2006
Courtesy: Dr Rachel Gorwitz, CDC
Pediatric SSTI:
Dominance and Seasonal Pattern of MRSA
(Baltimore, Nov 2003-Oct 2005)
Number of Isolates
Seasonality Trends of Culture-Proven MSSA and MRSA Infections Over the
Study140
Period by Quarter
24%
120
100
80
60
40
25%
27%
76%
MRSA
35%
75%
MSSA
73%
65%
20
*
0
1
2
3
4
Quarter
• 76-77% MRSA overall; 87% CA-MRSA
• Rates especially high during both SUMMER periods
– Quarter 3 = July/August/September
Adapted from: SZCZESIUL PIDJ 2007
Learning Objectives
• Understand the emergence and origin of
methicillin-resistant S. aureus (MRSA) strains
causing infections in healthy children
• Recognize the clinical presentations of
community staphylococcal infections
• Learn how to work with your local laboratory to
understand local antibiotic susceptibility
patterns
• Develop an approach to the management of
suspected staphylococcal infections in children
in the face of high rates of community MRSA
Greater Susceptibility to Other Antibiotics but Varies by Region
Reproduced with permission. Fridkin et al. NEJM April 2005
Antibiotic Susceptibility (%) of Isolates from
Pediatric Staphylococcal SSTIs
MRSA (n = 217)
Antibiotic
HA (n = 28)
CA (n = 189)
All MRSA
Erythromycin
11
6
7
Clindamycin
93
97
96
100
100
100
Gatifloxacin
4
10
9
Tetracycline
82
83
83
TMP-SMX
Adapted from. SZCZESIUL PIDJ 2007
• Highest levels of susceptibility to TMP-SMX and to Clindamycin for CAMRSA and for ALL S. aureus
• Variations in susceptibility by region and over time
• Ask local laboratory/experts for trends in your area
Interpreting Clindamycin Susceptiblity
• Initial susceptiblity report….
– Erythro-R & Clinda-R  Resistant to clindamycin
– Erythro-S & Clinda-S  Susceptible to clindamycin
– Erythro-R but Clinda-S  Need D test to confirm clinda resistance
• D test
– NEGATIVE = Clindamycin susceptible (efflux mechanism of
erythro resistance)
– POSITIVE = Inducible clindamycin resistance (iMLSB)
• Inducible clindamycin resistance
– Avoid clindamycin for serious infections if iMLS present
– Clindamycin treatment: Inducible strain-> selection of mutant with
consitutive production -> treatment failure
– Occurs without macrolide exposure in patient
– Less certain relevance in less serious infections
– Frequency varies by region and over time
D Test for Inducible Clindamycin Resistance
On LEFT plate, blunting of zone of inhibition around clindamyin (C) disk on side adjacent to
erythromycin (E) disk is a positive D-test, indicating presence of iMLS. On RIGHT plate, there is
circular zone of inhibition around clindamycin disk, a negative D-test that indicates the absence of iMLS
and confirms clindamycin susceptibility.
NEGATIVE D TEST
POSITIVE D TEST
Erythro
disk
Clinda
disk
C
E
Blunted “D”
No blunting
Reproduced with permission. Siberry ASCP Tech Sample Microbiology No. MB-3, pp. 19-23
Learning Objectives
• Understand the emergence and origin of
methicillin-resistant S. aureus (MRSA) strains
causing infections in healthy children
• Recognize the clinical presentations of
community staphylococcal infections
• Learn how to work with your local laboratory to
understand local antibiotic susceptibility
patterns
• Develop an approach to the management of
suspected staphylococcal infections in children
in the face of high rates of community MRSA
Management Principles:
SSTI where CA-MRSA Prevalent
• Drain purulent collections
– Fitch MT, Manthey DE, McGinnis HD, Nicks BA,
Pariyadath M. Abscess Incision and Drainage.
NEJM 2007; 357:e20 [Videos in Clinical Medicine]
• Send specimens for culture [change from
previous practice!]
• Assessment of severity of illness
– Outpatient management if non-severe illness and
reliable follow up
• Empiric antibiotics
– Know local trends in antibiotic resistance
Drainage of Skin Abscesses is Essential
• 50 adults with cutaneous abscesses
• Random assigmnent to cephadrine vs
placebo
• Incision & Drainage for all
• 7 day follow-up:
– Ceph: 26/27 improved
– Placebo: 22/23 improved
• No cultures; Pre C-MRSA
Llera et al. Ann Emerg Med 1985;14:15-19
Good Outcome Despite Use of “Ineffective”
Antibiotic Pediatric CAMRSA SSTI
•
•
•
•
Children with CA-MRSA skin abscesses
96% I&D
62 (93%)- “ineffective antibiotic”
94% improved at follow-up (1-6d)
– Most NOT changed to effective antibiotic
• Risk factors for hospitalizaont at 1st f/u
– Larger Size (>5cm)
– NOT ineffective antibiotic
Lee MC et all PIDJ 2004; 23(2):123.
Antibiotics May Improve Outcome in a Minority of
MRSA SSTI Patients – But Which Ones?
• Observational study: adults with CA-MRSA SSTI
• Rates of Treatment failure….
– 16 (5%) of 312 episodes with active Abx
– 29 (13%) of 219 episodes with inactive ABx (p=.001)
• Small reduction in treatment failure rate if “active
antimicrobial therapy” prescribed at the time of
initial I&D or wound culture
• Independent predictor of treatment failure in MV
analysis
– Use of inactive Abx
– NOT size of the lesion
• Importance of antibiotics for most patients
Ruhe CID 2007
remains unclear
Specimens for Cellulitis
• Especially if associated with severe illness or
non-response to empiric therapy
• Better yield from point of maximal inflammation
21 children (3mos-16 yrs old) with cellulitis
– PMI positive in 57%: 29% SA, 10% GABHS
– Leading edge positive 5%: only CoNS
• Method
– Aspirate using 20-gauge needle (22-gauge for face)
on tuberculin syringe with 0.2ml of non-bacteriostatic
saline
– Saline used to flush sample onto plate
Howe PIDJ 1987;6(7):685
Initial Management of Suspected S. aureus Skin/Soft Tissue Infections
Reproduced
with
permission.
Baker
AAP
News
2008
I & D
Oral antibiotic Rx
 TMP/SXT†
 Clindamycin§
 Doxycycline
(if >7 years)
Follow-up at 48h
Hospitalize
I & D (when indicated)
Empirical vancomycin
or clindamycin§ until
culture results known
Hospitalize
I & D (when
indicated)
Empirical
vancomycin PLUS
nafcillin  other
agents
Initial Management of Suspected S.
aureus Skin/Soft Tissue Infections
Reproduced with permission. Baker AAP News 2008
Initial Management of Suspected S. aureus Skin/Soft Tissue
Infections
Reproduced with
permission. Baker AAP
News 2008
I & D
Oral antibiotic Rx
 TMP/SXT†
 Clindamycin§
 Doxycycline
(if >7 years)
Follow-up at 48h
Manage as for Severe
Infection
* Immunocompromise: any chronic illness except asthma or eczema
† TMP/SXT = trimethoprim/sulfamethoxazole if group A Streptococcus unlikely
§ Consider prevalence of clindamycin susceptible and “D” test negative CA-MRSA
strains in the community
Initial Management of Suspected S. aureus Skin/Soft Tissue Infections
Hospitalize
I & D (when indicated)
Empirical vancomycin
or clindamycin§ until
culture results known
Hospitalize
I & D (when
indicated)
Empirical
vancomycin PLUS
nafcillin  other agents
Reproduced
with
permission.
Baker
AAP
News
2008
• Evaluation and treatment for other pathogens and processes
• Consultation with an expert in management of CA MRSA infections
Athletics Associated MRSA
Infections
• Recommendations for infection control
– Avoid body shaving
– Reduce turf burns
– Exclude until MRSA infection healed
– Cover open wounds
– Change water and disinfect whirlpool between
uses
Begier EM et al CID 2004;39:1446-53.
Recurrent Infections
• MRSA Skin/Abscess study – Dallas*
– 12% with prior cutaneous abscess
– 4.3% recurrent abscess within 2-6 months
•
•
•
•
“Ping-pong” of infections in household
Poor predictors of who will get recurrent infections
Mixed data about role of (nasal) colonization
Consider trial of decolonization
– If anterior nares culture positive
– 5 days intranasal mupirocin BID +/- chlorhexidine
– Efficacy not proven!
*Lee MC et all PIDJ 2004; 23(2):123.
Concern for Immunodeficiency
• Recurrent, severe infections, especially if
due to different S. aureus strains
• Principal defenses against S. aureus
– Skin and mucosal surfaces
– Phagocytes
• If evaluating, focus on abnormal number
or function of phagocytes:
– Neutropenia, CGD, Job (Hyper IgE), LAD
Invasive Infections
CA-MRSA: SSTI Typical…but
Invasive Disease Alarming
• Sepsis/invasive disease less common– increasing?
– 2003-4: 3/21 pediatric influenza deaths assoc with MRSA
– 2006-07: 15/72 pediatric influenza deaths associated
with MRSA [CDC Health advisory 268, Jan 2008 ]
– 2 children with MRSA sepsis and WaterhouseFriedrichson syndrome [Adem NEJM 2005]
– 62% of invasive SA due to CA MRSA [Gonzalez CID 2005]
• 67% had pulmonary disease
• 43% with osteomyelitis + pneumonia (emboli)
– Adolescents with CA MRSA sepsis [Gonzalez Ped 2005]
• bone/joint, pulmonary, thrombosis
Approach to Management
• “Amid a sea of boils, an invasive disease
case will leap out and bite you!”
• Invasive illness
– Usually systemically ill at presentation
– Does not usually progress from a boil
– Blood cultures often positive
– **MRSA common in your community->
increase suspicion of MRSA in serious illness
Incidence of Invasive CA-MRSA
Varies by Age and Race*
Active Bacterial Core Surveillance (ABCS), 2005
Rate per 100,000
persons
White
Black
Overall Incidence:
4.6 per 100,000
25
20
15
10
5
0
<1
1
2-4
Courtesy: Dr Rachel Gorwitz, CDC
5-17
18-34
35-49
50-64
>64
Age in years
*Preliminary Results (Courtesy of Monina Klevens and Melissa Morrison)
Distribution of CA-MRSA Cases by
Syndrome, ABCs 2005
Disease Syndrome
Bacteremia
Pneumonia
Cellulitis
Osteomyelitis
Endocarditis
Septic shock
Total
(%)
529 (65%)
115 (14%)
189 (23%)
64 (8%)
106 (13%)
40 (5%)
813 (100%)
Bacteremia with TRIAD: Lung lesions + Osteomyelitis + Thrombosis
Adapted from Dr Rachel Gorwitz, CDC
Treatment of Suspected Invasive S.
Aureus Infections
• Hospitalize – consider ID consult
• Empiric
–
–
–
–
Vancomycin (or Linezolid)*
Add gentamicin or rifampin, if severe illness
Add oxacillin if endocarditis suspected
Alternative for less serious illness: clindamycin (if
clinda-S MRSA prevalent) or oxacillin (if MRSA not
common in the community)
• Culture-proven MRSA
– Endocarditis: Vanco + [gent or rifampin] + ID consult
– Skin, Bone, Other tissue focus
• Susceptibility report
• Vancomycin, Linezolid, Clindamycin (Dtest negative)
• Other options: TMP/SMX, Doxycycline (>8 yr old)
*(Dapto, Tigecycline- adults); ceftobiprole under study
HOSPITAL
SETTING
COMMUNITY
SETTING
Hospital Transmission of CA-MRSA
• 8 MRSA skin/soft tissue infections in postpartum
women without risk factors
– Delivered August 2002 (NYC)
– Mean 23 days (4-73 days)
– 4 mastitis/abscess, 1 each: wound, cellulitis,
pustulosis, pustulosis/UTI
– 3 readmitted
• Infants not affected or colonized
• Identical MRSA with CA characteristics
– PFGE idential; PVL, scc type IV
Saiman CID 2003;37:1313
Role of CA-MRSA in Bacteremia
• 116 consecutive MRSA BSI isolates from
Grady Hospital over 7.5 months in 2004
– 39/116 (34%) were due to the USA300
genotype
– 10/49 (20%) of the nosocomial isolates were
USA300
– 30/107 (28%) of the healthcare-associated
isolates were USA300
• “CA” MRSA has become a healthcareassociated pathogen
Naimi et al. JAMA. 2003;290(22):2976-84
Seybold et al. Clin Infect Dis. 2006;42:647-56
Vignette
• 2 year old with painful red swelling on thigh, T
102, otherwise well. August.
• Started as a “spider bite” (Baltimore)
• Exam reveals fluctuant lesion, that yields
copious pus with lancing, leaving a “crater”
• Mother and 6 year old brother have had similar
skin infections in past 2 months
• Treated with cephalexin
• Culture grows MRSA
• 2 day follow-up: no fever; no drainage; lesion
healing
Thank You
Questions?