Upload
milo-gregory
View
216
Download
1
Tags:
Embed Size (px)
Citation preview
Management of Suspected Staphylococcal Infections in
Children in the Era of Community MRSA
Thursday, May 15, 200812:00 – 1:00 p.m. EDT
© American Academy of Pediatrics 2008
Moderator: Marlene R. Miller, MD, MSc, FAAPVice President, Quality - NACHRIDirector of Quality and Safety & Associate ProfessorJohns Hopkins Children’s CentersBaltimore, Maryland
This activity was funded through an educational grant from the
Physicians’ Foundation for Health Systems Excellence.
Visit our website:http://www.aap.org/saferhealthcare
Resources: Useful strategies, valuable information links, and expert advice on reducing or eliminating medical errors affecting children.
Webinars: Register for an upcoming, live Webinar, and earn a maximum of 1.0 AMA PRA Category 1 Credit™. Or, access a full archive, including
audio, from one of the past Webinar offerings. Or, download just the Podcast or slide set from an archive.
Latest News: Links to recent articles relating to pediatric patient safety.
Email List: An e-community dedicated to pediatric patient safety issues and information exchange with other clinicians.
Parents’ Corner: Resources to help parents understand what they can do to help ensure their optimal safety in the health care that their child
receives.
DISCLOSURESNone of the individuals involved in this webinar
(Speakers, Moderator, Project Advisory Committee members, or Staff) has disclosed
any relevant financial relationships or any financial relationships with the manufacturer(s) of any commercial product(s) and/or provider of commercial services discussed in CME activities.
None of the individuals (Speakers, Moderators, Project Advisory Committee members, or Staff)
has disclosed that they intend to discuss or demonstrate pharmaceuticals and/or medical
devices that are not approved.
Refer to full AAP Disclosure Policy & Grid available below for download.
CME CREDITLive Webinar Only
The American Academy of Pediatrics (AAP) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AAP designates this educational activity for a
maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
This activity is acceptable for up to 1.0 AAP credits.
These credits can be applied toward the AAP CME/CPD Award available to Fellows and Candidate Fellows of the American Academy of Pediatrics.
OTHER CREDITLive Webinar Only
This program is approved for 1.0 NAPNAP contact hours of which 0 contain pharmacology (Rx) content per the National Association of Pediatric Nurse Practitioners Continuing Education Guidelines.
The American Academy of Physician Assistants
accepts AMA PRA Category 1 Credit(s)TM from organizations accredited by the ACCME.
Speaker: George K. Siberry, MD, MPH, FAAPAssistant Professor of PediatricsMedical Director, Harriet Lane ClinicJohns Hopkins Medical InstitutionsBaltimore, Maryland
MRSA
George K Siberry, MD, MPHPediatric Infectious Diseases
General Pediatrics & Adolescent MedicineJohns Hopkins Medical Institutions
May 15, 2008Disclosure: 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
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
9080706050
PFT SCCmecMLST pvl
USA300 8 IV POS
USA700 72 IV NEG
USA100 5 I I NEG
USA800 5 IV NEG
USA400 1 IV POS
USA500 8 IV, I I NEG
USA1000 59 IV NEG/POS
USA900 15 MSSA NEG
USA600 45 I I NEG
USA200 36 I I NEG
USA1100 30 IV POS
USA1200 MSSA POS
S. aureus Pulsed-Field Types
McDougal et al J Clin Micro 2003;41:5113-20
Prevalence of MRSA Nasal Colonization by Age, 2001-02 and 2003-04
NHANES Nasal Swab Survey*
0
0.51
1.5
2
2.53
3.5
1-5 6-11 12-19 20-29 30-39 40-49 50-59 60+
Age in years
Percent MRSA
Colonized
2001-02 2003-04
Overall MRSA Prevalence:2001-02: 0.8%2003-04: 1.5%
*Preliminary ResultsCourtesy: 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 forclinical management of MRSA in the community: Summary of an experts’ meetingconvened by the CDC 2006. Available athttp://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html.
Brown Recluse Spider: Be Skeptical!
http://spiders.ucr.edu/images/colorloxmap.gif By permission of Dr Rick Vetter
54%
51%
60%60%
67%
74%
39%
15%
55%
68%
72%
MRSA Was the Most Commonly Identified Cause of Purulent SSTIs Among Adult ED Patients
(EMERGEncy ID Net), August 2004
Moran et al NEJM 2006Courtesy: Dr Rachel Gorwitz, CDC
97% MRSA -> USA 300
Pediatric SSTI: Dominance and Seasonal Pattern of MRSA
(Baltimore, Nov 2003-Oct 2005)
• 76-77% MRSA overall; 87% CA-MRSA• Rates especially high during both SUMMER periods
– Quarter 3 = July/August/September
0
20
40
60
80
100
120
140
1 2 3 4
Quarter
Num
ber
of Is
olat
es
MSSA
MRSA 35%
65%
25%
24%
76% 27%
73% 75%
*
Seasonality Trends of Culture-Proven MSSA and MRSA Infections Over the Study Period by Quarter
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
Reproduced with permission. Fridkin et al. NEJM April 2005
Greater Susceptibility to Other Antibiotics but Varies by Region
Antibiotic Susceptibility (%) of Isolates from Pediatric Staphylococcal SSTIs
• Highest levels of susceptibility to TMP-SMX and to Clindamycin for CA-MRSA and for ALL S. aureus
• Variations in susceptibility by region and over time
• Ask local laboratory/experts for trends in your area
Adapted from. SZCZESIUL PIDJ 2007
MRSA (n = 217)
Antibiotic
HA (n = 28) CA (n = 189) All MRSA
Erythromycin 11 6 7
Clindamycin 93 97 96
TMP-SMX 100 100 100
Gatifloxacin 4 10 9
Tetracycline 82 83 83
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
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.
EErythrodisk
CClindadisk
POSITIVE D TEST NEGATIVE D TEST
Blunted “D”No blunting
Reproduced with permission. Siberry ASCP Tech Sample Microbiology No. MB-3, pp. 19-23
D Test for Inducible Clindamycin Resistance
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
• 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
Drainage of Skin Abscesses is Essential
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 remains unclear Ruhe CID 2007
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
Repro-duced with permis-sion. Baker AAP News 2008
I & DOral antibiotic Rx
TMP/SXT† Clindamycin§ Doxycycline (if >7 years)
Follow-up at 48h
HospitalizeI & D (when indicated)Empirical vancomycin or clindamycin§ until culture results known
HospitalizeI & 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
Manage as for Severe Infection
Initial Management of Suspected S. aureus Skin/Soft Tissue Infections
Reproduced with permission. Baker AAP News 2008
I & DOral antibiotic Rx
TMP/SXT† Clindamycin§ Doxycycline (if >7 years)
Follow-up at 48h
* 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
• Evaluation and treatment for other pathogens and processes
• Consultation with an expert in management of CA MRSA infections
HospitalizeI & D (when indicated)Empirical vancomycin or clindamycin§ until culture results known
HospitalizeI & D (when indicated)Empirical vancomycin PLUS nafcillin other agents
Repro-duced with permis-sion. Baker AAP News 2008
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
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 Waterhouse-Friedrichson 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-MRSAVaries by Age and Race*
Active Bacterial Core Surveillance (ABCS), 2005
0
5
10
15
20
25
<1 1 2-4 5-17 18-34 35-49 50-64 >64
Age in years
White BlackRate per 100,000 persons
*Preliminary Results (Courtesy of Monina Klevens and Melissa Morrison)
Overall Incidence:4.6 per 100,000
Courtesy: Dr Rachel Gorwitz, CDC
Distribution of CA-MRSA Cases by Syndrome, ABCs 2005
Disease Syndrome (%)
Bacteremia 529 (65%)Pneumonia 115 (14%)Cellulitis 189 (23%)Osteomyelitis 64 (8%)Endocarditis 106 (13%)Septic shock 40 (5%)Total 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 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 healthcare-associated pathogen
Naimi et al. JAMA. 2003;290(22):2976-84Seybold 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