Community Associated Community Associated Resistant Bacteria:What Resistant Bacteria:What Bugs and What Drugs Bugs and What Drugs Work Against Them?Work Against Them?

Lilly Immergluck, MDLilly Immergluck, MDAssociate Professor of PediatricsAssociate Professor of Pediatrics

Divisions of General Pediatrics and Pediatric Infectious DiseasesDivisions of General Pediatrics and Pediatric Infectious Diseases

Morehouse School of MedicineMorehouse School of Medicine

March 1, 2006March 1, 2006

Background InformationBackground Information

New Resistant Bacteria

Mutations

XX

Emergence of Antimicrobial Emergence of Antimicrobial ResistanceResistance

Susceptible Bacteria

Campaign to Prevent Antimicrobial Resistance in Healthcare Settings

Resistant Bacteria

Resistance Gene Transfer

Resistant StrainsRare

xx

Resistant Strains Dominant

Antimicrobial Exposure

xxxx

xx

xx

xx

Selection for antimicrobial-Selection for antimicrobial-resistant Strainsresistant Strains

Campaign to Prevent Antimicrobial Resistance in Healthcare Settings

What “Bugs” are we talking What “Bugs” are we talking about…in about…in PediatricsPediatrics? ?

Community-associated Methicillin Community-associated Methicillin Resistant Resistant Staphylococcus aureusStaphylococcus aureus

Drug Resistant Drug Resistant Streptococcus Streptococcus pneumoniaepneumoniae

Methicillin Resistant Methicillin Resistant Staphylococcus aureusStaphylococcus aureus

Lowy, Frank,Staphylococcus Infections. NEJM. August, 1998

Types of MRSATypes of MRSA

BRSA- Borderline BRSA- Borderline MRSAMRSA

MRSA- related to MRSA- related to mecmecA gene=ORSAA gene=ORSA

Hospital associated Hospital associated MRSAMRSA

Community Community associated MRSAassociated MRSA

Mechanism of Resistance for Mechanism of Resistance for MRSAMRSA

Staphylococcal chromosomal Staphylococcal chromosomal cassette cassette mec IV, type 4mec IV, type 4

(SCC (SCC mec type IV)mec type IV)

Derensinski S. Clin Infect Dis 2005:562-73

Emergence of USA 300 cloneEmergence of USA 300 clone

Result of insertion of SCCResult of insertion of SCCmecAmecA type IV type IV Donor staph isolate is MSSADonor staph isolate is MSSA Differences from HA-MRSA:Differences from HA-MRSA:

Gene cassette coding for methicillin Gene cassette coding for methicillin resistanceresistance

Carriage of plasmids encoding resistance to Carriage of plasmids encoding resistance to antibiotics of other classesantibiotics of other classes

Associated virulence factorAssociated virulence factor

SCCSCCmecmec types I-V types I-V

SCCmec type

Size of SCCmec

Other Antibiotic Resistance elements on SCCmec

Origin of S. aureus isolates

Presence of Panton Valentine leukocidin

I 34 ... Hospital Infrequent

II 53PUB110 (aadD)b, Tn554 (ermA)c Hospital Infrequent

III 67 PUB110 (aadD)b, PT181 (tetK)d Hospital Infrequent

IV21–24 ... Community Frequent

V 28 ... Community Unknown

Derensinski S. Clin Infect Dis 2005:562-73

Staphylococcus sp.Staphylococcus sp.

““Isolates of staphylococci that are shown Isolates of staphylococci that are shown to carry the mecA gene, or that produce to carry the mecA gene, or that produce PBP2a, the gene product, should be PBP2a, the gene product, should be reported as oxacillin resistant”reported as oxacillin resistant”

Epidemiology of MRSAEpidemiology of MRSA

First described in 1961First described in 1961 Approximately 50% of Approximately 50% of Staphylococcus Staphylococcus

aureus aureus infections in ICU in US due to infections in ICU in US due to MRSAMRSA

Risk Factors for Hospital Risk Factors for Hospital acquired MRSA in Adultsacquired MRSA in Adults

Prolonged/recurrent antibiotic exposureProlonged/recurrent antibiotic exposure Prolonged hospitalization or ICUProlonged hospitalization or ICU Chronically illChronically ill Nursing home residenceNursing home residence Dialysis or MalignancyDialysis or Malignancy

HA-MRSA PrevalenceHA-MRSA Prevalence

Lowy, Frank,Staphylococcus Infections. NEJM. August, 1998

Definition of Community-Definition of Community-associated MRSAassociated MRSA

Salgado, Farr, Calfee Clin Infect Dis, 2003

Epidemiology of Community Epidemiology of Community acquired MRSAacquired MRSA

Case Report in ChicagoCase Report in Chicago Outbreak among high school wrestling Outbreak among high school wrestling

team in Vermontteam in Vermont Reports have occurred in Chicago, Reports have occurred in Chicago,

Minnesota, North Dakota, Dallas, Minnesota, North Dakota, Dallas, Winnipeg, Toronta, and in AustraliaWinnipeg, Toronta, and in Australia

Headlines to catch our attention…Headlines to catch our attention…

• Methicillin-Resistant Staphylococcus aureus Infections Among Competitive Sports Participants --- Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000—2003

Four Pediatric Deaths from Community-Acquired Methicillin-Resistant Staphylococcus aureus -- Minnesota and North Dakota, 1997-1999

Study Finds Spread of Resistant Staph

By THE ASSOCIATED PRESS

Published: April 7, 2005

Study Finds Spread of Resistant Staph

By THE ASSOCIATED PRESS

Published: April 7, 2005

““Study Finds Spread of Study Finds Spread of Resistant Staph”Resistant Staph”

By THE ASSOCIATED PRESS By THE ASSOCIATED PRESS Published: April 7, 2005, NY TimesPublished: April 7, 2005, NY Times

“PRO FOOTBALL; After Medical Scare, Giants' Center Improves”

November 4, 2004, Thursday By LYNN ZINSER (NYT); Sports Desk Late Edition - Final, Section D, Page 4,

“At first, Giants center Shaun O'Hara said he had no idea why his swollen calf was causing so much alarm among team trainers last week. He knew nothing about the staph infections that had struck seven Miami Dolphins last year, hospitalizing two of them, or of…”

Fatal Pediatric Infections from Fatal Pediatric Infections from CA-MRSACA-MRSA

Case 1 Case 2 Case 3 Case 4

Age 7 years 16 months 13 years 12 months

Syndrome septic arthritis, sepsis, pneumonia/ empyema

severe sepsis

necrotizing pneumonia, severe sepsis

necrotizing pneumonia, severe sepsis

Antimicrobial susceptibility*

t/s, tet, cip, gent, ery, clind, vanc

t/s, tet, cip, gent, ery, clind, vanc

t/s, cep, cip, gent, ery, clind, vanc

t/s, tet, cip, gent, ery, clind, vanc

Toxin test+ SEC positive

SEC positive SEB positive

SEB positive

Source: Centers for Disease Control and Prevention, Atlanta , October 1999 / HOSPITAL INFECTION CONTROL

Minnesota Surveillance Study, Minnesota Surveillance Study, 19971997

Naimi,LeDell et al Clin Infect Dis 2001

Summary of Age Distribution of CA-Summary of Age Distribution of CA-MRSA in MinnesotaMRSA in Minnesota

N=354 Age Median 16 years (1-78) 1-10 years 38% <6 years 23% Race Native Americans 40%* Blacks 18% Other (Unknown) 4% (18%) *excluded Hospital F which predominantly served native Americans Naimi, TS et al CID 2001: 33

Clinical PresentationClinical Presentation

Maybe as simple as this…Maybe as simple as this…

courses.washington.edu, accessed from web 2/28/06courses.washington.edu, accessed from web 2/28/06

Or more severe as this…Or more severe as this…

www.emedicine.com/ped, accessed Feb 28, 2006

MRSA Pneumonia/EmpyemaMRSA Pneumonia/Empyema

Clinical Presentation of Children Clinical Presentation of Children with CA-MRSAwith CA-MRSA

Herold, Immergluck, et al JAMA 1998

Summary of Risk Factors for Summary of Risk Factors for CA-MRSACA-MRSA

Risk factor type 1 Risk factor type 2 Risk factor type 3 Risk factor type 4

Previously healthy Patient with primary skin infections (e.g. furuncles, impetigo,

scalded skin syndrome)

Ethic minority group Age: risk decreases as age increases

No recent direct or indirect hospital/care facility exposure (e.g. via family member) Patients with risk factor for MSSAb

Patients with abscesses or cellulitis

Low socioeconomic status

Risk factor from one group

Low overall risk – culture and susceptibilities not required

Risk factors from all four groups

Risk indicated that culture and susceptibilities not performed

aAdopted as a working definition; will include H-MRSA with these characteristics. bSee case control study in Moreno et al. [25].

Eady, Cove, Curr Opin Infect Dis, 2003

What Drugs Can Treat This What Drugs Can Treat This Bug?Bug?

Inducible clindamycin resistance(erm-mediated)

…another example

“D Test” – positive reaction

15 - 26 mm15 - 26 mm

Photos courtesy of J. Jorgensen and K. FiebelkornPhotos courtesy of J. Jorgensen and K. Fiebelkorn..

“D Test” – negative reaction

NO induction

(msrA-mediated erythromycin resistance)

MRSA—MRSA—Erythromycin/Erythromycin/

Clindamycin StoryClindamycin StoryMechanismMechanism PathwayPathway ErythroErythro ClindaClinda

EffluxEfflux msrAmsrA RR SS

Ribosome Ribosome alterationalteration

ermerm RR R*R*

Treatment of CA-MRSATreatment of CA-MRSA

Options are better than hospital acquired-Options are better than hospital acquired-MRSAMRSA

Almost all are clindamycin susceptibleAlmost all are clindamycin susceptible Trimethoprim-sulfamethoxazoleTrimethoprim-sulfamethoxazole Role of quinolonesRole of quinolones

HA-MRSA HA-MRSA susceptibility patternsusceptibility pattern

Profile 1Profile 1 ClindamcinClindamcin RR ErythromycinErythromycin RR OxacillinOxacillin RR PenicillinPenicillin RR VancomycinVancomycin SS

Profile 2Profile 2 CefazolinCefazolin SS ClindamycinClindamycin RR ErythromycinErythromycin RR OxacillinOxacillin RR PenicillinPenicillin RR VancomycinVancomycin SS

CA-MRSA often susceptible to:CA-MRSA often susceptible to:

ClindamycinClindamycin ErythromycinErythromycin FluoroquinolonesFluoroquinolones LinezolidLinezolid

RifampinRifampin TetracyclinesTetracyclines Trimeth-sulfaTrimeth-sulfa VancomycinVancomycin

Treatment RegimensTreatment Regimens

Severe infections, multi drug resistant infectionsSevere infections, multi drug resistant infections VancomycinVancomycin DaptomycinDaptomycin Linezolid (pneumonia)Linezolid (pneumonia) Quinopristin/dalfopristinQuinopristin/dalfopristin

Limited infections, less severeLimited infections, less severe TMP-SMZTMP-SMZ LinezolidLinezolid ?No treatment?No treatment

Data in Atlanta AreaData in Atlanta Area

Adult studiesAdult studies Pediatric studiesPediatric studies

Risk Factors for CA-MRSA Risk Factors for CA-MRSA Colonization in AdultsColonization in Adults

HIV infectionHIV infection Lower risk if HIV infected and receiving Lower risk if HIV infected and receiving

antibiotics within 3 months before admissionantibiotics within 3 months before admission History of skin or soft tissue infectionHistory of skin or soft tissue infection Hospitalization within preceding yearHospitalization within preceding year Receipt of antibiotics within 3 months Receipt of antibiotics within 3 months

before admissionbefore admission

Hidron, AI, Kourbatova, EV, et al, Clin Infect Dis 2005

Susceptibility of Isolates, by pulsed-Susceptibility of Isolates, by pulsed-field typefield type

Hidron, AI, Kourbatova, EV, et al, Clin Infect Dis 2005

Preliminary Data for Atlanta Preliminary Data for Atlanta ChildrenChildren

3169 3169 Staphylococcus aureusStaphylococcus aureus isolates isolates from 1/2002-12/2004from 1/2002-12/2004

656 (21%) CA-MRSA isolates by phenotype656 (21%) CA-MRSA isolates by phenotype 485 (15%) HA-MRSA isolates by phenotype485 (15%) HA-MRSA isolates by phenotype

Based on data collected from Egleston and Scottish Rite HospitalsBased on data collected from Egleston and Scottish Rite Hospitals

Proportional Proportional S.aureusS.aureus isolates at isolates at Scottish RiteScottish Rite

0%10%20%30%40%50%60%70%80%90%

100%

MSSA HA-MRSA CA-MRSA

Isol

ates

Proportional Proportional S. aureusS. aureus isolates isolates at Eglestonat Egleston

0%10%20%30%40%50%60%70%80%90%

100%

MSSA HA-MRSA CA-MRSA

Isol

ates

Incidence of SSTI due to Incidence of SSTI due to S. aureusS. aureus isolates among Scottish Rite ER isolates among Scottish Rite ER

Patients, 2002-2004Patients, 2002-2004

0

5

10

15

20

25

1 2 3 4 5 6 7 8 9 10 11

CA-MRSA HA-MRSA MSSA

Iso

late

s/10

,000

ER

vis

its

Incident CA-MRSA Isolates from Incident CA-MRSA Isolates from SSTI’s at Egleston and Scottish SSTI’s at Egleston and Scottish

Rite ER PatientsRite ER Patients

0

5

10

15

20

25

1 2 3 4 5 6 7 8 9 10 11

EGL CA-MRSA SCO CA-MRSA

Iso

late

s/10

,000

ER

vis

its

Where do we go from here?Where do we go from here?

Surveillance of children who are colonized Surveillance of children who are colonized with CA-MRSAwith CA-MRSA

Understand risk factors for colonization Understand risk factors for colonization and subsequent infections due to CA-and subsequent infections due to CA-MRSAMRSA

Understand household transmission of Understand household transmission of CA-MRSACA-MRSA

Develop strategies for eradication of Develop strategies for eradication of colonizationcolonization