CA-MRSA: What You Need to Know

CA-MRSA:CA-MRSA:What You Need to KnowWhat You Need to Know

Mahesh C. Patel, M.D.Mahesh C. Patel, M.D.Internal Medicine-IDInternal Medicine-ID

NBHNNBHNNovember 10, 2009November 10, 2009

Need More Information?Need More Information?

http://www.cdc.gov/ncidod/dhqp/pdf/ar/CAMRSA_ExpMtgStrategies.pdf

Daum, RS. Skin and soft tissue infections caused by MRSA. NEJM 2007. 357:380-390.

Wallin, et al. Community-Associated MRSA. Emerg Med Clin N AM 2008. 26:431-455.

Community-Associated MRSA:Community-Associated MRSA:CDC Population-Based Surveillance CDC Population-Based Surveillance

DefinitionDefinition MRSA culture in outpatient setting or 1MRSA culture in outpatient setting or 1stst 48 48

hours of hospitalization AND patient lacks hours of hospitalization AND patient lacks risk factors for healthcare-associated MRSA:risk factors for healthcare-associated MRSA:– HospitalizationHospitalization– SurgerySurgery– Long-term careLong-term care– DialysisDialysis– Indwelling devicesIndwelling devices– History of MRSAHistory of MRSA

www.cdc.gov

MicrobiologyMicrobiology

Methicillin resistance is Methicillin resistance is mediated by the mecA gene mediated by the mecA gene (PBP2A)(PBP2A)

mecA gene on SCCmecmecA gene on SCCmec– HA-MRSA: SCCmec I-IIIHA-MRSA: SCCmec I-III– CA-MRSA: SCCmec IV-VCA-MRSA: SCCmec IV-V– II and III carry resistance for non-II and III carry resistance for non-

beta lactams as wellbeta lactams as well

PathophysiologyPathophysiology

PVL: Panton-Valentine PVL: Panton-Valentine LeukocidinLeukocidin

– Exotoxin that is lethal to leukocytesExotoxin that is lethal to leukocytes

– May be responsible for enhanced May be responsible for enhanced pathogenicity of CA-MRSApathogenicity of CA-MRSA

– NOT opportunistic NOT opportunistic

King, M. D. et. al. Ann Intern Med 2006;144:309-317

Clinical and molecular epidemiology of Staphylococcus aureus skin and soft-tissue infection

Outbreaks of MRSA in the Outbreaks of MRSA in the CommunityCommunity

Often first detected as clusters of Often first detected as clusters of abscesses or “spider bites”abscesses or “spider bites”

Various settingsVarious settings– Sports participantsSports participants– Inmates in correctional facilitiesInmates in correctional facilities– Military recruitsMilitary recruits– Daycare attendeesDaycare attendees– Native Americans / Alaskan NativesNative Americans / Alaskan Natives– Men who have sex with menMen who have sex with men– Tattoo recipientsTattoo recipients– Hurricane evacuees in sheltersHurricane evacuees in shelters– HIV-infected individualsHIV-infected individuals– African AmericansAfrican Americans– Pregnant and postpartum womenPregnant and postpartum women

Slide adapted from Gorwitz, R. CDC 2007.

Contaminated Surfacesand Shared Items

Frequent Contact

Cleanliness

Crowding

Factors that Facilitate TransmissionFactors that Facilitate Transmission

Antimicrobial Use

Compromised Skin

Slide Courtesy of Gorwitz, R. CDC 2007.

CA-MRSA Infections are Mainly Skin CA-MRSA Infections are Mainly Skin InfectionsInfections

Disease Syndrome (%)

Skin/soft tissue 1,266 (77%)Wound (Traumatic) 157 (10%)Urinary Tract Infection 64 (4%)Sinusitis 61 (4%)Bacteremia 43 (3%)Pneumonia 31 (2%)

Fridkin et al NEJM 2005;352:1436-44 Slide Courtesy of Gorwitz, R. CDC 2007.

Most Invasive MRSA Infections Are Most Invasive MRSA Infections Are Healthcare-AssociatedHealthcare-Associated

Healthcare-Associated

Community-Associated

Klevens et al JAMA 2007;298:1763-71

14% 86%


Incidence of Invasive CA-MRSA Infections and Incidence of Invasive CA-MRSA Infections and Deaths by AgeDeaths by Age

Active Bacterial Core surveillance (ABCS), 2005Active Bacterial Core surveillance (ABCS), 2005

0

2

4

6

8

10

<1 1 2-4 5-17 18-34 35-49 50-64 >64

Age in years

Infections DeathsIncidence per 100,000 persons

Klevens et al JAMA 2007;298:1763-71

Overall Incidence (all ages):Infections: 4.6 per 100,000Deaths: 0.5 per 100,000


Age Group (yr)

Atlanta, 2001-2002 Baltimore, 2002

0

10

20

30

40

50

60

70

80

<2 2-18 19-64 >64

01020304050607080

<2 2-18 19-64 >64

Incidence, Cases per 100,000

Age Group (yr)

BlackWhite

BlackWhite

CA-MRSA Incidence Varies by Age and Race

26 per 100,000 18 per 100,000

•Fridkin et al NEJM 2005;352:1436-44Slide Courtesy of Gorwitz, R. CDC 2007.

54%

51%

60%60%

67%

74%

39%

15%

55%

68%

72%

59%(97% USA300)

MRSA Was the Most Commonly Identified Cause MRSA Was the Most Commonly Identified Cause of Purulent SSTIs Among Adult ED Patients of Purulent SSTIs Among Adult ED Patients

((EMERGEEMERGEncy ID Net), August 2004ncy ID Net), August 2004

Moran et al NEJM 2006;355:666-674Slide Courtesy of Gorwitz, R. CDC 2007.

0

5

10

15

20

Year 1 Year 2 Year 3

% C

linda

myc

in R

esis

tant

Community Onset, Healthcare-associated MRSA

Community-associated MRSA

Clindamycin Resistance Among MRSA Isolates, Texas Children’s Hospital, Houston Texas,2001-2004

n=551

n=915 n=1192n=198

n=163

n=181

Source: Hulten et al. PIDJ 2006;25:349-53, and Kaplan et al. Clin Infect Dis 2005;40:1785-91


Emerging Multi-Drug Resistance in Emerging Multi-Drug Resistance in USA300?USA300?

Clusters of USA300 isolates with multiple Clusters of USA300 isolates with multiple resistance to erythromycin, clindamycin, resistance to erythromycin, clindamycin, tetracycline, ciprofloxacin, and mupirocintetracycline, ciprofloxacin, and mupirocin11

Resistance to Resistance to ≤ ≤ one class of antibiotics other one class of antibiotics other than beta-lactams is still the most common than beta-lactams is still the most common resistance pattern in MRSA USA300resistance pattern in MRSA USA300

TMP/SMX resistance rare in MRSA USA300 TMP/SMX resistance rare in MRSA USA300

1Diep et al Lancet 2006. Han et al J Clin Micro 2007. Slide Courtesy of Gorwitz, R. CDC 2007.

Strategies for Clinical Management of MRSA Strategies for Clinical Management of MRSA in the Communityin the Community

http:www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html

Clinical Considerations - EvaluationClinical Considerations - Evaluation

MRSA belongs in the differential MRSA belongs in the differential diagnosis of skin and soft tissue diagnosis of skin and soft tissue infections (SSTI’s) compatible with infections (SSTI’s) compatible with S. aureusS. aureus infection: infection:

Abscesses, pustular Abscesses, pustular lesions, “boils”lesions, “boils”

““Spider bites”Spider bites”

Cellulitis?Cellulitis?


Clinical Considerations - EvaluationClinical Considerations - Evaluation MRSA should also be considered in differential diagnosis MRSA should also be considered in differential diagnosis

of severe disease compatible with of severe disease compatible with S. aureusS. aureus infection: infection:

– OsteomyelitisOsteomyelitis

– EmpyemaEmpyema

– Necrotizing pneumoniaNecrotizing pneumonia

– Septic arthritisSeptic arthritis

– EndocarditisEndocarditis

– Sepsis syndromeSepsis syndrome

– Necrotizing fasciitisNecrotizing fasciitis

– Purpura fulminansPurpura fulminans


Management of Skin Infections Management of Skin Infections in the Era of CA-MRSAin the Era of CA-MRSA

I&D should be routine for purulent skin I&D should be routine for purulent skin lesionslesions

Obtain material for cultureObtain material for culture– Possible ExceptionsPossible Exceptions: Uncomplicated abscess : Uncomplicated abscess

not needing rx; active CA-MRSA abx to be not needing rx; active CA-MRSA abx to be given immediately. given immediately.

No data to suggest molecular typing or No data to suggest molecular typing or toxin-testing should guide managementtoxin-testing should guide management

Empiric antimicrobial therapy may be Empiric antimicrobial therapy may be neededneeded

Alternative agents have +’s and –’s: More Alternative agents have +’s and –’s: More data needed to identify optimal data needed to identify optimal strategiesstrategies

Use local data for treatmentUse local data for treatment Patient education is critical!Patient education is critical! Maintain adequate follow-upMaintain adequate follow-upSlide Courtesy of

Gorwitz, R. CDC 2007.

Uncomplicated Abscess DataUncomplicated Abscess Data

No benefit with antibiotics in all No benefit with antibiotics in all prospective studies (4 total).prospective studies (4 total).

Rajendran, et al:Rajendran, et al:– CA-MRSA cure CA-MRSA cure – 84% cured with cephalexin vs. 90% in 84% cured with cephalexin vs. 90% in

placebo groupplacebo group– >90% isolates were + for PVL genes>90% isolates were + for PVL genes

Rajendran, et al. AAC. 2007; 51: 4044.

When to Use Antibiotics?When to Use Antibiotics?

Complicated abscess (fever, Complicated abscess (fever, lymphangitis, or surrounding lymphangitis, or surrounding cellulitis)cellulitis)

Rapidly progressive or severe local Rapidly progressive or severe local diseasedisease

Abscess > 5cm diameterAbscess > 5cm diameter Comorbidities or immunosuppresionComorbidities or immunosuppresion Inability to completely drain abscessInability to completely drain abscess Extremes of ageExtremes of age Failed prior I&DFailed prior I&D

Wallin, et al. Emerg Med Clin North Amer. 2008; 26: 431.

King, M. D. et. al. Ann Intern Med 2006;144:309-317

Antimicrobial Susceptibility Patterns of Methicillin-Resistant Staphylococcus aureus Isolates according to Pulsed-Field Type

Oral Agents for Outpatient Treatment of Oral Agents for Outpatient Treatment of CA-MRSACA-MRSA

Daum, RS. NEJM. 2007. 357:380.

Parenteral Agents for Inpatient Treatment of Parenteral Agents for Inpatient Treatment of CA-MRSACA-MRSA

Daum, RS. NEJM. 2007. 357:380.

Clinical Considerations - Clinical Considerations - ManagementManagement

Antimicrobial Selection (SSTIs) Antimicrobial Selection (SSTIs) Alternative agents (More data needed to Alternative agents (More data needed to

establish effectiveness!):establish effectiveness!):– ClindamycinClindamycin – Potential for inducible – Potential for inducible

resistance, Relatively higher risk of resistance, Relatively higher risk of C. C. difficiledifficile associated disease? associated disease?

– TMP/SMXTMP/SMX – Group A strep isolates – Group A strep isolates commonly resistantcommonly resistant

– TetracyclinesTetracyclines – Not recommended for – Not recommended for <8yo<8yo

– RifampinRifampin – Not as a single agent – Not as a single agent– LinezolidLinezolid – Expensive, Potential for – Expensive, Potential for

resistance with inappropriate useresistance with inappropriate use Slide Courtesy of Gorwitz, R. CDC 2007.

Clinical Considerations - Clinical Considerations - ManagementManagement

Antimicrobial Selection (SSTIs) Antimicrobial Selection (SSTIs)

Not optimal for MRSA (High Not optimal for MRSA (High prevalence of resistance or prevalence of resistance or potential for rapid development of potential for rapid development of resistance):resistance):

– MacrolidesMacrolides

– FluoroquinolonesFluoroquinolonesSlide Courtesy of Gorwitz, R. CDC 2007.

D-zone test for Inducible Clindamycin D-zone test for Inducible Clindamycin ResistanceResistance

CCE

-Perform on erythromycin-resistant, clindamycin-susceptible S. aureus isolates-Clinical implications unclear, but treatment failures have occurred-Does not require pre-treatment or co-treatment with erythromycin in vivo Slide Courtesy of

Gorwitz, R. CDC 2007.

MRSA: MRSA: Clindamycin vs. TMP/SMXClindamycin vs. TMP/SMX

Adult Adult EDED

Peds EDPeds ED OPDOPD

ClindamycinClindamycin 85%85% 89%89% 72%72%

TMP/SMXTMP/SMX 98%98% 100%100% 98%98%

Adult Adult EDED

Peds EDPeds ED OPDOPD

ClindamycinClindamycin 89%89% 100%100% 94%94%

TMP/SMXTMP/SMX 98%98% 100%100% 97%97%

JAC

OB

IN

CB

Treatment algorithm for SSTIsTreatment algorithm for SSTIs

•Cellulitis

•Impetigo

Uncomplicated Abscess

•Complicated Abscess (significant cellulitis)

•Immunocompromised•Infected wound, foot ulcer, etc.

•Cover Group A Strep•Cephalexin +/- TMP/SMX

•Surgical Treatment•Strongly consider no abx•If abx used, cover CA-MRSA•Doxycyline or TMP/SMX alone

•Consider surgical tx•Cover CA-MRSA and Group A Strep

PO Therapy

•Cephalexin + TMP/SMXOr

•Clindamycin alone

IV Therapy

•Vancomycin + ClindamycinOr

•Vancomycin +Zosyn(if Gram neg. suspected)

Wallin, et al. Emerg Med Clin North Amer. 2008; 26: 431.

Linezolid vs. VancomycinLinezolid vs. Vancomycin

Patients with suspected or proven Patients with suspected or proven methicillin-resistant methicillin-resistant Staphylococcus aureusStaphylococcus aureus (MRSA) infections that involved substantial (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or cellulitis, abscesses, infected ulcers, or

burns (<10% of total body surface area).burns (<10% of total body surface area). ITT: 92.2% and 88.5% (Linezolid vs. Vanco.)ITT: 92.2% and 88.5% (Linezolid vs. Vanco.) TOC: 88.6% vs. 66.9% TOC: 88.6% vs. 66.9% DAE were the same for both groupsDAE were the same for both groups

Weigelt J., et al. AAC. 2005; 49: 2260.

Other InfectionsOther Infections PyomyositisPyomyositis

– Bacteremia with seeding of damaged tissue.Bacteremia with seeding of damaged tissue.– S aureus 60+%S aureus 60+%– Surgical drainage with Vanco/clindamycin/linzeolidSurgical drainage with Vanco/clindamycin/linzeolid

Septic Arthritis/OsteomyelitisSeptic Arthritis/Osteomyelitis– May be more severe with CA-MRSAMay be more severe with CA-MRSA– Joint drainage and irrigation with iv abx (namely, Joint drainage and irrigation with iv abx (namely,

vancomycin and clindamcyin)vancomycin and clindamcyin) Community-Acquired PneumoniaCommunity-Acquired Pneumonia

– CA-MRSA is rare (<2%); MSSA is more commonCA-MRSA is rare (<2%); MSSA is more common– Influenza-like illnessesInfluenza-like illnesses– Linezolid and/or clindamycin may be better than Linezolid and/or clindamycin may be better than

vancomycinvancomycin

Management of Severe / Invasive Management of Severe / Invasive InfectionsInfections

Vancomycin remains a 1Vancomycin remains a 1stst-line therapy for severe -line therapy for severe infections possibly caused by MRSAinfections possibly caused by MRSA

Other IV agents may be appropriate Other IV agents may be appropriate Consult an Consult an infectious disease specialist.infectious disease specialist.

Final therapy decisions should be based on Final therapy decisions should be based on results of culture and susceptibility testingresults of culture and susceptibility testing

Severe community-acquired pneumonia: Severe community-acquired pneumonia: Vancomycin or linezolid if MRSA is a Vancomycin or linezolid if MRSA is a consideration*consideration*

*IDSA/ATS Guidelines for treatment of CAP in adults: Mandell et al. CID 2007;44:S27-72


DecolonizationDecolonization

Limited Data and no published trials Limited Data and no published trials Consider in:Consider in:

– Multiple CA-MRSA SSTIs Multiple CA-MRSA SSTIs – Multiple household contacts are infectedMultiple household contacts are infected– Households with extremes of age, Households with extremes of age,

immunosuppressed membersimmunosuppressed members

Sample Decolonization RegimenSample Decolonization Regimen

If nares screen is positive:If nares screen is positive:– Intranasal mupirocin x5d Intranasal mupirocin x5d ANDAND– 2% chlorhexidine showers (2x/day)2% chlorhexidine showers (2x/day)

If nares screen negative, but others If nares screen negative, but others are positive:are positive:– 2% chlorhexidine shower only2% chlorhexidine shower only

If all sites are negative:If all sites are negative:– No decolonization recommendedNo decolonization recommended

Guidelines for Patients with Recurrent MRSA Skin InfectionsGuidelines for Patients with Recurrent MRSA Skin InfectionsAt Weiler Hospital. Courtesy of Chris Coyle, MDAt Weiler Hospital. Courtesy of Chris Coyle, MD

Role of PetsRole of Pets Greatest risk of Greatest risk of Staph aureusStaph aureus / MRSA / MRSA

exposure in most humans is other humansexposure in most humans is other humans When household pet animals carry MRSA, When household pet animals carry MRSA,

likely acquired from a humanlikely acquired from a human Transmission of MRSA from an infected or Transmission of MRSA from an infected or

colonized pet to a human is possible, but colonized pet to a human is possible, but likely accounts for a very small proportion likely accounts for a very small proportion of human infectionsof human infections

Reasonable to consider pet as a source if Reasonable to consider pet as a source if transmission continues in a household transmission continues in a household despite optimizing other control strategiesdespite optimizing other control strategies

Little evidence that antimicrobial-based Little evidence that antimicrobial-based eradication therapy is effective in pets; eradication therapy is effective in pets; however, colonization tends to be short-however, colonization tends to be short-term*term*

Barton et al 2006;Can J Infect Dis Med MicrobiolSlide Courtesy of Gorwitz, R. CDC 2007.

Preventing TransmissionPreventing Transmission Exclusion of patients from school, work, Exclusion of patients from school, work,

sports activities, etc should be reserved for sports activities, etc should be reserved for those that are unable to keep the infected those that are unable to keep the infected skin covered with a clean, dry bandage and skin covered with a clean, dry bandage and maintain good personal hygiene.maintain good personal hygiene.

In general, it is not necessary to close schools In general, it is not necessary to close schools to “disinfect” them when MRSA infections to “disinfect” them when MRSA infections occur.occur.

In ambulatory care settings, use standard In ambulatory care settings, use standard precautions for all patients (hand hygiene precautions for all patients (hand hygiene before and after contact, barriers such as before and after contact, barriers such as gloves, gowns as appropriate for contact with gloves, gowns as appropriate for contact with wound drainage and other body fluids).wound drainage and other body fluids).

www.cdc.gov

Preventing TransmissionPreventing Transmission Persons with skin infections should Persons with skin infections should

keep wounds covered, wash hands keep wounds covered, wash hands frequently (always after touching frequently (always after touching infected skin or changing dressings), infected skin or changing dressings), dispose of used bandages in trash, dispose of used bandages in trash, avoid sharing personal items.avoid sharing personal items.

Uninfected persons can minimize risk Uninfected persons can minimize risk of infection by keeping cuts and of infection by keeping cuts and scrapes clean and covered, avoiding scrapes clean and covered, avoiding contact with other persons’ infected contact with other persons’ infected skin, washing hands frequently, skin, washing hands frequently, avoiding sharing personal items. avoiding sharing personal items.

www.cdc.gov

http://www.princetoncme.com/public/2006-151/report2.php

Antimicrobials In DevelopmentAntimicrobials In Development

GlycopeptidesGlycopeptides– DalbavancinDalbavancin– OritavancinOritavancin– Telavancin Telavancin

CephalosporinsCephalosporins– CeftobiproleCeftobiprole

Need More Information?Need More Information?

http://www.cdc.gov/ncidod/dhqp/pdf/ar/CAMRSA_ExpMtgStrategies.pdf

Daum, RS. Skin and soft tissue infections caused by MRSA. NEJM 2007. 357:380-390.

Wallin, et al. Community-Associated MRSA. Emerg Med Clin N AM 2008. 26:431-455.

CA-MRSA: What You Need to Know

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