Outpatient and Inpatient MRSA: Outpatient and Inpatient MRSA: the New IDSA Guidelinesthe New IDSA Guidelines

Presented by Susan Kline, MD, MPHPresented by Susan Kline, MD, MPHUniversity of Minnesota Medical SchoolUniversity of Minnesota Medical School

Department of MedicineDepartment of MedicineDivision of Infectious DiseasesDivision of Infectious Diseases

Minneapolis , MNMinneapolis , MNPresented to: Burnett Medical Center staff , Presented to: Burnett Medical Center staff ,

Grantsburg, WI Grantsburg, WI Jan. 19, 2012Jan. 19, 2012

Disclosure SlideDisclosure Slide

I have served as a member of the I have served as a member of the Speakers Bureau and have received Speakers Bureau and have received honoraria and research support from honoraria and research support from Pfizer PharmaceuticalsPfizer Pharmaceuticals

ObjectivesObjectives

Review the new MRSA treatment Review the new MRSA treatment guidelinesguidelines

Focus on adultsFocus on adults

Focus on common clinical conditionsFocus on common clinical conditions– Skin and soft tissue infections Skin and soft tissue infections – Bacteremia and endocarditisBacteremia and endocarditis– Pneumonia, community and hospital acquiredPneumonia, community and hospital acquired

2011 Clinical Practice Guidelines by the Infectious Diseases Society of America: for the treatment

of MRSA infections in Adults and Pediatrics

Clinical Topics

1.Skin and soft tissue infections 2.Recurrent skin and soft tissue infections 3.MRSA bacteremia and endocarditis 4.MRSA pneumonia 5.MRSA bone and joint infections 6.MRSA central nervous system infections

7.Role of combination or adjunctive therapies 8.Vancomycin dosing and monitoring 9.Vancomycin susceptibility testing 10.Management of persistent bacteremia and vancomycin treatment failures 11.MRSA neonatal infections

Clinical Infectious Diseases 2011:52;1-38.

Strength of recommendation A Good evidence to support a recommendation for or against use B Moderate evidence to support a recommendation for or against use C Poor evidence to support a recommendation

Quality of evidence I Evidence from >= 1 properly randomized, controlled trial II Evidence from >= 1 well-designed clinical trial, without randomization; from cohort or case-controlled analytic studies (preferably from > 1 center); from multiple time-series; or from dramatic results from uncontrolled experiments III Evidence from opinions of respected authorities; based on clinical experience, descriptive studies, or reports of expert committees.

Evidence Grading System

What is the management of skin and soft tissue What is the management of skin and soft tissue infections (SSTIs) in the era of community associated infections (SSTIs) in the era of community associated

MRSA (CA-MRSA) ?MRSA (CA-MRSA) ?

For cutaneous abscess incision and For cutaneous abscess incision and drainage (I &D) is the primary treatment drainage (I &D) is the primary treatment (A-II)(A-II)

For simple abscess I &D alone should be For simple abscess I &D alone should be adequateadequate

Additional data needed to determine role Additional data needed to determine role of antibiotics, if anyof antibiotics, if any

Antibiotic therapy recommendedAntibiotic therapy recommended

In addition to I & D forIn addition to I & D for– Severe abscessesSevere abscesses– Multiple abscessesMultiple abscesses– Rapid progression with cellulitisRapid progression with cellulitis– Signs or symptoms of systemic illnessSigns or symptoms of systemic illness

Send culture to guide antibiotic therapy if Send culture to guide antibiotic therapy if neededneeded

Antibiotic therapy recommendedAntibiotic therapy recommended

In addition to I & D forIn addition to I & D for– Co-morbidities or immunosuppressionCo-morbidities or immunosuppression– Extremes of ageExtremes of age– Difficult to drain abscess site (face, hand, Difficult to drain abscess site (face, hand,

genital)genital)– Septic phlebitisSeptic phlebitis– Lack of response to I & D alone (A-III)Lack of response to I & D alone (A-III)

For Outpatients with purulent cellulitisFor Outpatients with purulent cellulitis

Send cultureSend culture

Empiric therapy for CA-MRSAEmpiric therapy for CA-MRSA

5-10+ days (follow patient response)5-10+ days (follow patient response)

Empiric therapy for Beta-hemolytic Empiric therapy for Beta-hemolytic streptococcus likely not needed (A-II)streptococcus likely not needed (A-II)

For outpatients with non-purulent For outpatients with non-purulent cellulitis cellulitis ((nono purulent exudate, pus or abscess) purulent exudate, pus or abscess)

Empiric therapy for beta hemolytic strep Empiric therapy for beta hemolytic strep recommendedrecommended

Role of CA-MRSA unknownRole of CA-MRSA unknown

Add CA-MRSA coverage ifAdd CA-MRSA coverage if– No response to strep treatment –or-No response to strep treatment –or-– Systemic toxicitySystemic toxicity

Treat for 5-10+ days, need to follow Treat for 5-10+ days, need to follow patient responsepatient response

Treatment options for CA-MRSA Treatment options for CA-MRSA outpatient empiric therapyoutpatient empiric therapy

Drug Adult Dose Evidence Grade

TMP-SMX 1-2 DS BID AII Doxycycline or

Minocycline 100 BID AII Clindamycin 300-450 TID AII Linezolid 600 BID AII

For coverage for For coverage for bothboth beta hemolytic beta hemolytic streptococcus streptococcus andand CA-MRSA CA-MRSA

Clindamycin alone (A-II)Clindamycin alone (A-II)OROR

TMP/SMX or a tetracycline (doxy or mino)TMP/SMX or a tetracycline (doxy or mino)PLUSPLUSA beta-lactam (i.e.. amoxicillin, cephalexin, A beta-lactam (i.e.. amoxicillin, cephalexin,

dicloxacillin ) (A-II)dicloxacillin ) (A-II)ORORLinezolid alone (A-II)Linezolid alone (A-II)

32 y/o M with 3 days of an enlarging, painful lesion on his L thigh that he attributes to a “spider bite”. T 36.9 BP 118/70 P 82

What is the appropriate management of this patient?

A. Incision and drainage alone

B. Incision and drainage plus oral anti- MRSA antimicrobial agent

C. Oral anti-MRSA antimicrobial agent alone

D. Therapy for Group A streptococcus alone

Treatment of Complicated SSTIs Treatment of Complicated SSTIs hospitalized hospitalized

Deeper soft tissue infectionsDeeper soft tissue infectionsSurgical/traumatic wound infectionSurgical/traumatic wound infectionMajor abscessesMajor abscessesCellulitisCellulitisInfected ulcers/burnInfected ulcers/burn

Surgical debridementSurgical debridement Send culturesSend cultures Start empiric therapy for MRSAStart empiric therapy for MRSA

Inpatient therapy for complicated Inpatient therapy for complicated SSTIs SSTIs (empiric to cover MRSA) (empiric to cover MRSA)

Vancomycin IV 15-20mg/kg/dose q 8-12 Vancomycin IV 15-20mg/kg/dose q 8-12 hours (A-I)hours (A-I)

Linezolid (IV / PO) 600mg q 12 hours (A-I)Linezolid (IV / PO) 600mg q 12 hours (A-I)

Daptomycin 4mg/kg IV q 24 hours (A-I)Daptomycin 4mg/kg IV q 24 hours (A-I)

Televancin 10mg/kg IV q 24 hours (A-I)Televancin 10mg/kg IV q 24 hours (A-I)

Clindamycin 600mg IV/PO TID (A-III)Clindamycin 600mg IV/PO TID (A-III)

Inpatient therapy for non-purulent Inpatient therapy for non-purulent cellulits cellulits

Could start a beta lactam alone Could start a beta lactam alone

(e.g. cefazolin) (e.g. cefazolin)

Then add MRSA coverage if no response Then add MRSA coverage if no response (A-II)(A-II)

Length of therapy for inpatient Length of therapy for inpatient SSTIsSSTIs

7-14 days + of therapy7-14 days + of therapy

Need to individualize based on patient Need to individualize based on patient response response

Usually start with IV and don’t switch to Usually start with IV and don’t switch to PO until the cellulitis is nearly resolved to PO until the cellulitis is nearly resolved to prevent relapse, exception to rule is prevent relapse, exception to rule is linezolid which has excellent oral linezolid which has excellent oral absorption nearly 100%absorption nearly 100%

Management of recurrent MRSA Management of recurrent MRSA SSTIsSSTIs

Emphasize good personnel hygiene, Emphasize good personnel hygiene, wound care and environmental cleaningwound care and environmental cleaning– Regular bathingRegular bathing– Frequent hand washing, esp. if touch woundFrequent hand washing, esp. if touch wound– Keep draining wound coveredKeep draining wound covered– Avoid sharing or reusing razors, linens, towelsAvoid sharing or reusing razors, linens, towels– Clean high touch surfaces with commercial Clean high touch surfaces with commercial

cleanerscleaners

Consider decolonization ifConsider decolonization if

Recurrent SSTI despite good wound care, Recurrent SSTI despite good wound care, hygiene and cleaning hygiene and cleaning

Ongoing household transmissionOngoing household transmission

Nasal mupirocin BID x 5-10 days +/-Nasal mupirocin BID x 5-10 days +/-

Daily chlorhexidine gluconate baths/showers x Daily chlorhexidine gluconate baths/showers x 5-14 days5-14 days

Reserve oral antibiotics for active infectionsReserve oral antibiotics for active infections

Use oral agent plus rifampin plus topical agents Use oral agent plus rifampin plus topical agents if have relapse despite doing all of the aboveif have relapse despite doing all of the above

What is the management of MRSA What is the management of MRSA bacteremia and endocarditis?bacteremia and endocarditis?

Uncomplicated bacteremiaUncomplicated bacteremia– No prosthesis, lines removed, fevers resolved No prosthesis, lines removed, fevers resolved

in 72 hours, blood cultures negative after 2-4 in 72 hours, blood cultures negative after 2-4 days, no metastatic focus of infectiondays, no metastatic focus of infection

– Endocarditis excludedEndocarditis excludedEchocardiogram recommended, TEE>TTEEchocardiogram recommended, TEE>TTE

Give antibiotics x at least 14 daysGive antibiotics x at least 14 days– Vancomycin 15-20mg/kg IV q 12 hours (A-II)Vancomycin 15-20mg/kg IV q 12 hours (A-II)– Daptomycin 6mg/kg IV q 24 hours (A-I)Daptomycin 6mg/kg IV q 24 hours (A-I)

Complicated MRSA bacteremiaComplicated MRSA bacteremia

4-6 weeks of antibiotics recommended4-6 weeks of antibiotics recommended– Vancomycin 15-20mg/kg IV q 12 hoursVancomycin 15-20mg/kg IV q 12 hours– Daptomycin 6mg/kg IV q 24 hoursDaptomycin 6mg/kg IV q 24 hours– Some experts recommend high dose Some experts recommend high dose

daptomycin 8-10mg/kg IV q 24 hours (B-III)daptomycin 8-10mg/kg IV q 24 hours (B-III)Off label dosingOff label dosing

MRSA endocarditisMRSA endocarditis

6 weeks of antibiotics recommended6 weeks of antibiotics recommended– Vancomycin 15-20mg/kg IV q 12 hoursVancomycin 15-20mg/kg IV q 12 hours– Daptomycin 6mg/kg IV q 24 hoursDaptomycin 6mg/kg IV q 24 hours– Some experts recommend high dose Some experts recommend high dose

daptomycin 8-10mg/kg IV q 24 hours (B-III)daptomycin 8-10mg/kg IV q 24 hours (B-III)Off label dosingOff label dosing

Addition of gentamicin or rifampin Addition of gentamicin or rifampin not not recommended for native valve endocarditisrecommended for native valve endocarditis

Prosthetic valve MRSA Prosthetic valve MRSA endocarditis treatment (B-II)endocarditis treatment (B-II)

Vancomycin IV 15-20mg/kg IV q 8-12 Vancomycin IV 15-20mg/kg IV q 8-12 hours x 6 weekshours x 6 weeks

Plus gentamicin 1mg/kg IV q 8 hours x 2 Plus gentamicin 1mg/kg IV q 8 hours x 2 weeksweeks

Plus rifampin 300mg PO/IV q 8 hours Plus rifampin 300mg PO/IV q 8 hours X 6 weeksX 6 weeks

May need early valve replacement surgeryMay need early valve replacement surgery

Indications for surgery for MRSA endocarditisIndications for surgery for MRSA endocarditis

Large vegetations > 1 cmLarge vegetations > 1 cmOccurrence of embolic events during 1Occurrence of embolic events during 1stst 2 weeks 2 weeks of therapyof therapySevere valvular insufficiencySevere valvular insufficiencyValve perforation or dehiscenceValve perforation or dehiscenceDecompensated heart failureDecompensated heart failurePerivalvular or myocardial abscessPerivalvular or myocardial abscessNew heart blockNew heart blockPersistent fevers or bacteremiaPersistent fevers or bacteremia

Vancomycin dosing guidanceVancomycin dosing guidance

For serious infections dose based actual For serious infections dose based actual weightweight

15-20mg/kg IV q 8-12 hours15-20mg/kg IV q 8-12 hours

Trough goal is 15-20 microgram/ml Trough goal is 15-20 microgram/ml

Need to adjust dosing interval upward for Need to adjust dosing interval upward for decreased creatinine clearance decreased creatinine clearance

60 year old male presents with 4 days of fevers and chills

T 38.5 BP 102/71 P 104 R 20 O2 sat 98% RA weight 100 kg

Heart: 2/6 systolic murmur at apex Chest: CTAB Skin: no peripheral stigmata of endocarditis

Labs: 15.5> 39 > 350 Cr 0.8

Started on IV vancomycin 1 gram every 12 hours

HD #1 blood cx: 3/4 MRSA (vanco MIC 1)

HD # 5

T 37.8 BP 138/70 P 113 R 16 O2 sat 96% RA

Alert and interactive, no new physical exam findings

Blood cx: 2/2 MRSA (vanco MIC 1) Vancomycin trough 7 microgm/mL

2 cm mitral valve vegetation on echocardiogram

What changes to the patient’s antibiotics should be made?

A. Add gentamicin to vancomycin

B. Add rifampin to vancomycin

C. Increase vancomycin dose to 1.5 gram IV Q12 hrs, target goal trough of 15-20 microgm/mL

D. Discontinue vancomycin and start IV daptomycin 6 mg/kg Q24 hrs

Treatment for health care Treatment for health care associated MRSA pneumoniaassociated MRSA pneumonia

Vancomycin 15-20mg.kg IV q 8-12 hours Vancomycin 15-20mg.kg IV q 8-12 hours (A-II)(A-II)

Linezolid 600mg PO/IV q 12 hours (A-II)Linezolid 600mg PO/IV q 12 hours (A-II)

Clindamycin 600mg PO/IV TID (B-III)Clindamycin 600mg PO/IV TID (B-III)– If strain susceptibleIf strain susceptible

7-21 day course depends on 7-21 day course depends on severity/extent of infectionseverity/extent of infection

Hospitalized patients with severe Hospitalized patients with severe community acquired pneumonia (CAP)community acquired pneumonia (CAP)

Start treatment for MRSA pending sputum Start treatment for MRSA pending sputum gram stain and culture (AIII)gram stain and culture (AIII)

Severe CAP defined asSevere CAP defined as– ICU admitICU admit– Necrotizing or cavitary infiltratesNecrotizing or cavitary infiltrates– Empyema Empyema (also need drainage)(also need drainage)

35 y/o F previously healthy with 4 days of fever, chills, myalgias, and cough. Now with increasing dyspnea and hemoptysis x 24 hrs

T38.7 P120 BP96/60 R24 89%RA

Moderate respiratory distress with coarse rhonchi

WBC 15, Hct 44, Plt 425

Rapid flu: + influenza A

Sputum gram stain/ cx: pending

Intubated, admitted to ICU

In addition to starting anti-influenza therapy,

would you treat with antibiotics and if so which?

A. None

B. Ceftriaxone and azithromycin

C. Vancomycin and ceftriaxone and azithromycin

D. Linezolid and cefepime

E. DaptomycinE. Daptomycin

MRSA pneumonia

Daptomycin should not be used for Rx of pneumonia, (inactivated by pulmonary surfactant)

Empiric Rx for MRSA recommended for severe CAP (ICU admission, necrotizing or cavitary infiltrates, or empyema) Discontinue empiric Rx if cultures do not grow MRSA

Questions/DiscussionQuestions/DiscussionReferences: References:

Clinical Practice Guidelines by the Infectious Disease Society of America for the Treatment of Methicillin- Clinical Practice Guidelines by the Infectious Disease Society of America for the Treatment of Methicillin- Resistant Resistant Staphylococcus aureusStaphylococcus aureus Infections in Adults and Children Infections in Adults and Children

Panel Members / Authors

Catherine Liu, MD Henry “Chip” Chambers, MD Arnold S. Bayer, MD Sara E. Cosgrove, MD Robert S. Daum, MD Scott K. Fridkin, MD Rachel J. Gorwitz, MD Sheldon L. Kaplan, MD A.W. Karchmer, MD Donald P. Levine, MD Barbara E. Murray, MD Michael J. Rybak, PharmD David A. Talan, MD

SPGC Liaison Stan Deresinski, M.D.

Published in: Clinical Infectious Diseases Feb. 1, 2011 Published in: Clinical Infectious Diseases Feb. 1, 2011