Table 1: Risk Factors for Infective Endocarditis

Non-cardiac

Cardiac

IV drug abuse

Male

Advancing age

Recent dental surgery or other invasive

      procedures

Nosocomial bacteremia

Permanent venous access lines

Surgically constructed pulmonary shunts

Degenerative valvular lesions

Congenital heart disease

Prosthetic valves

Mitral valve prolapse with insufficiency

Rheumatic heart disease

Previous infective endocarditis

Hypertrophic cardiomyopathy

 

 

 

Table 2: Considerations for Testing in Culture Negative IE

Special Culture Requirements

Serologies

Other Testing

Histoplasma capsulatum (fungal cultures)

H. capsulatum

Tropheryma whippelii (PCR of tissue)

Aspergillus (fungal cultures)

Coxiella burnetii

 

Blastomycosis dermatidis (fungal culture)

Chlamydia psittaci

 

Bartonella species (prolonged incubation)

Legionella species

 

Erysipelothrix sp. (fungal cultures)

Brucella species

 

 

Bartonella quintana or henselae

 

 

 

Table 3. Epidemiological Clues in Etiological Diagnosis of Culture-Negative Endocarditis  

Epidemiological Feature

Common Microorganism(s)

Injection drug use

S aureus, including community-acquired oxacillin-resistant strains Coagulase-negative staphylococci, ß-Hemolytic streptococci; Fungi; Aerobic Gram-negative bacilli, including Pseudomonas aeruginosa, Polymicrobial

Indwelling cardiovascular medical devices

S aureus, Coagulase-negative staphylococci; Fungi; Aerobic Gram-negative bacilli; Corynebacterium sp

Genitourinary disorders, infection, manipulation, including pregnancy, delivery, and abortion

Enterococcus sp, Group B streptococci (S agalactiae), Listeria monocytogene, Aerobic Gram-negative bacilli, Neisseria gonorrhoeae

Chronic skin disorders, including recurrent infections

S aureus, ß-Hemolytic streptococci

Poor dental health, dental procedures

Viridans group streptococci, "Nutritionally variant streptococci", Abiotrophia defectiva, Granulicatella sp, Gemella sp, HACEK* organisms

Alcoholism, cirrhosis

Bartonella sp, Aeromonas sp, Listeria sp, S pneumoniae, ß-Hemolytic streptococci

Burn patients

S aureus, Aerobic Gram-negative bacilli, including P aeruginosa; Fungi

Diabetes mellitus

S aureus, ß-Hemolytic streptococci ,S pneumoniae

Early (≤1 y) prosthetic valve placement

Coagulase-negative staphylococci, S aureus, Aerobic Gram-negative bacilli; Fungi Corynebacterium sp Legionella sp

Late (>1 y) prosthetic valve placement

Coagulase-negative staphylococci, S aureus, Viridans group streptococci, Enterococcus species, Fungi, Corynebacterium sp

Dog–cat exposure

Bartonella sp, Pasteurella sp, Capnocytophaga sp

Contact with contaminated milk or infected farm animals

Brucella sp, Coxiella burnetii, Erysipelothrix sp

 

Homeless, body lice

Bartonella sp

AIDS

Salmonella sp, S pneumoniae, S aureus

Pneumonia, meningitis

S pneumoniae

Solid organ transplant

S aureus, Aspergillus fumigatus, Enterococcus sp, Candida sp

Gastrointestinal lesions

S bovis, Enterococcus sp, Clostridium septicum

*Haemophilus parainfluenzae, H. aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae 

------ 

Adapted from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis. Diagnosis,

Antimicrobial therapy, and management of complications. Circ 2005;111:3167-84.

 

 

Table 4. Modified Duke Criteria for the Diagnosis of Infective Endocarditis.

 

1.      Definite diagnosis of infective endocarditis

     A.  Pathologic criteria

a.       Histological and/or microbiologic evidence of infection at surgery or autopsy           

     B. Clinical criteria

            a.   2 major criteria; or

            b.   1 major/3 minor; or

            c.   5 minor

2.      Possible diagnosis:

a.   1 major criteria and 1 minor criterion; or

            b.   3 minor

3.      No endocarditis:

a.       Firm alternate diagnosis

b.      Clinical resolution with ≤4 days of antimicrobial therapy

c.       No evidence of infective endocarditis at surgery or autopsy with ≤4 days

                   of antimicrobial therapy; or

d.      Failure to meet criteria for possible infective endocarditis, as above 

Major Criteria

1. Blood culture

            a.   2 separate blood cultures positive for:

                        i. viridans streptococci, Streptococcus bovis, HACEK*, Staphylococcus aureus.

                        ii. Community-acquired enterococci, in absence of primary focus.

b.      Microorganisms consistent with endocarditis isolated from:

i. at least 2 blood cultures drawn >12 hours apart.

ii. 3 of 3, or a majority of 4 or more with 1st and last obtained >1hour apart.

c.       Single positive blood culture for Coxiella burnetii or antiphase 1 IgG antibody >1:800

2. Evidence of endocardial involvement

a.  Echocardiography: Positive for oscillating intracardiac mass on valve or supporting structure,

     in path of regurgitant jet, or on implanted material in the absence of an alternative anatomic

     explanation; or valve ring abscess; or new partial dehiscence of valvular prosthesis.

b.  New valvular regurgitant murmur (increasing or changing or pre-existing murmur not sufficient).

Minor Criteria

1.   Predisposing heart condition or injection drug use.

2.   Fever, >380C.

3.   Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage,

      conjunctival hemorrhage, and Janeway lesions.

4.      Immunologic phenomena: glomerulonephritis, Roth’s spot, Osler’s node, and rheumatoid factor.

5.     Positive blood culture that does not meet major criterion (as noted above) or serologic evidence

      of active infection with organism consistent with infective endocarditis.

*Haemophilus parainfluenzae, H. aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae

------ 

Modified from Li JS, Sexton DJ, Mick N, et al. Proposed modification to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633-8.

 

 

Table 5. In Vitro Assays           

Microorganism

Test

Result

Viridans streptococcus

Broth dilution test

Penicillin MIC

Enterococcus

Broth dilution test

 

Growth in:

  500 ug/ml of Gentamicin

  1000 ug/ml Streptomycin

Nitrocephin degradation

Penicillin MIC

Vancomycin MIC

High-level resistancea:

  Gentamicin

  Streptomycin

Beta-lactamase production

S. aureus and Coagulase-Negative Staphylococci

Nitrocephin degradation

Oxacillin/methicillin sensitivity

Broth dilution test

Beta-lactamase production

MRSA/MRCNS

Vancomycin MIC

Rifampin MIC

Gentamicin MIC

TMP/SMX MIC

Other pathogens

Broth dilution tests

Antibiotic MIC/MBCb

All pathogens

Serum antibiotic concentrations

Peak and trough vancomycinc

and aminoglycosided

concentrations

No pathogen isolated

Histochemical stains of vegetations/

   emboli

Immunohistology of vegetations/

   emboli

Broad-spectrum bacterial and fungal

PCR and DNA sequencing on

Vegetation/emboli

Serology

Legionella urinary antigen assay

 

a. The infecting strain of enterococcus recovered from patients with endocarditis should be tested for susceptibility to high levels of both gentamicin and streptomycin but not other aminoglycosides. Strains that are resistant to high levels of gentamicin are resistant to other aminoglycosides, except some of these strains may be susceptible to high levels of streptomycin.

    Choice of an aminoglycoside for synergy should be based on in vitro high-level aminoglycoside susceptibility testing. If the strain is susceptible to high levels of both gentamicin and streptomycin, gentamicin is preferred because determination of gentamicin serum levels is more generally available. If the strain exhibits high-level resistance to one of these aminoglycosides, use only the aminoglycoside to which the strain is sensitive. If the strain is resistant to high levels of both gentamicin and streptomycin, no aminoglycoside is available to synergize with a cell wall-active antibiotic.  

b. MIC/MBC testing may be useful for nonstandard antimicrobial regimens or unusual pathogens

c. Vancomycin “peak” serum levels should be obtained 1 h after completion of a 1-2h infusion and should be in the range of 30-45 ug/ml. Vancomycin trough levels obtained just before the next dose should be 10-15 ug/ml.

d.  Gentamicin “peak” serum levels obtained 1 h after start of a 20-30 min IV infusion or IM injection of 1 mg/kg should be about 3-4 ug/ml and trough level should be <1 ug/ml. Streptomycin peak serum level 1h after IM administration of 7.5 mg/kg is about 15-20 ug/ml and trough should be about 5 ug/ml.        

MIC, minimal inhibitory concentration; MBC, minimal bactericidal concentration; MRSA, methicillin-resistant S. aureus; MRCNS, methicillin-resistant coagulase-negative staphylococci; TMP/SMX ( trimethoprim/sulfamethoxazole);

------ 

Modified from Levison ME: In vitro assays. In Kaye D (ed.): Infective Endocarditis. 2nd Ed. New York, Raven Press, 1992:151-167.

 

 

Table 6a. Standard Antibiotic Therapy for Native Valve Endocarditis due to Common Pathogens (Doses are for Adults with Normal Renal Function) 

Bacteria

Primary Regimen(s)

Duration

Alternative Regimen(s)

Duration

Viridans group Streptococcus

and Streptococcus bovis (PCN MIC <0.12 ug/ml)

PCN G 12-18 million

units IV daily0

OR

Ceftriaxone 2 grams

IV daily

OR

Vancomycin2

(trough goal ~15-20)

4 weeks

PCN G 12-18 million daily0 + gentamicin1

3 mg/kg IV daily

OR

Ceftriaxone 2 grams

IV daily+ gentamicin1

3 mg/kg IV daily

OR

Daptomycin8 6 mg/kg

IV daily

2 weeks (only if uncomplicated right sided endocarditis6 and 2 weeks of gentamicin given)

OR

4 weeks (for daptomycin)

Viridans group Streptococcus

and Streptococcus bovis (PCN MIC >0.12-<0.5 ug/ml)

PCN G 24 million IV daily0 + gentamicin1 3mg/kg

IV daily

OR

Ceftriaxone 2 grams IV daily + gentamicin1 3 mg/kg

IV daily

4 weeks of PCN or Ceftriaxone + 2 weeks of gentamicin

 

 

Vancomycin2

(trough goal ~15-20)

OR

Daptomycin8 6 mg/kg

IV daily

4 weeks

Penicillin-resistant Streptococci (MIC >0.5 ug/ml), Enterococcus3, and Abiotrophia species4 (nutritionally variant streptococci)

Ampicillin 2 grams IV every 4 hours + gentamicin1

1 mg/kg IV every 8 hrs

OR

PCN G 18-30 million units IV daily0 + gentamicin1

1 mg/kg IV every 8 hrs

6 weeks

Vancomycin2

(trough goal 15-20)

+/- gentamicin1 1 mg/kg

IV every 8 hrs

OR

Daptomycin8 6 mg/kg

IV daily +/- gentamicin1 1 mg/kg IV every 8 hrs

6 weeks

Methicillin-sensitive Staphylococcus aureus

Oxacillin 2 grams IV every

4 hours +/- gentamicin

1 mg/kg IV every 8 hrs

(for up to 2 weeks)

OR

Cefazolin5 1.5 grams

IV every 8 hours +/- gentamicin1 1 mg/kg

IV every 8 hrs

(for up to 2 weeks)

2 weeks (uncomplicated6 right sided endocarditis only and treatment must include 2 weeks of gentamicin)

OR

6 weeks (all others)

Daptomycin8 6 mg/kg

IV daily +/- gentamicin1 1 mg/kg IV every 8 hrs

OR

Daptomycin8 6 mg/kg

IV daily + rifampin 600 mg PO or IV daily

OR

Vancomycin2

(trough goal ~15-20)

6 weeks

Methicillin-resistant Staphylococcus aureus

Daptomycin8 6 mg/kg

IV daily +/- gentamicin1

1 mg/kg IV every 8-12 hrs

OR

Vancomycin (trough goal ~15-20) +/- gentamicin1

1 mg/kg IV every 8-12 hrs

6 weeks (duration of gentamicin will vary by clinical scenario)

Daptomycin8 6 mg/kg

IV daily +/- Rifampin 600 mg PO or IV daily +/- gentamicin1 1 mg/kg IV every 8-12 hrs

OR

Quinupriston-Dalfopristin 7.5 mg/kg IV every 8 hrs

6 weeks

HACEK7 organisms

Ceftriaxone 2 grams IV daily

4 weeks

Ampicillin/sulbactam 3 g IV every 6h

OR

Ciprofloxacin 400 mg

IV every 12 hours

or 500 mg PO

every 12 hours

4 weeks

All other bacteria or fungal species

Please refer to Antimicrobial Therapy and Vaccines Volume I: Microbes for further guidance.

Varies

 

 

0 PCN can be dosed via continuous infusion or every 4 hrs

1Gentamicin should not be used in patients with creatinine clearance <30 ml/min, or patients with impaired 8th cranial nerve function. Other potentially nephrotoxic drugs, e.g., non-steroidal anti-inflammatory drugs, should be used with caution in patients receiving gentamicin.  Caution when using gentamicin with vancomycin due to increased risk of nephrotoxicity.  Adjust dose of gentamicin based on renal function.

2Vancomycin is used only for patients with immediate type penicillin-allergic reactions, i.e., urticaria, angioedema, or anaphylaxis, to penicillin. Caution when using gentamicin with vancomycin due to risk of nephrotoxicity.   Vancomycin is inferior to beta-lactams for the treatment of methicillin-sensitive Staphylococcus aureus.

3 Enterococcus sensitive to penicillin, vancomycin and aminoglycosides.

4Because of technical difficulties in susceptibility testing of Abiotrophia species and virulence of these organisms, many experts recommend treating endocarditis due to these strains with the standard regimen recommended for enterococci.  Strongly consider dual antibiotic therapy.

5Cefazolin is used for patients with a non-immediate-type penicillin allergy

6Uncomplicated right-sided IE: normal renal function, no extra-pulmonary metastatic infection, no left-sided valvular IE.

7HACEK: Haemophilus parainfluenzae, H. aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae

8Daptomycin is equivalent to beta-lactam antibiotics for the treatment of methicillin-sensitive Staphylococcus aureus.   Endocarditis data is for Staphylococcal aureus only.

 ------ 

*Adapted and modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis. Diagnosis, Antimicrobial therapy, and management of complications. Circ 2005;111:3167-84.  Utility of daptomycin, linezolid, quinupriston/dalfopriston and treatment of VRE are not part of the original guidelines.

 

Table 6b. Standard Antibiotic Therapy for Prosthetic Valve Endocarditis due to Common Pathogens

(Doses are for Adults with Normal Renal Function) 

Bacteria

Primary Regimen(s)

Duration

Alternative Regimen(s)

Duration

Viridans group Streptococcus and Streptococcus bovis (PCN MIC <0.12 ug/ml)

PCN G 12-18 million units IV daily0 +/- gentamicin

3 mg/kg IV daily

OR

Ceftriaxone 2 grams IV daily +/- gentamicin

3 mg/kg IV daily

6 weeks (gentamicin for 2 weeks only)

Vancomycin2

(trough goal ~15-20)

OR

Daptomycin8 6mg/kg

IV daily

6 weeks

Viridans group Streptococcus and Streptococcus bovis (PCN MIC >0.12-<0.5 ug/ml)

PCN G 24 million IV daily0 + gentamicin1

3 mg/kg IV daily

OR

Ceftriaxone 2 grams IV daily + gentamicin1

3 mg/kg IV daily

6 weeks (gentamicin for 2 weeks only)

 

 

Vancomycin2

(trough goal ~15-20)

OR

Daptomycin8 6 mg/kg

IV daily

 

6 weeks

Penicillin-resistant Streptococci (MIC >0.5 ug/ml), Enterococcus3, and Abiotrophia species4 (nutritionally variant streptococci)

Ampicillin 2 grams IV every 4 hours + gentamicin1 1 mg/kg IV every 8 hrs

OR

PCN G 18-30 million units IV daily0 + gentamicin1

1 mg/kg IV every 8 hrs

6 weeks

Vancomycin2

(trough goal 15-20) +/- gentamicin1 1 mg/kg

IV every 8 hrs

OR

Daptomycin8 6 mg/kg

IV daily +/- gentamicin1 1 mg/kg IV every 8 hrs

6 weeks

Methicillin-sensitive Staphylococcus aureus

Oxacillin9 2 grams

IV every 4 hours + gentamicin 1 mg/kg

IV every 8 hrs + Rifampin 600 mg PO/IV daily

OR

Cefazolin5 1.5 grams

IV every 8 hours + gentamicin1 1 mg/kg

IV every 8 hrs + rifampin 600 mg IV/PO daily

6+ weeks (2 weeks of gentamicin)

Vancomycin2 (trough goal ~15-20) + gentamicin

1 mg/kg IV every 8 hrs + Rifampin 600 mg IV/PO daily

OR

Daptomycin8 6 mg/kg

IV daily + gentamicin1 1 mg/kg IV every 8 hrs + rifampin 600 mg

PO/IV daily

6+ weeks (2 weeks of gentamicin)

Methicillin-resistant Staphylococcus aureus

Daptomycin8 6 mg/kg

IV daily + Rifampin 600 mg PO or IV daily + gentamicin1 1 mg/kg

IV every 8 hrs

OR

Vancomycin (trough goal ~15-20) + gentamicin1 1 mg/kg IV every 8 hrs

+/- rifampin 600 mg

PO/IV daily

6+ weeks (2 weeks of gentamicin)

Please refer to Antimicrobial Therapy and Vaccines Volume I: Microbes for further guidance.

6+ weeks

HACEK7 organisms

Ceftriaxone 2 grams

IV daily

6 weeks

Ampicillin/sulbactam 3 g IV every 6h

OR

Ciprofloxacin 400 mg

IV every 12 hours or

500 mg PO every

12 hours

6 weeks

All other bacteria or fungal species

Please refer to Antimicrobial Therapy

and Vaccines Volume I: Microbes for further guidance.

Varies

 

 

0 PCN can be dosed via continuous infusion or every 4 hrs

1Gentamicin should not be used in patients with creatinine clearance <30 ml/min, or patients with impaired 8th cranial nerve function. Other potentially nephrotoxic drugs, e.g., non-steroidal anti-inflammatory drugs, should be used with caution in patients receiving gentamicin.  Caution when using gentamicin with vancomycin due to increased  risk of nephrotoxicity.  Adjust dose of gentamicin based on renal function.

2Vancomycin is used only for patients with immediate type penicillin-allergic reactions, i.e., urticaria, angioedema, or anaphylaxis, to penicillin. Caution when using gentamicin with vancomycin due to risk of nephrotoxicity.   Vancomycin is inferior to beta-lactams for the treatment of methicillin-sensitive Staphylococcus aureus.

3 Enterococcus sensitive to penicillin, vancomycin and aminoglycosides.

4Because of technical difficulties in susceptibility testing of Abiotrophia species and virulence of these organisms, many experts recommend treating endocarditis due to these strains with the standard regimen recommended for enterococci.  Strongly consider dual antibiotic therapy.

5Cefazolin is used for patients with a non-immediate-type penicillin allergy

6Uncomplicated right-sided IE: normal renal function, no extra-pulmonary metastatic infection, no left-sided valvular IE.

7HACEK: Haemophilus parainfluenzae, H. aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae

8Daptomycin is equivalent to beta-lactam antibiotics for the treatment of methicillin-sensitive Staphylococcus aureus.  Only data for daptomycin in prosthetic valve infections is anecdotal case reports.  Endocarditis data is for Staphylococcal aureus only.

9 Oxacillin and nafcillin can be used interchangeably.

 ------

*Adapted and modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis. Diagnosis, Antimicrobial therapy, and management of complications. Circ 2005;111:3167-84.  Utility of daptomycin, linezolid, quinupriston/dalfopriston and treatment of VRE are not part of the original guidelines.

 

 

Table 7: Indications for Surgical Intervention with Infective Endocarditis

Clinical Situations

Echocardiography Findings

Refractory CHF secondary to valvular dysfunction

Persistent vegetations after a major systemic embolic episode

>2 serious systemic embolic episode

Large (>1cm diameter) anterior mitral valve vegetation

Uncontrolled infection (persistent bacteremia)

Acute mitral insufficiency

Endocarditis caused by certain pathogens (Candida sp, Fungi, Enterococci with synergistic treatment options, left sided MRSA endocarditis)

Increase in vegetation size 4 weeks after antibiotic therapy

Ineffective antimicrobial therapy

Valve perforation or rupture

Most cases of prosthetic valve IE (if no perivalvular involvement, medical treatment may be considered)

Periannular extension of infection including perivalvular or myocardial abscess

Resection of mycotic aneurysms

Physiologically significant valve dysfunction as demonstrated by echo

 

 

Table 8. Reasons For Inadequate Clinical Response

·        Inadequate therapy: wrong drug, wrong dose

·        Infarcts secondary to emboli

·        Metastatic abscesses of the spleen, kidney, brain, etc., which may require surgical drainage

·        Suppurative thrombophlebitis at site of an IV catheter, with or without superinfecting endocarditis.

·        Other superinfections: e.g., C. difficile colitis, urinary tract infection

·        Febrile reaction to the antimicrobial agent or other another drug

·        Another unrelated febrile illness, e.g., deep vein thrombophlebitis

 

 

Table 9: Cardiac Conditions Associated with Highest Risk of Adverse Outcome from Endocarditis for which Prophylaxis with Dental Procedures is Recommended.

1. Prosthetic cardiac valve

2. Previous endocarditis

3. Congenital heart disease*

            a. Unrepaired cyanotic CHD, including palliative shunts and conduits

b. Completely repaired congenital heart defect with prosthetic material or

    device, whether placed by surgery or by catheter intervention, during the

    first 6 months after the procedure†

c. Repaired CHD with residual defects at the site or adjacent to the site of a

    prosthetic patch or prosthetic device (which inhibit endothelialization)

4.  Cardiac transplantation recipients who develop cardiac valvulopathy

*Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for any other form of CHD.

†Prophylaxis is recommended because endothelialization of prosthetic material occurs within 6 months after the procedure.

 

 

Table 10. Procedures for Which Antibiotic Prophylaxis is Recommended for Patients in Table 9.

•  Dental/oral surgery likely to cause bleeding (manipulation of gingival tissue or periapical

    region of the teeth or perforation of the oral mucosa).

•   Tonsillectomy and/or adenoidectomy

•   Invasive procedure of respiratory tract which involves biopsy or incision of mucosa

•   Surgical procedures involving infected soft tissue or musculoskeletal tissue

 

 

Table 11a. Regimens for Dental Procedures (give 30-60 minutes prior to procedure)

      •         Oral

•         Amoxicillin 2 g PO

•         Unable to take PO

•         Ampicillin 2 g IV/IM

•         Cefazolin 1 g IV/IM

•         Ceftriaxone 1 g IV/IM

•         Penicillin allergy-oral

•         Cephalexin 2 g PO

•         Clindamycin 600 mg PO or IV/IM

•         Azithromycin 500 mg PO

•         Penicillin allergy-unable to take PO

•         Cefazolin 1 g IV/IM

•         Ceftriaxone 1 g IV/IM

•         Clindamycin 600 mg IV/IM

     

 

Table 11b: Regimens Involving Non-Dental Procedures of Patients Listed in Table 9.

·        Respiratory Procedures

o       Antibiotics as recommended in table 5

o       If Staphylococcal infection is known or suspected, then substitution with an anti-staphylococcal penicillin (Oxacillin, nafcillin) should be utilized

o       If MRSA infection known or suspected, then substitution with Vancomycin should be utilized.

·        Genitourinary Procedures

o       Antibiotics only indicated if infection is present

o       Ampicillin, amoxicillin, vancomycin should be considered to ensure enterococcal coverage

·        Skin and Soft Tissue Procedures

o       Prophylactic antibiotics to prevent endocarditis indicated if infection is present

o       Oxacillin, cefazolin, clindamycin should be considered.  Utilize vancomycin if MRSA known or suspected.