The American Heart Association's (AHA's) Scientific Statement for Healthcare Professionals, which has received IDSA endorsement, served as the source of the infective endocarditis treatment recommendations offered here (Infectious Diseases Society of America) [Ref].

The following definitions describe the recommendations and types of evidence:

Level 1: Numerous meta-analyses and randomized controlled trials were used to create Class I recommendations. Level II: Class I recommendations come from either a single randomized controlled experiment or several non-randomized clinical trials. Level III: Class I advice is gleaned from case studies, professional judgments, or accepted practices.

The following is a list of the recommendation classes:

Class I: The advantages exceed the disadvantages. The intervention is recommended and ought to be used. Class IIa: Class IIa recommendations denote a plausible and likely suggestion for the intervention. Class IIb: The intervention may be taken into consideration under Class IIb. It is uncertain if the intervention will be effective or useful. Class III: Class III suggestions should not be followed since they may be dangerous.caption id="attachment_17061" align="aligncenter" width="600"] Class and levels of evidence[/caption]

General Infective Endocarditis Treatment Guidelines Recommendations

• Before beginning antimicrobial medication, contact a specialist in infectious diseases to determine the best course of treatment. 

(Class I; Level of Evidence B)

• In circumstances where blood cultures were initially positive, it is reasonable to start counting the days for the duration of antimicrobial medication on the first day that they are negative. 

(Class IIa; Level of Evidence C)

• Until the bloodstream infection has cleared, it is appropriate to get at least two sets of blood cultures every 24 to 48 hours. 

(Class IIa; Level of Evidence C).

• After valve surgery, an entire antimicrobial course is feasible if the surgical tissue cultures are positive. 

(Class IIa; Level of Evidence B)

• It may be fair to include the days of antimicrobial therapy given prior to surgery in the total number of days of therapy if the surgical tissue cultures are negative.

(Class IIb; Level of Evidence C)

• For regimens containing more than one antimicrobial agent, it is appropriate to administer antimicrobial therapy concurrently with or shortly after each other.

(Class IIa; Level of Evidence C)

Likely causative organisms in patients with risk factors:

It is crucial to be on the lookout for potential organisms in particular risk groups. This is especially useful when an empiric treatment plan is started, such as in situations of infective endocarditis with a culture-negative result, or when the results of blood cultures are waiting.

• Patients who have undergone pregnancy, delivery, or abortion as well as genitourinary disorders, infections, or manipulation:

  • Enterococcus sp
  • Group B streptococci (S agalactiae)
  • Listeria monocytogenes
  • Aerobic Gram-negative bacilli
  • Neisseria gonorrhoeae
• IDU (Intravenous drug users)
  • Fungi Gram-negative bacteria, such as Pseudomonas aeruginosa, are aerobic 
  • S. aureus, including oxacillin-resistant strains obtained in the community
  • Staphylococci without coagulase 
  • Polymicrobial
  • Histolytic streptococci

• • Cardiovascular patients with indwelling medical devices:

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

  • Patients with recurring infections and a persistent skin condition:

    • S aureus
    • β-Hemolytic streptococci

  • Those with unsatisfactory dental health or who had a dental experience:

    • Viridans group streptococci.
    • Nutritionally variant streptococci
    • Abiotrophia defectiva
    • Granulicatella sp
    • Gemella sp
    • HACEK organisms

  • Alcoholics and Cirrhosis patients:

    • Bartonella sp
    • Aeromonas sp Listeria sp
    • S pneumoniae
    • β-Hemolytic streptococci

  • Burns patients:

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

  • Diabetes mellitus:

    • S aureus
    • β-Hemolytic streptococci
    • S pneumoniae

  • Patients with Gastrointestinal lesions:

    • S gallolyticus (bovis)
    • Enterococcus sp
    • Clostridium septicum

  • 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

  • Patients with pneumonia or meningitis:

    • S pneumoniae

  • Dog or cat exposure:

    • Bartonella sp
    • Capnocytophaga sp
    • Pasteurella sp

  • Contact with contaminated milk or infected farm animals:

    • Brucella sp
    • Coxiella burnetii
    • Erysipelothrix sp

  • Homeless patients with body lice:

    • Bartonella sp

  • AIDS patients:

    • Salmonella sp
    • S pneumoniae
    • S aureus

  • Patients with Solid-organ transplantation:

    • S aureus
    • Aspergillus fumigatus
    • Enterococcus sp
    • Candida sp

  Note:

  A combination of the letters HACEK stand for Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species.

  ---

  Infective Endocarditis Treatment Guidelines:

  In this section, the suggested first- and second-line medications, as well as the doses of each pathogen, are listed. The following subtopics are covered: 

  • Infectious endocarditis brought on by Viridans group streptococci, Streptococcus gallolyticus (Formerly Known as Streptococcus bovis), Abiotrophia defectiva, and Granulicatella species Streptococcus pneumoniae, Streptococcus pyogenes, and Groups B, C, F, and G -Hemolytic Streptococci 
    Staphylococci 
    Enterococci 
    organisms HACEK 
    Organs that Are Not Hacek 
    Endocarditis-causing fungi with a negative culture

  Antimicrobial therapy for Viridans Group Streptococci, Streptococcus gallolyticus, Abiotrophia defectiva, and Granulicatella Species

  Native valve Infective Endocarditis:

  Treatment of S gallolyticus (bovis) and VGS, two pathogens that are extremely susceptible to penicillin (MIC: 0.12 g/mL)

  Recommendations:

  • • Ceftriaxone and aqueous crystalline penicillin G are both suitable alternatives for a 4-week course of therapy. 

  (Class IIa; Level of Evidence B)

  • • In individuals with simple infective endocarditis, rapid response to medication, and no underlying renal illness, a 2-week treatment course with gentamicin is appropriate. 

  (Class IIa; Level of Evidence B)

  • • In individuals who are unable to tolerate penicillin or ceftriaxone therapy, a four-week course of vancomycin is an acceptable alternative. 

  (Class IIa; Level of Evidence B)

  • • Vancomycin levels at the trough should be between 10 and 15 g/mL.

  (Class I; Level of Evidence C)

  Regimen, Dose, and Duration:

  • • Drug:
      • Ceftriaxone sodium/aqueous crystalline penicillin G sodium 
         
    • Dose
      • 12–18 million U/24 h IV, given continuously or in four to six equally spaced doses. 
      • 2 g/24 h IV or IM in one dosage of ceftriaxone 
    • Time:
      • four weeks
    • Comments:
      • Most individuals over the age of 65 who also have impaired renal or function of the eighth cranial nerve prefer this regiment. 
      • If there is a penicillin scarcity, ampicillin 2 g IV every 4 h is a viable substitute.

  (Class IIa; Level of Evidence B)

  • • Drug:
      • Penicillin G sodium aqueous crystalline or Ceftriaxone sodium in addition to gentamicin sulfate 
    • Dose
      • 12–18 million U/24 h IV, continuously or in 6 equally spaced doses, is the recommended dose of penicillin. 
      • 2 g/24 h IV or IM in a single dosage of ceftriaxone 
      • Gentamicin sulfate: 3 mg/kg every 24 hours IV or IM, given as a single dosage 
    • Duration:
      • Two weeks
    • Comments:

      • The 2-week regimen is not recommended for people who have a known cardiac or extracardiac abscess, a creatinine clearance of less than 20 mL/min, deteriorated function of the eighth cranial nerve, or infections with Abiotrophia, Granulicatella, or Gemella spp. 

      • When three divided doses are utilized, the dose of gentamicin should be changed to obtain a peak serum concentration of 3–4 g/mL and a trough serum concentration of 1 g/mL. 

      • There aren't any drug concentrations that are best for a single daily dose.

  Class IIa; Level of Evidence B

  •  
  • • Drug:
      • Vancomycin hydrochloride
    • Dose
      • 30 mg/kg IV over 24 hours in two equally spaced doses 
    • Duration:
      • Four weeks
    • Comments:

      • Only patients who are unable to tolerate penicillin or ceftriaxone are candidates for vancomycin therapy. 

      • The dosage of vancomycin should be changed to achieve a trough concentration range of 10-15 g/mL.

  Class IIa; Level of Evidence B

  VGS and S gallolyticus (bovis) are relatively penicillin-resistant (MIC >0.12-0.5 ug/ml)

  Recommendations

  • For the first two weeks of therapy, it is normal to combine a single daily dose of gentamicin with penicillin for 4 weeks.

  (Class IIa; Level of Evidence B)

  • Ceftriaxone alone may be used if the isolate is ceftriaxone sensitive.

  (Class IIb; Level of Evidence C)

  • In individuals who are unable to tolerate -lactam therapy, vancomycin alone may be a viable alternative.

  (Class IIa; Level of Evidence C)

  Regimen, Dose, and Duration:

  • • Drug:
      • Aqueous crystalline penicillin G sodium PLUS Gentamicin sulfate
    • Dose
      • Penicillin dose: 24 million U/24 h IV either continuously or in 4–6 equally divided doses
      • Gentamicin dose: 3 mg/kg per 24 h IV or IM in 1 dose
    • Duration:
      • Penicillin duration: 4 weeks
      • Gentamicin duration: 2 weeks
    • Comments:
      • It is reasonable to treat patients with IE caused penicillin-resistant (MIC ≥0.5 μg/mL) VGS strains with a combination of ampicillin or penicillin plus gentamicin as done for enterococcal IE with infectious diseases consultation (Class IIa; Level of Evidence C).
      • Ampicillin 2 g IV every 4 h is a reasonable alternative to penicillin if a penicillin shortage exists.
      • Ceftriaxone may be a reasonable alternative treatment option for VGS isolates that are susceptible to ceftriaxone (Class IIb; Level of Evidence C).

  Class IIa; Level of Evidence B

  • • Drug:
      • Vancomycin hydrochloride:
    • Dose
      • 30 mg/kg per 24 h IV in 2 equally divided doses
    • Duration:
      • 4 weeks
    • Comments:
      • Vancomycin therapy is reasonable only for patients unable to tolerate penicillin or ceftriaxone therapy

  Class IIa; Level of Evidence C

  A defectiva and Granulicatella Species and VGS With a Penicillin MIC ≥0.5 µg/mL:

  Recommendations

  • It is reasonable to treat patients with IE caused by A defectiva, Granulicatella species, and VGS with a penicillin MIC ≥0.5 µg/mL with a combination of ampicillin or penicillin plus gentamicin as done for enterococcal IE with infectious diseases consultation

  (Class IIa; Level of Evidence C)

  • If vancomycin is used in patients intolerant of ampicillin or penicillin, then the addition of gentamicin is not needed

  (Class III; Level of Evidence C)

  • Ceftriaxone combined with gentamicin may be a reasonable alternative treatment option for VGS isolates with a penicillin MIC ≥0.5 µg/mL that is susceptible to ceftriaxone

  (Class IIb; Level of Evidence C)

  Prosthetic Valve or Valvular Prosthetic Material

  Endocarditis of Prosthetic Valves or Other Prosthetic Material Caused by VGS and S gallolyticus (bovis)

  Recommendations

  • Aqueous crystalline penicillin G or ceftriaxone for 6 weeks with or without gentamicin for the first 2 weeks is reasonable

  (Class IIa; Level of Evidence B)

  • It is reasonable to extend gentamicin to 6 weeks if the MIC is >0.12 µg/mL for the infecting strain

  (Class IIa; Level of Evidence C)

  • Vancomycin can be useful in patients intolerant of penicillin, ceftriaxone, or gentamicin

  (Class IIa; Level of Evidence B)

  Regimen, Dose, and Duration for Penicillin-susceptible strains (≤0.12 μg/mL)

  • • Drugs:
      • Aqueous crystalline penicillin G sodium OR
      • Ceftriaxone with or without Gentamicin
    • Dose:
      • Penicillin dose: 24 million U/24 h IV either continuously or in 4–6 equally divided doses
      • Ceftriaxone Dose: 2 g/24 h IV or IM in 1 dose
      • Gentamicin Dose: 3 mg/kg per 24 h IV or IM in 1 dose
    • Duration:
      • Penicillin duration: 6 weeks
      • Ceftriaxone duration: 6 weeks
      • Gentamicin duration: 2 weeks
    • Comments:
      • Penicillin or ceftriaxone together with gentamicin has not demonstrated superior cure rates compared with monotherapy with penicillin or ceftriaxone for patients with the highly susceptible strain;
      • gentamicin therapy should not be administered to patients with creatinine clearance <30 mL/min.
      • Ampicillin 2 g IV every 4 h is a reasonable alternative to penicillin if a penicillin shortage exists.

  Class IIa; Level of Evidence B

  • • Drug:
      • • Vancomycin hydrochloride
    • Dose:
      • 30 mg/kg per 24 h IV in 2 equally divided doses
    • Duration:
      • 6 weeks
    • Comments:
      • Vancomycin is reasonable only for patients unable to tolerate penicillin or ceftriaxone

  Class IIa; Level of Evidence B

  Regimen, Dose, and Duration for Penicillin relatively or fully resistant strain (MIC >0.12 μg/mL)

  • • Drug:
      • Aqueous crystalline penicillin sodium OR
      • Ceftriaxone PLUS Gentamicin sulfate
    • Dose:
      • Penicillin dose: 24 million U/24 h IV either continuously or in 4–6 equally divided doses
      • Ceftriaxone dose: 2 g/24 h IV/IM in 1 dose
      • Gentamicin dose: 3 mg/kg per 24 h IV/IM in 1 dose
    • Duration:
      • 6 weeks
    • Comments:
      • Ampicillin 2 g IV every 4 h is a reasonable alternative to penicillin if a penicillin shortage exists

   Class IIa; Level of Evidence B

  • • Drug:
      • Vancomycin hydrochloride
    • Dose:
      • 30 mg/kg per 24 h IV in 2 equally divided doses
    • Duration:
      • 6 weeks
    • Comments:
      • Vancomycin is reasonable only for patients unable to tolerate penicillin or ceftriaxone

  Class IIa; Level of Evidence B

  [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Treatment of Streptococcus pneumonia, Strep Pyogenes, and Beta hemolytic Streptococci" collapse_text="Treatment of Streptococcus Pneumoniae, Strep Pyogenes, and Beta hemolytic Streptococci"]

  Infective Endocarditis Treatment Guidelines -

  Infections caused by Streptococcus pneumoniae, Streptococcus pyogenes, and Groups B, C, F, and G β-Hemolytic Streptococci

  Recommendations

  • Four weeks of antimicrobial therapy with a penicillin, cefazolin, or ceftriaxone is reasonable for infective endocarditis caused by S.pneumoniae; vancomycin can be useful for patients intolerant of β-lactam therapy

  (Class IIa; Level of Evidence C)

  • Six weeks of therapy is reasonable for PVE (prosthetic valve endocarditis) caused by S pneumoniae

  (Class IIa; Level of Evidence C)

  • High-dose penicillin or a third-generation cephalosporin is reasonable in patients with IE caused by penicillin-resistant S pneumoniae without meningitis; if meningitis is present, then high doses of cefotaxime (or ceftriaxone) are reasonable

  (Class IIa; Level of Evidence C)

  • The addition of vancomycin and rifampin to cefotaxime (or ceftriaxone) may be considered in patients with IE caused by S pneumoniae that are resistant to cefotaxime (MIC >2 µg/mL)

  (Class IIb; Level of Evidence C)

  • Because of the complexities of IE caused by S pneumoniae, consultation with an infectious diseases specialist is recommended

  (Class I; Level of Evidence C)

  • For infective endocarditis caused by S pyogenes, 4 to 6 weeks of therapy with aqueous crystalline penicillin G or ceftriaxone is reasonable; vancomycin is reasonable only in patients intolerant of β-lactam therapy

  (Class IIa; Level of Evidence C)

  • For IE caused by group B, C, or G streptococci, the addition of gentamicin to aqueous crystalline penicillin G or ceftriaxone for at least the first 2 weeks of a 4- to 6-week treatment course may be considered

  (Class IIb; Level of Evidence C)

  • Consultation with an infectious disease specialist to guide treatment is recommended in patients with IE caused by β-hemolytic streptococci

  (Class I; Level of Evidence C)

  [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Treatment of Infective endocarditis caused by Staphylococci" collapse_text="Treatment of Infective endocarditis caused by Staphylococci"]

  Infective Endocarditis Treatment Guidelines -

  Infections caused by Staphylococci

  Coagulase-Negative Staphylococci

  Recommendations:

  • Ongoing vigilance for IE complications, including perivalvular extension of infection and extracardiac foci of infection, is reasonable

  (Class IIa; Level of Evidence C)

  IE Caused by Staphylococci in the Absence of Prosthetic Valves or Other Prosthetic Material

  Right-Sided IE in IDUs

  Recommendation

  • Gentamicin is not recommended for the treatment of right-sided staphylococcal NVE (native valve endocarditis)

  (Class III; Level of Evidence B)

  Infective endocarditis in Non-IDUs

  Recommendations

  • Gentamicin should not be used for the treatment of NVE caused by MSSA or MRSA

  (Class III; Level of Evidence B)

  • In cases of brain abscess resulting from MSSA IE, nafcillin should be used instead of cefazolin; vancomycin should be given in cases of nafcillin intolerance

  (Class I; Level of Evidence C)

  • The usefulness of empirical combination therapy with vancomycin plus an antistaphylococcal β-lactam antibiotic in patients with S aureus bacteremia until oxacillin susceptibility is known is uncertain

  (Class IIb; Level of Evidence B)

  • IE caused by staphylococci that are penicillin-susceptible should be treated with antistaphylococcal β-lactam antibiotics rather than aqueous crystalline penicillin G because clinical laboratories are not able to detect penicillin susceptibility

  (Class I; Level of Evidence B)

  • Six weeks of nafcillin (or equivalent antistaphylococcal penicillin) is recommended for uncomplicated left-sided NVE caused by MSSA; at least 6 weeks of nafcillin (or equivalent antistaphylococcal penicillin) is recommended for complicated left-sided NVE caused by this organism

  (Class I; Level of Evidence C)

  • Daptomycin may be a reasonable alternative to vancomycin for the treatment of left-sided IE resulting from MRSA

  (Class IIb; Level of Evidence B)

  • The selection of daptomycin dosing should be assisted by infectious diseases consultation

  (Class I; Level of Evidence C)

  Antibiotics regimen, Dose, and Duration for NVE Caused by Staphylococci Susceptible to Oxacillin

  • • Drug
      • Nafcillin or oxacillin
    • Dose
      • 12 g/24 h IV in 4–6 equally divided doses
    • Duration
      • 6 weeks
    • Comments
      • For complicated right-sided IE and left-sided IE;
      • for uncomplicated right-sided IE, 2 wk.

  Class I; Level of Evidence C

  For penicillin-allergic (non-anaphylactoid type) patients:

  • Consider skin testing for oxacillin-susceptible staphylococci and questionable history of immediate-type hypersensitivity to penicillin.
    • Drug
      • Cefazolin
    • Dose
      • 6 g/24 h IV in 3 equally divided doses
    • Duration
      • 6 weeks
    • Comments
      • Cephalosporins should be avoided in patients with anaphylactoid-type hypersensitivity to β-lactams; vancomycin should be used in these cases.

  Class I; Level of Evidence B

  Antibiotics regimen, Dose, and Duration for NVE Caused by Staphylococci Resistant to Oxacillin

  • • Drug
      • Vancomycin
    • Dose
      • 30 mg/kg per 24 h IV in 2 equally divided doses
    • Duration
      • 6 weeks
    • Comments
      • Await additional study data to define optimal dosing.

  Class I; Level of Evidence C

  • • Drug
      • Daptomycin
    • Dose
      • ≥8 mg/kg/dose
    • Duration
      • 6 weeks
    • Comments
      • Adjust vancomycin dose to achieve trough concentration of 10–20 μg/mL (see text for vancomycin alternatives)

  Class IIb; Level of Evidence B

  Therapy of MSSA IE in Patients Allergic to or Intolerant of β-Lactams

  Recommendations

  • Cefazolin is reasonable in patients with a well-defined history of non-anaphylactoid reactions to penicillins

  (Class IIa; Level of Evidence B)

  • Allergy evaluation for tolerance to β-lactam therapy should be done in every case in which vancomycin is considered for the treatment of MSSA IE

  (Class I; Level of Evidence B)

  • Clindamycin is not recommended as a result of an increased IE relapse rate

  (Class III; Level of Evidence B)

  • Daptomycin is a reasonable alternative to vancomycin for NVE caused by MSSA

  (Class IIa; Level of Evidence B)

  Additional or Adjunctive Therapies

  Recommendations

  • Routine use of rifampin is not recommended for the treatment of staphylococcal NVE

  (Class III; Level of Evidence B)

  • IE caused by vancomycin-resistant staphylococci (hVISA, VISA, or VRSA) should be managed in conjunction with an infectious diseases consultant

  (Class I; Level of Evidence C)

  IE Caused by Staphylococci in the Presence of Prosthetic Valves or Other Prosthetic Material caused by Coagulase-Negative Staphylococci (CoNS)

  Recommendations

  • Vancomycin and rifampin are recommended for a minimum of 6 weeks, with the use of gentamicin limited to the first 2 weeks of therapy

  (Class I; Level of Evidence B)

  • If CoNS are resistant to gentamicin, then an aminoglycoside to which they are susceptible may be considered

  (Class IIb; Level of Evidence C)

  • If CoNS are resistant to all aminoglycosides, then substitution with a fluoroquinolone may be considered if the isolate is susceptible to a fluoroquinolone

  (Class IIb; Level of Evidence C)

  • Organisms recovered from surgical specimens or blood from patients who have had a bacteriological relapse should be carefully retested for complete antibiotic susceptibility profiles

  (Class I; Level of Evidence C)

  IE Caused by Staphylococci in the Presence of Prosthetic Valves or Other Prosthetic Material caused by Staphylococcus Aureus

  Recommendations

  • Combination antimicrobial therapy is recommended

  (Class I; Level of Evidence C)

  • Gentamicin should be administered for the initial 2 weeks of therapy with either β-lactam or vancomycin containing regimens

  (Class I; Level of Evidence C)

  Antibiotics Regimen, Dose, and Duration of Therapy for Endocarditis Involving a Prosthetic Valve or Other Prosthetic Material Caused by Oxacillin-Susceptible strains of Staphylococci

  • • Drug:
      • Nafcillin or oxacillin PLUS
      • Rifampin PLUS
      • Gentamicin
    • Dose:
      • Nafcillin/Oxacillin dose: 12 g/24 h IV in 6 equally divided doses
      • Rifampin dose: 900 mg per 24 h IV or orally in 3 equally divided doses
      • Gentamicin dose: 3 mg/kg per 24 h IV or IM in 2 or 3 equally divided doses
    • Duration:
      • Nafcillin/ Oxacillin: ≥6 weeks
      • Rifampin:  ≥6 weeks
      • Gentamicin: 2 weeks
    • Comments:
      • Vancomycin should be used in patients with immediate-type hypersensitivity reactions to β-lactam antibiotics
      • Cefazolin may be substituted for nafcillin or oxacillin in patients with non–immediate-type hypersensitivity reactions to penicillin.

  Class I; Level of Evidence B

  Antibiotics Regimen, Dose, and Duration of Therapy for Endocarditis Involving a Prosthetic Valve or Other Prosthetic Material Caused by Oxacillin-Resistant strains of Staphylococci

  • • Drug:
      • Vancomycin PLUS
      • Rifampin PLUS
      • Gentamicin
    • Dose:
      • Vancomycin dose: 30 mg/kg 24 h in 2 equally divided doses
      • Rifampin dose: 900 mg/24 h IV/PO in 3 equally divided doses
      • Gentamicin dose: 3 mg/kg per 24 h IV/IM in 2 or 3 equally divided doses
    • Duration:
      • Vancomycin: ≥6 weeks
      • Rifampin:  ≥6 weeks
      • Gentamicin: 2 weeks
    • Comments:
      • Adjust vancomycin to a trough concentration of 10–20 μg/mL. (see text for gentamicin alternatives)

  Class I; Level of Evidence B

  [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Infective endocarditis caused by Enterococci" collapse_text="Infective endocarditis caused by Enterococci"]

  Infective Endocarditis Treatment Guidelines -

  Infections caused by Enterococci

  Recommendations

  • Enterococci should be tested routinely in vitro for susceptibility to penicillin and vancomycin (MIC determination) and for high-level resistance to gentamicin to predict synergistic interactions

  (Class I; Level of Evidence A)

  • In vitro susceptibility to daptomycin and linezolid should be obtained for strains that are resistant to β-lactams, vancomycin, or aminoglycosides

  (Class I; Level of Evidence C)

  Regimen, Dose, and Duration for Endocarditis Involving a Native or Prosthetic Valve or Other Prosthetic Material caused by Enterococcus Species Susceptible to Penicillin and Gentamicin in Patients Who Can Tolerate β-Lactam Therapy

  • • Drugs:
      • Either Ampicillin sodium OR Aqueous penicillin G sodium PLUS
      • Gentamicin sulfate
    • Dose:
      • Ampicillin dose: 2 g IV every 4 h
      • Penicillin G dose: 18–30 million U/24 h IV either continuously or in 6 equally divided doses
      • Gentamicin dose: 3 mg/kg ideal body weight in 2–3 equally divided doses
    • Duration:
      • Ampicillin duration: 4 - 6 weeks
      • Penicillin G duration: 4 - 6 weeks
      • Gentamicin duration: 4 - 6 weeks
    • Comments:
      • Native valve: 4-wk therapy recommended for patients with symptoms of illness for 3 months and for patients with prosthetic valve or prosthetic material.
      • Recommended for patients with creatinine clearance >50 mL/min.

  Class IIa; Level of Evidence B

  OR

  • • Drug:
      • Double β-lactam Ampicillin PLUS
      • Ceftriaxone
    • Dose:
      • Ampicillin dose: 2 g IV every 4 h
      • Ceftriaxone dose: 2 g IV every 12 h
    • Duration:
      • 6 weeks
    • Comments:
      • Recommended for patients with initial creatinine clearance

  Class IIa; Level of Evidence B

  Role of Aminoglycosides in the Treatment of Patients With Enterococcal IE: Special Considerations:

  Recommendations

  • Gentamicin should be administered in daily multiple divided doses (total ≈3 mg/kg/day) rather than a single daily dose to patients with enterococcal IE and normal renal function

  (Class I; Level of Evidence B)

  • It is reasonable to administer gentamicin every 8 hours with the dose adjusted to achieve a 1-hour serum concentration of ≈3 µg/mL and a trough concentration of <1 µg/mL

  (Class IIa; Level of Evidence B)

  Infective Endocarditis caused by enterococcal endocarditis susceptible to Penicillin, Vancomycin, and Aminoglycosides

  Recommendations

  • Therapy that includes either ampicillin or aqueous crystalline penicillin G plus gentamicin or ampicillin plus ceftriaxone is reasonable

  (Class IIa; Level of Evidence B)

  • Either 4 or 6 weeks of therapy is reasonable for NVE, depending on the duration of IE symptoms before the initiation of therapy if ampicillin or penicillin plus gentamicin is used

  (Class IIa; Level of Evidence B)

  • Six weeks of therapy is reasonable if ampicillin plus ceftriaxone is selected as the treatment regimen, regardless of symptom duration

  (Class IIa; Level of Evidence B)

  • Six weeks of antimicrobial therapy is reasonable for PVE

  (Class IIa; Level of Evidence B)

  • Streptomycin should be avoided in patients with creatinine clearance <50 mL/min

  (Class III; Level of Evidence B)

  • If the strain of Enterococcus is susceptible to both gentamicin and streptomycin, it is reasonable to use gentamicin rather than streptomycin for therapy

  (Class IIa; Level of Evidence C)

  • When gentamicin therapy is not an option, then a double–β-lactam regimen (see later section) is reasonable

  (Class IIa; Level of Evidence B)

  Infective Endocarditis caused by E faecalis

  • Susceptible to Penicillin,
  • Resistant to Aminoglycosides, or
  • Gentamicin Resistant and Streptomycin Susceptible

  Recommendations

  • Ceftriaxone-ampicillin combination therapy is reasonable for IE caused by aminoglycoside resistant enterococcal strains

  (Class IIa; Level of Evidence B)

  • For gentamicin-resistant and streptomycin-susceptible Enterococcus species, ampicillin-ceftriaxone combination therapy is reasonable

  (Class IIa; Level of Evidence B)

  Antibiotics regimen, dose, and duration of Therapy for Endocarditis Involving a Native or Prosthetic Valve or Other Prosthetic Material caused by Enterococcus species:

  • Susceptible to Penicillin and Resistant to Aminoglycosides or
  • Streptomycin-Susceptible Gentamicin-Resistant in Patients Able to Tolerate β-Lactam Therapy
    • Drug:
      • Double β-lactam Ampicillin PLUS
      • Ceftriaxone
    • Dose:
      • Ampicillin dose: 2 g IV every 4 h
      • Ceftriaxone dose: 2 gm IV every 12h
    • Duration:
      • 6 weeks
    • Comments:
      • Double β-lactam is reasonable for patients with normal or impaired renal function abnormal cranial nerve VIII function or if the laboratory is unable to provide rapid results of streptomycin serum concentration;
      • native valve infection with symptoms of infection 3 months or treatment with a double β-lactam regimen require a minimum of 6 wk of therapy.

  Class IIa; Level of Evidence B

  An alternative for streptomycin susceptible/gentamicin resistant strains:

  • • Drug:
      • Either Ampicillin sodium OR Aqueous penicillin G sodium PLUS
      • Streptomycin sulfate
    • Dose:
      • Ampicillin dose: 2 g IV every 4 h
      • Penicillin dose: 18–30 million U/24 h IV either continuously or in 6 equally divided doses
      • Streptomycin dose: 15 mg/kg ideal body weight per 24h IV or IM in 2 equally divided doses
    • Duration:
      • 4 - 6 weeks
    • Comments
      • Use is reasonable only for patients with the availability of rapid streptomycin serum concentrations.
      • Patients with creatinine clearance <50 mL/min or who develop creatinine clearance <50 mL/min during treatment should be treated with double–βlactam regimen.
      • Patients with abnormal cranial nerve VIII function should be treated with double–β-lactam regimen.

  Class IIa; Level of Evidence B

  Vancomycin Therapy for Enterococcal IE in Patients Unable to Tolerate β-Lactams or Patients With E faecalis Resistant to Penicillin

  Recommendations

  • Vancomycin should be administered only if a patient is unable to tolerate penicillin or ampicillin

  (Class I; Level of Evidence B)

  • It is reasonable that patients with NVE receive 6 weeks of vancomycin-gentamicin therapy and that patients with PVE receive at least 6 weeks of therapy

  (Class IIa; Level of Evidence B)

  • Patients with E faecalis IE caused by strains that are intrinsically resistant to penicillin should be treated with a combination of vancomycin plus gentamicin

  (Class I; Level of Evidence B)

  Vancomycin-Containing Regimens for Vancomycin- and Aminoglycoside-Susceptible Penicillin-Resistant Enterococcus Species for Native or Prosthetic Valve (or Other Prosthetic Material) IE in Patients Unable to Tolerate β-Lactam

  • • Drugs:
      • Vancomycin PLUS
      • Gentamicin
    • Dose:
      • Vancomycin dose: 30 mg/kg per 24 h IV in 2 equally divided doses
      • Gentamicin dose: 3 mg/kg per 24 h IV or IM in 3 equally divided doses
    • Duration:
      • 6 weeks
    • Comments:

  Penicillin resistance; intrinsic or β-lactamase producer

  • • Drug:
      • Vancomycin PLUS
      • Gentamicin
    • Dose:
      • Vancomycin dose: 30 mg/kg per 24 h IV in 2 equally divided doses
      • Gentamicin dose: 3 mg/kg per 24 h IV or IM in 3 equally divided doses
    • Duration:
      • 6 weeks
    • Comments:
      • For β-lactamase–producing strain, if able to tolerate a β-lactam antibiotic, ampicillin-sulbactam§ plus aminoglycoside therapy may be used.

  Class IIb; Level of Evidence C

  Enterococcal Endocarditis Resistant to Penicillin, Aminoglycosides, and Vancomycin

  Recommendations

  • Patients with IE attributable to Enterococcus species resistant to penicillin, aminoglycosides, and vancomycin should be managed by specialists in infectious diseases, cardiology, cardiovascular surgery, clinical pharmacy, and, if necessary, pediatrics

  (Class I; Level of Evidence C)

  • If daptomycin therapy is selected, then doses of 10 to 12 mg·kg−1·24 h−1 may be considered

  (Class IIb; Level of Evidence C)

  • Combination therapy with daptomycin and ampicillin or ceftaroline may be considered, especially in patients with persistent bacteremia or enterococcal strains with high MICs (ie, 3 µg/mL) to daptomycin within the susceptible range

  (Class IIb; Level of Evidence C)

  Therapy for Endocarditis Involving a Native or Prosthetic Valve or Other Prosthetic Material Resulting From Enterococcus Species Caused by Strains Resistant to Penicillin, Aminoglycosides, and Vancomycin

  • • Drugs:
      • Linezolid OR
      • Daptomycin
    • Dose:
      • Linezolid dose: 600 mg IV or orally every 12 h
      • Daptomycin dose: 10–12 mg/kg per dose
    • Duration:
      • > 6 weeks
    • Comments:
      • Linezolid use may be associated with potentially severe bone marrow suppression, neuropathy, and numerous drug interactions.
      • Patients with IE caused by these strains should be treated by a care team including specialists in infectious diseases, cardiology, cardiac surgery, clinical pharmacy, and, in children, pediatrics.
      • Cardiac valve replacement may be necessary for a cure.

  Class IIb; Level of Evidence C

  [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Infective endocarditis caused by HACEK organisms" collapse_text="Infective endocarditis caused by HACEK organisms"]

  Infective Endocarditis Treatment Guidelines -

  IE caused by HACEK Microorganisms

  Recommendations

  • Unless growth is adequate in vitro to obtain susceptibility testing results, HACEK microorganisms are considered ampicillin-resistant, and penicillin and ampicillin should not be used for the treatment of patients with IE

  (Class III; Level of Evidence C)

  • Ceftriaxone is reasonable for the treatment of HACEK infective endocarditis

  (Class IIa; Level of Evidence B)

  • The duration of therapy for HACEK native valve endocarditis of 4 weeks is reasonable

  (Class IIa; Level of Evidence B)

  • for HACEK prosthetic valve endocarditis, the duration of therapy of 6 weeks is reasonable

  (Class IIa; Level of Evidence C)

  • Gentamicin is not recommended because of its nephrotoxicity risks

  (Class III; Level of Evidence C)

  • A fluoroquinolone (ciprofloxacin, levofloxacin, or moxifloxacin) may be considered an alternative agent for patients unable to tolerate ceftriaxone (or other third- or fourth-generation cephalosporins)

  (Class IIb; Level of Evidence C)

  • Ampicillin-sulbactam may be considered a treatment option for HACEK IE

  (Class IIb; Level of Evidence C).

  • Patients with HACEK IE who do not tolerate ceftriaxone therapy should be treated in consultation with an infectious diseases specialist

  (Class I; Level of Evidence C)

  Drugs, Dosage, and Duration of Therapy for Endocarditis Involving a Native or Prosthetic Valve or Other Prosthetic Material Caused by HACEK Microorganisms

  • • Drug:
      • Ceftriaxone sodium
    • Dose:
      • 2 g/24 h IV or IM in 1 dose
    • Duration:
      • Native valve endocarditis: 4 weeks
      • Prosthetic valve endocarditis: 6 weeks
    • Comments:
      • Preferred therapy: cefotaxime or another third- or fourth-generation cephalosporin may be substituted.

  Class IIa; Level of Evidence B

  OR

  • • Drug:
      • Ampicillin sodium
    • Dose:
      • 2 g IV every 4 h
    • Duration:
      • NVE: 4 weeks
      • PVE: 6 weeks
    • Comments:
      • Ampicillin sodium may be an option if the growth of the isolate is sufficient to permit in vitro susceptibility results.

  Class IIa; Level of Evidence B

  OR

  • • Drug:
      • Ciprofloxacin
    • Dose:
      • 1000 mg/24 h orally or 800 mg/24 h IV in 2 equally divided doses
    • Duration:
      • NVE: 4 weeks
      • PVE: 6 weeks
    • Comments:
      • Fluoroquinolone therapy may be considered for patients unable to tolerate cephalosporin and ampicillin therapy;
      • levofloxacin or moxifloxacin may be substituted;
      • fluoroquinolones generally are not recommended for patients <18 y old.
      • Treatment for 6 wk is reasonable in patients with PVE (Class IIa; Level of Evidence C).

  Class IIa; Level of Evidence B

  [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Infective Endocarditis caused by Non-HACEK Gram-Negative Bacilli" collapse_text="Infective Endocarditis caused by Non-HACEK Gram-Negative Bacilli"]

  Infective Endocarditis Treatment Guidelines - 

  IE caused by Non-HACEK Gram-Negative Bacilli

  Recommendations

  • Cardiac surgery is reasonable in combination with prolonged courses of combined antibiotic therapy for most patients with IE caused by non-HACEK Gram-negative aerobic bacilli, particularly P aeruginosa

  (Class IIb; Level of Evidence B)

  • Combination antibiotic therapy with a β-lactam (penicillins, cephalosporins, or carbapenems) and either an aminoglycoside or fluoroquinolone for 6 weeks is reasonable

  (Class IIa; Level of Evidence C)

  • Consultation with an infectious disease expert in IE should be sought because of the various mechanisms of antibiotic resistance that can be found in the nonHACEK Gram-negative aerobic bacilli

  (Class I; Level of Evidence C)

  [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Culture Negative Endocarditis" collapse_text="Culture Negative Endocarditis"]

  Infective Endocarditis Treatment Guidelines -

  IE recommendations for culture-negative Endocarditis

  Recommendations

  • Evaluation of epidemiological factors, history of prior infections including cardiovascular infections, exposure to antimicrobials, clinical course, severity, and extracardiac sites of infection of the current infection should be performed in all culture-negative endocarditis cases

  (Class I; Level of Evidence C)

  • Consultation with an infectious disease specialist to define the most appropriate choice of therapy in patients with culture-negative endocarditis is recommended

  (Class I; Level of Evidence C)

  • For patients with acute (days) clinical presentations of native valve infection, coverage for S aureus, β-hemolytic streptococci, and aerobic Gramnegative bacilli is reasonable

  (Class IIa; Level of Evidence C)

  • For patients with a subacute (weeks) presentation of NVE, coverage of S aureus, VGS, HACEK, and enterococci is reasonable

  (Class IIa; Level of Evidence C)

  • For patients with culture-negative PVE, coverage for staphylococci, enterococci, and aerobic Gram-negative bacilli is reasonable if the onset of symptoms is within 1 year of prosthetic valve placement

  (Class IIa; Level of Evidence C)

  • If symptom onset is >1 year after valve placement, then IE is more likely to be caused by staphylococci, VGS, and enterococci, and antibiotic therapy for these potential pathogens is reasonable

  (Class IIa; Level of Evidence C)

  • If subsequent blood culture results or other laboratory methodologies define a pathogen, then empirical therapy should be revised to focused therapy that is recommended for the specific pathogen identified

  (Class I; Level of Evidence C)

  [/bg_collapse]   [bg_collapse view="button-blue" color="#f7f2f2" icon="arrow" expand_text="Fungal Endocarditis" collapse_text="Fungal Endocarditis"]

  Infective Endocarditis Treatment Guidelines:

  IE caused by Fungi:

  Recommendations

  • Valve surgery should be done in most cases of fungal IE

  (Class I; Level of Evidence B)

  • After completion of initial parenteral therapy, lifelong suppressive therapy with an oral azole is reasonable

  (Class IIa; Level of Evidence B)

  [/bg_collapse]




 
•