Rx of Endocarditis

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					          Empiric, acute endocarditis: [nafcillin or oxacillin 2g IV q4h
      + gentamicin or tobramycin1mg/kg IV q8h] OR [vancomycin 15mg/kg IV q12h
      + gentamicin 1mg/kg IV q8h].
          Empiric, subacute endocarditis: [ampicillin/sulbactam 3g IV q 6h
      + gentamicin or tobramycin1mg/kg IV q8h] OR [vancomycin 15mg/kg q12h +
      [ceftriaxone 2g IV q12hORgentamicin/tobramycin 1 mg/kg IV q8h].
          Culture and sensitivity results when available will define treatment.
          See "Pathogen Specific therapy" below for specifics.




    Drug          Recommendations/Comments
    Cefotaxime    Good activity against penicillin-sensitive Staph and Strep, synergistic
                  with aminoglycosides, extensive and favorable experience with
                  endocarditis.
    Ceftazidime   Anti-Pseudomonal. Combine with Tobramycin or Gentamicin for
                  treatment of endocarditis.
    Nafcillin     Common empirical choice for Staph (MSSA) and Strep coverage while
                  awaiting culture results.
    Oxacillin     Common empirical choice for Staph (MSSA) and Strep coverage while
                  awaiting culture results.
    Tobramycin    Recommended as synergistic treatment with beta-lactams as anti-
                  pseudomonal therapy.
    Vancomycin Increasing empirically chosen in populations at higher risk for MRSA,
               e.g., IDU populations, nosocomially-related endocarditis. Should be
               dosed 15mg/kg q 12h with trough goal of 15-20mcg/ml.
    Linezolid     Disadvantages are the relative lack of experience and bacteriostatic
                  rather than bacteriocidal activity.
    Daptomycin    Can be used for vancomycin-resistant enterococci (VRE), although
                  development of resistance while on therapy has been described.
Pathogen Specific Therapy



Pathogen             1st Line Agent                               2nd Line Agent
Culture Negative     Ampicillin/sulbactam 3gm IV q 6h +           Vancomycin 15mg/kg IV q12h x 4-6 wks (if unable to
Endocarditis         aminoglycoside (gentamicin 1 mg/kg IV        tolerate PCN)+ gentamicin 1mg/kg IV q8h x 4-6wks
                     q8h) x 4-6 wks + ciprofloxacin 500mg         + ciprofloxacin 500mg PO twice daily or 400mg IV q12h
                     PO twice daily or 400mg IV q12h
Brucellaspecies      Doxycycline 100 mg IV/PO q12h                Doxycycline + gentamicin or streptomycin
                     +rifampin 300 mg PO q12h x 6 wks
Staphylococcus       Oxacillin/nafcillin 2 g IV q4h x 4 wks +/-   Beta-lactam allergic: cefazolin 2 g IV q8h x 4-6 wks +/-
aureus (MSSA)        gentamicin 1 mg/kg IV or IM q8h x 3-5         gentamicin 1 mg/kg IV q8h x 3-5 d
                     d                                            OR vancomycin 15mg/kg IV q12h x 4-6 wks
Staphylococcus       Vancomycin 15mg/kg IV q12h x 4-6 wks. Daptomycin 6 mg/kg/d x 4-6 wks
aureus (MRSA)
Staphylococcus       Nafcillin/oxacillin 2g IV                    Vancomycin 15mg/kg IV q12h x 4-6 wks
aureus (IDU,         q4h+ gentamicin 1mg/kg IV q8h x 2
tricuspid valve)     wks.
Viridans             MIC <0.1 mcg/ml:                             MIC >0.1 and <0.5:
Streptococci         Penicillin G 12-18 mU IV/24h                 Penicillin G 18 mU/24h (continuously or divided q4h) x 4
                     (continuously or divided q4h) x 4 wks        wks with gentamicin 1 mg/kg IV/IM q8h x 2 wks.
                     Ceftriaxone 2 g IV/IM q24h x 4 wks           (Ceftriaxone 2gm/d IV/IM single dose.
                     Penicillin G 12-18 mU/24h (continuously      Vancomycin 15mg/kg IV q12h x 4 wks.
                     or divided q4h) x 2 wks                      MIC >0.5: Follow standard treatment regimen for
                     with gentamicin 1 mg/kg IV/IM q8h            enterococcal endocarditis
                     Penicillin allergy: vancomycin 1 g IV
                     q12h x 4 wks.
Streptococcus        MIC <0.1                                     MIC >0.1 and <0.5:
bovis                Follow treatment regimen for viridans        Follow treatment regimen for viridans streptococci
                     streptococci                                 MIC >0.5:
                                                                  Follow treatment regimen for enterococcal endocarditis.
Enterococci and      Penicillin G 18-30 mU/24h (continuously      Vancomycin 15mg/kg IV q12h + gentamicin1 mg/kg
streptococci with    or divided q4h) + gentamicin 1 mg/kg         IV/IM q8h x 4-6 wks.
pen MIC >            IV/IM q8h x 4-6 wks (4 wks if sx             (Vancomycin if allergic to penicillin. Use doses for
0.5mcg/ml            duration< 3 months).                         resistant Enterococci. Check for high level
                     Ampicillin 12 g/24h continuously or          aminoglycoside resistance. Cephalosporins cannot be
                     divided q4h + gentamicin 1 mg/kg IV/IM       used.)
                     q8h x 4-6 weeks.                             Vancomycin resistant
                                                                  enterococci: considerdaptomycin (6mg/kg/IV/d dosing).
HACEK Organisms      Ampicillin-sulbactam 3gm IV q 6h x 4         Ceftriaxone or other third generation cephalosporins.
                     wks or ceftriaxone 2 g IV/IM q24h x 4
                     wks.
Enteric gram         Cephalosporin (2nd or 3rd generation)        Betalactam-betalactamase inhibitors
Negative Bacilli     +/- aminoglycoside x 4 wks.                  Fluoroquinolones
                                                                  Carbapenem (imipenem, meropenem)
Candidaspecies       Amphotericin B 0.8-1.0 mg/kg/24h IV          Fluconazole 400 mg IV q24h x 4-6 wks (if organism
                     +Flucytosine 100-150 mg/kg/24h for           susceptible)
                     total dose of Amphotericin B 30-40
                     mg/kg plus valve removal
Coagulase            Follow treatment regimen for S. aureus.
Negative
Staphylococci
Coxiella             Doxycycline 100 mg IV/PO q12h
burnetii (Q Fever)   and
                     ciprofloxacin (200 mg IV q12h or 500 mg
                     PO q8h
                     x 3-4 Years
    Pathogen Specific Therapy



    Pathogen                                 1st Line Agent                                        2nd Line Agent
    PCN                                      Penicillin G 18-24 mU IV/24h (continuously or         Ceftriaxone 2g IV/IM qd x 6 wks + gentamicin 1 mg/kg IV or IM q8h x 2 wks
    susceptibleStrep(MIC<=0.1ug/ml)          divided q4h) x 6 wks + Gentamicin 1 mg/kg IV or       Penicillin allergy: vancomycin 15mg/kg IV q12h x 6 wks
                                             IM q8h x 2 wks

    PCN resistantStrep(MIC>0.1ug/ml)         Penicillin G 24-30 mU IV/24h (continuously or         Ceftriaxone 2g IV/IM qd x 6 wks + Gentamicin 1 mg/kg IV or IM q8h x 4 wks
                                             divided q4h) x 6 wks + Gentamicin 1 mg/kg IV or       Penicillin allergy: Vancomycin 15mg/kg IV q12h x 6 wks
                                             IM q8h x 4 wks
    Staphylococci(Methicillin-susceptible) Oxacillin/Nafcillin 2g IV q4h x 6-8 wks                 Beta lactam Allergic: Cefazolin 2 g IV q8h x 6-8 wks + Gentamicin 1 mg/kg IV or IM
                                           + Gentamicin 1 mg/kg IV or IM q8h x 2 wks               q8h x 2 wks +Rifampin 300mg po q8h x 6-8 wks
                                           + Rifampin 300mg po q8h x 6-8 wks                       If allergy is IgE mediated anaphylaxis, then desensitize or Vancomycin 15mg/kg IV q12h
                                                                                                   x 6-8 wks + Gentamicin 1 mg/kg IV or IM q8h x 2 wks +Rifampin 300mg po q8h x 6-8
                                                                                                   wks
    Staphylococci(Methicillin-resistant)     Vancomycin 15mg/kg IV q12h x 6-8 wks                  Linezolid 600mg IV or PO bid x 6-8 wks (no/little experience)
                                             + Gentamicin 1 mg/kg IV/IM q8h x 2 wks                Synercid (no/little experience)
                                             + Rifampin300mg po q8h x 6-8 wks                      Daptomycin (no/little experience)

    Enterococci                              Penicillin G 24-30 mU IV/24h (continuously or       Vancomycin 15mg/kg IV q12h + Gentamicin 1 mg/kg IV or IM q8h x 6 wks
                                             divided q4h) +Gentamicin 1 mg/kg IV or IM q8h x 6 Vancomycin if allergic to PCN. Cephalosporins cannot be used.
                                             wks                                                 Check for high level aminoglycoside resistance. If resistant to Gentamicin,
                                             Ampicillin 12g IV/24h (continuously or divided q4h) test Streptomycin
                                             +Gentamicin 1 mg/kg IV or IM q8h x 6 wks            Vancomycin resistant enterococci: considerlinezolid or quinupristin/dalfopristin
                                                                                                 orchloramphenicol
    Diphtheroids (nondiphtheria              Penicillin G 18-24 mU IV/24h (continuously or         Penicillin allergy or Gentamicin resistance:Vancomycin 15mg/kg IV q12h x 6 wks
    corynebacteria)                          divided q4h) x 6 wks + Gentamicin 1 mg/kg IV or
                                             IM q8h x 6 wks
    HACEK organisms                          Ceftriaxone 2g IV/IM q24h x 6wks                      Ampicillin-sulbactam 12g IV/24h (continuously or divided q4h) x 6 wks
                                                                                                   + Gentamicin 1 mg/kg IV or IM q8h x 4 wks

    Candida                                  Amphotericin B 0.8-1.0 mg/kg/24h IV                   Fluconazole 400mg IV q24h x 4-6 wks (if organism susceptible)
                                             + Flucytosine 100-150 mg/kg/24h for a total dose      Caspofungin (no/little experience)
                                             ofAmphotericin B 30-40 mg/kg                          Voriconazole (no/little experience)
    Culture-negative                         Vancomycin 15mg/kg IV q12h
                                             +Gentamicin 1mg/kg IV or IM q8h x 6wks +/-
                                             Cefepime 2 g IV q8h x 6 wks




    Basis for Recommendations



                 Baddour LM, Wilson WR, Bayer AS, et al.; Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare
        professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology,
        Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America.; Circulation; 2005; Vol. 111; pp. e394-434;
        ISSN: 1524-4539;
        PUBMED: 15956145
        Rating: Basis for recommendation
        Comments:AHA recommendations used for this module.
Infectious Endocarditis Prophylaxis (2007 Revised AHA guidelines)

Basics Points:

      2007 AHA Guidelines dramatically reduce situations under which Infectious
       Endocarditis (IE) prophylaxis is indicated.

      IE is more likely to result from random bacteremias due to daily activities (e.g.
       chewing, tooth brushing) than medical procedures. This exposure ratio may
       exceed 5 million to one.

      No level A (AHA classification system) evidence exists that prophylaxis is
       beneficial, even in the highest risk patients.

      Maintenance of optimal oral health is recommended, may reduce risk of IE, and is
       more important than antibiotic prophylaxis to prevent IE resultant from dental
       procedures

Patients in the highest risk category for IE (any of the following):

      Previous IE

      Prosthetic cardiac valve (or other prosthetic material used in valve repair: e.g.
       prosthetic ring to which porcine valve is attached).

      Cardiac transplant recipients with cardiac valvulopathy

      Patients with Congenital Heart Disease, if the following specific situations apply:
           o Un-repaired CHD, including palliative shunts/conduits
           o Completely repaired congenital heart defects, but only during the six
               months after the procedure (during which endothelialization occurs)
           o Repaired CHD, with lack of endothelialization, such as when residual
               defects exist that prevent endothelialization.

Who needs prophylaxis?
Prophylaxis is indicated in patients with the highest risk of IE undergoing the following
procedures (see also special circumstances* below):

      Dental Procedures (Class IIa, evidence grade B): Any dental procedure that may
       result in manipulation of gingival tissue or the periapical region of teeth, or
       perforation of the oral mucosa. Specifically excludes injections through non-
       infected tissue, adjustment / placement of orthodontic appliances.

      Respiratory Procedures (Class IIa, evidence grade C): Bronchoscopy with incision
       or biopsy, tonsillectomy, adenoidectomy. Specifically excludes routine
       bronchoscopy.
      Surgical procedures involving infected skin/soft tissue, including musculoskeletal
       tissue (Class IIb, evidence grade C)
           o Antibiotic treatment of infected skin/soft tissue, when indicated, routine
               covers staphylococci and streptococci, which are also the organism of
               concern in IE. Therefore, treatment of the infection will also result in
               prophylaxis against IE. Consider possibility of MRSA.

Special Circumstances and Considerations:

      The above recommendations do NOT supercede general peri-operative antibiotic
       recommendations, such as the need for antibiotics peri-operatively for cardiac
       surgery.

      Highest risk patients undergoing GI/GU system procedures do NOT require
       prophylaxis (Class III, evidence grade B).
          o Exception 1: the antibiotic treatment of GI/GU infections may not
              routinely include coverage of enteroccoci; thus, broadening coverage to
              include prophylaxis against enteroccoci is reasonable in a patient with a
              pre-existing infection of the GI/GU system undergoing a GI/GU
              procedure, if the patient is also in the highest risk category for IE (Class
              IIb, evidence level B).
          o Exception 2: consider anti-enteroccoci therapy in patients colonized with
              enteroccoci who are undergoing elective cystoscopy or urinary tract
              manipulation, or in those undergoing emergent urinary tract procedures
              (Class IIb, evidence level B).


Prophylactic Regimens (Dental and Respiratory Procedures):

      Designed to cover strep veridans, the oral flora most likely to cause IE
      Administer 30-60 minutes before procedure

   Standard PO therapy: amoxicillin 2 g PO OR cephalexin 2 g PO. For penicillic
   allergic patients: clindamycin 600 mg PO OR azithromycin/clarithromycin 500 mg
   PO

   Non-oral therapy: ampicillin 2 g IM/IV OR ceftriaxone 1 g IM/IV OR cefazolin 1 g
   IM/IV. For penicillic allergic patients: clindamycin 600 mg IM/IV

				
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