INFECTIVE ENDOCARDITIS

MADDIE TOMPKINS, PHARMD

PGY1 PHARMACY RESIDENT
 MODIFIED DUKE CRITERIA
 Major:
 Blood cultures + for organism consistent with IE

1 major 1 major
 Echocardiogram +: TEE recommended for prosthetic valve

majorcondition 3 minor
2Predisposing 5Possible
minor
 Minor:

+1Feverminor +3 minor

 >38℃
 Vascular phenomena: septic emboli, pulmonary infarcts, mycotic aneurisms, Janeway lesions
 Blood culture + for other potential organism
 Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor
INFECTIVE ENDOCARDITIS

 Consider:
 Organism(s)
 Susceptibilities (MIC)
 Native or prosthetic valve
 Days of therapy begin on first day of NEGATIVE blood cultures; repeat q24-48h
 If valve surgery with OR cx + or perivalvular abscess: begin days of therapy after surgery
 If OR cx -: then continue count from first day of negative bcx
 Medication allergies
 Renal/hepatic impairment
 NVE HIGHLY PCN SUSCEPTIBLE (MIC ≤0.12) VGS AND S. BOVIS

Regimen Dose Duration Comments

Aqueous PCN G Sodium 12-18 million U CIV 4 wks Ampicillin 2g IV Q4H
Or 4-6 equally divided If PCN shortage
doses
Ceftriaxone 2g IV Q24H 4 wks If pt cannot tolerate PCN
Vancomycin 15 mg/kg IV Q12H 4 wks If pt cannot tolerate PCN
or ceftriaxone
Aqueous PCN G Sodium 12-18 million U CIV 2 wks 2 wk regimen for
OR 6 equally divided uncomplicated right-
+ Gentamicin doses sided in IVDU
3 mg/kg IV daily NOT for extracardiac
Ceftriaxone 2g IV Q24H 2 wks infection, or CrCl<20
+ Gentamicin 3 mg/kg IV daily
 NVE RELATIVELY RESISTANT TO PCN(MIC >0.12 AND <0.5) VGS AND S.
BOVIS

Regimen Dose Duration Comments

Aqueous PCN G Sodium 24 million U CIV 4 wks Ampicillin 2g IV Q4H
Or 4-6 equally divided If PCN shortage
doses
+Gentamicin 3 mg/kg IV daily 2 wks
Ceftriaxone 2g IV Q24H 4 wks If pt cannot tolerate PCN
Vancomycin 15 mg/kg IV Q12H 4 wks If pt cannot tolerate PCN
or ceftriaxone
 PVE HIGHLY PCN SUSCEPTIBLE (MIC≤0.12) VGS AND S. BOVIS

Regimen Dose Duration Comments

Aqueous PCN G Sodium 24 million U CIV 6 wks Ampicillin 2g IV Q4H
Or 4-6 equally divided If PCN shortage
doses
+/- Gentamicin 3 mg/kg IV daily 2 wks
Ceftriaxone 2g IV Q24H 6 wks If pt cannot tolerate PCN
+/- Gentamicin 3 mg/kg IV daily 2 wks
Vancomycin 15 mg/kg IV Q12H 6 wks If pt cannot tolerate PCN
or ceftriaxone
 PVE RELATIVELY RESISTANT TO PCN (MIC >0.12) VGS AND S. BOVIS

Regimen Dose Duration Comments

Aqueous PCN G Sodium 24 million U CIV 6 wks Ampicillin 2g IV Q4H
Or 4-6 equally divided If PCN shortage
doses
+Gentamicin 3 mg/kg IV daily 6 wks
Ceftriaxone 2g IV Q24H 6 wks If pt cannot tolerate PCN
+Gentamicin 3 mg/kg IV daily 6 wks
Vancomycin 15 mg/kg IV Q12H 6 wks If pt cannot tolerate PCN
or ceftriaxone
NVE OXACILLIN-SUSCEPTIBLE STAPHYLOCOCCI
Regimen Dose Duration Comments
Nafcillin or oxacillin 12g/24h IV in 4-6 equally 6 wks 2 wk regimen IF
divided doses uncomplicated right-sided
+/- gent synergy
Cefazolin 2g IV Q8H 6 wks If pt cannot tolerate
nafcillin or oxacillin
Vancomycin 15 mg/kg IV Q12H 6 wks If pt cannot tolerate beta-
Or Daptomycin ≥ 8 mg/kg/dose lactams

NVE OXACILLIN-RESISTANT STAPHYLOCOCCI

Regimen Dose Duration Comments
Vancomycin 15 mg/kg IV Q12H 6 wks
Daptomycin ≥8 mg/kg/dose 6 wks Less evidence
PVE OXACILLIN SUSCEPTIBLE STAPHYLOCOCCI
Regimen Dose Duration Comments
Nafcillin or oxacillin 12g/24h IV in 6 equally ≥6 wks If CoNS resistant to gent,
divided doses use susceptible AG
+ Rifampin 300mg IV or PO Q8H ≥6 wks If CoNS resistant to all
+ Gentamicin 3 mg/kg/24h IV in 2-3 2 wks AGs, use FQ
equally divided doses
Cefazolin 2g IV Q8H ≥6 wks If pt cannot tolerate
+ Rifampin 300mg IV or PO Q8H nafcillin or oxacillin
+ Gentamicin 3 mg/kg/24h IV in 2-3 ≥6 wks
equally divided doses 2 wks
Vancomycin 15 mg/kg IV Q12H ≥6 wks If pt cannot tolerate beta
+ Rifampin 300mg IV or PO Q8H lactams
+ Gentamicin 3 mg/kg/24h IV in 2-3 ≥6 wks
equally divided doses 2 wks
PVE OXACILLIN RESISTANT STAPHYLOCOCCI
Regimen Dose Duration Comments
Vancomycin 15 mg/kg IV Q12H ≥6 wks
+ Rifampin 300mg IV or PO Q8H
+ Gentamicin 3 mg/kg/24h IV in 2-3 ≥6 wks
equally divided doses 2 wks
NVE/PVE ENTEROCOCCUS
Regimen Dose Duration Comments
Ampicillin 2g IV Q4H 4-6 wks NVE with symptoms
+ Gentamicin 3 mg/kg IBW in 2-3 equally 4-6 wks <3mo: 4wks
divided doses PVE or NVE with
symptoms >3 mo: 6 wks
Aqueous PCN G 18-30 million U CIV or in 6 4-6 wks
sodium equally divided doses
3 mg/kg IBW in 2-3 equally 4-6 wks
+ Gentamicin divided doses
Ampicillin 2g IV Q4H 6 wks Recommended if CrCl
+ Ceftriaxone 2g IV Q12H 6 wks <50 or gent R

Ampicillin/sulbactam 3g IV Q6H 6 wks If PCN R

+ Gentamicin 3 mg/kg IBW in 3 equally 6 wks
divided doses
Vancomycin 15 mg/kg IV Q12H 6 wks If pt cannot tolerate beta-
+ Gentamicin 3 mg/kg IBW in 3 equally 6 wks lactams or PCN R
divided doses
NVE/PVE HACEK
Regimen Dose Duration Comments
Ceftriaxone 2g IV daily
Ampicillin 2g IV Q4H
4 wks NVE
Ciprofloxacin 1000mg PO daily or 400 6 wks PVE If unable to tolerate
mg IV Q12H beta-lactams

Haemophilus, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens, Kingella

QUESTIONS

A 36-year-old man with a history of intravenous drug use and NKDA is admitted to the hospital with a 1-week history
of fever and weakness and a physical examination positive for petechiae on his distal extremities. His TEE
(transesophageal echocardiogram) is positive for a 0.8-cm vegetation on his tricuspid valve, and blood cultures are
positive for Staphylococcus aureus. Susceptibilities (S) for the organism are as follows:

Oxacillin 1 S Penicillin > 8 R Levofloxacin ≤ 1 S

Clindamycin ≤ 0.5 S TMP/SMX ≤ 0.5/9.5 S
Vancomycin 1 S Rifampin ≤ 0.5 S

The patient is 71 inches tall, weighs 77 kg, and has an SCr of 0.8 mg/dL. He is given a diagnosis of uncomplicated
endocarditis. Which is the best antimicrobial regimen for this patient?

1. Vancomycin 1200 mg IV every 12 hours x 6 weeks

2. Nafcillin 2 g IV every 4 hours and gentamicin 75 mg IV every 8 hours x 6 weeks
3. Gentamicin 75 mg IV every 8 hours x 5 days and nafcillin 2 g IV every 4 hours x 2 weeks
4. Gentamicin 75 mg IV every 8 hours x 2 weeks, nafcillin 2 g IV every 4 hours x 6 weeks, and rifampin 300 mg PO
every 8 hours x 6 weeks
QUESTIONS

 Which serum concentration target is appropriate when using gentamicin in combination with penicillin G
for a patient with viridans streptococcal endocarditis?
1. Trough of 3–5 mcg/mL (SI 6.3–10.5 µmol/mL)
2. Trough of 15–20 mcg/mL (SI 31.4–41.8 µmol/mL)
3. Peak of 3–5 mcg/mL (SI 6.3–10.5 µmol/mL)
4. Peak of 8–12 mcg/mL (SI 16.7–25.1 µmol/mL)
REFERENCES

Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy,
and Management of Complications. Circulation. 2015 Oct 13;132(15):1435-86. doi: 10.1161