2. CC: 2-3 months subjective fevers, chills, rigors, and
sweating.
62 yo WM c known CAD s/p CABGx5 June 2008 in
Tennessee . Prolonged hospitalization:
– Perforated duodenal ulcer with open repair, requiring
repeat laporotomy for recurrent bleeding
– TPN
– Sepsis (CNS) and fungemia (C. glabrata).
– C. diff
– Eventualy recovery and discharge to home via SNF and
VNS
3. August 2009 (~ 10 months later): fungemia and
native AoV endocarditis
– Decreased appetite,10 lbs unintentional wt loss,
and malaise over 2-3 months; cough 1 month ago
– Short course of azithromycin for cough, ineffective
for general malaise
– Several days of fever and cough in addition to
above
– Cultures obtained by PCP grew “yeast” ED,
where BCx subsequently grew 1/1 C. parapsilopsis
– Subsequent BCx 1/2 for C. para and 1/2 CNS
– Other cultures consistantly positive for C. para
5. – Initially started on Caspofungin and Vancomycin
– CNS actually differentiated into several strains and
Vanc was d/c’ed
– Caspofungin changed to Voriconazole due to lack
of clinical response
7. Follow-up s/p August 2009
hospitalization
• PICC line placed post-op
• Plan for 6 weeks Voriconazole 350 mg IV q12h
• Prior to d/c pt developed leukocytosis of 21
(while afebrile) additional 7 days of IV
vancomycin for empiric coverage of CNS
• TTE echo 3 weeks s/p d/c. No evidence of
significant valvular disease.
• At six weeks. All antibiotics stopped.
15. Empidemiology
• uncommon disease
• 1.3–6% of all cases of IE
• 1965-1995
– 2.22 male to female ratio
– 64% had >1 “valvular” risk factor
• previous valvular surgery, bacterial endocarditis, rheumatic heart
disease, nonrheumatic heart disease, or prolapsed mitral valve
– 135 (of 145 c prior valve surgery ) had replacement valves
(74 of which were with nonbiological)
– 18/145 presented >2 years s/p procedure
16. – In 257 pts where site of infx could be determined
• Aorta most common
• Ring abscess common: 25 of 55 patients classified as having FE of
AoV and another valve
CID 2001;32:50
17. • Previous valvular surgery
– 27/30 (90%) of prior AVR had FE confined to AoV
– Whereas 9/14 (64%) of prior MVR were found to
have FE on the same valve. 5/14 had AoV disease.
– Only 7/12 (58%) of other valve surgeries with
subsequent valve surgeries were had fungal
vegetations on corresponding valves.
23. Candida parapsilosis
• most common non-albicans
species
• Predominant fungal IE in
IVDU
• strains associated with
invasive disease more likely
to produce biofilm
structures
– Difficult to treat completely
– particularly it is a slow-
growing
– May explain late recurrence
24. Fungal Prosthetic Valve
Endocarditis (PVE)
• Cleveland Clinic Foundation
• Nov 1978 through Dec 1994, 184 patients
wereoperated on for PVE
• 12 cases of fungal PVE
Ann Thorac Surg 1995;60:538
30. Treatment – Per 2005
AHA/ACC/ISDA Guidelines
Circulation 2005;111:e394
31. Induction/infection control
• No randomized trials of various regimens
• Newer azoles
• Traditionally, amphotericin B +/- fluccytosine,
for synergy, has been cornerstone of tx.
32. One approach
Ampho B infused in d5w over 2 to 4 hours at
dose of 0.7 to 1.0/kg daily. (Larger doses for
Aspergillus).
After 1-2 weeks ampho surgery
Ampho – renal dysfunction
Flucytosine – bone marrow suppresion
33. Suppressive therapy
1. Baddour LM. Long-term suppressive therapy for fungal endocarditis. Clin Infect Dis
1996;23:1338–9.
2. Muehreke DD, Lytle BW, Cosgrove DM 3rd. Surgical and long-term antifungal therapy for
fungal prosthetic valve endocarditis. Ann Thorac Surg 1995;60:538–43.
3. Gilbert HM, Peters ED, Lang SJ, et al. Successful treatment of fungal prosthetic valve
endocarditis: case report and review. Clin Infect Dis 1996;22:348–54.
4. Penk A, Pittrow L. Role of fluconazole in the long-term suppressive therapy of fungal infections
in patients with artificial implants. Mycoses 1999;42(Suppl 2):91–6.
5. Melgar GR, Nasser RM, Gordon SM, et al. Fungal prosthetic valve endocarditis in 16 patients.
An 11-year experience in a tertiary care hospital. Medicine (Baltimore) 1997;76:94–103.
6. Nguyen MH, Nguyen ML, Yu VL, et al. Candida prosthetic valve endocarditis: prospective study
of six cases and review of the literature. Clin Infect Dis 1996;22:262–7
34. CCF Experience
• 11/12 pts – ampho B started pre-op
• 1/12 pt – post-op (dx made at surgery)
• “In general,operation was approached in an urgent
fashion as opposed toan emergent fashion.”
• average of 1.8 +/-0.7 g (range, 1 to 3 g) of
amphotericin B perioperatively
• 4 given flucytosine in additionto ampho B for
synergy against certain species of Candida
35. • 2/12 inpatient hospital deaths
• 5/10 fluconazole (200 to 400 mg/d)
• 3/10 ketoconazole(200 mg/d)
• 1/10 Itraconazole (220 mg/d)
• 1/10 allergic to itraconazole – no
suppressive tx
• 8/10 alive 51.5 +/- 61.0 months
postoperatively
• 4/8 recurrent fungal PVE
average of 25.75 +/- 14.7
months after the first
reoperation
• 3/4 pts with recurrence had self-
d/c’ed the oral suppressive
antifungal therapy 18, 36, and
40 months
37. Voriconazole cleared Candida from the
bloodstream as quickly as amphotericin B
(median 2 days) and showed a trend toward
better survival. Voriconazole was also
associated with fewer serious adverse events
and cases of renal toxicity, but a higher
incidence of visual disturbances.
Lancet 2005; 366: 1435–42
38. f/u
• Continuing IV voriconazole
• DIC – multiple tx of PRBC, platelets, cryo
• ARF
• Metabolic acidosis
• Awaiting surgery
Editor's Notes
Redo sternotomy, aortic root replacement with a #23 Medtronic Freestyle valve, Bentall procedure with direct reimplantation of the coronary arteries, bovine pericardial patch of subanular abscess involving the noncoronary anulus and mitral valve, irrigation and debridement with amphotericin B solution, redo sternotomy.
Non IVDU MRSA
Anecdotal case reports in nonaddicts with staphylococcal
endocarditis suggest that the use of gentamicin-nafcillin
therapy may be of benefit in patients who fail to respond to
monotherapy with nafcillin.
98 This issue was addressed in a
multicenter prospective trial comparing nafcillin alone for 6
weeks with nafcillin plus gentamicin (for the initial 2 weeks)
in the treatment of predominantly left-sided endocarditis
caused by S aureus.
99 Nafcillin-gentamicin therapy reduced
the duration of bacteremia by 1 day as compared with
nafcillin monotherapy. The combination therapy did not
reduce mortality or the frequency of cardiac complications,
however, but it did result in an increased frequency of
gentamicin-associated nephrotoxicity. Many authorities thus
recommend the use of combination therapy for the first 3 to
5 days of therapy for left-sided S aureus endocarditis,
especially in fulminant cases
The CoNS that cause prosthetic valve endocarditis usually are
oxacillin resistant, particularly when endocarditis develops
within 1 year after surgery.
79,122 Unless susceptibility to oxacillin
can be demonstrated conclusively, it should be assumed that the
organism is oxacillin resistant, and treatment should be planned
accordingly. Evidence from models of experimental endocarditis
caused by oxacillin-resistant staphylococci and limited clinical
experience in treating prosthetic valve endocarditis caused by
CoNS suggest that the optimal antibiotic therapy is vancomycin
combined with rifampin and gentamicin.
79,122 Vancomycin and
rifampin are administered for a minimum of 6 weeks, with the
use of gentamicin limited to the first 2 weeks of therapy
In comparison with streptococci, enterococci are relatively
resistant to penicillin, ampicillin, and vancomycin. Strepto-
cocci usually are killed by these antimicrobials alone,
whereas enterococci are inhibited but not killed. Killing of
susceptible strains of enterococci requires the synergistic
action of penicillin, ampicillin, or vancomycin in combina-
tion with either gentamicin or streptomycin
