1. Bloodstream Infections and Endocarditis
George Deepe, MD
Infectious Disease Division
University of Cincinnati College of Medicine
Cincinnati VA Medical Center

2. Outline Bacteremia Classification Treatment Endocarditis Diagnosis
Modified Duke’s criteria
Surgical Indications

3. Bacteremia classification
Continuous bacteremia
All cultures drawn are positive
Intravascular infections
Endocarditis, line infections, osteomyelitis
Intermittent bacteremia
Periods of bacteremia associated some cultures positive and some cultures negative
End-organ infections
Pneumonia, Pyelonephritis, cellulitis
Recurrent intermittent bacteria
Infected obstructed hollow organ with peristalsis
Pseudobacteremia

4. Bacteremia Management
Appropriate antibiotics with de-escalation as feasible
Adequate source control
Demonstration of clearance of bacteremia important
If not on antibiotics at time cultures report positive, repeat culture prior to administering antibiotics
Duration dependent on source, organism and host
Most infections duration decision not evidenced based
Staphylococcus aureus
Enterococcus
Pyelonephritis, Pneumococcal pneumonia

5. Staphylococcus aureus bacteremia Duration of therapy
Uncomplicated
Complicated
Rapid clearance of bacteria (negative cultures 2-4 days on effective therapy)
Defervescence with 72 hrs of effective antibiotics
No evidence of metastatic seeding
Removable source
At least 2 weeks of IV therapy
Non-removable deep-seated source of infection
Not meeting criteria for uncomplicated infection
Immunocompromised
4-6 weeks IV therapy depending on extent of infection

6. Staphylococcal bacteremia treatment options
MSSA
MRSA
Bacteriocidal agents
Cefazolin
Nafcillin/Oxacillin (CNS penetration)
Other β-lactams
All MRSA agents
Bacteriocidal agents
Vancomycin
Daptomycin
Ceftaroline
Telavancin
(Oritavancin/Dalbavancin)
Bacteriostatic
Clindamycin
Linezolid
Doxycycline

7. Question 1
48 yr male presents with a history of URI symptoms 2 weeks ago with fevers and severe myalgia. He was diagnosed as having Influenza H1N1 by his PCP. He now presents with fevers, cough, right sided chest pain and dyspnea. He is tachycardic, tachpneic, and has right sided crackles and on CXR has a RLL infiltrate. He is admitted and started on vancomycin, ceftriaxone and azithromycin. Blood cultures are reported with GPCs in clusters with mecA detected by molecular assay. The ceftriaxone is discontinued and vancomycin continued. He improves and is afebrile by 48 hrs

8. Question 1 Correct management at this stage would include:
Continue vancomycin for 4 weeks after negative blood cultures
Convert to oral vancomycin and discharge home to complete 14 days of vancomycin therapy
Complete 14 days of IV Vancomycin after negative blood cultures and unremarkable TTE
Convert to IV daptomycin for 14 days for ease of home administration
Complete 14 days of oral TMP-SMX once clinically stable

9. Question 1 continued
A) Continue vancomycin for 4 weeks after negative blood cultures B) Convert to oral vancomycin and discharge home to complete 14 days of vancomycin therapy C) Complete 14 days of IV Vancomycin after negative blood cultures and unremarkable TTE D) Convert to IV daptomycin for 14 days for ease of home administration E) Complete 14 days of oral TMP-SMX once clinically stable

10. Question 1 discussion
He has uncomplicated MRSA bacteremia with quick resolution of his bacteremia and clinical improvement. 2 weeks of IV therapy is appropriate. Oral therapy is not adequate.
He does not have complicated bacteremia warranting 4 weeks of treatment.
Vancomycin is not absorbed from the GI tract and oral vancomycin cannot be used for systemic infections
Daptomycin should not be used for pneumonia as it is inactivated by surfactant

11. Endocarditis Causes Temporal Native structure Prosthetic structure
Acute
Subacute
Causes
Bacterial
Gram positive
Gram negative
Fastidious (AACEK)
Fungi
Culture negative
Native structure
Valve
Congenital lesion
Prosthetic structure
Valve, Lead, Graft
Site of Infection
Right-sided
Left-sided

12. Etiology Organism Native Valve Prosthetic Valve PWID Community
Health-care assoc
Early
Late
Staphylococcus aureus 35 44 22 18 57
CNS 4 15 33 11
Streptococcus 32 8 31 12
Enterococcus 16 9
AACEK 3 6
GNR 5 13 7
Candida 1
Culture Negative

13. Microbiology talking points
Many organisms can cause endocarditis, relatively few account for the majority of disease
Staphylococcus aureus and Pneumococcus present as acute IE
Culture negative cases found in ~5% in all series
PWID may present with polymicrobial infections, Pseudomonas, Candida in addition Staph aureus

14. Diagnosis POSITIVE BLOOD CULTURES !!!!! Multiple positive cultures
Current automated culture systems support growth of fastidious gram negatives (AACEK) and Candida without modification
Moulds, Bartonella, Coxiella, Legionella require specialized media
Supportive history and physical findings
At-risk individual (predisposing conditions)

15. Clinical and laboratory manifestations
Feature
Frequency (%)
Fever, chills and sweats
80-90
Anorexia, weight loss
25-50
Myalgia, arthralgia
15-30
Back pain
7-15
Heart murmur
80-85
New/worsened regurgitant murmur
10-40
Embolic phenomena
20-50
Splenomegaly
15-50
Clubbing
10-20
Inflammatory phenomena
(Osler’s nodes, Janeway, Roth spots, splinters)
15-40
Neurological manifestations
20-40
Feature
Frequency (%)
Anemia
70-90
Leukocytosis
20-30
Microscopic hematuria
30-50
Elevated ESR
>90
Elevated CRP
Rheumatoid factor 50
Decreased Complement
5-40

16. Modified Duke Criteria
Major Criteria
Positive Blood cultures
- Typical organism on 2 cultures
SA, Strep viri, S. bovis, Enterococ, AACEK
- non Typical organism on 3 cultures or majority
of 5 cultures drawn at least 1 hour apart
- Single positive culture of Coxiella burnetti
Evidence of endocardial involvement
- Oscillating mass on valve, supporting
structure, implanted device
- abscess
- prosthetic valve dehiscence
Minor Criteria
Predisposition – predisposing heart condition or injection drug use
Fever > F (38.0 C)
Vascular Phenomena
arterial emboli, pulmonary infarcts, mycotic
aneurysm, stroke, conjunctival hemorrhage
Immunological Phenomena
Osler’s nodes, splinters, Roth spots, acute GN
Rheumatoid factor, hypocomplementemia
Microbiologic evidence
Positive blood cultures not meeting major
criteria
Serological
Definite Endocarditis Possible Endocarditis
Pathological evidence major and 1 minor
2 major criteria minor criteria
1 major and 3 minors
5 minor criteria

17. Atypical Microbiology
AACEK (HACEK) organisms
Culture Negative Endocarditis
Aggregatibacter (Haemophilus) aphyrophilus
Aggregatibacter (Actinobacillus) actinomycetecomitans
Cardiobacterium hominis
Eikenella corrodens
Kingella kingae
Preculture antibiotics
Fungi (Histo, Aspergillus, Candida)
Bartonella spp
Tropheryma whipplei
Legionella spp
Chlamydia psittaci
Coxiella burnetti
Abiotrophia spp, Gemella spp and Granicutella spp

18. Management Bacteriocidal agents necessary
High concentrations for good tissue penetration
Intravenous therapy
Prolonged course of therapy
PVE usually same agents but longer (exception Staph aureus)

19. Specific therapies Streptococci Dependent on level of resistance
Sensitive – PCN or ceftriaxone x 4 wks or PCN/Gent x 2 wks
Relative resistant – PCN/Ceftriaxone x 4 wks plus Gent x 2 wk
Mod resistance – PCN/Ceftriaxone x 6 wks plus Gent x 6 wks
Enterococcus
PCN (or Amp) plus Gent x 6 weeks
PCN (or Amp) plus Ceftriaxone x 6 weeks-This is typically employed when there is a lack of gentamicin or streptomycin synergy

20. Specific therapies Staphylococcus aureus MSSA
Cefazolin 2 gms q8 x 4-6 weeks
Nafcillin second-line agent
Vancomycin for β-lactam allergic patients
MRSA
Vancomycin x 4-6 weeks
Daptomycin x 4-6 weeks
PVE – β-lactam plus Gentamicin plus rifampin x 6-8 wks

21. AACEK treatment
Ceftriaxone x 4 weeks
Ampicillin x 4 weeks

22. Surgical Management of Endocarditis
Heart failure refractory to medical management
Resistant organisms with no bacteriocidal therapy
Coxiella, fungi, MDRs
Aortic root or valvular abscess, heart block
PVE with instability, relapse, resistant organisms
Persistent bacteremia at least 7 days into appropriate therapy
New embolic episodes on adequate therapy
Large vegetation

23. Question 2
46 yr male with history of IVDU, diabetes and chronic back pain presents with fevers and pleuritic chest pain. Exam reveals thin febrile tachypneic and tachycardic male. He has splinter hemorrhages, splenomegaly and bilateral crackles. Chest CT shows multiple lesions suggestive of septic emboli. He is started on vanc and cefepime but remains febrile. 3 sets of blood cultures are reported positive with budding yeast identified as C. albicans. He is started on micafungin. TTE shows a mobile 2 cm vegetation on his tricuspid valve. He develops blurred vision and fundoscopic exam reveals endophthalmitis.

24. Question 2
As an IVDU, he should remain on vancomycin for Staph aureus coverage
He should be referred for valve replacement with a bioprosthetic valve
He can be converted to fluconazole for completion of 6 weeks of therapy
If his cultures convert to negative, he is no longer at risk for embolic phenomena
His eye changes are likely retinopathy secondary to his diabetes

25. Question 2
As an IVDU, he should remain on vancomycin for Staph aureus coverage
He should be referred for valve replacement with a bioprosthetic valve
He can be converted to fluconazole for completion of 6 weeks of therapy
If his cultures convert to negative, he is no longer at risk for embolic phenomena
His eye changes are likely retinopathy secondary to his diabetes

26. Question 2 discussion
Fungal endocarditis is an indication for surgical referral
Definitive antimicrobial therapy should be targeted to organisms isolated
Fluconazole is a fungistatic agent and if deemed not a surgical candidate therapy should continue with micafungin which is cidal
Embolic risk is greatest with large vegetations and early in the course of treatment regardless of culture clearance
Fundscopic exam is required for all candidemic patients due to risk of endophthalmitis

27. Prevention of Endocarditis
Cardiac condition
Prosthetic cardiac material
Congenital heart conditions
unrepaired, incomplete repair, early post complete repair
Post transplant valvulopathy
Prior endocarditis
Procedures
Dental procedures causing bleeding
Respiratory tract procedures cutting through mucosa

28. Question 3
A 35 yr old female with known mitral valve prolapse with an late systolic murmur is undergoing a colonoscopy too rule out inflammatory bowel disease. Her GI physician sends her for evaluation for prophylactic antibiotics to prevent endocarditis. She has a known penicillin allergy with development of anaphylaxis.

29. Question 3 Which of the following is the appropriate recommendation.
She should be prescribed 600 mg of clindamycin to be given prior to her procedure
Her heart condition does not warrant prophylactic antibiotics
She can be given IV gentamycin to cover enteric organisms prior to her procedure
She should undergo an ECHO prior to her procedure
She can be given 2 gm cephalexin 1 hr prior to he procedure

30. Question 3
She should be prescribed 600 mg of clindamycin to be given prior to her procedure
Her heart condition does not warrant prophylactic antibiotics
She can be given IV gentamycin to cover enteric organisms prior to her procedure
D) She should undergo an ECHO prior to her procedure
E) She can be given 2 gm cephalexin 1 hr prior to he procedure

31. Question 3 discussion
The cardiac conditions requiring prophylactic antibiotics has been narrowed to only the highest risk lesions
Antibiotics are recommended for dental and certain respiratory procedures, no longer for GI or GU procedures
Agents appropriate to oral flora are appropriate
Cephalosporins should not be administered to PCN allergic patients with analphylaxis for cross reactivity concerns