Download Updates to the Infective Endocarditis Diagnosis and

Megan Patch MS, PharmD, BCPS
Antimicrobial Stewardship Pharmacist
9/28/2016
Don’t Go Veggin’ my Heart:
Updates to the Infective Endocarditis Diagnosis and Treatment
Guidelines
Objectives
• Describe updated diagnosis criteria for infective endocarditis (IE)
• Discuss changes to treatment recommendations within the updated
guidelines
• Apply new treatment recommendations for IE from various
microbial sources
• Evaluate the role of the pharmacist in management of IE
Infective Endocarditis
• Annual incidence: 3-7/100,000 person-years
• Remained stable
• 4th most common life-threatening infectious process
• High morbidity and mortality
• Staphylococcus aureus is the most common causative organism
Baddour LM et al. Circulation 2015
Infective Endocarditis
• Shift in causative organism to S. aureus dominance
• Also increase in mean age of patient
• Higher portion of prosthetic valve IE
• Increase in other cardiac devices
• Decrease in rheumatic heart disease as cause
• Outcomes have not improved despite advances in care
• Product of increase in Staphylococcal origin
Baddour LM et al. Circulation 2015
2015 Update
American Heart Association - IDSA
Baddour LM et al. Circulation 2015
Duke Criteria
• Have been modified over the years
• Used to aid in determining
diagnosis
• Endocarditis is heterogenous and
these criteria should be paired
with a complete clinical workup for
a diagnosis
• Major and minor criteria
Baddour LM et al. Circulation 2015
Duke Criteria
Baddour LM et al. Circulation 2015
Diagnosis
• Early identification is key
• High risk patients who can benefit from surgery
• Reliable history of patient
• Risk factor profile
• Valve replacement
• Intravenous drug use (IVDU)
• Clinical picture
• Duke Criteria
Baddour LM et al. Circulation 2015
Diagnostic Testing
• At least 3 sets of cultures should be
obtained
• 1st and last drawn at least 1 hour apart
• Different venipuncture sites
• Commonly, only 2 sets of cultures will
be drawn
Imaging
• Transthoracic echocardiogram (TTE)
• Transesophageal echocardiogram (TEE)
http://www.bd.com/ds/productCenter/442192.asp
Baddour LM et al. Circulation 2015
Antibiotic Therapy - Goals
• Eradicate infection
• Sterilize vegetation
• Prevent sequelae
• Challenges of treatment
• High bacterial density
• Penetration into vegetation
• Slow rate of bacterial growth in biofilms
• Goal + Challenges = prolonged IV antibiotics
Baddour LM et al. Circulation 2015
Inoculum Effect
• High bacterial density at vegetation
• Higher minimum inhibitory concentration (MIC) at vegetation site
• Antimicrobials can be less effective with a high inoculum
• β-lactams (ceftriaxone) and glycopeptides (vancomycin)
• Require higher antimicrobial doses to overcome higher MIC
• More β-lactamase produced
• In large densities, some organisms can become resistant to
bactericidal effects of some antibiotics
• Resistant subpopulations with higher inoculum
Baddour LM et al. Circulation 2015
Antimicrobial Therapy
• Drug penetration
• Mechanical barrier to drug target
• Bactericidal drugs
• May need combination to achieve bactericidal activity
• β-lactam + aminoglycoside
• Duration of therapy
• 2-6 weeks
Baddour LM et al. Circulation 2015
Antimicrobial Therapy
• Pharmacokinetic and pharmacodynamic properties
• Penicillins and cephalosporins require free drug to exceed the MIC for
60-70% of the dosing interval for bactericidal action
• Less than 60% only achieves bacteriostatic effects
• When administering antibiotics to achieve synergy, administration
together or as close as possible can maximize synergistic effect
Baddour LM et al. Circulation 2015
Other Treatment Considerations
• Broad empiric therapy based on most likely organisms
• Complete and thorough history should be obtained
• Infectious Diseases consultation should be obtained when IE is
suspected
• Duration of treatment should start with the first negative culture
• Keep in mind some organisms involved in IE are hard to culture
• Two sets of blood cultures should be drawn every 24-48 hours while
still positive
• Native valve IE with prosthetic valve replacement, no consensus on
how to treat
Baddour LM et al. Circulation 2015
Treatment
Viridans Group Streptococcus
Streptococcus gallolyticus
Abiotrophia defectiva
Granulicatella species
NVE: Highly PCN-susceptible S. gallolyticus
Baddour LM et al. Circulation 2015
NVE: Relatively PCN-resistant S. gallolyticus and VGS
Baddour LM et al. Circulation 2015
NVE: Highly PCN-resistant S. gallolyticus and VGS
• Ampicillin 12g/day (2g every 4 hours)
-OR• Penicillin 18-30 million units/day divided or continuous infusion
-PLUS• Gentamicin 3 mg/kg/day in 2-3 divided doses
• Treatment is the same for Abiotrophia defectiva and Granulicatella
spp
Baddour LM et al. Circulation 2015
PVE: Penicillin-susceptible S. gallolyticus and VGS
Baddour LM et al. Circulation 2015
PVE: Penicillin-resistant S. gallolyticus and VGS
Baddour LM et al. Circulation 2015
Treatment
Streptococcus pneumoniae,
Streptococcus pyogenes,
and Groups B, C, F, and G
β-Hemolytic Streptococci
Highly PCN-susceptible Streptococcus pneumoniae
• Penicillin MIC < 0.1 µg/mL
• NVE
• 4 weeks of antibiotic therapy
• Penicillin, cefazolin, or ceftriaxone
• Vancomycin therapy recommended with β-lactam allergy
• PVE
• 6 weeks of antibiotic therapy
• Penicillin, cefazolin, or ceftriaxone
• Vancomycin therapy recommended with β-lactam allergy
Baddour LM et al. Circulation 2015
PCN-resistant Streptococcus pneumoniae
• Penicillin MIC > 0.1 µg/mL
• If no meningitis present
• High-dose penicillin or 3rd generation cephalosporin
• If meningitis present
• High-dose cefotaxime or ceftriaxone
Baddour LM et al. Circulation 2015
Other Streptococci
• Streptococcus pyogenes (group A Streptococci)
• Penicillin for 4-6 weeks
• Groups B, C, F, and G Streptococci
• Slightly more PCN resistance
• Penicillin
-OR• Ceftriaxone for 4-6 weeks
-PLUS• Gentamicin for at least 2 weeks
• Early cardiac surgical intervention
Baddour LM et al. Circulation 2015
Patient Case #1
• QR is a 46 year old male with a past history of gout, depression, and
hypertension. He presented to the ER with weakness and fatigue. He
was hospitalized 2 months prior with pneumonia.
• Blood cultures were positive 2/2 for Streptococcus pneumoniae.
• Vancomycin was initiated until sensitivity results are known. A TTE
and TEE were performed and showed a large vegetation on his mitral
valve. He has no history of endocarditis or valve replacement.
Culture results show highly susceptible penicillin sensitivity.
• What therapy should be used for QR?
Patient Case #1 continued
• What is the appropriate treatment duration for QR?
A. 2 weeks
B. 4 weeks
C. 6 weeks
D. 8 weeks
Patient Case #1 continued
• What is the appropriate treatment duration for QR?
A. 2 weeks
B. 4 weeks
C. 6 weeks
D. 8 weeks
Treatment
Staphylococci
History and Current State
• Staphylococcal species (specifically S. aureus) are the most common
cause of IE
• Previously, S. aureus was traditionally associated with NVE and
coagulase-negative Staphylococci (CoNS) was associated with PVE
• S. aureus becoming a larger cause of PVE
• Prevalence of CoNS NVE is increasing
• Increase in the incidence of S. aureus IE due to healthcare contact
• Treatment is complicated with increasing resistance
Baddour LM et al. Circulation 2015
Staphylococcus aureus IE
• Intravenous drug users (IVDU) • Non-intravenous drug users (non-IDUs)
• Mainly right-sided (tricuspid)
• Mainly left-sided (mitral/bicuspid valve)
http://www.heart.org/idc/groups/heartpublic/@wcm/@hcm/documents/image/~extract/UCM_451092~2~staticrendition/large.jpg
Coagulase-Negative Staphylococci (CoNS)
• Similar risk factors and outcomes as S. aureus IE
• High methicillin resistance rate
• These organisms are also resistant to cephalosporins and carbapenems
• Staphylococcus lugdunensis
• More virulent form of IE
Baddour LM et al. Circulation 2015
Staphylococcal IE in IDUs
• Gentamicin has previously been standard treatment for right-sided IE
in patients with NVE
• β-lactam + gentamicin for 2 weeks for uncomplicated IE
• Increasing risk of nephrotoxicity without added benefit
• Vancomycin + gentamicin (short-course) less effective
• Difficult to penetrate vegetation
• Slowly bactericidal
• Increased drug clearance in this patient population
• Longer duration of therapy with vancomycin treatment in MRSA IE is
warranted
Baddour LM et al. Circulation 2015
Staphylococcal IE in non-IDUs
• MSSA
• Treatment with nafcillin + gentamicin shortened duration of bacteremia by
roughly one day
• No effect on clinical outcomes
• Increase in nephrotoxicity with dual therapy
• MRSA
• Increased risk of nephrotoxicity when vancomycin + gentamicin are given
concomitantly
Baddour LM et al. Circulation 2015
NVE: Staphylococci
Baddour LM et al. Circulation 2015
PVE: Staphylococci
MSSA
MRSA
Baddour LM et al. Circulation 2015
Abscess with Staphylococcal IE
• Brain abscess with MSSA
• Nafcillin is preferred over cefazolin due to increased penetration at the blood
brain barrier
• If allergy prohibits nafcillin use, vancomycin should be substituted
• Septic pulmonary emboli
• Daptoymcin can be used for MRSA
Baddour LM et al. Circulation 2015
Oral Therapy for MSSA IE in IDU
• Two studies
•
•
•
•
•
Right-sided MSSA IE in IDU
Ciprofloxacin + rifampin
4 weeks treatment
Many patients HIV+
Cure rate >90%
• Increasing rates of resistance of MSSA to fluoroquinolones
• Effective absorption – must be taken correctly
Baddour LM et al. Circulation 2015
Treatment
Enterococcus
NVE and PVE: Enterococcus
Baddour LM et al. Circulation 2015
NVE and PVE: Enterococcus
Baddour LM et al. Circulation 2015
NVE and PVE: Resistant Enterococcus
Baddour LM et al. Circulation 2015
Linezolid
• Not FDA approved for treatment of IE (off-label use)
• Not often used
• Dosing 600 mg IV every 12 hours
• Bacteriostatic
• Problematic for patients with immunosuppression
• Side effects with long-term use
• Myelosuppression including thrombocytopenia
Baddour LM et al. Circulation 2015
Daptomycin
• Approved for treatment of right-sided IE
• Often used off label for left-sided endocarditis
• Dosing (with CrCl >30 mL/min)
• Package insert: 6 mg/kg daily
• Some experts: 8-10 mg/kg daily
• Other experts: 10-12 mg/kg daily
• Monitor weekly CPK
• May need to monitor more frequently with higher doses or concomitant statin
therapy
• Generic projected for Summer 2016 (hopefully by early 2017)
Smith JR, et al. Journal of Antimicrobial Chemo. 2015
Baddour LM et al. Circulation 2015
Daptoymcin/Beta-lactam Synergy
• Enterococcus species with daptomycin resistance are increasing
nationally
• The rate of daptomycin resistance for E. faecalis and E. faecium have
been measured around 0.5% and 4.7%, respectively
• Addition of ceftaroline, ertapenem, cefepime, ceftraixone, and
ampicillin have shown to provide synergy to daptomycin and decrease
time to blood clearance compared to monotherapy
• Ceftaroline has been shown to restore daptomycin susceptibility in nonsusceptible strains
Smith JR, et al. Journal of Antimicrobial Chemo. 2015
Patient Case #2
• MP is a 64 year old male who has been experiencing fever and chills
for the past 3.5 months. The patient has positive blood cultures for
Gram-positive cocci in pairs. The patient has a history of
hypertension, hyperlipidemia, chronic kidney disease (CrCl ~40
mL/min), and mitral valve replacement.
• What is the likely causative organism in this patient based on the
Gram-stain?
• What treatment should be recommended and how long should this
patient receive antibiotic therapy?
HACEK Organisms
• Haemophilius species
• Aggregatibacter species
• Cardiobacterium hominis
• Eikenella corrodens
• Kingella species
• Historically, all strains were susceptible to ampicillin
• Increased β-lactamase production
• Most all susceptible to ceftriaxone
• 4-6 weeks of treatment
Baddour LM et al. Circulation 2015
NVE or PVE: HACEK Organisms
Baddour LM et al. Circulation 2015
Culture-negative IE
• Failure to isolate an organism in IE patients can lead to problematic
treatment regimens
• Risk of not covering organism
• Risk of treating with extra agents
• Most studies estimate around 5-10% of IE is culture negative
• Study of 820 patients with confirmed IE showed around 20% of
patients were culture negative
• Fastidious organisms
• Fungi
• Low bacterial concentration in blood
• Antibiotics prior to blood cultures
Baddour LM et al. Circulation 2015
Patient Case #3
• MR is a 30 year old intravenous drug user with a history of
hypertension. She presents to the emergency department 1 day ago
with fatigue over the past 3 days, a fever of 102oF, and chills. The
patient was empirically started on vancomycin and
piperacillin/tazobactam.
• Blood cultures were positive for Gram-positive cocci in clusters still
awaiting sensitivities.
• How would you adjust antimicrobial therapy in this patient?
Pharmacist’s Role in Management of Endocarditis
• Follow culture and sensitivity results – communication with
microbiology lab
• Recommend appropriate antimicrobial therapy
• Provide pharmacokinetic services
• Vancomycin, aminoglycosides
• Optimize dosing of antibiotics
• Analyze overall medication regimen and screen for drug-drug
interactions
• Patient education of antibiotics
Self-assessment Question
• A patient with suspected endocarditis reveals blood cultures positive
for Streptococcus gallolyticus (S. bovis). Which additional testing is
recommended for this patient?
A.
B.
C.
D.
CT of the chest with contrast
MRI of the head
Colonoscopy
Endoscopy
Self-assessment Question
• A patient with suspected endocarditis reveals blood cultures positive
for Streptococcus gallolyticus (S. bovis). Which additional testing is
recommended for this patient?
A.
B.
C.
D.
CT of the chest with contrast
MRI of the head
Colonoscopy
Endoscopy
Megan Patch MS, PharmD, BCPS
Antimicrobial Stewardship Pharmacist
9/28/2016
Don’t Go Veggin’ my Heart:
Updates to the Infective Endocarditis Diagnosis and Treatment
Guidelines