DPT III Exam 2 (escobar)

infective endocarditis

-an infection of the endocardial surface

-usually involves valves of the heart, but can occur on endocardium or intracardiac devices

endocardium

inner lining of heart chambers and valves

risk factors for infective endocarditis

-structural heart disease

-foreign bodies

-co-morbidities

-intravenous drug use

structural heart disease

-congenital heart disease

-mitral regurgitation (MR)

-heart failure

foreign bodies

-prosthetic valve

-pulmonary surgical shunts

-pacemakers or other mechanical devices

co-morbidities

-poor dental hygiene

-diabetes mellitus

-HIV

pathophysiology of infective endocarditis

bacterial injury

↓

bacterial adherence to damaged endothelium and microthrombi

↓

bacterial proliferation, neutrophil, and macrophage infiltration

↓

vegetation formation

acute clinical presentation of infective endocarditis

-sudden onset

-high fever

-systemic toxicities

-death within days if untreated

subacute clinical presentation of infective endocarditis

-slow, indolent infection

-often in patients with prior valvular disease

-non-specific symptoms

signs of infective endocarditis

roth spots

osler nodes

janeway lesions

roth spots

-hemorrhagic lesions of the retina with pale centers

-highly suggestive

osler nodes

-painful, tender purple-ish papules or nodules

-located on fingers and toes

-highly suggestive of subacute IE

janeway lesions

-painless purple or brown hemorrhagic lesions

-located on palms, soles, fingers, and/or toes

-highly suggestive of acute IE

labs found in infective endocarditis

prolonged bacteremia

leukocytosis

normocytic anemia

elevated ESR or CRP

proteinuria

hematuria

types of echocardiography

transthoracic (TTE) and transesophageal (TEE)

echocardiography

-should be performed in all patients with suspected IE

-TTE detection rate is ~50%

-TEE is more sensitive and specific

does a lack of vegetation on an ECHO exclude infective endocarditis?

no

definite infective endocarditis

any pathological criteria

-(+) vegetation or abscess

-(+) microorganism in vegetation

-pathological lesion

clinical critieria

-2 major

-1 major + 3 minor

-5 minor

possible infective endocarditis

clinical criteria

-1 major + 1 minor

-3 minor

rejected infective endocarditis

-resolution of IE syndrome < 4 days of antibiotics

-no pathological evidence at surgery with < 4 days of antibiotics

-firm alternative diagnosis

major criteria

2 positive blood cultures for typical IE organisms

-Viridans streptococci, S. gallolyticus, HACEK group, S. aureus, enterococcus)

-persistently positive blood cultures with microorganisms consistent with IE

ECHO positive for IE

vegetation, abscess, new partial dehiscence of prosthetic valve, new valvular regurgitation

minor criteria

predisposing heart condition of IVDU

fever (> 38ºC or >100.4ºF)

vascular phenomena

major arterial emboli, septic pulmonary infarcts, intracranial hemorrhage, Janeway lesions

immunologic phenomena

glomerulonephritis, Osler nodes, Roth spots, or rheumatoid factor

microbiologic evidence

positive blood culture that do not meet major criteria or serologic evidence of active infection consistent with IE

principles of infective endocarditis treatment

prolonged treatment

treatment is generally 4-6 weeks

parenteral

high doses of intravenous administration of antibiotics are typically required

bactericidial

-typically recommended to eliminate vegetations

-may require combination therapy for synergy

treatment considerations for infective endocarditis

location

-where is the vegetation? which valve is affected?

-native or prosthetic valve?

organism

-which pathogens should we be concerned about?

-acute vs Subacute

-history of IVDU?

treatment

-what is the susceptibility (MIC) of the organism?

-what are treatment options for resistant bugs?

patient-specific factors

does the patient have a penicillin allergy?

what is the patient's renal function?

treatment for methiciilin-susceptible native valve: staphylococci (s.aureus or CoNS) endocarditis

antibiotic

IV nafcillin or oxacillin

duration

6 weeks

comments

antibiotic

IV cefazolin

duration

6 weeks

comments

alternative for patients with non-anaphylatic PCN allergy

treatment for methiciilin-resistant native valve: staphylococci (s.aureus or CoNS) endocarditis

antibiotic

IV vancomycin

duration

6 weeks

comments

antibiotic

IV daptomycin

duration

6 weeks

comments

treatment for methiciilin-susceptible prosthetic valve: staphylococci (s.aureus or CoNS) endocarditis

*antibiotic*

IV nafcillin or oxacillin

PLUS

rifampin

PLUS IV gentamicin

*duration*

≥ 6 weeks

2 weeks (for gentamicin)

*comments*

cefazolin may be substituted for not-immediate type reactions to PCN

treatment for methiciilin-resistant prosthetic valve: staphylococci (s.aureus or CoNS) endocarditis

*antibiotic*

IV vancomycin

PLUS

rifampin

PLUS

IV gentamicin

*duration*

≥ 6 weeks

2 weeks (for gentamicin)

*comments*

rifampin = STRONG CYP3A4 inducer *check for drug interactions*

treatment for native/prosthetic valve: enterococci susceptible to aminoglycosides and PCN endocarditis

antibiotic

IV ampicillin or IV penicillin

PLUS

IV gentamicin

duration

4-6 weeks

comments

4 weeks if NVE and symptoms <3 months

or

6 weeks if NVE and symptoms >3 months or if PVE

antibiotic

IV ampicillin

PLUS

IV ceftriaxone

duration

6 weeks

comments

recommended for CrCl <50 mL/min or if renal dysfunction occurs with gentamicin-containing regimen

treatment for native/prosthetic valve: enterococci PCN susceptible but aminoglycoside resistant endocarditis

antibiotic

IV ampicillin

PLUS

IV ceftriaxone

duration

6 weeks

comments

antibiotics

IV ampicillin or IV penicillin

PLUS

IV streptomycin

duration

4-6 weeks

comments

4 weeks if NVE and symptoms <3 months

6 weeks if NVE and symptoms >3 months or if PVE

B-lactams synergy

2 different β-lactams may be used for synergy against a Gram-positive organism due to the different binding affinity for different penicillin-binding proteins

treatment for native/prosthetic valve: enterococci PCN resistant or allergy endocarditis

antibiotic

IV vancomycin

PLUS

IV gentamicin

duration

6 weeks

antibiotic

IV vancomycin or IV ampicillin-sulbactam

PLUS

IV gentamicin

duration

6 weeks

treatment for native/prosthetic valve: enterococci PCN, AG, and vancomycin resistant endocarditis

antibiotic

linezolid

duration

> 6 weeks

comments

may cause bone marrow suppression, neuropathy, and interacts with MAO-Is and SSRIs

antibiotic

daptomycin

duration

> 6 weeks

comments

-monitor CK

-may consider combination with ampicillin or ceftaroline in persistent bacteremia or if MIC is near breakpoint

out of the enterococci, which is more resistant: faecalis or faecium?

faceium

what are the fastidious, gram-negative bacilli that make up the HACEK group?

Haemophilus spp.

Aggregatibacter spp.

Cardiobacterium hominis

Eikenella corrodens

Kingella spp

true or false: bacteremia with organisms from the HACEK group is highly suggestive of infective endocarditis

true

treatment for native/prosthetic valve: HACEK endocarditis

antibiotic

ceftriaxone

duration

4-6 weeks

comments

preferred therapy

antibiotic

ampicillin

duration

4-6 weeks

comments

antibiotic

ciprofloxacin

duration

4-6 weeks

comments

fluoroquinolones are highly active in vitro but limited clinical data

true or false: 10% of patients with IE will not have an organism grow in their cultures

true

why may a culture negative IE occur?

-inadequate microbiological techniques

-infection with highly fastidious bacteria

-infection with non-bacterial pathogens

-antibiotics started before blood cultures obtained

treatment for culture negative IE

-consider prior infections, recent antibiotic use, clinical course, extracardiac sites of infection

-consult infectious disease specialists

what organisms account for the majority of fungal IEs?

Candida and Aspergillus spp.

regarding fungal IE, what organism is associated with culture negative PVE?

aspergillus

what is the inital drug of choice for fungal IE?

amphotericin B

duration of therapy for fungal IE

>6 weeks

what is often indicated in fungal IE?

surgery

what may be reasonable if someone develops a fungal IE?

lifelong suppresion with -azole antifungal

TDM for infective endocarditis

-repeat blood cultures usually become negative within 48-72 hours of starting treatment

-if not, repeat MIC and redraw cultures until negative

-repeat blood cultures 1-2x per week within 8 weeks after therapy is completed

AUC target level when treating IE with vancomycin

400-600 mg*h/L

trough target level when treating IE with vancomycin

10-20 mcg/mL

trough target level when treating IE with vancomycin (S. aureus treatment)

15-20 mcg/mL

if the MIC of vancomycin is ≥ 2mcg/mL, what should be considered?

alternative therapies

when are lower doses used with gentamicin?

for synergy (1 mg/kg Q8H)

target peak of gentamicin when treating IE

3-4 mcg/mL

target trough of gentamicin when treating IE

<1 mcg/mL

toxicities of beta-lactams

seizures

toxicities of aminoglycosides

ototoxicity and nephrotoxicity

toxicities of vancomycin

infusion related syndrome and nephrotoxicity

outpatient parenteral antimicrobial therapy (OPAT)

-due to the long treatment durations, patients may receive therapy outside of the hospital

-must consider drug stability, dosing frequency, equipment access, and insurance coverage

contraindications to outpatient parenteral antimicrobial therapy (OPAT)

-severe congestive heart failure

-cardiac arrhythmias

-persistent bacteremia or relapsing infections

-fulminant Staphylococcal infections

-lack of reliable IV access

-history of IVDA

indications for surgical intervention for IE

-moderate-severe HF symptoms

-left-sided IE caused by S. aureus, fungi, VRE, MDR GNB

-heart block

-perivalvular abscess

-valvular obstruction

-antimicrobial failure (bacteremia or fever >5 days)

-NVE with mobile vegetations >10 mm

-PVE and relapsed infection

-recurrent emboli and persistent or enlarging vegetations

IE prophylaxis

maintain adequate oral hygiene

what patients are at a high risk of IE and should receive a one-time antibiotic dose?

-prosthetic cardiac valves

-previous IE

-cardiac transplant with valve regurgitation

-unrepaired cyanotic congenital heart disease

oral options for IE prophylaxis

amoxicillin

if PCN allergy:

cephalexin

azithromycin

clarithromycin

parenteral options for IE prophylaxis

ampicillin

if PCN/ampicillin allergy:

cefazolin

ceftriaxone