Endocarditis

Lobna AL JuffaliDecember2013

Introduction

3-4 cases per 100,000 population per year

Platlet –fibrin complex becomes infected with microorganisms (vegetation)

Definition

Endocarditis is an inflammation of the endocardium, the membrane lining the chambers of the heart and covering the cusps of the heart valves.

Infective endocarditis (IE) refers to infection of the heart valves by microorganisms, primarily bacteria.

Pathogenisis

Pathogenesis

Risk factors

Presence of a prosthetic valve (highest risk) Previous endocarditis (highest risk) Complex cyanotic congenital heart disease (e.g.,

single ventricle states) Surgically constructed systemic pulmonary

shunts Acquired valvular dysfunction (e.g., rheumatic

heart disease) Hypertrophic cardiomyopathy Mitral valve prolapse with regurgitation IV drug abuse

Clinical Presentation

Symptoms fever, chills, weakness, dyspnea, night

sweats, weight loss, and/or malaise.Signs Fever heart murmur The patient may or may not have embolic

phenomenon, splenomegaly,

Clinical Presentation (skin manifestations)

Osler’s nodes

Clinical Presentation (skin manifestations)

Splinter hemorrhage

Laboratory Findings

The hallmark laboratory finding is continuous bacteremia; (+ve blood culture) three sets of blood cultures should be collected over

24 hours. Leukocytosis Anemia (normocytic, normochromic) ESR C-reactive protein altered urinary analysis

(proteinuria/microscopic hematuria

Duke criteria for the diagnosis of infective endocarditis and proposed

modifications Pathological criteria

– Microorganisms demonstrated by culture or histological in a vegetation

– Active endocarditis demonstrated by histological examination

Major criteria– Positive blood cultures– Evidence of endocardial involvement

Duke criteria for the diagnosis of infective endocarditis and proposed

modificationsMinor criteria predisposing heart disease fever >38°C vascular phenomena immunological phenomena microbiological evidence (no major

criterion) suspect echocardiography (no major

criterion

Duke criteria for the diagnosis of infective endocarditis and proposed

modifications CategoriesDefinite: Pathological criteria positive or 2 major criteria positive or 1 major and 2 minor criteria positive or 5 minor criteria positivePossible:All cases which cannot be classified as definite or rejected

1 major and 1 minor criterion positive 3 minor criteria positive

Rejected: Alternative diagnosis Resolution of the infection with antibiotic treatment for 4

days No histological evidence

Other diagnostic tests

An electrocardiogram, chest radiograph, echocardiogram (valvular vegetations)

Causitive microorganism Streptococci

Viridans Other streptococci

Staphylococci Coagulase positive Coagulase negative

Enterococci Gram-negative aerobic bacilli Fungi Miscellaneous bacteria Mixed infections “Culture negative”

60–80 30–40 15–25 20–35 10–27 1–3 5–18 1.5–13 2–4 <5 1–2 <5–24

%

DESIRED OUTCOME

Relieve the signs and symptoms of disease. Decrease morbidity and mortality associated with

infection. Eradicate the causative organism with minimal

drug exposure. Provide cost-effective antimicrobial therapy. Prevent IE in high-risk patients with appropriate

prophylactic antimicrobials.

Factors associated with increased mortality include the following:

Congestive heart failure Culture-negative endocarditis Endocarditis caused by resistant organisms such

as fungi and gram- negative bacteria Left-sided endocarditis caused by Staphylococcus

aureus Prosthetic valve endocarditis (PVE)

GENERAL PRINCIPLES

The most important approach to treatment of IE includes

isolation of the infecting pathogen determination of antimicrobial

susceptibilities followed by high-dose, bactericidal

antibiotics for an extended period.

Treatment usually is started in the hospital, but in selected patients, it may be completed in the outpatient setting.

GENERAL PRINCIPLES

Large doses of parenteral antimicrobials usually are necessary to achieve bactericidal concentrations within vegetations.

An extended duration of therapy is required, even for susceptible pathogens, because microorganisms are enclosed within valvular vegetations and fibrin deposits.

Nonpharmamcological Therapy

Surgery is an important adjunct to management of endocarditis in certain patients.

valvectomy and valve replacement The most important indications for

surgical intervention in the past have been

– heart failure in left-sided IE – persistent infections in right-sided IE.

Treatment

Duration wks

Recommeded Therapy

organism

mild, delayed allergy to penicillin

Immedate type hyppersensitivity reaction to peniciilin

42424

Penicillin GPenicillin G + gentamicinCeftriaxoneCeftriaxone +gentamicinVancomycin

Viridans streptococci (with penicillin MIC <0.12mcg/ml)

4 wk + 2Wk4 wk + 2Wk4

Penicillin G + gentamicinCeftriaxone +gentamicinVancomycin

Viridans streptococci (with penicillin MIC >0.12mcg/ml)

• In patients with endocarditis of prosthetic valves or other prosthetic material caused by viridans streptococci and Streptococcus bovis, treatment courses are extended to 6 weeks

Treatment

The following conditions should all be present to consider a 2-week treatment regimen

The isolate is penicillin sensitive. There are no cardiovascular risk factors. No evidence of thrombotic disease. Native valve infection. No vegetation greater than 5 mm

diameter. Clinical response is evident within 7 days.

Staphylococci endocarditis

Endocarditis caused by staphylococci is becoming more prevalent,mainly because of

– increased IVDA– more frequent use of peripheraland

central venous catheters– increased frequency of valve

replacement surgery. Staphylococcus aureus is the most common

organism causing IE among those with IVDA and persons with venous catheters.

Coagulase-negative staphylococci (usually S. epidermidis) are prominent causes of PVE

Is the organism methicillin resistant?

Should combinationtherapy be used?

Is the infection on a native or prosthetic valve?

Does the patient have a history of IVDA?

Is the infection on the left or right side of the heart?

Staphylococci endocarditis

TreatmentDuration wks

Recommeded Therapy

organism

6

6

6

Oxacillin or nafcillin+/- Gentamicin for 3-5daysPlus rifampin in prosthetic valves Cefazolin +/- Gentamicin for 3-5daysPlus rifampin in prosthetic valvesVancomycinPlus rifampin in prosthetic valves

Staphylococci- Methicillin sensitive

6 or more VancomycinPlus rifampin in prosthetic valves

Staphylococci- Methicillin resistant

2 Oxacillin or nafcillin + Gentamicin Right sided Endocarditis in IDUs

* In patients with endocarditis of prosthetic valves or other prosthetic material addition of aminoglycosides is must for the first two weeks

Duration wks

Recommeded Therapy

organism

4-6

6

Penicillin G or ampicillin +gentamicinVancomycin +gentamicin

Enterococci

6 Ampicillin/ Sulbactam or vancomycin +gentamicn

Enterococci – penicillin resistant

8 or more8 or more

LinezolidQuinupristin/dalfopristin

E.Faecium –penicillin,amioglycoside,and vancomycin resistant

8 or more8 or more

Imipenem/cliastatin+ampicillinCeftriaxone+ampicillin

E.Faecialispenicillin,amioglycoside,and vancomycin resistant

Treatment

HACEK Infective Endocarditis

Haemophilus spp. Actinobacillus actinomycetemcomitans Cardiobacterium hominis Eikenella corrodens Kingella kingae

Slow growing, fastidious Gram negatives likelycause of Culture Negative Endocarditis

Treatment

the treatment of HACEK infective endocarditis ceftriaxone ampicillin-sulbactam oral ciprofloxacin for selected patients Treatment is usually for 4 weeks, but it should be

extended to 6 weeks in PVE caused by one of these organisms.

Aminoglycosides and Endocarditis

Aminoglycosides are ototoxic and nephrotoxic

Want to limit therapy to as short a period of time as possible to avoid toxicity

– Staphylococci < 5 days – Enterococci will require 4-6 weeks

Aminoglycosides and Endocarditis

Control peak and trough concentrations

Elderly and/or renally impaired patients treated for extended periods of time are at greatest risk

Maintain gentamicin Cpmax 3-5 mg/L & Cpmin < 1 mg/L

Present data would not support SDD

Vancomycin

Trough serum vancomycin concentrations are the most accurate and practical method for monitoring efficacy.

just before the fourth dose trough level Above 15-20mg/dl Red neck syndrome Ototoxicity nephrotoxicity

EVALUATION OF THERAPEUTIC OUTCOMES

assessment of signs and symptoms Persistence of fever beyond 1 week may indicate

ineffective antimicrobial therapy, emboli, infections of intravascular catheters, or drug reactions.

In some patients, low-grade fever may persist

even with appropriate antimicrobial therapy.

EVALUATION OF THERAPEUTIC OUTCOMES

blood cultures should be negative within a few days, although microbiologic response to vancomycin may be unusually slower.

blood cultures should be rechecked until they are negative. During the remainder of the therapy, frequent blood culturing is not necessary.

EVALUATION OF THERAPEUTIC OUTCOMES

For all isolates from blood cultures, MIC should be determined.

When aminoglycosides are used for endocarditis caused by gram-positive cocci with a traditional three-times daily regimen, peak serum concentrations are recommended to be on the low side of the traditional ranges (3 to 4 mcg/mL for gentamicin).

Serum concentrations of the antimicrobial should generally exceed the MBC of the organism; however, in practice this principle is usually not helpful in monitoring patients with endocarditis.

Endocarditis prophylaxis

Conditions in which prophylaxis is necessary

Prosthetic cardiac valves Previous infective endocarditis Congenital heart disease (CHD) Unrepaired cyanotic CHD Completely repaired congenital heart defect with prosthetic

material or device, during the first 6 months after the procedure

Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device

Cardiac transplantation recipients who develop cardiac valvulopathy

Prophylaxis in Dental procedures

Endocarditis prophylaxis is recommended for all dental procedures that involve manipulation of the gingival tissue of the periapical region of teeth or perforation of the oral mucosa.

When antibiotic prophylaxis is appropriate, a single 2-g dose of amoxicillin for adult patients at risk, given 30 to 60 minutes before undergoing procedures associated with bacteremia.

Other procedures that require prophylaxis

Respiratory tract: Tonsillectomy and or adenoidectomy Surgical operations that involve an incision

or biopsy of the respiratory mucosa

Case

T.S. is a 48-year-old man who presents to the emergency department complaining of fever, chills, nausea/vomiting, anorexia, lymphangitis in his right hand, and lower back pain. He has no significant medical history except for kidney stones 4 years ago. He has no known drug allergies. He is homeless and an IV drug abuser (heroin) for the past year but quit 2 weeks ago. On physical examination, he is alert and oriented, with the following vital signs: temperature 100.8ºF (38ºC); heart rate 114 beats/minute; respiratory rate 12 breaths/minute; and blood pressure 127/78 mm Hg. He has a faint systolic ejection murmur, and his right hand is erythematous and swollen.

Case

His laboratory values were all within normal limits. He had an HIV test done a year ago, which was negative. One blood culture was obtained that later grew MSSA. Two more cultures were obtained that are now growing gram-positive cocci in clusters. A transesophageal echocardiogram shows vegetation on the mitral valve.

Case

Which one of the following therapeutic regimens is appropriate for T.S.?

A. nafcillin IV therapy—antibiotic duration: 2 weeks.

B. nafcillin IV plus rifampin therapy—antibiotic duration: ≥ 6 weeks.

C. nafcillin IV plus gentamicin IV therapy—antibiotic duration: 2 weeks of both antibiotics.

D. nafcillin IV plus gentamicin—antibiotic duration: 6 weeks (nafcillin) with first 3-5 days of gentamicin.