Endocarditis

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Infective endocarditis

Epidemiology

- incidence difficult to determine but in UK probably 20/million/yr
- 20% mortality

Clinical features

- fever and heart murmurs are most common features but signs and symptoms can involve any organ system
- murmur may not be present in right sided endocarditis
- peripheral manifestations present in about 50% of cases
- embolic phenomena include mycotic aneurysms, retinal emboli, CVAs, petechiae although the latter may also be due to local vasculitis. Petechiae differ from those due to ¯ platelets in that they tend to occur on palms and soles rather than in dependent areas. Also tend to be larger and have irregular edges. Osler’s nodes: painful, tender, bluish-purple, nodular lesion on pads of fingers or toes. Janeway lesion (uncommon): painless, pink, non-tender macular lesion usually found on palms or soles.
- retinal haemorrhages and Roth’s spots (haemorrhages with pale centre).
- glomerulonephritis is usually due to circulating immune complexes
- the predominant underlying valvular process has shifted from rheumatic valvulitis to mitral valve prolapse and infection of prosthetic valves. The risk of endocarditis in patients with mitral valve prolapse is approximately 8 times that of control populations.

Incidence of clinical features in infective endocarditis

>75%	Fever, heart murmur
50-75%	Embolic phenomena, previous heart disease
25-50%	Chills, weakness, splenomegaly
< 25%	Weight loss, anorexia, arthralgia, back pain, glomerulonephritis, clubbing

Investigations

prevalence of staphylococcal endocarditis has increased substantially over the past 30 years and now accounts for approximately 30% of cases in the USA. Viridans and enterococcal streptococci account for slightly more than half.
- at least 3 sets of blood cultures should be taken in the first 24 hours at no less than hourly intervals. In patients who have received antibiotics in the previous 2 weeks at least 6 sets should be taken. At least 10 ml of blood should be taken for each innoculum as the bacteraemia associated with endocarditis tends to be low grade
- the presence of a bacteraemia in a patient with a prosthetic valve does not necessarily imply an associated endocarditis. Prosthetic valves are relatively resistant to infection with most gram negative bacilli. If there is an identifiable source for the bacteraemia and the bacteraemia clears promptly with antibiotics the patient can usually be treated for bacteraemia alone. However gram positive bacteraemia is more frequently associated with prosthetic valve infection
- polymicrobial endocarditis occurs most commonly in IV drug abusers. Detection of all organisms is essential for the selection of the appropriate antibiotics. If one of the organisms is a fastidious slow-growing organism positive blood cultures may be discarded before the fastidious organism can be isolated
- culture negative endocarditis is usually due to organisms that do not grow readily in blood cultures (eg Coxiella burnetti, Chlamydia spp, Mycoplasma spp, Legionella spp, Mycobacterium spp, Brucella spp, Histoplasma capsulatum, Candida spp and Aspergillus spp)
– endocarditis due to slow-growing fastidious gram negative bacilli of the HACEK group accounts for 5-10% of native valve endocarditis in patients who are not IV drug abusers. (HACEK = Haemophilus parainfluenzae, H. aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae). These organisms grow slowly in standard media and may require prolonged incubation. Bacteraemia caused by HACEK organisms in the absence of an obvious focus of infection is highly suggestive of endocarditis even in the absence of typical physical findings
- 2D echocardiography is the noninvasive technique of choice for defining vegetations. Transoesophageal echo is more sensitive than transthoracic ( >90%). It is also the method of choice for delineating periannular complications such as perivalvular abscess, septal abscess, prosthetic valve dehiscence
- ECG evidence of conduction defects often due to abscess or aneurysm formation

Laboratory findings

Abnormality	Prevalence
Positive blood cultures	90-98%
Positive serology	Variable
Normochromic, normocytic anaemia	50-80%
Elevated white cell count	75%
Elevated ESR	90%
Rheumatoid factor +ve	35-50%

Complications

Congestive heart failure

- due to incompetence of aortic and/or mitral valves
- most common cause of death
- aortic valve endocarditis more commonly associated with haemodynamic instability. This tends to progress rapidly and unpredictably. Early detection of aortic incompetence is important but difficult. LV is often not notably enlarged, stroke volume and pulse pressure are small and the diastolic murmur is usually soft and brief. Rapid regurgitation into a non-compliant LV results in a rapid rise in LVEDP and premature mitral valve closure; if mitral valve closure determined by echo occurs before the Q wave it implies that LVEDP is very high and surgical intervention is urgently required
- large mitral vegetations may cause mitral stenosis, low cardiac output and pulmonary oedema

Paravalvular infection and abscesses

- more common in aortic valve endocarditis
- usually associated with S. aureus and other virulent organisms
- clinical clues: fever despite appropriate antibiotics, new ECG conduction defects, purulent pericarditis
- most easily confirmed with TOE

Neurological

- CVA due to emboli or mycotic aneurysm rupture
- cerebral abscess
- toxic and psychiatric states
- meningoencephalitis
- cranial nerve lesions
- dyskinesia
- spinal cord involvement
- peripheral nerve involvement

Antibiotics

- bactericidal drugs should be used. In most infections, once bacterial replication is inhibited, phagocytic cells eradicate the causative organism. However in endocarditis the organisms are situated inside the vegetations which cannot be penetrated by phagocytes. Use of bacteriostatic agents is associated with a high incidence of relapse or failure to control the infection
- administration should be delayed until blood cultures have been taken. In acute endocarditis these should be taken over a 2-3 hour period
- prolonged courses are necessary. The density of organisms within the vegetations is very high and at these densities their metabolic and reproductive activity is reduced, thus reducing their susceptibility to bactericidal antibiotics. With rare exceptions courses of at least 4 weeks should be given. The exceptions are:

- endocarditis due to penicillin sensitive Strep viridans
- selected cases of right sided S. aureus endocarditis associated with IV drug abuse

These can be treated with a 2 week course of 2 antibiotics

Recommended antibiotic therapy for treatment of SBE

Condition	Antibiotics	Dose	Duration
Penicillin-susceptible Viridans strep or Strep bovis endocarditis	Penicillin G or Penicillin G and gentamicin or streptomycin	10-20 MU/day 10-20 MU/day 1 mg/kg 8 hrly 7.5 mg/kg 12 hrly	4 weeks } } 2 weeks }
As above but penicillin allergic patients	1st generation cephalosporin (eg cephazolin) or vancomycin	1 g 8 hrly 30 mg/kg/day	} 4 weeks }
Viridans strep or Strep bovis relatively resistant to penicillin	Penicillin G and gentamicin or streptomycin	20 MU/day 1 mg/kg 8 hrly 7.5 mg/kg 12 hrly	4 weeks } 2 weeks }
Enterococci or Viridans strep resistant to pencillin	Penicillin G and gentamicin or streptomycin or Ampicillin and gentamicin or streptomycin	20-30 MU/day 1 mg/kg 8 hrly 7.5 mg/kg 12 hrly 12 g/day 1 mg/kg 8 hrly 7.5 mg/kg 12 hrly	} } } 4-6 weeks } } }
As above but penicillin allergic patients	Vancomycin and gentamicin or streptomycin	30 mg/kg/day 1 mg/kg 8 hrly 7.5 mg/kg 12 hrly	} } 4-6 weeks }
Native valve, methicillin-sensitive Staph endocarditis	Cloxacillin or flucloxacillin ± gentamicin	1 mg/kg 8hrly	} 4-6 weeks 3-5 days
As above but penicillin allergic patients	1st generation cephalosporin (eg cephazolin) ± gentamicin or vancomycin	1-2 g 8 hrly 1 mg/kg 8hrly 30 mg/kg/day	4-6 weeks 3-5 days 4-6 weeks
Native valve, methicillin-resistant Staph endocarditis	Vancomycin*	30 mg/kg/day	4-6 weeks
Prosthetic valve, methicillin sensitive Staph endocarditis	Cloxacillin or flucloxacillin and rifampicin and gentamicin	300 mg PO 8 hrly 1 mg/kg 8 hrly	³ 6 weeks ³ 6 weeks ³ 2 weeks
Prosthetic valve, methicillin resistant Staph endocarditis	Vancomycin, rifampicin and gentamicin	30 mg/kg/day 300 mg PO 8 hrly 1 mg/kg 8 hrly	³ 6 weeks ³ 6 weeks ³ 2 weeks
HACEK organisms	Ceftriaxone (or other 3^rd generation cephalosporin)	2g od IV/IM	} 3-4 weeks }(native valve) }6 weeks }(prosthetic }valve)

* NB this regime has been associated with a high incidence of treatment failure (up to 38%). Unclear what regime should be given to patients who do not respond to vancomycin. Adding rifampicin &/or aminoglycoside may be of benefit. Other regimes that may work include: minocycline, cotrimoxazole or ciprofloxacin/rifampicin

Monitoring adequacy of therapy

Careful clinical observation is the most important method. NB Persistent or recurrent fever can also be due to a variety of other causes, including drug hypersensitivity or thrombophlebitis
Blood cultures should be obtained during treatment of staphylococcal endocarditis to ensure eradication of the organism. Additional cultures should also be performed once or twice per week for 8 weeks after completion of treatment

Prognosis

- depends on underlying valve disease, presence of decompensation, organism, speed of diagnosis and adequacy of treatment
- mortality ranges from 14% with no/mild heart failure, to 100% with severe heart failure when treated medically. 6% and 33% when treated surgically
- cure rates higher for native valve endocarditis with streptococci (75-90%) than with staphylococci (mortality as high as 30-40%)
- mortality higher with left sided endocarditis and in patients with prosthetic valve endocarditis

Prophylaxis against SBE

Indications

- should be given to all patients whose endocardium is damaged or rendered defective by acquired or congenital disease. Patients with mitral valve prolapse should be given antibiotics only when it is associated with a systolic murmur.

Antibiotics

UK recommedations

1. Dental procedures under GA

amoxycillin IM 1g in 2.5ml 1% lignocaine just before induction and 0.5g PO 6 hours later
OR amoxycillin 3g PO 4 hours before induction and a further 3g as soon as possible after operation
OR amoxycillin 3g with probenicid 1g PO 4 hours before operation.
patients who have prosthetic valves OR are allergic to penicillin OR have had penicillin more than once in the past month AND are to have a GA should be admitted to hospital. As should patients who have had a previous attack of endocarditis. Recommended regimes for these patients:
- amoxycillin 1g IV/IM plus gentamicin 120mg IM/IV just before induction and 0.5g amoxycillin PO 6 hours later
- for patients who are allergic to penicillin or who have had it more than once in the past month: vancomycin 1g over 1 hour (or teicoplanin 400mg IV) followed by gentamicin 120mg IV at induction or 15 min before surgical procedure; or clindamycin 300mg IVI over at least 10 min at induction followed by 150 mg IVI/PO 6h later

2. Surgery or instrumentation of upper respiratory tract
- as for dental procedures

3. GU surgery or instrumentation

patients with sterile urine: as for dental patients admitted to hospital
infected urine: also cover appropriate organisms

4. O&G procedures and GI procedures

only required for patients with prosthetic valves or who have had a previous attack of endocarditis. Regime as for dental patients who require admission but clindamycin not suitable.

Australian recommendations

Low risk patients (ie without prosthetic valve or previous endocarditis) undergoing dental procedures, oral or upper respiratory tract surgery.
- Not on long term penicillin: amoyxcillin 3g one hour prior to procedure
- On long term penicillin or penicillin hypersensitive: clindamycin 600 mg PO 1-2 h before procedure followed by 300 mg 6 h later OR vancomycin 1g IV over at least 1 h with the infusion finishing just before the procedure
- Under GA: Ampicillin or amoxycillin 1 g IV just before procedure (IM 30 mins before) plus 500 mg IV/IM/PO 6 h later
High risk patients (ie prosthetic valves, previous endocarditis) undergoing dental procedures, oral or upper respiratory tract surgery, GI or GU procedures.
- Ampicillin/amoxycillin as above plus gentamicin 1.5 mg/kg IV just before procedure or IM 30 mins earlier
- Penicillin hypersensitive: vancomycin followed by gentamicin as above
Special situations such as renal failure, specific known infections, prolonged labour: specialist consultation indicated

American recommendations

http://www.americanheart.org/Scientific/statements/1997/079701.html

Infective endocarditis

Epidemiology

Clinical features

Investigations

Laboratory findings

Complications

Congestive heart failure

Paravalvular infection and abscesses

Neurological

Antibiotics

Recommended antibiotic therapy for treatment of SBE

Monitoring adequacy of therapy

Prognosis

Prophylaxis against SBE

Indications

Antibiotics

UK recommedations

Australian recommendations

American recommendations

Further reading