Infective endocarditis Learning objectives When you have completed this you should understand: 1. 2. 3. 4. 5. The diagnosis of infective endocarditis The role of investigations including echocardiography in infective endocarditis Organisms associated with infective endocarditis Rational antibiotic treatment of patients with infective endocarditis The significance of large vegetations A 70 year old man presented with microscopic haematuria and proteinuria and a fever five months after having a transurethral resection of the prostate (TURP). Initially urological review was arranged as the family doctor thought that a urinary infection was the most likely diagnosis. The patient was concerned that he was not getting better and he self-referred to a physician. He had continuing fever, weight loss, and malaise. The physician detected a mitral pan-systolic murmur that had not been heard before. On the basis of this finding infective endocarditis was suspected and investigations begun. His subsequent course and its management are discussed in an interactive case presentation. Case History 70 year old man presented with a three month history of malaise, lethargy, and 8 kg weight loss. Five months previously he had a transurethral resection of the prostate (TURP) for benign prostatic hypertrophy. The early postoperative period was complicated by retention of urine requiring reinsertion of a temporary catheter. On examination there was a pansystolic murmur consistent with mitral regurgitation. The apex beat was not displaced and no other cardiac abnormality was documented. The patient had a temperature of 37°C Table 1 Results of routine investigations Haematology Biochemistry Hb (g/dl) 11.3 Na (mmol/l) 130 WCC (x 109/l) 11.5 K (mmol/l) 4.9 Platelets (x 109l) 490 Urea (mmol/l) 5.9 MCV (fl) 83 Creatinine (mmol/l) 109 Hb, haemoglobin; MCV, mean cell volume; WCC, white cell count Liver function tests were also normal. Table 2 Inflammatory markers and urinalysis CRP (mg/l) 110 ESR (mm/1st hour) 85 Urinalysis Blood ++ MSU: no growth Protein ++ CRP, C reactive protein; ESR, erythrocyte sedimentation rate; MSU, midstream urine 2 “True or False” Questions Question 1: A. The patient probably has endocarditis and must be started on antibiotics while the results of blood cultures are awaited B. A white cell count of 11.5 x 109/l is unusually low for a patient with active infective endocarditis C. The most important investigation in the diagnosis of endocarditis is the blood culture D. Haematuria is an uncommon finding in endocarditis E. An elevated C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are required for the diagnosis of endocarditis Question 2: A. Enterococcus is very rarely the pathogen in patients with endocarditis B. Enterococci are part of the normal gut flora C. If the blood cultures had been positive for viridans streptococci this can almost always be considered diagnostic of endocarditis D. If a patient is clinically septic on presentation it is unlikely that they have endocarditis E. If endocarditis is suspected clinically but blood cultures remain negative after 48 hours then an alternative diagnosis should be sought Clinical data continued The patient's ECG on admission is shown in (fig 2). Figure 2 12 lead ECG on admission: sinus rhythm with left axis deviation The chest xray was normal. However, a transthoracic echocardiogram suggested that there may be a vegetation on the mitral valve, but this was not definite because the quality of the images were poor for technical reasons. 3 Question 3 (True or False): A. All patients with suspected endocarditis and a negative transthoracic echocardiogram (TTE) study should undergo a transoesophageal echocardiogram (TOE, or TEE in the USA) B. A normal TOE scan cannot rule out the diagnosis in a patient with clinically suspected endocarditis C. Once infective endocarditis has been diagnosed a TTE need be repeated only when clinically indicated D. Ideally all patients with fever should have an echocardiogram to rule out infective endocarditis E. The left axis deviation on the 12 lead ECG means that there is a significant risk of an aortic root abscess involving the conduction system Clinical data continued The patient was transferred to the care of the cardiology team and was started on intravenous amoxycillin. Question 4: A. Providing the patient responds appropriately after antibiotics are started he would be suitable for a two week course of antibiotics B. Vancomycin should be added to the amoxycillin as the organism is resistant to both gentamicin and streptomycin C. A cephalosporin such as cefotaxime is unlikely to be effective as an alternative to penicillin D. The patient should be anticoagulated to decrease the risk of embolic complications E. The risk of emboli drops significantly after the first week of treatment Question 5: A. The large vegetation is a very strong indication for emergency surgery to remove the vegetation and implant a new valve so as to avoid systemic embolisation and particularly stroke. B. Endocarditis caused by intravenous drug use is associated with a high mortality C. If haemodynamic deterioration occurs the surgical result is improved by one week of antibiotic treatment before surgery to prevent infection recurring at the operation site. D. Candida endocarditis can usually be cured with antibiotics, providing the valve damage is not too severe. E. Recurrence of fever is usually caused by a hospital acquired infection. Clinical data continued The provisional plan was to give the patient at least six weeks of high dose intravenous amoxycillin and review the need for surgery according to the patient's progress. It was decided not to operate solely because there was a large vegetation. The patient had twice weekly full blood count, ESR, CRP, U&E, liver function text, urine dipstick, repeat transthoracic echocardiograms, and ECGs. The patient made an uneventful recovery. Pre-discharge TOE revealed moderate residual mitral regurgitation and good left ventricular function. He has since been reviewed in out patients and is well with no symptoms and on no medication. 4 Final Questions (“True or False”): Infective endocarditis Question 1: In patients suspected of having endocarditis: 1A. Patients with valvar heart disease require antibiotic prophylaxis before having a transoesophageal echocardiogram. 1B. TOE will detect vegetations in approximately 90% of patients with proven endocarditis. 1C. According to the Duke criteria infective endocarditis can be excluded if no vegetations are seen on TOE and blood cultures are negative. 1D. According to the Duke criteria auscultation of a new murmur is a major criterion for the diagnosis of infective endocarditis. 1E. The Duke criteria recognise the importance of intravenous drug use Question 2: In the surgical management of endocarditis: 2A. Published data show that the mortality of infective endocartitis is decreased by surgery in patients with large (>10mm) vegetations. 2B. Patients in pulmonary oedema should have surgery delayed until the pulmonary oedema has been treated medically because of the high operative mortality 2C. Prosthetic valve endocarditis can often be treated successfully with aggressive antibiotic therapy 2D. Increasing prolongation of the PR interval strongly suggests an abscess in the interventricular septum and the need for urgent surgery. 2E. Patients with fungal endocarditis are rarely cured with antimicrobial agents and will normally require cardiac surgery Question 3: The microbiology of infective endocarditis: 3A. Prosthetic valve endocarditis is often caused by coagulase negative staphylococci 3B. Streptococcus bovis is an enterococcus and may be associated with an underlying colonic malignancy 3C. The proportion of cases of infective endocarditis caused by Staphylococcus aureus is increasing 3D. Infective endocarditis caused by bacteria from the HACEK group should be treated with intravenous amoxycillin 3E. Infective endocarditis caused by S aureus can be rapidly fatal, and is more dangerous in drug addicts than non-addicts Question 4: Antibiotic treatment of infective endocarditis: 4A. Once the blood cultures are taken then usually treatment should be begun with a combination of intravenous penicillin and vancomycin 4B. Staphylococcus can sometimes be effectively treated with benzyl penicillin and gentamicin 4C. It may be possible to treat uncomplicated endocarditis caused by viridans streptococci with two weeks of intravenous benzyl penicillin and gentamicin 4D. If a patient with enterococcal endocarditis is allergic to penicillin they should usually be treated with an intravenous cephalosporin 4E. Vancomycin can be substituted for penicillin and used in combination with gentamicin as first line "blind therapy" before the blood culture results are known Question 5: The use of gentamicin: 5A. Gentamicin is bactericidal 5B. Gentamicin is nephrotoxic and is contraindicated in patients with renal dysfunction 5C. Gentamicin can be given at a dose that is less than the full therapeutic dosage in combination with amoxycillin to produce a synergistic effect—for example, in the treatment of enterococcal infective endocarditis 5D. A gentamicin trough concentration of >5 mg/l is acceptable 5E. If gentamicin peak concentration is high and the trough concentration is satisfactory then the dose given should be reduced and the dosing interval kept the same