61-Year-Old Woman With Knee Pain and Confusion

Abstract

A 61-year-old woman was admitted to the hospital in August 2004 from an urgent care center, where she had presented with acute-onset confusion and bilateral knee pain. Four days before admission, she had been examined by a physician for evaluation of frontal sinus headaches, and a viral syndrome had been diagnosed. Her medical history, including drug allergies, was unremarkable. On physical examination at hospital admission, the patient was delirious and febrile (temperature, 39.3°C). Her pulse rate was 90/min, blood pressure was 130/70 mm Hg, and a newly appreciated grade 2/6 apical pansystolic cardiac murmur was noted. The patient's knee joints were warm and painful, with small bilateral effusions (more extensive on the right than on the left). A homonymous left-sided visual field deficit was present, and she displayed fluent aphasic speech errors. No other neurologic signs were evident, and the rest of the physical examination findings were unremarkable. Initial laboratory studies revealed thrombocytopenia (platelet count, 87 × 109/L), hyponatremia (sodium level, 125 mEq/L), hypokalemia (potassium concentration, 2.9 mEq/L), microscopic hematuria, and proteinuria. The leukocyte count was normal (9.4 × 109/L). 1.At this point, which one of the following is the most likely explanation for this patient's symptoms? a.Transient ischemic attack or strokeb.Urinary tract infection and sepsis (ie, urosepsis)c.Encephalitisd.Connective tissue disease (CTD)e.Infective endocarditis (IE) The multisystem presentation in this patient suggests a systemic illness. Although a focal neurologic lesion can occur secondary to systemic processes, it is unlikely that the converse is true, making transient ischemic attack or stroke an unlikely diagnosis. When left untreated, urinary tract infections may progress to bacteremia and sepsis.1Marco CA Schoenfeld CN Hansen KN Hexter DA Stearns DA Kelen GD Fever in geriatric emergency patients: clinical features associated with serious illness.Ann Emerg Med. 1995; 26: 18-24Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar However, bacteremia and sepsis alone are an unlikely explanation for the concurrent symptoms of focal neurologic deficits, acute arthralgias with joint effusions, and a new cardiac murmur. The geographic (midwestern United States) and seasonal (summer) factors in this case make arbovirus infections (eg, West Nile virus, eastern and western equine encephalomyelitis) and encephalitis more probable. Nevertheless, the patient's localized joint symptoms and new cardiac murmur are inconsistent with this diagnosis. Although fever, altered mental status, and rheumatologic symptoms could be consistent with 1 of the 5 major CTDs, the patient's age, the sudden onset of her symptoms, and the nature of her combined neurologic and cardiac findings make CTD less likely. Infective endocarditis must be considered in any potentially bacteremic patient with a new heart murmur. The presence of localized joint pain with effusions and focal neurologic deficits implicates both a systemic and an embolic disease. Bacterial endocarditis is the most plausible diagnosis broad enough to account for this patient's infectious, cardiovascular, rheumatologic, and neurologic symptoms. Computed tomography of the head showed multiple cerebral infarctions, and confirmatory magnetic resonance imaging (MRI) revealed both acute and subacute cortical and subcortical right-sided embolic infarcts. 2.Which one of the following investigations would be least helpful in the further evaluation of this patient? a.Arthrocentesisb.Blood and urine culturesc.Lumbar punctured.Echocardiographye.Cardiac nuclear MRI (CMR) Septic joints are not always erythematous, and delayed treatment is the best predictor of an unfavorable outcome.2Pinals RS Polyarthritis and fever.N Engl J Med. 1994; 330: 769-774Crossref PubMed Scopus (72) Google Scholar This patient requires prompt arthrocentesis to minimize joint damage or destruction and to provide additional microbiological data. Because urinary tract infections and bacteremia with sepsis are 2 of the 3 most common diagnoses among older adults with fever, blood and urine cultures must be obtained.1Marco CA Schoenfeld CN Hansen KN Hexter DA Stearns DA Kelen GD Fever in geriatric emergency patients: clinical features associated with serious illness.Ann Emerg Med. 1995; 26: 18-24Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Nonhospitalized patients with new-onset delirium in the presence of fever and headache urgently need lumbar puncture to rule out community-acquired meningitis. The presence of acute and subacute cortical and subcortical embolic infarcts in this patient directly implicates a cardioembolic source of disease.3Flemming KD Brown Jr, RD Cerebral infarction and transient ischemic attacks: efficient evaluation is essential to beneficial intervention.Postgrad Med. May 15, 2000; 107 (72-74, 79-80.): 55-62Crossref PubMed Scopus (5) Google Scholar Both the American College of Cardiology/American Heart Association practice guidelines on echocardiography and the American Heart Association scientific statement on IE acknowledge that echocardiography should be performed in all suspected cases.4Cheitlin MD Armstrong WF Aurigemma GP et al.ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography).J Am Coll Cardiol. 2003; 42: 954-970Abstract Full Text Full Text PDF PubMed Scopus (432) Google Scholar, 5Baddour LM Wilson WR Bayer AS et al.Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professsionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association.Circulation. 2005; 111: e394-e433Crossref PubMed Google Scholar Echocardiographic evidence of endocardial involvement, as defined in the modified Duke criteria guidelines, is a major criterion in the diagnosis of endocarditis and directly defines patient management.5Baddour LM Wilson WR Bayer AS et al.Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professsionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association.Circulation. 2005; 111: e394-e433Crossref PubMed Google Scholar Currently, CMR has no major role in the assessment of cardiac manifestations of IE. Although advances in the spatial resolution of CMR may enhance the technique's future usefulness, its limited ability to assess dynamic physiology adequately makes CMR the least helpful investigation in this scenario.6Sachdev M Peterson GE Jollis JG Imaging techniques for diagnosis of infective endocarditis.Cardiol Clin. 2003; 21: 185-195Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Lumbar puncture yielded an opening pressure of 200 cm H2O, a protein value of 138 mg/dL, and a cerebrospinal fluid (CSF) glucose level of 28 mg/dL (serum glucose, 141 mg/dL). Within 12 to 16 hours, Janeway lesions and subconjunctival hemorrhages developed. Cultures of blood, CSF, and right knee synovial fluid specimens all grew methicillin-sensitive Staphylococcus aureus (MSSA). Transesophageal echocardiography revealed moderate mitral regurgitation with 3 mobile mitral valve vegetations; the largest was 11 × 11 mm and was attached to the posterior mitral leaflet. 3.Which one of the following is the most appropriate antibacterial regimen for this patient? a.Vancomycin hydrochloride for 4 to 6 weeksb.Nafcillin sodium or oxacillin sodium for 8 weeks with gentamicin sulfate for the first 3 to 5 daysc.Nafcillin sodium or oxacillin sodium plus rifampin for 4 to 6 weeks with gentamicin sulfate for the first 3 to 5 daysd.Nafcillin sodium or oxacillin sodium with gentamicin sulfate for 2 weekse.Nafcillin sodium or oxacillin sodium plus rifampin for at least 6 weeks with gentamicin sulfate for 2 weeks By satisfying 2 of the major modified Duke criteria for the diagnosis of IE—S aureus-positive blood cultures and echocardiographic evidence of an oscillating mass on the mitral valve—this patient's condition can now definitely be diagnosed as IE.5Baddour LM Wilson WR Bayer AS et al.Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professsionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association.Circulation. 2005; 111: e394-e433Crossref PubMed Google Scholar Although no prospective randomized, controlled trials assessing the efficacy of treatment regimens for IE exist, the American Heart Association has generated consensus recommendations based on expert opinion and current clinical and experimental data. Vancomycin for 4 to 6 weeks is recommended only for the treatment of native valve methicillin-resistant staphylococcal endocarditis5Baddour LM Wilson WR Bayer AS et al.Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professsionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association.Circulation. 2005; 111: e394-e433Crossref PubMed Google Scholar or for the treatment of native valve MSSA infections in penicillin-allergic patients. Neither indication applies to this patient. Four to 6 weeks of intravenously administered synthetic penicillinase-resistant penicillin with the optional concurrent use of an aminoglycoside for the first 3 to 5 days is the currently recognized standard of care for patients with MSSA endocarditis.5Baddour LM Wilson WR Bayer AS et al.Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professsionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association.Circulation. 2005; 111: e394-e433Crossref PubMed Google Scholar Eight weeks of therapy exceeds the accepted standard. In addition to native valve MSSA endocarditis, this patient has meningitis and septic arthritis. Rifampin is strongly active against S aureus and has excellent penetration into many bodily fluids, especially the CSF. Rifampin combined with a semisynthetic penicillin is also associated with improved clinical outcomes in the treatment of S aureus meningitis.7Gordon JJ Harter DH Phair JP Meningitis due to Staphylococcus aureus.Am J Med. 1985; 78: 965-970Abstract Full Text PDF PubMed Scopus (50) Google Scholar Therefore, the addition of rifampin to the recommended 4- to 6-week course of nafcillin or oxacillin with gentamicin for the first 3 to 5 days is the most appropriate treatment regimen for this patient. Two weeks of therapy with nafcillin or oxacillin plus an aminoglycoside is used only for intravenous drug abusers with MSSA endocarditis limited to the right heart valves. A 6-week course of nafcillin or oxacillin and rifampin with 2 weeks of gentamicin is the consensus recommendation for prosthetic valve MSSA endocarditis,5Baddour LM Wilson WR Bayer AS et al.Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professsionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association.Circulation. 2005; 111: e394-e433Crossref PubMed Google Scholar not for the left-sided native valve disease seen in this patient. The patient's initial broad-spectrum intravenous antimicrobial therapy was changed to nafcillin and rifampin for 6 weeks with gentamicin for the first 5 days. On hospital day 4, despite prophylaxis with graduated compression stockings and intermittent pneumatic compression, deep venous thrombosis (DVT) developed in the peroneal veins of her right upper and mid calf. 4.In this complex clinical situation, which one of the following is most reasonable for management of this patient's venous thrombosis? a.Subcutaneously administered low-molecular-weight heparin (LMWH) or intravenously administered unfractionated heparin for at least 5 days with vitamin K antagonism for 3 monthsb.Subcutaneous LMWH or intravenous unfractionated heparin for at least 5 days with vitamin K antagonism for at least 6 to 12 monthsc.Vena caval interruption with placement of an inferior vena caval filterd.Subcutaneous LMWH or intravenous unfractionated heparin with strict bed rest for at least 5 dayse.Subcutaneous LMWH or unfractionated heparin prophylaxis with concurrent use of graduated compression stockings and intermittent pneumatic compression and follow-up ultrasonography to rule out proximal extension Left-sided S aureus endocarditis is associated with a high prevalence of embolic episodes and increased risk of hemorrhagic transformation of ischemic infarcts and arterial rupture.8Tornos P Almirante B Mirabet S Permanyer G Pahissa A Soler-Soler J Infective endocarditis due to Staphylococcus aureus: deleterious effect of anticoagulant therapy.Arch Intern Med. 1999; 159: 473-475Crossref PubMed Scopus (175) Google Scholar Standard treatment of a first episode of DVT secondary to a reversible risk factor is at least 5 days of initial treatment with subcutaneous LMWH or unfractionated heparin and long-term treatment (3 months) with vitamin K antagonism.9Buller HR Agnelli G Hull RD Hyers TM Prins MH Raskob GE Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 401S-428SCrossref PubMed Scopus (1309) Google Scholar Given this patient's multiple acute and subacute cortical and subcortical embolic infarcts and the grave risk of further central nervous system insult, full therapeutic anticoagulation would not be reasonable at this point.8Tornos P Almirante B Mirabet S Permanyer G Pahissa A Soler-Soler J Infective endocarditis due to Staphylococcus aureus: deleterious effect of anticoagulant therapy.Arch Intern Med. 1999; 159: 473-475Crossref PubMed Scopus (175) Google Scholar The use of vitamin K antagonism for at least 6 to 12 months with possible extension to indefinite therapy is recommended for patients with a first idiopathic DVT9Buller HR Agnelli G Hull RD Hyers TM Prins MH Raskob GE Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 401S-428SCrossref PubMed Scopus (1309) Google Scholar but is inappropriate for this patient. An inferior vena caval filter can be placed when anticoagulation is contraindicated but only for proximal vein thromboses.9Buller HR Agnelli G Hull RD Hyers TM Prins MH Raskob GE Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 401S-428SCrossref PubMed Scopus (1309) Google Scholar Strict bed rest in combination with initial anticoagulation is no longer recommended. Early ambulation and leg compression produce much faster resolution of pain and swelling without increasing the incidence of pulmonary embolism.9Buller HR Agnelli G Hull RD Hyers TM Prins MH Raskob GE Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 401S-428SCrossref PubMed Scopus (1309) Google Scholar Given our patient's comorbidities, the most reasonable clinical decision is prevention of subsequent DVT development with prophylactic subcutaneous LMWH or unfractionated heparin, concurrent use of graduated compression stockings, and follow-up ultrasonography to rule out proximal extension.10Geerts WH Pineo GF Heit JA et al.Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 338S-400SCrossref PubMed Scopus (2824) Google Scholar Prophylactic administration of heparin does not increase the risk of cerebral hemorrhage in such patients.10Geerts WH Pineo GF Heit JA et al.Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 338S-400SCrossref PubMed Scopus (2824) Google Scholar, 11Alikhan R Cohen AT A safety analysis of thromboprophylaxis in acute medical illness [letter].Thromb Haemost. 2003; 89: 590-591PubMed Google Scholar Repeated brain MRI revealed organization of the acute infarcts into cerebral abscesses. Serial transesophageal echocardiography was performed to monitor vegetation size and mitral regurgitation. 5.Which one of the following would represent an immediate indication for cardiac surgery in this patient? a.Development of moderate or severe (New York Heart Association class III or IV) heart failure due to valvular dysfunctionb.Hemorrhagic conversion of a cerebral infarctc.Persistent fever despite 7 days of appropriate antibiotic therapyd.Persistence of a mobile 10-mm or larger valvular vegetatione.Development of new-onset atrioventricular conduction disturbances Moderate or severe heart failure secondary to valvular dysfunction is the most common and best-validated indication for surgery in patients with IE.12Olaison L Pettersson G Current best practices and guidelines: indications for surgical interventions in infective endocarditis.Infect Dis Clin North Am. 2002; 16: 453-475Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar Those with a recent hemorrhagic infarction are at high risk of intracranial bleeding during cardiopulmonary bypass. Current recommendations encourage a 2- to 3-week interval between the neurologic event and a cardiac operation.12Olaison L Pettersson G Current best practices and guidelines: indications for surgical interventions in infective endocarditis.Infect Dis Clin North Am. 2002; 16: 453-475Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar Failure of antibiotic therapy is defined as persistent bacteremia in the absence of an extracardiac source despite at least 7 days of appropriate antibiotic therapy. Persistent bacteremia implies intracardiac suppurative disease requiring surgical intervention. Fever during the first week of treatment is not synonymous with persistent bacteremia and is noncardiac related in more than 40% of cases.12Olaison L Pettersson G Current best practices and guidelines: indications for surgical interventions in infective endocarditis.Infect Dis Clin North Am. 2002; 16: 453-475Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar Mobile valvular vegetations that are 10 mm or larger are associated with a higher incidence of embolization. Nevertheless, surgery is not recommended solely to prevent embolization but is limited to situations in which 2 or more embolic events have occurred during therapy.12Olaison L Pettersson G Current best practices and guidelines: indications for surgical interventions in infective endocarditis.Infect Dis Clin North Am. 2002; 16: 453-475Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar New-onset atrioventricular block has a 77% positive predictive value for the presence of a perivalvular abscess but has a sensitivity of only 42%.12Olaison L Pettersson G Current best practices and guidelines: indications for surgical interventions in infective endocarditis.Infect Dis Clin North Am. 2002; 16: 453-475Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar Despite the fact that emergent surgical intervention limits further cardiac compromise and subsequent perioperative risk in most patients, this indication alone is diagnostically limited and fails to present the same level of clinical urgency as moderate or severe heart failure. The severity of the patient's mitral regurgitation remained moderate without evidence of ongoing leaflet destruction or perforation. After she completed 6 weeks of antimicrobial therapy, the vegetations resolved completely, and she regained baseline cognitive function. Less than 12 months after diagnosis, the patient returned to full-time employment. Initially described by William Osler in 1885,12Olaison L Pettersson G Current best practices and guidelines: indications for surgical interventions in infective endocarditis.Infect Dis Clin North Am. 2002; 16: 453-475Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar the clinical syndrome of IE was predominantly diagnosed in patients younger than 60 years with a history of rheumatic heart disease. During the past 60 years, however, the proportion of IE cases occurring in persons aged 60 years and older has progressively increased from less than 10% of the total cases reported in 1940 to more than 50% of currently documented cases.13Terpenning MS Buggy BP Kauffman CA Infective endocarditis: clinical features in young and elderly patients.Am J Med. 1987; 83: 626-634Abstract Full Text PDF PubMed Scopus (178) Google Scholar S aureus is now the most common cause of IE in industrialized nations, and the overall incidence of IE continues to increase, with 15,000 to 20,000 new cases in the United States each year. More importantly, IE represents the fourth-leading cause of life-threatening infectious disease syndromes, behind urosepsis, pneumonia, and intra-abdominal sepsis.14Tak T Reed KD Haselby RC McCauley Jr, CS Shukla SK An update on the epidemiology, pathogenesis and management of infective endocarditis with emphasis on Staphylococcus aureus.WMJ. 2002; 101: 24-33PubMed Google Scholar The primary factors responsible for these epidemiological and pathogenic changes include longer life spans in industrialized nations, increased incidence of nosocomial infections with organisms associated with IE, increased applications of cardiac surgery, increased use of indwelling intravascular lines and implantable devices, and increased application of standardized clinical and echocardiographic criteria for diagnosis.15Crawford MH Durack DT Clinical presentation of infective endocarditis.Cardiol Clin. 2003; 21: 159-166Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Consequently, the clinical manifestations of this heterogeneous disease have likewise changed, reflecting its varied forms of presentation. Particularly in elderly persons, symptoms are subtler and less revealing, making the diagnosis of IE especially challenging. Fever remains the single most common presenting symptom, regardless of patient age. Numerous studies have observed that in approximately 95% of all confirmed IE cases, patients presented with a temperature higher than 38.0°C.13Terpenning MS Buggy BP Kauffman CA Infective endocarditis: clinical features in young and elderly patients.Am J Med. 1987; 83: 626-634Abstract Full Text PDF PubMed Scopus (178) Google Scholar, 16Di Salvo G Thuny F Rosenberg V et al.Endocarditis in the elderly: clinical, echocardiographic, and prognostic features.Eur Heart J. 2003; 24: 1576-1583Crossref PubMed Scopus (125) Google Scholar, 17Robbins N DeMaria A Miller MH Infective endocarditis in the elderly.South Med J. 1980; 73: 1335-1338Crossref PubMed Scopus (30) Google Scholar, 18Roder BL Wandall DA Frimodt-Moller N Espersen F Skinhoj P Rosdahl VT Clinical features of Staphylococcus aureus endocarditis: a 10-year experience in Denmark.Arch Intern Med. 1999; 159: 462-469Crossref PubMed Scopus (151) Google Scholar, 19Watanakunakorn C Staphylococcus aureus endocarditis at a community teaching hospital, 1980 to 1991: an analysis of 106 cases.Arch Intern Med. 1994; 154: 2330-2335Crossref PubMed Google Scholar Nevertheless, patients with IE who are older than 60 years exhibit a more attenuated febrile response than their younger counterparts.20Gregoratos G Infective endocarditis in the elderly: diagnosis and management.Am J Geriatr Cardiol. 2003; 12: 183-189Crossref PubMed Scopus (27) Google Scholar A new or changing murmur, evident in 50% to 86% of newly diagnosed cases of IE, is the next most common finding at presentation.13Terpenning MS Buggy BP Kauffman CA Infective endocarditis: clinical features in young and elderly patients.Am J Med. 1987; 83: 626-634Abstract Full Text PDF PubMed Scopus (178) Google Scholar, 15Crawford MH Durack DT Clinical presentation of infective endocarditis.Cardiol Clin. 2003; 21: 159-166Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 16Di Salvo G Thuny F Rosenberg V et al.Endocarditis in the elderly: clinical, echocardiographic, and prognostic features.Eur Heart J. 2003; 24: 1576-1583Crossref PubMed Scopus (125) Google Scholar, 17Robbins N DeMaria A Miller MH Infective endocarditis in the elderly.South Med J. 1980; 73: 1335-1338Crossref PubMed Scopus (30) Google Scholar, 18Roder BL Wandall DA Frimodt-Moller N Espersen F Skinhoj P Rosdahl VT Clinical features of Staphylococcus aureus endocarditis: a 10-year experience in Denmark.Arch Intern Med. 1999; 159: 462-469Crossref PubMed Scopus (151) Google Scholar, 19Watanakunakorn C Staphylococcus aureus endocarditis at a community teaching hospital, 1980 to 1991: an analysis of 106 cases.Arch Intern Med. 1994; 154: 2330-2335Crossref PubMed Google Scholar Interestingly, the tendency among clinicians to classify murmurs in elderly patients as nonspecific inappropriately limits suspicion for IE.17Robbins N DeMaria A Miller MH Infective endocarditis in the elderly.South Med J. 1980; 73: 1335-1338Crossref PubMed Scopus (30) Google Scholar Although 86% of IE cases in patients 65 years or older present with a new or changing murmur, 59% are incorrectly diagnosed at admission.13Terpenning MS Buggy BP Kauffman CA Infective endocarditis: clinical features in young and elderly patients.Am J Med. 1987; 83: 626-634Abstract Full Text PDF PubMed Scopus (178) Google Scholar, 16Di Salvo G Thuny F Rosenberg V et al.Endocarditis in the elderly: clinical, echocardiographic, and prognostic features.Eur Heart J. 2003; 24: 1576-1583Crossref PubMed Scopus (125) Google Scholar, 17Robbins N DeMaria A Miller MH Infective endocarditis in the elderly.South Med J. 1980; 73: 1335-1338Crossref PubMed Scopus (30) Google Scholar Even transthoracic echocardiography, a primary echocardiographic tool used for the diagnosis of IE, has a lower vegetation detection rate in older patients21Werner GS Schulz R Fuchs JB et al.Infective endocarditis in the elderly in the era of transesophageal echocardiography: clinical features and prognosis compared with younger patients.Am J Med. 1996; 100: 90-97Abstract Full Text PDF PubMed Scopus (151) Google Scholar and is more likely to be interpreted as normal in elderly patients with documented disease at surgery or autopsy.13Terpenning MS Buggy BP Kauffman CA Infective endocarditis: clinical features in young and elderly patients.Am J Med. 1987; 83: 626-634Abstract Full Text PDF PubMed Scopus (178) Google Scholar Nevertheless, prospective case studies using transesophageal echocardiography to evaluate suspected IE cases document equal diagnostic sensitivity among varying age groups.16Di Salvo G Thuny F Rosenberg V et al.Endocarditis in the elderly: clinical, echocardiographic, and prognostic features.Eur Heart J. 2003; 24: 1576-1583Crossref PubMed Scopus (125) Google Scholar, 21Werner GS Schulz R Fuchs JB et al.Infective endocarditis in the elderly in the era of transesophageal echocardiography: clinical features and prognosis compared with younger patients.Am J Med. 1996; 100: 90-97Abstract Full Text PDF PubMed Scopus (151) Google Scholar Rheumatologic complications, particularly arthralgias and peripheral arthritis, are documented in 20% to 40% of all IE cases.22Gonzalez-Juanatey C Gonzalez-Gay MA Llorca J et al.Rheumatic manifestations of infective endocarditis in non-addicts: a 12-year study.Medicine (Baltimore). 2001; 80: 9-19Crossref PubMed Scopus (90) Google Scholar S aureus is the organism most commonly cultured from both blood (32.6%) and synovial fluid (71.4%) specimens in IE patients with monoarticular and polyarticular arthritis. As observed in our patient, the incidence of septic cerebral emboli in IE patients with rheumatologic manifestations is almost twice that in those without rheumatologic manifestations (74% vs 39%).22Gonzalez-Juanatey C Gonzalez-Gay MA Llorca J et al.Rheumatic manifestations of infective endocarditis in non-addicts: a 12-year study.Medicine (Baltimore). 2001; 80: 9-19Crossref PubMed Scopus (90) Google Scholar Neurologic sequelae develop in approximately 10% to 50% of all confirmed cases of IE.8Tornos P Almirante B Mirabet S Permanyer G Pahissa A Soler-Soler J Infective endocarditis due to Staphylococcus aureus: deleterious effect of anticoagulant therapy.Arch Intern Med. 1999; 159: 473-475Crossref PubMed Scopus (175) Google Scholar, 13Terpenning MS Buggy BP Kauffman CA Infective endocarditis: clinical features in young and elderly patients.Am J Med. 1987; 83: 626-634Abstract Full Text PDF PubMed Scopus (178) Google Scholar, 16Di Salvo G Thuny F Rosenberg V et al.Endocarditis in the elderly: clinical, echocardiographic, and prognostic features.Eur Heart J. 2003; 24: 1576-1583Crossref PubMed Scopus (125) Google Scholar, 17Robbins N DeMaria A Miller MH Infective endocarditis in the elderly.South Med J. 1980; 73: 1335-1338Crossref PubMed Scopus (30) Google Scholar, 18Roder BL Wandall DA Frimodt-Moller N Espersen F Skinhoj P Rosdahl VT Clinical features of Staphylococcus aureus endocarditis: a 10-year experience in Denmark.Arch Intern Med. 1999; 159: 462-469Crossref PubMed Scopus (151) Google Scholar, 19Watanakunakorn C Staphylococcus aureus endocarditis at a community teaching hospital, 1980 to 1991: an analysis of 106 cases.Arch Intern Med. 1994; 154: 2330-2335Crossref PubMed Google Scholar Stroke is most common in patients with native valve IE, occurring in 71% of cases.8Tornos P Almirante B Mirabet S Permanyer G Pahissa A Soler-Soler J Infective endocarditis due to Staphylococcus aureus: deleterious effect of anticoagulant therapy.Arch Intern Med. 1999; 159: 473-475Crossref PubMed Scopus (175) Google Scholar, 23Bertorini TE Gelfand M Neurological complications of bacterial endocarditis.Compr Ther. 1990; 16: 47-55PubMed Google Scholar More than two thirds of all IE-associated strokes are ischemic, presumably secondary to embolization,8Tornos P Almirante B Mirabet S Permanyer G Pahissa A Soler-Soler J Infective endocarditis due to Staphylococcus aureus: deleterious effect of anticoagulant therapy.Arch Intern Med. 1999; 159: 473-475Crossref PubMed Scopus (175) Google Scholar and mitral valve lesions are associated with stroke twice as often as aortic valve lesions.8Tornos P Almirante B Mirabet S Permanyer G Pahissa A Soler-Soler J Infective endocarditis due to Staphylococcus aureus: deleterious effect of anticoagulant therapy.Arch Intern Med. 1999; 159: 473-475Crossref PubMed Scopus (175) Google Scholar, 23Bertorini TE Gelfand M Neurological complications of bacterial endocarditis.Compr Ther. 1990; 16: 47-55PubMed Google Scholar Encephalopathy, the second most common neurologic complication, often presents without focal lesions and may contribute considerably to diagnostic and management errors in the elderly population.13Terpenning MS Buggy BP Kauffman CA Infective endocarditis: clinical features in young and elderly patients.Am J Med. 1987; 83: 626-634Abstract Full Text PDF PubMed Scopus (178) Google Scholar, 17Robbins N DeMaria A Miller MH Infective endocarditis in the elderly.South Med J. 1980; 73: 1335-1338Crossref PubMed Scopus (30) Google Scholar, 23Bertorini TE Gelfand M Neurological complications of bacterial endocarditis.Compr Ther. 1990; 16: 47-55PubMed Google Scholar In native valve IE caused by S aureus, meningitis is 3 to 4 times more common than infection with other pathogens (<10% vs 33%).8Tornos P Almirante B Mirabet S Permanyer G Pahissa A Soler-Soler J Infective endocarditis due to Staphylococcus aureus: deleterious effect of anticoagulant therapy.Arch Intern Med. 1999; 159: 473-475Crossref PubMed Scopus (175) Google Scholar, 23Bertorini TE Gelfand M Neurological complications of bacterial endocarditis.Compr Ther. 1990; 16: 47-55PubMed Google Scholar Although the incidence of neurologic events is consistent across age groups,13Terpenning MS Buggy BP Kauffman CA Infective endocarditis: clinical features in young and elderly patients.Am J Med. 1987; 83: 626-634Abstract Full Text PDF PubMed Scopus (178) Google Scholar, 16Di Salvo G Thuny F Rosenberg V et al.Endocarditis in the elderly: clinical, echocardiographic, and prognostic features.Eur Heart J. 2003; 24: 1576-1583Crossref PubMed Scopus (125) Google Scholar, 17Robbins N DeMaria A Miller MH Infective endocarditis in the elderly.South Med J. 1980; 73: 1335-1338Crossref PubMed Scopus (30) Google Scholar one of the largest published series on IE in elderly patients identified cerebral embolism as an independent risk factor for in-hospital mortality.16Di Salvo G Thuny F Rosenberg V et al.Endocarditis in the elderly: clinical, echocardiographic, and prognostic features.Eur Heart J. 2003; 24: 1576-1583Crossref PubMed Scopus (125) Google Scholar After nearly 120 years, IE remains a grave and diagnostically challenging disease. A high degree of clinical suspicion is paramount to early diagnosis, and IE should be suspected in any patient aged 60 years or older who has central nervous system symptoms, a new or changing heart murmur, and fever. We thank Drs Larry M. Baddour and Charles J. Bruce for their assistance in the preparation of the submitted manuscript.