Histoplasma capsulatum Endocarditis: Multicenter Case Series with Review of Current Diagnostic Techniques and Treatment

Infective endocarditis is an uncommon manifestation of infection with Histoplasma capsulatum. The diagnosis is frequently missed, and outcomes historically have been poor. We present 14 cases of Histoplasma endocarditis seen in the last decade at medical centers throughout the United States. All patients were men, and 10 of the 14 had an infected prosthetic aortic valve. One patient had an infected left atrial myxoma. Symptoms were present a median of 7 weeks before the diagnosis was established. Blood cultures yielded H. capsulatum in only 6 (43%) patients. Histoplasma antigen was present in urine and/or serum in all but 3 of the patients and provided the first clue to the diagnosis of histoplasmosis for several patients. Antibody testing was positive for H. capsulatum in 6 of 8 patients in whom the test was performed.Eleven patients underwent surgery for valve replacement or myxoma removal. Large, friable vegetations were noted at surgery in most patients, confirming the preoperative transesophageal echocardiography findings. Histopathologic examination of valve tissue and the myxoma revealed granulomatous inflammation and large numbers of organisms in most specimens. Four of the excised valves and the atrial myxoma showed a mixture of both yeast and hyphal forms on histopathology.A lipid formulation of amphotericin B, administered for a median of 29 days, was the initial therapy in 11 of the 14 patients. This was followed by oral itraconazole therapy, in all but 2 patients. The length of itraconazole suppressive therapy ranged from 11 months to lifelong administration. Three patients (21%) died within 3 months of the date of diagnosis. All 3 deaths were in patients who had received either no or minimal (1 day and 1 week) amphotericin B.     

Obstructive mitral vegetations in bacterial endocarditis. Disappearance after migration as an embolism

An unusual form of mitral valve endocarditis was observed on echocardiography. A 49 year old female with well tolerated mitral stenosis and mild aortic incompetence contracted staphylococcal endocarditis. Pulmonary venous hypertension developed and the diastolic murmur increased. The echocardiogramme showed voluminous vegetations obstructing the stenosed mitral orifice in diastole, simulating a left atrial myxoma. An acute ischaemic episode of the lower limb occurred under antibiotic therapy. A voluminous fibrino-cruoric infected embolus was extracted from the iliac artery and a second echocardiogramme showed the intra mitral mass to have disappeared. Concurrently, the diastolic murmur decreased and the signs of intolerance disappeared. When the infective process seemed to have been controlled, the patient died suddenly. Post-mortem examination showed fresh mitral endocardial lesions and renal and splenic infarcts. Five cases of mitral obstruction by vegetations have been previously reported, three of which had echocardiographic studies. The echocardiographic image is stereotyped and resembles a myxoma wedged in the mitral orifice but without the intra atrial mass. This type of mitral obstruction complicated moderate mitral stenosis in all cases. Regression of the echographic appearances of valvular vegetations has been reported in rare cases, but we were unable to find another case of embolism of vegetations reducing the valvular obstruction.     

Pseudotumoral mitral endocarditis. Diagnostic and therapeutic problems apropos of a case report with review of the literature

The authors report an observation of infectious endocarditis of the mitral valve with voluminous pseudo-tumoral growth. The developmental, symptomatic and etiological characteristics of this form of endocarditis were specified through a review of the literature. Echocardiography provides the best means of early detection of these large vegetations but it is not always easy to distinguish them from other left intra-auricular tumors, more especially as several cases of infectious myxoma have been described. Spontaneous development of mitral endocarditis is very harmful, as are infected left intra-auricular tumors, and surgical treatment of these disorders seems essential as soon as the infectious process has been arrested.     

Infected cardiac myxoma

Infected cardiac myxomas are extremely rare with only forty cases described in the literature. We report a case of an infected cardiac myxoma that presented in a manner similar to bacterial endocarditis. Our case is the first to be diagnosed using previously defined criteria, and is unusual in that transesophageal echocardiography was required to make the diagnosis.     

Hemophilus aphrophilus endocarditis: Review of 23 cases

A case of bacterial endocarditis caused by Hemophilus aphrophilus is described, and 22 previously reported cases are reviewed. Eleven patients died and 12 survived; comparison of these two groups reveals that the patients who died were in the older population. The male/female ratio was 3.6:1. The organism was difficult to identify but had a wide range of in vitro bacteriologic sensitivities. This type of endocarditis is frequently associated with emboli and congestive heart failure; each occurred in 9 of 11 fatal cases and 3 of 12 nonfatal cases. Among the nonfatal cases, two patients had both emboli and congestive heart failure, requiring aortic valve replacement despite their precarious clinical condition. Initial drug therapy before results of antibiotic sensitivity tests are known should consist of penicillin combined with streptomycin. When emboli or congestive heart failure appears in Hemophilus aphrophilus endocarditis, early surgical intervention with valve replacement is indicated.     

Staphylococcus aureus bacteremia. Current clinical patterns.

One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics.     

Infective endocarditis of a native valve due to Acinetobacter: case report and review.

A case of community-acquired infective endocarditis of a native valve that was caused by Acinetobacter calcoaceticus subspecies anitratus is presented. The previously reported cases are reviewed, and therapy for this disorder is discussed. The presence of a transient maculopapular rash involving the palms and soles but sparing the face is suggested as a possible early clinical clue to the diagnosis. Native valve endocarditis caused by Acinetobacter species is an acute, aggressive illness that is more likely to be fatal than the prosthetic valve form; of the previously described patients, five of 15 with native valve endocarditis and one of six with prosthetic valve endocarditis died. In the appropriate clinical setting, we recommend therapy with an antimicrobial agent known to be active against Acinetobacter organisms when blood cultures are reported to yield oxidase-negative, gram-negative coccobacilli until the final identification of the microorganism is known.     

Haemophilus parainfluenzae endocarditis. Two cases and review of the literature in the past decade.

Twenty-five cases of Haemophilus parainfluenzae endocarditis have been reported in the past 10 years, providing a better current perspective of this disease. We have recently diagnosed and treated two patients with H. parainfluenzae endocarditis, and both underwent surgical intervention for complications of their disease. H. parainfluenzae and the other Haemophilus species causing endocarditis often present with a subacute course, often escape early cultural detection and mimic fungal endocarditis in the propensity for large vessel embolization. Multiple emboli and occlusion of major arterial vessels are especially notable features of H. parainfluenzae endocarditis and have occurred in approximately 30 per cent of the cases reported in the past 10 years. In contradistinction to other types of bacterial endocarditis, the most common cause of death in this series has been neurologic complications following embolization.Development of large vegetations appears to be common and may be an intrinsic property of the Haemophilus species, but it is likely that it also reflects the duration of the disease. Delay in recovery of the organism from blood cultures is characteristic of H. parainfluenzae endocarditis and may be due to the strict requirement for V factor exhibited by some strains. Echocardiography has proved useful in suggesting the diagnosis of endocarditis when blood cultures are negative.Optimal antibiotic therapy of H. parainfluenzae endocarditis has not been determined, but the reported clinical experience suggests that combination therapy with ampicillin and an aminoglycoside is the current treatment of choice. Failure to eradicate the organism after a prolonged trial of appropriate antibiotic therapy is not unusual. Indications for surgery in H. parainfluenzae endocarditis may have to be amended to include potential embolization, especially if large vegetations are demonstrated on echocardiography.     

Massa Valvar Mitral em Paciente com Suspeita de Lúpus Sistêmico: Tumor,Endocardite ou Ambos?

We present a case report of a patient with an infected mitral valve myxoma and a literature review on the subject. A 33-year-old female presented with a history of fever and dyspnea evolving over a few days. On admission, she had a lupus-like syndrome with positive blood cultures for Haemophilus species . Echocardiogram revealed a giant mass involving both mitral leaflets causing severe regurgitation, requiring biological mitral valve replacement. Microscopy showed an infected myxoma and the patient was discharged asymptomatic upon completion of antibiotics. She did well on follow-up. This is the sixth case of an infected mitral valve myxoma reported in the literature and the third case of a cardiac myxoma infected by the HACEK group. Exceedingly high incidence of embolic events makes prompt imaging, antibiotic therapy and surgery crucial for better outcomes. Time to diagnosis was much briefer than usually reported in other cases of HACEK endocarditis. Valve replacement was the most common surgical procedure and all patients from previous reports did well on follow-up.     

Histoplasma endocarditis: clinical and mycologic features and outcomes

OBJECTIVES: To define the salient clinical and microbiologic characteristics and outcome of infective endocarditis caused by Histoplasma capsulatum. METHODS: Case report and review of 43 literature cases. RESULTS: Infection involved both native (36 cases) and prosthetic (7) heart valves, had a high rate of systemic embolization (58%), and a more delayed diagnosis than bacterial endocarditis. Cardiac involvement generally occurred on mitral and/or aortic valves, and almost always in the setting of disseminated disease. Antemortem diagnosis was best made by serology (serum antibody titers or urinary antigen) or culture of blood (positive in <20% of cases), bone marrow, excised valves, and other non-blood specimens. Other diagnostic methods included histopathology and immunofluorescent staining of tissue samples. Untreated infection was uniformly fatal. Prolonged antifungal therapy with amphotericin B, without surgical intervention, appeared more effective than for Candida endocarditis. CONCLUSIONS: Histoplasma endocarditis is an infrequent but important cause of left-sided, blood culture-negative endocarditis. Its true prevalence may be underestimated because of the relative difficulty in making a precise microbiologic diagnosis. Amphotericin B therapy appears more effective than for Candida endocarditis, while the role for azole treatment and secondary prophylaxis remains uncertain. Indications for surgical valve replacement are similar to those for bacterial endocarditis.     

Infected left atrial myxoma with bacteremia simulating infective endocarditis.

A 58-year-old man had intermittent fever of eight months' duration following a dental extraction. There were no abnormal cardiac auscultatory findings. Multiple blood cultures yielded Streptococcus mutans. Treatment for infective endocarditis was initiated; however, an echocardiogram suggested the presence of a left atrial myxoma. The diagnosis was confirmed by angiography and the infected tumor was removed successfully. Differentiating features between left atrial myxoma and mitral valve endocarditis may not be obvious clinically, and bacteremia does not preclude atrial myxoma as a diagnostic possibility. We therefore suggest that all cases of infective endocarditis be evaluated by echocardiography to elucidate lesions such as large vegetations or left atrial myxoma, both of which may require urgent operative intervention.     

Infective endocarditis with negative blood cultures. An analysis of 52 cases.

The clinical records of 52 patients who were diagnosed clinically as having had infective endocarditis despite negative blood cultures have been reviewed. They differed at presentation from patients with positive blood cultures in more frequent receipt of antibiotics prior to culture and more frequent signs of major systemic emboli and congestive heart failure. Response of culture-negative patients with fever to empiric antibiotic therapy was correlated with survival, in that 92 per cent of the patients who became afebrile within the first week of therapy liver, whereas only 50 per cent of those who did not become afebrile lived. Deaths resulted primarily from major systemic emboli and from uncontrollable congestive heart failure due to valvular insufficiency. In 25 cases, valvular tissue was examined histologically. In 15 cases, vegetations were seen and organisms identified; in six cases, only vegetations were seen; and in four cases (16 per cent), the clinical diagnosis of infective endocarditis was not substantiated in the pathologic report.     

Left atrial myxoma: false negative echocardiographic findings in a tumor demonstrated by coronary arteriography.

A report of left atrial myxoma discovered at coronary arteriography by virtue of unusual tumor "vascularity" is presented in which establishing the diagnosis by means of echocardiography proved difficult. The difficulty may have been due to the highly vascular nature of the tumor with resultant loss of the acoustic reflectivity required for echocardiographic demonstration. Previous cases in which left atrial myxomas have shown arteriographically demonstrable "tumor vascularity" are reviewed.     

Endocarditis due to nutritionally deficient streptococci: therapeutic dilemma

Three cases of endocarditis due to nutritionally deficient (variant) streptococci are presented and the literature is reviewed. In all of the cases reviewed, the patient presented with an indolent subacute course. Prior heart disease was present in 90% of the patients, embolization occurred in 27%, relapse after therapy in 17%, and death in 17%. Bacteriologic failure occurred in 41% of cases, despite sensitivity of the organisms to the antibiotics used in two-thirds of these cases. Combination therapy with penicillin and an aminoglycoside has been recommended previously; however, in 38% of the cases reviewed, bacteriologic failures occurred and the patients required surgery. The results of in vitro antibiotic-sensitivity testing are difficult to interpret and to apply to the expected response to therapy. Further studies on these organisms are needed to reduce the high rates of failure, relapse, and fatality.     

Cardiac myxoma--clinical experience in 24 patients

We reviewed our clinical experience in 24 patients with cardiac myxoma. There were 8 males and 16 females, their ages ranged from 14 to 73 (mean, 48) years. Prior to echocardiographic examination, cardiac myxoma was suspected clinically in only 2 cases. The remaining patients were initially diagnosed as having mitral valvar disease (9 cases), infective endocarditis (3 cases), congestive cardiomyopathy (4 cases), pericardial effusion (1 case), systemic embolism of unknown cause (1 case), cerebrovascular accident (2 cases), ventricular septal defect (1 case) and Ebstein's malformation (1 case). The tumor was in the left atrium in 16, in the right atrium in 2, in the biatrium in 1, while one was in the right ventricle and peripheral arterial occlusion had been produced by myxoma without demonstrable cardiac tumors in the other two. Twenty-two patients underwent open heart surgery for excision of myxoma and there was no surgical mortality. Abdominal embolectomy was carried out in 2 patients; one of these 2 patients survived and 1 died. Follow-up for a mean period of 32 months (range 2 to 99 months) was possible in in 18 patients with no evidence of recurrence. We conclude that cardiac myxoma may mimic many cardiovascular diseases, so a high index of suspicion is important for its diagnosis. Echocardiography is the most useful diagnostic screening tool.     

Endocarditis due to Trichosporon beigelii: in vitro susceptibility of isolates and review

Infection with Trichosporon beigelii is an uncommon cause of endocarditis. Of the eight cases of T. beigelii endocarditis that have been reported (one herein and seven previously), six involved prosthetic heart valves and two involved native heart valves. The clinical manifestations of this infection included embolization of the superficial femoral artery or of the bifurcation of the posterior tibial and peroneal arteries in three of these patients (two with prosthetic valve and one with native valve endocarditis). In seven of the eight reported cases, blood cultures were positive for the organism. Although clinical isolates of the organism are generally reported to be susceptible to amphotericin B, isolates can vary in their sensitivities to antifungal agents in vitro depending on the methodology used, and clinical response to therapy with antifungal agents in a regimen that includes amphotericin B is generally poor. Only two of six patients who were treated with antifungal agents survived endocarditis caused by T. beigelii and were apparently cured; one of these patients was also managed surgically with valve replacement. Infection with T. beigelii should be considered in the differential diagnosis of endocarditis in immunocompetent patients, particularly those who have a prosthetic heart valve. Rapid, aggressive therapy may be necessary to eradicate this organism.     

Comparison of methicillin-resistant and methicillin-sensitive Staphylococcus aureus bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) has become endemic in Detroit, accounting for 50% of bacteremias in heroin abusers. To identify the salient epidemiologic and clinical features of MRSA bacteremia, case-control studies were performed comparing 28 cases of MRSA bacteremia to 28 cases of methicillin-sensitive S. aureus (MSSA) bacteremia in intravenous drug abusers. Infective endocarditis was diagnosed in 46.4% (13 of 28). In endocarditis and nonendocarditis bacteremia alike, the duration of fever, length of hospitalization, need for surgery, and mortality rates were similar. A history of recent antimicrobial therapy, especially cephalosporins, was more common in the MRSA group (p = 0.006). Complications including neurologic, renal, vascular, and musculoskeletal manifestations were more common in the MSSA endocarditis patients than MRSA endocarditis patients, although this difference was not significant. Complications related to antibiotic therapy were similar for both groups. The case-control studies indicate that MRSA and MSSA are similar in their virulence as measured by duration of hospitalization, duration of fever, complications, and mortality.     

Infected left atrial myxoma

A 47-year-old Japanese woman with a continuing high fever was promptly diagnosed as having infected atrial myxoma one day after admission based on transthoracic echocardiographic findings and positivity for bacteria in blood culture. The mass was removed by an urgent open heart surgery. Histopathological examination confirmed that this mass was a myxoma with gram-positive bacterial colonies. Generally, antemortem diagnosis is difficult and there is a high mortality of patients with infected myxoma; however, this patient completely recovered from the illness because of the prompt diagnosis. This is the 37th case of definite infected myxoma reported in the literature. The cause of infection of this patient might have been the acupuncture therapy she underwent for weight reduction.     

Endocarditis due to Neisseria mucosa: two case reports and review.

Two cases of endocarditis caused by Neisseria mucosa are reported, and the literature on N. mucosa endocarditis is reviewed. N. mucosa is a rare but serious cause of endocarditis that is associated with a high rate of embolic complications and high mortality and is not always highly sensitive to benzylpenicillin. Most patients with N. mucosa endocarditis have been treated with combined therapy with penicillin and an aminoglycoside, although the optimal regimen has not been defined.     

Some salient features of staphylococcus aureus endocarditis

Sixty-four cases of Staphylococcus aureus endocarditis between 1940 and 1971 were reviewed. There was no change in the incidence during these three decades. The over-all mortality was 41 and 86 per cent, respectively, in patients below and above age 50. The corresponding per cent mortality in the last decade of the study was lower, namely, 14 and 71 per cent. In four patients Staph. aureus endocarditis developed in the hospital. In two of these patients, endocarditis was associated with an infected indwelling intravenous catheter and in one, septic thrombophlebitis secondary to intravenous therapy was the presumed source. Endocarditis or bacteremia was not suspected clinically in 10 patients. Eight of them were over 70 years old; organic valvular heart disease was diagnosed in only one. A high index of suspicion is essential in the diagnosis of Staph, aureus endocarditis, since classic physical findings in subacute endocarditis are often absent. Endocarditis should be strongly suspected in the presence of Staph. aureus bacteremia.