Fever in a 40-Year-Old Intravenous Drug User

John L. Brusch, MD


January 12, 2015

The clinical course of fungal endocarditis is generally similar to that of bacterial endocarditis. Overall, 75% of patients are febrile; 51% develop a new or a change in a preexistent heart murmur. Focal and generalized neurologic abnormalities are found in 31% of cases. Heart failure develops in 24% of patients. Often, the infection may be subacute, with a delay in diagnosis of as long as 10 weeks. However, macroembolization (36%) is likely; 50% of these affect the intracranial blood vessels, with less frequent involvement of the legs and gastrointestinal tract. As many as 25% of patients develop endophthalmitis.

In puzzling cases, ophthalmologic examination can detect the pathognomonic appearance of Candida emboli. Similarly, examination of a retrievable peripheral macroembolus can provide both histopathologic and culture evidence of Candida. The pathognomonic signs of subacute bacterial endocarditis, such as Janeway lesions and Osler nodes, and the suggestive findings of Roth spots are not present in candidal endocarditis. These entities result from the immunologic aspects of subacute bacterial endocarditis. Such immune complexes do not occur in fungal valvular infections.[2,3]

Across the board, 75% of cases of IE in intravenous drug users involve previously normal hearts. The rate of underlying valvular pathology and the distribution between right-sided and left-sided candidal IE is not established. However, particulate material contained in the injected drug may cause progressive damage to the tricuspid valve. This material is small enough to migrate across the pulmonary capillary bed to the arterial circulation and ultimately scar the mitral or aortic valves. The end result of this process is formation on the valve of a sterile fibrin thrombus (nonbacterial thrombotic endocarditis) to which circulating Candida could attach. Alternatively, increased stimulation of the immune system by repeated exposure to these injected materials could also result in production of nonbacterial thrombotic endocarditis.

The most challenging type of candidal IE appears to be candidal prosthetic valve endocarditis, because the infected prosthetic material must be removed and the replacement must be inserted. Fungal prosthetic valve endocarditis that occurs within 60 days of implantation is classified as early. The infection becomes established during the surgery or in the perioperative period. Late prosthetic valve endocarditis occurs 12 months or more after surgery. Intermediate cases are diagnosed between 60 days and 12 months after implantation. High rates (11%-25%) of prosthetic valve endocarditis cases arise from nosocomial fungemia, in which the endocarditis eventually becomes clinically apparent after 26-690 days.

The cornerstone of diagnosis of any type of valvular infection is documenting the sustained presence in the bloodstream of the suspected pathogen (bacterial or fungal). The diagnosis of candidal IE is based primarily on blood culture evidence of a continuous fungemia. A continuous bloodstream infection is defined as at least two positive blood culture findings for the same pathogen obtained at least 12 hours apart or three positive blood culture findings positive for the same pathogen, with a first and last finding obtained at least 1 hour apart. The continuous fungemia separates valvular infection from candidemia, which represents intermittent entry of the fungus into the bloodstream from nonvalvular sources, such as lung or kidney.

Even if vegetations are detected by transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) should always be performed to detect complications of Candida infections, such as paravalvular abscess or large vegetation. The diagnostic usefulness of pathologic study of retrievable peripheral emboli and the presence of endophthalmitis have already been discussed. Serologic testing has not proven useful as a diagnostic approach.

A mean delay in diagnosis of Candida IE of approximately 32 days is noted. The inability to mount an inflammatory response, such as fever, because of immunosuppression in at-risk patients can significantly hinder its expeditious diagnosis.


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