Introduction

Septic thromboembolism is frequently seen with Infective Endocarditis (IE) and can lead to serious neurological complications including stroke, hemorrhage, intracranial aneurysm, meningoencephalitis, abscess, and seizures. Legionella as an etiology of native valve endocarditis is rare with only two previous cases reported in the literature, both without an associated embolic phenomenon. In this report, we present the first case of native valve Legionella endocarditis associated with recurrent embolic complications.

Materials and Methods

Case report and Literature Review.

Results and Discussion

A 42-year-old female nurse with supraventricular tachycardia status post ablation, Factor V Leiden (FVL) heterozygosity, migraine, thoracic astrocytoma at age two treated with radiotherapy, hyperlipidemia, and Barrett’s esophagus presented with severe headaches, left-sided homonymous hemianopia, and a brief episode of left arm numbness. Imaging revealed an acute right parietooccipital infarct. Over the next ten months, she had five further cryptogenic embolic strokes with debilitating neurological deficits despite medical management with different antithrombotic agents. She also had recurrent seizures, headaches, chills, and night sweats without fevers. MR and CT angiography along with conventional angiogram did not reveal any intrinsic vascular abnormality. Extensive neuro-rheumatologic serological tests along with CSF analysis were unremarkable. Hypercoagulability markers were negative with the exception of known FVL heterozygosity. Elaborative cardiac workup with serial Transthoracic (TTE) and Transesophageal (TEE) echocardiograms as well as an intracardiac echocardiogram was initially inconclusive for intracardiac shunt, thrombus, or vegetation. However, nine months after her initial presentation, a repeat TEE revealed small, hypermobile, filamentous masses on the mitral valve. Blood cultures throughout her disease course remained negative. Ultimately, an elevated serum Legionella pneumophila IgG titer (1:512) was found without concurrent gastrointestinal or lung disease. Treatment with levofloxacin led to prompt significant clinical improvement without recurrence of strokes, headaches, or seizures. A TEE six weeks following treatment showed reduced size of the filamentous structures and decreased Legionella titer (1:256).

Legionella are gram-negative aerobic bacilli found in natural and man-made aqueous environments that typically lead to pneumonia. Infection with Legionella most often results in pneumonia. L. pneumophila accounts for 90% of humanistic Legionella infections. Extrapulmonary manifestations are rare, though they can occur more frequently in immunocompromised individuals by Legionella species other than L. pneumophila [1]. These may include endocarditis, myopericarditis, meningitis, soft tissue abscesses, and septic arthritis. Legionella-associated IE typically affects prosthetic and homograft valves via direct inoculation with contaminated surgical equipment. To our knowledge, there are only two case reports of native valve endocarditis secondary to Legionella [2,3]. L. pneumophila and a novel H63 strain were the causative agents reported in those cases.

Neurologic complications of septic thromboembolism occur in up to 30% of IE cases and include ischemic and hemorrhagic strokes, intracranial mycotic aneurysms, meningoencephalitis, abscess, and seizures [4]. A retrospective study revealed an increased ischemic stroke risk ranging from four months prior to diagnosis of IE up to five months after [5]. Embolic phenomena, however, have only been found associated with Legionella endocarditis in one immunocompromised patient with prosthetic valve endocarditis [6,7]. Our patient suffered recurrent embolic ischemic strokes in multiple vascular territories resulting in severely debilitating aphasia, dysarthria, visual impairment, paresis, and sensory deficits (Figure). Recurrent focal seizures were treated with levetiracetam. (Figure).

MRI demonstrating Recurrent Embolic Strokes and TEE Demonstrating Mitral Valve Vegetation.

Diagnosis of Legionella endocarditis is complicated and often delayed due to many factors. As a fastidious intracellular organism, Legionella only grows in cultures on selective medium resulting in negative blood cultures [1]. In addition, Legionella endocarditis vegetations are rarely seen on echocardiography including TEEs [6]. Serology and urine antigen testing are most sensitive and specific for L. pneumophila [1]. Although IgG typically indicates a prior infection, the significantly elevated titer in our patient suggested an acute or more recent infection. Due to the prolonged disease course, IgM testing was not indicated. Urine antigen was negative and blood cultures sub-cultured onto buffered charcoal yeast extract agar did not yield any growth.

Extrapulmonary Legionella infections are typically treated with fluoroquinolones such as levofloxacin but there is no clear evidence-based treatment regimen or duration for Legionella endocarditis. Due to the severity of our patient’s condition, we pursued a 12-week course with levofloxacin. Although anticoagulation in active IE with embolic phenomena is controversial, a multidisciplinary decision was made to continue long-term therapeutic anticoagulation initially with enoxaparin and subsequently apixaban. While the infection source in our immunocompetent patient remains unknown, we cannot exclude exposure from the preceding cardiac ablation nor a nosocomial infection given her profession as a nurse. To our knowledge, this is the first-ever reported case of native valve Legionella pneumophila endocarditis with devastating embolic complications. We recommend maintaining a high clinical index of suspicion for culture-negative endocarditis for accurate diagnosis and successful treatment.

Acknowledgement

The authors thank Dr. Volpi for his mentorship.

Financial Disclosures

Dr. Poursheykhi, Dr. Imran, Dr. Drews, and Dr. Volpi report no disclosures.

References

1. Muder RR, Victor LY (2002) Infection Due to Legionella Species Other Than pneumophila. Clinical Infectious Diseases 35: 990-998.
2. Pearce MM, Theodoropoulos N, Noskin GA, Flaherty JP, Stemper ME, et al. (2011) Native valve endocarditis due to a novel strain of Legionella. J Clin Microbiol 49 : 3340‐3342.
3. Samuel V, Bajwa AA, Cury JD (2011) First case of Legionella pneumophila native valve endocarditis. Int J Infect Dis 15: e576-e577.
4. Jones HR JK, Siekert RG (1989) Neurological Manifestations of Infective Endocarditis: Review of Clinical and Therapeutic Challenges. Brain 112: 1295-1315.
5. Merkler AE, Chu SY, Lerario MP, Navi BB, Kamel H (2015) Temporal relationship between infective endocarditis and stroke. Neurology 85: 512-516.
6. Brouqui P, Raoult D (2001) Endocarditis Due to Rare and Fastidious Bacteria. Clinical Microbiology Reviews 14: 177-207.
7. Fukuta Y, Yildiz-Aktas IZ, Pasculle AW, Veldkamp PJ (2012) Legionella micdadei prosthetic valve endocarditis complicated by brain abscess: Case report and review of the literature. Scandinavian Journal of Infectious Diseases 44: 414-418.