Nocardiosis of the Central Nervous System

Central nervous system (CNS) nocardiosis is a rare disease entity caused by the filamentous bacteria Nocardia species. We present a case series of 5 patients from our hospital and a review of the cases of CNS nocardiosis reported in the literature from January 2000 to December 2011. Our results indicate that CNS nocardiosis can occur in both immunocompromised and immunocompetent individuals and can be the result of prior pulmonary infection or can exist on its own. The most common predisposing factors are corticosteroid use (54% of patients) and organ transplantation (25%). Presentation of the disease is widely variable, and available diagnostic tests are far from perfect, often leading to delayed detection and initiation of treatment. The optimal therapeutic approach is still undetermined and depends on speciation, but lower mortality and relapse rates have been reported with a combination of targeted antimicrobial treatment including trimethoprim/ sulfomethoxazole (TMP-SMX) for more than 6 months and neurosurgical intervention. (Medicine 2014;93: 19Y32) Abbreviations: CMV = cytomegalovirus, CNS = central nervous system, COPD = chronic obstructive pulmonary disease, CSF = cerebrospinal fluid, CT = computed tomography, GVHD = graftversus-host disease, HIV = human immunodeficiency virus, MGH = Massachusetts General Hospital, MRI = magnetic resonance imaging, PCR = polymerase chain reaction, TMP/SMX = trimethoprim/ sulfomethoxazole, TNF-> = tumor necrosis factor->. INTRODUCTION Nocardiosis is an uncommon disease caused by aerobic gram-positive bacteria in the genus Nocardia. Nocardia species have the ability to cause localized or systemic suppurative disease in humans and animals. Nocardiosis is primarily an opportunistic infection affecting immunocompromised patients, such as organ transplant recipients receiving pharmacologic immunosuppression, patients with low CD4 Tlymphocyte counts, and those with hematologic malignancies. However, roughly one-third of patients with nocardiosis are immunocompetent. The incidence of nocardiosis varies among different patient groups. In hospitalized patients, nocardiosis presents either as single-organ disease or as multifocal disease caused by dissemination of the microorganisms from a primary focus of infection. Single-organ infection most commonly manifests as lung disease (39% of cases in hospitalized patients), followed by infection of the central nervous system (CNS) (9% of cases). In this patient population disseminated disease is common and has been reported in 32% of cases. The genus Nocardia is composed of 13 medically important species. Nocardia asteroides, N. farcinica, N. nova and N. abscessus cause the majority of invasive infections. Patients with invasive nocardiosis are often seriously ill, and published reports on such infections are lacking. This is especially true of reports of CNS nocardiosis, which has a low prevalence. In the current review we focus on cases of CNS nocardiosis and examine the clinical manifestations, laboratory diagnosis, response to therapy, and outcome using clinical cases and the published literature. METHODS We identified 84 patients with nocardiosis seen during the 12 years from January 2000 to December 2011 by means of the research patient data registry at our hospital, Massachusetts General Hospital (MGH). We searched for patients using the International Classification of Disease-9th Revision (ICD-9) codes for nocardiosis. Approval of the study protocol was granted by the institutional review board of MGH. We accessed all electronic medical records and identified 5 cases of CNS nocardiosis. We recorded data on the patients’ index hospitalization, such as demographic information, including age, sex, and race. We also recorded each patient’s underlying illnesses and intake of medications, giving emphasis to their immunologic status. In particular, we looked for the presence of malignancy, human immunodeficiency virus (HIV), transplantation status, diabetes mellitus, neutropenia, tuberculosis, dialysis, chronic obstructive lung disease, and history of cytomegalovirus (CMV) infection. Neutropenia was defined as the presence of G1500 neutrophils per KL. Regarding the patient’s drug history, we were specifically interested in immunosuppressive drugs, such as chemotherapeutic agents, calcineurin inhibitors, tumor necrosis factor-> (TNF->) inhibitors, and corticosteroids. Patients were considered immunosuppressed if they took prednisone or a prednisone-equivalent pharmacologic agent in a dose Q10 mg per day for at least 3 months. Diagnostic methods involved imaging studies, such as computerized tomography (CT) scans of the head and magnetic resonance imaging (MRI) of the brain with and without contrast, as well as cultures of blood, cerebrospinal fluid (CSF), sputum, and aspirates of cerebral abscesses. Confirmed cases of CNS nocardiosis were those with cultures positive for Nocardia Medicine & Volume 93, Number 1, January 2014 www.md-journal.com 19 From Department of Medicine, Infectious Disease Division (TA, TKK, AD, HAC, EM), Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, and Department of Medicine, Infectious Disease Division (TA, MA, EM), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Financial support and conflicts of interest: The authors have no funding or conflicts of interest to disclose. Reprints: Eleftherios Mylonakis, MD, PhD, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903 (e<mail: [email protected]). Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0025-7974 DOI: 10.1097/MD.0000000000000012 Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. TA B LE 1. M G H Pa tie nt s W ith C N S N oc ar di os is C h ar ac te ri st ic P at ie n t