Nocardiosis: A Neglected Disease.

Nocardiosis is a neglected tropical disease. It has varied geographical presence and a spectrum of clinical presentations. This review aims to focus on the epidemiology of nocardial infections with a systematic approach to their diagnosis and treatment. Nocardiacauses chronic infections and ailments, and may remain cryptic but progressive in its course. Unless suspected, diagnosis can be easily missed resulting in increased morbidity and mortality. Thorough knowledge of local epidemiology, demography, clinical course and presentation, diagnostic modalities, and antibiotic susceptibility patterns of the prevalent Nocardia species is essential to curb spread of this infection. This is a systematic review in which internet search has been done for citation indices (Embase, PubMed, Ovid, and other individual journals) till March 2020 utilizing the following key words "Nocardia," "taxonomy," "prevalence," "clinical features," "diagnosis," "treatment," and "susceptibility." We selected a total of 87 review articles, case series, and case reports all in English language.

Nocardia bacteremia: A single-center retrospective review and a systematic review of the literature.

OBJECTIVES: Nocardia bacteremia is a rare but severe disease associated with high mortality. This systematic review is the largest and most comprehensive review performed over the past 20 years. METHODS: A single-center retrospective review of Nocardia bacteremia was performed using hospital microbiology records from January 1, 2010 to December 31, 2017. A systematic literature review was also performed to identify cases of Nocardia bacteremia described in the NCBI PubMed database in English between January 1, 1999 and December 31, 2018. RESULTS: Four new cases of Nocardia bacteremia are described. The systematic review identified 134 cases with sufficient information available for analysis. Of the total 138 cases, the median age was 58 years (interquartile range (IQR) 44-69 years) and 70% were male. Eighty-one percent were immunocompromised (corticosteroid use (49%), hematological malignancy (20%), solid organ transplant (20%), solid organ malignancy (19%), and hematopoietic stem cell transplantation (15%)) and 29% had endovascular devices. Pulmonary infection was the most common concurrent site of clinical disease (67%). The median incubation time to the detection of Nocardia bacteremia was 4 days (IQR 3-6 days). Blood cultures were the only positive microbiological specimen in 38% of cases. The median total duration of treatment was 75 days (IQR 25-182 days). Thirty-day all-cause mortality was 28% and overall all-cause mortality was 40%. CONCLUSIONS: Nocardia bacteremia is most frequently identified in immunocompromised patients and those with intravascular devices. Although rare, it represents a serious infection with high associated overall mortality.

Identification and functional characterization of Histone-like DNA-binding protein in Nocardia seriolae (NsHLP) involved in cell apoptosis.

Nocardia seriolae, a facultative intracellular bacterium, is the main pathogen of fish nocardiosis. Bioinformatic analysis showed that the histone-like DNA-binding protein (HLP) gene of N. seriolae (nshlp) encoded a secreted protein and might target the mitochondria in the host cell. To further study the preliminary function of HLP in N. seriolae (NsHLP), the gene cloning, extracellular products identification, subcellular localization, overexpression and apoptosis detection assay were carried out in this study. Mass spectrometry analysis of the extracellular products from N. seriolae showed that NsHLP was a secreted protein. Subcellular localization of HLP-GFP fusion proteins mainly assembled in the nucleus, which indicated that the NsHLP was co-located with the nucleus rather than mitochondria in fathead minnow (FHM) cells. Notably, the expression of NsHLP had changed the distribution of mitochondria into lumps in the FHM cell. In addition, apoptotic features were found in the transfected FHM cells by overexpression of NsHLP. Quantitative assays of mitochondrial membrane potential value, caspase-3 activity and pro-apoptotic genes mRNA (Bad, Bid and Bax) expression level demonstrated that the cell apoptosis was induced in the transfected FHM cells. All the results presented in this study provided insight on the function of NsHLP, which suggested that it may participate in the cell apoptosis regulation and play an important role in the pathogenesis of N. seriolae.

Granulomatous Thyroiditis: A Case Report and Literature Review.

BACKGROUND: Granulomatous disease in the thyroid gland has been linked to viral, bacterial and autoimmune etiologies. The most common granulomatous disease of the thyroid is subacute granulomatous thyroiditis, which is presumed to have a viral or post-viral inflammatory cause. Bacterial etiologies include tuberculosis, actinomycosis, and nocardiosis, but are extremely rare. Disseminated actinomycosis and nocardiosis more commonly affect organ-transplant patients with the highest susceptibility within the first year after transplant surgery. CASE: A 45-year-old African American male, who received his third kidney transplant for renal failure secondary to Alport Syndrome, presented with numerous subcutaneous nodules and diffuse muscle pain in the neck. Further workup revealed bilateral nodularity of the thyroid. Fine needle aspiration of these nodules demonstrated suppurative granulomatous thyroiditis. Subsequent right thyroid lobectomy showed granulomatous thyroiditis with filamentous micro-organisms, morphologically resembling Nocardia or Actinomyces. CONCLUSION: Disseminated granulomatous disease presenting in the thyroid is very rare, and typically afflicts immune-compromised patients. The overall clinical, cytologic and histologic picture of this patient strongly points to an infectious etiology, likely Nocardia, in the setting of recent organ transplantation within the last year.

Pulmonary Nocardiosis: A Clinical Analysis of 30 Cases.

Objective Pulmonary nocardiosis frequently develops as an opportunistic infection in patients with malignant tumor and is treated with steroids. This study was performed to clarify the clinical features of pulmonary nocardiosis in Japan. Methods The patients definitively diagnosed with pulmonary nocardiosis at our hospital between January 1995 and December 2015 were retrospectively investigated. Results Nineteen men and 11 women (30 in total) were diagnosed with pulmonary nocardiosis. Almost all patients were complicated by a non-pulmonary underlying disease, such as malignant tumor or collagen vascular disease, or pulmonary disease, such as chronic obstructive pulmonary disease or interstitial pneumonia, and 13 patients (43.3%) were treated with steroids or immunosuppressors. Gram staining was performed in 29 patients, and a characteristic Gram-positive rod was detected in 28 patients (96.6%). Thirty-one strains of Nocardia were isolated and identified. Seven strains of Nocardia farcinica were isolated as the most frequent species, followed by Nocardia nova isolated from 6 patients. Seventeen patients died, giving a crude morality rate of 56.7% and a 1-year survival rate of 55.4%. The 1-year survival rates in the groups with and without immunosuppressant agents were 41.7% and 59.7%, respectively, showing that the outcome of those receiving immunosuppressants tended to be poorer than those not receiving them. Conclusion Pulmonary nocardiosis developed as an opportunistic infection in most cases. The outcome was relatively poor, with a 1-year survival rate of 55.4%, and it was particularly poor in patients treated with immunosuppressant agents. Pulmonary nocardiosis should always be considered in patients presenting with an opportunistic respiratory infection, and an early diagnosis requires sample collection and Gram staining.

Clinical Analysis of Pulmonary Nocardiosis in Patients With Autoimmune Disease.

Nocardiosis is an opportunistic infection that most commonly involves the lung; however, only a few case reports of autoimmune disease complicated by pulmonary nocardiosis exist in the literature. We conducted a retrospective analysis of 24 cases of both autoimmune disease and pulmonary nocardiosis at the Peking Union Medical College Hospital between 1990 and 2012. Fifty-two cases were hospitalized with nocardiosis, 24 of whom had at least 1 autoimmune disease before the diagnosis of pulmonary nocardiosis. The cohort patients consisted of 5 men and 19 women, with a mean age of 44.2 years. All were negative for human immunodeficiency virus. All but 1 patient had received immunosuppressants, including corticosteroids, cyclophosphamide, azathioprine, methotrexate, or hydroxychloroquine. Fever (87.5%), cough (83.3%), and sputum (79.2%) were the most common clinical manifestations. Ten cases were accompanied by subcutaneous nodules and/or cutaneous abscesses, and 4 had brain abscess. Half of them were lymphocytopenic. Thirteen of the 16 cases who underwent lymphocyte subtype analysis had decreased CD4+ T-cell counts. Nineteen cases had decreased serum albumin levels. Nocardia was isolated from sputum (13/24), bronchoalveolar lavage fluid (4/6), lung tissue (5/6), pleural effusions (3/5), skin or cutaneous pus (7/10), and brain tissue (1/1). The most common imaging findings were air-space opacities (83.3%), followed by nodules (62.5%), cavitations (45.8%), and masses (37.5%). Five were administered co-trimoxazole only, and the others were treated with 2 or more antibiotics. All 5 cases with skin abscesses and 2 of the 4 cases with brain abscesses were treated by surgical incision and drainage. None underwent thoracic surgery. Corticosteroid dosages were decreased in all cases, and cytotoxic agents were discontinued in some cases. Twenty-two cases recovered, and 2 died. Pulmonary nocardiosis associated with an underlying autoimmune disease showed a female predominance and presentation at younger age. Immunosuppressant therapy, lymphocytopenia, particularly low CD4+ T-lymphocyte counts, and low serum albumin levels may be disease susceptibility factors. Air-space opacities and nodules were the most common chest imaging features, and disseminated nocardiosis with lung and skin involvement was more common among them. Early diagnosis and anti-nocardial antibiotics with modulation of the basic immunosuppressive therapy were important for them.

NOCARDIA CHOROIDAL ABSCESS: Risk Factors, Treatment Strategies, and Visual Outcomes.

PURPOSE: To describe the risk factors, clinical course, ancillary test findings, treatment strategies, and visual outcomes of a series of patients with choroidal abscesses caused by endogenous Nocardia. METHODS: This retrospective, consecutive noncomparative case series included all patients with Nocardia ocular infections at 3 tertiary medical centers over the past 20 years. RESULTS: Five eyes in 5 patients were identified with choroidal abscesses because of Nocardia. All patients were immunocompromised: one suffered from AIDS and four had autoimmune disorders. Three of the 5 patients (60%) underwent systemic evaluation, and in all 3, nonocular nocardiosis was identified. Four patients (80%) underwent diagnostic ophthalmic surgery and received systemic and intravitreal antibiotics. The final patient deferred these interventions. Outcomes at the last follow-up examination were 20/25, 1/200, hand motion at 1 foot, and 2 patients underwent enucleation. Mean follow-up (± standard deviation) was 159 (± 103) days. CONCLUSION: Immunosuppression is the most significant risk factor for developing Nocardia choroidal abscesses. Definitive diagnosis generally requires subretinal biopsy, which is also critical to implementing appropriate antibiotic therapy.

Disseminated nocardiosis during systemic steroid therapy for the prevention of esophageal stricture after endoscopic submucosal dissection.

An 85-year-old man underwent endoscopic submucosal dissection for a large superficial esophageal epithelial neoplasm, which required removal of 95% of the circumference of the esophageal mucosa. Steroids were given orally to prevent esophageal stricture starting on day 3 postoperatively. In the 6th week of steroid treatment, he developed high fever without other symptoms. Chest computed tomography revealed a nodular lesion in the lung. Sputum sample showed Gram-positive, branching, filamentous bacteria, and a diagnosis of nocardiosis was suspected. Brain magnetic resonance imaging revealed multiple focal lesions which indicated dissemination of nocardiosis. Trimethoprim-sulfamethoxazole was immediately started, which led to the disappearance of pulmonary and cerebral nocardiosis with alleviation of fever. Recently, oral steroid treatment has been widely used for the prevention of esophageal stricture. However, the present case indicates the risk of life-threatening infection and the importance of close monitoring of this treatment.

[Thoracic nocardiosis with thoracic manifestations in two immunocompetent patients].

Nocardiosis is a rare infectious disease caused by bacteria of the genus nocardia, which causes considerable morbidity and mortality. We report two unusual cases of nocardiosis in young, immunocompetent patients; the first case involved a nocardia farcinica pulmonary and chest-wall infection, while the second was an anterior mediastinal nocardia asiaticum infection mimicking a mediastinal tumor. These cases reflect the need for a broad differential diagnosis during exploration of thoracic findings, white the potentially ambiguous presentation of nocardiosis must be considered.

Pulmonary nocardiosis: a comparative analysis of Nocardia asteroides and non-asteroides species.

Our study compares the risk factors, clinical presentations and outcomes of pulmonary infections caused by Nocardia asteroides and non-asteroides species. We performed a retrospective cohort study comparing pulmonary infections by both species in patients presenting to a tertiary care hospital in Karachi, Pakistan. Forty-one patients were identified with pulmonary nocardiosis, with 58.5% belonging to the N. asteroids complex. The most common clinical findings were fever and a cough for both groups, with lobar infiltrates being the most common finding on chest radiographs. In vitro testing showed a sensitivity of all species to trimethoprim-sulfamethoxazole (TMP-SMZ), aminoglycosides, ceftriaxone and imipenem. The majority of the patients were treated with TMP-SMZ in combination with other drugs. The results of our study suggest that there is no significant difference in the risk factors, presentations and outcomes of pulmonary infections by N. asteroides and non-asteroides species. Immunocompromised patients are more likely to have unfavorable outcomes.

Clinical and microbiological characteristics of Nocardiosis including those caused by emerging Nocardia species in Taiwan, 1998-2008.

The genus of Nocardia is rapidly expanding and the species distribution varies with different geographical locations. We retrospectively reviewed the laboratory records of the bacteriology laboratory at National Taiwan University Hospital from January 1998 to June 2008 to identify patients with nocardiosis. During the study period, 164 isolates of Nocardia spp. were identified from 134 patients but only 113 patients had Nocardia infection. Nocardia brasiliensis (n = 54) was the most common pathogen, followed by N. asteroides (n = 36), N. farcinica (n = 7), N. flavorosea (n = 4), N. otitidiscaviarum (n = 3), N. nova (n = 3), N. beijingensis (n = 2) and one each of N. puris, N. jinanensis and N. takedensis. The major types of infection were cutaneous infection (56.6%), pulmonary infection (33.6%) and disseminated infection (7.1%). Eighty-eight patients received sulfonamide-containing antibiotic and eight of 100 patients with available data on outcomes died during the episode of nocardiosis. In conclusion, the clinical and microbiological manifestations of Nocardiosis vary with the different Nocardia species. Accurate identification of the species is crucial to make the diagnosis.

Port-A catheter-associated Nocardia bacteremia detected by gallium inflammation scan: a case report and literature review.

Central venous catheter-associated Nocardia bacteremia is rarely reported. We present the case of a 48-y-old male with a history of advanced T-cell lymphoma who suffered from recurrent fever and persistent Gram-positive bacillus bacteremia. Port-A catheter-associated Nocardia bacteremia was diagnosed on the basis of the clinical response to removal of the catheter and the finding of increased gallium uptake, along with the Port-A catheter presented in the gallium inflammation scan.

Nocardial infection in patients infected with the human immunodeficiency virus.

During the period 1981-2000, we diagnosed eight cases of HIV-Nocardia co-infection (0.38% of AIDS cases). Six were males, and the mean age was 28.6 years. The most common risk factor for HIV infection was intravenous drug abuse. Most patients were severely immunodepressed at the time of diagnosis (mean CD4+ count, 35 cells/ micro L). The clinical forms of nocardiosis seen were pulmonary infection in three, skin or soft tissue infection in three, disseminated in one, and pulmonary colonization in one. Most patients were given sulfonamides, and a clinical response was observed in six of seven treated patients. However, two patients with pulmonary disease died from progressive infection. Although its incidence is very low among AIDS patients, nocardiosis is associated with high morbidity and mortality among HIV-infected individuals.