Pulmonary Nocardiosis Caused by Nocardia sputorum Identified via 16S rRNA Gene Sequencing: A Case Report.

Nocardia sputorum, a novel Nocardia species discovered in Japan in 2023, has not been reported to infect humans. Here, we report a case of pulmonary nocardiosis in a 70-year-old immunocompetent woman infected with N. sputorum. The patient presented to the hospital with a chief complaint of weight loss. She worked at a fruit sorting facility where she was exposed to dust. Chest computed tomography revealed a single cavity and diffuse nodular opacities in both lungs. Nocardia species was isolated from tracheal sputum and bronchial lavage fluid and identified as N. sputorum via 16S rRNA gene sequencing. The patient was treated with oral sulfamethoxazole and trimethoprim but developed oral mucositis on the 12th day of treatment. Consequently, minocycline was prescribed, and the patient's condition improved after a six-month course of treatment. To our knowledge, this is the first reported case of pulmonary nocardiosis caused by N. sputorum in humans. Accurate species identification and antimicrobial susceptibility tests will be necessary to prescribe appropriate treatment for Nocardia infections.

Silent Manifestations of Disseminated Nocardia in a Renal Transplant Patient.

This case report describes a unique presentation of disseminated nocardiosis in a 45-year-old male transplant recipient who initially presented with acute left hip pain. Despite being asymptomatic for respiratory symptoms, the patient developed a fever and subsequently exhibited hypoxia. A diagnostic workup revealed a cavitary mass in the right upper lobe and multiple pulmonary nodules, confirming silent pulmonary nocardiosis. Concurrently, an MRI identified myositis and a possible abscess in the left hip musculature. Treatment involved a regimen including imipenem-cilastatin and linezolid, tailored for Nocardia species farcinica. This case underscores the importance of vigilant evaluation for metastatic infections in immunocompromised patients presenting with atypical symptoms, highlighting the necessity of imaging studies such as CT of the thorax for early detection of silent pulmonary involvement.

Multiple lymph nodes enlargement and fever as main manifestations of nocardiosis in immunocompetent individuals: Two case reports.

Nocardia farcinica is an aerobic gram-positive bacterium that is pathogenic to humans. It usually causes local and adjacent tissues' diseases at the entry of infection (most commonly occur in the lungs, skin, or central nervous system), which can also spread to other organs through the bloodstream such as joints, kidneys, and liver. However, these infections are often seen as opportunistic that occur in immunocompromised patients. Here, we report for the first time two immunocompetent patients lacking evidence of local infections, with multiple lymph node enlargements and fever as main clinical manifestations, finally diagnosed as nocardiosis by Metagenomic Next-Generation Sequencing testing (mNGS) from formalin-fixed and paraffin-embedded (FFPE) lymph node tissue, after all the other standard tests were negative. Both patients recovered after receiving anti-nocardia therapies. These two cases indicates that in healthy population, there may be more potential nocardia infections than we expected. Multiple lymph node enlargements and fever suggest a possibility of nocardiosis, especially in patients with fever of unknown origin (FUO). mNGS detection from FFPE lymph node tissue is an accurate, reliable and traceable method for diagnosis of nocardiosis.

The Pathogenic Role of Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Nocardiosis with the Central Nervous System Involvement.

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.

Pulmonary Nocardiosis Due to Nocardia exalbida Infection Following Living-donor Liver Transplantation.

Nocardia exalbida, an uncommon Nocardia, was first identified in 2006. We herein report a 70-year-old man with pulmonary nocardiosis caused by N. exalbida after living-donor liver transplantation. We also review 11 previously reported cases of N. exalbida infections. To our knowledge, there are no case reports available on nocardiosis consequent to N. exalbida infection following transplantation, thus highlighting the importance of identifying bacterial species for the successful management of infection.

Suppurative Thyroiditis: Coinfection by Nocardia spp. and Mycobacterium tuberculosis in an Immunocompromised Patient.

Suppurative thyroiditis is a rare entity with a low incidence in thyroid diseases, manifesting with pain, fever, dysphagia, and dysphonia. Its infrequency is explained by the thyroid gland's resistance to infections due to its encapsulated position, high blood flow, bactericidal action of iodine, and extensive lymphatic network. We present the first report in the literature of a 72-year-old woman with a history of inflammatory myopathy and immunosuppression diagnosed with suppurative thyroiditis co-infected with Nocardia spp. and Mycobacterium tuberculosis. This entity requires a high clinical suspicion, and fine-needle aspiration biopsy (FNAB) is preferred as the diagnostic method for microbiological sampling. Although rare, it carries high morbidity and mortality if not suspected in time.

Sulfonamide allergy label and the risk of opportunistic infections in solid organ transplant recipients - A retrospective matched cohort study.

BACKGROUND: While a penicillin allergy label has been linked to various negative clinical outcomes, limited studies have specifically characterized the implication of sulfonamide allergy labels (SAL) on clinical outcomes. We examined the impact of SAL on clinical outcomes of solid organ transplant recipients. METHODS: In this retrospective matched cohort study, we utilized the TriNetX US collaborative Network, a multicenter de-identified US database, and identified solid organ transplant recipients with and without SAL. The 1-year probability of developing Pneumocystis jirovecii pneumonia (PJP), toxoplasmosis, and nocardiosis was estimated and contrasted between the two study groups. The hazard ratio (HR) and the 95% confidence interval (CI) quantified the strength and direction of the association between SAL and these outcomes. RESULTS: When comparing 1571 solid organ transplant recipients with SAL to an equal number of matched controls, patients with SAL had a higher probability of developing nocardiosis (HR 3.85; 95% CI, 1.44-10.30; p = .004; corrected p = .04), and toxoplasmosis (HR, 1.87; 95% CI, 1.10-3.17; p = .019; corrected p = .19), but no difference in the risk of developing PJP (HR, 1.64; 95% CI, 0.68-3.95; p = .27). There was no mortality difference (HR, 1.31; 95% CI, 0.99-1.75; p = .061; corrected p = .6). SAL influenced antibiotic prescription with overutilization of dapsone, atovaquone, and pentamidine and underutilization of trimethoprim and sulfamethoxazole. CONCLUSION: SAL is associated with an increased risk of opportunistic infections following solid organ transplantation. Measures to evaluate and de-label sulfonamide allergy prior to transplantation or desensitizing shortly after transplantation are advisable.

Development and evaluation of immunological effects of a DNA vaccine encoding phosphoketolase family protein against Nocardia seriolae in hybrid snakehead.

Fish nocardiosis is a chronic disease mainly caused by Nocardia seriolae, which occurs in a variety of economically cultured freshwater and marine fish. Studies have shown that DNA vaccine is an effective treatment to protect fish from bacterial infection. In our previous experiment, an in vivo-induced gene of N. seriolae, encoding phosphoketolase (PK) family protein, was identified by in vivo-induced antigen technology. In the present study, the antigenic gene encoding PK family protein was analyzed by bioinformatics and further inserted into the eukaryotic expression vector pcDNA3.1-myc-his-A for DNA vaccine development. The immunological effects of pcDNA-PK DNA vaccine were assessed in hybrid snakehead (Channa maculata ♀ × Channa argus ♂), showing induction in several serum enzyme activity parameters (including LZM, SOD, ACP and AKP), increasing in specific-antibody IgM levels, as well as up-regulation in six immune-related genes (CD4, CD8α, TNFα, IL-1ß, MHCIα and MHCIIα). Moreover, an immune-protection with a relative survival rate was provided at 53.82 % following artificial challenge with N. seriolae in vaccinated fish in comparison to the control group. In summary, these results indicate that pcDNA-PK DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, which may be applied in aquaculture to control fish nocardiosis.

First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province.

Nocardiosis is an infectious disease caused by Nocardia spp., mainly affecting immunocompromised hosts. Nocardia infection is not common; especially Nocardia wallacei infection is even rarer. The patient, female, 61 years old, farmer, has been working in the field for a long time and has normal immune function. Her main clinical manifestation was persistent back pain. Chest-enhanced computed tomography showed pulmonary inflammation. Rare pathogen Nocardia wallacei was detected in alveolar lavage fluid using matrix-assisted laser destructive ionization time-of-flight mass spectrometry. She received treatment with linezolid and was discharged after her condition improved.

Nocardiosis in Solid Organ Transplant Recipients: 10-Year Single Center Experience and Review of Literature.

Solid organ transplant recipients (SOTRs) are at an increased risk of nocardiosis, a rare but life-threatening opportunistic infection. Universal PCP prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is used at our center, which is active in vitro against most species of the Nocardia genus and may have a role in preventing early infections. This is a single-center retrospective cohort study of nocardiosis in adult SOTRs at a large transplant center between January 2012 and June 2022, with comprehensive review of literature. Out of 6179 consecutive cases, 13 (0.2%) were diagnosed with nocardiosis. The patients were predominantly male (76.9%) and kidney transplant recipients (62%). Infection was diagnosed at median of 8.8 months (range, 3.7-98) after transplant. Patients were followed for a median of 457 days (range 8-3367). Overall mortality within one year after diagnosis was 46% (6/13), of which 17% (1/6) of deaths was attributable to Nocardia infection. No recurrence was reported. Nocardia infections were noted in a small proportion of our SOTRs and carried significant morbidity and mortality. TMP-SMX prophylaxis may be protective in some cases given low incidence of cases.

Comparison of Clinical Characteristics and Treatment Outcome Between Localized and Disseminated Nocardiosis in a Tertiary Hospital in China.

Background: In China, due to the large population, infections caused by Nocardia may not be as rare. Unfortunately, there is still inadequate knowledge of the clinical impact caused by Nocardia. This study aimed to compare the clinical characteristics and treatment of localized and disseminated nocardiosis. Methods: The clinical and microbiological data of patients diagnosed with nocardiosis in a tertiary hospital in Beijing from July 2011 to July 2021 were collected and retrospectively analyzed. Results: Among the 54 nocardiosis cases, 34 cases were in the localized infection group, while 20 cases in the disseminated infection group. The proportion of patients with chronic structural lung disease was higher in the localized group (P=0.010). In contrast, patients with disseminated infections were more prone to receive long-term glucocorticoids and/or immunosuppressants (P=0.027). Pulmonary nodules were prominent features of imaging changes in patients with disseminated infections (P=0.027) whereas bronchial dilatation was more common in patients with localized infections (P=0.025). In addition, the disseminated group had longer average hospitalization days relative to the localized group (P=0.016), but there was no significant difference in mortality between them (P=0.942). Conclusion: There were differences in the clinical profiles between patients with localized and disseminated nocardiosis in terms of clinical presentation, infection site, radiological features, treatment, and prognosis. These findings may provide references for the management and treatment of patients with nocardiosis.

[Cholestasis, delirium and pulmonary nocardiosis in a man with systemic lupus erythematosus of late onset]. / Colestasis, delirium y nocardiosis pulmonar en un varón con lupus eritematoso sistémico de inicio tardío.

A case is presented of a 64-year-old male patient who was admitted because of delirium, jaundice, a pattern of cholestasis in the liver profile and a right lung mass in the context of a constitutional syndrome and weight loss in the last eight months. The lung mass was punctured and the culture of the obtained material developed white colonies, identified by mass spectrometry (MALDI-TOF) as Nocardia cyriacigeorgica. Regarding the clinical diagnosis, it was considered as systemic lupus erythematosus (SLE), on the basis of fulfilling 8 criteria according to SLICC 2012 group, and 24 points according to EULAR/ACR 2019. The liver biopsy showed a mixt cellular infiltrate in portal spaces, with absence of interphase hepatitis and presence of peripheral ductular reaction. These findings were interpreted as liver compromise relate to SLE. Delirium was also considered as a neurological manifestation related to SLE on the basis of ruling out other causes. After being treated with antibiotics and documenting a reduction in the size of the lung mass he received cyclophosphamide in intravenous pulses, achieving normalization of his liver profile and his state of consciousness, and a progressively weight recovering. A year after he was in good health. The report of this case is justified because of the rare presenting form of late onset SLE, as well as the concomitant pulmonary nocardiosis in the absence of previous immunosuppressant treatment.

Se presenta el caso de un varón de 64 años que fue internado por delirium asociado a ictericia con patrón de colestasis en el hepatograma, y una masa en el pulmón derecho en el contexto de pérdida de peso y síndrome constitucional de 8 meses de evolución. Se realizó punción de la masa pulmonar cuyo cultivo desarrolló colonias blanquecinas identificadas como Nocardia cyriacigeorgica por espectrometría de masas (MALDI-TOF MS). Se llegó al diagnóstico de lupus eritematosos sistémico (LES) por presentar 8 de los criterios de acuerdo con el grupo SLICC 2012 y 24 puntos de acuerdo a los criterios EULAR/ACR 2019. La biopsia hepática mostró leve y variable infiltrado inflamatorio mixto en espacios porta, con ausencia de hepatitis de interfase y presencia de reacción ductular periférica. Se interpretaron estos hallazgos como vinculados a hepatopatía por LES. El delirium fue interpretado como afectación neurológica por LES en base al descarte de otras enfermedades. Recibió tratamiento antibiótico y tras constatarse reducción del tamaño de la masa pulmonar se administraron pulsos de ciclofosfamida intravenosa. Evolucionó favorablemente, con normalización del hepatograma y el estado de conciencia, y recuperación del peso en forma progresiva. Al año se lo encontró en buen estado de salud. Justifica el reporte del caso la rara forma de presentación del LES de comienzo tardío, así como la nocardiosis pulmonar concomitante sin tratamiento inmunosupresor previo.

Understanding the Risk Factors and Pathogenesis of Disseminated Nocardiosis in Immunocompromised Patients.

Nocardia is a genus of aerobic, Gram-positive, partially acid-fast, filamentous bacilli notoriously known for causing multisystemic infections in immunocompromised individuals. Notably, this genus of bacteria commonly infects the pleural and central nervous system, leading to pneumonia and brain abscesses, respectively. Our patient is a 71-year-old female who initially presented to the emergency department complaining of shortness of breath and altered mental status. Imaging revealed multiple enhancing brain lesions, a pleural effusion, and a paraspinal abscess, which upon aspiration and culture demonstrated Nocardia farcinica/kroppenstedtii. The patient underwent antibiotic treatment, including intravenous (IV) imipenem and trimethoprim/sulfamethoxazole (TMP-SMX), before being transitioned to oral TMP-SMX and amoxicillin/clavulanate. This case demonstrates the importance of diagnosing nocardiosis acutely and treating it appropriately.

Disseminated nocardiosis caused by Nocardia otitidiscaviarum-A case report.

In this article we report a case of disseminated nocardiosis caused by Nocardia otitidiscaviarum in an immunocompetent patient with chronic obstructive pulmonary disease (COPD) who complained of a cough, followed by skin and intracranial lesions. On metagenomic next-generation sequencing (mNGS) technology of respiratory samples (bronchoalveolar lavage fluid, BALF) Nocardia otitidiscaviarum was identified. The patient was treated with therapy combined with a low dose of TMP-SMX and imipenem cilastatin sodium and had a favorable outcome. The timely diagnosis of Nocardia with the help of mNGS technology and early rational treatment of TMP-SMX can help improve the prognosis.

Comparison of clinical outcomes of pulmonary nocardiosis between AIDS and non-AIDS patients.

BACKGROUND: Nocardia species can affect both immunocompetent and immunocompromised people. METHOD: This retrospective study, from 2009 to 2022, aims to compare the survival analyses of pulmonary nocardiosis in AIDS and non-AIDS patients in northeastern Thailand. RESULTS: A total of 215 culture-confirmed cases of pulmonary nocardiosis: 97 with AIDS and 118 without AIDS. The median CD4 count of AIDS patients was 11 cells/µL (range: 1-198), and 33% had concurrent opportunistic infections. 63.6% of 118 non-AIDS patients received immunosuppressive medications, 28.8% had comorbidities, and 7.6% had no coexisting conditions. Disseminated nocardiosis and pleural effusion were more prevalent among AIDS patients, whereas non-AIDS patients revealed more shock and respiratory failure. One hundred-fifty patients underwent brain imaging; 15 (10%) had brain abscesses. Patients with pulmonary nocardiosis have overall 30-day and 1-year mortality rates of 38.5% (95% CI: 32.3%, 45.4%) and 52.1% (95% CI: 45.6%, 58.9%), respectively. The Cox survival analysis showed that AIDS patients with disseminated nocardiosis had a 7.93-fold (95% CI: 2.61-24.02, p < 0.001) increased risk of death within 30 days compared to non-AIDS patients when considering variables such as age, Charlson comorbidity index, concurrent opportunistic infections, duration of illness, shock, respiratory failure, multi-lobar pneumonia, lung abscesses, and combination antibiotic therapy. While AIDS and pulmonary nocardiosis had a tendency to die within 30 days (2.09 (95% CI, 0.74-5.87, p = 0.162)). CONCLUSION: AIDS with pulmonary nocardiosis, particularly disseminated disease, is a serious opportunistic infection. Early diagnosis and empiric treatment with a multidrug regimen may be the most appropriate approach in a resource-limited setting.

Nocardia Infection in Patients With Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies: A Prospective Multicenter French Study.

Background: Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp, has recently been reported in patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, but insufficient data are available about disease presentation, outcomes, and occurrence of autoimmune pulmonary alveolar proteinosis (aPAP) in this population. Methods: We performed a prospective, multicenter, nationwide study in France and included patients with a Nocardia infection who had anti-GM-CSF autoantibodies. We describe their clinical, microbiological, and radiological characteristics, and their outcome at 1 year of follow-up. Results: Twenty patients (18 [90%] male) were included, with a median age of 69 (interquartile range, 44-75) years. The organs most frequently involved were the brain (14/20 [70%]) and the lung (12/20 [60%]). Half of the infections were disseminated (10/20 [50%]). Nocardia identification was predominantly made in abscess fluid (17/20 [85%]), among which 10 (59%) were brain abscesses. The 1-year all-cause mortality was 5% (1/20), and only 1 case of aPAP (1/20 [5%]) occurred during the follow-up period. Conclusions: Nocardiosis with anti-GM-CSF autoantibodies is associated with a low mortality rate despite a high incidence of brain involvement. Although the occurrence of aPAP was infrequent during the 1-year follow-up period, long-term clinical data are needed to fully understand the potential relationship between nocardiosis, anti-GM-CSF autoantibodies, and aPAP.

Fever of unknown origin revealing testicular nocardiosis: a case report and literature review.

BACKGROUND: Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis. CASE PRESENTATION: We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient's condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis. CONCLUSIONS: To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.

Weathering the storm: diagnosis and treatment of a life-threatening disseminated Nocardia otitidiscaviarum infection.

Nocardiosis demonstrates a temporal categorization that includes acute, subacute, and chronic stages alongside distinct typical localizations such as pulmonary, cutaneous, and disseminated forms. Disseminated nocardiosis, commonly caused by Nocardia asteroides, N. brasiliensis, and N. farcinica, continues to result in substantial morbidity and mortality. Herein, we report a life-threatening disseminated nocardiosis caused by Nocardia otitidiscaviarum in a patient with minimal change disease. This study emphasizes the difficulty in the diagnosis and treatment of unknown infections in clinical settings and highlights the important role played by laboratories in solving infectious diseases caused by rare pathogens.