Clinical characteristics of hospitalized patients with Nocardia genus detection by metagenomic next generation sequencing in a tertiary hospital from southern China.

OBJECTIVE: As an opportunistic pathogen, Nocardia often occurring in the immunocompromised hosts. As the unspecifc clinical presentation and low identification rate of the culture dependent methods, Nocardia infection may be under-diagnosis. Recent study have reported physicians could benefit from metagenomic next-generation sequencing (mNGS) in Nocardia diagnosis. Herein, we present patients with a positive detection of nocardiosis in mNGS, aiming to provide useful information for an differential diagnosis and patients management. METHODS: A total of 3756 samples detected for mNGS from March 2019 to April 2022 at the Fifth Affifiliated Hospital of Sun Yat-sen University, were screened. Clinical records, laboratory finding, CT images and mNGS results were reviewed for 19 patients who were positive for Nocardia genus. RESULTS: Samples from low respiratory tract obtained by bronchoscope took the major part of the positive (15/19). 12 of 19 cases were diagnosis as Nocardiosis Disease (ND) and over half of the ND individuals (7/12) were geriatric. Nearly all of them (10/12) were immunocompetent and 2 patients in ND group were impressively asymptomatic. Cough was the most common symptom. Nocardia cyriacigeorgica (4/12) was more frequently occurring in ND, followed by Nocardia abscessus (3/12). There are 3 individuals detected more than one kind of Nocardia species (Supplementary table 1). Except one with renal failure and one allergic to sulfamethoxazole, all of them received co-sulfonamide treatment and relieved eventually. CONCLUSION: Our study deciphered the clinical features of patients with positive nocardiosis detected by mNGS. Greater attention should be paid to the ND that occurred in the immunocompetent host and the geriatric. Due to the difficulties in establishing diagnosis of Nocardiosis disease, mNGS should play a much more essential role for a better assessment in those intractable cases. Co-sulfonamide treatment should still be the first choice of Nocardiosis disease.

Disseminated Nocardia infection with a lesion occupying the intracranial space complicated with coma: a case report.

BACKGROUND: Disseminated Nocardia infection is a disease that is easily overlooked in patients with lesions occupying the intracranial space complicated with coma. Early diagnosis and treatment are crucial. CASE PRESENTATION: A 65-year-old man was admitted to the First Affiliated Hospital of Zhejiang University in October 2018 with weakness in the right limbs for 3 days and altered consciousness for 1 day. Five months earlier, he had been diagnosed with membranous kidney disease and had received cyclophosphamide and prednisone. At admission, the white blood cell count was 1.37 × 1010/L (with 86.4% neutrophils), and C-reactive protein was 115.60 mg/L. Imaging examinations revealed a lesion occupying the intracranial space, lung infection, and multiple abscesses in the rhomboid muscle. The abscesses were drained. Pus culture confirmed Nocardia cyriacigeorgica infection. With antibiotics and vacuum-sealed drainage of the back wound, the patient improved and was discharged from the hospital. CONCLUSIONS: This case report shows that infection should be considered during the differential diagnosis of lesions in the intracranial space, especially in patients receiving immunosuppressive treatment. In patients with disseminated N. cyriacigeorgica infection, combination antibiotic therapy and surgical drainage of localised abscesses can be effective.

An Unusual Presentation From a Sporadic Partially Acid-Fast Aerobic Actinomycete Resistant to Common Antibiotics.

Nocardia causes rare opportunistic infections, that can be challenging to diagnose because of atypical features on conventional microbiological identification techniques. Immunosuppressed patients are more susceptible to infections from Nocardia and are associated with multi-organ involvement. We report a case of a 63-year-old male who developed peritonitis from Nocardia farcinica that rarely causes infections in humans. The nonspecific symptoms, negative blood cultures, and slow growth can make diagnosis difficult. Despite aggressive therapy, the virulence and inherent resistance to the antibiotics can result in high mortality from Nocardia farcinica infections.

Management of Nocardia Interface Keratitis After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To report the clinical course and management of graft-host interface Nocardia keratitis after Descemet membrane endothelial keratoplasty (DMEK). METHODS: A 70-year-old man presented with a corneal epithelial defect, stromal edema, graft infiltrate, and graft-host interface infection 5 months after an uneventful DMEK performed for bullous keratopathy in the left eye. Corneal scrapings from the margin of epithelial defect showed gram-positive bacillus, and the organism was identified as Nocardia asteroides. RESULTS: Intensive and appropriate topical and systemic antibiotic therapy resulted in complete resolution of infection. Three months later, the patient underwent a repeat DMEK, which resulted in clearing of corneal edema and improvement in visual acuity. CONCLUSIONS: Nocardia interface keratitis is a rare entity, which can occur after DMEK. Proper clinical evaluation and microbiological workup helped us in accurate diagnosis and management. Repeat DMEK after complete resolution of the infection resulted in good outcomes regarding corneal clarity and vision improvement.

Pulmonary nocardiosis mimicking small cell lung cancer in ectopic ACTH syndrome associated with transformation of olfactory neuroblastoma: a case report.

BACKGROUND: Pulmonary nocardiosis frequently develops as an opportunistic infection in cell-mediated immunosuppressive patients, and sometimes requires differentiation from pulmonary malignancy. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a neoplastic disorder which leads to impaired cell-mediated immunity, and is commonly associated with small cell lung cancer (SCLC). Because pulmonary infection and causative malignancy can appear as pulmonary lesions with EAS, differentiation of these diseases remains a critical issue for physicians. CASE PRESENTATION: A 52-year-old woman with progressive lower limb paralysis and general fatigue was referred to us. She had been diagnosed with olfactory neuroblastoma (ONB) and treated with surgery and radiation therapy 10 years before the referral and had required stereotactic radiosurgery and chemotherapy 4 years later for a relapse of the ONB. On referral, she presented with Cushing's syndrome with elevated cortisol and ACTH levels. Potassium supplement improved her symptoms; however, a month later, she was urgently hospitalized due to acute pleuritic chest pain on inspiration. Chest computed tomography revealed left lower lobular consolidations and a contralateral nodule in the right middle lobe. The clinical history and laboratory work-up suggested that her Cushing's syndrome had most likely arisen from EAS. Additionally, the lungs were suspected as the ACTH source due to high levels of progastrin-releasing peptide and progressive pulmonary consolidation with a contralateral nodule, suggesting SCLC. However, histological examination from bronchoscopy revealed no evidence of malignancy, and Nocardia cyriacigeorgica was isolated from bronchoalveolar lavage fluid. Sulfamethoxazole/trimethoprim improved her pulmonary lesions. Somatostatin receptor scintigraphy revealed strong tracer uptake in the ONB lesions, indicating that the origin of the EAS was the olfactory tumor. However, histological examination of ONB specimens resected 10 years earlier showed no intracytoplasmic immunopositivity for ACTH. CONCLUSIONS: We highlight a rare case of pulmonary nocardiosis, which was associated with EAS mimicking SCLC, and was related to ONB transformation. Nocardiosis has to be considered even though anamnestic, clinical, and radiological aspects suggest the presence of metastasis. Additionally, physicians should carefully monitor patients with ONB for the development of Cushing's symptoms because the tumor can transform into an ACTH-producing form, even after long-term follow-up.

Pulmonary co-infection with nocardia species and nontuberculous mycobacteria mimicking miliary tuberculosis in a patient with Crohn's disease under combined immunosuppressive therapy.

Nocardiosis is a rare infection caused by ubiquitous soil-born, acid-resistant, Gram-positive bacteria that can be life-threatening in immunocompromised patients. Originally usually diagnosed in HIV-positive patients, only few cases have been reported in patients on immunosuppressive therapy for inflammatory bowel disease or rheumatologic disorders. We present a case of a 32-year-old man who was treated with infliximab, prednisolone, and azathioprine for severe terminal ileitis. Although the clinical status improved under triple immunosuppressive therapy, weight loss, weakness, and fatigue persisted. Laboratory studies revealed iron deficiency anemia, hypalbuminemia and raised inflammatory markers. Chest computed tomography scan showed multiple pulmonary nodules and a large cavity in the left upper lobe (segment 3a). Empiric tuberculostatic therapy was introduced for suspected miliary tuberculosis but stopped for lack of clinical improvement and negative tuberculosis tests (interferon-gamma release assay, microscopy, polymerase chain reaction). Finally, the diagnosis of pulmonary nocardiosis with concomitant pulmonary Mycobacterium avium infection was confirmed microbiologically, and the patient was treated with high-dose co-trimoxazole, clarithromycin, ethambutol, and rifampicin for 12 months.This case report underlines the increased risk of severe and rare infections like nocardiosis with combination immunosuppressive therapy and the necessity for thorough diagnostic screening for opportunistic infection. Although long-term antibiotic treatment for nocardiosis is mandatory, the optimal timing to restart immunosuppressive therapy remains ambiguous.

Disseminated actinomycetoma due to Nocardia wallacei.

BACKGROUND: Actinomycetoma caused by Nocardia usually responds well to antibiotics. Emerging species of Nocardia, such as N. wallacei, can be a therapeutic challenge. AIMS: Confirm the therapeutic effectivity of linezolid in multidrug resistant Nocardia Wallacei actinomycetoma. MATERIALS AND METHODS: We evaluated the medical management of an 18-year-old man with multidrug resistant actinomycetoma of the left leg caused by N. transvalensis complex treated 17 years ago with linezolid 1200 mg a day. This bacteria was recently reclassified as Nocardia Wallacei by specific molecular biology technique. RESULTS: The infection was cured after 3 months of treatment; the patient remained asymptomatic for the past 17 years. No adverse effects were found. DISCUSSION: Frequently, strains of N. transvalensis complex have aminoglycoside resistance; in this case, we highlight the effectiveness of linezolid for the successful medical management of multidrug resistant actinomycetoma. CONCLUSION: Linezolid can be an alternative for the treatment of multidrug resistant Nocardia Wallacei.

A case of atypical nocardia asteroides sclerouveitis resistant to fourth-generation fluoroquinolones / Um caso atípico de esclero-uveíte por Nocardia Asteroides resistente a fluorquinolona de quarta-geração

ABSTRACT We describe an unusual case of Nocardia spp scleritis in a health girl resistant to topical fourth-generation fluoroquinolones. Clinically, there was only partial response of the scleritis to initial therapy. Treatment was changed to meropenem intravenously and topical amikacin. Following several weeks of antibiotic treatment, the patient's infection resolved but her vision was reduced to no light perception. Nocardia asteroides must be considered as a possible agent in cases of necrotizing scleritis in patients without a clear source. Antibiotic sensitivity testing has a definitive role in view of the resistance to these new medications.

RESUMO Nós descrevemos um raro caso de esclerite por Nocardia spp em uma criança sadia resistente a utilização tópica de fluorquinolona de quarta-geração. Clinicamente, a paciente apresentou apenas uma resposta parcial do quadro de esclerite a terapêutica inicial. O tratamento foi então modificado para meropenem intravenoso e amicacina tópica. Após várias semanas de tratamento com antibiótico, o quadro infeccioso regrediu porém a visao da pacientes evoluiu para perda da percepção luminosa. Em casos de esclerite necrotizante em pacientes sem fatores de risco aparente é necessário considerer a Nocardia Asteroides como possível agente causador. Os testes de sensibilidade medicamentosa apresentam importância significativa em virtude do aparecimento de resistência aos novos medicamentos.

Impact of immune status on the clinical characteristics and treatment outcomes of nocardiosis.

Nocardiosis occurs in both immunocompromised and immunocompetent patients. We aimed to assess how its characteristics differ depending on patients' immune status. Of a total of 54 patients with culture-proven nocardiosis diagnosed over 13 years, 18 (33%) were immunocompetent. Half of immunocompetent patients had chronic lung disease and were not receiving systemic corticosteroid. There were no significant differences in clinical, radiographic, and microbiologic characteristics, and treatment outcomes according to immune status, except that pulmonary cavitation (47% vs. 8%) and coexisting infections (17% vs. 0%) were more frequent in immunocompromised hosts. Nocardia farcinica, the most commonly identified isolates at the species level (51%), was highly susceptible to trimethoprim-sulfamethoxazole (100%) and highly resistant to ceftriaxone (94%). Nocardiosis should be considered in differential diagnosis of pneumonia, brain abscess, or soft tissue infection that does not respond to conventional antibiotic therapy such as ceftriaxone, regardless of whether the patient is immunocompromised or not.

Experience with linezolid for the treatment of nocardiosis in organ transplant recipients.

OBJECTIVES: Combination therapy with amikacin is recommended for treatment of nocardiosis in severely ill solid organ transplant recipients (SOT), but its use is complicated by nephrotoxicity. Linezolid has shown promise as an alternative in the empiric therapy of nocardiosis, but little is known about its effectiveness and safety in this setting. We describe the experience with linezolid for nocardiosis in SOT. METHODS: Retrospective review of cases of nocardiosis in SOT at a large center from 2006 to 2012. RESULTS: Nineteen cases were identified, 15/19 in lung transplant recipients. Median creatinine clearance at diagnosis was 56 ml/min. Eighteen patients were treated: 17/18 (94%) received trimethoprim/sulfamethoxazole and 15/18 (83%) received linezolid. Median duration of linezolid treatment was 21 days and it was discontinued in 10/15 (67%) due to side effects. Thrombocytopenia and anemia occurred in 14/15 (93%) and 9/15 (60%) of patients on linezolid, respectively, and were not different from patients not on linezolid. Cure was observed in 16/19 (84%), 33% of deaths were related to nocardiosis. CONCLUSIONS: Linezolid was acceptable as initial empiric therapy for nocardiosis. Myelosuppression was a limiting factor, but not exclusive to patients on linezolid and could have been aggravated by concomitant use of other myelosuppressive drugs.

Disseminated Nocardiosis caused by Nocardia concava with acute respiratory failure and central nervous system involvement treated with linezolid.

Nocardia concava was identified as a new species in 2005; however, the clinical manifestations of Nocardia concava infection have yet to be clarified. We herein present the case of an immunosuppressed patient who developed disseminated nocardiosis caused by N. concava with multiple abscesses in the lungs, cutis, subcutaneous tissue, skeletal muscles and kidneys accompanied by central nervous system involvement, including meningitis and ventriculitis. The patient was cured with appropriate treatment including linezolid after testing for susceptibility. Linezolid should be considered as an alternative agent for treating disseminated nocardiosis because of its effective distribution to multiple sites.

[Bacterial pneumonia in HIV-infected patients (excluding mycobacterial infection)]. / Pneumonies bactériennes chez les personnes infectées par le VIH (hors mycobactéries).

Respiratory infections are the most common complications in HIV patients, regardless of the degree of immunosuppression. Even though antiretroviral therapy has a protective effect on the risk of bacterial pneumonia, this still remains high (including those with CD(4)>500/mm(3)). The most frequently isolated bacteria are Streptococcus pneumoniae and Haemophilus influenzae. The clinical and radiological presentations of lower respiratory tract infections in HIV patients are quite variable. The clinical presentation is more severe and the radiological presentation is more atypical if the immunosuppression is severe. The first-line antibiotic therapy is an injectable third-generation cephalosporin (ceftriaxone or cefotaxime) or co-amoxiclav. Pneumococcal vaccination (as well as influenza vaccine) is recommended. Although rare, Nocardia spp. and Rhodococcus equi seem more common among AIDS patients.

Nocardia keratitis: clinical course and effect of corticosteroids.

PURPOSE: To compare the clinical course of Nocardia species keratitis with keratitis resulting from other bacterial organisms and to assess the effect of corticosteroids as adjunctive therapy using data collected from the Steroids for Corneal Ulcers Trial. DESIGN: Subgroup analysis of a randomized controlled trial. METHODS: setting: Multicenter randomized controlled trial. study population: Five hundred patients with bacterial keratitis randomized 1:1 to topical corticosteroid or placebo who had received at least 48 hours of topical moxifloxacin. intervention/observation procedure: Topical prednisolone phosphate 1% or placebo and clinical course of Nocardia keratitis. main outcome measures: Best spectacle-corrected visual acuity and infiltrate or scar size at 3 months from enrollment. RESULTS: Of 500 patients enrolled in the trial, 55 (11%) had a Nocardia corneal ulcer. Patients with Nocardia ulcers had better presentation visual acuity compared with non-Nocardia ulcers (median Snellen visual acuity, 20/45, compared with 20/145; P < .001) and comparable 3-month visual acuity (median, 20/25, vs 20/40; P = .25). Nocardia ulcers had approximately 2 lines less of improvement in visual acuity compared with non-Nocardia ulcers (0.21 logarithm of the minimal angle of resolution; 95% confidence interval, 0.09 to 0.33 logarithm of the minimal angle of resolution; P = .001). This difference may reflect the better starting visual acuity in patients with Nocardia ulcers. In Nocardia ulcers, corticosteroids were associated with an average 0.4-mm increase in 3-month infiltrate or scar size (95% confidence interval, 0.03 to 0.77 mm; P = .03). CONCLUSIONS: Nocardia ulcers responded well to treatment. They showed less overall improvement in visual acuity than non-Nocardia ulcers, but had better presentation acuity. Corticosteroids may be associated with worse outcomes.

Clinical and microbiological characteristics of infections caused by various Nocardia species in Taiwan: a multicenter study from 1998 to 2010.

This multicenter study in Taiwan investigated the clinical presentations of various Nocardia species infections based on 16S rRNA sequence analysis. Patients with nocardiosis in four large medical centers from 1998 to 2010 were included. A total of 100 preserved nonduplicate isolates causing human infection were identified as Nocardia species. Sequencing analysis of 16S rRNA confirmed that 35 of 36 N. asteroides isolates identified by conventional tests were non-asteroides Nocardia species, and that two of 50 N. brasiliensis isolates had also been initially misidentified. N. brasiliensis (50%) was the most common pathogen, followed by N. cyriacigeorgica (18%). In addition, several rare pathogens were identified, including N. asiatica, N. rhamnosiphila, N. abscessus, N. transvalensis, N. elegans, and N. carnea. Primary cutaneous infection was the most common presentation, noted in 55 (55%) patients, while pulmonary infection presented in 26 (26%) patients. The crude mortality rate was 6.7% (6/89), and was lowest for primary cutaneous infection (2.2%) and highest for disseminated disease and pulmonary infection (16.7%). In conclusion, N. brasiliensis and N. cyriacigeorgica were the most common pathogens causing nocardiosis in Taiwan. Molecular methods for identifying Nocardia to the species level are mandatory for better understanding the epidemiology and clinical characteristics of patients with nocardiosis.

[Pulmonary nocardiosis with trimethoprime/sulphamethoxazole-resistant Nocardia paucivorans in a patient with no signs of immunosuppression]. / Pulmonale Nokardiose mit Trimethoprim/Sulfamethoxazol resistenter Nocardia paucivorans bei einem Patienten ohne Hinweise auf Immunsuppression.

This is so far the first published case report of a Nocardia paucivorans infection in an immunocompetent patient. A 54-year-old farmer was hospitalised with a history of coughing and fever for a period of five months. There was no indicator of either primary of secondary immunodeficiency in the prior medical history. A chest X-ray showed pneumonic infiltrates in the right middle und lower lobes, which progressed despite of antibiotic therapy with macrolides. A transbronchial biopsy revealed unspecific granulomatous inflammation of soft tissues. N. paucivorans - grew in cultures of sputum, bronchoalveolar lavage, and transbronchial biopsy. Oral antibiotic therapy was started with trimethoprime-sulphamethoxazole (TMP/SMX) and amoxicillin plus clavulanic acid. Susceptibility testing revealed high level resistance to TMP/SMX, which was consequently replaced by ciprofloxacin. Six months later, infiltrates had completely resolved and the patient did not report any residual clinical symptoms. The present case showed once again that nocardiosis is not limited to patients with immunodeficiencies. However, conservative combination therapy with oral antibiotics seems to be sufficiently effective for nocardiosis in the immunocompetent patient. For cases of suspected nocardiosis, a step-wise, risk-based diagnostic and therapeutic procedure is proposed.

Nocardiosis pulmonar como causa de reagudizaciones en un paciente EPOC / Pulmonary nocardiosis due to reagudizations in a COPD patient

La infección pulmonar por Nocardia sp. es una enfermedad poco frecuente que afecta fundamentalmente a pacientes inmunodeprimidos, aunque también puede hacerlo a pacientes inmunocompetentes. Su diagnóstico se basa en el aislamiento en esputo de Nocardia sp. siendo la clínica y la radiología inespecíficas. El tratamiento se realiza con trimetropin (TMP) sulfametoxazol (SMX), aunque ya se han encontrado casos de resistencia. La duración del tratamiento sigue siendo desconocida recomendándose durante 6 semanas-12 meses. Presentamos el caso de un varón de 81 años con antecedentes de EPOC en tratamiento con corticosteroides de forma crónica que ingresa en nuestro servicio por episodios febriles recidivantes en los tres meses previos al ingreso junto con pérdida de peso e infiltrados densos en Rx de tórax de nueva aparición con cultivo de esputo positivo para Nocardia sp. Y buena evolución tras el inicio de tratamiento con TMP-SMX con desaparición de la fiebre y de los infiltrados

Pulmonary infection due to Nocardia sp. is an infrequent disease that affects principally to immunodefficient patients although it can be also seen in patients with normal immunity. Diagnosis is based in isolation of micro-organism in respiratory samples while clinical presentation and radiology are non specific. Treatment is made with trimethropim-sulfametoxazole (TMP/SMX), though resistance has developed in some patients. The recommended length of treatment is 6 weeks to 12 months depending on the immunitaly status. We present the case of a male patient of 81 years old affected with COPD and treated with glucocorticoids in a chronic basis, who was admitted because relapsing fever episodes during 3 months before, weight loss and new hard pulmonary infiltrates with Nocardia sp. cultured sputum, and evolution to clinical, radiological and microbiologic resolution with TMP/SMX treatment

[Nocardia cyriacigeorgici: First report of invasive human infection]. / Nocardia cyriacigeorgici: Erstbeschreibung als invasive Infektion.

BACKGROUND: Diagnostic laboratories increasingly offer bacterial identification to the species level. The 17 nocardia species known to date differ in their clinical presentation, antibiotic resistance patterns and geographic distribution. The discovery of a new species with pathogenicity for humans calls for the characterization of its clinical and epidemiological properties. PATIENTS AND METHODS: Nocardia isolated from multifocal brain abscesses of an immunocompromised patient were further identified by the analysis of their cellular fatty acids and sequencing of the 16S ribosomal DNA. Quantitative antibiotic resistance testing was performed with E-tests. RESULTS: The 16S ribosomal DNA analysis showed a 99 % homology to Nocardia cyriacigeorgici. This is the first report of this species as an invasive human pathogen. N. cyriacigeorgici was found susceptible for meropenem, amikacin, ceftriaxon and cotrimoxazole. The combination of surgical drainage and antibiotic treatment for 13 months was curative. CONCLUSIONS: N. cyriacigeorgici has the potential to cause invasive infections at least in immunocompromised patients. Comparing clinical and in vitro characteristics with N. asteroides, the main causative agent of nocardial infections in Europe, we found no clinically relevant differences.