Nocardia Research Articles

The species distribution and antimicrobial resistance profiles of Nocardia species in China: A systematic review and meta-analysis.

Nocardia species can cause local or disseminated infection. Prompt diagnosis and appropriate treatment of nocardiosis are required, because it can cause significant morbidity and mortality. Knowledge of local species distribution and susceptibility patterns is important to appropriate empiric therapy. However, knowledge on the epidemiology and antimicrobial susceptibility profiles of clinical Nocardia species remains limited in China. The data of isolation of Nocardia species were collected from databases such as Pubmed, Web of Science, Embase as well as Chinese databases (CNKI, Wanfang and VIP). Meta-analysis was performed using RevMan 5.3 software. Random effect models were used and tested with Cochran's Q and I2 statistics taking into account the possibility of heterogeneity between studies. In total, 791 Nocardia isolates were identified to 19 species levels among all the recruited studies. The most common species were N. farcinica (29.1%, 230/791), followed by N. cyriacigeorgica (25.3%, 200/791), N. brasiliensis (11.8%, 93/791) and N. otitidiscaviarum (7.8%, 62/791). N. farcinica and N. cyriacigeorgica are widely distributed, N. brasiliensis mainly prevalent in the Southern, N. otitidiscaviarum mainly distributed in the east coastal provinces of China. Totally, 70.4% (223/317) Nocardia were cultured from respiratory tract specimens, 16.4% (52/317) from extra-pulmonary specimens, and 13.3% (42/317) from disseminated infection. The proportion of susceptible isolates as follows: linezolid 99.5% (197/198), amikacin 96.0% (190/198), trimethoprim-sulfamethoxazole 92.9% (184/198), imipenem 64.7% (128/198). Susceptibility varied by species of Nocardia. N. farcinica and N. cyriacigeorgica are the most frequently isolated species, which are widely distributed in China. Pulmonary nocardiosis is the most common type of infection. Trimethoprim-sulfamethoxazole can still be the preferred agent for initial Nocardia infection therapy due to the low resistance rate, linezolid and amikacin could be an alternative to treat nocardiosis or a choice in a combination regimen.

Disseminated nocardiosis in a patient with alcoholic liver cirrhosis: a case report

BackgroundNocardia are Gram-positive, aerobic, filamentous bacteria that can cause localized or disseminated infections. Immunocompromised patients are at a higher risk of developing Nocardia infection and further dissemination of the disease. To date, limited data have documented the relationship between nocardiosis and alcoholic liver disease.Case presentationWe report the case of a 47-year-old man with a known history of alcoholic liver cirrhosis. The patient presented to our emergency department with redness, swelling in the left eye, and diminished bilateral vision. Fundus examination of the left eye was obscured, while that of the right eye was consistent with subretinal abscess. Therefore, endogenous endophthalmitis was suspected. Imaging revealed two ring-enhancing lesions in the brain, and multiple bilateral small cystic and cavitary lung lesions. Unfortunately, the left eye eventually eviscerated due to the rapid progression of the disease. Cultures from the left eye were positive for Nocardia farcinica. The patient was started on imipenem, trimethoprim/sulfamethoxazole, and amikacin based on culture sensitivity. The patient’s hospitalization course was complicated by his aggressive and advanced condition, which led to his death.ConclusionsAlthough the patient’s condition initially improved with the recommended antibiotic regimens, it led to death owing to the patient’s advanced condition. Early detection of nocardial infection in patients with typical or atypical immunosuppressive conditions may improve overall mortality and morbidity. Liver cirrhosis disrupts cell-mediated immunity and may increase the risk of Nocardia infection.

Outcomes of transplant recipients with pretransplant Nocardia colonization or infection.

Specific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied. We performed a retrospective study from three centers in Arizona, Florida, and Minnesota of patients with Nocardia infection or colonization who subsequently underwent solid organ or hematopoietic stem cell transplantation from November 2011 through April 2022. Outcomes included posttransplant Nocardia infection and mortality. Nine patients with pretransplant Nocardia were included. Two patients were deemed colonized with Nocardia, and the remaining seven had nocardiosis. These patients underwent bilateral lung (N = 5), heart (N = 1), heart-kidney (N = 1), liver-kidney (N = 1), and allogeneic stem cell transplantation (N = 1) at a median of 283 (interquartile range [IQR] 152-283) days after Nocardia isolation. Two (22.2%) patients had disseminated infection, and two were receiving active Nocardia treatment at the time of transplantation. One Nocardia isolate was resistant to trimethoprim-sulfamethoxazole (TMP-SMX) and all patients received TMP-SMX prophylaxis posttransplant, often for extended durations. No patients developed posttransplant nocardiosis during a median follow-up of 1.96 (IQR 0.90-6.33) years. Two patients died during follow-up, both without evidence of nocardiosis. This study did not identify any episodes of posttransplant nocardiosis among nine patients with pretransplant Nocardia isolation. As patients with the most severe infections may have been denied transplantation, further studies with larger sample sizes are needed to better analyze any impact of pretransplant Nocardia on posttransplant outcomes. However, among patients who receive posttransplant TMP-SMX prophylaxis, these data suggest pretransplant Nocardia isolation may not impart a heightened risk of posttransplant nocardiosis.

Bronchiectasis with Nocardia infection was designated as Lady Windermere-like syndrome: a retrospective study.

Bronchiectasis with Nocardia infection was designated as Lady Windermere-like syndrome: a retrospective study.

Disseminated Nocardia transvalensis complex and farcinica: First case in an immunocompetent

BackgroundNocardiae is an opportunistic infection mainly of the immunocompromised patient without sparing the immunocompetent subject or without any identified risk factors. They can be localized or disseminated. The extreme rarity of this infection often results in a deleterious diagnostic delay. Case presentationWe report a first case of community acquired pneumonia with asymptomatic disseminated brain abscess due to Nocardia transvalensis/wallacei and farcinica in an immunocompetent man. The patient fully recovered after receiving optimized antimicrobial therapy. ConclusionsThis case suggests that health care professionals should always evoke this diagnosis when confronted to atypical community-acquired pneumonia, even in immunocompetent patients.

Use of Interferon Gamma in Female Carriers of X-linked Chronic Granulomatous Disease

IntroductionChronic granulomatous disease (CGD) is characterized by increased frequency and severity of certain infections, autoimmune disease, and hyperinflammation. Heterozygous female carriers of X-linked CGD may experience similar symptoms. Guidance for management of female carriers is limited. We describe the use of interferon gamma (IFNγ) in X-linked CGD carriers. MethodsA multi-center retrospective chart review identified 4 carriers of X-linked CGD who received prophylaxis with IFNγ. Results of dihydrorhodamine (DHR) assay, infections and autoinflammatory features were documented and adverse events (AE) related to IFNγ were recorded. ResultsFour females (mean age 40 [range 0.5–71] years) received IFNγ (75–100 µg 3 times per week via subcutaneous injection) for a mean duration of 43 (range 16–63) months. Infections prior to the start of IFNγ included sepsis/bacteremia, pneumonia, skin and soft tissue infection, osteomyelitis, and gastroenteritis with CGD-associated pathogens including Serratia marscescens, Burkholderia cepacia, Nocardia spp, and methicillin-resistant Staphylococcus aureus (MRSA). Inflammatory complications (some in more than one subject) included dermatologic (pyoderma gangrenosum [n = 1], unspecified dermatitis [n = 2]), rheumatologic (arthritis [n = 1], Raynaud's syndrome [n = 1]), and gastrointestinal (inflammatory diarrhea [n = 1], Barrett's esophagus [n = 1]). Each carrier exhibited two populations of neutrophil oxidative burst. The populations expressing DHR were as follows: 0.08, 1, 3, and 10.8 +DHR%. Antibacterial prophylaxis was administered in all 4 subjects, and antifungal prophylaxis in 3 subjects. Pre-medications were not administered, and AE associated with IFNγ were mild or moderate in 3 of 4 subjects (one subject had no AE) and did not result in any treatment discontinuations. One patient discontinued prophylaxis with IFNγ after correction of CGD following hematopoietic stem cell transplant. The average length of follow-up since starting IFNγ was 38 months. While on IFNγ therapy, one patient developed atypical mycobacterial and cytomegalovirus pneumonia and MRSA chronic osteomyelitis thought related to poor compliance, while another developed Serratia olecranon abscess/. None developed autoimmune/inflammatory disease while on therapy. ConclusionsThis is the first report to our knowledge of IFNγ use for prophylaxis in carriers of X-linked CGD. IFNγ was well tolerated, and should be considered for prophylaxis in female carriers with very low neutrophil oxidative burst or frequent or severe CGD-associated infections.

CASE SERIES OF ISOLATED PULMONARY NOCARDIOSIS AMONG POST-COVID-19 INDIVIDUALS

Nocardia infections are rare in an immunocompetent and healthy individual. It is frequently diagnosed and reported very late during the disease. Here we present an interesting case series of isolated pulmonary nocardiosis among post COVID-19 patients. A 45-year-old male presented to general medicine OPD with breathlessness and cough with expectoration. The patient was a known case of diabetes. A Sputum sample was sent for culture, gram, and acid-fast stain, and the nasopharyngeal swab was sent for RT-PCR and turned out to be COVID-19 negative. Gram stain showed numerous pus cells with filamentous hyphae-like structures. Nocardiosis was strongly considered based on imaging morphology. A 65-year-old female presented to OPD with fever, respiratory distress, and expectorating cough for one month. The patient was a not known case of diabetes and hypertension. The patient was diagnosed with pneumonia and had a history of COVID-19. The microscopic examination of the sputum sample revealed no fungal elements. The Gram and Ziehl-Neelsen stain showed pus cells with filamentous bacilli and no acid-fast bacilli. A 50-year-old male presented to general medicine OPD with breathlessness and expectorating cough for four weeks. The patient was a not known case of diabetes and hypertension. The sputum sample was negative for ZN stain; the Gram stain showed numerous pus cells with filamentous hyphae-like structures. The modified acid-fast staining was done for sputum and BAL samples in all cases showed filamentous weak acid-fast bacilli resembling Nocardia species. The patient did well with cotrimoxazole and was discharged later. The differential diagnosis of nocardia should always be in mind in case of lung infections. All respiratory samples must also be screened for Nocardia. The early diagnosis and management of pulmonary nocardiosis decide the patient’s prognosis.

Dried Blood Spot Analyses for the Diagnosis of Anti-cytokine Autoantibodies

BackgroundHigh-titer neutralizing anti-cytokine autoantibodies have been shown to be involved in several acquired diseases, including pulmonary alveolar proteinosis, cryptococcal meningitis, and disseminated/extrapulmonary Nocardia infections (anti-GM-CSF autoantibodies), disseminated mycobacterial disease (anti-IFN-γ autoantibodies), and some cases of severe COVID-19 infection (anti-type 1 interferons). Currently, patient blood samples are shipped via courier and require temperaturecontrolled conditions for transfer. This method is expensive and requires patients to have access to medical personnel to draw the blood. However, the well-established technique of collecting blood on a paper card as a dried blood spot (DBS) for diagnosis offers a point of care alternative which can be performed with a simple finger prick. This method is less invasive, cheaper, and allows for easy transport of patient samples. Methods30 uL of whole blood from patients was blotted on filter paper and stored at 4C until use. The filter paper was hole punched and each punched spot was eluted with 150 uL of a 0.05% Tween PBS solution at room temperature overnight. The eluate was screened for anti-cytokine autoantibodies using a particle-based approach. Patient plasma was also screened in conjunction for comparison. ResultsWe confirmed the presence of autoantibodies in the DBS eluate from 4 previously diagnosed patients with anti-GM-CSF autoantibodies and 2 patients with anti-IFN-γ autoantibodies. Functional studies showed the DBS eluate from a patient with anti-GM-CSF autoantibodies was able to block GM-CSF-induced STAT-5 phosphorylation in normal PBMC. As a proof of concept and to increase the number of patients evaluated, we also confirmed the presence of anti-cytokine autoantibodies using dried plasma eluate from 9 patients with known anti-GM-CSF autoantibodies and 9 patients with anti-IFN-γ autoantibodies. Levels detected in DBS analyses were comparable to the levels found in plasma from the same patients not subjected to blotting and elution. Temperature studies showed that the autoantibodies were detected at similar levels when stored at 4C, 25C, and 40C for a week. ConclusionsThe diagnosis of pathogenic anti-cytokine autoantibodies should be considered in the context of unusual or adult-onset infections, and screening for this diagnosis can be performed with dried blood spot testing.

P028 Oh No-Cardiosis! A case of systemic Nocardia nova infection

Abstract Background/Aims Nocardiosis is a rare infectious disease caused by the aerobic bacteria genus Nocardia and can cause severe suppurative disease affecting virtually any organ. It tends to affect the immunocompromised, making rheumatology patients a particular risk group for this infection. It is not normal human flora and is found in soil, decaying vegetable matter and aquatic environments. It can become airborne and the most common means of entry is thought to be dust inhalation. Methods Our patient is a 75-year-old woman with giant cell arteritis (GCA) treated with prednisolone, SC methotrexate and tocilizumab (started 4 months before her acute illness). Symptoms began with a fall in the garden sustaining a nasty laceration to her leg and an injury to her back worsening some chronic lower back pain (X-rays did not show any fracture). Over the next 5 weeks due to a productive cough and sweats she was prescribed oral antibiotics with no improvement. She was then admitted to hospital due to an acute increase in the severity of her lower back pain alongside a change in character to a burning pain. Her presenting CRP was 32, likely due to having held tocilizumab due to a presumed chest infection. MRI showed a collection in the right erector spinae muscle extending from C7 to the iliac crest and another large collection in the right thigh. A mass in the left sub-mammary area led to a chest CT that showed a chest wall abscess alongside a spiculated lesion in the lung, and further nodular changes. Peripheral blood cultures were negative and eventually draining of the erector spinae abscess led to culture of Nocardiosis nova. Imipenam and Septrin were given as per sensitivities. Unfortunately, our patient has had a difficult clinical course. During her hospital stay she has had possible DRESS syndrome/Septrin-induced liver injury alongside drug induced neutropaenia and lymphopaenia and a possible stroke (this was thought less likely to represent CNS Nocardiosis). Results Her rheumatology management initially involved stopping her DMARDs however due to flares in symptoms her doses of prednisolone have been up and down. It has been difficult to separate symptoms that may be due to cervical spine collections and a possible CNS lesion from GCA symptoms. Conclusion This case demonstrates the need to thoroughly investigate immunosuppressed patients when they are not responding as expected to antibiotics or present with atypical symptoms. It also demonstrates the importance of obtaining a microbiological diagnosis. Cellular immunity is generally thought to be key in preventing Nocardia dissemination however in our patient’s case she was only taking 2.5mg prednisolone when admitted. This is one of only a few case reports of patients developing Nocardia infection whilst on tocilizumab. Disclosure R.J. Crowder: None. H. Mills: None. O. Savanovic-Abel: None. J. King: None. O. Moore: None. M. Perry: None. S. Hewagamage: None. M. Gunathilaka: None.

Molecular identification and antimicrobial resistance pattern of Nocardia isolated from 14 diseased dogs and cats.

Nocardia are ubiquitous, saprophytic and opportunistic bacteria. They cause a set of pyogenic clinical infections in animals and humans, particularly immunocompromised patients, mostly affecting the skin and respiratory tract, with refractoriness to conventional therapy. The most descriptions of nocardial infections in companion animals involve case reports, and there are scarce case series studies focused on canine and feline nocardiosis in which diagnosis has been based on molecular techniques. We investigated epidemiological aspects, clinical findings, in vitro susceptibility profile, and molecular identification of Nocardia using PCR-based method targeted 16S rRNA gene in twelve dogs and two cats. Among dogs were observed cutaneous lesions (8/12 = 67%), pneumonia (3/12 = 25%), and encephalitis (2/12 = 17%), whereas cats developed cutaneous lesions and osteomyelitis. Nocardia and canine morbillivirus coinfection was described in six dogs (6/12 = 50%). A high mortality rate (6/8 = 75%) was seen among dogs. Three dogs (3/4 = 75%) and one cat (1/2 = 50%) with systemic signs (pneumonia, encephalitis, osteomyelitis), and 83% (5/6) of dogs with a history of concomitant morbillivirus infection died. N. nova (5/12 = 42%), N. cyriacigeorgica (3/12 = 25%), N. farcinica (2/12 = 17%), N. veterana (1/12 = 8%), and N. asteroides (1/12 = 8%) species were identified in dogs, whereas N. africana and N. veterana in cats. Among the isolates from dogs, cefuroxime (12/12 = 100%), amikacin (10/12 = 83%), gentamycin (10/12 = 83%), and imipenem (10/12 = 83%) were the most effective antimicrobials, whereas cefuroxime, cephalexin, amoxicillin/clavulanic acid, imipenem, and gentamycin were efficient against isolates from cats. Multidrug resistance was observed in 36% (5/14) of isolates. We describe a variety of Nocardia species infecting dogs and cats, multidrug-resistant ones, and a high mortality rate, highlighting a poor prognosis of nocardiosis in companion animals, particularly among animals systemically compromised or coinfected by canine morbillivirus. Our study contributes to species identification, in vitro antimicrobial susceptibility profile, clinical-epidemiological aspects, and outcome of natural Nocardia-acquired infections in dogs and cats.

Analysis of clinical manifestations and imaging characteristics of in vivo confocal microscopy for Nocardia keratitis

Objective: To analyze the clinical manifestations and imaging characteristics of in vivo confocal microscopy (IVCM) for Nocardia keratitis. Methods: It was a retrospective case series study. Medical records of 16 consecutive patients (16 eyes) with Nocardia keratitis were collected from the Department of Ophthalmology at Beijing Tongren Hospital, Capital Medical University between 2018 and 2022. The group consisted of 11 males and 5 females. The inclusion criteria for the study were the presence of typical clinical manifestations of Nocardia keratitis and at least one positive pathogenic test (corneal scraping or microbial culture) indicating Nocardia infection. The medical history, clinical and microbiological examination data of the patients were analyzed, including risk factors, diagnosis time, clinical manifestations, diagnostic methods, strain isolation, cure time, and best corrected visual acuity before and after treatment. This study utilized techniques such as slit lamp microscopy, in vivo confocal microscopy (IVCM), scraping cytology, microbial culture, and mass spectrometry identification. Results: The main risk factors for Nocardia keratitis included plant or foreign body injuries (5 out of 16 cases), contact lens use (4 out of 16 cases), and surgery (2 out of 16 cases). The average time to diagnosis was (20.8±11.8) days, with the shortest time being 8 days and the longest being 60 days. The best corrected visual acuity was less than 0.05 in 7 patients, between 0.05 to 0.3 in 7 patients, and greater than or equal to 0.3 in 2 patients. The typical symptoms included superficial gray-white infiltration in a wreath-like pattern on the cornea, corneal ulcers with dry and gray-white necrotic tissue coverage, and in severe cases, corneal ulcer perforation. Nocardia corneal infection was identified in 12 out of 16 cases by scraping cytology, 9 out of 16 cases by mass spectrometry, and 8 out of 16 cases by both methods. IVCM showed the presence of fine and moderately reflective filamentous hyphae in the subepithelial and superficial stromal layer of the cornea, arranged in elongated, beaded, and branched structures. Infiltration of many hyper-reflective round inflammatory cells was also seen around the hyphae. Fourteen cases were treated with medication and 2 cases were treated with corneal transplantation. The average cure time was (37.5±25.2) days and there were no cases of recurrence during the follow-up period (all greater than 6 months). Conclusions: Nocardia keratitis is primarily characterized by dense, round, or wreath-like infiltration in the early stage, and by gray-white dry necrotic secretion and hypopyon on the surface of corneal ulcers in the middle and late stages. Fine, branched or beaded, and moderately reflective filamentous structures are the hallmark of the corneal lesion on the IVCM images.

CASE OF DISSEMINATED NOCARDIOSIS PRESENTING IN AN IMMUNOCOMPROMISED PATIENT

Patients with deciencies in cell mediated immunity are at high risk of 1 infection with opportunistic pathogens such as Nocardia . It is challenging to diagnose and can have multisystem manifestations. Failure to diagnose and appropriately treat can result in signicant 2,3 mortality . Nocardiosis is known as an opportunistic infection in immunocompromised hosts, but occasionally it has been reported in 4 immunocompetent patient . Nocardia infects the lungs, skin, central nervous system (CNS) or other organs presenting as localized or disseminated infections. Pulmonary nocardiosis is the main type of 5 nocardiosis. Nocardiosis involves the lung in 60–70% of cases . The data about worldwide incidence of Nocardia infection is limited and unclear. In An American study, Annual incidence of nocardiosis in 6 United State is about 500–1000 cases per year .Patients with the greatest susceptibility to this include those with solid organ transplant, hematopoietic stem cell transplant recipients, human immunodeciency virus (HIV) infected patients, patients taking corticosteroids for a long time or patients with ongoing malignant 7 processes .

Otomastoiditis Caused by Nocardia Farcinica: A Case Report and Literature Review.

Nocardia farcinica usually infects people with impaired immune status and usually manifests in the lungs. Otomastoiditis caused by Nocardia infection is extremely rare, with only 4 cases reported to date. This report describes a case of otomastoid N. farcinica infection in an immunocompetent patient. The case was a 10-month-old immunocompetent infant who presented with an approximately 3-month history of right ear discharge for which treatment with various antibiotics had not resulted in significant improvement. Multiple cultures of secretions and pathologic examination failed to identify the causative organism. The patient then underwent right mastoidectomy. Finally, metagenomic next-generation sequencing identified the pathogen to be N. farcinica. The patient was infection-free at the 6-month follow-up but had developed labyrinthitis ossificans. Otomastoid Nocardia infection has characteristic clinical features, namely, formation of a large amount of granulation tissue and coexistence of bone destruction and new bone formation. Traditionally, Nocardia is challenging to diagnose. Metagenomic next-generation sequencing of lesions is helpful. Complete local debridement and free drainage are key to treatment.

Pulmonary Nocardiosis Caused by <i>Nocardia otitidiscaviarum</i> and <i></i>Successfully Treated with Ciprofloxacin Based on Bacterial Identification and Antimicrobial Susceptibility Testing

We report a case of pulmonary nocardiosis caused by Nocardia otitidiscaviarum in a man diagnosed with idiopathic thrombocytopenia who was on oral prednisolone therapy. A chest PET/CT examination 13 days after the start of prednisolone therapy revealed a nodular shadow, and it progressively worsened and was accompanied by cavity formation over time. N. otitidiscaviarum was identified in bronchoalveolar lavage fluid by matrix assisted laser desorption ionization time of flight mass spectrometry. The isolate was eventually confirmed to be N. otitidiscaviarum by a 16S rRNA analysis. There was no evidence of disseminated disease. Combination therapy consisting of oral sulfamethoxazole-trimethoprim (SMX-TMP) and intravenous amikacin and imipenem was initiated, but the SMX-TMP was discontinued because of adverse effects. Antimicrobial susceptibility testing revealed that the isolate was non-susceptible to ceftriaxone, imipenem, minocycline, and clarithromycin. The patient declined long-term intravenous therapy. Oral ciprofloxacin was administered instead, and the pulmonary nocardiosis improved after 6 months of therapy. Bacterial identification and antimicrobial susceptibility testing influence the choice of treatment regimens for nocardia infections by N. otitidiscaviarum, which may be resistant to multiple antimicrobial agents.

Loop-mediated Isothermal Amplification Test for Rapid Identification of Clinical Nocardia Isolates

Background: Nocardia is a Gram-positive and partially acid-fast bacterium. The species are widely distributed in the environment and cause severe human infections. Nocardiosis is not easily identifiable due to the lack of pathognomonic clinical signs. Objectives: The present study was designed to develop and evaluate a simple and quick method based on a loop-mediated isothermal amplification (LAMP) assay for detecting Nocardia spp isolated from bronchoalveolar lavage (BAL) samples. Methods: In this cross-sectional study, 357 BAL samples were collected from two teaching hospitals. The polymerase chain reaction (PCR) was performed using a set of species-specific primers for the 16S rRNA gene. Kinyoun acid-fast staining and culture were done on the Sabouraud dextrose plate. The optimal LAMP reaction condition was set at 65°C for 45 min, with the recognition limit as 1 pg DNA/tube and 100 CFU/reaction. In addition to calcein and manganous ions, agarose gel electrophoresis was used to visualize the amplified LAMP products. Results: Out of 357 BAL samples, 0 (0.0%), 4 (1.1%), 9 (2.5%), and 10 (2.8%) Nocardia strains were identified by direct staining of partial acid-fast, streak culture plate, PCR, and LAMP methods, respectively. Conclusions: We developed a new LAMP technique for the recognition of Nocardia, which is fast, very precise, simple, and low-cost. According to our knowledge, this is the first report of the LAMP method to detect Nocardia in clinical samples.

Clinical characteristics, susceptibility profiles, and treatment of nocardiosis: a multicenter retrospective study in 2015-2021

ObjectivesThis study aimed to investigate the microbiological characteristics, antimicrobial resistance profiles, antibiotic choice, and outcomes of Nocardia infection in various centers over a 7-year period (from 2015 to 2021). MethodsWe retrospectively analyzed the medical records of all hospitalized patients diagnosed with Nocardia between 2015 and 2021. The isolates were identified to the species level through the sequencing of 16S ribosomal RNA or secA1 or ropB genes. The susceptibility profiles were determined using the broth microdilution method. ResultsOf the 130 nocardiosis cases, 99 (76.2%) were established as pulmonary infection, of which the most common underlying disease was chronic lung disease (40.4%, 40/99), including bronchiectasis, chronic obstructive pulmonary disease, and chronic bronchitis. Among 130 isolates, 12 species were identified, with the most common species being Nocardia cyriacigeorgica (37.7%) and Nocardia farcinica (20.8%). All Nocardia strains were susceptible to linezolid and amikacin, and the susceptibility rate of trimethoprim-sulfamethoxazole (TMP-SMX) was 97.7%. Of the 130 patients, 86 (66.2%) received TMP-SMX monotherapy or multidrug regimen. Furthermore, 92.3% patients who were treated achieved clinical improvement. ConclusionTMP-SMX was the treatment of choice for nocardiosis, and other combination drugs with TMP-SMX therapy yielded even better results.

Mycetoma by Nocardia blacklockiae: The first case

The present report describes a first case of N. blacklockiae as a causative agent of mycetoma of foot. It is an unusual Nocardia species and a member of the Nocardia transvalensis complex. N. blacklockiae has been isolated from cases of pulmonary nocardiosis earlier but this is a first case of mycetoma caused by this bacteria. The organism was isolated from the lesion. This case is reported to emphasise the importance of the species identification and its association with this rare disease.

Design of a multi-epitope vaccine against six Nocardia species based on reverse vaccinology combined with immunoinformatics.

Nocardia genus, a complex group of species classified to be aerobic actinomycete, can lead to severe concurrent infection as well as disseminated infection, typically in immunocompromised patients. With the expansion of the susceptible population, the incidence of Nocardia has been gradually growing, accompanied by increased resistance of the pathogen to existing therapeutics. However, there is no effective vaccine against this pathogen yet. In this study, a multi-epitope vaccine was designed against the Nocardia infection using reverse vaccinology combined with immunoinformatics approaches. First, the proteomes of 6 Nocardia subspecies Nocardia subspecies (Nocardia farcinica, Nocardia cyriacigeorgica, Nocardia abscessus, Nocardia otitidiscaviarum, Nocardia brasiliensis and Nocardia nova) were download NCBI (National Center for Biotechnology Information) database on May 1st, 2022 for the target proteins selection. The essential, virulent-associated or resistant-associated, surface-exposed, antigenic, non-toxic, and non-homologous with the human proteome proteins were selected for epitope identification. The shortlisted T-cell and B-cell epitopes were fused with appropriate adjuvants and linkers to construct vaccines. The physicochemical properties of the designed vaccine were predicted using multiple online servers. The Molecular docking and molecular dynamics (MD) simulation were performed to understand the binding pattern and binding stability between the vaccine candidate and Toll-like receptors (TLRs). The immunogenicity of the designed vaccines was evaluated via immune simulation. 3 proteins that are essential, virulent-associated or resistant-associated, surface-exposed, antigenic, non-toxic, and non-homologous with the human proteome were selected from 218 complete proteome sequences of the 6 Nocardia subspecies epitope identification. After screening, only 4 cytotoxic T lymphocyte (CTL) epitopes, 6 helper T lymphocyte (HTL) epitopes, and 8 B cell epitopes that were antigenic, non-allergenic, and non-toxic were included in the final vaccine construct. The results of molecular docking and MD simulation showed that the vaccine candidate has a strong affinity for TLR2 and TLR4 of the host and the vaccine-TLR complexes were dynamically stable in the natural environment. The results of the immune simulation indicated that the designed vaccine had the potential to induce strong protective immune responses in the host. The codon optimization and cloned analysis showed that the vaccine was available for mass production. The designed vaccine has the potential to stimulate long-lasting immunity in the host, but further studies are required to validate its safety and efficacy.

Lung and Cerebral Nocardiosis Caused by Nocardia elegans in a Lung Transplant Recipient: A Case Report and Literature Review.

Patients after lung transplantation are at risk for Nocardia infections. We herein report a case of lung and cerebral nocardiosis caused by Nocardia elegans, a rare species of Nocardia, in a lung transplant recipient. Antibiotic therapy, including sulfamethoxazole-trimethoprim (ST), and brain abscess drainage improved symptoms and imaging findings. A literature review of N. elegans infections showed that 12 of 14 cases (85.7%) were reported from East Asia, particularly Japan (9 cases, 64.2%). The lungs were the predominant site (12/14 cases, 85.7%), and most of the cases were susceptible to ST (9/10 cases, 90%).

Nocardia seriolae mediates liver granulomatous chronic inflammation in Micropterus salmoides through pyroptosis.

Granulomatous diseases caused by Nocardia seriously endanger the health of cultured fish. These bacteria are widely distributed, but prevention and treatment methods are very limited. Chronic granulomatous inflammation is an important pathological feature of Nocardia infection. However, the molecular mechanisms of granuloma formation and chronic inflammation are still unclear. Constructing a granuloma infection model of Nocardia is the key to exploring the pathogenesis of the disease. In this study, we established a granuloma model in the liver of largemouth bass (Micropterus salmoides) and assessed the infection process of Nocardia seriolae at different concentrations by analysing relevant pathological features. By measuring the expression of pro-inflammatory cytokines, transcription factors and a pyroptosis-related protein, we revealed the close relationship between pyroptosis and chronic inflammation of granulomas. We further analysed the immunofluorescence results and the expression of pyroptosis-related protein of macrophage infected by N. seriolae and found that N. seriolae infection induced macrophage pyroptosis in vitro. These results were proved by flow cytometry analysis of infection experiment in vivo. Our results indicated that the pyroptosis effect may be the key to inducing chronic inflammation in the fish liver and further mediating granuloma formation. In this study, we explored the molecular mechanism underlying chronic inflammation of granulomas and developed research ideas for understanding the occurrence and development of granulomatous diseases in fish.