Nocardia Otitidiscaviarum Research Articles

Recurrent pulmonary nocardiosis due to Nocardia Otitidiscaviarum in a patient with isolated CD4 lymphocytopenia: a case report

BackgroundIdiopathic CD4 lymphocytopenia (ICL) is an underdiagnosed immunodeficiency syndrome characterised by persistent low CD4 counts in the absence of HIV and other causes of lymphocytopenia. ICL patients are susceptible to opportunistic infections, with human papillomavirus, cryptococcal, and tuberculosis being the most common infections reported. Nocardiosis is rarely reported in patient with ICL.Case PresentationWe herein discuss a 46-year-old female presented with complaints of weight loss, low grade fever and cough with expectoration from last four months. The patient was diagnosed with pulmonary nocardiosis and aspergillosis co-infection four years back; in addition she also had ICL. Subsequently, the patient was lost in follow-up and readmitted four years later. Bronchoalveolar lavage sample shows the presence of acid-fast bacilli in modified gram stain, which later identified as Nocardia otitidiscaviarum by metagenomic next-generation sequencing. Her CD4 counts were still found low (298 cells/mm3). After an initial improvement with trimethoprim-sulfamethoxazole (TMP-SMX), she was commenced on indefinite secondary prophylaxis.ConclusionsNocardiosis without usual risk factors should be evaluated for ICL. This case emphasize the importance of periodic follow-up with CD4 count monitoring and secondary prophylaxis therapy to prevent recurrence or the emergence of new infections in ICL.Clinical trial numberNot applicable.

Nucleic acid-functionalized nanoscale porous carbon-based electrochemical genosensor for detection of Nocardia spp. in real samples

In this study, a porous carbon derived from a metal-organic framework (PCMOF) as a target-responsive material functionalized with Nocardia particular antisense ssDNA oligonucleotide (ssDNA capture probe) was developed to construct a simple genosensor based on biogatekeeper strategy for sensitive detection of Nocardia in complex biological samples. The PCMOF with suitable pores volume was used to encapsulate electroactive dye methylene blue (MB), and the ssDNA capture probe was used as a gatekeeper to cap PCMOF. Without the presence of Nocardia target, the electrochemical signal of trapped MB was high. Upon adding the target, the hybridization of ssDNA capture probe and target led to the formation of a probe-target double-stranded (dsDNA) structure which dissociated from PCMOF and allowed MB molecules to be released. Therefore, the electrochemical signal of the genosensor decreased. The detection of Nocardia was accomplished by observing variations in the MB peak current intensity in a dose-dependent manner. For this genosensor, a linearity range from 10−18 to 10−7 M for synthetic ssDNA target and 10 to 108 copies/mL for two standard isolates, Nocardia farcinica PTCC 1309 and Nocardia brasiliensis ATCC 19296 as well as for clinical isolates (identified as Nocardia otitidiscaviarum) was observed, respectively. The detection limit (DL) values were 0.54 aM for synthetic ssDNA target and 5, 7, and 4 copies/mL for N. farcinica, N. brasiliensis, and N. otitidiscaviarum, respectively. This genosensor was also characterized by good specificity, reproducibility, and stability.

Clinical utility of metagenomic next-generation sequencing in pathogen detection for lower respiratory tract infections and impact on clinical outcomes in southernmost China.

Today, metagenomic next-generation sequencing (mNGS) has emerged as a diagnostic tool for infections. However, since Hainan has a complicated pathogen spectrum, the diagnostic value and impact on patient outcomes of mNGS in Hainan are to be explored. From April 2020 to October 2021, 266 suspected lower respiratory tract infections (LRTIs) patients in Hainan were enrolled, and specimens were collected before antibiotic treatment. Bronchoalveolar lavage fluid (BALF) samples were subjected to mNGS and culture to compare the diagnostic performance. Other conventional microbiological tests (CMT) were also performed. Patients' treatments and clinical outcomes were recorded, and the antibiotic resistance genes (ARGs) were detected via mNGS workflow. The positive rate of mNGS outperformed that of culture (87.55% vs. 39.30%, p<0.001) and CMT (87.12% vs. 52.65%, p<0.001). Specifically, mNGS detected more P. aeruginosa (12.03% vs 9.02%, p<0.05), H. influenzae (9.77% vs 2.26%, p<0.001), Aspergillus fumigatus (3.00% vs 0.75%, p<0.05), Candida albicans (26.32% vs 7.52%, p<0.001) and uncommon pathogens. It also demonstrated great diagnostic advantages in Mycobacterium tuberculosis with 80% sensitivity and 97.4% specificity. Over half of the patients (147, 55.26%) had modified empirical treatment according to mNGS results and 89.12% of them responded well. For three deaths with modified treatment, multiple drug resistance was predicted by mNGS and confirmed by antibiotic susceptibility test. The application of mNGS can benefit clinics in pathogen identification and antimicrobial treatment stewardship. Physicians should be alert to some emerging uncommon pathogens, including Chlamydia Psittaci, Nocardia otitidiscaviarum, and rare NTM.

Clinical and microbiological characteristics ofnocardiosis: A 5-year single-center study inCrete, Greece.

Nocardiosis is a rare disease affecting both immunocompromised and immunocompetent hosts, presented in various clinical forms ranging from localized to disseminated infection. Aim of the present study was to investigate the clinical and microbiological characteristics of nocardiosis, antimicrobial resistance profiles, treatment, and outcomes of Nocardia infection over the last 5 years at our institution. The medical records and microbiological data of patients affected by nocardiosis and treated at the university hospital of Heraklion, Crete, Greece, between 2018 and 2022, were retrospectively analyzed. The isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and through sequencing of 16S rRNA. Antimicrobial susceptibility for 17 agents was determined by E-test and results were interpreted according to CLSI guidelines. Among the 28 Nocardia isolates, eight species were identified, with Nocardia brasiliensis being the most prevalent (32.1%), followed by Nocardia otitidiscaviarum (25%), and Nocardia farcinica (14.3%). Skin and soft tissue infections were the most common presentations, noted in 13 (50%) patients, followed by pulmonaryinfection presented in 10 (38.5%) patients. Fifteen patients (57.7%) had at least one underlying disease, and 11 (42.3%) were on immunosuppressive or long-term corticosteroid treatment. Susceptibility rates of linezolid, tigecycline, amikacin, trimethoprim-sulfamethoxazole, moxifloxacin, and imipenem were 100, 100, 96.4, 92.9, 82.1, and 42.9%, respectively. The 26 patients in this study were treated with various antibiotics. Mortality rate was 3.8%, and the patient who died had disseminated infection. Since epidemiology and antimicrobial susceptibility are evolving, continuous surveillance is mandatory in order to initiate appropriate treatment in a timely manner.

Pleural effusion-related Nocardia otitidiscaviarum, Anaplasma platys and Ehrlichia canis coinfection in a dog.

The coinfections by some microorganisms have been related to severe diseases in humans and animals, where immunosuppressive agents favor opportunistic behavior of other pathogens. A 4-month-old, female mixed-breed dog with a two-week history of inappetence, prostration, emaciation, and respiratory distress was admitted at a veterinary hospital in Brazil. Tachycardia, pale mucous membranes, severe respiratory distress, and a large number of ticks (Rhipicephalus sanguineus s.l.) in different body regions were observed at clinical examination. Hematological examination of dog showed leukocytosis, neutrophilia, mild anemia, and thrombocytopenia, whereas unremarkable values in biochemical tests. Thoracic radiography revealed a pleural effusion image. Blood and the pleural fluid (purulent aspect) samples were subjected to qPCR (16S rRNA and dsb genes) and sequencing, which identified Ehrlichia canis and Anaplasma platys coinfection. An aggregate of coccoid-to-branching or long filamentous microorganisms, surrounded by pyogranulomatous inflammatory reaction was seen at the cytology of the pleural fluid. Bacteriological culture of pleural effusion showed colonies compatible with the genus Nocardia, which revealed gram-positive filamentous organisms with a tendency of fragmentation and were identified as Nocardia otitidiscaviarum in mass spectrometry (MALDI-TOF MS). Therapy of N. otitidiscaviarum isolate using levofloxacin (supported by a previous in vitro susceptibility testing) and doxycycline for E. canis and A. platys resulted in complete resolution of the clinical picture. Here, we report for the first time a triple coinfection by Nocardia otitidiscaviarum, A. platys, and E. canis in a dog with pleural effusion, where debilitating or immunosuppressive conditions induced by A. platys and E. canis coinfection probably contributed to the opportunistic behavior of N. otitidiscaviarum.

Pulmonary Nocardiosis Caused by &lt;i&gt;Nocardia otitidiscaviarum&lt;/i&gt; and &lt;i&gt;&lt;/i&gt;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.

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.

Multiple Discharging Nodules Over the Trunk.

Actinomycetoma, a chronic subcutaneous infection, is caused by filamentous aerobic bacteria. A 40-year-old male farmer, presented with 8 month history of multiple pus discharging nodules and sinuses over the right posterior trunk with edema and erythema [Figure 1a]. Histopathology revealed non-specific predominantly mononuclear inflammatory infiltrate in upper and mid-dermis with collagen deposition [Figure 2a]. The culture showed Nocardia otitidiscaviarum [Figure 2b]. Routine investigations were normal.Figure 1: (a) Multiple draining nodules and sinuses over the right posterior trunk at presentation. (b) Improvement at 2 months, and (c) complete healing with atrophic scarring at 6 monthsFigure 2: (a) Histopathology showing hyperkeratotic and acanthotic epidermis. Mononuclear infiltrate and collagen deposition in upper and mid-dermis (H&E 40x). (b) Nocardia otitidiscaviarum growth on culturePatient was managed with Rifampicin (600 mg) once daily, and double strength cotrimoxazole (800 mg of sulfamethoxazole + 160 mg of trimethoprim) twice daily for 3 months.[1] Significant improvement was seen at 2 months with atrophic scarring and complete healing at 6 months [Figure 1b and 1c]. Consent for publication The authors certify that they have obtained appropriate patient consent. The patient has given his consent for his images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Control of parallelized bioreactors II: probabilistic quantification of carboxylic acid reductase activity for bioprocess optimization

Autonomously operated parallelized mL-scale bioreactors are considered the key to reduce bioprocess development cost and time. However, their application is often limited to products with very simple analytics. In this study, we investigated enhanced protein expression conditions of a carboxyl reductase from Nocardia otitidiscaviarum in E. coli. Cells were produced with exponential feeding in a L-scale bioreactor. After the desired cell density for protein expression was reached, the cells were automatically transferred to 48 mL-scale bioreactors operated by a liquid handling station where protein expression studies were conducted. During protein expression, the feed rate and the inducer concentration was varied. At the end of the protein expression phase, the enzymatic activity was estimated by performing automated whole-cell biotransformations in a deep-well-plate. The results were analyzed with hierarchical Bayesian modelling methods to account for the biomass growth during the biotransformation, biomass interference on the subsequent product assay, and to predict absolute and specific enzyme activities at optimal expression conditions. Lower feed rates seemed to be beneficial for high specific and absolute activities. At the optimal investigated expression conditions an activity of 1153 U mL^{-1} was estimated with a 90% credible interval of [992, 1321] U mL^{-1}. This is about 40-fold higher than the highest published data for the enzyme under investigation. With the proposed setup, 192 protein expression conditions were studied during four experimental runs with minimal manual workload, showing the reliability and potential of automated and digitalized bioreactor systems.

Disseminated Nocardia otitidiscaviarum presenting as septic arthritis in a nephrotic syndrome patient on immunosuppressants

Rationale: Septic arthritis due to Nocardia is rare, with Nocardia otitidiscaviarum being the rarest Nocardia species isolated from septic arthritis. Patient concerns: Here we present a case of a 47-year-old man with a history of nephrotic syndrome on active treatment who developed signs and symptoms of septic arthritis. Diagnosis: Initial Laboratory test results showed high inflammatory markers, Right knee joint ultrasound revealed effusion. Therefore, knee arthrocentesis was performed, which revealed a milky orange fluid that grew gram-positive branching forms identified as moderate Nocardia otitidiscaviarum. Despite being asymptomatic, the patient underwent Head computed tomography, which revealed dissemination to the brain. Intervention: The patient was started on appropriate antibiotics, immunosuppressant medications were stopped, and arthroscopic drainage was performed. Outcomes: Repeated arthrocentesis after 2 weeks was sterile. After 1 month, the patient felt better, pain-free, and was able to ambulate. Lessons: Nocardial arthritis is rare, and joint management requires an internist, a rheumatologist, a surgeon, and an infectious disease expert because early identification of the bacteria can improve the outcomes and quality of life.

Nocardia otitidiscaviarum as Possible Etiologic Agent of Non-resolving Pneumonia

Nocardia otitidiscaviarum as Possible Etiologic Agent of Non-resolving Pneumonia

A fatal case of disseminated nocardiosis due to Nocardia otitidiscaviarum resistant to trimethoprim–sulfamethoxazole: case report and literature review

BackgroundDisseminated nocardiosis still causes significant morbidity and mortality and is often caused by Nocardia asteroides, N. basiliensis, and N. farcinica and are often treated with trimethoprim–sulfamethoxazole (TMP–SMX). Nocardia otitidiscaviarum (N. otitidiscaviarum) rarely causes disseminated disease and resistance to TMP–SMX is even more rare.Case presentationA 37-year-old woman with metastatic breast cancer and right ear deafness with recent occupational gardening and manipulating soil, presented to the hospital with first time seizure and multiple skin nodules. Magnetic resonance imaging (MRI) showed ring enhancing lesions, biopsy of the skin and brain lesions grew N. otitidiscaviarum. She was empirically treated with TMP–SMX and Imipenem–Cilastatin, however, almost three weeks into therapy, susceptibility results revealed it to be resistant to both antimicrobials, she was subsequently changed to Amikacin, Linezolid, Moxifloxacin, and Doxycycline but ultimately died.ConclusionsThis case report highlights the importance of suspecting a rare Nocardia species in patients at risk with proper occupational exposure, moreover, TMP–SMX resistance should be suspected with lack of clinical response, this may have important implications on clinical practice when facing similar infections.

Epidemiology and Antimicrobial Resistance Profiles of the Nocardia Species in China, 2009 to 2021.

ABSTRACTThe genus Nocardia includes ubiquitous environmental saprophytes and the most frequently isolated aerobic actinomycete human pathogen responsible for localized or disseminated infection. Herein, the species distribution and antimicrobial susceptibility profiles of 441 nonrepetitive Nocardia strains are reported, collected from 21 provinces/cities in China over 13 years (from 2009 to 2021). These isolates were identified to species level by mass spectrometry or targeted DNA sequencing. The susceptibility profiles of Nocardia species for 15 antibiotics were determined by the broth microdilution method. Among these Nocardia isolates, Nocardia farcinica was the most commonly isolated species (39.9%, 176 of 441), followed by Nocardia cyriacigeorgica (28.6%, 126), Nocardia abscessus (6.6%, 29), and Nocardia otitidiscaviarum (5.9%, 26). Furthermore, 361 Nocardia strains (81.9%) were collected from lower respiratory tract (sputum, lung tissue, and bronchoalveolar lavage fluid), 50 (11.3%) were collected from skin and soft tissues, 9 were collected from blood, 9 were collected from eye, 4 were collected from cerebrospinal fluid and brain abscesses, and 2 were collected from pleural effusion. All of the Nocardia strains were susceptible to linezolid, followed by amikacin (99.3%) and trimethoprim-sulfamethoxazole (TMP-SMX) (99.1%). The antibiotic resistance profiles of other antibiotics varied tremendously among different Nocardia species. This demonstrated that accurate species identification and/or antibiotic susceptibility testing should be performed before the usage of these antibiotics. In summary, this is the largest study on the species and antibiotic resistance profiles of the genus Nocardia circulating in China, and our data will contribute to a better understanding of clinical nocardiosis.IMPORTANCE The genus Nocardia has the potential to cause nocardiosis, which might be underrecognized and underdiagnosed. Herein, the demographical features of 441 nonrepetitive nocardiosis cases and species distribution of their Nocardia strains in China, 2009 to 2021, are summarized. The susceptibility profiles for 15 antibiotics against all of the above Nocardia strains were also determined by the broth microdilution method. To date, this is the largest study on the genus Nocardia contributing to nocardiosis in China. Our study will be helpful for understanding the species diversity of Nocardia isolates distributed in China and for decision-making in the context of nocardiosis diagnosis and treatment.

Disseminated Nocardiosis in a Breast Cancer Patient Caused by Nocardia otitidiscaviarum: A Case Report of Tertiary Centre in Saudi Arabia

Nocardiosis is a rare opportunistic disease that primarily affects patients with deficient immune systems. Nocardia otitidiscaviarum is one of the rare species of Nocardia and it represents less than 3% of all Nocardia cases. Clinical presentation can be varied according to the affected organ. This study describes a case of a breast cancer patient who is immunocompromised due to the chemotherapy. This patient presented with a feature of febrile neutropenia. Investigations of this case led to the diagnosis of Nocardia otitidiscaviarum. Treatment of this underlying infection required to hold the chemotherapy for good time and to adapt patient-specific cancer treatment according to the balance between both need of cancer control and infection treatment according to the susceptibility test as in our case.

Nocardiosis in Free-Ranging Cetaceans from the Central-Eastern Atlantic Ocean and Contiguous Mediterranean Sea.

Simple SummaryCharacterization, description, and geographical location of harmful bacterial agents in cetaceans are important for population surveillance and health monitoring around the world. This research compiles the pathologic features of nocardiosis in five free-ranging delphinids from the Canary Islands and Andalusia. All examined animals showed a disseminated pattern of infection with characteristic suppurative to pyogranulomatous lesions with thromboembolism in two or more organs. The obtained results provide the first record of N. otitidiscaviarum in cetaceans, the first account of N. farcinica in free-ranging dolphins, and confirmation of nocardiosis in central eastern Atlantic Ocean.We report the pathologic features of nocardiosis in five free-ranging delphinids from the Canary Islands and Andalusia, namely four striped dolphins (Stenella coerulealba) and one bottlenose dolphin (Tursiops truncatus). All animals had a multiorgan (disseminated) pattern of infection involving suppurative to pyogranulomatous and thromboembolic lesions in two or more organs. Most affected organs were (by decreasing order) lung, pulmonary lymph nodes, liver, kidney, adrenal glands, and central nervous system. Typical intralesional and intravascular branched and filamentous bacteria were highlighted by Grocott’s methenamine silver and Gram stains. Bacterial analysis including 16S rRNA gene sequencing identified Nocardia farcinica in two striped dolphins and Nocardia otitidiscaviarum in one striped dolphin and the bottlenose dolphin. All dolphins tested (n = 4) for cetacean morbillivirus were negative; one dolphin had concurrent cutaneous herpesvirosis. These results provide the first record of N. otitidiscaviarum in cetaceans, the first account of N. farcinica in free-ranging dolphins, and confirmation of nocardiosis in central eastern Atlantic Ocean. These results expand the known geographic range of nocardiosis in cetaceans.

A ten-year retrospective analysis of nocardiosis in a tertiary care center of South-coastal India.

Nocardiosis is an uncommon life-threatening infection caused by Nocardia spp. This study aimed to review the distribution of risk factors, clinical characteristics, microbiological findings, treatment and outcome of patients diagnosed with nocardiosis. This study was a retrospective case record review of all nocardiosis cases that were diagnosed at our tertiary care hospital from January 2008 to December 2019. A total of 48 patients with a mean age of 52.2±16.28 years were included. Out of which forty one (85%) were diagnosed as pulmonary nocardiosis and seven (14.6%) as disseminated disease. Chronic lung disease 25 (52.1%), long term steroid use 22 (45.8%) followed by diabetes mellitus 11 (22.9%) were common predisposing factors. The common symptoms were fever (87.5%), cough (79.2%) and breathlessness (52.1%). The most frequent radiologic finding included consolidation in 38 (79.1%), cavitation with thickened wall in 2 (4.1%), reticulonodular shadows in 2 (4.1%), and unilateral pleural effusion in 5 (10.4%). Nocardia otitidiscaviarum (22.9%) was frequently isolated from cultures. Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) was observed in 21% cases. Mortality was noted in 6 (12.5%) patients and all were with pulmonary involvement. The percentage of death among those with and without pulmonary tuberculosis was 33.3% and 5% respectively. Patients affected by pulmonary nocardiosis with previous history of pulmonary tuberculosis showed significant association with poor outcome (p-value=0.05). In conclusion, nocardiosis mainly affects patients with structural lung disease or immunocompromised hosts with adverse outcome. Awareness of this infection is crucial for a clinician, and any suspicion should lead to make an early diagnosis and choose an appropriate empirical treatment to improve the outcome in this population.

DISSEMINATED NOCARDIOSIS PRESENTING AS ACUTE LIVER FAILURE AND INTRAPARENCHYMAL HEMORRHAGE

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Nocardiosis is an opportunistic infection that most commonly manifests as pulmonary disease. Disseminated nocardiosis is rare and is associated with high mortality. We present a case of a woman with disseminated nocardiosis presenting with acute liver failure complicated by intraparenchymal hemorrhage. CASE PRESENTATION: A 30-year-old woman with a history of alcohol abuse presented with jaundice, bloating, and diarrhea for 2 weeks. Laboratory examination revealed hemoglobin of 5.2 g/dL, platelets 60,000/µL, INR 3.4, AST 113 U/L, ALT 38 U/L, and total bilirubin of 30 mg/dL. MRCP revealed a normal biliary tree, nodular liver contour and evidence of portal hypertension. Acetaminophen level and acute viral hepatitis panel were negative. HIV serology and autoimmune hepatitis panel were negative. Chest CT revealed a 5 x 3.5 cm subpleural mass in the left upper lobe with areas of gas density (Fig 1). Her hospital course was complicated by a rapid deterioration in mental status and DIC. Head CT revealed an acute left occipital-parietal intraparenchymal hemorrhage. She was intubated and transferred to the ICU. Bronchoscopy with BAL grew Nocardia otitidiscaviarum. Brain MRI revealed FLAIR signal hyperintensity lining the ventricles, concerning for ventriculitis or abscess (Fig 2). An external ventricular drain was placed for interval development of hydrocephalus. The patient received IV trimethoprim-sulfamethoxazole and intrathecal amikacin. Given her poor prognosis, her family elected to withdraw care. DISCUSSION: Nocardia is a branching, filamentous gram-positive bacilli found ubiquitously in soil. Infection usually occurs by inhalation of aerosolized bacteria resulting in predominant lung involvement with potential hematogenous spread to other organs. Patients with impaired T-cell mediated immunity, such as HIV, chronic steroid use, diabetes, or alcoholism are at risk of developing severe infection. Our patient had a longstanding history of heavy alcohol use, likely predisposing her to disseminated infection. Nocardiosis is considered disseminated when two or more nocardial abscesses are found at two or more locations. Up to 20% of all Nocardia infections involve the brain. Current guidelines recommend imaging of the brain for any patient with confirmed or suspected pulmonary nocardiosis. Prognosis is usually poor, and mortality can be as high as 64%. First-line treatment is trimethoprim-sulfamethoxazole. However some species, such as N. otitidiscaviarum found in our patient, are occasionally resistant. Due to suspected CNS involvement, dual coverage was recommended with the addition of IV amikacin at dosing for CNS penetrance. CONCLUSIONS: In patients presenting with a cavitary lung lesion and associated brain lesion, nocardiosis should be considered in the differential. Early brain imaging may be warranted in patients presenting with severe disease. REFERENCE #1: Pulmonary nocardiosis: risk factors and outcomes. AU Martínez Tomás R, Menéndez Villanueva R, Reyes Calzada S, Santos Durantez M, Vallés Tarazona JM, Modesto Alapont M, Gobernado Serrano M SO Respirology. 2007;12(3):394. REFERENCE #2: Conville PS, Witebsky FG. Nocardia, Rhodococcus, Gordonia, Actinomadura, Streptomyces, and other Aerobic Actinomycetes. In: Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA, editors. Manual of Clinical Microbiology. 9th ed. Washington, DC: ASM Press; 2007. p. 515. DISCLOSURES: No relevant relationships by Muhammad Arif, source=Web Response No relevant relationships by Abdul Rahman Halawa, source=Web Response No relevant relationships by MAYKEL IRANDOST, source=Web Response no disclosure on file for Sean Marco; No relevant relationships by Andrew Talon, source=Web Response No relevant relationships by Anthony Vaccarello, source=Web Response

Identification and antimicrobial susceptibility profiles of Nocardia species clinically isolated in Japan

The aims of the present study were to profile the antimicrobial susceptibility patterns of a diverse range of Nocardia species isolated in Japan, and to determine the ability of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for species/complex identification. Identification of 153 clinical isolates was performed by full-length 16S rRNA gene sequencing as a reference method to evaluate the usefulness of MALDI-TOF MS identification. Antimicrobial susceptibility testing (AST) for 14 antibiotics was performed using the broth microdilution method against 146 of the isolates. Among the total 153 clinical isolates, Nocardia farcinica complex (25%) was the most common species, followed by Nocardia cyriacigeorgica (18%), Nocardia brasiliensis (9%), Nocardia nova (8%), and Nocardia otitidiscaviarum (7%). Among 150 isolates identified to the species/complex level by 16S rRNA gene sequencing, MALDI-TOF MS with the use of a supplemental Nocardia library (JMLD library ver.ML01) correctly identified 97.3% (n = 146) to the species/complex level and 1.3% (n = 2) to the genus level. Among the 146 Nocardia isolates that underwent AST, the susceptibilities were 100% to linezolid, 96% to amikacin, 94% to trimethoprim-sulfamethoxazole, and 76% to imipenem. None of the trimethoprim-sulfamethoxazole-resistant isolates carried either plasmid-mediated sulfonamide-resistant genes (sul1, sul2) or trimethoprim-resistant genes (dfrA).

Molecular identification and antibiotic resistance pattern of actinomycetes isolates among immunocompromised patients in Iran, emerging of new infections

Recent advancements in DNA-based approaches have led to the identification of uncommon and rare bacterial pathogens. In this study, by utilizing a DNA-based approach, a total of 1043 clinical specimens were processed for the identification of actinobacteria targeting the 16S rRNA and gyrB genes. Drug susceptibility testing was also conducted using micro-broth dilution and PCR. Two isolates of Nocardia flavorosea and Rhodococcus erythropolis were reported for the first time in Iran. Also, Nocardiopsis dassonvillei, Streptomyces olivaceus, and Streptomyces griseus were reported for the first time in Asia. Infections caused by Nocardia caishijiensis and Prauserella muralis have also been reported in this study. The first Asian case of pulmonary infection caused by Nocardia ignorata and the first global case of brain abscess caused by Nocardia ninae and Nocardia neocaledoniensis have been reported in this study. Overall 30 isolates belonging to 6 genera (Nocardia, Streptomyces, Rodoccoccus, Nocardiopsis, Rothia, and Prauserella) were detected in 30 patients. All 30 isolates were susceptible to amikacin and linezolid. Three isolates including Nocardia otitidiscaviarum (n = 2) and Nocardia flavorosea (n = 1) were resistant to trimethoprim-sulfamethoxazole which were the first trimethoprim-sulfamethoxazole resistant clinical actinomycetes in Iran. Isolation of rare species of actinomycetes particularly Nocardia spp. requires urgent action before they spread clinically particularly among immunocompromised patients.

Production of the Carboxylate Reductase from Nocardia otitidiscaviarum in a Soluble, Active Form for in vitro Applications.

Accessing aldehydes from carboxylate moieties is often a challenging task. In this regard, carboxylate reductases (CARs) are promising catalysts provided by nature that are able to accomplish this task in just one step, avoiding over‐reduction to the alcohol product. However, the heterologous expression of CARs can be quite difficult due to the excessive formation of insoluble protein, thus hindering further characterization and application of the enzyme. Here, the heterologous production of the carboxylate reductase from Nocardia otitidiscaviarum (NoCAR) was optimized by a combination of i) optimized cultivation conditions, ii) post‐translational modification with a phosphopantetheinyl transferase and iii) selection of an appropriate expression strain. Especially, the selection of Escherichia coli tuner cells as host had a strong effect on the final 110‐fold increase in the specific activity of NoCAR. This highly active NoCAR was used to reduce sodium benzoate to benzaldehyde, and it was successfully assembled with an in vitro regeneration of ATP and NADPH, being capable of reducing about 30 mM sodium benzoate with high selectivity in only 2 h of reaction.