Nocardia Species Research Articles

MLSA phylogeny and antimicrobial susceptibility of clinical Nocardia isolates: a multicenter retrospective study in China

BackgroundWith the increase of detection rate and long treatment period, nocardiosis has become a noticeable problem in China. However, there are limited large-scale studies on the epidemiology and antimicrobial susceptibility profiles of clinical Nocardia spp. in China. The present study aimed to explore the species distribution and drug susceptibility pattern of 82 clinical Nocardia isolates from three tertiary hospitals in China by multilocus sequence analysis (MLSA) and broth microdilution (BMD) method.ResultsPulmonary nocardiosis (90.2%) was the most common clinical presentation of infection. N. cyriacigeorgica (n = 33; 40.2%) and N. farcinica (n = 20; 24.4%) were the most frequently encountered Nocardia species, followed by N. otitidiscaviarum (n = 7; 8.5%), N. abscessus (n = 5; 6.1%), N. asiatica (n = 4; 4.9%), and N. wallacei (n = 4; 4.9%). Trimethoprim/sulfamethoxazole (SXT) remained high activity against all Nocardia isolates (susceptibility rate: 98.8%). Linezolid and amikacin were also highly active; 100 and 95.1% of all isolates demonstrated susceptibility, respectively. Except for N. otitidiscaviarum, all the Nocardia isolates exhibited high susceptibility rates to imipenem. The resistance rates of all isolates to clarithromycin and ciprofloxacin were 92.7 and 73.2%, respectively, but the resistance rate of N. farcinica to ciprofloxacin was only 25%.ConclusionsThe clinically isolated Nocardia spp. had diverse antimicrobial susceptibility patterns, which were similar to the reports by other groups elsewhere, but some differences were also observed, mainly including imipenem and ciprofloxacin. According to this study, SXT still can be the first choice for empirical therapy due to the low resistance rate. Linezolid can be chosen when a patient is allergic to SXT, and amikacin and imipenem can be the choice in a combination regimen.

Recurrent nocardiosis in solid organ transplant recipients: An evaluation of secondary prophylaxis.

Immunocompromised individuals are at risk for Nocardia infection, with a recurrence rate of approximately 5%. Solid organ transplant (SOT) recipients often receive secondary prophylaxis due to their requirement of lifelong immunosuppression. However, data supporting this practice is sparse. We sought to evaluate Nocardia recurrence in SOT recipients, specifically evaluating secondary prophylaxis. We conducted a retrospective cohort study of SOT recipients diagnosed with nocardiosis from 2000 through 2020. We included adult SOT recipients who completed their course of Nocardia therapy and had at least 6months of posttherapy follow-up. The primary outcome was Nocardia recurrence, which included relapse and reinfection. One hundred two patients met inclusion criteria. Sixty-six (64.7%) were male and mean age was 58.6 ± 11.7years. Most common SOT types were kidney (46.1%), heart (18.6%), kidney-pancreas (11.8%), and lung (10.8%). Most common sites of infection were lung (85.3%), skin (17.6%), and brain (14.7%). Secondary prophylaxis was utilized in 53 (52.0%) patients. Trimethoprim-sulfamethoxazole (TMP-SMX) single-strength daily was the most common prophylaxis agent and dose. Five patients (4.9%) experienced Nocardia recurrence, three of which were receiving secondary prophylaxis at time of recurrence. Two recurrences were with the same Nocardia species. Factors associated with recurrence were lung transplantation (p=.011), chronic lung disease (p=.032), and treatment ≤120days (p=.006). Time from treatment completion to recurrence ranged from 107 to 875days. Nocardia recurrence in SOT recipients is an uncommon event. TMP-SMX secondary prophylaxis is incompletely protective and recurrence may be dependent upon other factors. Further study of secondary prophylaxis is warranted.

Insights from the comparative genome analysis of natural rubber degrading Nocardia species.

Nocardia are known to be a facultative human pathogen and can cause infection in immune compromised patients. Though the details research on the virulence factors of Nocardia are scanty but numerous genes that code such factors were reported from different species of Nocardia. Despite of the presence of several virulence factors, species of this genus have been shown to have role in remediation of many toxic and hazardous materials from the environment. In this study, genome sequences of rubber degrading Nocardia sp. BSTN01 and N.nova SH22a have been analyzed to locate the potential virulence genes. Also, the genomes of facultative pathogenic Nocardia like, N.africana, N. brasiliensis, N. kruczakiae, N. transvalensis and N. veterana have been analyzed to find the gene encoding latex clearing protein (Lcp), a rubber oxygenase enzyme of Gram-positive action bacteria. The study provides an insight about the potentiality of rubberdegrading Nocardia species to emerge as future human pathogens and also the probability of a serious concern if the studied facultative pathogens of Nocardia like N. africana, N. brasiliensis, N. kruczakiae, N. transvalensis and N. veterana are capable of degrading rubber, a regularly used material in clinics. Moreover, use of such possible pathogenic strains for their known role in bioremediation of rubber waste from the environment might be deleterious.

Treatment of Nocardial Brain Abscess in a Patient With Systemic Lupus Erythematosus and Idiopathic Thrombocytopenic Purpura: Case Report and a Review of the Literature

Brain abscesses due to Nocardia species account for 1-2% of all cerebral abscesses, often in immunosuppressed individuals, with a mortality three times higher than other cerebral abscesses. Early diagnosis and management are vital for good outcomes.We report a case of a right frontal Nocardia brain abscess in an immunosuppressed 38-year-old female. She presented with headaches, confusion, memory deficits, and personality change. She remained systemically well, with normal inflammatory markers. She underwent two open surgical drainages, with excision of the abscess wall. She made an excellent recovery with minimal edema and no contrast enhancement on imaging at eight weeks postoperatively.Management of Nocardia brain abscess includes a prompt diagnosis with direct microscopic examination and initiation of correct antibiotic therapy for good outcomes. We recommend open surgical resection, including excision of the abscess wall, followed by long-term antimicrobial therapy, to enhance the rate of recovery.

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).

Case report: pulmonary nocardiosis caused by Nocardia exalbida in an immunocompetent patient

BackgroundNocardiosis is known as an opportunistic infection in immunocompromised hosts, but it occasionally has been reported in immunocompetent patient. The Nocardia exalbida is first-reported in 2006 from Japan, and a few cases of have been reported in only immunocompromised host, and the characteristic is still unclear. We herein describe the first case of pulmonary nocardiosis caused by N. exalbida in an immunocompetent patient.Case presentationA77 -year-old Japanese man was admitted to our hospital on November 2, 2018. He was a lifelong non-smoker with no childhood history of respiratory disease. He had a medical history of dyslipidemia. One month before this admission fevers, sputum, mild cough were developed and he was evaluated in a clinic near our hospital. His diagnosis was community acquired pneumonia within his right middle lobe. He was treated with ceftriaxone 1 g/day intravenously for a week, however his symptoms relapsed a few days later. So, the physician retried ceftriaxone for another 3 days, but his symptoms did not improve. He was referred to our hospital. He was treated with sitafloxacin as an outpatient for a week, however his symptoms got worse. The chest CT showed consolidation and atelectasis in his right middle lobe. Low density area was scattered in consolidation, and right pleural effusion was observed.The patient was diagnosed with pulmonary abscess and he was admitted. Administration of piperacillin/tazobactam improved his condition. We switched antibiotics to amoxicillin/clavulanate, and he was discharged. After 2 weeks, he relapsed and was admitted again. After administration of piperacillin/tazobactam for 3 weeks, we perform bronchoscopy and Nocardia species were cultured from samples of the bronchial wash. The isolates were identified as N. exalbida using 16S rRNA gene sequencing. We prescribed Trimethoprim / Sulfamethoxazole (TMP/SMX) for 4 months. Then we switched to minocycline for renal dysfunction caused from TMP-SMX for 1 more month. After 5 months therapy, Consolidation on CT disappeared, and Nocardiosis was cured.Conclusionwe reported the first case of pulmonary nocardiosis caused by N. exalbida in an immunocompetent patient. N. exalbida infection might be associated with a good response to treatment.

Empyema necessitans with osteomyelitis of fifth rib due to Nocardia farcinica: a case report

BackgroundEmpyema necessitans is a rare pulmonary condition described as the presence of pus in the pleural cavity with insidious extension into the surrounding soft tissue. The common microbial aetiology of empyema necessitans is tuberculosis. Nocardiosis a cause of empyema necessitans is rarely described in the literature. We herein present a case of an 80-year-old male with empyema necessitans with osteomyelitis of rib caused by Nocardia farcinica.Case presentationAn 80-year-old male presented with complaints of soft swelling on the left lower posterior chest wall associated with dry cough and breathlessness on exertion. Computed Tomography (CT) thorax demonstrated empyema necessitans with features of left fifth rib osteomyelitis. Radiological guided aspiration of the chest wall collection revealed Nocardia species and surgical drainage of abscess was performed. Matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry (MALDI-TOF-MS) identified the isolate as Nocardia farcinica. He was treated with three-drug regimen: Trimethoprim-sulfamethoxazole, amikacin and ceftriaxone for 2 weeks. After showing improvement patient was discharged and advised to take oral Trimethoprim-sulfamethoxazole for the next 6 months with periodic follow-up.ConclusionsAs our case demonstrates, the possibility of invasive Nocardiosis should not be overlooked even in immunocompetent patients. Clinicians should aware of this rare entity while treating patients with empyema necessitans.

Genotypic and phenotypic prevalence of Nocardia species in Iran: First systematic review and meta-analysis of data accumulated over years 1992-2021.

Nocardia species belong to the aerobic actinomycetes group of bacteria which are gram-positive and partially acid-fast Bacilli. These bacteria may sometimes be associated with nosocomial infections. Nocardia diseases are not required to be reported to public health authorities in Iran. Hence, the present study was designed to determine the prevalence of human Nocardia spp. in Iran by using a systematic review and meta-analysis according to the preferred reporting items for systematic reviews and meta-Analyses statement. The data of the prevalence of Nocardia species were collected from databases such as Embase, PubMed/MEDLINE via Ovid, Web of Science, Scopus and Google Scholar as well as national Iranian databases, including SID, Magiran. Analyses were conducted by STATA 14.0. The meta-analyses showed that the proportion of Nocardia spp. in Iranian studies varied from 1.71(1.17, 2.24) to 0.46(0.09, 0.83). N. asteroides (21% [95% CI 1.17, 2.24]), N. cyriacigeorgica (17% [95% CI 0.99, 1.77]), N. facanica (10% [95% CI 0.75, 1.00]) were considered to be common causative agents. Our study presents that despite the fact that Nocardia spp. are normally are saprophytic organisms, are currently accounts as emerging pathogens due to an increase in immunocompromised patients among Iranian populations. Considering our results, the establishment of advanced diagnostic facilities for the rapid detection of Nocardia infections are required for optimal therapeutic strategies of Nocardia spp. in Iran. Our findings could help the programmatic management of the disease within the context of Nocardia control programs.

A case report of Nocardia asiatica in a renal transplant recipient

Nocardiosis is a life-threatening disease in solid organ transplant recipients. It is an uncommon but important infection in these patients. Nocardiosis is caused by a Gram-positive, weakly acid fast, branching filamentous aerobic bacteria belonging to the order Actinomycetales. It causes pulmonary and systemic infections in immunocompromised patients. The common species of Nocardia causing infections are Nocardia asteroids, Nocardia brasiliensis, Nocardia farscinica, and Nocardia nova. Here, we report a case of a 32-year-old female postrenal transplant recipient developing pulmonary nocardiosis by a rare species of Nocardia called Nocardia asiatica. A modified Ziehl–Neelsen stain using 1% H2SO4 in the endotracheal (ET) secretion revealed numerous acid fast branching filamentous organisms morphologically resembling Nocardia spp., and the culture grew Nocardia and it was confirmed as N. asiatica by MALDI TOF. Our patient had cytomegalovirus co-infection. The patient was started on trimethoprim-sulfamethoxazole. This case shows the importance of keeping nocardiosis as a differential diagnosis in immunocompromised patients.

Evaluation of anti-biofilm potential of biosurfactant extracted from Nocardia species.

Bacterial natural products such as biosurfactants and surface-active agents are important compounds which exhibit many applications in the fields of medicine. The aim of the present study was to isolate and identify Nocardia strains with high biosurfactant production and antibiofilm ability. In the present study, a biosurfactant producing Nocardia species was isolated and identified by a laboratory method. Nocardia species were initially screened and then tested for their ability to produce biosurfactant. The oil spreading test and the surface tension measurements showed that one strain was a biosurfactant producer. The strain with the best surface activity results was selected for further studies and identified by 16S rRNA gene sequencing method. Fourier transform infrared spectroscopy (FTIR) and compositional analysis proved a biosurfactant structure. Oil spreading test and blue agar plate test confirmed biosurfactants and extracellular anionic glycolipids. E24% assay using olive oil revealed strong emulsifying characteristic of the extracted biosurfactant with 100% emulsifying strength. FTIR spectrum indicated the presence of aliphatic hydrocarbon chain (lipid) along with the polysaccharide portion, confirming the glycolipid nature of the biosurfactant. The stability of the biosurfactant produced in different conditions was significant. Increasing concentration of BS significantly inhibited Pseudomonas aeruginosa biofilm. N. coubleae can be a representative of the genus Nocardia for the production of biosurfactants with beneficial physicochemical properties.

Identification and immunogenicity of NFA47650 protein from Nocardia farcinica

Objective To construct the prokaryotic expression vector of NFA47650 protein from Nocardia farcinica, induce the expression and purification of NFA47650 protein, and analyze its immunogenicity. Methods The primers were designed and synthesized based on nfa-47650 gene sequence of N. farcinica; pET30a (+) expression vector was constructed by PCR amplification; NFA47650 protein was purified after expressing in E. coli BL21. The subcellular localization and immunogenicity with NFA47650 mice anti-serum were analyzed by Western Blot. Results The prokaryotic recombinant expression vector of N. farcinica NFA47650 protein was successfully constructed, which was efficiently expressed in BL21 E. coli as inclusion bodies. Western Blot showed that NFA47650 protein was mainly located in the culture supernatant. In addition, this protein could not only be specifically identified by the antisera from mice and rabbits infected with N. farcinica, but also cross-reacted with antisera from mice infected with N. brasiliensis and N. cyriacigeorgica. Conclusion The NFA47650 protein is an important secreted protein, which can trigger immune response by reacting with the antisera of different Nocardia species.

Isolation and Characterization of Nocardiae Associated with Foaming Coastal Marine Waters.

Nocardiosis is an infectious disease caused by Nocardia species that occurs worldwide, albeit more prevalently in tropical/subtropical regions. It can appear as either acute, subacute or as a chronic infection mostly with those with a compromised/weakened immune system. Inhalation of spores and or mycelium fragments is the main transmission route for developing pulmonary nocardiosis. In contrast, cutaneous nocardiosis usually occurs via direct contact. In the subtropical region of the Sunshine Coast in Australia foaming events with thick and persistent and orange-brown color foam have been observed during summer seasons in the near shore marine environments. This study reports the existence of nocardiae in these near shore marine environments by the use of a novel isolation method which used the gas requirements of nocardiae as a selective battery. A total of 32 nocardiae were isolated with the use of this novel method and subsequently conducted molecular identification methods confirmed that the isolates belonged to the genus Nocardia. Twenty-one isolates out of the 32 were closely related to N. nova strains MGA115 and one was related to CBU 09/875, in addition when compared with human pathogenic nocardiae twenty of the isolates were found to be related to N. nova strain JCM 6044. Isolates displayed varied resistance against some of the antibiotics tested when interpretation threshold recommended the Comite de L’Antibiogramme de la Societe Francaise de Microbiologie were used. The highest level of resistance against cefotaxime (n = 27) and ceftriaxone (n = 24). Some of the isolates (n = 6) that displayed resistance to selected antibiotics also possessed potential human pathogenic characteristics such as adherence and translocation through human long epithelial cells as well as displaying phage resistance (n = 26). They might thus present a potential public health risk if frequently encountered through exposure to aerosols generated by the foam as well as direct contact through a wound. Preventative measures to control the growth of nocardiae in such environments such as the control of pollutants, might prevent potential infections that might be caused by these bacteria in humans as well as in marine animals.

Recurrent Subcutaneous Abscess Due to Nocardia farcinica in an Immunocompetent Patient: A Case Report

Nocardia farcinica differs from other species of Nocardia due to its multi-drug resistance and propensity to disseminate hematogenously. Cutaneous nocardiosis in immunocompetent patients is rare. To describe the treatment and clinical trajectory of a 37-year-old male patient who was not immunocompromised and presented with a history of minor trauma from a canister and palpable subcutaneous draining nodules in the forearm. Purulent drainage was present. The injury had occurred 3 months before presentation. Magnetic resonance imaging revealed multiple abscess foci up to 3 cm in diameter in the forearm muscles. The wound culture obtained after debridment indicated Nocardia farcinica as the cause. The case was difficult to manage despite serial debridements, negative pressure wound dressings, and culture-specific antibiotic treatments. The entire treatment process took approximately 7 months. The patient had 5 surgical interventions and more than 6 months of antibiotic treatment. Healing was eventually achieved but with a painful scar. Although nocardiosis has been documented to occur primarily in immunocompromised patients, it should be considered in the differential diagnosis of immunocompetent patients if there is a history of skin injury and a late-onset subcutaneous draining abscess resistant to common treatment regimens.

Clinical Presentation, Management, and Outcomes of Patients With Brain Abscess due to Nocardia Species.

BackgroundNocardial brain abscesses are rare, and published literature describing brain abscesses due to Nocardia species is limited to individual case reports or small series. We report one of the largest contemporary retrospective studies describing risk factors, diagnostic evaluation, management, and outcomes of nocardial brain abscess.MethodsRetrospective review of all adults with brain abscess due to culture-confirmed Nocardia species at our institution between January 1, 2009, and June 30, 2020.ResultsOverall, 24 patients had nocardial brain abscesses during the study period. The median age at presentation was 64 years, and 62.5% were immunocompromised. Pulmonary and cutaneous infections were the most common primary sites of nocardial infection. All 24 patients had magnetic resonance imaging performed, and the frontal lobe was the most commonly involved. The most common organism isolated was Nocardia farcinica, followed by Nocardia wallacei and Nocardia cyriacigeorgica. Thirteen patients were managed with antimicrobial therapy alone, while 11 had both medical and surgical management. In all patients, dual therapy was recommended for the initial 6 weeks of treatment, and 22 patients received at least 1 oral agent as part of their final antibiotic regimen, predominantly trimethoprim-sulfamethoxazole and linezolid. Fourteen patients achieved complete clinical and radiographic resolution of infection.Conclusions Nocardia is an important cause of brain abscess in the immunocompromised host. Early diagnostic and therapeutic aspiration may help health care providers confirm the diagnosis, choose an appropriate antimicrobial regimen, and achieve source control.

An autopsy case of Nocardia meningitis patient presenting with multiple folliculitis

Abstract Rationale: Nocardia is widespread in the soil and causes life-threatening infections in the central nervous system, such as meningitis. Nocardia infection can develop in immunocompetent individuals, not just in immunocompromised persons. Nocardia is a slow-growing bacterium, which makes its detection difficult during routine microbial examinations, resulting in a delayed diagnosis and poor prognosis. Patient concerns: A 64-year-old Japanese man was admitted with fever, headache with meningeal irritation, and multiple folliculitis on his face and neck. Cerebrospinal fluid revealed neutrophilic pleocytosis. All cultures, including cerebrospinal fluid examination, were negative, and serum procalcitonin levels were normal. Diagnoses: The tentative diagnosis was culture-negative bacterial meningitis or meningeal neuro-Behçet disease. Intervention: Meropenem was administered for 12 days, along with corticosteroids. His symptoms were temporarily relieved but worsened again, and finally, he died suddenly on the 37th day of hospitalization. An autopsy revealed extensive infiltration of inflammatory cells in the subarachnoid space, especially the brain stem, cerebellum, whole spinal cord, and cerebral base, where Nocardia species were detected. The final diagnosis was Nocardia meningitis. Lessons: Given the very close timing of the onset of signs of meningitis and multiple folliculitis, the most reasonable and probable idea is that the patient had disseminated nocardiosis. In patients with meningitis with multiple skin infection lesions, such as folliculitis, nocardiosis should be considered a differential diagnosis.

Invasive Nocardiosis in Transplant and Nontransplant Patients: 20-Year Experience in a Tertiary Care Center.

ObjectiveTo present the clinical characteristics and outcome of transplant and nontransplant patients with invasive nocardiosis.Patients and MethodsWe conducted a retrospective chart review of 110 patients 18 years and older diagnosed with culture-proven invasive nocardiosis (defined as the presence of clinical signs and/or radiographic abnormalities) between August 1, 1998, and November 30, 2018. Information on demographic, clinical, radiographic, and microbiological characteristics as well as mortality was collected.ResultsOne hundred ten individuals with invasive nocardiosis were identified, of whom 54 (49%) were transplant and 56 nontransplant (51%) patients. Most transplant patients were kidney and lung recipients. The overall mean age was 64.9 years, and transplant patients had a higher prevalence of diabetes and chronic kidney disease. A substantial proportion of nontransplant patients were receiving corticosteroids (39%), immunosuppressive medications (16%), and chemotherapy (9%) and had chronic obstructive pulmonary disease (20%), rheumatologic conditions (18%), and malignant neoplasia (18%). A higher proportion of transplant patients (28%) than nontransplant patients (4%) received trimethoprim-sulfamethoxazole prophylaxis. In both groups, the lung was the most common site of infection. Seventy percent of all Nocardia species isolated were present in almost equal proportion: N brasiliensis (16%), N farcinica (16%), N nova (15%), N cyriacigeorgia (13%), and N asteroides (11%). More than 90% of isolates were susceptible to trimethoprim-sulfamethoxazole, linezolid, and amikacin. There was no significant difference in mortality between the 2 groups at 1, 6, and 12 months after the initial diagnosis.ConclusionThe frequency of invasive Nocardia infection was similar in transplant and nontransplant patients and mortality at 1, 6, and 12 months was similar in both groups. Trimethoprim-sulfamethoxazole prophylaxis failed to prevent Nocardia infection.

Actinomycetoma laboratory-based diagnosis: a mini-review

Mycetoma is a chronic granulomatous inflammatory disease that is caused either by fungi (eumycetoma) or bacteria (actinomycetoma). The latter is caused by various actinomycetes of the genera Nocardia, Streptomyces and Actinomadura. They have different geographical distributions within mycetoma-endemic regions. In parts of Latin America, Nocardia species are more often encountered while in Africa, Streptomyces species dominate. For instituting a proper patient treatment plan, accurate identification of the causative organism is vital. For actinomycetoma, different laboratory-based techniques have been developed during recent decades. These include direct microscopy, cytology, histopathology and serology. More recently, different molecular techniques and matrix-assisted laser desorption ionisation-time of flight mass spectrometry have been included as diagnostic methods for actinomycetoma. In this review, an update on the laboratory techniques currently in use for the identification of actinomycetoma-causative agents to the species level is presented.

323. First case of Prosthetic joint infection due to Nocardia veterana-elegans

BackgroundNocardia are Gram-positive filamentous bacteria that cause Nocardiosis, a rare opportunistic infection. The most common site of infection is the lungs, with metastatic spread usually to the central nervous system. Prosthetic joint infection due to Nocardia is very rare.MethodsWe report the first case of prosthetic joint infection due to Nocardia veteran-elegans, and review the literature regarding Nocardia septic arthritis, with particular attention to prosthetic joint infection.ResultsThe patient was a 35 year old male with history of Hodgkin’s Lymphoma for which he received chemotherapy previously, poorly controlled diabetes, motor vehicle accident in 2003 with right open tibial plateau fracture requiring hardware placement, who was admitted with a two week history of right knee pain and swelling. Knee aspiration revealed purulent fluid and synovial culture grew Nocardia species. He underwent right knee arthrotomy and debridement with removal of hardware. The Nocardia species was speciated as N. veterana-elegans, sensitive to trimethoprim/sulfamethoxazole, linezolid, clarithromycin, imipenem and amikacin. He was placed on oral linezolid for four weeks, which was then switched to oral trimethoprim/sulfamethoxazole, with a plan for a six month course of therapy. He has completed two months of therapy thus far and is doing well clinically.Nocardia is an uncommon cause of septic arthritis. We found only 37 cases reported in the English literature thus far. Amongst these, only six involved prosthetic joints, including our case, which is the first one to be caused by N. veterana-elegans.Three cases were caused by N. nova and one each by N. farcinica and asteroides. Septic arthritis due to Nocardia has a favorable outcome with a combination of surgical debridement and prolonged antimicrobial therapy of three to six months. For prosthetic joint infections, removal of hardware seems to carry a better prognosis. Trimethoprim/sulfamethoxazole is the preferred antimicrobial, including for bone and joint infection, although susceptibilities can vary amongst the different species.ConclusionNocardia is an uncommon cause of septic arthritis. Prosthetic joint infection is very rare. Prognosis is fair with a combination of hardware removal and prolonged antibiotic therapy.Disclosures All Authors: No reported disclosures

1081. Characteristics and Outcomes of Nocardiosis in a Solid Organ Transplant Cohort

BackgroundSolid organ transplant (SOT) recipients are at increased risk for nocardiosis, an infection associated with high risk of relapse and/or mortality. Novel antimicrobial regimens may be associated with improved outcomes. Here we describe a cohort of SOT recipients with Nocardia infection, to address knowledge gaps regarding the epidemiology of, risk factors for, and outcomes of nocardiosis in SOT.MethodsThis is a single center retrospective study performed at a 700 bed academic transplant center. Cases of nocardiosis were identified via review of microbiology laboratory records; transplant status was ascertained via the electronic medical record. All SOT recipients with a culture growing Nocardia species between 1/1/2007 and 12/31/2019 were included.Figure 1. Epidemiologic curve ResultsWe identified 27 SOT recipients with nocardiosis. The incidence of nocardiosis increased over the study period (Figure 1). Demographic data are shown in Table 1. Induction immunosuppression varied; 37% received an interleukin-2 receptor antagonist, 30% received anti-thymocyte globulin, and 18% received steroids alone. The majority of positive cultures were from respiratory specimens (63%) and the most common species identified were N. nova complex and N. farcinica (Table 2). The majority of patients were lymphocytopenic and received treatment for rejection. 92% of subjects received a sulfonamide agent as part of their treatment regimen and 73% received an oxazolidinone (Table 3). 73% of subjects had resolution of infection without relapse; 15% expired. ConclusionThe epidemiology and risk factors for nocardiosis in this SOT cohort are consistent with established literature. Less than a third of cases occurred in subjects who had received lymphocyte-depleting induction immunosuppression; however, most subjects were lymphocytopenic at diagnosis. While nearly all subjects received a sulfonamide as part of their treatment, the majority also received an agent from the newer drug class of oxazolidinones. Overall outcomes were positive, but treatment varied, thus limiting the ability to determine if a particular combination regimen is beneficial. Multicenter randomized studies are needed to better address knowledge gaps particularly pertaining to treatment.Disclosures All Authors: No reported disclosures

Antibiotic analysis and whole genome sequencing of two nocardia farcinica strains causing joint infection

Objective: To analyze the molecular characteristics and antibiotic susceptibility of two strains of Nocardia farcinica isolated from patients with joint infection using whole genome sequencing. Methods: Two strains of Nocardia farcinica causing knee-joint infections in two elderly patients were collected in January 2020. Whole genome sequencing was used to determine the nocardia species. Drug sensitivity test was performed using the micro-broth dilution and E-test method according to CLSI M24 guideline. ABRicate was used to analyze drug resistance and virulence genes. Snippy and other bioinformatic tools were used for genomic comparison, and to construct SNP homologous tree. Results: The clinical isolates in this study were both Nocardia farcinica. Antimicrobial susceptibility test showed the isolates were resistant to ceftriaxone, cefepime, cefotaxime and trimethoprim/sulfamethoxazole (TMP/SMX). Imipenem, linezolid and amoxicillin-clavulanic acid showed good activity. Four antibiotic resistance genes including class A β-lactamase gene far-1, RNA polymerase binding protein gene RbpA, multi-drug resistance efflux pump transcription activator gene MtrA and regulatory transcription factor gene vanR-O were identified in the Nocardia farcinica genomes, which conferred resistance to beta-lactams, rifampicin, macrolides and vancomycin respectively. No acquired TMP/SMX resistance genes were identified. There are multiple missense mutations in the dihydrofolate reductase family genes. Four virulence genes of icl, mbtH, phoP, and relA that are homologous to Mycobacterium tuberculosis were found. SNP homologous tree analysis showed the two Nocardia strains were closely related, and there were only ten SNP sites, six compound substitutions and one deletion mutation between them. Conclusions: Whole genome sequencing technology is helpful to explore the molecular characteristics and resistance mechanisms of Nocardia species. Nocardia farcinica has a trend of spreading in China. Resistance to TMP/SMX is worthy of attention. The mutation of genes involved in the metabolic pathway of dihydrofolate might be one of multiple TMP/SMX resistance mechanisms.