Disseminated Nocardia brasiliensis Causing Septic Arthritis in a Patient with Non-Small Cell Lung Adenocarcinoma: A Case Report

Disseminated Nocardia brasiliensis Causing Septic Arthritis in a Patient with Non-Small Cell Lung Adenocarcinoma: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Disseminated Nocardia brasiliensis Causing Septic Arthritis in a Patient with Non-Small Cell Lung Adenocarcinoma: A Case Report Issa Jundi, Wafa Asad, Priyanka Mehotra, Andres Reyes-Corcho This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9528362/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Nocardia brasiliensis is classically associated with localized cutaneous infection and is a rare cause of disseminated disease. Septic arthritis due to Nocardia species is atypical and has rarely been reported without antecedent trauma. We present a case of N. brasiliensis septic arthritis in a patient with active solid organ malignancy. Case presentation An 80-year-old male with non-small cell lung adenocarcinoma, chronic obstructive pulmonary disease, and chronic kidney disease stage 3b presented with refractory soft tissue infections of the left upper and right lower extremities despite prior incision and drainage and oral antibiotics. Hospital course was complicated by progressive right knee effusion. Synovial fluid analysis demonstrated 87,000 white blood cells per microliter (95% neutrophils), glucose less than 20 mg/dL, and no crystals. Nocardia brasiliensis was cultured from multiple noncontiguous sites, including the left upper extremity abscess, right knee synovial fluid, and right lower extremity lesions. Susceptibility testing demonstrated a broad antimicrobial profile but resistance to imipenem and ciprofloxacin. Trimethoprim-sulfamethoxazole and aminoglycosides were relatively contraindicated due to renal function. The patient required right knee arthroscopy with irrigation, debridement, and complete synovectomy, multiple interventional radiology-guided drainages, and prolonged combination antimicrobial therapy with ceftriaxone, linezolid, and minocycline. His course was further complicated by persistent encephalopathy and severe malnutrition requiring enteral nutrition. At the time of reporting, the patient demonstrated clinical improvement of cutaneous and musculoskeletal lesions but remained hospitalized for non-infectious complications. Conclusions This case highlights that Nocardia brasiliensis can cause disseminated musculoskeletal infection including septic arthritis in immunocompromised patients without clear environmental exposure. In patients with chronic kidney disease, standard first-line therapies may be contraindicated, making early species identification and susceptibility-guided therapy essential, particularly given the potential for carbapenem resistance. Nocardia brasiliensis disseminated nocardiosis septic arthritis immunocompromised case report Figures Figure 1 Background Nocardiosis is an uncommon infection caused by aerobic actinomycetes first described by Edmond Nocard in 1888 [ 1 ], with an estimated 500 to 1,000 new cases annually in the United States. It disproportionately affects immunocompromised individuals, including those with solid organ or hematopoietic stem cell transplants, lymphoreticular and other malignancies, chronic corticosteroid use, and human immunodeficiency virus infection [ 2 , 3 ]. The clinical spectrum ranges from localized cutaneous disease to life-threatening disseminated infection involving the lungs, central nervous system, skin, bone, and soft tissues. Among pathogenic Nocardia species, N. brasiliensis has historically been a common cause of human nocardiosis, though its relative frequency varies considerably by geographic region [ 4 ]. The historically broad term "Nocardia asteroides " was reclassified in the 1990s using molecular methods into distinct species including N. farcinica, N. cyriacigeorgica, N. abscessus , and N. nova complex , a distinction with important clinical implications given significant differences in susceptibility profiles and disease tropism among species [ 1 ]. N. brasiliensis is classically associated with cutaneous and lymphocutaneous infection following percutaneous inoculation in tropical and subtropical regions [ 4 ], and disseminated disease is typically observed in immunocompromised hosts; early cases have documented its potential to cause invasive disease including septic arthritis [ 4 , 5 , 6 ]. A 2022 literature review identified only 20 reported cases of non-traumatic Nocardia septic arthritis, three attributed to N. brasiliensis , with the knee most affected and 75% of cases occurring in immunosuppressed patients [ 7 ]; a subsequent review identified 37 total cases, noting favorable outcomes with combined surgical debridement and prolonged antimicrobial therapy [ 8 ]. Treatment of disseminated nocardiosis typically requires combination antimicrobial therapy for a minimum of six months, with trimethoprim-sulfamethoxazole (TMP-SMX) as the preferred first-line agent [ 9 , 10 ]. TMP-SMX remains relatively contraindicated in significant renal impairment given the risks of nephrotoxicity and hyperkalemia, and aminoglycosides carry similar limitations, creating a challenging therapeutic landscape for patients with chronic kidney disease. The coexistence of active malignancy further complicates management. Malignancy has been identified as a strong independent predictor of mortality in pulmonary nocardiosis, with rates exceeding 60% in some series [ 11 , 12 ], and the prolonged antimicrobial course required for disseminated disease may preclude concurrent oncologic treatment. We report a case of disseminated N. brasiliensis with multifocal musculoskeletal involvement, including culture-confirmed septic arthritis of the knee, in an 80-year-old male with concurrent non-small cell lung adenocarcinoma and chronic kidney disease stage 3b, and provide an updated summary of reported Nocardia septic arthritis cases. Case presentation An 80-year-old male with non-small cell lung adenocarcinoma (treated with chemoradiation, now with progressive pulmonary disease), prostate cancer, COPD, hypertension, hyperlipidemia, CKD stage 3b (baseline creatinine ~ 2.0 mg/dL), gout, and severe osteoarthritis presented to the emergency department with a left upper extremity soft tissue infection. He was a former smoker with no occupational or environmental soil exposures. He underwent incision and drainage and was discharged on doxycycline, cephalexin, and a methylprednisolone taper. He returned four days later (HD1) with persistent left upper extremity cellulitis, new right lower extremity swelling and pain after a mechanical fall, and generalized weakness. Empiric IV ceftriaxone and vancomycin were initiated. Bedside drainage of a small left upper extremity fluid collection was performed and wound cultures were sent. Over subsequent days he developed progressive right knee pain and swelling. CT revealed a 3.4 × 3.5 × 7.5 cm complex collection within the anterior tibialis. On HD6, IR aspirated 70 mL of turbid fluid from the right knee; synovial analysis showed WBC 87,000 cells/µL (95% PMNs), glucose < 20 mg/dL, protein 3.0 g/dL, and no crystals, consistent with septic arthritis and effectively excluding crystalline arthropathy. Ultrasound-guided aspiration of the tibial collection yielded 30 mL of purulent material. The patient underwent right knee arthroscopy with irrigation, debridement, and synovectomy; intraoperative findings demonstrated diffuse synovitis. Cultures from the left upper extremity abscess, right knee synovial fluid, right tibial collection, and right lower extremity skin pustules grew Nocardia brasiliensis. Gram stain of the tibial fluid showed branching gram-positive bacilli. Blood, AFB, and fungal cultures were all negative. On HD6, empiric antibiotics were discontinued and the patient was started on imipenem-cilastatin 500 mg IV q12h and linezolid 600 mg IV q12h. TMP-SMX, the preferred agent, was withheld due to nephrotoxicity risk given his CKD and frailty; aminoglycosides were similarly avoided. Susceptibility results returned HD12–13 and demonstrated susceptibility to amikacin, amoxicillin-clavulanate, ceftriaxone, clarithromycin, doxycycline, linezolid, minocycline, moxifloxacin, tobramycin, and TMP-SMX, with resistance to imipenem and ciprofloxacin, indicating approximately six days of suboptimal therapy. The regimen was modified: imipenem was replaced with ceftriaxone 2 g IV q12h, linezolid was continued, and minocycline 100 mg PO q12h was added. A planned four-week IV course was to be followed by an oral regimen for a total treatment duration of 6–12 months. Workup for disseminated disease on HD8 included chest CT (stable right upper lobe mass, bilateral pulmonary nodules, mediastinal lymphadenopathy, trace right pleural effusion — no new acute findings, though pulmonary nocardiosis can be radiographically indistinguishable from malignancy) and MRI brain (limited by motion; indeterminate focus at the posterior limb of the right internal capsule, possibly artifact or hyperacute infarct). Non-contrast CT head on HD15 showed no acute intracranial abnormality. EEG on HD11 demonstrated moderate encephalopathy without epileptiform activity. Altered mental status was attributed to multifactorial causes including systemic infection, metabolic derangements, and underlying illness. On HD9, ultrasound identified a recurrent 4.8 cm left upper extremity intramuscular abscess, re-aspirated on HD11. Plastic surgery deemed the patient a poor operative candidate; IR performed bedside drainage the following day. (Place Fig. 1 A and 1 B here) The hospital course was complicated by anemia, severe malnutrition with hypoalbuminemia, dysphagia requiring nasogastric tube placement, mild transaminitis, and persistent renal impairment near baseline. COPD was managed with bronchodilators and supplemental oxygen. His functional decline was rapid and striking at admission he was ambulatory, independent, and cognitively intact; within one week he was nearly bedbound, encephalopathic, and intermittently unresponsive. Palliative Performance Scale was 30% and FRAIL score 5/5. Speech-language pathology identified moderate-to-severe receptive, expressive, and cognitive-linguistic deficits. Palliative care was involved early; the patient was designated DNR with his wife as surrogate. After goals-of-care discussions weighing progressive malignancy, the prolonged treatment required for disseminated nocardiosis, and severe debility, the family elected to continue aggressive management while acknowledging hospice as a future possibility. Further oncologic therapy was recognized as untenable during active treatment. At the time of writing (HD19), the patient remained encephalopathic and dependent on nasogastric feeds. Labs showed hemoglobin 7.4 g/dL, platelets 201 × 10⁹/L, and WBC 4.8 × 10⁹/L, with no evidence of linezolid-induced thrombocytopenia. Skin and soft tissue lesions showed measurable improvement — reduced pustule size, improving bilateral extremity lesions, and no new lesions identified. Overall prognosis remained guarded given disseminated infection, progressive malignancy, severe frailty, and multiple comorbidities. Discussion and conclusions This case describes disseminated Nocardia brasiliensis presenting as multifocal musculoskeletal infection, including septic arthritis without antecedent trauma, in an immunocompromised host. The involvement of multiple noncontiguous musculoskeletal sites is rarely reported for this species and highlights its potential for atypical invasive presentations in patients with malignancy and impaired host defenses. N. brasiliensis is classically associated with primary cutaneous and lymphocutaneous infection following percutaneous inoculation, particularly in tropical and subtropical regions [ 4 ]. Disseminated disease is uncommon and typically occurs in immunocompromised individuals. In a 2022 systematic review, Chandramohan et al. identified 20 cases of non-traumatic Nocardia septic arthritis, of which only three were attributed to N. brasiliensis; the knee was most involved, and 75% of patients were immunosuppressed [ 7 ]. Subsequent reports have reinforced the rarity of this presentation and the importance of combined surgical and prolonged antimicrobial therapy [ 9 ]. More recent cases have involved N. farcinica [ 13 , 14 ], with no additional N. brasiliensis septic arthritis cases reported, underscoring the uncommon nature of this presentation. Our case similarly demonstrates knee involvement and underlying immunosuppression but is notable for concurrent multifocal soft tissue and intramuscular disease, a pattern that may suggest underrecognized musculoskeletal tropism in disseminated infection. Unlike the lymphoreticular or transplant-associated hosts most reported in nocardiosis series, our patient's immunosuppression stemmed from solid organ malignancy and prior chemoradiation, a less frequently described predisposing condition for disseminated N. brasiliensis. (Place Table 1 here) Table 1 Reported cases of non-traumatic Nocardia septic arthritis Author, Year Age/Sex Species Joint Immunosuppression Treatment / Outcome Bross & Gordon, 1980 [ 7 ] 55/M N. asteroides Knee Corticosteroids TMP-SMX / Improved Asmar & Bashour, 1991 [ 7 ] 30/M N. asteroides Knee None TMP-SMX / Cured Koll et al., 1992 [ 7 ] 52/M N. brasiliensis Knee Corticosteroids (dexamethasone) Minocycline, amikacin / Died (other causes) Ostrum, 1993 [ 7 ] 35/M N. asteroides Hip Corticosteroids (renal transplant) TMP-SMX, surgery / Improved Crouzet et al., 1994 [ 7 ] 86/M N. asteroides Knee Corticosteroids TMP-SMX / Cured Ray et al., 1994 [ 7 ] 36/M N. asteroides Knee HIV/AIDS TMP-SMX / Cured Arnal et al., 1997 [ 7 ] 37/F N. asteroides Knee (prosthetic) SLE, corticosteroids TMP-SMX / Cured Gurevitch et al., 1999 [ 7 ] 73/M N. asteroides Knee Renal transplant TMP-SMX / Cured Nizam et al., 2007 [ 7 ] 55/F N. nova Knee (prosthetic) None (obese) Clarithromycin, TMP-SMX, AMX/CLV / Cured Uçkay et al., 2010ᵃ [ 7 ] 34/M Novel species Ankle None (trauma) AMC, TMP-SMX / Cured Kapur et al., 2013 [ 7 ] 4/F N. brasiliensis PIP joint None TMP-SMX / Cured Naija et al., 2014 [ 7 ] 60/M N. cyriacigeorgica Knee Corticosteroids TMP-SMX, imipenem / Cured Chaussade et al., 2015 [ 7 ] 63/M N. farcinica Knee Renal transplant TMP-SMX, imipenem / Cured Chaussade et al., 2015 [ 7 ] 64/M N. farcinica Knee Corticosteroids TMP-SMX / Cured Chaussade et al., 2015 [ 7 ] 65/M N. nova Wrist HIV TMP-SMX, AMC / Cured Chandramohan et al., 2022 [ 7 ] 64/M N. brasiliensis Knee Corticosteroids (membranous nephropathy) Linezolid, AMX/CLV, then TMP-SMX / Improved Fazili et al., 2022 [ 8 ] 78/F N. veterana/elegans Knee None TMP-SMX / Cured Thakur et al., 2023 [ 13 ] 78/F N. farcinica Shoulder None reported Debridement + antibiotics / Improved Kessler et al., 2024 [ 14 ] 74/M N. farcinica Knee ANCA vasculitis, immunosuppressants Linezolid, debridement / Improved Present case 80/M N. brasiliensis Knee NSCLC, chemoradiation, CKD 3b Ceftriaxone, linezolid, minocycline; arthroscopy + synovectomy / Ongoing – clinical improvement on current regimen Cases originally reported between 1980 and 2015 are adapted from the systematic review by Chandramohan et al. [ 7 ]; the 2022 case of N. veterana/elegans knee infection (Fazili et al.) is adapted from this review [ 8 ]. The Chandramohan et al. 2022 publication [ 7 ] is additionally represented as an independent case entry in this table. All remaining cases were identified through primary literature review. AMC, amoxicillin-clavulanate; AMX/CLV, amoxicillin-clavulanate; ANCA, antineutrophilic cytoplasmic antibody; CKD, chronic kidney disease; HIV, human immunodeficiency virus; NSCLC, non-small cell lung carcinoma; PIP, proximal interphalangeal; SLE, systemic lupus erythematosus; TMP-SMX, trimethoprim-sulfamethoxazole. ᵃUçkay et al. 2010 involved minor antecedent trauma; this case was retained as originally included in the Chandramohan et al. systematic review, which classified it among non-traumatic cases based on the authors’ judgment No clear environmental exposure or inoculation event was identified. Although the initial presentation may suggest a cutaneous portal of entry, the distribution of lesions, including inaccessible areas such as the back, favors hematogenous dissemination. This occurred despite persistently negative blood cultures, which does not exclude dissemination given the low reported rates of Nocardia bacteremia (1.3–7.7%) [ 15 ]. A pulmonary source remains possible, particularly as up to one-third of pulmonary nocardiosis cases disseminate [ 16 ], although imaging could not distinguish infection from underlying malignancy [ 17 , 18 ]. Brief corticosteroid exposure may have contributed, though likely played a minor role relative to the patient’s underlying immunocompromised state. Evaluation for central nervous system involvement was limited by motion artifact on MRI, and further testing was not feasible. No definitive CNS disease was established, and encephalopathy was attributed to multifactorial causes. Management was complicated by chronic kidney disease, limiting use of first-line agents including trimethoprim-sulfamethoxazole and aminoglycosides. Notably, the isolate demonstrated resistance to imipenem (MIC 32 µg/mL), consistent with reports of high carbapenem non-susceptibility in N. brasiliensis [ 19 ]. Given the frequent inclusion of imipenem in empiric regimens for severe nocardiosis [ 9 ], this highlights the importance of early species identification and susceptibility-guided therapy. Following susceptibility results, treatment was transitioned to ceftriaxone, linezolid, and minocycline. While linezolid offers reliable activity against Nocardia species [ 1 , 20 ], prolonged use necessitates careful monitoring for hematologic and neurologic toxicity, particularly in patients with limited physiologic reserve. This case also illustrates the complexity of managing prolonged infection in the setting of advanced malignancy. The patient’s progressive lung adenocarcinoma and prior chemoradiation likely contributed to impaired cell-mediated immunity and susceptibility to disseminated infection. At the same time, the need for extended antimicrobial therapy limited the feasibility of further oncologic treatment. Malignancy has been associated with increased risk of dissemination and mortality in nocardiosis [ 12 , 21 ], and outcomes are influenced by host immune status, infection burden, species, and adequacy of therapy. Although the absence of confirmed CNS involvement and infection with N. brasiliensis rather than N. farcinica may be relatively favorable prognostic features [ 22 , 23 ], overall prognosis remains guarded given the patient’s functional decline and comorbidities. Early palliative care involvement was appropriate and highlights the importance of aligning treatment decisions with patient goals in the setting of competing life-limiting conditions. This report has several limitations. The patient’s clinical course remains ongoing, and long-term outcomes are not yet known. CNS involvement could not be definitively excluded due to limited imaging. Molecular speciation beyond culture-based identification was not performed, although N. brasiliensis was consistently isolated from multiple sites. The mechanism of primary infection also remains uncertain. In summary, this case adds to the limited literature on disseminated N. brasiliensis and represents a rare instance of septic arthritis without antecedent trauma or clear environmental exposure. The combination of multifocal musculoskeletal involvement, renal-limited antimicrobial options, and carbapenem resistance underscores the importance of early microbiologic diagnosis and tailored therapy. It also highlights the clinical challenges that arise when prolonged infectious treatment intersects with advanced malignancy, where multidisciplinary management and early palliative care are essential. Abbreviations AFB acid-fast bacilli COPD chronic obstructive pulmonary disease CKD chronic kidney disease CNS central nervous system CT computed tomography EEG electroencephalography HD hospital day HIV human immunodeficiency virus IR interventional radiology IV intravenous MRI magnetic resonance imaging NSCLC non-small cell lung cancer PMN polymorphonuclear neutrophil PPS Palliative Performance Scale TMP-SMX trimethoprim-sulfamethoxazole. Declarations Ethics approval and consent to participate Ethics approval was not required for this case report in accordance with institutional and national guidelines for single-patient case reports without experimental intervention. Consent for publication Written informed consent for publication of this case report was obtained from the patient’s healthcare surrogate (wife), due to the patients inability to consent. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing interests. Funding No external funding was received for the preparation of this manuscript. All work was supported by institutional resources. Author Contribution IJ: Conceptualization, Data curation, Writing – Original Draft. WA: Data curation, Literature review, Writing – Original Draft. PM: Data curation, Writing – Review & Editing. ARC: Supervision – Review & Editing. All authors read and approved the final manuscript. Acknowledgements The authors acknowledge the contributions of the infectious diseases, orthopedic surgery, interventional radiology, and palliative care teams involved in the management of this patient. We also thank the microbiology laboratory staff for their assistance with culture processing and susceptibility testing. Availability of data and materials The datasets generated and analyzed during the current case report are not publicly available due to patient privacy but are available from the corresponding author on reasonable request. References Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ Jr. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev. 2006;19(2):259–82. Wilson JW. Nocardiosis: updates and clinical overview. Mayo Clin Proc. 2012;87(4):403–407. Steinbrink J, Leavens J, Kauffman CA, Miceli MH. Manifestations and outcomes of Nocardia infections: comparison of immunocompromised and nonimmunocompromised adult patients. Med (Baltim). 2018;97(40):e12436. Smego RA Jr, Gallis HA. The clinical spectrum of Nocardia brasiliensis infection in the United States. Rev Infect Dis. 1984;6(2):164–80. Margaretten ME, Kohlwes J, Moore D, Bent S. Does this adult patient have septic arthritis? JAMA. 2007;297(13):1478–88. 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Cureus. 2022;14(11):e31246. Garcia Rueda JE, Garcia Rueda KY, Bermudez Florez AM, et al. Nocardia in an immunocompetent patient simulating pulmonary carcinoma: a case report and literature review. Cureus. 2024;16(7):e64491. Toyokawa M, Ohana N, Ueda A, Imai M, Tanno D, Honda M, et al. Identification and antimicrobial susceptibility profiles of Nocardia species clinically isolated in Japan. Sci Rep. 2021;11(1):16742. Davidson N, Grigg MJ, McGuinness SL, Baird RJ, Anstey NM. Safety and outcomes of linezolid use for nocardiosis. Open Forum Infect Dis. 2020;7(8):ofaa090. Du B, Song Z, Ren Z, et al. The global epidemiology, risk factors, and mortality prediction of nocardiosis: an easily missed opportunistic infection. Sci Rep. 2025;15:42090. Meena DS, Kumar D, Bohra GK, Midha N, Garg MK. Clinical characteristics and treatment outcome of central nervous system nocardiosis: a systematic review of reported cases. Med Princ Pract. 2022;31(4):333–41. Vega Brizneda M, Miranda C, Cober E, Misra A, Harrington S, Yetmar ZA. Risk factors and outcomes of disseminated nocardiosis across host risk groups. Open Forum Infect Dis. 2026;13(1):ofag008. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 05 May, 2026 Editor invited by journal 04 May, 2026 Editor assigned by journal 02 May, 2026 Submission checks completed at journal 02 May, 2026 First submitted to journal 25 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9528362","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":637860431,"identity":"86dc9122-8f30-46ad-a69e-41538bedc40b","order_by":0,"name":"Issa Jundi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAq0lEQVRIiWNgGAWjYBACNoYDDAw8BjYMBqRqSYNqSSBWHw/DYRK08DGeMXvwpuB8tDn/AbYHH38Q5bAz5oZzDG7n7pyRwG44gxhbgFrMpHmAWjbcYGCT5iFBy7ncDecPsEn/IUHLgdwNBxLYpInyPhvDsTLJOQbJQIcltkn2pBGhRX7G4W0Sb/7YAR12+JjEDxsitDBIHICxGBuIUQ8E/MQqHAWjYBSMgpELABqANLi8yB/cAAAAAElFTkSuQmCC","orcid":"","institution":"Memorial Healthcare System Hollywood","correspondingAuthor":true,"prefix":"","firstName":"Issa","middleName":"","lastName":"Jundi","suffix":""},{"id":637860432,"identity":"f28c97cc-6db0-49bd-9639-891010928be0","order_by":1,"name":"Wafa Asad","email":"","orcid":"","institution":"Nova Southeastern University","correspondingAuthor":false,"prefix":"","firstName":"Wafa","middleName":"","lastName":"Asad","suffix":""},{"id":637860433,"identity":"4519d759-6de1-4f36-8362-7e0446e4bdca","order_by":2,"name":"Priyanka Mehotra","email":"","orcid":"","institution":"Memorial Healthcare System Hollywood","correspondingAuthor":false,"prefix":"","firstName":"Priyanka","middleName":"","lastName":"Mehotra","suffix":""},{"id":637860434,"identity":"a1a3aaa7-f642-4123-b2a9-e62a69e384aa","order_by":3,"name":"Andres Reyes-Corcho","email":"","orcid":"","institution":"Memorial Healthcare System Hollywood","correspondingAuthor":false,"prefix":"","firstName":"Andres","middleName":"","lastName":"Reyes-Corcho","suffix":""}],"badges":[],"createdAt":"2026-04-25 21:53:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9528362/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9528362/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109286537,"identity":"8b2e640d-1c8a-437f-8d83-d62429c1453c","added_by":"auto","created_at":"2026-05-15 02:35:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1561005,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e1A: \u003c/strong\u003eErythema and soft tissue changes of the left upper extremity following incision and drainage. The wound demonstrates features consistent with a partially drained subcutaneous abscess with surrounding cellulitis. \u003cem\u003eNocardia brasiliensis\u003c/em\u003e was subsequently cultured from this site.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1B: \u003c/strong\u003ePustular lesions of the right lower extremity in a patient with disseminated \u003cem\u003eNocardia brasiliensis\u003c/em\u003e infection. Multiple discrete pustules are visible overlying the thigh, consistent with cutaneous dissemination.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9528362/v1/5f7accfbc6dcf59603f9d6d5.png"},{"id":109297870,"identity":"a26f3f3e-ddfd-49fc-96dd-3502155e8d68","added_by":"auto","created_at":"2026-05-15 09:07:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2189498,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9528362/v1/92f13dc0-f644-4f47-8e8b-70062459dda2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eDisseminated \u003cem\u003eNocardia brasiliensis\u003c/em\u003e Causing Septic Arthritis in a Patient with Non-Small Cell Lung Adenocarcinoma: A Case Report\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eNocardiosis is an uncommon infection caused by aerobic actinomycetes first described by Edmond Nocard in 1888 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], with an estimated 500 to 1,000 new cases annually in the United States. It disproportionately affects immunocompromised individuals, including those with solid organ or hematopoietic stem cell transplants, lymphoreticular and other malignancies, chronic corticosteroid use, and human immunodeficiency virus infection [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The clinical spectrum ranges from localized cutaneous disease to life-threatening disseminated infection involving the lungs, central nervous system, skin, bone, and soft tissues.\u003c/p\u003e \u003cp\u003eAmong pathogenic \u003cem\u003eNocardia\u003c/em\u003e species, \u003cem\u003eN. brasiliensis\u003c/em\u003e has historically been a common cause of human nocardiosis, though its relative frequency varies considerably by geographic region [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The historically broad term \u003cem\u003e\"Nocardia asteroides\u003c/em\u003e\" was reclassified in the 1990s using molecular methods into distinct species including \u003cem\u003eN. farcinica, N. cyriacigeorgica, N. abscessus\u003c/em\u003e, and \u003cem\u003eN. nova complex\u003c/em\u003e, a distinction with important clinical implications given significant differences in susceptibility profiles and disease tropism among species [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. \u003cem\u003eN. brasiliensis\u003c/em\u003e is classically associated with cutaneous and lymphocutaneous infection following percutaneous inoculation in tropical and subtropical regions [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and disseminated disease is typically observed in immunocompromised hosts; early cases have documented its potential to cause invasive disease including septic arthritis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A 2022 literature review identified only 20 reported cases of non-traumatic \u003cem\u003eNocardia\u003c/em\u003e septic arthritis, three attributed to \u003cem\u003eN. brasiliensis\u003c/em\u003e, with the knee most affected and 75% of cases occurring in immunosuppressed patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]; a subsequent review identified 37 total cases, noting favorable outcomes with combined surgical debridement and prolonged antimicrobial therapy [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTreatment of disseminated nocardiosis typically requires combination antimicrobial therapy for a minimum of six months, with trimethoprim-sulfamethoxazole (TMP-SMX) as the preferred first-line agent [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. TMP-SMX remains relatively contraindicated in significant renal impairment given the risks of nephrotoxicity and hyperkalemia, and aminoglycosides carry similar limitations, creating a challenging therapeutic landscape for patients with chronic kidney disease.\u003c/p\u003e \u003cp\u003eThe coexistence of active malignancy further complicates management. Malignancy has been identified as a strong independent predictor of mortality in pulmonary nocardiosis, with rates exceeding 60% in some series [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and the prolonged antimicrobial course required for disseminated disease may preclude concurrent oncologic treatment. We report a case of disseminated \u003cem\u003eN. brasiliensis\u003c/em\u003e with multifocal musculoskeletal involvement, including culture-confirmed septic arthritis of the knee, in an 80-year-old male with concurrent non-small cell lung adenocarcinoma and chronic kidney disease stage 3b, and provide an updated summary of reported \u003cem\u003eNocardia\u003c/em\u003e septic arthritis cases.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eAn 80-year-old male with non-small cell lung adenocarcinoma (treated with chemoradiation, now with progressive pulmonary disease), prostate cancer, COPD, hypertension, hyperlipidemia, CKD stage 3b (baseline creatinine\u0026thinsp;~\u0026thinsp;2.0 mg/dL), gout, and severe osteoarthritis presented to the emergency department with a left upper extremity soft tissue infection. He was a former smoker with no occupational or environmental soil exposures. He underwent incision and drainage and was discharged on doxycycline, cephalexin, and a methylprednisolone taper.\u003c/p\u003e\n\u003cp\u003eHe returned four days later (HD1) with persistent left upper extremity cellulitis, new right lower extremity swelling and pain after a mechanical fall, and generalized weakness. Empiric IV ceftriaxone and vancomycin were initiated. Bedside drainage of a small left upper extremity fluid collection was performed and wound cultures were sent.\u003c/p\u003e\n\u003cp\u003eOver subsequent days he developed progressive right knee pain and swelling. CT revealed a 3.4 \u0026times; 3.5 \u0026times; 7.5 cm complex collection within the anterior tibialis. On HD6, IR aspirated 70 mL of turbid fluid from the right knee; synovial analysis showed WBC 87,000 cells/\u0026micro;L (95% PMNs), glucose\u0026thinsp;\u0026lt;\u0026thinsp;20 mg/dL, protein 3.0 g/dL, and no crystals, consistent with septic arthritis and effectively excluding crystalline arthropathy. Ultrasound-guided aspiration of the tibial collection yielded 30 mL of purulent material. The patient underwent right knee arthroscopy with irrigation, debridement, and synovectomy; intraoperative findings demonstrated diffuse synovitis.\u003c/p\u003e\n\u003cp\u003eCultures from the left upper extremity abscess, right knee synovial fluid, right tibial collection, and right lower extremity skin pustules grew \u003cem\u003eNocardia brasiliensis.\u003c/em\u003e Gram stain of the tibial fluid showed branching gram-positive bacilli. Blood, AFB, and fungal cultures were all negative.\u003c/p\u003e\n\u003cp\u003eOn HD6, empiric antibiotics were discontinued and the patient was started on imipenem-cilastatin 500 mg IV q12h and linezolid 600 mg IV q12h. TMP-SMX, the preferred agent, was withheld due to nephrotoxicity risk given his CKD and frailty; aminoglycosides were similarly avoided. Susceptibility results returned HD12\u0026ndash;13 and demonstrated susceptibility to amikacin, amoxicillin-clavulanate, ceftriaxone, clarithromycin, doxycycline, linezolid, minocycline, moxifloxacin, tobramycin, and TMP-SMX, with resistance to imipenem and ciprofloxacin, indicating approximately six days of suboptimal therapy. The regimen was modified: imipenem was replaced with ceftriaxone 2 g IV q12h, linezolid was continued, and minocycline 100 mg PO q12h was added. A planned four-week IV course was to be followed by an oral regimen for a total treatment duration of 6\u0026ndash;12 months.\u003c/p\u003e\n\u003cp\u003eWorkup for disseminated disease on HD8 included chest CT (stable right upper lobe mass, bilateral pulmonary nodules, mediastinal lymphadenopathy, trace right pleural effusion \u0026mdash; no new acute findings, though pulmonary nocardiosis can be radiographically indistinguishable from malignancy) and MRI brain (limited by motion; indeterminate focus at the posterior limb of the right internal capsule, possibly artifact or hyperacute infarct). Non-contrast CT head on HD15 showed no acute intracranial abnormality. EEG on HD11 demonstrated moderate encephalopathy without epileptiform activity. Altered mental status was attributed to multifactorial causes including systemic infection, metabolic derangements, and underlying illness. On HD9, ultrasound identified a recurrent 4.8 cm left upper extremity intramuscular abscess, re-aspirated on HD11. Plastic surgery deemed the patient a poor operative candidate; IR performed bedside drainage the following day.\u003c/p\u003e\n\u003cp\u003e(Place Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB here)\u003c/p\u003e\n\u003cp\u003eThe hospital course was complicated by anemia, severe malnutrition with hypoalbuminemia, dysphagia requiring nasogastric tube placement, mild transaminitis, and persistent renal impairment near baseline. COPD was managed with bronchodilators and supplemental oxygen. His functional decline was rapid and striking at admission he was ambulatory, independent, and cognitively intact; within one week he was nearly bedbound, encephalopathic, and intermittently unresponsive. Palliative Performance Scale was 30% and FRAIL score 5/5. Speech-language pathology identified moderate-to-severe receptive, expressive, and cognitive-linguistic deficits. Palliative care was involved early; the patient was designated DNR with his wife as surrogate. After goals-of-care discussions weighing progressive malignancy, the prolonged treatment required for disseminated nocardiosis, and severe debility, the family elected to continue aggressive management while acknowledging hospice as a future possibility. Further oncologic therapy was recognized as untenable during active treatment.\u003c/p\u003e\n\u003cp\u003eAt the time of writing (HD19), the patient remained encephalopathic and dependent on nasogastric feeds. Labs showed hemoglobin 7.4 g/dL, platelets 201 \u0026times; 10⁹/L, and WBC 4.8 \u0026times; 10⁹/L, with no evidence of linezolid-induced thrombocytopenia. Skin and soft tissue lesions showed measurable improvement \u0026mdash; reduced pustule size, improving bilateral extremity lesions, and no new lesions identified. Overall prognosis remained guarded given disseminated infection, progressive malignancy, severe frailty, and multiple comorbidities.\u003c/p\u003e"},{"header":"Discussion and conclusions","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003cp\u003eThis case describes disseminated Nocardia brasiliensis presenting as multifocal musculoskeletal infection, including septic arthritis without antecedent trauma, in an immunocompromised host. The involvement of multiple noncontiguous musculoskeletal sites is rarely reported for this species and highlights its potential for atypical invasive presentations in patients with malignancy and impaired host defenses.\u003c/p\u003e\n \u003cp\u003eN. brasiliensis is classically associated with primary cutaneous and lymphocutaneous infection following percutaneous inoculation, particularly in tropical and subtropical regions [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Disseminated disease is uncommon and typically occurs in immunocompromised individuals. In a 2022 systematic review, Chandramohan et al. identified 20 cases of non-traumatic Nocardia septic arthritis, of which only three were attributed to N. brasiliensis; the knee was most involved, and 75% of patients were immunosuppressed [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Subsequent reports have reinforced the rarity of this presentation and the importance of combined surgical and prolonged antimicrobial therapy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. More recent cases have involved N. farcinica [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], with no additional N. brasiliensis septic arthritis cases reported, underscoring the uncommon nature of this presentation. Our case similarly demonstrates knee involvement and underlying immunosuppression but is notable for concurrent multifocal soft tissue and intramuscular disease, a pattern that may suggest underrecognized musculoskeletal tropism in disseminated infection. Unlike the lymphoreticular or transplant-associated hosts most reported in nocardiosis series, our patient\u0026apos;s immunosuppression stemmed from solid organ malignancy and prior chemoradiation, a less frequently described predisposing condition for disseminated \u003cem\u003eN. brasiliensis.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e(Place Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e here)\u0026nbsp;\u003c/p\u003e\n \u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eReported cases of non-traumatic \u003cem\u003eNocardia\u003c/em\u003e septic arthritis\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAuthor, Year\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eAge/Sex\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eSpecies\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eJoint\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eImmunosuppression\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTreatment / Outcome\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eBross \u0026amp; Gordon, 1980 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e55/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. asteroides\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eCorticosteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX / Improved\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAsmar \u0026amp; Bashour, 1991 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e30/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. asteroides\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eKoll et al., 1992 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e52/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. brasiliensis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eCorticosteroids (dexamethasone)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eMinocycline, amikacin / Died (other causes)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eOstrum, 1993 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e35/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. asteroides\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eHip\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eCorticosteroids (renal transplant)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX, surgery / Improved\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCrouzet et al., 1994 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e86/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. asteroides\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eCorticosteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eRay et al., 1994 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e36/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. asteroides\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eHIV/AIDS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eArnal et al., 1997 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e37/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. asteroides\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee (prosthetic)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eSLE, corticosteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eGurevitch et al., 1999 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e73/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. asteroides\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eRenal transplant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eNizam et al., 2007 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e55/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. nova\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee (prosthetic)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eNone (obese)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eClarithromycin, TMP-SMX, AMX/CLV / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eU\u0026ccedil;kay et al., 2010ᵃ [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e34/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eNovel species\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eAnkle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eNone (trauma)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eAMC, TMP-SMX / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eKapur et al., 2013 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e4/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. brasiliensis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003ePIP joint\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eNaija et al., 2014 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e60/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. cyriacigeorgica\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eCorticosteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX, imipenem / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eChaussade et al., 2015 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e63/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. farcinica\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eRenal transplant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX, imipenem / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eChaussade et al., 2015 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e64/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. farcinica\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eCorticosteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eChaussade et al., 2015 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e65/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. nova\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eWrist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eHIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX, AMC / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eChandramohan et al., 2022 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e64/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. brasiliensis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eCorticosteroids (membranous nephropathy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eLinezolid, AMX/CLV, then TMP-SMX / Improved\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eFazili et al., 2022 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e78/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. veterana/elegans\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eTMP-SMX / Cured\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eThakur et al., 2023 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e78/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. farcinica\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eShoulder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eNone reported\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eDebridement\u0026thinsp;+\u0026thinsp;antibiotics / Improved\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eKessler et al., 2024 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e74/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. farcinica\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eANCA vasculitis, immunosuppressants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eLinezolid, debridement / Improved\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003ePresent case\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e80/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cem\u003eN. brasiliensis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eNSCLC, chemoradiation, CKD 3b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eCeftriaxone, linezolid, minocycline; arthroscopy\u0026thinsp;+\u0026thinsp;synovectomy / Ongoing \u0026ndash; clinical improvement on current regimen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eCases originally reported between 1980 and 2015 are adapted from the systematic review by Chandramohan et al.\u003c/em\u003e [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]; \u003cem\u003ethe 2022 case of N. veterana/elegans knee infection (Fazili et al.) is adapted from this review\u003c/em\u003e [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. \u003cem\u003eThe Chandramohan et al. 2022 publication\u003c/em\u003e [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] \u003cem\u003eis additionally represented as an independent case entry in this table. All remaining cases were identified through primary literature review.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eAMC, amoxicillin-clavulanate; AMX/CLV, amoxicillin-clavulanate; ANCA, antineutrophilic cytoplasmic antibody; CKD, chronic kidney disease; HIV, human immunodeficiency virus; NSCLC, non-small cell lung carcinoma; PIP, proximal interphalangeal; SLE, systemic lupus erythematosus; TMP-SMX, trimethoprim-sulfamethoxazole.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eᵃU\u0026ccedil;kay et al. 2010 involved minor antecedent trauma; this case was retained as originally included in the Chandramohan et al. systematic review, which classified it among non-traumatic cases based on the authors\u0026rsquo; judgment\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eNo clear environmental exposure or inoculation event was identified. Although the initial presentation may suggest a cutaneous portal of entry, the distribution of lesions, including inaccessible areas such as the back, favors hematogenous dissemination. This occurred despite persistently negative blood cultures, which does not exclude dissemination given the low reported rates of \u003cem\u003eNocardia\u003c/em\u003e bacteremia (1.3\u0026ndash;7.7%) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A pulmonary source remains possible, particularly as up to one-third of pulmonary nocardiosis cases disseminate [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], although imaging could not distinguish infection from underlying malignancy [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Brief corticosteroid exposure may have contributed, though likely played a minor role relative to the patient\u0026rsquo;s underlying immunocompromised state.\u003c/p\u003e\n \u003cp\u003eEvaluation for central nervous system involvement was limited by motion artifact on MRI, and further testing was not feasible. No definitive CNS disease was established, and encephalopathy was attributed to multifactorial causes.\u003c/p\u003e\n \u003cp\u003eManagement was complicated by chronic kidney disease, limiting use of first-line agents including trimethoprim-sulfamethoxazole and aminoglycosides. Notably, the isolate demonstrated resistance to imipenem (MIC 32 \u0026micro;g/mL), consistent with reports of high carbapenem non-susceptibility in N. brasiliensis [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Given the frequent inclusion of imipenem in empiric regimens for severe nocardiosis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], this highlights the importance of early species identification and susceptibility-guided therapy. Following susceptibility results, treatment was transitioned to ceftriaxone, linezolid, and minocycline. While linezolid offers reliable activity against Nocardia species [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], prolonged use necessitates careful monitoring for hematologic and neurologic toxicity, particularly in patients with limited physiologic reserve.\u003c/p\u003e\n \u003cp\u003eThis case also illustrates the complexity of managing prolonged infection in the setting of advanced malignancy. The patient\u0026rsquo;s progressive lung adenocarcinoma and prior chemoradiation likely contributed to impaired cell-mediated immunity and susceptibility to disseminated infection. At the same time, the need for extended antimicrobial therapy limited the feasibility of further oncologic treatment. Malignancy has been associated with increased risk of dissemination and mortality in nocardiosis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], and outcomes are influenced by host immune status, infection burden, species, and adequacy of therapy. Although the absence of confirmed CNS involvement and infection with N. brasiliensis rather than N. farcinica may be relatively favorable prognostic features [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], overall prognosis remains guarded given the patient\u0026rsquo;s functional decline and comorbidities. Early palliative care involvement was appropriate and highlights the importance of aligning treatment decisions with patient goals in the setting of competing life-limiting conditions.\u003c/p\u003e\n \u003cp\u003eThis report has several limitations. The patient\u0026rsquo;s clinical course remains ongoing, and long-term outcomes are not yet known. CNS involvement could not be definitively excluded due to limited imaging. Molecular speciation beyond culture-based identification was not performed, although \u003cem\u003eN. brasiliensis\u003c/em\u003e was consistently isolated from multiple sites. The mechanism of primary infection also remains uncertain.\u003c/p\u003e\n \u003cp\u003eIn summary, this case adds to the limited literature on disseminated N. brasiliensis and represents a rare instance of septic arthritis without antecedent trauma or clear environmental exposure. The combination of multifocal musculoskeletal involvement, renal-limited antimicrobial options, and carbapenem resistance underscores the importance of early microbiologic diagnosis and tailored therapy. It also highlights the clinical challenges that arise when prolonged infectious treatment intersects with advanced malignancy, where multidisciplinary management and early palliative care are essential.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAFB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacid-fast bacilli\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOPD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echronic obstructive pulmonary disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCKD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echronic kidney disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecentral nervous system\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecomputed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEEG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eelectroencephalography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehospital day\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehuman immunodeficiency virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterventional radiology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintravenous\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emagnetic resonance imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNSCLC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enon-small cell lung cancer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePMN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epolymorphonuclear neutrophil\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePPS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePalliative Performance Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTMP-SMX\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etrimethoprim-sulfamethoxazole.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eEthics approval was not required for this case report in accordance with institutional and national guidelines for single-patient case reports without experimental intervention.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003e Written informed consent for publication of this case report was obtained from the patient\u0026rsquo;s healthcare surrogate (wife), due to the patients inability to consent. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo external funding was received for the preparation of this manuscript. All work was supported by institutional resources.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eIJ: Conceptualization, Data curation, Writing \u0026ndash; Original Draft. WA: Data curation, Literature review, Writing \u0026ndash; Original Draft. PM: Data curation, Writing \u0026ndash; Review \u0026amp; Editing. ARC: Supervision \u0026ndash; Review \u0026amp; Editing. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eThe authors acknowledge the contributions of the infectious diseases, orthopedic surgery, interventional radiology, and palliative care teams involved in the management of this patient. We also thank the microbiology laboratory staff for their assistance with culture processing and susceptibility testing.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eThe datasets generated and analyzed during the current case report are not publicly available due to patient privacy but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBrown-Elliott BA, Brown JM, Conville PS, Wallace RJ Jr. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev. 2006;19(2):259\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilson JW. Nocardiosis: updates and clinical overview. Mayo Clin Proc. 2012;87(4):403\u0026ndash;407.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSteinbrink J, Leavens J, Kauffman CA, Miceli MH. Manifestations and outcomes of Nocardia infections: comparison of immunocompromised and nonimmunocompromised adult patients. Med (Baltim). 2018;97(40):e12436.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmego RA Jr, Gallis HA. The clinical spectrum of Nocardia brasiliensis infection in the United States. Rev Infect Dis. 1984;6(2):164\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMargaretten ME, Kohlwes J, Moore D, Bent S. Does this adult patient have septic arthritis? JAMA. 2007;297(13):1478\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoll BS, Brown AE, Kiehn TE, Armstrong D. Disseminated Nocardia brasiliensis infection with septic arthritis. Clin Infect Dis. 1992;15(3):469\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChandramohan D, Javeri H, Anstead GM. Septic arthritis due to Nocardia brasiliensis and a review of nocardiosis as a cause of arthritis. IDCases. 2022;29:e01590.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFazili T, Bansal E, Garner D, Bajwa V, Vasudeva S. Septic arthritis due to Nocardia: case report and literature review. Am J Med Sci. 2022;364(1):88\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLafont E, Conan PL, Rodriguez-Nava V, Lebeaux D. Invasive nocardiosis: disease presentation, diagnosis and treatment \u0026ndash; old questions, new answers? Infect Drug Resist. 2020;13:4601\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuggal SD, Chugh TD. Nocardiosis: a neglected disease. Med Princ Pract. 2020;29(6):514\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee HN, Do KH, Kim EY, Choe J, Sung H, Choi SH, et al. Comparative analysis of CT findings and clinical outcomes in adult patients with disseminated and localized pulmonary nocardiosis. J Korean Med Sci. 2024;39(11):e107.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTorres HA, Reddy BT, Raad II, Tarrand J, Bodey GP, Hanna HA, et al. Nocardiosis in cancer patients. Med (Baltim). 2002;81(5):388\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThakur A, Eapen J, Cherian SS. Septic arthritis by Nocardia farcinica: case report and literature review. IDCases. 2023;31:e01668.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKessler SA, Mansour MR, Khreisat A, Tahhan M. Unveiling the complexity of Nocardia septic arthritis in an immunocompromised patient: a case report. HCA Healthc J Med. 2024;5(4):473\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaunier F, Grange S, Rigaill J, Lutz MF, Gagneux-Brunon A, Botelho-Nevers E. Bacteremia and adrenal gland abscess due to Nocardia cyriacigeorgica: a case report and review. BMC Infect Dis. 2022;22(1):966.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmbrosioni J, Lew D, Garbino J. Nocardiosis: updated clinical review and experience at a tertiary center. Infection. 2010;38(2):89\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEmanuel N, Siddique N, Greene J, Pasikhova Y, Morrison A, Ledbetter M, et al. Nocardia niwae disseminated nocardiosis: a novel species presenting concurrently with lung adenocarcinoma. Cureus. 2022;14(11):e31246.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarcia Rueda JE, Garcia Rueda KY, Bermudez Florez AM, et al. Nocardia in an immunocompetent patient simulating pulmonary carcinoma: a case report and literature review. Cureus. 2024;16(7):e64491.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eToyokawa M, Ohana N, Ueda A, Imai M, Tanno D, Honda M, et al. Identification and antimicrobial susceptibility profiles of Nocardia species clinically isolated in Japan. Sci Rep. 2021;11(1):16742.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavidson N, Grigg MJ, McGuinness SL, Baird RJ, Anstey NM. Safety and outcomes of linezolid use for nocardiosis. Open Forum Infect Dis. 2020;7(8):ofaa090.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDu B, Song Z, Ren Z, et al. The global epidemiology, risk factors, and mortality prediction of nocardiosis: an easily missed opportunistic infection. Sci Rep. 2025;15:42090.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeena DS, Kumar D, Bohra GK, Midha N, Garg MK. Clinical characteristics and treatment outcome of central nervous system nocardiosis: a systematic review of reported cases. Med Princ Pract. 2022;31(4):333\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVega Brizneda M, Miranda C, Cober E, Misra A, Harrington S, Yetmar ZA. Risk factors and outcomes of disseminated nocardiosis across host risk groups. Open Forum Infect Dis. 2026;13(1):ofag008.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Nocardia brasiliensis, disseminated nocardiosis, septic arthritis, immunocompromised, case report","lastPublishedDoi":"10.21203/rs.3.rs-9528362/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9528362/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e \u003cem\u003eNocardia brasiliensis\u003c/em\u003e is classically associated with localized cutaneous infection and is a rare cause of disseminated disease. Septic arthritis due to \u003cem\u003eNocardia\u003c/em\u003e species is atypical and has rarely been reported without antecedent trauma. We present a case of \u003cem\u003eN. brasiliensis\u003c/em\u003e septic arthritis in a patient with active solid organ malignancy.\u003c/p\u003e\u003ch2\u003eCase presentation\u003c/h2\u003e \u003cp\u003eAn 80-year-old male with non-small cell lung adenocarcinoma, chronic obstructive pulmonary disease, and chronic kidney disease stage 3b presented with refractory soft tissue infections of the left upper and right lower extremities despite prior incision and drainage and oral antibiotics. Hospital course was complicated by progressive right knee effusion. Synovial fluid analysis demonstrated 87,000 white blood cells per microliter (95% neutrophils), glucose less than 20 mg/dL, and no crystals. \u003cem\u003eNocardia brasiliensis\u003c/em\u003e was cultured from multiple noncontiguous sites, including the left upper extremity abscess, right knee synovial fluid, and right lower extremity lesions. Susceptibility testing demonstrated a broad antimicrobial profile but resistance to imipenem and ciprofloxacin. Trimethoprim-sulfamethoxazole and aminoglycosides were relatively contraindicated due to renal function. The patient required right knee arthroscopy with irrigation, debridement, and complete synovectomy, multiple interventional radiology-guided drainages, and prolonged combination antimicrobial therapy with ceftriaxone, linezolid, and minocycline. His course was further complicated by persistent encephalopathy and severe malnutrition requiring enteral nutrition. At the time of reporting, the patient demonstrated clinical improvement of cutaneous and musculoskeletal lesions but remained hospitalized for non-infectious complications.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis case highlights that \u003cem\u003eNocardia brasiliensis\u003c/em\u003e can cause disseminated musculoskeletal infection including septic arthritis in immunocompromised patients without clear environmental exposure. In patients with chronic kidney disease, standard first-line therapies may be contraindicated, making early species identification and susceptibility-guided therapy essential, particularly given the potential for carbapenem resistance.\u003c/p\u003e","manuscriptTitle":"Disseminated Nocardia brasiliensis Causing Septic Arthritis in a Patient with Non-Small Cell Lung Adenocarcinoma: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-15 02:35:10","doi":"10.21203/rs.3.rs-9528362/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-05-06T03:59:27+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-05-04T12:41:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-02T09:59:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-02T09:59:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2026-04-25T21:44:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"da9faa21-4ee3-4c04-a192-53df2df7cd51","owner":[],"postedDate":"May 15th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewersInvited","content":"4","date":"2026-05-06T03:59:27+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-05-04T12:41:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-02T09:59:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-02T09:59:01+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T02:35:10+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-15 02:35:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9528362","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9528362","identity":"rs-9528362","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}