==== Front BMC Infect Dis BMC Infect Dis BMC Infectious Diseases 1471-2334 BioMed Central London 37393238 8421 10.1186/s12879-023-08421-7 Case Report Disseminated nocardiosis in a patient with alcoholic liver cirrhosis: a case report Alqurashi Rewaa AlqurashiRewaa@gmail.com 1 Alobida Husam 2 Albathi Abdullah 3 Aldraihem Moneera 4 1 grid.415277.2 0000 0004 0593 1832 Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia 2 grid.415277.2 0000 0004 0593 1832 Department of Infectious Disease, King Fahad Medical City, Riyadh, Saudi Arabia 3 grid.415277.2 0000 0004 0593 1832 Department of Radiology, King Fahad Medical City, Riyadh, Saudi Arabia 4 grid.415277.2 0000 0004 0593 1832 Department of Neurology, King Fahad Medical City, Riyadh, Saudi Arabia 1 7 2023 1 7 2023 2023 23 4457 5 2023 23 6 2023 © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Background Nocardia are Gram-positive, aerobic, filamentous bacteria that can cause localized or disseminated infections. Immunocompromised patients are at a higher risk of developing Nocardia infection and further dissemination of the disease. To date, limited data have documented the relationship between nocardiosis and alcoholic liver disease. Case presentation We report the case of a 47-year-old man with a known history of alcoholic liver cirrhosis. The patient presented to our emergency department with redness, swelling in the left eye, and diminished bilateral vision. Fundus examination of the left eye was obscured, while that of the right eye was consistent with subretinal abscess. Therefore, endogenous endophthalmitis was suspected. Imaging revealed two ring-enhancing lesions in the brain, and multiple bilateral small cystic and cavitary lung lesions. Unfortunately, the left eye eventually eviscerated due to the rapid progression of the disease. Cultures from the left eye were positive for Nocardia farcinica. The patient was started on imipenem, trimethoprim/sulfamethoxazole, and amikacin based on culture sensitivity. The patient’s hospitalization course was complicated by his aggressive and advanced condition, which led to his death. Conclusions Although the patient’s condition initially improved with the recommended antibiotic regimens, it led to death owing to the patient’s advanced condition. Early detection of nocardial infection in patients with typical or atypical immunosuppressive conditions may improve overall mortality and morbidity. Liver cirrhosis disrupts cell-mediated immunity and may increase the risk of Nocardia infection. Keywords Infectious diseases Nocardia Liver disease Neurology issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2023 ==== Body pmcBackground Nocardia are Gram-positive aerobic filamentous bacteria that can cause localized (such as pulmonary and primary cutaneous nocardiosis) or disseminated infections. Nocardiosis is uncommon, and an established bacterial infection usually affects immunocompromised patients with cell-mediated abnormalities; however, one-third of patients are immunocompetent [1, 2]. Between 1995 and 2004, 765 Nocardia cases were submitted to the Centers for Disease Control and Prevention (CDC): 28% N. nova complex, 14% N. brasiliensis, 14% N. farcinica, and 13% N. cyriacigeorgica [3]. Despite treatment, nocardiosis was reported to have a high morbidity, and 23.1% of patients had a chronic disease that could not be cured with a high risk of recurrence. Many of these patients developed complications such as scarring, impaired vision, limp amputation, and residual neurological impairment. Regarding mortality, 5.7% of patients died because of complications of the disease [4]. Major risk factors for nocardial infection include typical immunosuppressive conditions, such as cancer, bone marrow or solid organ transplantation, high doses of corticosteroids, and HIV/AIDS. Other atypical conditions include diabetes, connective tissue diseases, alcoholism, and pulmonary alveolar proteinosis [5]. Immunocompromising entities such as autoimmune diseases,and lymphopenia subjects patients to a higher risk of developing disseminated nocardiosis. Soueges et al. found that patient who were infected with Nocardia farcinica were at a higher risk of dissemination [6]. The pace and course of the disease are primarily related to the patient’s immune status. In immunocompetent patients, the disease usually has a chronic course and is likely to be localized to a single area or organ. Hematogenous dissemination is more common in immunocompromised hosts and usually involves the central nervous system and skin [2]. To date, limited data have documented the relationship between nocardiosis and alcoholic liver disease. In this report, we present a case of disseminated nocardia with endogenous endophthalmitis; two ring-enhancing lesions in the brain; and multiple bilateral small, cystic, and cavitary lung lesions in a patient with a medical history of alcoholic liver cirrhosis. Case presentation The patient was a 47-year-old man with a history of heavy alcohol intake over the past 4 years (3–4 drinks per day), which was complicated by alcoholic liver cirrhosis (Child–Pugh C/MELD 22), portal hypertension, and esophageal varices grade 2. He presented to our emergency department with redness and swelling in the left eye for 2 months and bilateral diminished vision, mainly in the left eye, over the previous month. The patient had no history of ocular trauma. The associated symptoms included mild right upper quadrant pain, jaundice, unintentional weight loss (approximately 22 kg in the past 3 months), pruritus, and dark-colored urine. Ophthalmic examination done upon presentation is shown in (Table 1).Table 1 Ophthalmic examination upon presentation Ophthalmic examination Right Left External Exam Normal Mild eyelid swelling, severe conjunctival congestion, hyperemia Visual acuity Accurate perception of light No light perception Slit Lamp Exam  Cornea Clear Clear  Anterior chamber Deep and quite  + 3 cells and + 2 flare  Iris Medically dilated Posterior synechiae  Lense Clear Clear  Vitreous Clear  + 4 cells Fundus exam  Macula Large sub-retinal white to yellow abscess measuring 6 mm, extending beyond temporal arcades and cover all macula Obscured The initial blood analysis was as follows: complete blood count: white blood cells: 10.3 × 103/µL (normal range 4.5 to 11.0 × 106/μL), red blood cells: 3.5 × 106/μL (normal range 4.7 to 6.1 × 106/μL), hemoglobin: 11.2 g/ldl (normal range 13.2 to 16.6 g/dl), platelets: 225 × 103/µL (normal range 150 to 400 × 103/µL); creatinine: 64 µmol/L (normal range 53 to 97.2 µmol/L), serum sodium: 131 mmol/L (normal range 136 and 145 mmol/L), serum potassium: 4.4 mmol/L (normal range 3.6 to 5.2 mmol/L), serum magnesium: 0.74 mmol/L (normal range 0.85 to 1.10 mmol/L), corrected calcium: 2.2 mmol/L (normal range 2.2 to 2.7 mmol/L), Erythrocyte sedimentation rate: 95 mm/hr (normal range 0 to 15 mm/hr); C-reactive protein level: 92 mg/L (normal range < 3 mg/L); total bilirubin: 132 µmol/L (normal range 1.71 to 20.5 µmol/L); alkaline phosphatase: 151 U/L (normal range 44 to 147 U/L); alanine aminotransferase: 33 U/L (normal range 4 to 36 U/L); albumin: 28.7 g/L (normal range 34 to 54 g/L); and lactic acid: 1.8 mmol/L (normal range 0.5 to 2.2 mmol/L). Computed tomography (CT) of the brain and orbits revealed two ring-enhancing lesions in the left frontal lobe along with orbital findings suggestive of left orbital endophthalmitis (Fig. 1). Contrast-enhanced magnetic resonance imaging was performed to confirm the diagnosis of supra- and infratentorial brain abscesses and left eye endophthalmitis with a subretinal abscess (Fig. 2).Fig. 1 Left image: Axial contrast-enhanced CT scan of the orbits showing generalized scleral thickness of the left eye with heterogeneous increase in density of the vitreous content. Also seen is soft tissue swelling, orbital proptosis, peri- and post-septal orbital fat stranding plus thickening, and enhancement of the globe wall. Findings that are suggestive of endophthalmitis and subretinal abscess. Enlargement of the lacrimal gland is also noted. Right image: Axial section of a contrast-enhanced CT of the brain shows a ring- enhancing lesion in the left frontal lobe measuring 0.9 cm with surrounding vasogenic edema. Findings consistent with intraparenchymal abscess Fig. 2 Contrast-enhanced T1-weighted images. Multiple supra- and infratentorial rim-enhancing lesions. Also noted surrounding vasogenic edema. Findings that are consistent with abscesses. Images on the right show enhancement of the left globe and surrounding soft tissue. Relatively hyperintense subretinal fluid is noted. Findings that are consistent with left eye endophthalmitis and subretinal abscess. The right orbit shows enhancement of the extra-conal soft tissue suggesting involvement Magnetic resonance cholangiopancreatography was performed to rule out malignancy and hepatic lesions; however, it only showed a cirrhotic liver with portal hypertension without any focal lesions. However, an incidental finding of bilateral lower-lobe pulmonary nodules was noted, for which a dedicated chest CT was planned. High-resolution chest CT revealed multiple small bilateral cystic and cavitary lung lesions (Fig. 3).Fig. 3 Axial sections of a contrast-enhanced CT scan of the chest show multiple bilateral cystic and cavitary lung lesions, predominantly involving the lower lobes. A cavitary nodule is seen in the superior segment of the left lower lobe showing thickened wall (upper left image) The patient underwent further investigations, including blood culture, bronchoalveolar lavage culture, AFB of three samples from saliva, QuantiFERON TB gold test, HIV tests, and syphilis serology. However, all tests had negative results. An ophthalmic examination shown in (Table 1) revealed a subretinal abscess in the right eye. The patient was initially suspected to have endogenous endophthalmitis and was started on intravitreal vancomycin, ceftazidime, and voriconazole. A few days later, the patient’s left eye failed to improve, and as a result, evisceration of the left eye was decided. Microbiological studies were performed on the left eye specimen; Ziehl–Neelsen (ZN) staining was negative; however, the modified ZN stain was positive. Partial acid-fast bacteria (AFB) stained positive. Culture of the left eye swab done in Blood agar and MacConkey agar confirmed the diagnosis of Nocardia farcinica infection. Identification was performed using MALDI-TOF and sensitivity using the manual E-test (Table 2).Table 2 Patient minimum inhibitory concentration with CLSI M24-A2 reference criteria for sensitivity Antibiotic Patient MICa CLSI M24-A2 MIC Susceptible CLSI M24-A2 MIC Intermediate CLSI M24-A2 MIC Resistant Trimethoprim-sulfamethoxazole 0.5 μg/mL  ≤ 2/38 -  ≥ 4/76 Linezolid 1.0 μg/mL  ≤ 8 - - Amoxicillin clavulanate 2.0 μg/ml  ≤ 8/4 16/8  ≥ 32/16 Ciprofloxacin 0.047 μg/mL  ≤ 1 2  ≥ 4 Amikacin 0.5 μg/mL  ≤ 8 -  ≥ 16 Ceftriaxone 2.0 μg/mL  ≤ 8 16–32  ≥ 64 Imipenem 0.5 μg/mL  ≤ 4 8  ≥ 16 Doxycycline 4 μg/mL  ≤ 1 2–4  ≥ 8 Minocycline 1.0 μg/mL  ≤ 1 2  ≥ 8 Clarithromycin 0.75 μg/mL  ≤ 2 4  ≥ 8 a MIC Minimum inhibitory concentration Histopathological examination revealed dense histiocytic and neutrophilic infiltrates consistent with an abscess (acute endophthalmitis). Special staining including Grocott’s methenamine silver, and periodic acid-Schiff staining yielded negative results, while Acid-fast bacteria (AFB) satin was partially positive. When disseminated nocardiosis was confirmed, the patient was started on Nocardia treatment (imipenem 500 mg every 8 h IV, trimethoprim/sulfamethoxazole 255 mg every 6 h, and amikacin 15 mg/kg once daily). Within a few days, the patient’s condition improved with complete resolution of the subretinal abscess in the right eye. Follow-up ophthalmic examination during treatment is shown in (Table 3).Table 3 Ophthalmic examination during treatment Ophthalmic examination Right Left External Exam Normal Eviscerated Visual acuity Counting fingers Slit Lamp Exam  Cornea Clear  Anterior chamber Deep and quite  Iris Medically dilated  Lense Clear  Vitreous Clear Fundus exam  Macula Resolved macular abscess. Retinal pigment epithelium (RPE) changes around the inferotemporal arcade Follow-up magnetic resonance imaging of the brain also showed interval regression in the size of multiple peripherally located bilateral ring-enhancing lesions. However, CT angiography of the chest, which was performed to rule out pulmonary embolism a month after the previous chest CT, revealed progression of multiple bilateral cavitary lung lesions with the development of pneumomediastinum (Fig. 4).Fig. 4 Axial sections of CT angiography of the pulmonary arteries, performed a month after the previous chest CT (Fig. 3), show progression of bilateral cavitary lung lesions and more evident traction bronchiectasis. It also shows development of bilateral peripheral patchy ground glass opacities and compressive atelectasis. Note is also made of pneumomediastinum During hospital stay, the patient developed acute pancreatitis and acute kidney injury, which were primarily treated with hydration and pain management. The patient received imipenem, amikacin, trimethoprim/sulfamethoxazole, and neomycin for 6 weeks. The patient was maintained on ocular prednisolone and cyclopentolate, as recommended by an ophthalmologist. The patient’s hospital course was complicated by his aggressive and advanced condition. He developed septic shock and died of cardiac arrest in the intensive care unit. Discussion In most cases, disseminated nocardiosis is transmitted from the lungs to the central nervous system, skin, and soft tissues. This is usually observed in severely immunocompromised patients (patients with AIDS and transplant recipients) [2]. We performed a literature review by searching the MEDLINE database using keywords, including “nocardia,” “nocardiosis,” “alcohol,” and “cirrhosis,” and we found that this is an extremity rare case of disseminated nocardiosis in a patient with a medical background of alcoholic liver cirrhosis. Torres et al. and Budzik et al. reviewed 53 and 67 cases of Nocardia farcinica, respectively. According to Torres et al., 85% of patients have predisposing factors, and Budzik et al. further investigated these factors. Most patients (61.2%) were immunosuppressed (on chemotherapy or steroids), 17% were solid organ transplant recipients, 13% had chronic obstructive pulmonary disease, 9% had diabetes mellitus, 7.5% were infected with human immunodeficiency virus, another 7.5% had solid neoplasms, and the last 3% had alcoholism [7, 8]. Budzik et al. reviewed 3 patients who were alcoholics that were infected with N. farcinica. Two out of the three patients had another underlying immunosuppressive condition, including renal transplant and diabetes. The third patient was exclusively alcoholic who had an infection involving the CNS, spine, and the psoas muscle [8]. (Table 4) shows the percentage of organ involvement in N. farcinica infection in both studies, where the lung was the most affected organ in both sets of patients, and the eye was infected in only two out of both sets of patients. A comparison of the antibiotic susceptibility of N. farcinica isolated in the cases reviewed by Torres et al. and those isolated in our case demonstrates that most patients were sensitive to trimethoprim-sulfamethoxazole, amikacin, and imipenem [7, 8].Table 4 Organ involvement in N. farcinica infection Organ involvement Torres et al. n = 53 (%) Budzik et al. n = 67 (%) Lung 23 (43%) 40 (59%) Brain 16 (30%) 22 (32%) Wound infections 8 (15%) 12 (17.9%) Spine 2 (3%) — Kidney 4 (8%) 1 (1.5%) Lymphatic 1 (1.5%) — The recommendation is for immunocompetent patients infected with N. farcinica who are susceptible to trimethoprim-sulfamethoxazole, moxifloxacin, amikacin, minocycline, linezolid, ciprofloxacin, and imipenem-cilastatin to be treated for at least 6 months, and the period could increase to at least 12 months if the central nervous system is involved [9–12]. In our case, the patient was started on imipenem, trimethoprim/sulfamethoxazole, and amikacin, and within a few days, the patient’s condition remarkably improved with complete resolution of the subretinal abscess in the right eye. However, owing to the patient’s advanced and aggressive disease, the he developed septic shock and died in the intensive care unit. Immunocompromised patients with nocardial infections often exhibit cell-mediated abnormalities [13, 14]. Liver cirrhosis is an atypical immunosuppressive condition associated with immune dysfunction regardless of the cause. This leads to alterations in the hemostatic role of the liver and disrupts the innate and acquired immunity by causing defects in both local and systemic immunity leading to a high mortality rate (30%) and an increase in systemic inflammation and immunodeficiency [15]. Conclusion Although the patient’s condition initially improved with imipenem, trimethoprim/sulfamethoxazole, and amikacin, the patient’s hospitalization course was complicated and led to death. Early detection of nocardial infection in patients with typical or atypical immunosuppressive conditions may improve overall mortality and morbidity. Acknowledgements None. Authors’ contributions Rewaa Alqurashi wrote and reviewed the manuscript Husam Alobida reviewed the manuscript Abdullah Albathi prepared figures, wrote captions, and reviewed the manuscript Moneera Aldraihem wrote the discussion. Funding This case report is not funded. Availability of data and materials The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Declarations Ethics approval and consent to participate It was taken from the hospital’s Institutional Review Board. Consent for publication Written informed consent was obtained from patient’s brother for publication of this case report. Competing interests The authors declare no competing interests. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. ==== Refs References 1. Brown-Elliott BA Brown JM Conville PS Wallace RJ Clinical microbiology reviews Clin Microbiol Rev 2006 19 2 259 282 10.1128/CMR.19.2.259-282.2006 16614249 2. Ambrosioni J Lew D Garbino J Nocardiosis: updated clinical review and experience at a tertiary center Infection 2010 38 2 89 97 10.1007/s15010-009-9193-9 20306281 3. Uhde KB Pathak S McCullum I Jr Jannat-Khah DP Shadomy SV Dykewicz CA Clark TA Smith TL Brown JM Antimicrobial-resistant nocardia isolates, United States, 1995–2004 Clin Infect Dis 2010 51 12 1445 1448 10.1086/657399 21058914 4. Martínez-Barricarte R Isolated nocardiosis, an unrecognized primary immunodeficiency? Front Immunol 2020 20 11 590239 10.3389/fimmu.2020.590239 5. Centers for Disease Control and Prevention. Nocardiosis: risk of infection. 2022. https://www.cdc.gov/nocardiosis/infection/index.html. Accessed 11 Oct 2022. 6. Soueges S Bouiller K Botelho-Nevers E Gagneux-Brunon A Chirouze C Rodriguez-Nava V Dumitrescu O Triffault-Fillit C Conrad A Lebeaux D Hodille E Prognosis and factors associated with disseminated nocardiosis: a ten-year multicenter study J Infect 2022 85 2 130 136 10.1016/j.jinf.2022.05.029 35654278 7. Torres OH Domingo P Pericas R Boiron P Montiel JA Vázquez G Infection caused by Nocardia farcinica: case report and review Eur J Clin Microbiol Infect Dis 2000 19 3 205 212 10.1007/s100960050460 10795594 8. Budzik JM Hosseini M Mackinnon AC Jr Taxy JB Disseminated Nocardia farcinica: literature review and fatal outcome in an immunocompetent patient Surg Infect (Larchmt) 2012 13 3 163 70 10.1089/sur.2011.012 22612440 9. Mamelak AN Obana WG Flaherty JF Rosenblum ML Nocardial brain abscess: treatment strategies and factors influencing outcome Neurosurgery 1994 35 622 631 10.1227/00006123-199410000-00007 7808604 10. Hansen G Swanzy S Gupta R Cookson B Limaye AP In vitro activity of fluoroquinolones against clinical isolates of Nocardia identified by partial 16S rRNA sequencing Eur J Clin Microbiol Infect Dis 2008 27 2 115 120 10.1007/s10096-007-0413-2 17992548 11. Jodlowski TZ Melnychuk I Conry J Linezolid for the treatment of Nocardia spp. infections Ann Pharmacother 2007 41 1694 9 10.1345/aph.1K196 17785610 12. Minero MV Marin M Cercenado E Rabadán PM Bouza E Muñoz P Nocardiosis at the turn of the century Medicine 2009 88 250 261 10.1097/MD.0b013e3181afa1c8 19593231 13. Lederman ER Crum NF A case series and focused review of nocardiosis: clinical and microbiologic aspects Medicine (Baltimore) 2004 83 5 300 313 10.1097/01.md.0000141100.30871.39 15342974 14. Palmer DL Harvey RL Wheeler JK Diagnostic and therapeutic considerations in Nocardia asteroides infection Medicine 1974 53 5 391 401 10.1097/00005792-197409000-00005 4604319 15. Noor MT Manoria P Immune dysfunction in cirrhosis J Clin Transl Hepatol 2017 5 1 50 58 10.14218/JCTH.2016.00056 28507927