Nocardia Infection Presented as Intramuscular Abscess in a Kidney Transplant Recipient: Case Report and Literature Review.

1. Introduction

Nocardia spp. are Gram-positive bacteria capable of causing both local and systemic infections. Although nocardiosis has been traditionally viewed as an opportunistic infection, immunocompetent subjects may also be infected. However, disease in immunocompromised patients tends to be more severe and disseminated [ 1 ]. Nocardia pseudobrasiliensis is a relatively newer species. It is distinguishable from N. brasiliensis given its distinctions in disease patterns and antibiotic susceptibility profiles. In particular, the former is more strongly associated with invasive and disseminated disease [ 1 ].

We report an unusual case of a nocardiosis presenting as a localised intramuscular abscess caused by N. pseudobrasiliensis in a renal transplant recipient.

2. Case Report

A 67-year-old man with end-stage kidney disease secondary to autosomal dominant polycystic kidney disease received a deceased-donor kidney transplant three years prior. His renal transplant was complicated by an episode of cytomegalovirus viraemia in the early post-transplant period which was treated with valganciclovir. Induction immunosuppressive therapy included antithymocyte globulin (ATG). His immunosuppressive regimen included tacrolimus and prednisolone. Mycophenolate was ceased due to significant leukopenia. His allograft function was stable with serum creatinine of 130 μmol/L (60–110 μmol/L).

His other comorbidities include type II diabetes mellitus, hypertension, gout, a previous posterior circulation embolic cerebrovascular accident and recent unproved pulmonary embolism for which he has been anticoagulated with apixaban.

Given his good allograft function, his left arteriovenous fistula was ligated 12 months post-kidney transplant. Swelling of the opposite right biceps brachii was noted 2 days after this procedure in the vicinity of an intravenous cannula inserted at the time of fistula ligation. Ultrasound showed a 10 × 20 × 20 mm intramuscular fluid collection presumed to be an intramuscular haematoma given the recent commencement of apixaban. The patient represented to hospital a few days later in the setting of increasing pain and swelling of the right biceps. Physical examination did not reveal a palpable mass. There were no accompanying constitutional symptoms and the patient was apyrexial. Repeat ultrasound showed a persistent heterogenous hypoechoic collection now measuring 71 × 48 × 47 mm. Computed tomography (CT) confirmed a deep collection in the right biceps with low density centrally and rim enhancement on delayed phase suggestive of an intramuscular abscess.

Laboratory investigations performed at this time showed a haemoglobin of 141 g/L (reference range 135–175 g/L) and white cell count of 4.86 × 10 9 /L (4–11 × 10 9 /L) with an absolute neutrophil count of 3.26 × 10 9 /L (1.80–7.5 × 10 9 /L). C-reactive protein was 146 mg/L (0.0–8.0 mg/L), and serum creatinine was 109 µmol/L (60–110 μmol/L). The tacrolimus level was 6.3 μg/L (5–15 μg/L).

Subsequent incision and drainage were performed with the intraoperative finding of a large collection of pus within the right bicep muscle. Microscopy of the intraoperative sample showed numerous polymorphonuclear leukocytes and branching Gram-positive bacilli resembling Nocardia . Modified Ziehl–Neelsen stain was positive. Empiric treatment included meropenem and linezolid. Species identification was confirmed as N. pseudobrasiliensis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with Version 10 of the Bruker database (Bruker Daltonics, Bremen, Germany). 16S rRNA gene sequencing and BLAST analysis showed 100% identity with N. pseudobrasiliensis type strains ATCC 51512 and DSM 44290. Susceptibility testing was performed by broth microdilution and showed characteristic resistance to imipenem and susceptibility to ciprofloxacin, SXT, amikacin, clarithromycin and linezolid. Blood cultures were negative.

Whole body CT showed an area of consolidation in the right middle lobe but no other foci of infection. The CT findings were present on previous imaging of the chest but were thought to represent a pulmonary infarct rather than infection given the appearance and the known occurrence of a recent pulmonary embolism. Magnetic resonance imaging (MRI) of the brain was also performed, showing no evidence of cerebral abscess.

The treatment regimen was subsequently changed to linezolid and trimethoprim/sulfamethoxazole (TMP-SMX). On discharge from hospital, the antibiotic regimen was further revised to oral ciprofloxacin and TMP-SMX due to the concern of linezolid causing bone marrow suppression. TMP-SMX was subsequently ceased due to persistent hyperkalaemia and replaced with azithromycin. Treatment with ciprofloxacin and azithromycin was given for 6 months with good response.

A repeat CT scan of the chest 2 months into treatment showed resolution of the right middle lobe consolidation. There has been no evidence of recurrence 30 months after ceasing antimicrobials.

3. Discussion

Nocardiosis is a rare bacterial infection which can affect immunocompetent individuals, but more frequently causes disease in immunocompromised patients, with glucocorticoid therapy as the leading risk factor [ 2 ]. Nocardiosis is caused by aerobic actinomycetes which are found in soil and putrefying plant matter, with infection typically caused by inhalation or direct inoculation [ 3 – 5 ]. Nocardia spp. cause both localised and systemic infections, with the most frequent clinical presentation being pulmonary infection [ 5 ]. Target organs affected by disseminated nocardiosis most commonly include the central nervous system (CNS) and cutaneous tissues [ 6 ]. N. asteroides is the most common organism within the genus to cause disease, followed by N. brasiliensis [ 7 , 8 ].

Infection in our case was caused by N. pseudobrasiliensis . This organism was first identified in 1996, with 16S rRNA gene sequence analysis and DNA-DNA hybridisation confirming that this taxon constituted a new species [ 8 ]. However, to date, few cases have been reported [ 7 – 9 ]. N. pseudobrasiliensis differs from N. brasiliensis by way of its adenine metabolism and nitrate reductase activity [ 7 ]. The species further differ in terms of clinical presentation; N. pseudobrasiliensis typically causes invasive and disseminated disease as opposed to localised disease, which is more commonly associated with N. brasiliensis [ 10 ]. Moreover, N. pseudobrasiliensis also causes disease in immunocompetent patients [ 10 ]. Importantly, the species differ in their susceptibility profiles, with N. pseudobrasiliensis showing variable susceptibility to carbapenems, while N. brasiliensis is inherently resistant to ciprofloxacin [ 10 , 11 ].

Extensive search of the literature revealed 17 cases ( Table 1 ) of N. pseudobrasiliensis, with only one other case of an intramuscular abscess [ 8 ]. This case involved a 79-year-old man with bilateral multifocal intramuscular leg abscesses in the setting of long-term steroid use for myasthenia gravis, as well as pulmonary infection with the abscesses presumed to be caused by dissemination [ 8 ]. This finding raises the possibility of a similar dissemination mechanism in our patient. After treatment with linezolid for less than 3 weeks, followed by moxifloxacin for 6 months, there was no recurrence at 1-year follow-up.

A further search of Nocardia presentations with intramuscular involvement yielded 23 cases in the English language, including the present case, as outlined in Table 2 . Of these, N. farcinica was the most frequent causative organism, occurring in 9 cases [ 4 , 23 – 25 , 32 , 35 – 38 ], followed by N. asteroides in 4 cases [ 30 , 33 , 34 , 39 ]. N. pseudobrasiliensis presented twice [ 8 ], including our case. Leg muscles, particularly involving the thigh, were most frequently affected, with back, shoulder and upper limb muscle abscesses presenting less frequently. This places our case in a rarer context, given it was the biceps brachii that was affected. Multiorgan involvement, usually of the lungs and brain, occurred in almost every case.

While immunosuppression was a leading risk factor, 30% did not report an immunosuppressive risk, suggesting that a Nocardia differential diagnosis should not be neglected in immunocompetent patients. Surgical intervention was required in 17 cases, with a minority resolving solely on medical treatment. Surgical drainage was the primary approach, as also seen in our case, although debridement was necessary in 4 cases. Concerning antibiotic choice, TMP-SMX has been recommended as the first-line agent [ 41 , 42 ] and was commonly utilised, as seen in 18 cases. However, given that dual coverage is recommended in complex cases, especially with CNS involvement [ 42 ], a combination of antibiotics was given to most patients, with agents including imipenem, meropenem, amikacin, linezolid, ciprofloxacin and ceftriaxone demonstrating effectiveness by either improving or resolving infection-related symptoms. Both our case and that of Veerappan Kandasamy et al. [ 8 ] featured nocardiosis due to N. pseudobrasiliensis with intramuscular involvement. Here, linezolid was an initial shared antibiotic. However, a key difference to note was that TMP-SMX was administered to our patient, before being substituted for azithromycin, with the patient's symptoms fully resolving with no recurrence to date.

Nocardiosis most commonly occurs in patients with malignancy, solid organ transplant, human immunodeficiency virus infection and long-term corticosteroid use [ 2 , 43 ]. Regarding the solid organ transplant population, Nocardia is responsible for 0.7%–3% of infections, predominantly in kidney, heart and liver transplant recipients [ 2 ]. Additional risk factors include supratherapeutic calcineurin inhibitor levels and prior cytomegalovirus infection [ 2 , 43 , 44 ]. Our case had a history of cytomegalovirus viraemia; however, not in the preceding 6 months, which was the timeframe the literature has demonstrated [ 2 , 43 ]. The other known case of N. pseudobrasiliensis in a renal transplant recipient was a 68-year-old man with pulmonary infection in the setting of supratherapeutic tacrolimus levels [ 17 ]. This patient's elevated mean calcineurin inhibitor levels in the 30 days prior were a risk factor for developing Nocardia infection [ 2 ].

Nocardiosis can be treated successfully with prolonged courses of sulfonamides, particularly for localised disease in combination with surgical drainage or debridement [ 45 ]. However, TMP-SMX, which is commonly prescribed for Pneumocystis jirovecii prophylaxis in transplant recipients, may not be sufficient to prevent Nocardia infection, and resistance has also been reported amongst N. pseudobrasiliensis isolates [ 46 ]. Disseminated disease in immunocompromised patients generally warrants a two-drug treatment regimen given the high mortality associated with Nocardia infection in these patients, the diversity of Nocardia species and their variable antibiotic susceptibility profiles [ 45 ]. Schlaberg et al. report linezolid as an effective agent against various nocardial strains, including N. pseudobrasiliensis, particularly given its extensive bioavailability and tissue distribution [ 46 ], Linezolid has been utilised in numerous Nocardia infections with intramuscular involvement as seen in Table 2 . Moreover, given its observed effectiveness against N. pseudobrasiliensis, fluoroquinolones have also been recommended [ 8 ], as further corroborated by our case. Clarithromycin or azithromycin and tobramycin have also demonstrated efficacy against N. pseudobrasiliensis [ 46 ]. While these cases point towards 4–6 months of therapy, the optimal duration of antibiotic therapy currently remains elusive. This should be addressed in future studies to mitigate the risk of under- and overprescribing antibiotics, both of which are associated with suboptimal clinical outcomes, especially in the context of multidrug-resistant strains of N. pseudobrasiliensis.

4. Conclusion

Nocardiosis requires consideration in the differential diagnosis of infections in immunocompromised patients especially with unusual presentations. This is particularly critical given the speciation, clinically relevant differences in disease patterns and antibiotic susceptibility between N. pseudobrasiliensis and N. brasiliensis . A multidrug antibiotic course for systemic infection alongside surgical drainage for the local manifestations proved to be an effective treatment approach. Nevertheless, evidence supporting a wider range of potential treatments needs to be explored, with continued investigation of optimal treatment regimens for patient outcomes especially in the context of multidrug-resistant strains of N. pseudobrasiliensis.

Funding Statement

No external funding was received or utilised for this project.

Ethics Statement

This article retrospectively reports on a patient case; the patient's written consent was obtained in line with local health network ethical practices.

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgements

Special thanks are due to Ms Lisa Shephard for her assistance with speciation.

References

1. Wuthrich Z., Freeman T., Lencioni A., Lindeque B. Disseminated Nocardiosis Masquerading as Soft-Tissue Malignancy: A Case Report. JBJS Case Connector . 2021;11(3):p. e20. doi: 10.2106/jbjs.cc.20.00988.

2. Peleg A. Y., Husain S., Qureshi Z. A., et al. Risk Factors, Clinical Characteristics, and Outcome of Nocardia Infection in Organ Transplant Recipients: A Matched Case-Control Study. Clinical Infectious Diseases . 2007;44(10):1307–1314. doi: 10.1086/514340.

3. Seol C. A., Sung H., Kim D. H., Ji M., Chong Y. P., Kim M. N. The First Korean Case of Disseminated Mycetoma Caused by Nocardia pseudobrasiliensis in a Patient on Long-Term Corticosteroid Therapy for the Treatment of Microscopic Polyangiitis. Annals of Laboratory Medicine . 2013;33(3):203–207. doi: 10.3343/alm.2013.33.3.203.

4. Ukai Y., Fujimoto N., Fujii N., et al. Case of Muscle Abscess due to Disseminated Nocardiosis in a Patient With Autoimmune Hemolytic Anemia, and Review of the Published Work. The Journal of Dermatology . 2012;39(5):466–469. doi: 10.1111/j.1346-8138.2011.01393.x.

5. Devi K. R., Singh L. R., Devi N. T., Singh N. S. Subcutaneous Nocardial Abscess in a Post-Renal Transplant Patient. Indian Journal of Medical Microbiology . 2007;25(3):279–281. doi: 10.1016/s0255-0857(21)02123-x.

6. Chapman S. W., Wilson J. P. Nocardiosis in Transplant Recipients. Seminars in Respiratory Infections . 1990;5(1):74–79.

7. Ruimy R., Riegel P., Carlotti A., et al. Nocardia pseudobrasiliensis Sp. Nov., a New Species of Nocardia Which Groups Bacterial Strains Previously Identified as Nocardia brasiliensis and Associated With Invasive Diseases. International Journal of Systematic Bacteriology . 1996;46(1):259–264. doi: 10.1099/00207713-46-1-259.

8. Veerappan Kandasamy V., Nagabandi A., Horowitz E. A., Vivekanandan R. Multidrug-Resistant Nocardia pseudobrasiliensis Presenting as Multiple Muscle Abscesses. BMJ Case Reports . 2015;2015:p. bcr2014205262. doi: 10.1136/bcr-2014-205262.

9. Lalitha P. Nocardia Keratitis. Current Opinion in Ophthalmology . 2009;20(4):318–323. doi: 10.1097/icu.0b013e32832c3bcc.

10. Javaid W., Rawling R. A., Granato P. Nocardia pseudobrasiliensis Systemic Infection in an Immunocompetent Patient. Clinical Microbiology Newsletter . 2012;34(9):72–73. doi: 10.1016/j.clinmicnews.2012.04.002.

11. Lebeaux D., Lanternier F., Degand N., et al. Nocardia pseudobrasiliensis as an Emerging Cause of Opportunistic Infection After Allogeneic Hematopoietic Stem Cell Transplantation. Journal of Clinical Microbiology . 2010;48(2):656–659. doi: 10.1128/jcm.01244-09.

12. Ji Y., Chen M., Hong X., Pan L., Cheng D., Ge Y. Nocardia pseudobrasiliensis Infection in a Patient With Arthritis. Journal of International Medical Research . 2023;51(12):p. 03000605231206959. doi: 10.1177/03000605231206959.

13. Besteiro B., Coutinho D., Fragoso J., et al. Nocardiosis: A Single-Center Experience and Literature Review. Brazilian Journal of Infectious Diseases . 2023;27(5):p. 102806. doi: 10.1016/j.bjid.2023.102806.

14. Stamos D. B., Barajas-Ochoa A., Raybould J. Nocardia pseudobrasiliensis Co-Infection in SARS-CoV-2 Patients. Emerging Infectious Diseases . 2023;29(4):696–700. doi: 10.3201/eid2904.221439.

15. Makadia S., Patel I., Soosaipillai I., Tarasiuk-Rusek A. First Case of Nocardia pseudobrasiliensis Causing Primary Cutaneous Nocardiosis in an Immunocompetent Patient. Journal of Investigative Medicine High Impact Case Reports . 2020;8:p. 2324709620938228. doi: 10.1177/2324709620938228.

16. Cunha L. P., Juncal V., Carvalhaes C. G., Leão S. C., Chimara E., Freitas D. Nocardial Scleritis: A Case Report and a Suggested Algorithm for Disease Management Based on a Literature Review. American Journal of Ophthalmology Case Reports . 2018;10:1–5. doi: 10.1016/j.ajoc.2018.01.018.

17. Mwandia G., Polenakovik H. Nocardia spp. Pneumonia in a Solid Organ Recipient: Role of Linezolid. Case Reports in Infectious Diseases . 2018;2018:1749691–1749693. doi: 10.1155/2018/1749691.

18. Branco L., Rodriguez-Nava V., Boiron P., Pinheiro D. Disseminated Nocardiosis: Report of Five Cases. JMM Case Reports . 2015;2(4) doi: 10.1099/jmmcr.0.000046.

19. Harent S., Vuotto F., Wallet F., et al. Pneumonie À Nocardia Pseudobrasiliensis Chez un Patient Transplanté Cardiaque. Medecine et Maladies Infectieuses . 2013;43(2):85–87. doi: 10.1016/j.medmal.2013.01.012.

20. Mongkolrattanothai K., Ramakrishnan S., Zagardo M., Gray B. Ventriculitis and Choroid Plexitis Caused by Multidrug-Resistant Nocardia pseudobrasiliensis. The Pediatric Infectious Disease Journal . 2008;27(7):666–668. doi: 10.1097/inf.0b013e31816a43bf.

21. Kageyama A., Sato H., Nagata M., et al. First Human Case of Nocardiosis Caused by Nocardia pseudobrasiliensis in Japan. Mycopathologia . 2003;156(3):187–192. doi: 10.1023/a:1023340624229.

22. Brown B. A., Lopes J. O., Wilson R. W., et al. Disseminated Nocardia pseudobrasiliensis Infection in a Patient With AIDS in Brazil. Clinical Infectious Diseases . 1999;28(1):144–145. doi: 10.1086/517180.

23. Thakur A., Eapen J., Cherian S. S. Septic Arthritis by Nocardia Farcinica: Case Report and Literature Review. IDCases . 2023;31:p. e01668. doi: 10.1016/j.idcr.2022.e01668.

24. Palomba E., Liparoti A., Tonizzo A., et al. Nocardia Infections in the Immunocompromised Host: A Case Series and Literature Review. Microorganisms . 2022;10(6):p. 1120. doi: 10.3390/microorganisms10061120.

25. Acuner B., Cömert F. Recurrent Subcutaneous Abscess due to Nocardia farcinica in an Immunocompetent Patient: A Case Report. Wound Management & Prevention . 2021;67(5):33–39. doi: 10.25270/wmp.2021.5.3339.

26. Balachandar A., Zhabokritsky A., Matukas L. M. Disseminated Nocardiosis With Multisite Involvement in an Immunocompetent Patient. Canadian Medical Association Journal . 2020;192(33):E956–E959. doi: 10.1503/cmaj.200153.

27. Yu M. H., Wu X. X., Chen C. L., et al. Disseminated Nocardia Infection With a Lesion Occupying the Intracranial Space Complicated with Coma: A Case Report. BMC Infectious Diseases . 2020;20(1):p. 856. doi: 10.1186/s12879-020-05569-4.

28. Wu Y., Yu S., Xie Q. Nocardia Infection in an Immunosuppressive Patient With Dermatomyositis. Journal of Clinical Rheumatology . 2020;26(1):p. e9. doi: 10.1097/rhu.0000000000000765.

29. Leite I. M., Trigueiros F., Martins A. M., Fonseca M., Marques T. Disseminated Nocardiosis: A Case Report. Cureus . 2019;11(8):p. e5294. doi: 10.7759/cureus.5294.

30. Hazim A. Z., Mansoor A. M. Disseminated Nocardiosis With Infective Endocarditis of a Transplanted Heart. BMJ Case Reports . 2018;2018:bcr2018225046–225046. doi: 10.1136/bcr-2018-225046.

31. Kuroda H., Sugawara H., Ishii A., Funazaki S. Nocardia Intramuscular Abscess in an Elderly Patient. Internal Medicine . 2016;55(18):2743–2744. doi: 10.2169/internalmedicine.55.7044.

32. Noh J. Y., Cheong H. J., Heo J. Y., et al. Pulmonary and Psoas Muscle Nocardiosis in a Patient With Lupus Nephritis: A Case Report and Review of the Literature. Rheumatology International . 2011;31(7):929–936. doi: 10.1007/s00296-009-1211-1.

33. Corti M., Solari R., Carolis L. D., Cangelos D., Bianchi M., Negroni R. Disseminated Nocardiosis With Psoas Abscess in a Patient With AIDS: First Reported Case. Revista do Instituto de Medicina Tropical de São Paulo . 2008;50(2):131–133. doi: 10.1590/s0036-46652008000200014.

34. Chatelus E., Javier R.-M., Sibilia J., Kuntz J.-L., Forestier E., Gaudias J. Nocardia Discitis in an Immunocompetent Patient. Joint Bone Spine . 2007;74(2):207–209. doi: 10.1016/j.jbspin.2006.08.003.

35. Daniel J. H., Ravenel J. G. Case of the Season: Disseminated Nocardiosis. Seminars in Roentgenology . 2007;42(1):4–6. doi: 10.1053/j.ro.2006.08.006.

36. Agterof M. J., van der Bruggen T., Tersmette M., ter Borg E. J., van den Bosch J. M., Biesma D. H. Nocardiosis: A Case Series and a Mini Review of Clinical and Microbiological Features. The Netherlands Journal of Medicine . 2007;65(6):199–202.

37. Malani A. K., Gupta C., Weigand R. T., Gupta V., Rangineni S. Thigh Abscess due to Nocardia farcinica. Journal of the National Medical Association . 2006;98(6):977–979.

38. Smit L. H., Leemans R., Overbeek B. P. Nocardia farcinica as the Causative Agent in a Primary Psoas Abscess in a Previously Healthy Cattle Inspector. Clinical Microbiology and Infection . 2003;9(5):445–448. doi: 10.1046/j.1469-0691.2003.00576.x.

39. Stamenkovic S. A., Madden B. P. Nocardia asteroides Abscess After Heart Transplantation. The Journal of Heart and Lung Transplantation . 2001;20(7):789–791. doi: 10.1016/s1053-2498(01)00252-2.

40. Berd D. Nocardia brasiliensis Infection in the United States: A Report of Nine Cases and a Review of the Literature. American Journal of Clinical Pathology . 1973;60(2):254–258. doi: 10.1093/ajcp/60.2.254.

41. Brown-Elliott B. A., Brown J. M., Conville P. S., Wallace R. J., Jr Clinical and Laboratory Features of the Nocardia spp. Based on Current Molecular Taxonomy. Clinical Microbiology Reviews . 2006;19(2):259–282. doi: 10.1128/cmr.19.2.259-282.2006.

42. McTaggart L. R., Doucet J., Witkowska M., Richardson S. E. Antimicrobial Susceptibility Among Clinical Nocardia Species Identified by Multilocus Sequence Analysis. Antimicrobial Agents and Chemotherapy . 2015;59(1):269–275. doi: 10.1128/aac.02770-14.

43. Coussement J., Lebeaux D., van Delden C., et al. Nocardia Infection in Solid Organ Transplant Recipients: A Multicenter European Case-Control Study. Clinical Infectious Diseases . 2016;63(3):338–345. doi: 10.1093/cid/ciw241.

44. Yetmar Z. A., Chesdachai S., Duffy D., et al. Risk Factors and Prophylaxis for Nocardiosis in Solid Organ Transplant Recipients: A Nested Case-Control Study. Clinical Transplantation . 2023;37(9):p. e15016. doi: 10.1111/ctr.15016.

45. Restrepo A., Clark N. M. Nocardia Infections in Solid Organ Transplantation: Guidelines From the Infectious Diseases Community of Practice of the American Society of Transplantation. Clinical Transplantation . 2019;33(9):p. e13509. doi: 10.1111/ctr.13509.

46. Schlaberg R., Fisher M. A., Hanson K. E. Susceptibility Profiles of Nocardia Isolates Based on Current Taxonomy. Antimicrobial Agents and Chemotherapy . 2014;58(2):795–800. doi: 10.1128/aac.01531-13.