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Table of Contents
CASE REPORT
Year : 2022  |  Volume : 16  |  Issue : 4  |  Page : 451-454

Disseminated nocardiosis and focal nontuberculous mycobacterial infection coexisting in a renal transplant recipient - A case report


1 Department of Nephrology, Aster Medcity, Kochi, Kerala, India
2 Department of Infectious Disease, Aster Medcity, Kochi, Kerala, India

Date of Submission05-Feb-2022
Date of Acceptance06-Sep-2022
Date of Web Publication30-Dec-2022

Correspondence Address:
Dr. K Vinod Kumar
Department of Nephrology, Aster Medcity, Cheranalloor, Kochi - 682 027, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_19_22

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  Abstract 


Solid organ transplant (SOT) recipients are at increased risk of opportunistic infections, as they are on immunosuppressive drugs. The risk increases if the cumulative immunosuppression is high, especially when the patient is treated for acute rejection episodes. Multiple opportunistic infections in the same patient are reported in SOT recipients. We report a 43-year-old man, renal allograft recipient, 15 years posttransplant, on dual immunosuppression who presented with fever, generalized skin rashes, and altered sensorium. He was recently treated with pulse methylprednisolone injections for acute graft rejection episode. He had multiple pustules all over the body, predominantly over the face, eyelids, chest, and lower limbs. Pus from the facial lesion grew Nocardia, and tissue culture of skin ulcer from the leg grew nontuberculous mycobacteria. Combined infection with these organisms posed diagnostic challenge as both can present with cutaneous manifestation, both organisms are acid-fast bacilli, and both organisms were detected and grown from the sample taken from one of the large skin ulcers. It was important to identify both the organisms from the skin ulcer as the treatment options are different.

Keywords: Kidney transplant, Nocardia, nontuberculous mycobacteria, skin ulcer


How to cite this article:
Kumar K V, Unni V N, Warrier A, Prasannan B. Disseminated nocardiosis and focal nontuberculous mycobacterial infection coexisting in a renal transplant recipient - A case report. Indian J Transplant 2022;16:451-4

How to cite this URL:
Kumar K V, Unni V N, Warrier A, Prasannan B. Disseminated nocardiosis and focal nontuberculous mycobacterial infection coexisting in a renal transplant recipient - A case report. Indian J Transplant [serial online] 2022 [cited 2023 Feb 8];16:451-4. Available from: https://www.ijtonline.in/text.asp?2022/16/4/451/364614




  Introduction Top


Solid organ transplant (SOT) recipients are at increased risk of opportunistic infections, as they are on immunosuppressive drugs. The risk increases if the cumulative immunosuppression is high, especially when the patient is treated for acute rejection episodes. Multiple opportunistic infections in the same patient are reported in SOT recipients. Nocardiosis is rare in kidney transplant recipients and usually affects the lung; however, disseminated infection can occur. Nontuberculous mycobacteria (NTM) commonly cause one of five different clinical syndromes: pleuropulmonary disease, skin and soft-tissue infection, osteoarticular infection, disseminated disease, including that caused by catheter-associated infection, and lymphadenitis.[1] We report a renal allograft recipient who had infection with Nocardia species and NTM at the same time posing significant diagnostic and therapeutic challenges.


  Case Report Top


A 43-year-old man, renal allograft recipient, on dual immunosuppression (azathioprine and prednisolone), presented with intermittent fever for 1 month, generalized skin rashes for 2 weeks, and altered sensorium for 3 days. He underwent kidney transplantation 15 years back, with mother as the donor, and was on triple immunosuppression initially, till cyclosporine was withdrawn 5 years after the transplantation. He was under follow-up in an outside hospital, and the detailed course of 15-year follow-up was not available to us; however, he had a smooth course without any hospital admission during that time. The patient denies any history of noncompliance to medications and is not clear about the reason for stopping cyclosporine. Four months before the admission to our hospital, he had acute graft dysfunction and had received methylprednisolone pulses for 5 days (total dose of 1.5 g), following which his graft function partially improved. On presentation to the hospital, he was febrile, had tachycardia (pulse rate: 120 beats/min) and tachypnea (respiratory rate of 31/min), and had multiple pustules all over the body predominantly over the face, eyelids, chest, and lower limbs with cervical lymphadenopathy. He was drowsy on presentation without any focal neurological deficit or sign of meningeal irritation. Examination of the eye showed ulcerative blepharitis and evidence of multifocal choroiditis [Figure 1]. Investigation reports are mentioned in [Table 1]. Serum creatinine on admission was 1.6 mg%. Pus from the facial lesion was cheesy in consistency and grew Gram-positive beaded branching filamentous bacilli on culture suggestive of Nocardia. Smear for AFB showed long filamentous branching acid-fast bacilli seen with 1% Ziehl–Neelsen staining which is typical of Nocardia. He had multiple skin ulcers in the leg, and the largest ulcer in the left thigh was biopsied. Multiple sections from the skin ulcer showed features of acute necrotic inflammatory exudate with surrounding epithelioid granulomatous reaction. Twenty percent Ziehl–Neelsen stain showed long beaded acid-fast bacilli in clusters, morphologically suggestive of NTM [Figure 2]. Culture from the tissue grew NTM-rapid grower. Gomori's methenamine silver stain in the same tissue showed positive branching filaments suggestive of Nocardia [Figure 2]b. Surprisingly, two different organisms were identified from the same tissue. Mycobacterium speciation by MALDI-TOF MS (matrix-assisted laser desorption ionization-mass spectrometry) isolated Mycobacterium abscessus. Two-dimensional echo was normal without evidence of vegetation. X-ray chest was normal. Blood and urine cultures were sterile. NTM infection was treated with doxycycline with moxifloxacin and azithromycin; doxycycline was stopped after a month. Disseminated Nocardia was treated with meropenem and cotrimoxazole. Ulcerative blepharitis was treated with topical antibiotic (moxifloxacin) ointment and eye drops. The patient responded to initial treatment with improvement in the clinical and hematological parameters, including the resolution of his eye lesions. Injection meropenem was stopped after 8 weeks. He was continued on cotrimoxazole, azithromycin, and moxifloxacin for a total of 12 months. He improved significantly; skin lesions and leg ulcers healed completely. The patient gained considerable weight and his appetite improved. He had persistent graft dysfunction as the immunosuppressive agents could not be escalated in view of life-threatening infection, and he was continued on immunosuppression with low-dose steroids and azathioprine.
Table 1: Laboratory parameters of the patient on admission

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Figure 1: Fundoscopic examination of eye shows evidence of multifocal choroiditis (arrows)

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Figure 2: (a) 20% Ziehl–Neelsen stain reveals clusters of long beaded acid-fast bacilli, morphologically suggestive of nontuberculous mycobacterium (arrow). (b) Gomori's methenamine silver stain shows positive branching filaments, suggestive of Nocardia (arrow)

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  Discussion Top


The risk of infection after SOT depends on the “net state of immunosuppression.” The treatment of rejection episodes increases the overall immunosuppression. Opportunistic infections are more common between 1 and 6 months posttransplant, as the degree of immunosuppression is maximal. Multiple infections coexisting in the same patient are seen in transplant recipients. A high-dose corticosteroid regimen is the most frequent risk factor for infection.[2] Our patient received high-dose parenteral steroids 4 months before the current episode. He had disseminated infection with Nocardia spp. and NTM. The other risk factors include higher tacrolimus levels, use of antilymphocyte globulin, and monoclonal antibody against B-lymphocytes like rituximab and cytomegalovirus disease in the preceding 6 months.[3]

Nocardia infection and kidney transplantation

Nocardia species are ubiquitous saprophytic Gram-positive bacteria which grow as filamentous, branching rods and are partially acid-fast and catalase positive. Nocardia spp. are found worldwide in soil, fresh, and saltwater. The route of transmission is mainly through inhalation, although penetrating cutaneous injury and ingestion are other potential routes.[4] The incidence rate of Nocardia infection among kidney transplant recipients is 0.2% and is more common (3.5%) following lung transplantation.[5]

Lungs are the primary site of infection. Transplant patients may have disseminated infection, defined as involvement of at least two noncontiguous organs.[6] The bloodstream and brain are most often involved; however, other typical locations for Nocardia dissemination include the eyes, adrenal gland, kidneys, bone, and joints.[4],[7] Nocardia can also infect the skin and subcutaneous tissues, either through direct inoculation or hematogenous spread. The most common skin lesions are cellulitis, ulcers, nodules, and abscess.[8]

Definitive diagnosis requires isolation of the organism by culture from the suspected site. Nocardia may take 2 days to several weeks to grow in culture. It will usually stain with modified acid-fast (Kinyoun) stain.[4] Biopsy from the affected tissue shows Gram-positive branching and beaded rods surrounded by a pyogenic inflammatory reaction as seen in our case. The main stay of treatment is antibiotic therapy and surgical debridement for a better source control. Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred agent to treat nocardiosis. The recommended initial dose is TMP-SM × 15 mg/kg/day orally or intravenously in 2–4 divided doses. For disseminated disease, imipenem + amikacin or trimethoprim-sulfamethoxazole combination is recommended. Ceftriaxone, cefotaxime, linezolid, or minocycline can be considered after initial therapy. The duration of treatment is 9–12 months. Our patient was treated with cotrimoxazole and meropenem.

Nontuberculous mycobacteria and kidney transplantation

Most NTM are ubiquitous free-living saprophytic organisms present in the environmental sources including soil, water, dust, aerosols, plant material, animals, and birds.[8] Limited data suggest an incidence rate for NTM infections to be between 0.16% and 0.38% among kidney transplant recipients.[9] Patients with suppressed cell-mediated immunity are predisposed to NTM infections, especially patients who have received corticosteroids and the use of rabbit antithymocyte globulin.

NTM commonly cause one of five different clinical syndromes: pleuropulmonary disease, skin and soft-tissue infection, osteoarticular infection, disseminated disease, including that caused by catheter-associated infection, and lymphadenitis. Constitutional symptoms are often absent.

Among nonlung SOT recipients, the most common presentation is cutaneous lesions involving the extremities, tenosynovitis, and septic arthritis, with more than half of patients with evidence of disseminated involvement of noncontiguous areas at the time of diagnosis.[10] Sites of dissemination can include skin, lymph nodes, bone marrow, visceral organs including the allograft, and musculoskeletal sites. Mycobacterium chelonae, M. abscessus, and Mycobacterium kansasii are the most frequently isolated organisms presenting in this manner. Typically, the skin lesions present as painful erythematous or violaceous subcutaneous nodules that can form abscesses or ulcerate.

There are no specific criteria for diagnosis of extrapulmonary disease, and an assessment of the clinical, histopathologic, and microbiologic (staining and culture) findings must be performed to establish a diagnosis. Auramine-phenol staining is preferred over the Ziehl–Neelsen and Kinyoun methods for AFB staining owing to its improved sensitivity. NTM that typically grow within 7 days can be isolated from routine bacterial cultures. Mycobacterial cultures should be performed on both solid and liquid media; liquid culture systems are more sensitive and rapid than solid media, but the latter allows for evaluation of colony morphology and identification of mixed infections. Matrix-assisted laser desorption ionization-mass spectrometry (MALDI-TOF MS) has emerged as a method to identify organisms and species identification. Antimicrobial treatment for NTM needs a multidrug regimen, as mentioned in [Table 2],[11] and therapy must be continued for months to years.
Table 2: Treatment recommendations for rapid growing nontuberculous mycobacteria

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Our patient received three-drug regimen, which included parenteral doxycycline with azithromycin and moxifloxacin. Doxycycline was stopped after a month.


  Conclusion Top


Our patient had disseminated nocardiosis as evidenced by involvement of the skin and soft tissue, eyes, and lymph node. Dissemination without involving the lung or brain is a very rare manifestation. It is very easy to overlook other infections when Nocardia was detected both by culture and specific staining methods. To our surprise, this patient also had focal NTM infection which was identified both by ZN staining and culture from the same cutaneous ulcer which had shown positivity for Nocardia. We had significant challenge in diagnosis as both infections can present in similar ways, both are AFB positive, and the definitive diagnosis could be established based on culture report. Therapeutic options are different and require long-term treatment to get a favorable outcome as seen in our patient. Simultaneous occurrence of both these infections at the same location is very rare, and to the best of our knowledge, this is the first case reported in the literature.

Declaration of patient consent

The authors certify that patient consent has been taken for participation in the study and for publication of clinical details and images. The patient understands that the names and initials would not be published, and all standard protocols will be followed to conceal their identity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Patel R, Roberts GD, Keating MR, Paya CV. Infections due to nontuberculous mycobacteria in kidney, heart, and liver transplant recipients. Clin Infect Dis 1994;19:263-73.  Back to cited text no. 1
    
2.
Minero MV, Marín M, Cercenado E, Rabadán PM, Bouza E, Muñoz P. Nocardiosis at the turn of the century. Medicine (Baltimore) 2009;88:250-61.  Back to cited text no. 2
    
3.
Restrepo A, Clark NM, Infectious Diseases Community of Practice of the American Society of Transplantation. Nocardia infections in solid organ transplantation: Guidelines from the infectious diseases community of practice of the American society of transplantation. Clin Transplant 2019;33:e13509.  Back to cited text no. 3
    
4.
Lerner PI. Nocardiosis. Clin Infect Dis 1996;22:891-903.  Back to cited text no. 4
    
5.
Peleg AY, Husain S, Qureshi ZA, Silveira FP, Sarumi M, Shutt KA, et al. Risk factors, clinical characteristics, and outcome of Nocardia infection in organ transplant recipients: A matched case-control study. Clin Infect Dis 2007;44:1307-14.  Back to cited text no. 5
    
6.
Beaman BL, Beaman L. Nocardia species: Host-parasite relation – Ships. Clin Microbiol Rev 1994;7:213-64.  Back to cited text no. 6
    
7.
Lederman ER, Crum NF. A case series and focused review of nocardiosis: Clinical and microbiologic aspects. Medicine (Baltimore) 2004;83:300-13.  Back to cited text no. 7
    
8.
Falkinham JO 3rd. Epidemiology of infection by nontuberculous mycobacteria. Clin Microbiol Rev 1996;9:177-215.  Back to cited text no. 8
    
9.
Doucette K, Fishman JA. Nontuberculous mycobacterial infection in hematopoietic stem cell and solid organ transplant recipients. Clin Infect Dis 2004;38:1428-39.  Back to cited text no. 9
    
10.
Yu X, Han F, Wu J, He Q, Peng W, Wang Y, et al. Nocardia infection in kidney transplant recipients: Case report and analysis of 66 published cases. Transpl Infect Dis 2011;13:385-91.  Back to cited text no. 10
    
11.
Longworth SA, Daly JS, AST Infectious Diseases Community of Practice. Management of infections due to nontuberculous mycobacteria in solid organ transplant recipients-guidelines from the American society of transplantation infectious diseases community of practice. Clin Transplant 2019;33:e13588.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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