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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2016  |  Volume : 27  |  Issue : 6  |  Page : 1246-1251
Disseminated mycobacteria chelonae infection in a kidney-pancreas transplant recipient: A case report and review of the literature


1 Department of Nephrology and Transplant, University Hospital of Wales, Cardiff, UK
2 Department of Medicine, McMaster University, Hamilton, Canada
3 Department of Medicine, Division of Transplant Infectious Diseases, Toronto General Hospital, Toronto, ON, Canada

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Date of Web Publication28-Nov-2016
 

   Abstract 

A 40-year-old male with a long-standing history of type 1 diabetes with end-stage renal failure underwent combined kidney-pancreas (KP) transplant from a standard criteria donor. Post-operative course was uncomplicated with good primary function of both transplant grafts. Induction was with thymoglobulin and maintenance immunosuppression was with tacrolimus, mycophenolate mofetil and prednisolone. Nine weeks post-transplant, the patient developed dysfunction of both grafts. Panel reactive antibody testing revealed that the patient had developed a de novo donor-specific antibody and considering an antibody-mediated rejection the patient was treated with intravenous pulse methyl prednisone 500 mg ×3 doses, IV immunoglobulin 2 mg/kg in two divided doses, and ATG 7 mg/kg (total dose of 700 mg). In addition, his baseline immunosuppression was increased. Cr decreased to baseline levels, and blood sugars were in the range of 7-8 mmol/L, serum amylase normalized to 63 U/L, and the patient was discharged home. Nine days post-discharge, the patient presented to the hospital with a five-day history of fever, pain, and swelling in the left knee along with subcutaneous, erythematous, tender, nodular lesions in both legs and both arms. Skin biopsy showed Ziehl-Neelsen stain positive rods and biopsy culture and blood culture grew Mycobacteria chelonae. Antimicrobials were switched to azithromycin 500 mg OD, moxifloxacin 400 mg OD, and linezolid 600 mg BID and baseline immunosuppression was reduced to tacrolimus trough target 8-10 ng/mL and MMF to 250 mg BID. The patient gradually improved and was discharged after 28 days in the hospital. Six weeks following the diagnosis of nontuberculous mycobacteria infection, the patient's pancreas graft failed, presumably due to reduction in immuno-suppression and he is now back on insulin treatment. His renal graft continued to function well. Although rapidly growing mycobacterial infections are rare among transplant recipients, it should be suspected among those who have received augmented immunosuppression. Blood cultures and skin biopsy of the lesions are important to establish the diagnosis.

How to cite this article:
Malik S, Ghosh A, Husain S. Disseminated mycobacteria chelonae infection in a kidney-pancreas transplant recipient: A case report and review of the literature. Saudi J Kidney Dis Transpl 2016;27:1246-51

How to cite this URL:
Malik S, Ghosh A, Husain S. Disseminated mycobacteria chelonae infection in a kidney-pancreas transplant recipient: A case report and review of the literature. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2020 Feb 24];27:1246-51. Available from: http://www.sjkdt.org/text.asp?2016/27/6/1246/194681

   Introduction Top


Infection due to nontuberculous mycobacteria is rare among solid organ transplant recipients. It is even rarer in kidney-pancreas (KP) transplant recipients with apparently only four published cases in literature so far. Of this, only one was due to rapid-growing mycobacteria. We report a case of a 40-year-old male who underwent a combined KP transplant for type 1 diabetes and three months later presented with fever and nodular skin lesions on both lower limbs. Biopsy of the lesions grew Mycobacteria chelonae. We discuss the timeline, risk factors, treatment of this infection, and review the existing literature


   Case Report Top


Our patient is a 40-year-old male with a longstanding history of type 1 diabetes complicated by end-stage renal failure requiring hemodialysis, peripheral neuropathy, retinopathy, and diabetic gastroparesis. He underwent a low immunological risk (as defined by the absence of donor-specific antibodies) combined kidney- pancreas (KP) transplant in May 2013 from a standard criteria donor. Post-operative course was uncomplicated and the patient made a good recovery with primary function of both transplant grafts. Induction was with thymoglobulin (ATG) 5 mg/kg (total dose: 550 mg). Maintenance immunosuppression comprised tacrolimus (target trough level 10-12 ng/mL), mycophenolate mofetil (MMF) 500 mg bid, and prednisone 15 mg once daily with plan to taper as outpatient to baseline 5 mg once daily. The patient was IgG positive for both cytomegalovirus (CMV) and Epstein-Barr virus (EBV) pre-transplant. Prior to the transplant, the patient worked as a grave digger.

Nine weeks post-transplant, the patient was noted to have renal graft dysfunction. Creatinine (Cr) increased to 244 mmol/L from a baseline of 118 mmol/L. Blood sugars were in the range of 5-7 mmol/L and serum amylase was 453 U/L (normal range: 25-125 U/L). Ultrasound of transplant kidney showed a good perfusion and no hydronephrosis. Computed tomography (CT) scan of the abdomen confirmed patent vascular supply to the pancreas graft and mild stranding and fluid collection around the pancreas in keeping with pancreatitis or graft rejection. The patient was clinically well. Kidney transplant biopsy was performed and this showed interstitial inflammation with focal tubulitis, focal intimal arteritis, and negative C4d staining in the peritubular capillaries. Panel reactive antibody testing revealed that the patient had developed a de novo donor-specific antibody, this in combination with vascular involvement in the biopsy was diagnostic of an antibody-mediated rejection and the patient was treated with intravenous (IV) pulse methyl prednisone 500 mg ×3 doses, IV immunoglobulin 2 mg/kg in two divided doses, and ATG 7 mg/kg (total dose of 700 mg). In addition, his baseline immunosuppression was increased, tacrolimus (trough target: 10-12), mycophenolate mofetil increased to 750 mg BID, and prednisone increased to 20 mg OD post-methyl prednisone pulse. Cr decreased to baseline levels, and blood sugars were in the range of 7-8 mmol/L, serum amylase normalized to 63 U/L, and the patient was discharged home.

Nine days post-discharge, the patient presented to the hospital with a five-day history of fever (temperature maximum 38°C), pain, and swelling in the left knee, this later progressed to involve the left ankle and right knee within 48 h of hospital admission. Blood and urine cultures were done along with CMV and EBV polymerase chain reaction, Parvovirus B19 serology - all of which were negative. Magnetic resonance imaging (MRI) of the left knee and left ankle showed preserved joint spaces, small effusion around the knee joint, and no evidence of osteomyelitis. Left knee aspirate showed white blood cell (WBC) = 59 × 10 6 cells (72% macrophages), culture of knee effusion aspirate showed no growth, and no crystals were seen on microscopy. Suspecting serum sickness, the dose of prednisone was increased from 20-40 mg OD. Three sets of blood cultures remained negative. Joint pains were better and fever subsided with an increased dose of prednisone. Renal and pancreas graft function remained stable during this period. The patient was discharged home with outpatient follow-up.

A day after discharge, the patient represented with worsening pain in both ankles and the left knee. In addition, the patient was noted to be developing subcutaneous, erythematous, tender, nodular lesions in both legs of 0.5 cm diameter mainly involving both shins. Some of these lesions were violaceous and some others were pustular. In the next 24 h, nodular lesions started appearing on both arms. Blood and urine cultures were repeated, and a skin biopsy was performed [Figure 1]. Skin biopsy was reported as showing necrotizing medium vessel vasculitis with neutrophilic infiltrate suggestive of Sweet's syndrome. Antineutrophil cytoplasmic antibody and antinuclear antibody were negative, C3 and C4 were normal, WBC count was 3.7 × 10 9 /L (normal range: 5-10 × 10 9 /L), and C-reactive protein was 102 mg/dL (normal range: 0-10 mg/dL). The patient's immunosuppression remained unchanged and prednisone dose was maintained at 40 mg OD. Culture of skin biopsy showed Gram-positive rods, Ziehl-Neelsen stain positive, and Nocardia was suspected. To confirm this diagnosis, a tender, palpable skin nodule from the right leg was injected with saline and contents aspirated for culture along with repeat skin biopsy. MRI of the brain and CT of the chest did not reveal any evidence of distant spread. Imipenem 500 mg IV QID and linezolid 600 mg BID were started to treat Nocardia. Blood culture sent along with repeat skin biopsy culture was reported to be growing Mycobacteria chelonae after 10 days of incubation and repeat skin biopsy culture too grew M. chelonae after 24 days of incubation. Antimicrobials were switched to azithromycin 500 mg OD, moxifloxacin 400 mg OD, and linezolid 600 mg BID. Baseline immunosuppression was reduced to tacrolimus trough target (8-10 ng/mL) and MMF to 250 mg BID. Joint symptoms started settling and the patient was able to weight bear normally. The patient was discharged after 28 days in the hospital and by this time, skin nodules were gradually decreasing in size and intensity. Six weeks following the diagnosis of nontuberculous mycobacteria (NTM) infection, the patient's pancreas graft failed presumably due to reduction in immuno suppression and he is now back on insulin treatment. His renal graft continued to function well.
Figure 1:

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   Discussion Top


Herein, we present the case of disseminated M. chelonae infection following the receipt of KP transplantation. The patient had received induction with 5 mg/kg of thymoglobulin. However, development of antibody-mediated rejection necessitated higher doses of thymoglobulin, making him more immunosuppressed and susceptible to opportunistic infections. [1]

Mycobacteria can be divided into four groups based on growth rate and pigmentation. The Runyon classification classifies them as follows: Group I consists of the photochromogenic (pigmented) species of slow growers; members of Group II are scotochromogenic slow growers; Group III contains the non-chromogenic slow growers; and Group IV consists of rapid growers (defined as maturing in <1 week). [2]

NTM can also be broadly classified into two main categories; slow growing and rapid growing, based on interval-to-colony formation by subculture on solid media. In a study comparing time-to-growth detection (TGD) of NTM, the mean TGD for rapid-growing mycobacteria (RGM) was 133 h and 269 h for slowgrowing mycobacteria (SGM) (P <0.001) in acid-fast bacilli (AFB)-negative specimens. In AFB-positive specimens, the mean TGD was 112 ± 37 h for RGM and 155 ± 125 h for SGM (P = 0.063). [3] RGM are ubiquitous organisms and are found in tap water, natural water, and soil. [4],[5] M. chelonae is a RGM, and Mycobacterium fortuitum and Mycobacterium abscessus are other closely related RGM species.

M. chelonae has been reported to cause cutaneous lesions, localized cellulitis, abscess, catheter-related infections, ocular lesions, pneumonia, and osteomyelitis. [6],[7],[8] They most often cause infection following local trauma and typically involve the lower extremities. [9] Predisposing factors include HIV and other immunosuppressed states such as solid organ transplant recipients. [8] M. chelonae causes disseminated infection and accounts for 75% of such infections. [6] Antituberculous drugs are ineffective in the treatment of infection due to M. chelonae.[10] Macrolides, quinolones, and amikacin are the drugs of choice. [11] RGM should be identified to species level to be able to direct appropriate antimicrobial therapy. [6] M. chelonae has been reported once previously in a KP transplant recipient. Moreover, this case also demonstrates the diagnostic conundrum with such presentations. RGM can initially be reported as Nocardia which is an acid-fast gram-positive Bacillus. [12],[13] Nocardia typically also occurs in immunocompromised patients and can present as disseminated infection. In total, to the best of our knowledge, there are only four previously reported cases of NTM in KP transplant recipients [Table 1]. The mean age of patients was 41.5 years, and in three of them, skin was the site of infection. This is most probably the first case of NTM in KP recipient to occur within three months after transplant.
Table 1: Recipient characteristics of KP transplant patients with NTM infection previously published in the literature.

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[16]


   Conclusion Top


RGM infection in kidney transplant recipients is rare. It should be suspected in solid organ transplant recipients who have received augmented immunosuppression with T-cell depleting antibodies, presenting with cutaneous skin lesions. Blood cultures and skin biopsy of the lesions are important to establish the diagnosis. RGM grow in special mediums and at specific temperatures and therefore infection by these organisms should be suspected early so that appropriate treatment may be initiated early. These organisms are not susceptible to antituberculous therapy, and sensitivity tests should be performed to guide therapy. It is often a fine balance between reducing immunosuppression to treat an infection and preventing rejection.

Conflict of interest: None declared.

 
   References Top

1.
Safdar N, Smith J, Knasinski V, et al. Infections after the use of alemtuzumab in solid organ transplant recipients: A comparative study. Diagn Microbiol Infect Dis 2010;66:7-15.  Back to cited text no. 1
    
2.
Rogall T, Wolters J, Flohr T, Böttger EC. Towards a phylogeny and definition of species at the molecular level within the genus Mycobacterium. Int J Syst Bacteriol 1990;40: 323-30.  Back to cited text no. 2
    
3.
Kim CJ, Kim NH, Song KH, et al. Differentiating rapidand slow-growing mycobacteria by difference in time to growth detection in liquid media. Diagn Microbiol Infect Dis 2013; 75:73-6.  Back to cited text no. 3
    
4.
Streit M, Bregenzer T, Heinzer I. Cutaneous infections due to atypical mycobacteria. Hautarzt 2008;59:59-70.  Back to cited text no. 4
    
5.
Bhambri S, Bhambri A, Del Rosso JQ. Atypical mycobacterial cutaneous infections. Dermatol Clin 2009;27:63-73.  Back to cited text no. 5
    
6.
Set R, Shastri J. Laboratory aspects of clinically significant rapidly growing mycobacteria. Indian J Med Microbiol 2011;29:343-52.  Back to cited text no. 6
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7.
Unai S, Miessau J, Karbowski P, Bajwa G, Hirose H. Sternal wound infection caused by Mycobacterium chelonae. J Card Surg 2013; 28:687-92.  Back to cited text no. 7
    
8.
Wallace RJ Jr., Brown BA, Onyi GO. Skin, soft tissue, and bone infections due to Mycobacterium chelonae chelonae: importance of prior corticosteroid therapy, frequency of disseminated infections, and resistance to oral antimicrobials other than clarithromycin. J Infect Dis 1992;166:405-12.  Back to cited text no. 8
    
9.
Hsiao CH, Tsai TF, Hsueh PR. Characteristics of skin and soft tissue infection caused by nontuberculous mycobacteria in Taiwan. Int J Tuberc Lung Dis 2011;15:811-7.  Back to cited text no. 9
    
10.
Wang HX, Yue J, Han M, et al. Nontuberculous mycobacteria: susceptibility pattern and prevalence rate in Shanghai from 2005 to 2008. Chin Med J (Engl) 2010;123:184-7.  Back to cited text no. 10
    
11.
Esteban J, Ortiz-Pérez A. Current treatment of atypical mycobacteriosis. Expert Opin Pharmacother 2009;10:2787-99.  Back to cited text no. 11
    
12.
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. 12
    
13.
Muñoz J, Mirelis B, Aragón LM, et al. Clinical and microbiological features of nocardiosis 1997-2003. J Med Microbiol 2007;56(Pt 4): 545-50.  Back to cited text no. 13
    
14.
Schmekal B, Janko O, Zazgornik J, et al. Skin tuberculosis with atypical mycobacteria 8 years after combined pancreas-kidney transplantation. Am J Nephrol 2002;22:566-8.  Back to cited text no. 14
    
15.
Stelzmueller I, Dunst KM, Wiesmayr S, Zangerie R, Hengster P, Bonatti H. Mycobacterium chelonae skin infection in kidney-pancreas recipient. Emerg Infect Dis 2005;11:352-4.  Back to cited text no. 15
    
16.
Jie T, Matas AJ, Gillingham KJ, Sutherland DE, Dunn DL, Humar A. Mycobacterial infections after kidney transplant. Transplant Proc 2005;37:937-9.  Back to cited text no. 16
    

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Correspondence Address:
Shafi Malik
University Hospital of Wales, Cardiff
UK
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DOI: 10.4103/1319-2442.194681

PMID: 27900974

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