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  Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 38  |  Issue : 1  |  Page : 124-127
 

Two cases of Nocardia bacteraemia in solid organ transplant recipients


1 Department of Clinical Microbiology and Infection Control, Gleneagles Global Hospitals, Hyderabad, Telangana, India
2 Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Medical Gastroenterology and Hepatology, Gleneagles Global Hospitals, Hyderabad, Telangana, India

Date of Submission28-May-2020
Date of Acceptance02-Jun-2020
Date of Web Publication25-Jul-2020

Correspondence Address:
Dr. Jangam Rekha Rao
Department of Clinical Microbiology and Infection Control, Gleneagles Global Hospitals, 6-1-1070/1 To 4, Lakdikapul, Hyderabad - 500 004, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_20_233

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 ~ Abstract 


Nocardiosis is an opportunistic infection occurring in immunosuppressed patients. While disseminated nocardiosis is common in immunosuppressed patients, Nocardia bacteraemia is rare. There are few reports of Nocardia bacteraemia following solid organ transplantation. We report two cases of Nocardia bacteraemia in solid organ transplant recipients-Nocardia cyriacigeorgica bacteraemia in liver transplant recipient and concomitant Nocardia farcinica bacteraemia and cyclosporiasis in a heart transplant recipient. Prompt recognition of early bacteraemia with initiation of antibiotic therapy may avoid the complications of disseminated disease in the solid organ transplant recipients.


Keywords: Nocardia bacteraemia, Nocardia cyriacigeorgica, Nocardia farcinica


How to cite this article:
Iyer RN, Rao JR, Rudramurthy SM, Kapoor D. Two cases of Nocardia bacteraemia in solid organ transplant recipients. Indian J Med Microbiol 2020;38:124-7

How to cite this URL:
Iyer RN, Rao JR, Rudramurthy SM, Kapoor D. Two cases of Nocardia bacteraemia in solid organ transplant recipients. Indian J Med Microbiol [serial online] 2020 [cited 2020 Aug 14];38:124-7. Available from: http://www.ijmm.org/text.asp?2020/38/1/124/290689





 ~ Introduction Top


Nocardiosis is an opportunistic infection occurring in immunosuppressed patients. The most common manifestation is pulmonary nocardiosis with concomitant extrapulmonary disease occurring due to hematogenous dissemination or contiguous spread from the primary site of infection. Whilst disseminated disease has been described in immunosuppressed patients, Nocardia bacteraemia is seldom encountered.[1] There are very few reports of Nocardia bacteraemia following liver and heart transplantation.[2]

We report two cases of Nocardia bacteraemia in solid organ transplant (SOT) recipients.


 ~ Case Reports Top


Case 1: Nocardia cyriacigeorgica bacteraemia

A 51-year-old male patient with a previous history of deceased donor orthotopic liver transplant done 9 months ago for hepatitis B virus-related chronic liver disease was admitted to the hospital with productive cough, dyspnoea, low-grade fever, generalised weakness and poor appetite of a week's duration. The patient was on stable immunosuppression (tacrolimus, mycophenolate mofetil and prednisolone) and tenofovir in the post-transplant period. There was no history of acute rejection episodes/exposure to sick contacts/recent travel/tuberculosis in the past.

On physical examination, his temperature was 99 °F, pulse – 110/min, blood pressure – 100/60 mmHg, and respiratory rate – 24 breaths/mine. Systemic examination revealed bilateral basal coarse crepitations. Other systems examination was unremarkable. The initial laboratory investigations showed haemoglobin 9.3 g/dl, white blood cell count 11,600 cells/μl (97% neutrophils), platelet count – 136,000/μl; normal renal and liver function tests and tacrolimus trough level of 17.4 ng/mL. Chest radiograph revealed right middle lobe pneumonitic patch with fluffy alveolar shadows in the left mid and lower zone. Abdominal ultrasound was normal. The following day, the patient was intubated and placed on mechanical ventilation (SIMV mode) in view of increasing respiratory distress. Aerobic blood cultures were drawn before initiating intravenous (IV) cefoperazone sulbactam 1.5 g twice daily, clarithromycin 500 mg twice daily, levosalbutamol 2.5 mg nebulisation, pantoprazole 40 mg once daily and IV fluids. Serum Aspergillus galactomannan assay was negative. Gram stain of the endotracheal secretions showed beaded Gram-positive, thin, branching filaments which were also partially acid fast by modified Kinyoun's staining. Ziehl–Neelsen (ZN) stain of endotracheal secretions for acid-fast bacilli was negative while 10% potassium hydroxide mounts did not reveal any fungal hyphae. The smear findings presumptively suggestive of pulmonary nocardiosis were informed to the physician while awaiting culture results, following which the patient was initiated on IV trimethoprim-sulfamethoxazole (TMP-SMX) (15 mg/kg/day in divided doses). Nocardia spp. and carbapenem-resistant Klebsiella pneumoniae were isolated from endotracheal secretions after 48 h. Blood cultures grew Nocardia spp. after an incubation period of 96 h. IV imipenem (500 mg IV 6 hourly) was added to the treatment regimen and cefoperazone-sulbactam was withdrawn. CT scan of the brain was unremarkable. The tacrolimus dose was reduced to obtain trough level of <5 ng/mL. The patient responded initially to the aforementioned treatment protocol but could not be weaned off organ support. This was followed by family's desire to withdraw active support in view of poor prognosis.

Case 2: Nocardia farcinica bacteraemia with cyclosporiasis

A 50-year-old male patient with a previous history of orthotopic heart transplant, done 6 months ago for ischemic cardiomyopathy was admitted to the hospital with complaints of watery diarrhoea (3–4 episodes/day), vomiting, generalised weakness and loss of appetite of a week's duration. He also complained of intermittent productive cough of 2 weeks duration. The patient was receiving triple-drug immunosuppression (tacrolimus, mycophenolate mofetil and prednisolone) in the post-transplant period. There was no history of acute rejection episodes/exposure to sick contacts/recent travel/tuberculosis in the past.

On physical examination, he was afebrile, pulse – 109/min, blood pressure – 110/70 mmHg, and respiratory rate – 32 breaths/min. Respiratory system examination showed reduced breath sounds on the left side. Other systems examination was unremarkable. The initial laboratory investigations showed haemoglobin 7.8 g/dl, white blood cell count 12,110 cells/μl (80% neutrophils), platelet count – 296,000/μl; normal renal and liver function tests and tacrolimus trough level of 15.6 ng/mL. Blood cultures, faeces and sputum specimens were sent for microbiological analysis initially. Serum Aspergillus galactomannan assay was negative. Gram stain of sputum revealed Gram-positive, thin, branching filaments. Modified Kinyoun stain and ZN stain for acid-fast bacilli and 10% potassium hydroxide mounts for fungal hyphae were negative. Faeces specimen was watery with no visible mucus or blood. Saline and iodine mounts of faeces did not reveal any cysts or ova of parasites. Modified ZN stain of faeces specimen showed oocysts of Cyclospora cayetanensis which were variably stained and measured about 8–10 μm in size [Figure 1]. Clostridium difficile toxin assay was negative. Spiral computed tomography (CT) scan of the chest without contrast showed minimal left side pleural effusion and multiple small nodular opacities with central cavitation scattered in both the lungs. The patient was already on Pneumocystis jirovecii prophylaxis with oral TMP-SMX single strength (80 mg/400 mg) once daily. In view of possible concomitant pulmonary nocardiosis and cyclosporiasis IV TMP-SMX (15 mg/kg/day in divided doses) was started. Initially, he responded to this treatment but on the 5th day, he developed a generalized tonic–clonic seizure, followed by another episode the next day for which he was started on IV phenytoin sodium. Spiral CT scan brain was unremarkable. On day 6, Nocardia spp was isolated from blood cultures. IV meropenem (1 g 8 hourly) and IV amikacin (10 mg/kg/day) were added to the treatment regimen in view of Nocardia bacteraemia. The dose of immunosuppression was reduced to enhance recovery. The sputum cultures grew carbapenem-resistant Klebsiella pneumoniae. Nocardia spp. was not isolated from sputum even after a week's incubation. Faeces bacteriology did not reveal any pathogens. The patient' symptoms and radiological findings improved a week after initiating combination treatment regimen. A repeat stool microscopy was negative for coccidian parasites. Parenteral antibiotics was administered for 3 weeks due to severity of disease, and the patient was discharged subsequently on oral TMP-SMX 160/800 mg twice daily to be continued for 12 months with regular follow-up.
Figure 1: Modified Ziehl Neelsen stain showing oocysts of Cyclospora cayetanensis

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Post-solid organ transplant prophylaxis against Cytomegalovirus and Pneumocystis jirovecii infection

Both SOT recipients received Cytomegalovirus prophylaxis (oral Valganciclovir 450 mg twice daily for 3 months) and P. jirovecii prophylaxis (oral TMP-SMX-80/400 mg once daily for 6 months) in the immediate post-transplant period.

Microbiology

Gram stain was done using Preston and Morrell's modification. Modified Kinyoun staining for Nocardia was done using 1% sulphuric acid as decolourizer. Modified ZN stain for coccidian parasites was done using cold carbol fuchsin as primary stain, 3% acid alcohol as decoloriser and methylene blue as counter stain.[3]

Aerobic blood cultures were done using BD BACTEC 9120 system (Becton, Dickinson and Company, Sparks, MD, 21152, USA). Gram stain of blood culture bottles that flagged positive revealed beaded Gram-positive, thin, branching filaments. On modified Kinyoun stain these filaments were partially acid fast suggestive of Nocardia spp. [Figure 2]. The isolates from case-1 and case-2 were identified as N. cyriacigeorgica and N. farcinica respectively based on the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) VITEK MS (bioMérieux, Marcy-l'Etoile, France) (99.9% confidential value). On 5% sheep blood agar, the colonies of N. cyriacigeorgica appeared chalky white, raised, dry, wrinkled and pitted, whereas N. farcinica colonies were yellow, raised, dry and pitted [Figure 3]. The identity of both the isolates were confirmed by sequencing 16s region of rDNA. Both the sequences showed >99% identity with the standard strain of the N. cyriacigeorgica and N. farcinica.
Figure 2: Gram stain (a) and Modified Kinyoun stain (b) of Nocardia spp. isolated from blood culture

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Figure 3: Growth of Nocardia cyriacigeorgica (a) and Nocardia farcinica (b) on 5% sheep blood agar

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Antimicrobial susceptibility testing of the Nocardia isolates was done by disk diffusion. Nocardia cyriacigeorgica was found to be susceptible to amoxicillin, ceftriaxone, gentamicin, linezolid, TMP-SMX, imipenem, levofloxacin and ciprofloxacin and resistant to amikacin. Nocardia farcinica was found to be susceptible to amoxicillin, ceftriaxone, ciprofloxacin, erythromycin, TMP-SMX and imipenem.


 ~ Discussion Top


Disseminated nocardiosis, especially with involvement of the central nervous system in SOT recipients has been reported frequently and has an unfavourable prognosis. However, early diagnosis with prompt intervention may result in successful outcome.[4],[5] On the other hand, Nocardia bacteraemia is rare. Nocardia bacteraemia in SOT recipients has been reported in renal transplant recipients both from India (2 case reports)[6],[7] and from overseas.[8],[9] Reports of Nocardia bacteraemia following liver, lung and heart transplant are scarce.[2],[10] The reasons for the low blood culture positivity of Nocardia in SOT recipients could be attributed to failure to obtain blood cultures in a seemingly localized pulmonary disease and associated concomitant bacteraemia due to less fastidious Gram negative bacteria, which may overgrow Nocardia.[11] Lastly, Gram-positive bacilli isolated from blood cultures may be discarded as contaminants unless one has a high index of suspicion. Gram stain followed by modified Kinyoun stain of positive blood cultures can provide a rapid presumptive diagnosis of Nocardia bacteraemia while awaiting culture results.

Our patients were on tacrolimus-based immunosuppression with high-trough levels of 17.4 ng/mL and 15.6 ng/mL at the time of diagnosis. A multicentre European case–control study revealed that the use of tacrolimus and high serum trough levels of calcineurin inhibitors (trough blood level >10 ng/mL for tacrolimus and >300 ng/mL for cyclosporine) at the time of diagnosis to be one of the risk factors for nocardiosis after SOT.[12] Hence, an attempt was made to reduce the immunosuppression by reducing the dose of tacrolimus to achieve trough levels <5 ng/mL.

No intervention has yet been shown to prevent nocardiosis in SOT recipients.[12] The liver transplant recipient was not on TMP-SMX prophylaxis for P. jirovecii at the time of diagnosis of Nocardia bacteraemia while the heart transplant recipient was on continued prophylaxis at the time of diagnosis of concomitant nocardiosis and cyclosporiasis. Coussement et al. found that low dose TMP-SMX prophylaxis against Pneumocystosis does not effectively prevent nocardiosis and breakthrough Nocardial infections have also occurred while on TMP-SMX prophylaxis.[12] Nocardiosis and cyclosporiasis in HIV-infected patients have been prevented by using higher doses of TMP-SMX (160/800 mg).[13],[14] Further studies may be needed to assess the role of high-dose TMP-SMX prophylaxis in preventing nocardiosis and cyclosporiasis in SOT recipients.

Silent Nocardia bacteraemia with or without extrapulmonary involvement is seen in SOT recipients thus highlighting the need for a high index of suspicion. The need for multiple sets of blood cultures in these patients cannot be overemphasised.

Dual opportunistic infections though infrequent can occur in solid organ transplant patients as exemplified by cyclosporiasis along with nocardiosis in our heart transplant recipient. Low dose prophylaxis with TMP-SMX, though necessary does not always protect against all pathogens.

Declaration of patient consent

The authors certify that they had obtained all appropriate consent forms. In the form, the patients have given their consent for their images, and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 ~ References Top

1.
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;19:259-82.  Back to cited text no. 1
    
2.
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. 2
    
3.
Winn W Jr., Allen S, Janda W, Koneman E, Procop G, Schreckenberger P, et al. Koneman's Color Atlas and Textbook of Diagnostic Microbiology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 1269.  Back to cited text no. 3
    
4.
Khadka P, Basnet RB, Khadka P, Shah DS, Pokhrel BM, Rijal BP, et al. Disseminated Nocardiosis in renal transplant recipient under therapy for pulmonary tuberculosis: A case report. BMC Res Notes 2017;10:83.  Back to cited text no. 4
    
5.
Hooda AK, Nandwani A, Kaur J, Bishnoi JS, Nair RK. Successful treatment of disseminated Nocardiosis in a renal transplant recipient. Med J Armed Forces India 2013;69:297-300.  Back to cited text no. 5
    
6.
Rudramurthy SM, Honnavar P, Kaur H, Samanta P, Ray P, Ghosh A, et al. Molecular identification of clinical Nocardia isolates from India. J Med Microbiol 2015;64:1216-25.  Back to cited text no. 6
    
7.
Wadhwa T, Baveja U, Kumar N, Govil D, Sengupta S. Clinical manifestations of Nocardiosis: Study of risk factors and outcomes in a tertiary care hospital. J Lab Physicians 2017;9:288-95.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Namnyak S, Uddin M, Ahmod N. Nocardia cyriacigeorgica bacteraemia presenting with cytomegalovirus disease and rapidly fatal pneumonia in a renal transplant patient: A case report. J Med Case Rep 2011;5:228.  Back to cited text no. 8
    
9.
Haussaire D, Fournier PE, Djiguiba K, Moal V, Legris T, Purgus R, et al. Nocardiosis in the south of France over a 10-years period, 2004-2014. Int J Infect Dis 2017;57:13-20.  Back to cited text no. 9
    
10.
Naik S, Mateo-Bibeau R, Shinnar M, Mahal M, Freudenberger R. Successful treatment of Nocardia nova bacteremia and multilobar pneumonia with clarithromycin in a heart transplant patient. Transplant Proc 2007;39:1720-2.  Back to cited text no. 10
    
11.
Kontoyiannis DP, Ruoff K, Hooper DC. Nocardia bacteremia. Report of 4 cases and review of the literature. Medicine (Baltimore) 1998;77:255-67.  Back to cited text no. 11
    
12.
Coussement J, Lebeaux D, van Delden C, Guillot H, Freund R, Marbus S, et al. Nocardia infection in solid organ transplant recipients: A multicenter European Case-control Study. Clin Infect Dis 2016;63:338-45.  Back to cited text no. 12
    
13.
Filice GA. Nocardiosis in persons with human immunodeficiency virus infection, transplant recipients, and large, geographically defined populations. J Lab Clin Med 2005;145:156-62.  Back to cited text no. 13
    
14.
Pape JW, Verdier RI, Boncy M, Boncy J, Johnson WD Jr. Cyclospora infection in adults infected with HIV. Clinical manifestations, treatment, and prophylaxis. Ann Intern Med 1994;121:654-7.  Back to cited text no. 14
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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