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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 15  |  Issue : 3  |  Page : 275-278

Varying presentations of pulmonary nocardiosis in kidney transplant recipients - Case series


1 Department of Nephrology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala, India
2 Department of Microbiology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala, India

Date of Submission28-Nov-2020
Date of Decision03-Jan-2021
Date of Acceptance19-Jan-2021
Date of Web Publication30-Sep-2021

Correspondence Address:
Dr. Sandeep Sreedharan
Assistant Professor, Department of Nephrology and Renal Transplantation, Amrita Institute of Medical Sciences, Amrita University Health Sciences Campus, Kochi, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_146_20

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  Abstract 

Infections continue to be a significant cause of morbidity and mortality after solid organ transplantation. Early identification of the pathogenic organism is extremely important as the disease process might progress rapidly resulting in fatality. In this case series, we describe varying presentations of pulmonary nocardiosis, an uncommon opportunistic bacterial infection that often complicates the diagnosis of pneumonia, especially in immunocompromised patients. Although cough, fever, expectoration and breathlessness are the most common symptoms of pulmonary nocardiosis, they can also manifest as night sweats, weight loss and malaise. Some are incidentally diagnosed while being evaluated for other causes. Radiological features are also non-specific, usual findings being irregular nodules, cavitation, reticulo nodular diffuse pneumonia and pleural effusions. Bronchoalveolar lavage has the best diagnostic yield, but may have to be repeated several times to confirm a diagnosis, if the index of suspicion is high. Initial therapy with high dose trimethoprim- sulfamethoxazole is found to be effective in most of the cases. Duration of treatment should be a minimum of 6 months, and at least 12 months if central nervous system is affected. Other agents used for treatment include imipenem, minocycline, third generation cephalosporins, linezolid and amikacin. A high index of suspicion, with aggressive evaluation in an immunosuppressed individual will enable an early diagnosis, leading to prompt treatment and limit dissemination of disease thus preventing fatality.

Keywords: Atypical pneumonia, Nocardia, nocardiosis, opportunistic infections, renal transplant


How to cite this article:
Shabeen K, Sreedharan S, Polachirakkal ZP, Shashindran N, Mathew A, Kumar V A, Kurian G, Nair RR. Varying presentations of pulmonary nocardiosis in kidney transplant recipients - Case series. Indian J Transplant 2021;15:275-8

How to cite this URL:
Shabeen K, Sreedharan S, Polachirakkal ZP, Shashindran N, Mathew A, Kumar V A, Kurian G, Nair RR. Varying presentations of pulmonary nocardiosis in kidney transplant recipients - Case series. Indian J Transplant [serial online] 2021 [cited 2021 Nov 29];15:275-8. Available from: https://www.ijtonline.in/text.asp?2021/15/3/275/327387


  Introduction Top


Renal transplantation has unquestionably increased the survival of patients with end-stage renal disease. However, infections continue to be a significant cause of morbidity and mortality after transplantation.[1] The potential pathogens vary from the common community-acquired bacteria to viruses, and to the uncommon opportunistic pathogens of clinical significance only in immunocompromised hosts. Early identification of the pathogenic organism in such a host is extremely important as the disease process might progress rapidly resulting in fatality.

We present three cases of an uncommon opportunistic infection in renal transplant recipients with varying clinico-radiological presentation.


  Case Series Top


Case 1

A 59-year-old male, who had undergone renal transplantation 7 years back, presented with fever, cough, and loss of appetite of 3-month duration. Clinical, immunological, and therapeutic details of the patients are shown in [Table 1]. On admission, he was febrile; normotensive and respiratory rate was 32/min. The patient had pallor, and on systemic examination, right infrascapular and infra-axillary crackels were heard. He had anemia (hemoglobin –9 g/dl), elevated C-reactive protein (CRP) –259 mg/l, neutrophilic leukocytosis (total leukocyte count –16,500/uL), stable graft function with serum creatinine 1.5 mg/dl, and hyponatremia (117 meq/L). Chest X-ray showed a well-defined heterogeneous opacity in the right lateral mid zone [Figure 1]. He was started on broad-spectrum intravenous antibiotics. Noncontrast computed tomography (CT) scan of the chest showed a well-defined hyperdense area with air bronchogram in the lateral segment of the right middle lobe. In view of clinical and radiological unresponsiveness and possible ineffectiveness of antibiotics, he underwent bronchoscopy on two occasions, which were inconclusive, except for the fungal smear growing budding yeast with pseudohyphae in the second test. Bronchoalveolar lavage (BAL) culture was negative for bacterial and fungal growth. GeneXpert for Mycobacterium tuberculosis (MTB) and smear for acid-fast bacilli were also negative. Cytopathology was negative for malignant cells. He was started on oral antifungal agent (fluconazole) in addition to the antibiotics. Since the patient had persistent symptoms and in view of nonresolving chest X-ray findings, he underwent bronchoscopy for the third time with cryobiopsy under general anesthesia. BAL culture grew Nocardia species, and then, he was initiated on organism-specific antimicrobial therapy (trimethoprim [TMP]-sulfamethoxazole and linezolid). With the above measures, he became symptomatically better and was discharged. On his latest visit to hospital 12 weeks after discharge, he is asymptomatic.
Table 1: Basic details of the patients

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Figure 1: Chest X-ray posteroanterior view showing right mid zone opacity suggestive of lobar pneumonia

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Case 2

A 55-year-old male, who underwent renal transplantation 2 years ago, presented to the transplant clinic with significant weight loss (13 kg over 6 months). He had no history of fever, cough, breathlessness, or hemoptysis. On admission, physical examination was inconclusive. Blood investigations revealed normal leukocyte counts with raised inflammatory markers (CRP –73 mg/L and erythrocyte sedimentation rate –29 mm/h). His graft function was normal with serum creatinine 0.6 mg/dl. Urine routine was normal and ultrasound abdomen showed altered echotexture of the liver without any features of portal hypertension and graft kidney showed normal sonomorphology with normal Doppler parameters. Chest X-ray did not reveal any obvious pathology. Echocardiography, upper gastrointestinal (GI) endoscopy, and colonoscopy were inconclusive. Sputum GeneXpert for MTB was negative. Positron emission tomography (PET)-CT which was done to rule out any occult malignancy revealed fluorodeoxyglucose (FDG)-avid consolidatory changes in the upper lobe of the right lung [Figure 2]. He underwent rigid bronchoscopy and multiple transbronchial lung cryobiopsies were taken from the anterior segment of the right upper lobe. BAL fluid showed weak acid-fast branching filamentous elements, suggestive of nocardiosis. He was initiated on TMP-sulfamethoxazole and linezolid (linezolid was later changed to ceftriaxone considering GI intolerance). After a follow-up of 4 weeks, his general condition improved and has gained 2 kg.
Figure 2: Positron emission tomography–computed tomography image showing fluorodeoxyglucose-avid wedge shape area of consolidation with air bronchogram involving right upper lobe

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Case 3

An 11-year-old boy who had undergone renal transplantation 1 year back presented with recurrent upper GI symptoms. Immediate posttransplant period, there was graft dysfunction; a graft biopsy done showed active antibody mediated rejection, and he was treated with intravenous methylprednisolone, plasmapheresis with intravenous immunoglobulin, and rituximab. On follow-up, his creatinine was stable around 1 mg/dl.

Three months back, he was evaluated for recurrent upper GI symptoms. He was found to have cytomegalovirus (CMV)-related erosive gastritis, for which he was started on intravenous ganciclovir followed by oral valganciclovir. After a few weeks of symptom-free interval, he was admitted with recurrence of GI symptoms. Upper GI endoscopy and colonoscopy were repeated. He was diagnosed to have posttransplant lymphoproliferative disorder (PTLD). Biopsy from the ulcerated lesion from the fundus was suggestive of PTLD with immunoprofile suggestive of diffuse large B-cell lymphoma. PET-CT, incidentally, showed an FDG-avid consolidation with cavitary changes in the anterior segment of the right upper lobe [Figure 3]. He underwent bronchoscopy, and BAL analysis done showed weak acid-fast branching filamentous elements, suggestive of nocardiosis. He was started on TMP-sulfamethoxazole, which had to be stopped later in view of pancytopenia, and he was started on imipenem and amikacin. After 1 month of treatment, a CT chest was repeated that showed significant improvement. However, later during the course of hospital stay, he had severe sepsis with graft dysfunction and he succumbed to the disease.
Figure 3: Fluorodeoxyglucose positron emission tomography–computed tomography image showing consolidation with mild cavitary changes in the anterior segment of the right upper lobe in the background of metabolically active right upper paratracheal, bilateral lower paratracheal, and subcarinal lymph nodes suggestive of a neoplastic pathology

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  Discussion Top


Pulmonary nocardiosis is an uncommon opportunistic bacterial infection that often complicates the diagnosis of pneumonia in immunocompromised patients, particularly solid organ transplant recipients. Due to the nonspecific clinical and radiological features, nocardiosis is often misdiagnosed or diagnosed very late in the course of disease.[2] Globally, there is a paucity of data on the true incidence of nocardiosis, although the prevalence of nocardiosis in renal transplant recipients was estimated to be 0.04%–0.7%.[2],[3] In a large follow-up study, nocardiosis was reported in 1.3% of renal transplant recipients at Christian Medical College, Vellore, South India.[4] Nocardiosis remains to be a diagnostic challenge even today and that is the reason why we chose to present and discuss these cases. Nocardia are Gram-positive, partially acid-fast rods, which grow slowly in branching chains belonging to the family Mycobacteriaceae.[5] Most of the human infections are caused by three species: Nocardia asteroides, Nocardia brasiliensis, and Nocardia caviae.[5] Mode of infection is by inhalation or contact with the bacteria through a cut or abraded skin, and the disease is not contagious.[6] Nocardia behaves like a pyogenic bacterium a metastasizing hematogenously to distant organ systems (lungs, skin, central nervous system, eye, kidney, subcutaneous tissue, and bone) resulting in disseminated disease and death.[7] Pulmonary nocardiosis comprises about 70% of all the total cases of nocardiosis.[8],[9] Disseminated disease is seen in about one-third of the cases with common secondary localizations to the skin/subcutaneous tissues and the brain.[2] Cough, fever, expectoration, and breathlessness are the most common symptoms of pulmonary nocardiosis.[10] However, they can also manifest as night sweats, weight loss, and malaise.[10] In this report, the first patient had classical symptoms of nocardiosis, but the other two patients did not have any of the classical symptoms described in nocardiosis. Such atypical presentations can make the diagnosis difficult with cases often misdiagnosed as pulmonary tuberculosis (TB), especially in a country like India, where TB is endemic. In one of the largest case series on nocardiosis from India, more than 60% of the cases were clinically misdiagnosed in the initial stages.[10] Most often cases are misdiagnosed as TB, community-acquired pneumonia, fungal infections, or malignancy. Pulmonary nocardiosis closely resembles TB clinically and radiologically, but first-line anti-TB treatment is not effective for its treatment, hence prompt differentiation of both species is very important for the treatment point of view. Only a few case reports of concomitant infection of Nocardia and TB have been published in the literature.[11] A prevalence of 1.4% concomitant infection of Nocardia and TB was also reported.[12]

There are no specific radiological features diagnostic for nocardiosis; usually, the findings are irregular nodules, cavitation, reticulonodular diffuse pneumonia, and pleural effusions. Singh et al. had reported that in 61% of the cases, there was unilateral involvement with upper lobe predominance (70%), out of which airspace disease and nodules were the most common radiographic abnormalities.[10] In our series, the first patient had classical radiological features, but the other two did not. In both these cases, lung involvement was obvious only in the CT scan. Although our first patient had classical symptoms, we had great difficulty in establishing the diagnosis, despite with bronchoscopy evaluation having to be done thrice. Diagnosis in the second case was also delayed because the patient did not have any classical features of nocardiosis and the index of suspicion was also low. In the third case, it was an incidental finding during workup for PTLD. The PET-CT scan was suggestive of an inflammatory disease with diagnosis made after bronchoscopy evaluation. BAL had the best diagnostic yield (90%), followed by transthoracic needle aspirate (80%).[10] Gram staining of the appropriate sample is the most sensitive method to detect Nocardia in clinical specimens. Modified acid-fast stain is not reliable and can be used only as confirmatory test for the acid fastness of organisms detected by Gram staining.[13] Prolonged use of glucocorticoids is one of major risk factors of nocardiosis. A study from China reported that 60% of their patients with pulmonary nocardiosis were on prolonged corticosteroid therapy.[14] Type 2 diabetes and CMV co-infections are also known to predispose to nocardiosis.[10] All the three of our patients were immunocompromised, as they were on triple immunosuppressants. The third patient had CMV co-infection too.

Initial therapy with high-dose TMP-sulfamethoxazole (15 mg/kg/day of TMP) is given for 3–6 weeks.[15] After this period, doses can be reduced safely. Duration of treatment should be a minimum of 6 months, and at least 12 months if central nervous system is affected. Other agents used for treatment include imipenem, minocycline, third-generation cephalosporins (ceftriaxone), linezolid, and amikacin.[16] Prophylactic dose of TMP-sulfamethoxazole is advised as secondary prophylaxis, especially in renal transplant recipients, ideally at the dose of one double-strength tablet/day or, if tolerance is low, one single-strength tablet/day.

In conclusion, studies indicate that nocardial infections are on the rise, on account of an increasing population of immunocompromised patients, namely due to increasing organ transplants, autoimmune diseases, malignancies, and the use of potent immunosuppressive drugs including steroids. Diagnosis is often missed or delayed because of the clinical and radiological resemblance to many other common as well as uncommon infections. Hence, only a high index of suspicion, with aggressive evaluation (microbiological isolation of Nocardia spp. from various clinical specimens) in an immunosuppressed individual, will enable an early diagnosis, leading to prompt treatment and limit dissemination of disease, thus preventing fatality.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient 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 her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgments

We acknowledge the help provided by the Departments of Nuclear Medicine, Radiology, Pulmonary and Respiratory Medicine, and Pathology at Amrita Institute of Medical Sciences in reaching at a diagnosis for the above mentioned cases.

 
  References Top

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Singh M, Sandhu RS, Randhawa HS, Kallan BM. Prevalence of pulmonary nocardiosis in a tuberculosis hospital in Amritsar, Punjab. Indian J Chest Dis Allied Sci 2000;42:325-39.  Back to cited text no. 12
    
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Saubolle MA, Sussland D. Nocardiosis: Review of clinical and laboratory experience. J Clin Microbiol 2003;41:4497-501.  Back to cited text no. 13
    
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