Coinfection With Nocardia exalbida and Mycobacterium tuberculosis Following Steroid Pulse Therapy: A Case Report and Literature Review

Abstract

We report a case of pulmonary nocardiosis and pulmonary tuberculosis following steroid pulse therapy for presumed myelitis. A 74-year-old man with transthyretin amyloid cardiomyopathy, chronic heart failure, and type 2 diabetes mellitus received two courses of steroid pulse therapy for suspected inflammatory myelitis. One month later, he developed progressive dyspnea and was admitted to our hospital. Chest computed tomography revealed multifocal right-sided infiltrates and pleural effusion. Although empirical piperacillin/tazobactam was initiated for presumed bacterial pneumonia, sputum Gram and Kinyoun stains revealed thin, branching, partially acid-fast bacilli, and sequencing of the secA1 gene identified Nocardia exalbida. Polymerase chain reaction (PCR) analysis was positive for Mycobacterium tuberculosis. Pleural fluid culture yielded Nocardia species. The patient’s condition improved following combined antituberculous and anti-nocardial therapy, along with optimized heart failure management. Coinfection with nocardiosis and tuberculosis should be considered in immunosuppressed patients following corticosteroid therapy.

Introduction

Acute transverse myelitis (TM) is a rare acquired neuroimmune disorder of the spinal cord that can present with rapidly progressive weakness, sensory disturbances, and autonomic dysfunction. Diagnostic accuracy is challenging because of the wide range of potential pathophysiologic mechanisms underlying myelopathy, including inflammatory, compressive, neoplastic, vascular, nutritional, and infectious etiologies. Idiopathic TM, an inflammatory myelopathy of unknown etiology, accounts for approximately 15% of TM cases and is often treated with high-dose corticosteroids after alternative causes have been excluded [1].

Nocardia species are ubiquitous environmental organisms found in soil, vegetation, and water that predominantly cause opportunistic infections in immunocompromised hosts. Corticosteroid therapy, diabetes mellitus, transplantation, malignancy, and impaired cell-mediated immunity are recognized risk factors, and pulmonary involvement is the most common clinical manifestation. A retrospective observational study of 60 patients with nocardiosis identified a strong association between systemic corticosteroid therapy and pulmonary nocardiosis (matched odds ratio (OR), 5.90; 95% confidence interval (CI), 2.75-12.66; p<0.001) [2]. Similarly, reactivation of latent tuberculosis may occur in patients with impaired cellular immunity, including those receiving corticosteroid therapy. Coinfection with Nocardia species and Mycobacterium tuberculosis is uncommon, and only a limited number of cases have been described in the literature [3-5]. Furthermore, Nocardia exalbida is a relatively rare species that has been reported to exhibit favorable antimicrobial susceptibility profiles and clinical outcomes compared with those of other pathogenic Nocardia species; however, the number of reported cases remains limited [6]. Pulmonary nocardiosis and pulmonary tuberculosis share several risk factors and may exhibit overlapping clinical and radiological features, making diagnosis challenging. Herein, we report a case of pulmonary coinfection with N. exalbida and M. tuberculosis that developed following steroid pulse therapy for presumed myelitis and provide a review of the literature.

Case presentation

A 74-year-old man undergoing treatment for transthyretin amyloid cardiomyopathy, chronic heart failure, chronic kidney disease, and type 2 diabetes mellitus developed occipital headaches four months before admission and was evaluated at another hospital. At that time, cranial magnetic resonance imaging (MRI) showed no abnormal findings. Loxoprofen, mirogabalin, and carbamazepine were administered with little effect. One month before admission, repeat MRI revealed an area of high signal intensity on contrast-enhanced T2-weighted imaging at the left C1-2 level of the spinal cord. Myelitis was suspected as the cause of the headaches, and two courses of steroid pulse therapy were administered. Subsequently, the occipital headaches persisted; however, no other neurological symptoms developed, and the abnormal MRI signal improved.

Approximately 20 days before admission to our hospital, the patient developed progressive exertional dyspnea and was subsequently admitted. Vital signs on admission were as follows: body temperature, 35.8°C; blood pressure, 118/70 mmHg; heart rate, 70 bpm; SpO₂, 98% on room air; and respiratory rate, 30 breaths/min. The patient was alert and oriented. Physical examination revealed no abnormalities on cardiac or pulmonary auscultation. Mild lower extremity edema was present.

Investigations

Laboratory investigations revealed leukocytosis with neutrophil predominance, elevated inflammatory markers, severe hyperglycemia with poor glycemic control, elevated brain natriuretic peptide levels, and hypoalbuminemia. The T-SPOT.TB test was negative (Table 1). Chest radiography showed a right pleural effusion (Figure 1), while chest CT revealed infiltrates in segments S7-10 of the right lower lobe, the right middle lobe, and segment S3, together with a predominantly right-sided pleural effusion (Figure 2). A sputum Gram stain obtained before treatment initiation showed numerous leukocytes and only a few bacterial cells; however, thin, branching, Gram-positive bacilli were identified, raising suspicion for Nocardia infection. Kinyoun staining subsequently demonstrated partially acid-fast, thin, branching bacilli (Figure 3). Analysis of colonies cultured on blood agar plates using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (VITEK MS; bioMérieux, Marcy l'Etoile, France) identified Nocardia spp. Drug susceptibility testing was performed using the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines (Table 2) [7]. To achieve species-level identification of the Nocardia isolate, the secA1 gene was sequenced. The primer sequences were as follows: 5’-GTA AAA CGA CGG CCA GGA CAG YGA GTG GAT GGG YCG SGT GCA CCG-3’ and 5’-CAG GAA ACA GCT ATG ACG CGG ACG ATG TAG TCC TTG TC-3’ [8]. The obtained sequence showed 99.14% identity (461/465 bp) with N. exalbida strain DSM 44883 (accession no. GU584191) using the Basic Local Alignment Search Tool (BLAST) database https://blast.ncbi.nlm.nih.gov/Blast.cgi and clustered within the N. exalbida clade on phylogenetic analysis (Figure 4). Fluorescent acid-fast staining of the sputum was negative; however, polymerase chain reaction (PCR) testing for Mycobacterium tuberculosis was positive. Pleural fluid analysis demonstrated an exudative effusion with a predominance of polymorphonuclear leukocytes. The adenosine deaminase level was 27.8 U/L and was not elevated, making tuberculous pleuritis less likely. Subsequently, Nocardia spp. was isolated from pleural fluid culture, suggesting that the pleural effusion was attributable to nocardial pleuritis rather than tuberculous pleuritis. Cerebrospinal fluid analysis showed no abnormalities, including pleocytosis, and cerebrospinal fluid cultures were negative.

Table 1. Laboratory workup.

H: high; L: low

Laboratory Test	Day 1	Day 16	Day 37	Day 58	Day 72	Reference Range
White blood cell count (×103 /µL)	11.0 H	5.6	4.9	4.4	4.4	3.30–8.60
Segmented neutrophils (%)	90.00 H	75.8 H	60.4	62.2	60.2	38–74
Hemoglobin (g/dL)	16.6	12.3 L	11.4 L	11.5 L	12.5 L	13.7–16.8
Platelet count (×103 /µL)	327	110 L	221	162	136 L	158–348
Serum albumin (g/dL)	2.2 L	1.9 L	2.5 L	3.1 L	3.1 L	4.1–5.1
Glucose (mg/dL)	479 H	102 H	82	109 H	104 H	73–93
Hemoglobin A1c (%)	11.30 H	N/A	N/A	N/A	N/A	4.6–6.2
Blood urea nitrogen (mg/dL)	43 H	21 H	19	46 H	29 H	8–20
Creatinine (mg/dL)	1.5 H	0.86	1.12 H	1.84 H	1.51 H	0.65–1.07
C-reactive protein (mg/dL)	27.0 H	4.38 H	2.57 H	1.07 H	1.20 H	0.0–0.14
Brain natriuretic peptide (pg/mL)	677 H	N/A	N/A	N/A	N/A	<18.4
T-SPOT.TB	Negative	N/A	N/A	N/A	N/A

Table 2. Minimum inhibitory concentrations of various antibiotics against Nocardia spp.

Note: Break points are derived from CLSI/NCCLS 2011 [7]

CLSI/NCCLS: Clinical and Laboratory Standards Institute/National Committee for Clinical Laboratory Standards

Antibiotic	MIC (μg/mL)	Result
Amoxicillin-clavulanic acid	0.38	Susceptible
Ceftriaxone	0.064	Susceptible
Cefepime	4	Susceptible
Imipenem/cilastatin	4	Susceptible
Clarithromycin	4	Intermediate
Doxycycline	4	Intermediate
Minocycline	4	Intermediate
Tobramycin	2	Susceptible
Amikacin	≤4	Susceptible
Moxifloxacin	8	Resistant
Ciprofloxacin	≥4	Resistant
Linezolid	1.5	Susceptible
Trimethoprim-sulfamethoxazole	≤10	Susceptible

Figure 1. Chest X-ray on day 1 of illness showing right pleural effusion.

Figure 2. Computed tomography scan of the thorax on day 1 of illness.

A: upper axial image; B: right panel: lower axial image. Both images demonstrate infiltrative opacities involving the right middle lobe, segment S3, and segments S7–10 of the right lower lobe, with pleural effusion predominantly on the right side.

Figure 3. Kinyoun staining showing acid-fast, thin, branching bacilli (1,000×).

Figure 4. Phylogenetic tree based on secA1 gene sequences.

Differential diagnosis

Exacerbations of pneumonia, pleurisy, and chronic heart failure were considered in the differential diagnosis of exertional dyspnea and pleural effusion. Pneumonia caused by common bacteria was considered unlikely because the dyspnea did not progress rapidly, and although Gram staining of the sputum revealed numerous leukocytes, only a small number of bacterial cells were observed. Based on the sputum microbiological findings, the patient was diagnosed with pulmonary coinfection due to Nocardia exalbida and Mycobacterium tuberculosis. Prolonged culture of the pleural fluid subsequently yielded Nocardia spp., suggesting concomitant nocardial pleuritis. In immunocompromised patients, central nervous system infections such as nocardial brain abscesses can occur; however, brain MRI and cerebrospinal fluid findings did not support central nervous system involvement. After confirming the patient's history of contact with individuals with tuberculosis, it was determined that the exposure had occurred during childhood. Although the T-SPOT.TB test was negative; this was considered to be attributable to the patient's immunosuppressed state resulting from advanced age, a history of immunosuppressive therapy, and chronic kidney disease. We considered that the pulmonary infection exacerbated the patient's chronic heart failure, which likely contributed to his exertional dyspnea.

Treatment, outcome, and follow-up

On day 1 of the index illness, the patient received piperacillin/tazobactam (4.5 g intravenously every 8 h) as empirical therapy. On day 7, because sputum PCR testing for Mycobacterium tuberculosis and sputum culture findings raised suspicion for tuberculosis and nocardiosis, antituberculous therapy (isoniazid 300 mg, rifampicin 600 mg, pyrazinamide 1,500 mg, and ethambutol 1,000 mg) was initiated for pulmonary tuberculosis, while imipenem/cilastatin (500 mg intravenously every 12 h) and trimethoprim/sulfamethoxazole (trimethoprim 720 mg/day in divided doses) were initiated for pulmonary nocardiosis. On day 12, trimethoprim/sulfamethoxazole was discontinued because of vomiting and anorexia. On day 16, treatment for pulmonary nocardiosis was changed to imipenem/cilastatin plus amikacin (dose adjusted to achieve a target peak serum concentration of 40-60 μg/mL and a trough concentration of ≤1 μg/mL). On day 28, cranial MRI revealed no findings suggestive of nocardial brain abscesses. On day 44, the patient developed impaired renal function (Table 1). As there were no findings suggestive of disseminated nocardiosis, amikacin was discontinued, and treatment was continued with imipenem/cilastatin alone.

Despite improvement of the pulmonary infection, the patient continued to experience exertional dyspnea, and chronic heart failure was considered the primary cause of the persistent respiratory symptoms and pleural effusion. Oral tolvaptan was administered as a diuretic; however, because rifampicin is a strong cytochrome P450 (CYP) 3A4 inducer and may decrease serum concentrations of tolvaptan, rifampicin was replaced with rifabutin 300 mg on day 48. Following intensification of diuretic therapy, the pleural effusion improved, and the exertional dyspnea gradually resolved. On day 58, treatment for pulmonary nocardiosis was switched from imipenem/cilastatin to oral amoxicillin-clavulanic acid (500 mg/125 mg orally every 12 h). On day 68, antituberculous therapy was de-escalated to isoniazid plus rifabutin, and the patient was discharged home on day 76. Serial laboratory evaluations demonstrated gradual improvement in inflammatory markers and nutritional status during treatment. The white blood cell count and C-reactive protein level decreased progressively, while serum albumin levels improved, consistent with clinical recovery (Table 1).

Because of the prolonged hospital stay and subsequent decline in physical activity, the patient received rehabilitation through home-visit nursing. Treatment for pulmonary nocardiosis and pulmonary tuberculosis was continued, and medication management was also provided through home-visit nursing. Although exertional dyspnea persisted, his physical activity gradually improved, and he became able to walk around his home. Oral amoxicillin-clavulanic acid, isoniazid, and rifabutin were discontinued on day 188 of the index illness. No recurrence of pulmonary nocardiosis or pulmonary tuberculosis has been observed since completion of treatment. Furthermore, chest radiography performed on day 211 demonstrated improvement of the pulmonary infiltrates and pleural effusion (Figure 5).

Figure 5. Chest X-rays on day 211 of illness showed improvement in infiltrative shadows and pleural effusion.

Discussion

This case illustrates that even short-term high-dose corticosteroid therapy may have contributed to the development of opportunistic coinfection with N. exalbida and Mycobacterium tuberculosis in susceptible patients with underlying immunocompromising conditions, such as diabetes mellitus and advanced age.

Inflammatory myelopathy is characterized by bilateral neurological symptoms, corresponding to innervation of the spinal cord, inflammatory findings in spinal fluid or MRI studies, and a clinical course in which symptoms are at their worst between four hours and 21 days after onset [1]. In the acute phase of this disease, the prompt use of high-dose corticosteroids is recommended after ruling out spinal cord infarction and infectious myelitis. In the present case, the cause of the myelitis was unclear; however, the continuous headaches and abnormal intramedullary signal change at C1-2 led to the use of methylprednisolone for myelitis.

Nocardiosis and reactivation tuberculosis occur predominantly in immunocompromised hosts. In the present case, several factors may have contributed to immunosuppression, including advanced age, chronic heart failure, poorly controlled type 2 diabetes mellitus, and recent corticosteroid therapy. Although the patient had no apparent history of soil exposure, such as gardening, he was considered susceptible to nocardiosis because of his immunocompromised condition. Notably, despite active pulmonary tuberculosis, the T-SPOT.TB test was negative. This result may have reflected impaired cell-mediated immune responses associated with the patient's immunocompromised state [9].

Pulmonary nocardiosis has non-specific clinical manifestations and imaging findings, and identification of Nocardia requires prolonged culture, making the diagnosis challenging. However, treatment for pulmonary nocardiosis differs from that for typical bacterial pneumonia or pulmonary tuberculosis, and the disease may be fatal if left untreated. In a study of sputum samples obtained from 189 patients with suspected pulmonary tuberculosis, the prevalence of coinfection with nocardiosis and tuberculosis was 6.25% among patients with HIV infection and 1.05% among all patients [3]. Furthermore, our literature search of the PubMed database, conducted in April 2026 using the search terms "(nocardia) AND (mycobacterium tuberculosis) AND (coinfection)", identified 13 case reports of coinfection with Nocardia spp. and M. tuberculosis (Table 3). Among these 13 previously reported cases, five patients had a history of immunosuppressive therapy [10-14], five had diabetes mellitus [10-12,15,16], three had chronic obstructive pulmonary disease [4,11,17], and one had acquired immunodeficiency syndrome [16]. Immunocompromised status, impaired airway clearance, and emphysematous lung changes may be risk factors for severe or fatal disease. The lungs were the most commonly affected site; however, involvement of other organs, including bone and the thyroid gland, has also been reported [13,14,18,19]. In immunocompromised patients, multiple concomitant infections may occur simultaneously. Therefore, even when pulmonary tuberculosis has been diagnosed during the evaluation of pulmonary infiltrates, the possibility of additional pathogens should be considered.

Table 3. Cases of nocardiosis and tuberculosis coinfection reported internationally.

AIDS: acquired immunodeficiency syndrome; ATT: antituberculous therapy treatment; CNS: central nervous system; COPD: chronic obstructive pulmonary disease; DM: diabetes mellitus; EB: ethambutol; FSGS: focal segmental glomerulosclerosis; HBV-MN: hepatitis B virus-associated membranous nephropathy; HPL: hyperlipidemia; IM: inflammatory myopathy; INH: isoniazid; LVFX: levofloxacin; MG: myasthenia gravis; PZA: pyrazinamide; RFP: rifampicin; TMP/SMX: trimethoprim/sulfamethoxazole

No.	Ref.	Age/Sex	Underlying comorbidity	Systemic immunosuppressive agents	Sites of infection	Isolated species	Treatment for nocardiosis and tuberculosis	Outcome
1	[4]	79/F	COPD	None	Lung	N. farcinica, M. tuberculosis	TMP/SMX, INH, RFP, PZA, EB	Unknown
2	[5]	43/M	Cerebral palsy, Chronic psychiatric illness	None	Lung	Nocardia spp., M. tuberculosis	Imipenem, linezolid, levofloxacin, TMP/SMX, INH, RFP, PZA, EB	Improved
3	[10]	57/M	HBV-MN, Type 2 DM	Methylprednisolone	Lung	N. nova, M. tuberculosis, Aspergillus fumigatus, Cytomegalovirus	TMP/SMX, imipenem, INH, EB, PZA, LVFX	Improved
4	[11]	49/M	COPD, DM	Steroid	Lung	Nocardia sp., M. tuberculosis	TMP/SMX, linezolid, INH, RFP, PZA, EB	Mortality
5	[12]	41/M	MG, Type 2 DM, HPL	Methylprednisolone	Lung	N. brasiliensis, M. tuberculosis, Pneumocystis jirovecii	TMP/SMX, linezolid, INH, RFP, PZA, EB	Not improved
6	[13]	72/F	IM	Methylprednisolone, Prednisolone, Methotrexate	Thyroid, CNS, Lung	Nocardia sp., M. tuberculosis	TMP/SMX, amikacin, imipenem, INH, RFP, PZA, EB	Mortality
7	[14]	25/M	Primary FSGS	Steroid, Tacrolimus	Ocular	N. arthritidis, M. tuberculosis	Imipenem, intravenous cefotaxime, amikacin, ATT	Improved
8	[15]	67/M	DM	None	Lung	Nocardia sp., M. tuberculosis	Meropenem, TMP/SMX, ATT	Improved
9	[16]	36/M	AIDS, Type 2 DM	None	Lung	Nocardia sp., M. tuberculosis	TMP/SMX, ATT	Unknown
10	[17]	75/M	COPD	None	Lung	N. otitidiscaviarum, M. tuberculosis	meropenem, ceftriaxone, ATT	Mortality
11	[18]	65/M	None	None	Bone	N. actinomycetes, M. tuberculosis	TMP/SMX, INH, RFP, EB	Improved
12	[19]	34/M	None	None	CNS	N. abscessus, M. tuberculosis	TMP/SMX, imipenem, linezolid, INH, RFP, PZA, EB	Mortality
13	[20]	59/M	None	None	Lung	N. abscessus, M. tuberculosis	amoxicillin-clavulanic acid, ATT	Improved

Identification of Nocardia species remains challenging because of non-specific clinical manifestations, slow growth in culture, and the difficulty of species-level discrimination using 16S ribosomal RNA (rRNA) gene sequencing. Sequencing of the 16S rRNA gene has become the gold standard for species-level identification of Nocardia isolates. However, the 16S rRNA gene sequences of some distinct Nocardia species have been shown to be highly similar [8]. We initially attempted species-level identification using 16S rRNA gene sequencing; however, definitive identification could not be achieved because of the high sequence similarity among several closely related Nocardia species. Subsequent secA1 gene sequence analysis supported identification of the isolate as Nocardia exalbida. N. exalbida was first reported in 2006 and has rarely been reported since then. A previous case report and literature review suggested that N. exalbida is susceptible to many antimicrobial agents, which may contribute to its generally favorable prognosis [6]. Although trimethoprim-sulfamethoxazole could not be continued in the present case because of gastrointestinal intolerance, treatment was successfully modified to other active agents based on antimicrobial susceptibility testing.

In patients at risk of immunosuppression, nocardiosis should be included in the differential diagnosis, and appropriate microbiological investigations may facilitate early diagnosis. Furthermore, when infections suggestive of impaired cellular immunity, such as tuberculosis, are identified, clinicians should also consider the possibility of concomitant opportunistic infections. In the present case, although detailed immunological investigations were not performed, the patient had diabetes mellitus, poor glycemic control following steroid therapy, and immunosuppression, consistent with the characteristics of the patient population described above.

Conclusions

This case highlights the importance of considering concomitant opportunistic infections, including nocardiosis and tuberculosis, in immunocompromised patients who develop pulmonary infiltrates following corticosteroid therapy. Clinicians should maintain a high index of suspicion for coinfection, even in patients with only mild impairment of cell-mediated immunity or after identification of an apparent causative pathogen, such as Mycobacterium tuberculosis. Careful microbiological evaluation is essential for establishing a timely diagnosis and initiating appropriate treatment.