TUTORIAL

https://doi.org/10.5005/jp-journals-10089-0037
Journal of Acute Care
Volume 1 | Issue 3 | Year 2022

A Case Report of Necrotic Lung Abscess due to Nocardia Otitidiscaviarum

Owais Tisekar¹ https://orcid.org/0000-0003-3751-469X, Ajith Kumar AK² https://orcid.org/0000-0001-5134-1698, Justin A Gopaldas³ https://orcid.org/0000-0002-0420-6925, Rajeev C Mathews⁴, Ranjeeta Adhikary⁵ https://orcid.org/0000-0003-4695-0135

^1-3Department of Critical Care Medicine, Manipal Hospital, Bengaluru, Karnataka, India

⁴Department of Internal Medicine, Manipal Hospital, Bengaluru, Karnataka, India

⁵Department of Laboratory Medicine–Microbiology, Manipal Hospital, Bengaluru, Karnataka, India

Corresponding Author: Owais Tisekar, Department of Critical Care Medicine, Manipal Hospital, Bengaluru, Phone: +91 9773841038, e-mail: waistisekar@gmail.com

Received on: 01 October 2022; Accepted on: 13 February 2023; Published on: 03 May 2023

ABSTRACT

Nocardia is a cause of localized or disseminated infection in humans. Nocardia otitidiscaviarum (N. otitidiscaviarum) is an infrequent cause of nocardiosis, accounting for <5% of the cases. N. otitidiscaviarum primarily affects the lungs, skin, and brain, with the lungs being the most common site. Diagnosis can be a challenge, and it requires a high index of suspicion among clinicians. A 52-year-old gentleman presented to our hospital with a 2-month history of fever, cough, and progressive breathlessness. He was started on a high-flow nasal cannula (HFNC) for respiratory failure. The positron emission tomography (PET) showed a left lower lobe mass lesion with a maximum standardized uptake value (SUV) of 17.4. The histopathological findings of the computed tomography (CT)-guided mass biopsy were consistent with an abscess. The identification of Nocardia species was made by Kinyoun staining after decolorization with 1% of sulfuric acid. According to the drug-sensitivity test, the patient was started on trimethoprim/sulfamethoxazole along with imipenem/cilastatin. There was clinical improvement in 3–4 days and the patient was weaned off the HFNC support. Nocardiosis should be an essential consideration for the differential diagnosis of many bacterial, fungal, and viral infections, even in immunocompetent individuals. Early diagnosis and treatment help to improve survival.

How to cite this article: Tisekar O, Ajith Kumar AK, Gopaldas JA, et al. A Case Report of Necrotic Lung Abscess due to Nocardia Otitidiscaviarum. J Acute Care 2022;1(3):163-167.

Source of support: Nil

Conflict of interest: Dr Ajith K, Dr Justin A Gopaldas and Dr Ranjeeta Adhikary are associated as the Editorial board members of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of these Editorial board members and their research group.

Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.

Keywords: Immunocompetent, Lung abscess, Nocardia, Otitidiscaviarum.

INTRODUCTION

Nocardia, an Actinomycetales, causes localized and disseminated infection in humans. To date, over 50 species of the family, Nocardiaceae, are clinically significant, asteroids being the most frequent.¹ It is a rare cause of opportunistic infection in immunosuppressed and healthy individuals. N. otitidiscaviarum most commonly affects the lungs via inhalation.¹ CT chest plays an important role in diagnosis; however, findings are nonspecific and require microbiological confirmation.² Diagnosis can be a challenge, and it requires a high index of suspicion among clinicians. We describe a case of N. otitidiscaviarum affecting the lungs in an immunocompetent individual with an emphasis on the approach for its diagnosis.

CASE DESCRIPTION

A 52-year-old cotton farmer was admitted to our hospital with fever, productive cough, and gradually progressive breathlessness for 2 months. There was no history of night sweats or weight loss, nor any history of tuberculosis. There was no other significant comorbid illness. Physical examination on admission showed a pulse rate of 96/minute, blood pressure of 112/78 mmHg, a skin temperature of 37.8°C with a room air saturation of 92%, and a respiratory rate of 30 cycles/minute. There were early to mid inspiratory crepitations in the left infrascapular area on auscultation. A complete hemogram showed a hemoglobin of 13.4 g/dL (normal range—13.5–18 g/dL), white cell count of 23030/μL (normal range—4000–11000/μL) with 86.4% neutrophils (normal range—45–76%), and 7.6% lymphocytes (normal range—17–44%). Screening for human immunodeficiency virus infection and diabetes mellitus was negative. The chest radiograph showed bilateral ill-defined nodular shadows with the largest coalescent opacity in the left lower zone. Blood and sputum cultures were sent for analysis, and cultures were negative. We started him on ceftriaxone and azithromycin empirically. On day 5 of the illness, we started him on HFNC for hypoxemic respiratory failure, not amenable to oxygen supplementation. Given the suspicion of tuberculosis versus malignancy, a PET-CT was undertaken. PET-CT (Fig. 1) showed a 9 × 7 cm heterogeneously enhancing mass lesion in the left lower lobe with internal hypodense areas, likely an abscess. The maximum SUV of the abscess was 17.4. There was no other lesion on PET-CT. We did a CT-guided biopsy from the left lower lobe necrotic mass from the most fluorodeoxyglucose (FDG) avid area. Histopathology revealed an acute inflammatory collection of many neutrophils, histiocytes, and extensive necrosis with few foreign body giant cells. Gram stain on the specimen revealed many branching, filamentous, and gram-positive bacteria, which were positive with Kinyoun staining for acid-fast bacteria after decolorization with 1% sulfuric acid (Fig. 2). The culture of the specimen grew N. otitidiscaviarum on 5% sheep and chocolate agar with species identification by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) spectrometry (Fig. 3). The isolate was susceptible to sulfamethoxazole-trimethoprim and aminoglycoside and resistant to amoxicillin/clavulanate as per the susceptibility testing by broth dilution method. Hence, we started the patient on trimethoprim/sulfamethoxazole (160/800 mg) thrice daily with imipenem/cilastatin 500/500 mg 4 times per day. Over the next 3–4 days, his symptoms gradually improved, and he got weaned off from the HFNC and was transferred to the ward. At 3 weeks of treatment for nocardiosis, imipenem/cilastatin was stopped, and he was discharged on trimethoprim/sulfamethoxazole (160/800 mg) every 8 hours. The patient was asked to review after four weeks; however, he was lost to follow-up. At the time of discharge, he had a clinical resolution of symptoms with a room air saturation of 96%.

Fig. 1: Chest radiograph demonstrates coalescent mass lesion in the left lower zone (black arrow) with nodular shadows bilaterally (red arrow)

Fig. 3: Left lower lobe heterogeneous mass with multiple internal necrotic areas and adjacent air bronchogram. There is right lower lobe mucous plugging and associated bronchiectasis

Fig. 2: Modified Kinyoun stain showing branching acid-fast bacilli after decolourization with 1% sulfuric acid

QUESTIONS AND ANSWERS

Enumerate the opportunistic pathogens affecting the lungs?

The following list of pathogens is considered in the differential diagnosis of infections when there is a loss of host immune responses (Table 1).

**Table 1:** List of the common opportunistic pathogens seen in the immunocompromised host
Bacteria	Nocardia, actinomycosis
Viruses	Respiratory viruses like influenza, adenovirus, parainfluenza, respiratory syncytial virus, and human metapneumovirus Cytomegalovirus Human herpes virus
Fungi	Pneumocystis jirovecii Aspergillus species Candida species Cryptococcus neoformans Molds like mucor and rhizopus Endemic mycosis Other filamentous fungi (Fusarium and Scedosporium)

Classify the immune defects and the typical organisms associated with the immune defects (See Table 2).

**Table 2:** Immune defects and the organisms commonly associated with them
Neutrophils
Neutropenia	Medications (methotrexate, valganciclovir, sulfamethoxazole, azathioprine, everolimus, antineoplastic agents)Hematological malignancies Bone marrow suppression	Bacteria Fungi Viruses Parasites Opportunistic pathogens like cytomegalovirus, cryptosporidium, parvovirus, Pneumocystis jirovecii
Neutrophil functional defect	Chronic granulomatous disease Corticosteroids Chronic exocrine insufficiency Chronic liver disease	Gram-positive cocci (Staphylococcus and Streptococcus) Gram-negative bacilli like E. coli, Klebsiella Fungi like Candida, Mucormycosis, and Aspergillus
T-cell defect	Organ transplantation like kidney, liver, heart Bone marrow transplant Hematological malignancies T-cell-depleting drugs like tacrolimus, everolimus, and cyclosporin	Community-acquired respiratory viruses Cytomegalovirus and varicella zoster virus Nocardia and ActinomycosisPneumocystis jirovecii Mycobacterial tuberculosis
B-cell defect	B-cell-depleting drugs like mycophenolate mofetil, rituximab, bortezomib Chronic leukemia and lymphomas HSCT	Encapsulated bacteria like H. influenza Human herpes virus
Complement abnormalities	Drug-induced like Eculizumab and Carfilzomib Systemic lupus erythematosus	Encapsulated bacteria
Asplenia	Postsplenectomy	Encapsulated bacteria

What are the most common nocardial species affecting the human population?

Nocardia is an anaerobic, filamentous, gram-positive, and weak acid-fast bacillus. Species most commonly causing human infection include Nocardia asteroids, Nocardia transvalensis, Nocardia brasiliensis, N. otitidiscaviarum, and Nocardia cyriacigeorgica.³ N. otitidiscaviarum accounts for roughly 2.9% of all Nocardia infections.⁴

What are the predisposing risk factors for Nocardiosis?

One-third of the cases are seen in immunocompetent individuals.⁷ In immunocompetent individuals, infection is mostly self-limiting.

Risk factors predisposing to infection are described below (Table 3).⁵

**Table 3:** Predisposing risk factors for nocardiosis
Acquired immune deficiency syndrome with CD4 counts <50	Lymphoproliferative diseases and carcinomas
Chronic steroid therapy	Liver cirrhosis
Solid organ transplant, especially lungs	Intravenous drug abuse
Bone marrow organ transplant	Chronic lung disease

**Table 4:** Common bacterial, fungal, and viral organisms coinfecting patients with *Nocardia*
Klebsiella pneumoniae	Coagulase negative Staphylococcus aureus	Escherichia coli
Pseudomonas	Tuberculosis	Aspergillus
Candida	Herpes	Cytomegalovirus

**Table 5:** Nocardial species and the corresponding antibiotic sensitivity pattern
N. abscessus	Sensitive to penicillins, cefalosporins, linezolid, and aminoglycosides. Resistant MICs for macrolides, carbapenems, etc.
N. otitidiscaviarum	Sensitive to aminoglycoside, sulfamethoxazole, and fluoroquinolone. Resistant to β-lactam antibiotics.
N. pseudobrasiliensis	Sensitive to penicillin, macrolide, and sulfamethoxazole. Resistant to aminoglycoside and minocycline
N. brasiliensis	Sensitive to penicillins, minocycline, and sulfamethoxazole Resistant to fluoroquinolone, aminoglycoside, and macrolide.
N. asteroides complex	Sensitive to ceftriaxone, carbapenems, and aminoglycoside Resistant to penicillins and macrolide
N. farcinica	Sensitive to fluoroquinolones, linezolid, and carbapenems Resistant to penicillins, cephalosporins, and macrolide
N. transvalensis complex	Sensitive to linezolid, fluoroquinolones, and carbapenems Resistant to macrolides and aminoglycosides
N. nova complex	Sensitive to ampicillin, macrolides, and linezolid Resistant to amoxicllin-clavulanate

MIC, minimum inhibitory concentration

Describe the clinical features of Nocardiosis?

Nocardiosis affects people between 20 and 60 years of age. Males are more frequently affected than females and are predominantly a disease in rural areas. Infection is acquired either through traumatic cutaneous inoculation or through inhalation (67% of cases). The cutaneous lymphocutaneous form arises through the skin, whereas the pleuropulmonary form arises via inhalation. Either of these two forms can lead to hematogenous dissemination to the pleura, brain, or abdominal organs like the liver.⁵

Nocardia can have an acute, subacute, or chronic suppurative presentation. Symptoms include fever, chills, night sweats, cough, and breathlessness which are usually seen to last from a few days to weeks.³
Why is N. otitidiscaviarum infrequently detected compared to other nocardial species?

The low incidence of N. otitidiscaviarum is attributed to the lower prevalence in soil and reduced pathogenicity requiring repeated inhalation or inoculation of large doses for causing disease besides infrequent reporting of cases.³
Describe the radiological features of N.otitidiscaviarum?

No characteristic radiological feature can be ascribed to nocardiosis. Radiologically, it presents in the respiratory tract as pneumonia, pleural effusion, abscess, cavitary, or nodular masses mimicking either infection or malignancy.²

PET-CT shows high uptake in the infected area with an SUV over 2.5.⁸ Biopsy commonly shows necrosis with neutrophils, macrophages, and lymphocytes in the acute or subacute phase. Fibrosis predominates in the chronic phase.³
Which organisms are frequently isolated from Nocardia species?

Concurrent infection is seen in 17% of cases, mainly with other bacteria, fungi, or viruses.⁶
How is the confirmatory diagnosis of Nocardiosis made?

Diagnosis is made by microscopic identification by Gram stain or modified Kinyoun stain. Microscopically, it is gram-positive, beaded, and branching filament, which is 1% acid-fast. Colonies on culture are chalky white or cotton ball-like.³
Which method is used for accurate diagnosis of N. otitidiscaviarum species?

Molecular techniques are now preferred for accurate species determination. Species identification is done by the MALDI-TOF mass spectrometry method, which has an accuracy of 95.9% in species identification.⁹ In addition, it helps in the identification of important Nocardia species.

Other molecular methods available are polymerase chain reaction, DNA sequencing, and restriction fragment length polymorphism.³
Describe the standard therapy for N. otitidiscaviarum and how does it differ from other Nocardia species?

The initial antibiotic most commonly used is trimethoprim + sulfamethoxazole monotherapy combination, which is similar to other Nocardia species. The isolate of N. otitidiscaviarum is frequently resistant to sulfonamides. The antibiotic pattern of N. otitidiscaviarum includes resistance to beta-lactams, cephalosporins, and carbapenems. However, isolates are usually sensitive to amikacin, fluoroquinolones, and first-line drug sulfonamide.³^,¹⁰ Indication for antibiotic susceptibility includes lack of response to initial therapy, relapse after therapy, contraindication to sulfonamide, or strains resistant to sulfonamides like Nocardia farcinica and N. otitidiscaviarum.⁵^,¹¹ The duration of treatment for the pulmonary disease is at least 6 months, which can be extended up to 12–18 months in immunosuppressed patients. In critical patients, combination drugs are used initially for 3–6 weeks. A longer duration of therapy is used in relapsed cases.¹²
How much time does it take to see a response in a patient on appropriate antibiotic therapy?

The response is seen in 8–10 days and in cases of combination therapy, the antibiotic is de-escalated to monotherapy after 3–6 weeks of initial therapy.¹² Radiological follow-up with a CT scan may be warranted every 2–3 months and before the stoppage of medication.

MAJOR COMMENTS

Though the case is uncommon and the work-up detailed, a more comprehensive approach in the discussion will increase the value of the report, which at this time is just a narrative of the clinical course.

13. What scientific messages are the authors trying to convey besides the events which lead to the diagnosis and therapy?

The authors’ scientific message is that even opportunistic infections like nocardiosis should be considered as a differential in immunocompetent individuals.
14. Discussion of the differential diagnosis in detail will be useful as the dense abscess/consolidation presentation is not a common entity.

The differential diagnoses of dense consolidation are as follows:
- • Fungal infections—aspergillosis, mucormycosis, histoplasmosis, blastomycosis, and cryptococcosis.
- • Actinomyces and nocardiosis.
- • Mycobacterial infections—including Mycobacterium tuberculosis.
- • Viral infections—cytomegalovirus.
- • Parasitic infections—toxoplasmosis.
- • Lung malignancy.
- • Lung infarction.
15. A detailed approach can also be part of the discussion, including aspects such as a CT scan with contrast would be the first detailed test rather than PET-CT.

Given the high likelihood of malignancy and the protracted course, PET CT was performed first.
16. What is the role of CT-guided biopsy vs bronchoscopy in making an accurate diagnosis?

Given the heterogeneous uptake on FDG, PET, and CT-guided biopsy is the preferred modality, and it would yield a better sample than bronchoscopic biopsy. The bronchoscopic biopsy would have aspirated central necrotic material, yielding a low yield.
17. Stage of presentation and impact on therapy and prognosis, especially as this case has bilateral disease and the chance of metastasis due to delayed presentation?

The patient had a delayed presentation and a high-risk of spreading. PET-CT ruled outspread to distant organs. The disseminated disease would have required 2–3 drugs in the initial phase, followed by 6–12 months of therapy, depending on the clinical-radiological response.
18. The role of conservative therapy and its complications as the medications such as trimethoprim/sulfamethoxazole (TMP-SMX) can have long-term side effects?

The first line of treatment is conservative therapy with antibiotics. Because different strains of Nocardia have different sensitivities, therapy should be guided by in vitro susceptibility testing at a specialized laboratory experienced in testing Nocardia strains. TMP-SMX long-term complications include agranulocytosis, aplastic anemia, thrombocytopenia, interstitial nephritis, thrombotic thrombocytopenic purpura, and hypersensitivity reactions. Before beginning therapy, a sulfa allergy should be investigated.
19. Any role of surgery in these cases

Indications of surgery in nocardiosis are as follows:
- • Largely localized abscess.
- • Pericarditis.
- • Rapidly progressive brain abscess despite two weeks of therapy.
20. Recurrence prevention and its importance due to occupational exposure being a major risk factor?

Patients must be monitored for at least 12 months after therapy to detect any late relapses.

Immunosuppressive therapy should be reduced or discontinued in patients at risk of Nocardia infection. Secondary prophylaxis with daily double-strength TMP-SMX may be considered in patients with prior nocardiosis infections who are on immunosuppressive therapy that cannot be discontinued.¹²

CONCLUSION

Although nocardiosis is considered an opportunistic infection in immunosuppressed individuals, physicians should consider it as a differential diagnosis even in immunocompetent individuals. Radiological techniques like CT chest and PET scans are valuable aids in diagnosis, but microbiological confirmation is the rule. Early detection and prompt treatment can reduce mortality rates, especially in cases of severe or disseminated nocardiosis.

ORCID

Owais Tisekar https://orcid.org/0000-0003-3751-469X

Ajith Kumar AK https://orcid.org/0000-0001-5134-1698

Justin A Gopaldas https://orcid.org/0000-0002-0420-6925

Ranjeeta Adhikary https://orcid.org/0000-0003-4695-0135

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