First Case of Nocardia wallacei From India: A Case Report and Literature Review

Nocardia is a type of bacteria that can cause infections in both immunocompromised and immunocompetent hosts. It is an obligate aerobe and is commonly found in the environment. Pulmonary nocardiosis may present as pneumonia, endobronchial inflammatory masses, lung abscess, and cavitary disease with contiguous extension, leading to effusion and empyema. We present a case of pulmonary nocardiosis in a 75-year-old male patient with type 2 diabetes mellitus. The patient presented with bilateral pneumonia and hypoxia with an oxygen saturation of 85%. Sputum samples were sent to the microbiology laboratory for testing. Acid-fast staining with 1% H2SO4 showed acid-fast branching filamentous rods, but Nocardia could not be isolated in culture. The sample was subjected to 16S rRNA gene sequencing, which identified the pathogen as Nocardia wallacei. The culture of the sputum did not grow any pathogenic organisms, and the blood culture was sterile. Unfortunately, the patient left the hospital against medical advice as he was advised for intubation. The patient could not survive and died the next day after leaving the hospital. N. wallacei can be fatal and cause disseminated infection in both immunosuppressed and immunocompetent patients. Only eight case reports of N. wallacei have been reported in the literature from various parts of the world. Our case is the first case report of N. wallacei from India.


Introduction
Nocardia is an obligate aerobic, Gram-positive, and branched filamentous bacteria.It is saprophytic in nature and is commonly found in the environment [1].Pulmonary nocardiosis can present as acute, subacute, or chronic suppurative infection with a tendency to remit or exacerbate.It can infect both immunocompromised and immunocompetent hosts.Clinically, it may present as pneumonia, endobronchial inflammatory masses, lung abscess, and cavitary disease with contiguous extension, leading to effusion and empyema [2].
Nocardia wallacei belongs to the Nocardia transvalensis complex, which is ubiquitous in the environment [3,4].It can involve organs such as the lungs, pleura, skin and soft tissues, and brain [5].Only a few cases of N. wallacei have been reported worldwide so far, which presented with few clinical features such as disseminated actinomycetoma and pulmonary abscess with dissemination to the brain [5,6].The bacteria cannot be identified by conventional biochemical tests and require advanced techniques such as sequencing for identification [4].All the previously published studies have confirmed the species by sequencing, so sequencing plays a major role in the identification of new or closely related species of Nocardia [5,6].N. wallacei is known to be resistant to many drugs, making them difficult to treat [6].Currently, there are no serological tests available for the diagnosis of active nocardiosis due to cross-reactivity among different Nocardia species, Mycobacterium tuberculosis, Mycobacterium leprae, and other Actinomycetes [4].

Case Presentation
A 75-year-old male patient was referred to our emergency department by a private physician with a provisional diagnosis of acute febrile illness with lower respiratory tract infection and bilateral pneumonia, along with severe hypoxia.The patient had been experiencing fever and shortness of breath for one month on-and-off basis, with cough and weakness.He had a known case of type 2 diabetes mellitus and epilepsy and was on treatment for the same.He was a non-smoker, non-alcoholic, and not hypertensive.There was no history of pulmonary tuberculosis, and he was a shopkeeper by profession.
On examination, the patient was conscious and oriented to time, place, and person.He was tachypneic and dyspneic, with a blood pressure of 121/86 mmHg, pulse rate of 92/minute, and respiratory rate of 25/minute.His SPO 2 was 85% in room air.Bilateral rhonchi and crepitations were heard on auscultation of the chest, and bilateral pedal edema was also present.The patient was started on non-invasive ventilation.

FIGURE 1: X-ray PA view chest.
X-ray showing bilateral nodular opacities and infiltrates, along with areas of consolidation.
HRCT of the chest shows multiple centrilobular nodules and multiple heterogeneously enhancing lesions of bilateral lung fields with consolidation of the right lower lobe (Figure 2).Sputum and blood cultures were sent, and the patient was started empirically on IV meropenem 1 g TID and IV clarithromycin 500 mg BD.The patient's condition was deteriorating, and the medical team planned to After 48 hours of incubation, no pathogenic microorganisms could be isolated from the sputum culture.The blood culture was negative after incubation for five days.A 10% potassium hydroxide mount (KOH) showed no fungal elements.M. tuberculosis complex was not detected by cartridge-based nucleic acid amplification test (CBNAAT) of sputum.
In the culture of sputum, Nocardia could not be isolated after 72 hours of incubation of Sabouraud's dextrose agar (SDA) and blood agar.However, Nocardia spp. was detected by direct microscopy, and the treating doctor was informed.Unfortunately, by that time, the patient had left the hospital against medical advice.When the medical team tried to contact the patient directly, the patient's relative informed them that the patient had died the next day after being discharged from the hospital.The sample was subjected to 16S rRNA sequencing and identified as N. wallacei (GenBank accession number: OR533615).
Antimicrobial susceptibility testing was not done as Nocardia could not be isolated in culture.

Discussion
This is the first case report of N. wallacei from India.The previous cases of N. wallacei reported had presented with few clinical features such as disseminated actinomycetoma and pulmonary abscess with dissemination to the brain [5,6].So far, eight case reports have been reported in the literature from various parts of the world.Of the eight cases, 50% were immunocompromised (two cases of HIV and two cases of carcinoma), and 50% were immunocompetent.Pulmonary involvement was there in 87.5% (seven out of eight) cases, and one case affected the skin and soft tissue.Four out of the seven cases (57%) of N. wallacei with pulmonary involvement had dissemination to the brain.Of the four cases of dissemination to the brain, 50% were immunocompromised and 50% were immunocompetent.The correlation between fatality and immune status is not conclusive as there are only a few case reports of N. wallacei.
From the literature, it is clear that N. wallacei can cause both pulmonary and extrapulmonary nocardiosis and can be fatal and disseminated [7].It is also clear that N. wallacei can cause disseminated infection even in immunocompetent patients [7].It is also evident that N. wallacei can cause disseminated infection in both immunosuppressed and immunocompetent patients.We could clearly conclude that N. wallacei has a predilection to the brain and is disseminated to the brain in almost 60% of cases, although more research is required to support this evidence.Our patient was a known diabetic and elderly, which could be the reason for immunosuppression and lead to fatality.Therefore, diagnosing and treating N. wallacei-infected patients early can save the patient's life.There are only a few cases discussed in the literature, and a short summary of all the cases is discussed in Table 1.

Conclusions
N. wallacei pulmonary cases had shown a predilection of dissemination to the brain in 60%.It is also known to be multidrug-resistant, including drugs such as amikacin and clarithromycin.N. wallacei can cause dissemination equally in immunocompetent and immunocompromised patients.Therefore, irrespective of the immune status of the patient, diagnosing N. wallacei and starting treatment as early as possible can be life-saving.To better understand the range of symptoms, spread, and mortality of N. wallacei, more case reports from different regions of the world are needed.

FIGURE 2 :
FIGURE 2: HRCT of the chest.HRCT of the chest showing multiple heterogeneously enhancing lesions of bilateral lung fields with consolidation of the right lower lobe.

FIGURE 4 :
FIGURE 4: Modified acid-fast stain of sputum.Modified acid-fast stain with 1% H 2 SO 4 showing acid-fast beaded branching filamentous rods.