A Fatal Case of Multidrug-Resistant Pleural Nocardiosis by Nocardia otitidiscaviarum in an Immunosuppressed Patient: A Case Report and Literature Review

Nocardiosis is known as an opportunistic infection in immunocompromised hosts. We present to you a case of pleural nocardiosis in a 38-year-old male patient who was a chronic smoker and presented with a left-sided pleural effusion. He was a known case of thrombocytopenia due to immune thrombocytopenia (ITP) and was on steroid therapy. On admission, he was found to be positive for HIV. Pleural fluid was sent to microbiology, where acid-fast staining with 1% sulfuric acid (H2SO4)showed acid-fast branching filamentous rods and cultures grew Nocardia, which was resistant to ampicillin, ceftriaxone, imipenem, cotrimoxazole, erythromycin, tetracycline, and susceptible to amikacin, linezolid, and levofloxacin. The isolate was identified as Nocardia otitidiscaviarum using 16S rRNA gene sequencing. Culture from the chest wall drain grew Escherichia coli and Stenotrophomonas maltophilia. Subsequently, the patient developed sepsis, and paired blood cultures grew Candida guilliermondii. Unfortunately, the patient could not survive despite aggressive efforts and died after 40 days of admission.


Introduction
Nocardia spp.are gram-positive bacteria found in soil, water, and decaying vegetation [1].Human immunodeficiency virus (HIV) infection, malignancy, diabetes mellitus, transplantation, and corticosteroid use predispose patients to nocardiosis, although infection can occur in immunocompetent hosts.[2] The clinical manifestations of nocardiosis can be diverse, but the most common sites are the lungs, where the infection occurs by inhalation or direct inoculation of Norcadia.[3] Nocardia otitidiscaviarum, first named Nocardia caviae, was first reported in humans in the 1960s [4].Nocardia otitidiscaviarum was previously reported in 1924 when it was isolated from a guinea pig's middle ear.[4]

Case Presentation
A 38-year-old male patient came to the emergency department with complaints of chest pain on the left side, shoulder pain, and dysphagia for two days.He denied shortness of breath, fever, and a productive cough.The patient had lost 10 kg in the last three months.The patient was a farmer by profession.The patient was a chronic smoker of tobacco (40 pack years) and an alcoholic for the past 10 years and consumed about 150-250 ml/day of alcohol once a day.There was no history of tuberculosis, diabetes mellitus, or hypertension.He had a known history of thrombocytopenia due to hemophagocytic lymphohistiocytosis (HLH)/ immune thrombocytopenia (ITP) and was on steroid therapy.
On examination, he was conscious and oriented to time, place, and person.He was afebrile, his blood pressure was 117/74 mmHg, his pulse was 97 beats per minute, he was hemodynamically stable, and his oxygen saturation was 97% on room air.On chest auscultation, left lung air entry was decreased.The chest X-ray showed left homogeneous opacity and consolidation suggestive of parapneumonic pleural effusion or empyema (Figure 1).

FIGURE 1:
The chest X-ray showed left homogeneous opacity.
High-resolution computed tomography (HRCT) of the chest was suggestive of a left cavitary and consolidatory lesion with effusion.Based on these findings, a left-side flexible chest tube was inserted for the drainage of pleural effusion, and the tube was left there as the effusion was not resolving.
Based on the clinico-radiological findings and biochemical analysis of the pleural fluid, which showed lactate dehydrogenase (LDH) of 820 IU/L, sugar of 23 g/dl, and total protein of 33 g/dl, tuberculosis was suspected, and anti-tubercular treatment was started.Intravenous (IV) piperacillin/tazobactam 4.5 g four times a day (QID), IV clindamycin 600 mg three times a day (TDS), and oral fluconazole 150 mg once a day (OD) were administered empirically after the samples were collected for culture.
The patient was diagnosed as HIV-reactive by third-generation HIV testing.The patient's CD4 count was 42 cells/ul (CD 4% = 5).Pleural fluid was sent for microbiological examination.On the gram stain, branching filamentous beaded gram-positive bacilli were seen (Figure 2).No pathogenic microorganism could be isolated from sputum after 48 hours of incubation.Blood cultures (one set) were negative after five days of incubation.A 10% potassium hydroxide mount of pleural fluid and sputum was done, and no fungal elements were seen.Mycobacterium tuberculosis complex was not detected by the cartridge-based nucleic acid amplification test (CBNAAT) of the sputum and pleural fluid.On stool examination by saline mount, iodine mount, and modified acid-fast stain with 1% H 2 SO 4 , no ova, cyst, or oocyst of parasites were found.
The isolate was resistant to ampicillin, ceftriaxone, imipenem, cotrimoxazole, erythromycin, and tetracycline.The isolate was susceptible to amikacin, linezolid, and levofloxacin.The patient was started on IV levofloxacin 750mg OD and IV amikacin 750mg OD.Anti-retroviral treatment was initiated.
To cover the potential hospital-acquired pathogens, IV meropenem 1 gm TDS and IV teicoplanin 400 mg twice a day (BD) were added empirically.Repeat pleural fluid culture after five days grew Nocardia otitidiscaviarum, carbapenem-resistant Acinetobacter baumannii complex susceptible to minocycline and colistin, and carbapenem-resistant Escherichia coli susceptible to amikacin, gentamicin, tigecycline, and colistin.
Culture from a chest wall drain tube grew carbapenem-resistant Escherichia coli susceptible to amikacin, gentamicin, tigecycline, and colistin, and Stenotrophomonas maltophilia susceptible to levofloxacin, minocycline, and TMP-SMX.Subsequently, the patient developed sepsis.Paired blood culture samples grew Candida guilliermondii, which was susceptible to voriconazole, caspofungin, and micafungin.
After 40 days of admission, even after continuous efforts and treatment, unfortunately, the patient could not survive.

Discussion
Our case report presents a rare instance of empyema caused by Nocardia otitidiscaviarum.As it is described as an opportunistic pathogen in individuals with weakened immune systems.Patients with various immunocompromised states are at higher risk of acquiring infections from Nocardia otitidiscaviarum.[4] Similarly, in our case, the patient was HIV-infected and was on steroids for ITP.
Sulphonamides were used for the treatment of Nocardia infections in the past, and treatment was effective in most of the patients.However, when we handle a patient infected with Nocardia otitidiscaviarum, it is very important to do the antimicrobial susceptibility testing before starting the treatment, as previous studies have reported resistance to beta-lactam drugs like ampicillin, amoxicillin-clavulanic acid, and imipenem, along with variable susceptibility to sulphonamides.
This case report highlights the importance of early diagnosis, species identification, and susceptibility testing for choosing the right treatment for the patient in order to improve the outcome.The treatment of Nocardia infections depends on the susceptibility pattern, and long-term treatment is also required depending on the severity of the underlying systemic disease.Careful consideration needs to be given when a case of nocardiosis is being treated.
We have summarized 10 recent case reports of Nocardia otitidiscaviarum reported in the literature in Table 1 below.

Conclusions
Cases of Nocardia otitidiscaviarum presented in the past literature show a case fatality rate of more than 50%.The infection can be fatal if it happens to an immunocompromised patient.Therefore, early diagnosis and treatment according to the susceptibility patterns are very important in treating and saving the patient.

FIGURE 2 :
FIGURE 2: Gram stain of the pleural fluid showed gram-positive beaded branching filamentous bacilli.

FIGURE 5 :
FIGURE 5: Chalky white dry colonies on blood agar

India [ 7 ]
year-old female with systemic lupus erythematosus (SLE).Multi-organ involvement, including autoimmune hemolytic anemia, cerebritis, lupus nephritis, cardiomyopathy with an ejection fraction of 33%, and non-specific interstitial pneumonia.On steroid therapy.Case 1: A 70-year-old female with no predisposing condition.Pulmonary cough with expectoration, on and off fever, difficulty in breathing, and chest pain.al. Cureus 16(1): e52071.DOI 10.7759/cureus.52071Case two: A 70-year-old male diagnosed with pulmonary tuberculosis over 10 years ago.Smoking and alcohol consumption off