Disseminated nocardiosis involving the central nervous system in the context of newly diagnosed HIV infection: A case report

Introduction

Nocardia is regarded as an opportunistic infection in immunocompromised patients. Haussaire et al. ¹ studied 34 patients with nocardiosis in the south of France over a 10-year period (2004–2014), and none of the patients had HIV infection. Similarly Rosman et al. ² studied 39 patients with nocardiosis in a tertiary medical center in Israel over a 15-year period, and none of them had HIV infection. Pupaibool et al. ³ reported Nocardia as uncommon bacteria that can cause pulmonary infection in patients living with HIV with a low CD4 cell count, including central nervous system (CNS) ailments. ⁴ This study reports a patient with tuberculosis-like symptoms who was finally diagnosed with disseminated nocardiosis.

Case presentation

A 44-year-old male Han patient was admitted to local hospital on March 17, 2017, because of “fever and headache for more than 10 days.” He underwent relevant examinations: erythrocyte sedimentation rate (ESR) was 90 mm/h; lumbar puncture revealed white blood cell (WBC) at 97 × 10⁶/L, lymphocytic percentage (LYMP) at 70%, protein level at 1087.2 mg/L, glucose at 1.68 mmol/L, and chlorine at 114.6 mmol/L in the cerebrospinal fluid (CSF); CSF was negative for IFN-γ, as well as Gram staining and ink staining. The empirical oral anti-tuberculosis treatment of isoniazid 300mg once daily, rifampicin 450md once daily, ethambutol 1000mg once daily and pyrazinamide 450mg three times daily was initiated on March 18, 2017, and the patient was transferred to our hospital on March 20, 2017, following positive HIV screening results (DIG-FA method). The patient reported no convulsion, cough, or shortness of breath. Physical examination on admission revealed normal vital signs. A dark red papule was present at the left lower limb (about 7 mm in diameter), with no skin itching or pain upon touch. In addition, a mass with good mobility was observed above the right ankle, measuring about 2 × 2 cm. After admission, blood routine examination revealed WBC at 26.9 × 10⁹/L, neutrophil percentage (NE%) at 86.3%, hemoglobin (Hb) at 108 g/L, and C-reactive protein (CRP) >200 mg/L. CD4⁺ T lymphocytes were 45/µl, the mycobacterium tuberculosis interferon-gamma release assay (IGRA) was negative, cytomegalovirus-DNA (CMV-DNA) level was <500 copies/mL, and cryptococcal antigen was negative. CSF examination (March 23, 2017) showed total nucleated cell (TNC) at 20×10⁶/L, monocyte percentage at 70%, weakly positive Pandy’s test, protein at 1169.8 mg/L, glucose at 2.7 mmol/L, chlorine at 114 mmol/L, and adenosine deaminase (ADA) at 1.0 U/L. Chest computed tomography (CT) showed a mass in the lower lobe of the right lung (Figure 1). Brain magnetic resonance imaging (MRI) revealed long T1 and T2 signal changes in the left temporal and occipital lobes with edema around in plain MRI; DWI showed flaky high signals in the anterior horn of the left lateral ventricle and basal ganglia; ring enhancement was observed on enhanced MRI scanning (Figure 2). OPEN IN VIEWER

Figure 1.

Chest computed tomography scans on admission and after treatment. Lung lesions were overtly absorbed and improved on (b) April 1, the 15th day of antituberculosis treatment and the 1st day of anti-Nocardia therapy, compared with (a) March 20, the 3rd day of antituberculosis treatment and the day of admission.

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Figure 2.

Brain magnetic resonance imaging scans before and after treatment. T2-FLAIR imaging showing multiple abnormal signals in the left temporal lobe, occipital lobe, anterior horn of the left lateral ventricle, and basal ganglia on admission and during treatment. The intracranial lesion found on April 1 (b) (15th day of antituberculosis treatment) had progressed compared with that observed on March 21 (a) (4th day of antituberculosis treatment). On April 5 (c) (5th day of anti-nocardiosis therapy), the lesion was significantly improved.

Cryptococcal meningitis infection and suppurative meningitis were excluded based on CSF culture and related symptoms. Upon admission, empirical antituberculosis treatment was administered. Based on complete blood count (CBC) data indicating infection (WBC at 26.9 × 10⁹/L, NE% at 86.3%, and CRP >200 mg/L), moxifloxacin (0.4 g/d, intravenously (iv)) and linezolid (0.6 g, bid, iv) were added to inhibit common bacteria and mycobacteria. The patient had pyrexia the second day after admission (peak at 39.5°C), as well as headache, severe weakness, and poor mental state; therefore, dexamethasone (10 mg/d, iv) and mannitol (25 g, q8h, iv) were administered for anti-inflammation and hydration, respectively, and other symptomatic supportive treatments were performed. The patient showed a poor response to treatment until April 1, 2017 (15th day of antituberculosis treatment). Brain MRI revealed a remarkable progression of the lesion (Figure 2).

On April 1, results of blood culture initiated on March 17 suggested mycobacterial growth and positive acid-fast staining. The involved strain was identified as Nocardia. Thus, the anti-infective therapeutic regimen was changed to the combined anti-Nocardia therapy of cefotaxime sodium and sulbactam sodium (2.25 g, qid, iv), linezolid (0.6 g, bid, iv), moxifloxacin (0.4 g, qd, iv), sulfamethoxazole (1.44 g, qid, po), and amikacin (0.4 g, qd, iv). The day after regimen adjustment, the temperature returned to normal and skin nodules began to shrink, and the patient had a slightly improved mental state. Re-examination by chest CT and brain MRI suggested improvement compared with the pre-treatment situation (Figures 1 and 2). Thus, the therapeutic response of multiple brain, lung, and skin lesions confirmed the diagnosis of disseminated nocardiosis.

Discussion

Nocardia is a gram-positive aerobic filamentous actinomycete. Depending on the cell wall of mycotic acid and different colorants, Nocardia shows varying degrees of resistance to acid. Nocardia is often an opportunistic pathogen, mainly occurring in people with low immune function, for example, patients with AIDS, lymphoma, other malignant tumors, solid organ transplantation, stem cell transplantation, or long-term hormone therapy and immunosuppressive patients.^1–3The most common location of Nocardia is the lung, with typical symptoms such as cough, phlegm or dry cough, shortness of breath, chest pain, hemoptysis, fever, night sweats, weight loss, and progressive fatigue and chest imaging findings such as focal lesions or multiple lesions with nodules, voids, and/or combined infiltration. Extra-pulmonary nocardiosis is also fairly common and may present with cutaneous and CNS involvement. In severe cases, patients may be infected with disseminated Nocardia infection. At present, there are few reports of disseminated Nocardia infection involving the CNS in HIV patients in China. This case report will help to enhance the understanding of disseminated Nocardia infection. In the process of clinical diagnosis and treatment, the case was initially misdiagnosed as disseminated TB because (1) tuberculosis in HIV/AIDS is very common in the population and clinical thinking tends to consider the common disease, (2) both diseases can affect the lungs and the CNS and have similar clinical manifestations and imaging findings, (3) both of them are caused by acid-fast stained positive bacilli, and (4) when the CNS is involved, the routine and biochemical changes of the cerebrospinal fluid in both diseases are similar. In fact, the patient also had some indicators that did not support TB, such as significantly increased levels of WBC and neutrophils, low levels of CSF interferon gamma and ADA, and a negative TB interferon-gamma release test. However, these indicators could not exclude TB. The final definitive diagnosis of this case is as a result of a positive blood culture. Therefore, for the purpose of differential diagnosis of disseminated tuberculosis suspected clinically, blood culture and other tests are still required to exclude other diseases that may lead to similar clinical manifestations. Scheer et al. found that blood culture positivity was 50.6% among patients with sepsis who did not receive antibiotics and only 27.7% in those who were already receiving antibiotics (p < 0.001). ⁵ In this case, the patient received antibiotic treatment before and after admission, and the positive rate of blood culture decreased, so it was difficult to make a definite diagnosis depending on blood culture.

For the treatment, we referred to The Sanford Guide to Antimicrobial Therapy ⁶ and searched PubMed-related literature,^7–9 and adjusted the treatment according to the useful drugs in the literature. The patient improved after treatment and was discharged to the local hospital for sequential treatment. He has survived to date. ART therapy was initiated once the lesions were smaller after treatment and once pyrexia had subsided. His HIV viral load is now undetectable.

HIV-RNA testing was not performed during the patient’s hospitalization due to economic reasons. In this case, antiretroviral therapy was not initiated during hospitalization in our hospital. Of note, the sub-species and drug resistance of Nocardia were not determined.