A 44-year-old immunocompromised male presented to an outside hospital with new-onset seizures and altered mental status. Relevant past medical history included pure red cell aplasia, concomitant autoimmune hemolytic anemia, and T-cell large granular lymphocytic (LGL) leukemia for which he received chemotherapy with cladribine two years prior to presentation. A CT of the brain revealed a small ring-enhancing lesion (measuring 0.9 (AP) x 0.9 (TR) x 0.9 (CC) cm) in the right parietal lobe with surrounding edema. A lumbar puncture was performed which revealed 11 WBC (41% lymphocytes, 7% monocytes, 52% granulocytes), glucose of 83 mg/dL, and protein of 94 mg/dL. The routine cerebrospinal fluid (CSF) bacterial culture was negative for growth. The fungal smear was negative; however, the fungal CSF culture grew Candida parapsilosis. Based on these findings, he was initiated on fluconazole for treatment.
Since the patient did not exhibit clinical improvement following ten days of fluconazole therapy, a brain biopsy was performed of the right parietal lesion. All bacterial, fungal, and acid-fast bacilli smears and cultures from the biopsy were negative. Tissue was sent for pathology, and upon initial review, it was believed that the organisms, which were positive by acid-Schiff (PAS) and Grocott Methenamine-Silver (GMS), had a size similar to Cryptococcus spp. Of note, serum cryptococcal antigen was negative. Consequently, the patient was empirically started on liposomal amphotericin B and flucytosine for presumed CNS cryptococcal infection. After an additional review by the pathologists, it was felt that these "microorganisms" were most consistent with corpora amylacea, not Cryptococcus spp. Additionally, postbiopsy MRI scan suggested that the lesion in question was not sampled during the biopsy. Consequently, the decision was made to continue the liposomal amphotericin B but discontinue the flucytosine. After four weeks of amphotericin B, a repeat MRI revealed mild improvement (3 mm reduction of ring-enhancing lesion); therefore, a decision was made to stop amphotericin therapy and start fluconazole therapy. A repeat MRI one week later revealed an increase in the size of the right parietal lobe lesion. Therefore, the patient was restarted on liposomal amphotericin B and flucytosine therapy.
After receiving 53 days of combination antifungal therapy without clinical improvement, it was determined that the patient had failed medical therapy and surgical intervention was indicated. The patient was then transferred to our institution for craniotomy with incision and drainage of the right intraparietal lesion. A biopsy sample was sent to anatomic pathology for analysis. The tissue was stained with hematoxylin and eosin to demonstrate a cerebral abscess with features of encapsulation (see Figure 1). The abscess is composed of a necrotic center with a surrounding rim of granulation tissue, which contains a dense polymorphous inflammatory infiltrate composed of neutrophils, macrophages, lymphocytes, and plasma cells. A capsule with embedded fibroblasts and capillaries separates the abscess from the adjacent reactive brain. Cultures from this procedure revealed branching Gram-positive rods on Gram stain.
Given the concern for Nocardia, the patient was initiated on ceftriaxone and sulfamethoxazole/trimethoprim (TMP/SMX), in addition to metronidazole and amphotericin B. Once the patient was clinically stable, the patient was transferred back to the outside institution for further care. At the outside institution, ceftriaxone was discontinued and meropenem was initiated. Over the next two days, the patient developed severe headaches and profound left-sided weakness. A repeat CT of the brain revealed an interval increase in vasogenic edema involving the right frontoparietal, occipital, and temporal regions with the development of 5 mm midline shift. Given worsening of his clinical status and imaging, he was transferred back to our institution. The day following the transfer, the Gram-positive rods on Gram stain were identified to be Nocardia thailandica by 16S rDNA sequencing with a 99.8% match to the N. thailandica type strain IFM 10145.
Upon definitive identification, ceftriaxone 2 g IV daily was initiated, TMP/SMX was continued on a dose of 15 mg/kg/day of the trimethoprim component, and meropenem was discontinued. Metronidazole and amphotericin were not continued given the findings. Two weeks after the identification of N. thailandica, susceptibility testing at the University of Texas revealed susceptibility to ceftriaxone. Given the susceptibility results and the development of significant hyperkalemia, the decision was made to discontinue TMP/SMX after 19 total days of therapy.
Following the optimization of the antimicrobial regimen, the patient improved both clinically and radiographically. He was discharged from the hospital 63 days from the brain biopsy that revealed N. thailandica. The patient completed a total of five and a half months of ceftriaxone monotherapy.
MRI of the brain obtained four months after initiation of therapy revealed a stable associated mass effect and surrounding edema. A subsequent MRI obtained 7 months from the initiation of therapy revealed slightly decreased interval size of the surgical cavity and no significant interval change in vasogenic edema/gliosis. The patient did not experience any additional seizures or neurologic deficits after starting ceftriaxone therapy.