Unusual cases of melioidosis infection in cancer patients in North India: Covert peril for oncology care

Case 1

A 47-year-old female resident of Jaunpur district, Uttar Pradesh, visited our outpatient department with the chief complaint of a lump in her left breast along with a history of on-and-off fever for the past 6 months. Fever is of low grade and associated with fatigue, myalgia, and pain, especially in the breast lump. There is an occupational history of agriculture in the family. There was no history of cough, breathlessness, skin rashes or skin lesions, or trauma. The tissue sample received in the microbiology laboratory was cultured in Blood agar and MacConkey agar, and a Gram stain was prepared. The sample was also sub-cultured in brain heart infusion broth for enrichment. The culture plates were incubated at 37°C, and reading was done in the next 18-24 hours. Gram staining of the tissue sample revealed plenty of pus cells and occasional epithelial cells with plenty of Gram-negative bacilli (GNB) (bipolar and having a safety pin appearance) [Figure 1].

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Figure 1:

(A) Maximum intensity projection image showing hypermetabolic mass in the left breast region (red curved arrow), metastatic paratracheal node (red arrow head), and left femur lesion (arrow). (B) Axial fused fludeoxyglucose positron emission tomography/computed tomography images showing a hypermetabolic primary left breast lesion (arrow). (C) Gross picture of the mastectomy specimen shows skin ulceration and fibrinosuppurative slough formation. (D) Biopsy from the left breast shows a well-formed granuloma (black arrows) surrounded by the invasive breast carcinoma cells [Hematoxylin and eosin (H&E), ×10]. (E) The granuloma is composed of numerous multinucleated giant cells (black arrows) adjacent to the tumor nests (red arrow heads), (H&E, x40). (F) Extensive areas of necrosis are seen amidst large tumor nests (Red Triangle depicts as star), (H&E, x20). Scale Bar of D: 10×200 µm, E: 20×100 µm, and F 40×40 µm

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The culture showed the growth of non-lactose-fermenting colonies in MacConkey agar, which were further identified by an automated identification and susceptibility system (Vitek-2 BioMérieux, Germany, and MALDI-TOF, Bruker). The minimum inhibitory concentration (μg/mL) interpretation for susceptible (S), intermediate (I), and resistant (R) in terms of antibiotic susceptibility was performed using Clinical and Laboratory Standards Institute - M45-A2 guidelines.^[6] The organism was identified as B. pseudomallei (99% probability) and the strain was sensitive to piperacillin-tazobactam (=8 μg/mL), ceftazidime (=4 μg/mL), cefoperzone-sulbactam (≤8 μg/mL), cefepime (≤1 μg/mL), aztreonam (≤4 μg/mL), doripenem, (<0.25 μg/mL), imipenem (≤2 μg/mL), meropenem (≤0.25 μg/mL), amikacin (≤2 μg/mL), gentamicin (≤4 μg/mL), ciprofloxacin (≤0.25 μg/mL), and levofloxacin (<0.25 μg/mL). Based on the clinical symptoms and investigations, the patient was prescribed meropenem in a dose of 500 mg IV TDS as intensive therapy. Counseling was done regarding the compliance with long-term oral intake of antibiotics for the eradication phase of treatment. In the gastro-oncology outpatient department, the patient was monitored for the same oral antimicrobial therapy, and the cancer treatment was continued. She was restarted on the 2^nd cycle of chemotherapy, paclitaxel. The patient is currently on follow-up, receiving maintenance adjuvant chemotherapy.

Case 2

A 66-year-old female resident of Bihar came with chief complaints of a left-sided neck swelling for the past month. There was a history of an enlarging, painful mass on the left side of the neck, fever, poor appetite, and an approximate weight loss of 5 kg since the initiation of the chief complaints. The fever was of low grade and associated with fatigue, myalgia, and anorexia. There is no history of cough, breathlessness, skin rashes, skin lesions, or trauma. There was an occupational history of agriculture in the family. On clinical examination, a 2.5 cm × 2.5 cm swelling was palpable in the left region. The mass was firm, mobile, and tender. There was no history of voice change, dysphagia, or breathlessness. A fine-needle aspiration cytology report from a laboratory showed metastatic deposits of adenocarcinoma. A positron emission tomography-computed tomography (PET-CT) was done, and it showed multiple hypermetabolic lesions involving the left supraclavicular and mediastinal regions [Figure 2a-c]. Given the PET-CT findings, a core-needle biopsy of the left supraclavicular node was done. Histopathological analysis: The left supraclavicular biopsy showed lymph nodal tissue infiltrated by a tumor arranged in sheets and vague glands. The individual cells were round to oval and showed a severe degree of pleomorphism, a high N/C ratio, coarse chromatin, inconspicuous nucleoli, and a moderate amount of cytoplasm. Many well-formed granulomas composed of multinucleate giant cells (arrow), histiocytes, and fibroblasts were noted [Figure 2d]. A final impression of metastatic adenocarcinoma with chronic granulomatous infection was given. Based on histopathological findings, the patients were advised to have four cycles of pemetrexed and carboplatin chemotherapy for 3 weeks. A few months after treatment, the patient presented in the hospital with a history of high-grade fever, weakness, and shortness of breath. Routine laboratory investigations were done, and paired blood culture was collected in automated Bact-Alert bottles and sent to the microbiology lab for further analysis. Blood culture flashed positive for GNB and was subcultured in blood and MacConkey agar and kept in an incubator at 37°C. After 24-48 hours of incubation, blood agar showed smooth, creamy, white colonies at 24 h, which became dry and wrinkled after 48 hours. In MacConkey agar, pink to metallic brown colonies were noted at 24-48 hours [Figure 2e]. Isolated colonies were picked up, and further automated identification and sensitivity testing were done in VITEK-2 (Germany, BioMérieux). Vitek-2 identified the organism as B. pseudomallei (99% probability), and the strain was sensitive to cefoperazonesulbactam (≤8 μg/mL), piperacillin-tazobactam (=8 μg/mL), ceftazidime (=4 μg/mL), cefepime (≤1 μg/mL), aztreonam (≤4 μg/mL), doripenem (<0.25 μg/mL), imipenem (≤2 μg/mL), and cotrimoxazole (≤20 μg/mL) and resistant to ciprofloxacin and levofloxacin. Based on culture findings, the patients were given injections of cefoperazone-sulbactam in a dose of 1.5 mg IV TDS and meropenem (500 mg) IV every 8 hours. After the patient was stable, she was counseled for a long course of antibiotics with cotrimoxazole. The patient was followed up for the negative blood culture report and discharged with advice to follow up after 3 weeks. In the follow-up visit, the patients were advised to restart the cancer treatment, and chemotherapy was restarted with pemetrexed and carboplatin. The patient is currently on follow-up, receiving maintenance adjuvant chemotherapy.

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Figure 2:

(A) Maximum intensity projection image showing multiple hypermetabolic lesions involving the left supraclavicular and mediastinal region (red arrow). (B) Histopathological examination of the cervical lymph nodes shows many large well-formed granulomas composed of multinucleated giant cells (black arrows), histiocytes, and fibroblasts [Hematoxylin and eosin, ×40]. (C) Contrast-enhanced axial computed tomography (CT) and fused axial fludeoxyglucose positron emission tomography/CT images showing glucose hypermetabolism in multiple enlarged, rounded, enhancing left supraclavicular nodes (arrows). (D) Gram staining of the tissue sample revealed plenty of pus cells and occasional epithelial cells with plenty of gram-negative-bacilli (Bipolar and having a safety pin appearance). (E) In Blood agar: Smooth, creamy, white colonies at 24 hours. May become dry and wrinkled, as shown in the image, often with a purplish hue at 48-72 hours in MacConkey agar: Pink to metallic brown colonies at 24-48 hours.

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