ACTINOMYCETES SPECIES INFECTION IN A PATIENT OF T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) PRESENTING WITH LOCULATED PLEURAL EFFUSION

Actinomycosis is an uncommon infectious disease caused predominantly by Actinomyces israelii. Infection with bacteria of the genus Actinomyces is not common but may occur in patients with malignant disease. The simultaneous occurrence of Actinomyces viscosus and T-cell ALL has not, to our knowledge, been described previously. Here we report a case who presented with symptomatic pleural effusion due to opportunistic infection caused by Actinomyces viscosus.

CASE REPORT

A 17-year-old female presented with generalized lymphadenopathy and anemia of 1 month duration, with fever and bleeding from nose and gums, and skin purpura for 20 days. On examination, she had moderate pallor, purpura, and generalized lymphadenopathy (size 3 × 4 cm bilateral cervical, 2.5 × 2 cm bilateral axillary, 3 × 3.5 cm bilateral inguinal), spleen palpable 10 cm, liver 2 cm.

On investigation we found hemoglobin 6.3 g/dL, white blood cell count 21,350/mm³ with N₁₀L₅₄M₃E₁Blast₃₂, platelet count 60,000/mm³. Baseline biochemistry was normal. Bone marrow aspiration and biopsy cytomorphologically was suggestive of ALL-L₂ with 74% blasts. Immunophenotype of the blasts suggested T-cell (CD3–76%, CD5–65%, CD7–64%, CD2–53%) origin. Cytogenetics was normal. CSF examination, chest X-ray (PA), and contrast-enhanced CT (CECT) chest imaging were normal. CECT abdomen revealed spleen 15 cm, liver 2 cm, and no retroperitoneal lymph nodes. Final diagnosis was T-cell ALL without CNS involvement.

On the 6th day of induction therapy (with prednisolone, vincristine, daunorubicin, and l-asparaginase), the patient developed continuous fever, hovering around 102°F, and maculopapules, vesicles, and scabs in various stages of evolution. These lesions, evolved from maculopapules to vesicles over hours to days, appeared on trunk and face, and rapidly spread to involve other areas of the body. Most were small and had an erythematous base with diameter of 5–10 mm. These classical rashes were suggestive of varicella. She also developed tachypnea and pain on the left side of the chest.

Chemotherapy was withheld for 2 days because initially we suspected drug rash. Chemotherapy was restarted after 2 days along with oral acyclovir. Chest X-ray (PA and lateral) showed airspace consolidation involving the left mid and lower zone. CECT chest imaging showed a central area of low attenuation ring-like rim enhancement, localized pleural effusion along with multiple nodules involving left mid and lower lobe, and no external sinus or fistula. Blood cultures were negative for aerobic and anaerobic bacteria and fungus.

Pleural fluid was tapped under aseptic precautions and sent for biochemical and microbiological evaluation. Pleural fluid examination revealed (1) glucose 88 mg/dL (plasma glucose 102 mg/dL), (2) protein 4.9 g/dL (serum protein 6.5 g/dL), (3) LDH 540 IU/L (serum LDH 240 IU/L), (4) cell count 90/mm³, granulocytes 35%, lymphocytes 65%, and no malignant cells. (5) Fungal stain and culture were negative. (6) PCR for tuberculosis, varicella antigen, and antibody were also negative. (7) Acid-fast stain and culture for Mycobacterium tuberculosis were negative. Pleural fluid Gram-stained smear showed pleomorphic gram-positive bacilli. Direct plating of the fluid was done both aerobically and anaerobically. There was no growth on aerobic plates after 24 h of incubation at 37°C. But anaerobic plates (brain–heart infusion blood agar) after incubation in an anaerobic jar at 37°C for 48 h showed minute cream-colored metronidazole resistant colonies, which on staining showed nonsporing gram-positive bacilli. The colonies were subcultured both aerobically and anaerobically and the same growth could be obtained in 5% CO₂ in blood agar. Gram stain of colonies confirmed the previous finding. The colonies were further processed for identification. The organism was catalase-positive, urease-positive, indole-negative, and nitrate-reducing and thus was identified provisionally as Actinomyces visosus. The organism was confirmed by RapID ANA II (Innovative Diagnostic system, Norcross, Georgia).

The antibiogram of the isolate showed the organism to be susceptible to penicillin, vancomycin, chloramphenicol, ciprofloxacin, levofloxacin, imipenem, and meropenem and resistant to kanamycin, amikacin, clindamycin, erythromycin, azithromycin, and metronidazole.

The patient was treated with antibiotics, imipenem, and cilastatin (500 mg intravenously 4 times a day) for 6 weeks. After 6 weeks, the patient became afebrile. Repeat CECT chest imaging was normal. At present the patient is on maintenance chemotherapy without any complications.

DISCUSSION

Actinomycosis, a rare bacterial disease, is caused by actinomyces species. The actinomycetes most commonly associated with infection are Actinomyces israeli. Infection with Actinomyces viscosus and other species are relatively uncommon [1]. Actinomyces is a gram-positive, non-acid-fast, filamentous or diphtheroidal organism and facultative anaerobic or microaerophilic bacteria. There has been no report of Actinomyces viscosus as an opportunistic pathogen in an ALL patient. One case of actinomycosis has been reported in a patient of acute myeloblastic leukemia who presented with febrile neutropenia and splenic abscess due to opportunistic infection by Actinomyces [2]. Actinomyces species are normal flora of the mouth and consequently the majority of these infections occur in the cervicofacial area. Pulmonary infections can occur when oropharyngeal material is aspirated and thoracic and abdominal infections can result from trauma or surgery. In our patient the most likely source of Actinomyces vicosus infection might have been erosions in oral mucosa as the patient also had concurrent varicella infection with ulcerative lesions.

This strain was resistant to metronidazole, supporting the previous findings that Actinomyces viscosus is usually resistant to metronidazole [3]. Fastidious gram-positive, nonsporing bacilli isolated from clinical specimens must not be neglected and should be identified to the species level so as not to miss potential yet rare pathogens such as Actinomyces viscosus. Awareness of such pathogens is important for clinicians as well as microbiologists.

In this case, the patient of T-cell ALL developed two infections simultaneously (varicella and actinomycosis). Initially we thought the parencymal and pleural lesions of the lung were a complication of varicella. Actinomycosis was isolated from the pleural fluid. As the patient's CECT chest exam revealed extensive pulmonary infiltrates, multiple pulmonary nodules, and loculated pleural effusion, actinomycosis was never a strong suspicion initially. In fact, pulmonary lesions, unless specifically suspected as actinomycosis, have a high probability of being mistakenly diagnosed as a neoplasm or a common form of pneumonia in the absence of a sinus tract [4].

Actinomycetes are rare opportunistic agents in immunocompromised patients; thus, the disease deserves special attention in such patients [5].