Mycobacterium kansasii septicaemia in an AIDS patient complicated by acute respiratory distress syndrome and acute liver failure

Introduction

Mycobacterium kansasii is the most common cause of non-tuberculous mycobacterium (NTM) lung disease in the central United States, parts of the United Kingdom and South Africa. ¹

The most common presentation of M. kansasii is a chronic pulmonary infection that resembles pulmonary tuberculosis. It may also infect other organs including liver, spleen, lymph nodes and bone marrow resulting in disseminated infection. ² In patients with the human immunodeficiency virus (HIV) infection, it is the second most common NTM infection after Mycobacterium avium-intracellulare. ³ We present the first case, to our knowledge, of disseminated M. kansasii infection with acute respiratory distress syndrome (ARDS) and acute liver failure in an acquired immunodeficiency syndrome (AIDS) patient.

Case presentation

A 38-year-old African-American woman with a past medical history of HIV/AIDS diagnosed 10 years prior to admission (contracted through sexual intercourse, CD4 count of 19 cells/mm³ recorded one month prior to admission), who presented at our institution with complaints of a 2-week duration of fever, chills and rigors associated with a productive cough with white sputum production. She admitted to having night sweats, weight loss of 6.8 kg with associated fatigue over the past two months. She complained of chest pain, shortness of breath, haemoptysis and pleurisy. She admitted to having occasional diffuse abdominal discomfort but denied any nausea, vomiting or diarrhoea.

She was poorly compliant with medications and could not recall their names. She smoked one pack per day for the past 25 years and also snorted cocaine. She denied any infectious diseases or tuberculosis exposure. She reported no recent travel and had a negative PPD two years ago. Soon after presentation to the emergency room, she developed hypoxic respiratory failure and became unconscious. She had to be intubated and was placed on mechanical ventilation with positive end-expiratory pressure, high fraction of inspired oxygen (FIO₂) and inverse ratio ventilation. The central venous pressure was 5 mmHg, pulmonary artery pressure 22/13 mmHg, wedge pressure 11 mmHg and the cardiac output was 16 L/min.

On physical examination the patient was febrile (temperature 38.3℃) with a respiratory rate of 20, heart rate of 115 and blood pressure of 110/89 mmHg. Oxygen saturation was 91%. On auscultation of posterior lung fields she had diffuse bilateral crackles audible. Initial arterial blood gases on room air, prior to intubation, revealed a PaO₂ of 50 mmHg and a pH of 7.50. Admission lab abnormalities included a white blood cell count of 2200/µL with 7% bands, haemoglobin of 8.3 g/dL, haematocrit of 26.5 g/dL, platelets 100/µL, aspartate transaminase (AST) 462 IU/L (normal 5–40 IU/L), alanine transaminase (ALT) 117 IU/L (7–56 IU/L), alkaline phosphatase 1097 IU/L, lactate dehydrogenase 558 IU/L, total bilirubin 9.2 mg/dL, direct bilirubin 5.4 mg/dL, serum albumin 1.8 g/dL (normal 3.5–5.5 g/dL) and an international normalized ratio (INR) of 3.1 (normal 0.9–1.2). On Day 1, blood cultures, urine culture and urine legionella antigen were all negative, as well as the blood cryptococcal antigen. Viral hepatitis profile was negative for active viral causes for elevated aminotransferases. Her chest X-ray revealed diffuse interstitial infiltrates.

During hospitalization, sputum for acid-fast bacilli (AFB) came back strongly positive and the patient was immediately placed on respiratory isolation. She was started on anti-tuberculosis therapy that included isoniazid (INH) 300 mg PO daily, ethambutol 800 mg PO daily, rifampin 600 mg PO daily and pyrazinamide (PZA) 1 g PO daily.

A computed tomography scan of the chest (Figure 1) revealed diffuse interstitial infiltrates with ground glass appearance. To evaluate for increased alkaline phosphatase, ultrasound of the abdomen was done that revealed a normal common bile duct size with some tiny cysts in the liver and spleen. OPEN IN VIEWER

The patient then underwent bronchoscopy and the bronchoalveolar lavage (BAL) was sent for evaluation and it revealed AFB which were identified to be M. kansasii. Bone marrow aspirations revealed necrotic inflammatory granulomas with many AFB. The AFB were later confirmed by polymerase chain reaction (PCR) to be also M. kansasii. The pancytopaenia, cholestatic hepatitis and ARDS were attributed to disseminated M. kansasii infection.

On hospital day 4, aminotransferases started to increase after initiation of INH therapy. After diagnosis of disseminated M. kansasii infection was made, INH and PZA were discontinued. The susceptibility isolates of the M. kansasii revealed resistance to PZA and sensitivity to INH, rifampin, ethambutol and levofloxacin. In light of these results and with the aim to treat this severe infection utilizing a treatment regimen with lesser hepatotoxic potential, levofloxacin 400 mg PO QD was added to the ethambutol and rifampin.

There was tremendous clinical improvement after initiation of antibiotics with concomitant regression of AST/ALT to normal values two weeks later. Her haematological parameters normalized. Her respiratory status improved and she was successfully weaned off the mechanical ventilator on hospital day 19. A blood culture drawn on the day of admission returned positive for M. kansasii 20 days later; the organisms were sensitive to ethambutol, streptomycin, clofazimine, rifampin, amikacin, ciprofloxacin and isoniazid. No other organisms were detected.

On hospital day 27, the patient was discharged and was advised to be compliant with ethambutol, rifampin and levofloxacin for 18 months. She was also advised to take combination anti-retroviral therapy. She continues to follow up with our HIV outpatient clinic for monitoring of her response to therapy.

Discussion

The incidence of M. kansasii infection is 2.4 cases per 100,000 adults annually. ⁴ In the immunocompromised/HIV patients, infection usually manifests in the late stages of disease. The symptoms related to disseminated M. kansasii infection may be less severe and more chronic compared to infection with Mycobacterium tuberculosis. ⁵ The most common symptoms of lung infection include cough, sputum production, weight loss, breathlessness, chest pain, haemoptysis, and fever or sweats. Sometimes disseminated disease can present clinically with cutaneous manifestations of M. kansasii which resemble sporotrichosis secondary to local lymphatic spread. ⁶ Pneumonia is the most common clinical presentation. Disseminated disease with M. kansasii occurs in almost 20% of patients infected with HIV.^4,5 Meningitis similar to M. tuberculosis meningitis has been reported in patients infected with HIV, and it may be associated with higher mortality rates despite appropriate antibiotic administration. ⁷ Other clinical manifestations of M. kansasii infection in AIDS patients include bacteraemia, pericarditis with cardiac tamponade, oral ulcers, chronic sinusitis, osteomyelitis and scalp abscesses. ⁷ Mycobacterium kansasii causes pulmonary disease resembling tuberculosis. The major predisposing factor to lung infection is chronic pulmonary disease, which is present in over two-thirds of cases; other underlying conditions may include malignancy, immunosuppressive drugs, alcohol abuse, pneumoconiosis and HIV infection. ⁸ Affected patients tend to be in their fifth decade or older, with an approximate 3 : 1 male predominance. Certain occupational groups are at increased risk, including miners, welders, sandblasters and painters.^7–9

Sepsis is the most common cause of ARDS. ¹⁰ Diagnosis of M. kansasii infection is difficult, but a combination of clinical, radiologic and microbiological features consistent with an infection by this organism in the absence of another cause is very suggestive. ¹¹ Disseminated infection was documented in this patient by positive cultures for M. kansasii in the bronchoalveolar lavage and bone marrow and M. kansasii septicaemia associated with ARDS. Disseminated M. kansasii infection is usually determined by positive blood cultures. The combination of positive blood cultures at the time of ARDS, the presence of M. kansasii on bronchoalveolar lavage and bone marrow, confirms that M. kansasii caused the ARDS in this patient. The current recommendation for treatment of pulmonary disease caused by M. kansasii in adults is the regimen of isoniazid (300 mg), rifampin (600 mg) and ethambutol (25 mg/kg for the first two months, then 15 mg/kg) given daily for 18 months with at least 12 months of negative sputum cultures.^12,13 In patients who are unable to tolerate one of these three drugs, clarithromycin appears to be a reasonable alternative. Pyrazinamide is not an option as an alternate or third drug for M. kansasii because all isolates are resistant. For treatment of extrapulmonary disease in adults, the regimen of anti-mycobacterial drugs should be the same as for pulmonary disease.^9–13