Mycobacterium kansasii Infection

Etiology

Mycobacterium Kansasii is a slow-growing acid-fast bacillus. It grows best at 32 degrees Celcius, but can be cultured at 37 degrees. Its in-vitro and chemical characteristics are similar to those of M. marinum and M. szulgai . It produces mature colonies in greater then 7 days. Like other mycobacteria in the family, M. kansasii is strictly a gram-positive, non-motile and non-spore-forming organism. Colony morphology ranges from flat to raised and smooth to rough. When grown in the dark M. kansasii colonies are at first non-pigmented but turn yellow after exposure to light due to deposition of beta-carotene crystals.[5] Microscopic examinations show that when compared to M. tuberculosis, M. kansasii appears longer and broader and are often beaded or cross-barred in appearance when stained with Ziehl Neelsen or Kinyoun stain.[6] In Runyon classification, M. kansasii belongs to the group photochromogens. Biochemical characteristics include Catalase positive, nitrate reduction, tween hydrolysis, and urea hydrolysis. Identification using traditional methods could take as long as two months.

Although M. Kansasii was long thought to be homogenous species, genetic studies have shown that there are at least seven subtypes, with subtype one being most frequently isolated in human infections.[7] Pulsed-field gel electrophoresis techniques demonstrate that the clinical isolates are very closely related and may be clonal worldwide. Clinical isolates from Japan are similar those from Europe and USA. Pathogenic strains are highly Catalase positive.

M. kansasii is widely prevalent in the environment but has seldom been isolated from soil. Some documented sources include city tap water, swimming pools, fish tanks, fish bites, brackish water, and seawater.[8] Tap water appears to be the major reservoir. Infection is mostly acquired through the aerosol route. Infectivity is low in regions of endemicity. Transmission from humans to humans is not thought to occur, except in two cases where familial clustering was noted.[9] Clustering was thought to be due to a shared environment, susceptibility or genetic predisposition rather than true human to human transmission.[10]

Epidemiology

M. kansasii infection mostly occurs in males, at an average patient age of 45–62 years.[11] Lung infections caused by M. kansasii occur in geographic clusters.[12] In the United States, M. kansasii infections are more common in southern and central states with the highest incidence seen in the southern states of Texas, Louisiana and Florida, as well as the central states of Illinois, Kansas, and Nebraska. M. kansasii infections are more likely to occur in urban areas than rural areas, and several studies have reported an association with mining practices.[13] In the United Kingdom, M. kansasii infections are most frequent in Wales. Of all countries in Europe, Poland has the highest M. kansasii isolation rate (35% of all NTM compared to 5% in Europe).[4][14][4]

M. kansasii infections are also prevalent in areas where HIV infection is common due to the susceptibility of the hosts.

M. kansasii infections were the most common non-tuberculosis mycobacterial infections during the 1960s and 70s, before being surpassed by M. avium-intracellulare. In the 80s with the rise of HIV infections, there was a resurgence of M. kansasii, which has now decreased in the antiretroviral therapy (AR) era. M. kansasii infections can occur in both immunocompetent and immunosuppressed patients.[15][16] In the 1980s the overall prevalence of M. kansasii infections was estimated to be 0.5 cases per 100,000 persons. Since mycobacterial infections are not reported, there is no reliable data for M. kansasii infections in transplant patients. Generally in transplant patients mycobacterial infections present as disseminated infections.[17] Fifty percent of patients with pulmonary disease also have dissemination. Renal transplant patients have been the most frequently reported to have disseminated disease. M. abscesses, M. chelonae, and M.kansasii are the mycobacteria most commonly present with dissemination. Even in HIV and late-stage AIDS patients, M. kansasii presents with pulmonary disease. In one study from California, the prevalence of mycobacterial infections was 0.75 /100 000 in HIV-negative patients, 115/100000 in HIV-positive patients, and 647/100000 persons in AIDS patients.[18][19]

History and Physical

Mycobacterial infections, including M. kansasii infections, can be categorized into six clinical patterns: pulmonary disease, skin, and soft tissues, musculoskeletal infections (monoarticular septic arthritis and tenosynovitis), disseminated disease, catheter-associated disease, and lymphadenitis.[20] Chronic pulmonary cavitary disease in the upper lobe is the most common presentation of M. kansasii infections. Not surprisingly these patients may be initially diagnosed with pulmonary tuberculosis. In one study, the mean age of patients with M. kansasii infection was 58 years, and 64% were men. However, M. kansasii can infect adults of any age, sex, or race. Infection results in symptoms in 85% of cases.

The most common symptoms of pulmonary M. kansasii infection include a cough (91%), sputum production (85%), weight loss (53%), breathlessness (51%), chest pain (34%), hemoptysis (32%), and fever or sweats (17%). Of all the NTM infections, M. kansasii infections most often resemble Mycobacterial tuberculosis infections.[21] Risk factors for M. kansasii infections are the same as those for other mycobacteria, namely, smoking, pneumoconiosis, silicosis, chronic obstructive pulmonary disease, malignancy, immunosuppressed state, chronic kidney disease, alcoholism and concurrent or prior M. tuberculosis infection.[3]

While cavitary disease occurs in 90% M. kansasiiI infections, nodular and brochiectatic disease can also occur. If left untreated pulmonary infections (both cavitary and nodular) are characterized by the persistence of AFB in the sputum and progressive destruction of the lung architecture. Pulmonary disease may be present in AIDS patients but there is less likelihood of cavitations; hilar lymphadenopathy and interstitial infiltrates are more common. However, if the CD4 count is high there is an increased chance of cavitary disease.

The second most frequent organ involved in M. kansasii infection is the skin.[22] Cutaneous infection resembles secondary to local lymphatic spread. Cutaneous lesions may include nodules, pustules, verrucous lesions, erythematous plaques, abscesses, and ulcers. In HIV and immunocompromised patients, the presentation can be atypical and include bacteremia, osteomyelitis, abscesses, and cellulitis. Pericarditis with cardiac tamponade has been reported in HIV patients.[23]

In disseminated disease, the symptoms are vague and nonspecific. In a series of 49 patients, fever was present in 60%, hepatosplenomegaly in 40%; pulmonary infiltrates in 25% and lymphadenopathy in 10%. Bone involvement, such as vertebral osteomyelitis and sacroiliitis, is common with M. kansasii disseminated diseases. Psoas abscess, bone marrow granuloma, liver granuloma, and possible spleen abscesses have been described.

In patients with an advanced immunocompromised state, HIV and M. kansasii co-infection can occur and reported average CD count in these patients has been less than <50/mm3.[24]

Evaluation

Since the symptoms are not specific and the differential diagnosis is broad, microbiologic isolation is required to make the diagnosis. M. kansasii rarely represents colonization or environmental contamination. Therefore any isolation of the organism needs to be evaluated for therapy.[25] Highly sensitive and specific PCR tests are available for M. kansasii.[26][25]

Culture results along with clinical and radiological diagnosis are recommended for accurate diagnosis of M. kansasii. As per the guidelines from ATS (American Thoracic Society) and IDSA (Infectious Disease Society of America) diagnosis of NTM should include a minimal radiological evaluation which includes a chest X-ray (or computed tomography of the chest if there is an absence of cavitation), combined with positive sputum cultures and exclusion of other diagnoses clinically. Cultures are considered positive when two consecutive positive sputum cultures, one positive culture from bronchoscopy specimens, or one positive sputum culture with compatible pathology is present.[25] Cultures are considered to be positive when a) 2 sputum cultures are consecutively positive, b) bronchoscopy specimens with one positive culture or c) one sputum culture is positive and a compatible pathology is present.[25]

Treatment / Management

Rifampin is the cornerstone of M kansasii therapy. The first line therapy recommended by IDSA-ATS guidelines for M. kansasii is rifampin, ethambutol, and isoniazid plus pyridoxine.[27][28][29] The recommended duration of therapy is at least 12 months or more with the goal to have culture negative results for 12 months on therapy. M. kansasii are predictably resistant to pyrazinamide. Isoniazid (INH) resistance should be interpreted with caution as a higher concentration is needed for M. kansasii when compared to M. tuberculosis. M. kansasii organisms show resistance to isoniazid at one mcg/mL but are susceptible at five mcg/mL. In a treatment naïve patient, INH is effective regardless of concentration achieved in the serum. Rifampin-containing regimens have low failure rates (1.1%) and low long-term relapse rates (< 1%). Based on M. kansasii susceptibilities in vitro, patients with rifampin-resistant M kansasii disease should be treated with a 3-drug regimen, which should include clarithromycin or azithromycin. The other two drugs should be chosen from moxifloxacin, ethambutol, sulfamethoxazole, or streptomycin.[3] The Clinical and Laboratory Standards Institute (CLSI) recommends that all initial isolates of M. kansasii be tested only for clarithromycin and rifampin susceptibility. INH and streptomycin susceptibility should be tested as secondary agents.(B2)

M. kansasii in HIV patients:

One strategy to treat M. kansasii infection in HIV-positive patients is to use an NRTI-based regimen, allowing for a full dose of rifampin, which is the cornerstone of therapy for M. kansasii. If a protease inhibitor (PI) such as darunavir or atazanavir or non-nucleoside reverse transcriptase inhibitor [NNRTI] such as efavirenz or nevirapine is included in HIV treatment regimens, rifabutin can be used instead of rifampin. Clarithromycin can be added to improve efficacy, but rifabutin-related toxicity can increase when combined with clarithromycin.

Monitoring therapy:

Serial sputum samples for AFB should be obtained regularly so patients failing therapy are recognized early and susceptibility testing for additional drugs can be done. Serial CXR can be administered, although lung disease is likely to evolve at a slow pace. Routine monitoring for adverse effects of medications and drug-drug interactions is recommended.

Differential Diagnosis

• Mycobacterium tuberculosis
• NTM other such as MAC
• Endemic fungi
• Actinomyces group
• Cancer
• Wegener’s

Prognosis

With appropriate treatment, the prognosis is usually good.[30] Mortality is higher and can go up to 50% in patients with HIV who have M. kansasii infection.[24] In HIV patients who have a pulmonary infection with M. kansasii, survival predictors include higher CD4 cell count, negative smear microscopy, antiretroviral therapy and adequate treatment for M. kansasii.[24]

Complications

Complications can include disseminated disease. Bone involvement, such as vertebral osteomyelitis and sacroiliitis are common with disseminated diseases.[31] Pneumothorax, Psoas abscess, bone marrow granuloma, liver granuloma, and possible spleen abscesses have also been described in the literature.[32] CNS complications like meningoencephalitis are very rare and are usually fatal.