- Email: [email protected]
Mycobacterium kansasii: A Rare Cause of Brain Abscess
CASE-LETTER
Mycobacterium kansasii: A Rare Cause of Brain Abscess
M
ycobacterium kansasii is a photochromogenic, slow-growing, nontuberculous mycobacterium that causes pulmonary disease and disseminated infection.1 It is a common nontuberculous mycobacterial infection, second only to Mycobacterium avium complex, with an incidence of 2.4 cases per 100,000 adults annually in the United States, with the highest incidence in the central and southern United States.2,3 Human immunodeficiency virus (HIV) infection is a condition that increases the risk for M kansasii infection.2 The well-recognized risk factors for M kansasii infection among HIV-negative and HIV-unknown status patients include preexisting pulmonary disease (pneumoconiosis, obstructive pulmonary disease), previous mycobacterial disease, malignancy and alcoholism.2 Despite increasing reports of extrapulmonary M. kansasii disease in both HIV-positive and HIV-negative persons, central nervous system disease is very rare. An extensive literature review revealed only 4 published cases of proven M kansasii brain abscess.4,5 A 44-year-old male with advanced HIV (CD4 count of 199 cells/mm3; CD4% of 15.4) presented with a chief complaint of headache, fever and cough for 1 month. The patient carried a history of HIV, diagnosed in 1989, with a history of medication nonadherence. The patient was recently started on a regimen of combination antiretroviral therapy. He also had a history of shingles 1 year before presentation, as well as oral candidiasis. The patient was in his usual state of health until 1 month before admission, at which time he endorsed onset of sinus congestion, sore throat, fever, chills and productive cough with occasional dizziness. He endorsed coughing for an entire month relentlessly with production of quarter-sized amount of yellow sputum. He reported that his headaches were associated with his coughing. He described his headache as pounding and throbbing mostly in the right frontal area, and sometimes occurring in the frontal regions bilaterally. The patient noted occasional episodes of lightheadedness. He denied any weight loss, night sweats, hemoptysis, chest pain, shortness of breath or sick contacts. Upon presentation, he had a low-grade fever of 38.31C. Vital signs were otherwise within normal limits. Cardiopulmonary examination was unremarkable. No focal findings were noted on an extensive neurological examination. Glasgow Coma Scale was 15 with normal mentation and
orientation. Cranial nerves were intact. No focal strength, sensory or cerebellar abnormalities were noted. Deep tendon reflexes were 2 of 4 symmetrically throughout. He had a negative Babinski sign and was negative for clonus bilaterally. Initial laboratory data revealed a white blood cell count of 6.2 109 cells/L mm3 (reference range: 4.5-11.0 109 cells/L mm3) with a normal differential, as well as a hemoglobin of 8.5 g/dL (reference range: 12.0-16.0 g/dL) with an mean cell volume of 90.6. The initial 2-view chest radiograph showed no evidence of cardiopulmonary disease. A head computed tomography (CT) with iodinated contrast revealed a 2.3 1.8 cm2 ring-enhancing hypodensity within the anterior, right temporal lobe with surrounding edema (Figure). This finding was not visualized on a noncontrast head CT 3 months prior. These findings were confirmed and further characterized on an magnetic resonance imaging of the brain with gadolinium contrast (Figure). As toxoplasmosis was near the top of our differential diagnosis, Toxoplasma gondii antibodies were obtained. Toxoplasma IgM antibodies were low at 0.10 IU/mL (reference range o0.80 IU/mL), as were the IgG antibodies at 0.0 IU/mL (reference range o7.5 IU/mL), thus making the diagnosis of toxoplasmosis unlikely. An 18F-fluorodeoxyglucose positron emission tomography or low-dose CT was performed and showed that the lesion was hypometabolic compared with the surrounding brain parenchyma on the positron emission tomography images, not consistent with lymphoma. Neurosurgery was then consulted to obtain a diagnostic brain biopsy. Open brain biopsy revealed a brain abscess in the temporal lobe, which was removed and cultured, while the surrounding area was copiously irrigated. Histology of the brain biopsy revealed benign brain tissue with reactive gliosis and chronic inflammation, whereas the removed mass revealed acute inflammatory cells along with histiocytes and lymphocytes associated with large areas of necrosis, consistent with abscess. The initial stains were 2þ acid-fast bacilli (AFB) positive, with the cultures ultimately growing M kansasii 9 days later. Owing to the patient's respiratory complaints and despite his negative chest radiograph, a chest CT with iodinated contrast was obtained to further evaluate for pulmonary involvement. This revealed axillary and mediastinal lymphadenopathy, as well as an 8 mm right middle lobe nodule. Sputum smears were initially negative for AFB; however, the cultures grew M kansasii within 24 days. Axillary lymph node biopsies were negative for mycobacterium or lymphoma. Upon results of the AFB positive brain lesion, the patient was initially started on rifampin, isoniazid, pyrazinamide and ethambutol therapy pending culture results. He was subsequently placed on isoniazid, rifabutin and ethambutol þ Vitamin B6 once cultures were resulted. The patient was continued on treatment and repeat brain magnetic resonance imaging at 10 months and 14 months posttreatment initiation showed continued improvement of previous inflammatory abnormalities. Unfortunately, this
Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. www.amjmedsci.com www.ssciweb.org
1
Onor et al
FIGURE. (A) Computed tomography of brain with intravenous contrast showing a 2.3 1.8 cm2 ring-enhancing hypodensity within the anterior right temporal lobe with surrounding edema. (B) Magnetic resonance T2 image with gadolinium contrast showing a 2.3 1.8 cm2 ringenhancing lesion in the right temporal lobe with surrounding edema.
patient succumbed to a separate HIV-associated illness nearly 15 months after his diagnoses of disseminated M. kansasii. M kansasii's major reservoir is tap water and local water supplies.2 The mode of transmission of M kansasii infection is most likely via ingestion or inhalation from the gastrointestinal or respiratory tract.2 There is no evidence to support person-to-person transmission of M kansasii.2 Cases of M kansasii infection have been well documented in both immunocompetent and immunocompromised patients. The infection typically manifests clinically with bronchopulmonary symptoms and chest radiographic findings similar to pulmonary Mycobacterium tuberculosis infection.2 Disseminated infection can also commonly occur and typically affect immunocompromised individuals such as HIV-infected patients, solidorgan transplant recipients, patients with hematologic malignancy or patients on chronic steroid regimens.2 The most frequent presentation of clinical M kansasii is that of a pulmonary infection with nearly identical symptoms and radiographic findings to that of M tuberculosis.2 The pulmonary symptoms of nontuberculous mycobacterium (NTM) infection are nonspecific and typically include chronic cough, sputum production, fever, dyspnea and malaise.2 Radiographically, NTM pulmonary disease may present either as cavitary or nodular. Although subtle radiographic differences may exist, none are specific enough to exclude M tuberculosis from the differential diagnosis, and thus isolation of M kansasii from expectorated sputum or bronchial lavage is necessary for the diagnosis.2 When evaluating for NTM pulmonary infections, multiple samples should be obtained to decrease the likelihood of a falsepositive or a contaminated specimen. The American Thoracic Society and the Infectious Disease Society of America recommend that the evaluation of patients with suspected pulmonary NTM should include, at the minimum, chest imaging, 3 or more sputum specimens for acid fast bacilli analysis, and exclusion of other pulmonary disorders such as M tuberculosis and lung malignancy.2
2
In patients with advanced HIV, the clinical presentation of disseminated NTM if fairly nonspecific. M kansasii is the second most prevalent disseminated NTM in HIV-infected patients, less common only than M avium complex (MAC).2 In contrast to MAC, most patients with disseminated M kansasii also have active pulmonary disease, and central nervous system involvement is rarely described.6 Although pulmonary M kansasii should be diagnosed with the methods previously described, disseminated infections should be isolated from the particular site of involvement. In a study by Campo and Campo of 46 sequential patients with M kansasii infections, 21.7% had disseminated disease. Extrapulmonary isolates were obtain from several sources, including pleural fluid, pericardial fluid, stool, lymph nodes, blood and bone.6 In our reported case, confirmation of central nervous system involvement was obtained by direct biopsy. As there are no randomized trials of the treatment of M kansasii, recommendations for treatment regimens have been based on retrospective data.2 Initial reports of treatment regimens before the use of rifampin showed low sputum conversion rates and a high incidence of relapsing infection. Later studies using rifampin-based regimens reported sputum conversion rates near 100% and a very low relapse rate, usually due to rifampin resistant organisms.7 The currently recommended regimen for treatment of pulmonary M kansasii includes rifampin 600 mg per day, isoniazid 300 mg per day, and ethambutol 15 mg/kg per day for at least 12 months of continuously negative sputum cultures.2 There is no surgical role in treatment of routine pulmonary M kansasii.2 The treatment regimen for patients with disseminated M kansasii infections is typically the same as for those with pulmonary disease.2 The treatment regimen for HIV-infected patients should be constructed with an infectious disease specialist as to best avoid interactions with antiretroviral therapy. The duration of treatment for patients with disseminated M kansasii is the same as the recommended duration for disseminated THE AMERICAN JOURNAL
OF THE
MEDICAL SCIENCES
VOLUME ] NUMBER ]
] 2016
Mycobacterium kansasii Brain Abscess
MAC, and there are no recommends for prophylaxis against M kansasii.5 M kansasii is a common NTB infection seen in the HIV population, most commonly presenting with a bronchopulmonary infection similar to that of M tuberculosis. Although it is the second most common cause of disseminated NTB, focal brain abscess is a rare presentation. We present this case as evidence that M kansasii should remain in the differential for an immunocompromised patient with a ring-enhancing brain lesion. IfeanyiChukwu O. Onor, PharmD Meagan E. Piazza, PharmD Mona F. Khashan, Pharm D Seema Walvekar, MD *Shane G. Guillory, MD * Department of Internal Medicine, Division of Hospital Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana
*E-mail: [email protected].
The authors have no financial or other conflicts of interest to disclose.
REFERENCES 1. Bloch KC, Zwerling L, Pletcher MJ, et al. Incidence and clinical implications of isolation of Mycobacterium kansasii: results of a 5-year, population-based study. Ann Intern Med 1998;129(9):698–704. 2. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175(4): 367–416. 3. Canueto-Quintero J, Caballero-Granado FJ, Herrero-Romero M, et al. Epidemiological, clinical, and prognostic differences between the diseases caused by Mycobacterium kansasii and Mycobacterium tuberculosis in patients infected with human immunodeficiency virus: a multicenter study. Clin Infect Dis 2003;37(4):584–90. 4. Tabatabaei N, Stout J, Goldschmidt-Clermont P, et al. Central nervous system infection and cutaneous lymphadenitis due to Mycobacterium kansasii in an immunocompetent patient. Infection 2007;35(4):291–4. 5. Berger GA, Yangco BG, Adelman HA. Central nervous system infection with Mycobacterium kansasii. Ann Int Med 1993;118(5):396. 6. Campo RE, Campo CE. Mycobacterium kansasii disease in patients infected with human immunodeficiency virus. Clin Infect Dis 1997;24(6): 1233–8. 7. Ahn CH, Lowell JR, Ahn SS, et al. Short-course chemotherapy for pulmonary disease caused by Mycobacterium kansasii. Am Rev Respir Dis 1983;128(6):1048–50.
Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. www.amjmedsci.com www.ssciweb.org
3
Mycobacterium kansasii: A Rare Cause of Brain Abscess
M
ycobacterium kansasii is a photochromogenic, slow-growing, nontuberculous mycobacterium that causes pulmonary disease and disseminated infection.1 It is a common nontuberculous mycobacterial infection, second only to Mycobacterium avium complex, with an incidence of 2.4 cases per 100,000 adults annually in the United States, with the highest incidence in the central and southern United States.2,3 Human immunodeficiency virus (HIV) infection is a condition that increases the risk for M kansasii infection.2 The well-recognized risk factors for M kansasii infection among HIV-negative and HIV-unknown status patients include preexisting pulmonary disease (pneumoconiosis, obstructive pulmonary disease), previous mycobacterial disease, malignancy and alcoholism.2 Despite increasing reports of extrapulmonary M. kansasii disease in both HIV-positive and HIV-negative persons, central nervous system disease is very rare. An extensive literature review revealed only 4 published cases of proven M kansasii brain abscess.4,5 A 44-year-old male with advanced HIV (CD4 count of 199 cells/mm3; CD4% of 15.4) presented with a chief complaint of headache, fever and cough for 1 month. The patient carried a history of HIV, diagnosed in 1989, with a history of medication nonadherence. The patient was recently started on a regimen of combination antiretroviral therapy. He also had a history of shingles 1 year before presentation, as well as oral candidiasis. The patient was in his usual state of health until 1 month before admission, at which time he endorsed onset of sinus congestion, sore throat, fever, chills and productive cough with occasional dizziness. He endorsed coughing for an entire month relentlessly with production of quarter-sized amount of yellow sputum. He reported that his headaches were associated with his coughing. He described his headache as pounding and throbbing mostly in the right frontal area, and sometimes occurring in the frontal regions bilaterally. The patient noted occasional episodes of lightheadedness. He denied any weight loss, night sweats, hemoptysis, chest pain, shortness of breath or sick contacts. Upon presentation, he had a low-grade fever of 38.31C. Vital signs were otherwise within normal limits. Cardiopulmonary examination was unremarkable. No focal findings were noted on an extensive neurological examination. Glasgow Coma Scale was 15 with normal mentation and
orientation. Cranial nerves were intact. No focal strength, sensory or cerebellar abnormalities were noted. Deep tendon reflexes were 2 of 4 symmetrically throughout. He had a negative Babinski sign and was negative for clonus bilaterally. Initial laboratory data revealed a white blood cell count of 6.2 109 cells/L mm3 (reference range: 4.5-11.0 109 cells/L mm3) with a normal differential, as well as a hemoglobin of 8.5 g/dL (reference range: 12.0-16.0 g/dL) with an mean cell volume of 90.6. The initial 2-view chest radiograph showed no evidence of cardiopulmonary disease. A head computed tomography (CT) with iodinated contrast revealed a 2.3 1.8 cm2 ring-enhancing hypodensity within the anterior, right temporal lobe with surrounding edema (Figure). This finding was not visualized on a noncontrast head CT 3 months prior. These findings were confirmed and further characterized on an magnetic resonance imaging of the brain with gadolinium contrast (Figure). As toxoplasmosis was near the top of our differential diagnosis, Toxoplasma gondii antibodies were obtained. Toxoplasma IgM antibodies were low at 0.10 IU/mL (reference range o0.80 IU/mL), as were the IgG antibodies at 0.0 IU/mL (reference range o7.5 IU/mL), thus making the diagnosis of toxoplasmosis unlikely. An 18F-fluorodeoxyglucose positron emission tomography or low-dose CT was performed and showed that the lesion was hypometabolic compared with the surrounding brain parenchyma on the positron emission tomography images, not consistent with lymphoma. Neurosurgery was then consulted to obtain a diagnostic brain biopsy. Open brain biopsy revealed a brain abscess in the temporal lobe, which was removed and cultured, while the surrounding area was copiously irrigated. Histology of the brain biopsy revealed benign brain tissue with reactive gliosis and chronic inflammation, whereas the removed mass revealed acute inflammatory cells along with histiocytes and lymphocytes associated with large areas of necrosis, consistent with abscess. The initial stains were 2þ acid-fast bacilli (AFB) positive, with the cultures ultimately growing M kansasii 9 days later. Owing to the patient's respiratory complaints and despite his negative chest radiograph, a chest CT with iodinated contrast was obtained to further evaluate for pulmonary involvement. This revealed axillary and mediastinal lymphadenopathy, as well as an 8 mm right middle lobe nodule. Sputum smears were initially negative for AFB; however, the cultures grew M kansasii within 24 days. Axillary lymph node biopsies were negative for mycobacterium or lymphoma. Upon results of the AFB positive brain lesion, the patient was initially started on rifampin, isoniazid, pyrazinamide and ethambutol therapy pending culture results. He was subsequently placed on isoniazid, rifabutin and ethambutol þ Vitamin B6 once cultures were resulted. The patient was continued on treatment and repeat brain magnetic resonance imaging at 10 months and 14 months posttreatment initiation showed continued improvement of previous inflammatory abnormalities. Unfortunately, this
Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. www.amjmedsci.com www.ssciweb.org
1
Onor et al
FIGURE. (A) Computed tomography of brain with intravenous contrast showing a 2.3 1.8 cm2 ring-enhancing hypodensity within the anterior right temporal lobe with surrounding edema. (B) Magnetic resonance T2 image with gadolinium contrast showing a 2.3 1.8 cm2 ringenhancing lesion in the right temporal lobe with surrounding edema.
patient succumbed to a separate HIV-associated illness nearly 15 months after his diagnoses of disseminated M. kansasii. M kansasii's major reservoir is tap water and local water supplies.2 The mode of transmission of M kansasii infection is most likely via ingestion or inhalation from the gastrointestinal or respiratory tract.2 There is no evidence to support person-to-person transmission of M kansasii.2 Cases of M kansasii infection have been well documented in both immunocompetent and immunocompromised patients. The infection typically manifests clinically with bronchopulmonary symptoms and chest radiographic findings similar to pulmonary Mycobacterium tuberculosis infection.2 Disseminated infection can also commonly occur and typically affect immunocompromised individuals such as HIV-infected patients, solidorgan transplant recipients, patients with hematologic malignancy or patients on chronic steroid regimens.2 The most frequent presentation of clinical M kansasii is that of a pulmonary infection with nearly identical symptoms and radiographic findings to that of M tuberculosis.2 The pulmonary symptoms of nontuberculous mycobacterium (NTM) infection are nonspecific and typically include chronic cough, sputum production, fever, dyspnea and malaise.2 Radiographically, NTM pulmonary disease may present either as cavitary or nodular. Although subtle radiographic differences may exist, none are specific enough to exclude M tuberculosis from the differential diagnosis, and thus isolation of M kansasii from expectorated sputum or bronchial lavage is necessary for the diagnosis.2 When evaluating for NTM pulmonary infections, multiple samples should be obtained to decrease the likelihood of a falsepositive or a contaminated specimen. The American Thoracic Society and the Infectious Disease Society of America recommend that the evaluation of patients with suspected pulmonary NTM should include, at the minimum, chest imaging, 3 or more sputum specimens for acid fast bacilli analysis, and exclusion of other pulmonary disorders such as M tuberculosis and lung malignancy.2
2
In patients with advanced HIV, the clinical presentation of disseminated NTM if fairly nonspecific. M kansasii is the second most prevalent disseminated NTM in HIV-infected patients, less common only than M avium complex (MAC).2 In contrast to MAC, most patients with disseminated M kansasii also have active pulmonary disease, and central nervous system involvement is rarely described.6 Although pulmonary M kansasii should be diagnosed with the methods previously described, disseminated infections should be isolated from the particular site of involvement. In a study by Campo and Campo of 46 sequential patients with M kansasii infections, 21.7% had disseminated disease. Extrapulmonary isolates were obtain from several sources, including pleural fluid, pericardial fluid, stool, lymph nodes, blood and bone.6 In our reported case, confirmation of central nervous system involvement was obtained by direct biopsy. As there are no randomized trials of the treatment of M kansasii, recommendations for treatment regimens have been based on retrospective data.2 Initial reports of treatment regimens before the use of rifampin showed low sputum conversion rates and a high incidence of relapsing infection. Later studies using rifampin-based regimens reported sputum conversion rates near 100% and a very low relapse rate, usually due to rifampin resistant organisms.7 The currently recommended regimen for treatment of pulmonary M kansasii includes rifampin 600 mg per day, isoniazid 300 mg per day, and ethambutol 15 mg/kg per day for at least 12 months of continuously negative sputum cultures.2 There is no surgical role in treatment of routine pulmonary M kansasii.2 The treatment regimen for patients with disseminated M kansasii infections is typically the same as for those with pulmonary disease.2 The treatment regimen for HIV-infected patients should be constructed with an infectious disease specialist as to best avoid interactions with antiretroviral therapy. The duration of treatment for patients with disseminated M kansasii is the same as the recommended duration for disseminated THE AMERICAN JOURNAL
OF THE
MEDICAL SCIENCES
VOLUME ] NUMBER ]
] 2016
Mycobacterium kansasii Brain Abscess
MAC, and there are no recommends for prophylaxis against M kansasii.5 M kansasii is a common NTB infection seen in the HIV population, most commonly presenting with a bronchopulmonary infection similar to that of M tuberculosis. Although it is the second most common cause of disseminated NTB, focal brain abscess is a rare presentation. We present this case as evidence that M kansasii should remain in the differential for an immunocompromised patient with a ring-enhancing brain lesion. IfeanyiChukwu O. Onor, PharmD Meagan E. Piazza, PharmD Mona F. Khashan, Pharm D Seema Walvekar, MD *Shane G. Guillory, MD * Department of Internal Medicine, Division of Hospital Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana
*E-mail: [email protected].
The authors have no financial or other conflicts of interest to disclose.
REFERENCES 1. Bloch KC, Zwerling L, Pletcher MJ, et al. Incidence and clinical implications of isolation of Mycobacterium kansasii: results of a 5-year, population-based study. Ann Intern Med 1998;129(9):698–704. 2. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175(4): 367–416. 3. Canueto-Quintero J, Caballero-Granado FJ, Herrero-Romero M, et al. Epidemiological, clinical, and prognostic differences between the diseases caused by Mycobacterium kansasii and Mycobacterium tuberculosis in patients infected with human immunodeficiency virus: a multicenter study. Clin Infect Dis 2003;37(4):584–90. 4. Tabatabaei N, Stout J, Goldschmidt-Clermont P, et al. Central nervous system infection and cutaneous lymphadenitis due to Mycobacterium kansasii in an immunocompetent patient. Infection 2007;35(4):291–4. 5. Berger GA, Yangco BG, Adelman HA. Central nervous system infection with Mycobacterium kansasii. Ann Int Med 1993;118(5):396. 6. Campo RE, Campo CE. Mycobacterium kansasii disease in patients infected with human immunodeficiency virus. Clin Infect Dis 1997;24(6): 1233–8. 7. Ahn CH, Lowell JR, Ahn SS, et al. Short-course chemotherapy for pulmonary disease caused by Mycobacterium kansasii. Am Rev Respir Dis 1983;128(6):1048–50.
Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. www.amjmedsci.com www.ssciweb.org
3