Nontuberculous Mycobacterial Meningitis - Clinical Infectious ...

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cm 1996;23 (December) Nontuberculous Mycobacterial Meningitis 1271 Table 1. (Continued) CSF findings WBCs, 400/mm'; protein, 20 mg/dL; glucose, 20 mg/dL WBCs, 200/mm' Normal Cloudy; WBCs, 1,085/mm'; protein and glucose levels, normal Normal Increased number of cells and protein level NA WBCs, 200/mm' (70% lymphocytes); glucose, 27 mg/dL WBCs, 70/mm' (90% PMNs); protein, 500 mg/dL; glucose, 20 mg/dL Protein, 60 mg/dL; glucose, 18 mg/dL Treatment INH, Rif, Eth, Stm; laminectomy and Dox Em, INH, Km, and partial resection of abscess; Dox, Ethi, and intrathecal Amik added None Pen, TMP-SMZ, Gm; INH and drainage of abscess and fistula INH, Rif, Eth " Antituberculous therapy" Pen, Strn, PAS Pen, sulfonamides, Clm, Strn, INH, cortisone "Antituberculous therapy" INH, Rif, PZA, Prd Outcome Infection persisted; improved after laminectomy Improved after intrathecal therapy Cured Improved Progressive lethargy; died of PCP * Given for 79 days. tMean ± SD. I Fifteen patients had weight loss, eight had fever, two had seizures, four had confusion, and five had headaches and vomiting. § Autopsy was performed in three cases. II Given for 1 year, then given again for 5 years. alus (case 40 [28]) and an adult with myeloma (case 39 [23]). The first patient was cured by removal of an infected derivative shunt; the other patient, who was treated with aminoglycosides and isoniazid, died. Meningitis due to M. fortuitum has been clearly documented (four definitive cases ofNTMM) and related to previous CNS surgery and trauma, and a neurocutaneous fistula that lasts for years has been described in these cases; drainage and/or removal of a foreign body has been demonstrated to be the best therapy. Intrathecal treatment with aminoglycosides has also been described [31]. Of the patients with M. fortuitum meningitis, only one died (this patient also had AIDS). Since abscesses are frequently present in cases of M. fortuitum meningitis, it Downloaded from http://cid.oxfordjournals.org/ by guest on April 9, 2013 Died Died 5 weeks after laparotomy Died after 5 d Died Died after 7 d Antibiotic susceptibilities (result) Cpm (S), Dox (S) Amik (S), Km (R), Dox (R) NA Amik (S), Tm (S), Dox (S), INH (R), TMP-SMZ (R), Strn (R) NA NA NA INH (R), PAS (R) NA NA Classification ofNTMM Definitive Definitive Doubtful Definitive Probable Definitive Probable Probable Definitive Definitive is not surprising that the CSF biochemical findings in these cases generally include a predominance of polymorphonuclear cells. The severity of meningitis due to M. kansasii and the associated high mortality are striking. Of the six cases found in the literature, three were definitive (case 48 [18], case 51 [36], and case 52 [37]; table 1), and three were probable (case 47 [8], case 49 [34] and case 50 [35]) by our definition. M. kansasii causes disseminated disease that is similar to meningitis due to M. tuberculosis. Until culture results are available, tuberculous meningitis is initially suspected in these cases when the CSF biochemical profile is consistent with lymphocytic meningitis. In the two cases of M. kansasii
1272 Flor et al. CID 1996;23 (December) Table 2. Mycobacterial species isolated among 52 patients with nontuberculous mycobacterial meningitis and predisposing underlying conditions. Mycobacterium isolate recovered Underlying Runyon condition MAC group II Mfortuitum M kansasii None 6 7 3 4 Chronic otitis media 0 1 0 Hematologic disease 2 0 AIDS 21 0 I I Hydrocephalus 0 I 0 0 Back trauma 0 0 0 Neurosurgery 0 0 0 NOTE. MAC = Mycobacterium avium complex. meningitis in which autopsies were performed, caseous granulomata were found in the patients' lungs and meninges. Despite institution of antituberculous therapy, all of the patients died. The majority ofNTMM cases present as lymphocytic meningitis. The CSF is normal or close to normal in patients with AIDS, and polymorphonuclear cells predominate in the CSF of patients with meningitis due to M. fortuitum. In all but two cases, direct smears of CSF for acid-fast bacilli were negative for mycobacteria. Concomitant pathogens were isolated in six (11 %) ofthe 52 cases of NTMM. We consider these cases to be mixed infections and have classified them as probable NTMM. The combined isolates recovered were M. tuberculosis and a Runyon group II mycobacterium (case 38 [27], table 1), M. tuberculosis andM. kansasii (case 50 [35]), M. tuberculosis and MAC (case 9 [23]), Cryptococcus neoformans and MAC (case 4 [19]), cytomegalovirus and MAC (case 7 [21]), and Escherichia coli and MAC (case 8 [22]). NTMM is frequently associated with immunosuppression: the incidence of immunosuppression in these 52 cases was 54% (28 cases). Among the immunosuppressed patients, AIDS was the most common underlying condition (24 [46%] of the 52 patients). However, NTMM has also been reported in association with other immunosuppressive states (e.g., hematologic malignancy and immunosuppression due to treatment with corticoid drugs): two (8%) of these 24 cases were due to MAC (cases 8 [22] and 10 [23]), one was due to M. kansasii (case 52 [37]), and one was due to M. gordonae (case 39 [23]). It is surprising that NTMM has not been observed in patients receiving hemodialysis or in transplant recipients even though mycobacterial disease is a well-recognized complication under such circumstances [15, 23, 42, 43]. In summary, nontubercu10us mycobacterial microorganisms are able to cause meningitis, and when these organisms are isolated in cultures of CSF, they should not routinely be assumed to be contaminants. M. avium is the most commonly Downloaded from http://cid.oxfordjournals.org/ by guest on April 9, 2013 isolated species in patients with NTMM, especially since the beginning of the AIDS epidemic. M. fortuitum meningitis is clearly associated with previous neurosurgery or spinal trauma and with chronic infection; the prognosis is good when the concomitant abscess is drained. The clinical characteristics of patients with M. kansasii meningitis are similar to those of patients with tuberculous meningitis, but mortality due to M. kansasii is higher despite adequate therapy. Acknowledgment The authors thank Celine L. Cavallo for her editorial assistance. References 1. Horowitz EA, Sanders WE Jr. Other mycobacterium species. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett's principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone, 1995:2264-73. 2. Havlir DV, Ellner JJ. Mycobacterium avium complex. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett's principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone, 1995:2250-64. 3. Masur H, Michelis MA, Wormser G, et al. Opportunistic infection in a previously healthy woman. Initial manifestations of a communityacquired cellular immunodeficiency. Ann Intern Med 1982;97:533-9. 4. Greene JB, Sidhu G, Lewin S, et al. Mycobacterium avium complex: a cause of disseminated life-threatening infection in homosexuals and drug abusers. Ann Intern Med 1982;97:539-46. 5. Snider WD, Simpson DM, Nielsen S, Gold JWM, Metroka CE, Posner JB. Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients. Ann Neuro11983; 14:403-18. 6. Elliot JL, Hoppes WL, Platt MS, Thomas JG, Patel IP, Gansar A. The acquired immunodeficiency syndrome and Mycobacterium avium-intracellulare bacteremia in a patient with hemophilia. Ann Intern Med 1983; 98:290-3. 7. Reichert CM, O'Leary TJ, Levens DL, Sirnrell CR, Macher AM. Autopsy pathology in the acquired immune deficiency syndrome. Am J Pathol 1983; 112:357 -82. 8. Kopple BS, Wormser GP, Tuchman AJ, Maayan S, Hewlett D Jr, Daras M. Central nervous system involvement in patients with acquired immune deficiency syndrome (AIDS). Acta Neurol Scand 1985;71:337-53. 9. Levy RM, Bredesen DE, Rosembem ML. Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. J Neurosurg 1985; 62:475-95. 10. Maayan S, Wormser G, Hewlett D, et al. Acquired immunodeficiency syndrome (AIDS) in an economically disadvantaged population. Arch Intern Med 1985; 145:1607-12. II. Anders K, Steinsapir KD, Iverson DJ, et al. Neuropathological findings in the acquired immunodeficiency syndrome (AIDS). Clin Neuropathol 1986;5:1-20. 12. Helwelg-Larsen S, Jakobsen J, Boesen F, Arlien-S0borg P. Neurological complications and concomitants of AIDS. Acta Neurol Scand 1986;74: 467-74. 13. Hawkins CC, Gold JWM, Whimbey E, et al. Mycobacterium avium complex in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1986; 105:184-8. 14. Henin D, Duyckaerts C, Chaunu MP, et al. Etude neuropathologique de 31 cas de syndrome d'immuno-depression acquise. Rev Neurol (paris) 1987; 143:631-42. 15. Santamaria JM. Meningitis por micobacterias no tuberculosas. Enferm Infecc Microbiol Clin 1989;7:329-31.
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