Nontuberculous Mycobacterial Meningitis - Clinical Infectious ...

em 1996;23 (December) Nontubercu1ous Mycobacterial Meningitis 1267
clinical samples in our laboratory. Of these isolates, 308
(11.9%) were MAC. Between 1982 and 1989, 51 MAC isolates
were recovered from 24 patients, and between 1990 and 1994,
257 MAC isolates were recovered from 100 patients. Over the
entire study period, only two nontuberculous mycobacterial
isolates were recovered from CSF cultures.
Case Reports
A summary of the findings for the two patients at our center
who had AIDS and disseminated MAC disease is presented in
table 1. One of the patients had meningitis with hemiparesis,
and she died despite institution of antimycobacterial therapy.
The other patient had only persistent fever without meningism,
and MAC was isolated from a culture of CSF. This patient
received therapy with isoniazid, rifampin, and ciprofloxacin,
but he died 2 months later.
Literature review. We identified 50 cases of NTMM in the
English-language literature. The main characteristics of these
cases are shown in table 1 [8, 17 -37], and their relations with
underlying conditions are shown in table 2. Of the 50 cases
of reported NTMM, we determined that 27 were definitive
meningitis, 18 were probable meningitis, and five were doubtful
meningitis according to the criteria described. The first case at
our center was defined as definitive meningitis, and the second
was defined as doubtful meningitis.
Discussion
Isolation of a single colony of Mycobacterium tuberculosis
is always clinically significant; however, other species of my cobacteria
may be pathogens or simply contaminants. Assessment
of the pathogenicity of mycobacteria is aided by the following
data: repeated isolation of the same organism; identity of the
species; underlying predisposing conditions; and specimens
cultured [1, 38-40]. Isolation of nontuberculous mycobacteria
from a sterile fluid such as CSF is a significant finding; thus,
we based our review on this finding.
The species of nontuberculous mycobacteria reported to
cause meningitis include the four groups of the Runyon classification
[1]. There is considerable variation in the incidence of
these species: 31 (60%) of the 52 cases were caused by MAC,
nine (17%) were caused by mycobacteria from Runyon group
II, six (11.5%) were caused by Mycobacterium kansasii, and
six (11.5%) were caused by Mycobacterium fortuitum.
NTMM occurred in all age-groups; however, the relative
incidence of each species was more evenly distributed among
children than among the total population of patients: 29% (4
of 14 isolates) were MAC, 29% (4 of 14) were M kansasii,
29% (4 of 14) were from Runyon group II, and 14% (2 of 14)
were M fortuitum. The majority of cases in adults have been
caused by MAC.
It is interesting to note that most ofthe children with NTMM
(all except one with lymphoma [37]) have been immunocompe-
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tent. Three had underlying predisposing conditions including
chronic otitis and mastoiditis [20, 31] and a CSF shunt for
hydrocephalus [28].
Since the appearance of the AIDS epidemic, the number of
cases of MAC meningitis has increased [7, 9, 21, 24-26]; 22
(71 %) ofthe 31 reported cases occurred in patients with AIDS.
We found enough data to classify these cases: 18 were considered
definitive; three, probable; and one, doubtful. In most (18
of 22) of these patients, MAC caused disseminated disease
before invading the meninges.
Autopsy was performed in four cases and disclosed extensive
involvement of the liver, spleen, lymph nodes, bone marrow,
and gastrointestinal tract in each case. CNS involvement was
usually characterized by low-grade inflammation and the presence
of perivascular lesions, poorly formed granulomas without
giant cells, and numerous acid-fast bacilli. There was no evidence
of other opportunistic infections.
The clinical findings varied, but all patients had a history of
weight loss; one-half were febrile, and one-third had headache
and altered mentation [21, 24, 26]. The CSF biochemical profiles
showed moderate alterations with lymphocytosis; however,
levels of glucose and protein were close to normal, perhaps
because of the poor immunologic response in patients
with AIDS.
The two cases of MAC meningitis that we report (cases
30 and 31) occurred in patients with AIDS. These patients
presented with fever, weakness, somnolence, and behavioral
disorders. Analysis of CSF samples showed an increased
protein level and a decreased glucose level in one case and
normal levels of these constituents in the other. In both cases,
cultures of blood, CSF, and bone marrow were repeatedly
positive for MAC.
The overall death rate for patients with MAC disease has
been high (77%); however, incomplete documentation makes
it difficult to determine the crude death rate of meningitis due
to this microorganism. The treatment administered has not been
reported for a large number of patients [21,24-26], and some
of the patients were lost to follow-up. In one series of 15
patients with AIDS, Jacob et al. [26] found that the in-hospital
death rate was 67%. This rate may indicate that MAC meningitis
is a terminal event in the clinical evolution of AIDS. CNS
disease caused by MAC in patients with AIDS who have no
evidence of meningitis has also been reported [5, 9, 11, 14].
These cases, which clearly show the pathogenicity of MAC
in the CNS, are differentiated from probable or doubtful cases
of infection due to other pathogens or other underlying conditions
(e.g., severe necrotizing cytomegalovirus encephalitis or
primary brain lymphoma) [7, 11, 14, 21] and from cases of
disseminated MAC disease in which MAC is isolated from
brain tissue specimens [6, 13]. In 1986, Hawkins et al. [13]
reviewed postmortem culture results for patients with AIDS
and disseminated MAC disease and found that cultures of brain
tissue were positive in 39%, of the cases; however, in a 1989
review of autopsy findings for patients with AIDS, Santamaria