INTRODUCTION Granulomatous inflammation is a distinctive ...

disease and can be used as a basis for diagnosis and treatment (Bouza et al., 1981).
The traditional treatment of C. immitis meningitis consists of the administration of amphotericin
B directly into the cerebrospinal fluid by the lumbar or cisternal route or into the ventricles or
other sites through a reservoir (David, 1995).To minimize the possibility of side effects, such as
fever, neuropathy, and back pain, it is advisable to begin with a low dose and increase it gradually.
Amphotericin B should be given daily at first, then tapered (from every other day to once every
six weeks) as clinical improvement occurs, as indicated by signs, symptoms, cerebrospinal fluid
leukocyte counts and antibody titers (Drutz, 1983).
Therapy is usually required for at least a year. The cerebrospinal fluid should be examined for
one to two years after therapy (at first weekly and eventually every six weeks) if the patient has a
complete remission of meningitis, because relapse is common. The drug is delivered by barbotage
(gradual instillation and mixing of the drug with cerebrospinal fluid withdrawn into the
syringe).or by suspension in hypertonic glucose while the patient is lying on his or her side, with
the head of the table tilted down. Complications may include pain, headaches, paresthesias, and
nerve palsies. These complications are attributed to arachnoiditis or direct neurotoxic effects and
are usually transient, although some neurological deficits may become permanent. The cisternal
route of administration places the drug closest to the site of maximal involvement but may entail
additional complications, including hypertension, arrhythmias, and impairment of upper motor
neurons, as well as the risk of hemorrhage or direct puncture of the brain. Ventricular therapy
may be necessary if ventriculitis is present. If the flow of cerebrospinal fluid is obstructed by
infection or fibrosis, detected by imaging studies, therapy into several fluid compartments may be
necessary. Shunting of the cerebrospinal fluid may be required if hydrocephalus develops (Drutz,
1983).
The oral azoles offer a useful alternative treatment of meningeal disease, at the same doses as
those used for nonmeningeal disease, are associated with a high rate of response (67 to 88 percent
in various series). Responses with azoles have been seen when used as the primary therapy, after
the failure of amphotericin B therapy, or to lessen the amount of intracerebrospinal fluid therapy
usually needed to achieve a remission. Unfortunately, preliminary data suggest very high rates of
relapse (about 75 percent) after azole therapy is stopped. Even if C. immitis infection cannot be
cured with azole therapy and lifelong suppression is required, the facts that these medications are
well tolerated, do not have the toxic effects of amphotericin B, and do not require administration
into the cerebrospinal fluid may represent important advantages in patients with an otherwise
fatal illness (Tucker et al., 1990a; Tucker et al., 1990b; Galgiani et al., 1993).
Candida
Candida is present as a part of the normal intestinal flora. It rarely cause CNS disease unless host
defenses have been impaired. The factors that encourage spread of candida in the blood include
prematurity, broad spectrum antibiotics, hyperalimentation, malignancy, indwelling catheters,
corticosteroids, neutropnia, diabetes, and parentral drug abuse (Buchs and Pfister, 1983).
Candida are present as yeast forms, with reproduction resulting from budding and the formation
of pseudohyphae, which, in general, are smaller than hyphal forms. There are seven clinically
important species of Candida, including C albicans, C tropicalis, C krusei, C stellatoidea, C
parapsilosis, C pseudotropicalis, and C guilliermondii. Of these, C albicans most often causes CNS
infection, although there have been reports of meningitis due to C tropicalis and embolic abscess
due to C guilliermondii (Salaki et al., 1984; Lyons and Andriole, 1986).
In patients with disseminated Candida, the most common organ involved is the kidneys with the
brain being the second most common organ involved (Salaki et al., 1984). The frequency of CNS