John N. Galgiani,1,2,3 Neil M. Ampel,1,2,3 Janis E. Blair,4 Antonino Catanzaro,5 Royce H. Johnson,6 David A. Stevens,7,8 and Paul L. Williams9
1Valley Fever Center for Excellence, 2Southern Arizona Veterans Affairs Health Care System, and 3University of Arizona, Tucson, and 4Mayo Clinic,Scottsdale, Arizona; and 5University of California, San Diego, 6Kern Medical Center, Bakersfield, 7Santa Clara Valley Medical Center and 8StanfordUniversity, San Jose, and 9Kaiser Permanente Medical Center, Fresno, California
EXECUTIVE SUMMARY INTRODUCTION
Management of coccidioidomycosis first involves rec-
Coccidioidomycosis (also known as valley fever) results
ognizing that a coccidioidal infection exists, defining
from inhaling the spores (arthroconidia) of Coccidioides
the extent of infection, and identifying host factors that
species (Coccidioides immitis or Coccidioides posadasii)
predispose to disease severity. After these assessments,
. Most infections in the United States are acquired
patients with localized acute pulmonary infections and
within the major regions of endemicity of southern
no risk factors for complications often require only
Arizona, central or other areas of California, southern
periodic reassessment to demonstrate resolution of
New Mexico, and west Texas. Travelers who have re-
their self-limited process. On the other hand, patients
cently visited the region of endemicity or previously
with extensive spread of infection or who are at high
infected patients with immunosuppression who expe-
risk of complications because of immunosuppression
rience reactivation of latent infections can develop clin-
or other preexisting factors require a variety of treat-
ical disease and require medical management outsideof the region of coccidioidal endemicity .
ment strategies that may include antifungal drug ther-
The estimated numbers of infections per year has
apy, surgical debridement, or a combination of both.
risen to ∼150,000 as a result of population increases in
Azole antifungals, primarily fluconazole and itracona-
southern Arizona and central California. Of these in-
zole, have replaced amphotericin B as initial therapy
fections, one-half to two-thirds are subclinical, and vir-
for most chronic pulmonary or disseminated infections.
tually all patients with these infections are protected
Amphotericin B is now usually reserved for patients
from second primary infections. The most common
with respiratory failure due to infection with Cocci-
clinical presentation of coccidioidomycosis is a self-
dioides species, those with rapidly progressive cocci-
limited acute or subacute community-acquired pneu-
dioidal infections, or women during pregnancy. Ther-
monia that becomes evident 1–3 weeks after infection.
apy often ranges from many months to years in
Such illnesses are usually indistinguishable from bac-
duration, and in some patients, lifelong suppressive
terial or other infections without specific laboratory
therapy is needed to prevent relapses.
tests, such as fungal cultures or coccidioidal serologicaltesting. For such patients, symptoms—especially fatigueinterfering with normal activities—may last for weeksto many months. Approximately 5%–10% of infectionsresult in residual pulmonary sequelae, usually nodules
Received 12 July 2005; accepted 13 July 2005; electronically published 20
or peripheral thin-walled cavities. An even smaller pro-
These guidelines were developed and issued on behalf of the Infectious
portion of all infections result in illnesses related to
chronic pulmonary or extrapulmonary infection. For
Reprints or correspondence: Dr. John N. Galgiani, Valley Fever Center for
Excellence, 3601 S. 6th Ave., VA Med Ctr. and Univ. of Arizona, Tucson, AZ 85723
extrapulmonary complications, estimates range as low
as 0.5% of infections for persons of Caucasian ancestry,
Clinical Infectious Diseases 2005; 41:1217–23
several-fold higher for persons of African or Filipino
2005 by the Infectious Diseases Society of America. All rights reserved.
ancestry (possibly also for persons of Asian, Hispanic,
Treatment Guidelines for Coccidioidomycosis • CID 2005:41 (1 November) • 1217
or Native American ancestry), and as high as 30%–50% of
absorption is satisfactory. Cyclodextrin suspensions of itracon-
infections for heavily immunosuppressed patients, such as those
azole afford greater absorption, although published clinical tri-
with AIDS, lymphoma, receipt of a solid-organ transplant, or
als of itraconazole for the treatment of coccidioidomycosis have
receipt of rheumatologic therapies, such as high-dose corti-
not used this formulation. In general, the more rapidly pro-
costeroids or anti-TNF medications. Disseminated infections
gressing a coccidioidal infection, the more likely amphotericin
also appear to be more frequent in adults than in children.
B will be selected by most authorities for initial therapy. Con-
Although virtually any site in the body may be involved, ex-
versely, subacute or chronic presentations are more likely to be
trapulmonary dissemination most frequently involves the skin,
treated initially with an azole antifungal.
the skeletal system, and the meninges [3–6].
Newly available antifungal agents of possible benefit for the
The objective of this practice guideline is to pro-
treatment of refractory coccidioidal infections are voriconazole
vide recommendations for which patients with coccidioido-
and caspofungin. Voriconazole has not been approved by the
mycosis are likely to benefit from treatment and which therapies
United States Food and Drug Administration (FDA) for the
are most appropriate for various forms of infection.
treatment of coccidioidomycosis. Although there are no reports
of voriconazole therapy for experimental coccidioidal infec-
broad spectrum of illness. At one end of that spectrum, it may
tions, case reports have suggested that voriconazole may be
produce a mild respiratory syndrome or an uncomplicated
effective in selected patients [7–9]. Caspofungin has been ef-
community-acquired pneumonia, either of which may resolve
fective in treating experimental murine coccidioidomycosis
spontaneously. At the other end of that spectrum, infection
, but in vitro susceptibility of isolates varies widely ,
may result in progressive pulmonary destruction or lesions in
and there is only 1 report regarding its value . Posaconazole,
other parts of the body. Because severity varies widely, the
not yet approved by the FDA, was shown to be an effective
optimal management strategies also vary widely among indi-
treatment in a small clinical trial  and in patients with
vidual patients. Although the vast majority of patients who
refractory infections . Its efficacy relative to other triazole
present with early infections will resolve their infection without
specific antifungal therapy, management should routinely in-
Combination therapy with members of different classes of
clude repeated patient encounters every 3–6 months for up to
antifungal agents has not been evaluated in patients, and there
2 years, either to document radiographic resolution or to iden-
is a hypothetical risk of antagonism . However, some cli-
tify evidence of pulmonary or extrapulmonary complications
nicians feel that outcome in severe cases is improved when
as early as possible. Patients who present with severe pneu-
amphotericin B is combined with an azole antifungal. If the
monia soon after infection warrant antifungal therapy. Patients
patient improves, the dosage of amphotericin B can be slowly
who develop chronic pulmonary or disseminated disease also
decreased while the dosage of azole is maintained.
warrant antifungal therapy, which is typically prolonged—po-
Despite there being several antifungal therapies available for
tentially lifelong—especially in patients with overt immuno-
treatment of coccidioidomycosis, occasional patients have ex-
compromising conditions. Exact management guidelines for
ceptionally widespread, debilitating, and potentially life-threat-
these clinical forms will vary according to disease type and, to
ening complications, either at the time of first diagnosis or
an extent, must be individualized. For example, the role of
despite therapy. This is especially true for patients with coc-
surgical debridement, which, in some patients, is a critical com-
cidioidal meningitis. Because of the regional nature of coccid-
ponent of therapy, is not addressed in this guideline. However,
ioidomycosis, many of the clinicians most familiar with such
all patients with progressive or disseminated disease will require
problems practice in the southwestern regions of endemnicity.
some combination of periodic physical examinations, labora-
Occasionally seeking advice or obtaining a second opinion from
tory studies, and imaging studies to guide management
a specialist who is particularly familiar with coccidioidomycosis
may be of benefit in formulating a treatment plan that best fits
Specific antifungal drugs and their usual dosages for treat-
ment of coccidioidomycosis include amphotericin B deoxy-
Desired outcomes of treatment are resolution
cholate (0.5–1.5 mg/kg per day or alternate day administered
of signs and symptoms of infection, reduction of serum con-
intravenously), lipid formulations of amphotericin B (2.0–5.0
centrations of anticoccidioidal antibodies, and return of func-
mg/kg or greater per day administered intravenously), keto-
tion of involved organs. It would also be desirable to prevent
conazole (400 mg every day administered orally), fluconazole
relapse of illness on discontinuation of therapy, although cur-
(400–800 mg/day administered orally or intravenously), and
rent therapy is often unable to achieve this goal.
itraconazole (200 mg twice per day or 3 times per day admin-
Evidence to support recommendations.
istered orally). If itraconazole is used, measurement of itra-
ability of antifungal therapy, initial uncomplicated pulmonary
conazole concentration in serum samples may determine if
infections in the absence of comorbidity resolved in at least
1218 • CID 2005:41 (1 November) • Galgiani et al.
95% of patients. Randomized, prospective clinical trials of an-
available at considerably lower cost. For managing critically ill
tifungal drugs have not been completed to determine whether
patients with coccidioidomycosis, there are considerable ad-
drug therapy hastens the resolution of immediate symptoms
ditional costs, including intensive care support for many days
or prevents subsequent complications.
or weeks. In a recent Centers for Disease Control and Preven-
Published reports of intravenous amphotericin B treatment
tion (CDC) analysis, hospital costs in Arizona during 1998–
of chronic pulmonary or extrapulmonary nonmeningeal coc-
2001 were a mean of $33,762 per patient with coccidioido-
cidioidomycosis are limited to small numbers of patients treated
in open-label, nonrandomized studies . Coccidioidal men-
Below are descriptions of management strat-
ingitis treatment with intrathecal amphotericin B has been re-
egies for several manifestations of coccidioidomycosis. A re-
ported as the accumulated experience of individual investiga-
vision of the original Practice Guidelines for Coccidioidomy-
cosis  was circulated among the authors. Subsequently
The response of symptomatic chronic pulmonary and ex-
revised drafts were reviewed for comment by members of the
trapulmonary disseminated infections to several oral azole an-
Arizona Infectious Diseases Society (6–7 March 2004) and by
tifungal agents has been studied in large, multicentered, open-
health care professionals who attended the 48th Annual Coc-
label, nonrandomized trials by the Mycoses Study Group, as
cidioidomycosis Study Group Meeting (held on 3 April 2004).
well as by other investigators [17–26]. The majority of patients
The strength of and evidence for recommendations, expressed
in these studies were treated for periods ranging from months
using the Infectious Diseases Society of America–US Public
to years and exhibited decreased numbers of symptoms, im-
Health Service grading system for ranking recommendations
proved appearance of chest radiographs or extrapulmonary le-
in clinical guidelines (table 1), is shown following each specific
sions, decreased concentrations of complement fixing-type an-
tibodies in their serum or CSF samples, and sputum culturesthat converted from positive for Coccidioides species to negative. MANAGEMENT OF CLINICAL ENTITIES
Follow-up cultures of samples obtained from extrapulmonary
Primary Respiratory Infection
lesions often would have required invasive procedures and fre-
Primary infections due to Coccidioides species most frequently
quently were not carried out. Moreover, when therapy was
manifest as community-acquired pneumonia 1–3 weeks after
stopped, these abnormalities often recurred, suggesting that
exposure [30, 31]. Distinguishing coccidioidomycosis from
sterilization of lesions was not accomplished. A randomized
other etiologies is usually difficult without specific laboratory
trial of oral itraconazole (200 mg administered twice per day)
confirmation, such as detection of anticoccidioidal antibodies
versus oral fluconazole (400 mg administered every day) has
in serum samples  or identification of Coccidioides species
been published . In the primary analysis, there was no
in sputum samples or another respiratory specimen. Therefore,
difference between these 2 treatments when analyzed at the 8-
residents of and recent travelers to regions where community-
month time point. Subanalyses indicated that itraconazole ther-
acquired pneumonia is endemic should be evaluated for Coc-
apy may be more potent in the treatment of skeletal lesions
cidioides species as a possible etiologic agent. Coccidioides spe-
and superior when analyzed at 12 months overall.
cies are listed by the CDC as Select Agents, and their growth
Principal value is afforded to patients who receive
in culture requires handling in a secure and contained fashion
treatment. Coccidioidomycosis is not contagious by the respi-
ratory route and therefore control of individual infections will
Uncomplicated acute coccidioidal pneumonia.
not have additional public health benefit.
to manage primary respiratory coccidioidal infections is an
Benefits, harms, and costs.
unsettled issue because of the lack of prospective controlled
mycosis in itself may benefit a patient by (1) reducing the use
trails. For many (if not most) patients, management may rely
of unnecessary antibacterial therapies, (2) avoiding further di-
on periodic reassessment of symptoms and radiographic find-
agnostic evaluations, (3) allaying patient anxiety about an oth-
ings to assure resolution without antifungal treatment. On the
erwise uncertain respiratory condition, and (4) affording pa-
other hand, some authorities propose treatment of all symp-
tomatic patients to decrease the intensity or duration of symp-
treatment of complications will decrease the amount of tissue
toms. Although physicians speculate that early treatment may
destruction and resulting morbidity. Effective therapy is po-
decrease the frequency or severity of dissemination, there are
no data to support this speculation (C-III). Several special cir-
Use of amphotericin B often engenders untoward effects.
cumstances are usually considered to warrant initiation of ther-
Surgical risks depend on the specific procedure.
apy. Chief among these is concurrent immunosuppression, such
The cost of antifungal medication can be as high as $20,000
as that which accompanies AIDS, receipt of an organ transplant,
per year of treatment. Recently, generic fluconazole has become
therapy with high-dose corticosteroids, or receipt of inhibitors
Treatment Guidelines for Coccidioidomycosis • CID 2005:41 (1 November) • 1219 Infectious Diseases Society of America–US Public Health Service Grading System for ranking recommendations in clinical guidelines.
Good evidence to support a recommendation for use; should always be offered
Moderate evidence to support a recommendation for use; should generally be offered
Poor evidence to support a recommendation; optional
Moderate evidence to support a recommendation against use; should generally not be offered
Good evidence to support a recommendation against use; should never be offered
Evidence from у1 properly randomized, controlled trial
Evidence from у1 well-designed clinical trial, without randomization; from cohort or case-
controlled analytic studies (preferably from 11 center); from multiple time-series; or fromdramatic results from uncontrolled experiments
Evidence from opinions of respected authorities, based on clinical experience, descriptive
of TNF (such as etanercept or infleximab). Also, other patients
tablishing the nodule’s etiology at a future time. Identifying
who are likely to handle pulmonary coccidioidal infection less
dissemination is accomplished with histologic examination and
well include those with diabetes mellitus or preexisting cardio-
culture of suspicious skin lesions, analysis of aspirates of joint
pulmonary disease (A-II). The diagnosis of primary infection
effusions, and lumbar puncture of patients who develop pro-
during pregnancy, especially in the third trimester or imme-
gressively severe or persistent headaches, mental status changes,
diately postpartum, frequently prompts the initiation of treat-
or other meningeal signs. Although extrapulmonary dissemi-
ment (A-III). During pregnancy, amphotericin B is the treat-
nation is infrequent, early detection of patients in whom dis-
ment of choice because fluconazole (and likely other azole
semination does occur would afford benefit by earlier initiation
antifungals) are teratogenic (A-III). Persons of Filipino or Af-
of treatment and a resulting reduction in tissue destruction.
rican descent have a higher risk for dissemination, and this
may also be taken into consideration (B-III). Finally, patients
infiltrates produced by Coccidioides species suggest either an
who are judged to have exceptionally severe primary infections
underlying immunodeficiency state with concurrent fungemia
may be more likely to benefit from treatment than those pa-
or an exposure to a high inoculum of fungal spores, as may
tients with a more mild illness. Although opinion varies as to
occur as a result of laboratory accidents or at archeology sites.
the most-relevant factors for judging severity of illness, com-
In such patients, therapy is usually begun either with ampho-
monly used indicators include weight loss of 110%, intense
tericin B or high-dose fluconazole. Amphotericin B is more
night sweats persisting longer than 3 weeks, infiltrates involving
frequently used as initial therapy if significant hypoxia is present
more than one-half of one lung or portions of both lungs,
or if deterioration is rapid (A-III). Several weeks of therapy are
prominent or persistent hilar adenopathy, anticoccidiodial
often required to produce clear evidence of improvement. After
complement-fixing antibody concentrations in excess of 1:16
this time, during convalescence, amphotericin B therapy may
(as determined by a reference method or equivalent titer) ,
be discontinued and replaced with treatment with an oral azole
inability to work, symptoms that persist for 12 months, or age
antifungal (B-III). In combination, the total length of therapy
155 years. Commonly prescribed therapies include currently
should be at least 1 year, and for patients with severe immu-
available oral azole antifungal agents at dosages of 200–400 mg
nodeficiency, oral azole therapy should be continued as sec-
per day. Courses of typically recommended treatment range
ondary prophylaxis (A-III). Because diffuse pneumonia due to
Coccidioides species is usually a manifestation of fungemia, pa-
As the patient’s illness improves, either with or without an-
tients should be evaluated for the possibility of other extra-
tifungal therapy, continued monitoring at 1–3-month intervals
pulmonary lesions that may also require attention.
for 1 year or longer is advised to assess the resolution of pul-monary infiltrates and to identify, as early as possible, thosepatients who develop infection outside of the chest. Monitoring
Pulmonary Nodule, Asymptomatic
usually should include patient interviews, physical examina-
If a stable solitary nodule is determined to be due to Coccidioides
tions (as appropriate), serologic tests, and radiographic ex-
species by noninvasive means or by fine-needle aspiration, spe-
aminations. Determining pulmonary lesions that evolve into
cific antifungal therapy or resection is unnecessary (E-II). Sim-
residual nodules is useful because it obviates the need for es-
ilarly, in the absence of significant immunosuppression, anti-
1220 • CID 2005:41 (1 November) • Galgiani et al.
fungal therapy is not recommended if the lesion is completely
management approaches are less uniform and may include
resected and the diagnosis is determined from the excised tissue.
courses of therapy with amphotericin B or oral azole antifungal
Stability can be determined by repeated radiographic exami-
drugs prior to surgery or chest tube drainage without surgery
nation of the chest for 2 years demonstrating no change in the
size of the nodule. Should enlargement of the nodule occur,reevaluation with sputum cultures and measurement of coc-
Chronic Progressive Fibrocavitary Pneumonia
cidioidal serum antibodies may help to determine whether the
Initial treatment with oral azole antifungal agents is recom-
patient’s infection is active and warrants therapy. Consideration
mended (A-II). If the patient improves sufficiently, therapy
also should be given to the possibility of cancer coexistent with
should be continued for at least 1 year. If therapy is not sat-
the coccidioidal infection, in which case resection of the nodule
isfactory, switching to an alternative azole antifungal, raising
the dosage of the azole, or therapy with amphotericin B arealternative strategies (B-III). Surgical resection may be a useful
option for refractory lesions that are well localized or in cases
Many cavities caused by Coccidioides species
in which significant hemoptysis has occurred.
are benign in their course and do not require intervention. Such cavities may harbor viable fungus, and cultures of samples
Disseminated Infection (Extrapulmonary)
of sputum or other respiratory secretions commonly yield col-
Initial therapy is usually initiated with oral
onies of Coccidioides species. Many authorities do not consider
azole antifungal agents, most commonly fluconazole or itra-
these characteristics of asymptomatic cavities sufficient reason
conazole (A-II). Clinical trials have used 400 mg per day of
to initiate treatment. Moreover, in the absence of controlled
ketoconazole, itraconazole, or fluconazole. Some experts rec-
clinical trials, evidence is lacking that antifungal therapy has a
ommend higher dosages (up to 2000 mg per day of fluconazole;
salutary effect on the course of asymptomatic coccidioidal cav-
up to 800 mg per day of itraconazole, administered in 200-mg
ities (B-III). With the passage of time, some cavities disappear,
doses) (B-III). Amphotericin B is recommended for alternative
obviating the need for intervention. Although an indefinite
therapy, especially if lesions are appearing to worsen rapidly
follow-up period without intervention is appropriate for many
and are in particularly critical locations, such as the vertebral
patients, eventual resection from 1 to several years after the
column (B-III). Amphotericin B dosage is similar to that for
cavity is identified may be recommended to avoid future com-
diffuse coccidioidal pneumonia, although the duration of ther-
plications, especially if the cavity is still detectable after 2 years,
apy may be longer. In patients experiencing failure of conven-
if it demonstrates progressive enlargement, or if it is imme-
tional deoxycholate amphotericin B therapy or experiencing
diately adjacent to the pleura (B-III).
intolerable drug-related toxicities, lipid amphotericin B for-
Complications of coccidioidal cavities in-
mulations have been demonstrated to be safe and to cause less
clude local discomfort, superinfection with other fungi or pos-
nephrotoxicity and may be considered. Animal model studies
sibly bacteria, or hemoptysis. Should these complications occur,
have indicated that the higher amphotericin B dosages that can
oral therapy with azole antifungals may result in improvement,
be given via lipid formulations produce results superior to those
although recurrence of symptoms (at least in some patients)
seen with the maximally tolerated deoxycholate amphotericin
may occur on cessation of therapy. If a bacterial superinfection
B [35–37]. However, there have been no clinical trials assessing
is present, treatment for several weeks with an oral antibacterial
the efficacy of lipid formulations of amphotericin B.
may also reduce symptoms. However, such therapies usually
Combination therapy with amphotericin B and an azole has
do not result in the closure of the cavity. In cases in which the
been administered to some patients, especially when infection
surgical risks are not unusually high, resection of localized cav-
is widespread or in cases in which there has been disease pro-
ities is likely to resolve the problem and may be recommended
gression during treatment with a single agent. Although com-
as an alternative approach to chronic or intermittent therapy.
bination therapy may improve responses, there is no evidence
Rupture of a coccidioidal cavity into the pleural
that such an approach is superior to treatment with a single
space, resulting in a pyopneumothorax, is an infrequent but
agent, and for other fungal infections, there are examples of
serious complication of a necrotizing coccidioidal pneumonia
antagonism with combination therapy , as has been dem-
. In young, otherwise-healthy patients, surgical closure by
onstrated in vitro with Coccidioides species .
lobectomy with decortication is the preferred management (A-
Surgical debridement or stabilization is an occasionally im-
II). Antifungal therapy is recommended for treatment, partic-
portant, if not critical, adjunctive measure. Factors that favor
ularly in cases with delay of diagnosis and coexistent diseases
a recommendation for surgical intervention are large size of
(C-III). For patients in whom the diagnosis was delayed a week
abscesses, progressive enlargement of abscesses or destructive
or more or for patients in whom there are coexistent diseases,
lesions, presence of bony sequestrations, instability of the spine,
Treatment Guidelines for Coccidioidomycosis • CID 2005:41 (1 November) • 1221
or impingement on critical organs (such as a pericardial ef-
Management of Patients Infected with HIV-1
fusion on the heart) or tissues (such as an epidural abscess on
Before the introduction of HAART, coccidioidomycosis was a
major opportunistic infection in the area of endemicity among
Therapy with oral fluconazole is currently pre-
individuals infected with HIV-1 . The incidence of clinically
ferred by most clinicians. The dosage used in reported clinical
apparent coccidioidal infection has since decreased. Prevention
trials was 400 mg per day (A-II). Some physicians begin therapy
of coccidioidomycosis among HIV-1–infected patients living in
with 800 or 1000 mg per day of fluconazole (B-III). Itracon-
the area of coccidioidal endemicity by prophylactic use of an
azole, administered in dosages of 400–600 mg per day, has also
antifungal is not effective for most patients . Treatment is
been reported to be comparably effective  (B-II). Some
recommended for all patients with HIV-1 infection and pe-
physicians also initiate therapy with intrathecal amphotericin
ripheral blood CD4+ lymphocyte counts !250 cells/mL who have
B in addition to an azole on the basis of their belief that re-
clinically active coccidioidomycosis. Therapy should be con-
sponses are more prompt with this approach. The dose and
tinued as long as the CD4+ cell count is !250 cells/mL [45, 47].
duration of intrathecal amphotericin B in this circumstance
However, it may be reasonable to stop therapy in those patients
ranges between 0.1 mg and 1.5 mg per dose (C-III). Patients
with higher CD4+ cell counts if there is clinical evidence of
who respond to azole therapy should continue this treatment
control of the coccidioidal infection (except for patients with
indefinitely  (A-III). Hydrocephalus nearly always requires
meningitis, for whom therapy should be life-long).
a shunt for decompression (A-III). Hydrocephalus may developregardless of the therapy being used and need not require
switching to alternative therapy (B-III). Patients who do not
Supported in part by the US Office of Veterans
respond to fluconazole or itraconazole would be candidates for
intrathecal amphotericin B therapy with or without continu-
Potential conflicts of interest.
Schering and has lectured for Pfizer. J.N.G. has received research support
ation of azole treatment. The intrathecal dosage of amphoter-
or has been a consultant for Pfizer, Janssen, Merck, Schering, Enzon, and
icin B normally ranges between 0.1 mg and 1.5 mg per dose,
Lilly. R.H.J. has received grant support from Pfizer; is a member of the
administered at intervals ranging from daily to weekly, begin-
speakers’ bureaus for Sanofi-Aventis, Enzon, and Merck; and has been onthe speakers’ bureau of Bristol Myers-Squibb and Bayer. D.A.S. has received
ning at a low dosage and increasing the size of the dosage until
research support from and has been a consultant for Janssen, Ortho-
the appearance of patient intolerance (indicated by severe vom-
McNeil, Pfizer, Gilead, Enzon, and Schering. All other authors: no conflicts.
iting, prostration, or transient dose-related mental status) .
The most common life-threatening complication of cocci-
dioidal meningitis in the modern era is CNS vasculitis leading
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to cerebral ischemia, infarction, and hemorrhage . Some
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prophylaxis, whereby patients with certain risk factors for coc-
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thus far, the results are encouraging .
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