,
Antimicrobials
for Eukaryal organisms
and fungal toxins
sections)
Table of contents :
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Generalities on fungal infections :
(severity is directly related to duration and severity of the neutropenia
: immunodeficiencies;
CGD;
acute
leukemias;
liver, kidney, heart or bone marrow transplant recipient, ...).
or papillomas that may or may not ulcerate; microscopically, the lesions
are characterized by round, brown bodies (sclerotic bodies) that reproduce
by equatorial splitting and not by budding. It is usually caused by
and meningitis
(cerebral phaeohyphomycosis), chromoblastomycosis
(subcutaneous phaeohyphomycosis)
and tinea nigra
/ cladosporiosis epidermica
.
ref
(ethmoiditis) with aspergilloma => blackish sputum
ref.
Important risk factors for IA are neutropenia and defects in the phagocyte
cell functionref.
On the other hand, there is an increasing body of evidence that adaptive
immune response also plays a critical role in the host defense against
Aspergillus
fumigatus, the most frequent cause of IA. For example, IA has been
reported with increasing frequency in patients with advanced
AIDSref,
and up to two-thirds of patients with IA diagnosed after allogeneic SCT
are not neutropenicref.
In contrast to neutrophil recovery, which generally occurs within the first
2 to 3 weeks after SCT, the number of functional T cells and T-cell function
increase slowly over the first few months after transplantationref.
Prolonged immune suppression due either to transplant conditioning and
GvHD prophylaxis or to treatment of GVHD further increase the risk of IA
in SCT patientsref1,
ref2.
It has recently been shown that a significant antigen-specific proliferation
of IFN-g-producing T cells occurred in healthy
individuals and in patients surviving IAref,
which confirms the crucial role of a Th1 reactivity in the control
of infectionref1,
ref2,
ref3
/tazobactamref1,
ref2,
ref3
,
otitis
media,
primary cutaneous infection, endocarditis,
pneumonia,
and disseminated infection, the latter cases occurring largely among immunocompromised
hosts such as HSCT recipients. All previously reported cases occurred sporadically
in diverse medical centers. Infections caused by A. ustus may be
of particular concern, as the organisms exhibit low susceptibility to multiple
antifungal drugs, and outcomes have been uniformly poor. 3 infections each
occurred in HSCT
patients in both 2001 and 2003 at the Fred Hutchinson Cancer Research Centerref
and endophthalmitis;
fungemia
in patients with indwelling vascular catheter
in bear (a dermatophytia). Hypersensitivity => distant blisters.
(Hebra marginated eczema, a dermatophytia)..
Hypersensitivity => distant blisters.
(ectothrix
in hair, a dermatophytia). Hypersensitivity => distant blisters. After
puberty long chain fatty acids in sebum are fungicides.
(ectothrix
in hair) with kerion celsi
(inflammatory reaction). Hypersensitivity => distant blisters.
(in Malaysia, Pacific and Far Eastern countries, and parts of Central and
South America)
.
Hypersensitivity => distant blisters.
(a suppurative trichophytia on head)
(a suppurative trichophytia on bear)
(Hebra marginated eczema) (a hyperkeratotic form of athlete's
foot, a dermatophytia). Hypersensitivity => distant blisters. Hypersensitivity
=> distant blisters..
Hypersensitivity => distant blisters.
(a dermatophytia)..
Hypersensitivity => distant blisters. Sometimes lethal brain
abscesses.
(a suppurative trichophytia on head)
(a suppurative trichophytia on bear)
(a suppurative trichophytia on head)
(a suppurative trichophytia on bear)
,
lymphadenitis,
abscesses, ulcers, acneiform papules,
septic
arhritis.
,
generally acute self-limiting, rarely evolving to chronic histoplasmoma
with satellite lymphadenitis
and ulcers of respiratory and digerent mucosae (=> diarrhea);
related to spelunking (potholing); ocular
histoplasmosis syndrome (OHS),
endophthalmitis
polarization results in formation of granulomas, which is usually succesful
at limiting the infection and preventing serious, disseminated disease
: while the initial infection is contained, it does persist in the host
in a dormant state within calcified granulomas and is capable of causing
disease by reactivation if immunological dysfunction develops.
for anti-Histoplasma antibody detection are widely applied; sensitivity
rates are 95-100% and 82-90% for pulmonary and disseminated histoplasmosis,
respectively. Some limitations occur, including the need for 2 to 6 weeks
for antibody production after infection, impaired production of antibodies
in immunosuppressed patients, and presence of cross-reaction mainly due
to paracoccidioidomycosis, blastomycosis, and aspergillosisref.
initially, itraconazole
or fluconazole
are used for maintenance therapy.
production.
),
subcutaneous tissues, liver, spleen, and kidneys
or amphotericin B.
.,
pleurodynia,
weight loss, headache,
malaise),
sometimes with pneumonia,
cavitation or recovery with sclerosis, and occasionally erythema
nodosum
or erythema
multiforme
(bumps). In 10% coccidioidomas and cavitary chronic coccidiomycosis
occur),
CNS, and lungs, with anemia, phlebitis, and a variety of allergic responses.
It may be either a new infection or a reactivation of arrested primary
disease, such as in immunocompromised patients. Ocular coccidiomycosis
: the anterior segment manifestations appear to be a mild hypersensitivity
response; the disease may present as a chronic granulomatous iridocyclitis.
In the posterior eye, the manifestations may range from asymptomatic focal
chorioretinitis
(somewhat similar to the peripheral atrophic lesions of the ocular
histoplasmosis syndrome (OHS))
to a fulminating granulomatous process involving the entire eye. The ocular
lesions can occur in the asymptomatic form of systemic coccidioidomycosis.
Diagnosis may be confirmed by skin tests and serologic tests.
or fluconazole
or itraconazole
infection may increase the susceptibility to infection with L. loboiref.
which have the histologic appearance of a keloid. Lesion progression is
slow, with new lesions arising by contiguity with other lesions or through
the lymphatic routeref1,
ref2.
Clinically, lacaziosis manifests as keloidal lesions of solid consistency
and variable size that contain small scales and crustsref.
The lesions are most frequently located in the auricle and on the upper
and lower limbs. Cutaneous dissemination of the disease is observed in
a relatively small number of cases
,
pulmonary symptoms, and cachexia may occur. An hypersensitivity
state has been demonstrated in asymptomatic individuals. Males/females
30:1. Paracoccidioidomycosis is rare in HIV-infected patients, perhaps
in part because of the use of trimethoprim–sulfamethoxazole as prophylaxis
for pneumocystis infectionref
unless the illness is serious enough for hospitalization, in which case,
IV amphotericin B
is given, followed by itraconazole.
and respiratory irritation
,
sinusitis, cellulitis, endophthalmos
,
eye
infections
tend to remain local and have a better outcome than those that develop
in patients with hematological malignancies and HSCT
patients
(involvement of the cornea) and, less commonly, endophthalmitis (involvement
of the inner part of the eye). Other infections associated with this mold
include those of nail, skin, lung, heart valve, peritoneum, joint, and
central venous catheter. Disseminated infections with or without fungemia
due to
Fusarium spp. have been reported in immunoincompetent hosts
primarily. 39 cases of Fusarium keratitis occurred in Singapore
from May 2005 to January 2006 because of contamination of disposable Bausch
and Lomb's ReNu soft contact lenses, which were cleaned and stored with
multi-purpose contact lens solution : 3 patients had to undergo urgent
corneal transplantationref1,
ref2.
130 confirmed cases in USA since 1 Jun 2005 to 18 May 2006 : cases have
been reported from 26 states and one territory.* Patients had a median
age of 41 years (range: 12-83 years), and 85 of 127 (67%) were female.
As a result of this infection, corneal transplantation was required in
37 of 120 (31%) cases. Among the 130 patients with confirmed cases, 125
reported wearing contact lenses, and 118 were able to identify which contact
lens solution(s) they had used during the month before onset of infection.
75 (64% reported using Bausch & Lomb's ReNu with MoistureLoc alone,
14 (12%) reported using MoistureLoc in combination with another product,
8 (7%) reported using an unspecified Bausch & Lomb solution, and 21
(18%) reported using only products other than MoistureLoc, from various
manufacturersref1,
ref2.
21 patients, including 12 soft-lens wearers (29 millions in USA) have been
infected in South Florida since January to March 2006 (typically 21 per
year, virtually all among patients with eye trauma that lets the fungus
penetrate the cornea. The fungus is common in soil and plants in tropical
regions like South Florida : wearers should clean their lenses well and
not wear them while sleeping, even those models approved for overnight
use. 3 cases were reported in the New York metropolitan area and eye specialists
in Tampa, Atlanta, Texas and California also had casesref1,
ref2,
ref3.
In USA the annual incidence of microbial keratitis is estimated to be 4-21
per 10 000 soft contact lens users, depending on whether users wear lenses
overnightref.
Fungal keratitis is a condition more prevalent in warm climates; in the
southernmost USA, up to 35% of microbial keratitis cases are fungal keratitis,
compared with one percent in New Yorkref1,
ref2.
The proportion of fungal keratitis attributable to Fusarium spp.
also varies by region, from 25% to 62%ref1,
ref2,
ref3.
Alexidine
is an antiseptic in the biguanide family that has bactericidal propertiesref.
Fusarium
keratitis is not transmitted from person to person. It is safe and effective,
but under certain extreme conditions -- such as when the solution is allowed
to evaporate, the solution is not regularly replaced in the lens case,
when the bottle is kept open in between uses or when the case is not cleaned
properly or changed regularly -- the concentration of polymers included
in the formula to enhance comfort may make the solution more likely to
be contaminated with Fusarium in the environment
ref
(20% require corneal allograft)
ref
.
Itraconazole
and terbinafine
has offered synergy against various moulds including S. prolificans.
In
vivo success is reported with the azole (itraconazole or voriconazole)/terbinafine
combination in S. apiospermum pulmonary infection and Pythium
insidiosum periorbital cellulitis
scratch or bite; puncture wounds caused by barberry thorns (he disease
should be suspected in all persons with subcutaneous lesions who handle
thorny plants, timber or sphagnum moss)
)
and musculoskeletal tissues, viscera, mucous membranes, CNS, eye, or genitourinary
system;
an hypersensitivity state to sporotrichin, an experimental antigen
derived from the organism, has been demonstrated in some asymptomatic individuals.
It produces dermatitis in workers who strip the stalks
,
a superficial phaeohyphomycosis
and kidney abscess => acute
renal failure;
endophtalmitis,
meningitis.
Diarrhea
after broad-spectrum antimicrobial chemotherapy. Oidomycin, an extra