5 research outputs found
Epidemiology and management of invasive fungal infections in immunocompromised hosts
Fungal infections in man usually are divided into three categories based upon
their major pathophysiological characteristics: superficial and cutaneous, subcutaneous
and, systemic infections. The last category consists of two separate entities.
First there are the so called "endemic mycoses" caused by dimorphic fungi
including Coccidioides immiiis, Paracoccidioides brasiliensis, Histoplasma
capsula tum and Blastomyces dermatitidis which occur in patients who live in, or
have travelled through geographical regions in which these pathogenic fungi have
their habitat. Although the consequences of endemic mycoses are sometimes
very severe, these infections were not viewed as a very major subject in the field
of infectious diseases, probably due to their relatively rare and geographically
restricted occurrence. The second entity consists of opportunistic infections
caused by fungi that are ubiquitously present around the globe. The number of
these infections has increased dramatically during the last three decades. For
example, in 1966 invasive aspergillosis was called a disease of medical progress,
and world literature on this subject was reviewed in a paper only six pages in
length. In contrast in 1990, Denning et al. used 55 pages only to review the
literature on the treatment of such infections. Several factors have been recognized
to be responsible for this rapid increase, all of which are the consequence of
advances in medicine. The use of antibacterial agents, the use of cytotoxic
chemotherapy, organ transplantation combined with the use of immunosuppressive
therapy, the use of indwelling catheters all one way or the other,
compromise the defence mechanisms of the human host (Table 1 ) Some of
these factors disrupt more than one line of defence; for example, longterm use of
steroids, influences cellular immunity, macrophage function and neutrophil
function, whereas the integrity of the skin and mucous membranes is little
affected
Density and molecular epidemiology of Aspergillus in air and relationship to outbreaks of Aspergillus infection
After five patients were diagnosed with nosocomial invasive aspergillosis
caused by Aspergillus fumigatus and A. flavus, a 14-month surveillance
program for pathogenic and nonpathogenic fungal conidia in the air within
and outside the University Hospital in Rotterdam (The Netherlands) was
begun. A. fumigatus isolates obtained from the Department of Hematology
were studied for genetic relatedness by randomly amplified polymorphic DNA
(RAPD) analysis. This was repeated with A. fumigatus isolates
contaminating culture media in the microbiology laboratory. The density of
the conidia of nonpathogenic fungi in the outside air showed a seasonal
variation: higher densities were measured during the summer, while lower
densities were determined during the fall and winter. Hardly any variation
was found in the numbers of Aspergillus conidia. We found decreasing
numbers of conidia when comparing air from outside the hospital to that
inside the hospital and when comparing open areas within the hospital to
the closed department of hematology. The increase in the number of
patients with invasive aspergillosis could not be explained by an increase
in the number of Aspergillus conidia in the outside air. The short-term
presence of A. flavus can only be explained by the presence of a point
source, which was probably patient related. Genotyping A. fumigatus
isolates from the department of hematology showed that clonally related
isolates were persistently present for more than 1 year. Clinical isolates
of A. fumigatus obtained during the outbreak period were different from
these persistent clones. A. fumigatus isolates contaminating culture media
were all genotypically identical, indicating a causative point source.
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Liposomal amphotericin B (AmBisome) reduces dissemination of infection as compared with amphotericin B deoxycholate (Fungizone) in a rate model of pulmonary aspergillosis
The efficacy of AmBisome, a liposomal formulation of amphotericin B, was
compared with that of Fungizone (amphotericin B desoxycholate), in a rat
model of unilateral, pulmonary aspergillosis. Repeated administration of
cyclophosphamide resulted in persistent, severe granulocytopenia. The left
lung was inoculated with a conidial suspension of Aspergillus fumigatus,
thus establishing an unilateral infection. Antifungal treatment was
started 40 h after fungal inoculation, at which time mycelial disease was
confirmed by histological examination. Both Fungizone 1 mg/kg and AmBisome
10 mg/kg resulted in increased survival in terms of delayed as well as
reduced mortality. Quantitative cultures of lung tissue showed that only
AmBisome 10 mg/kg resulted in reduction of the number of fungal cfus in
the inoculated left lung. Compared with Fungizone, both AmBisome 1
mg/kg/day and AmBisome 10 mg/kg/day significantly prevented dissemination
from the infected left lung to the right lung. In addition, both AmBisome
regimens reduced hepatosplenic dissemination, and the 10 m/kg dosage fully
prevented this complication. In conclusion, when compared with Fungizone,
in this model AmBisome is more effective in reducing dissemination of
unilateral, pulmonary aspergillosis, even when given in relatively low
dosage. Such low dosages may have a place in prophylactic settings
Molecular epidemiology of apparent outbreak of invasive aspergillosis in ahematology ward
During a 2-month period, five patients suffering from invasive infections
caused by Aspergillus flavus or Aspergillus fumigatus were identif