Also read
Fungal-Disease-Treatment
Medical Infection Therapies
[very important article]
New Advances in the Epidemiology and Management of Mold Infections in
Immunocompromised Patients
Elias Anaissie, MD Tahsine H. Mahfouz, MD, on medscape.com
Introduction
With the important advances in the management of bacterial and viral
infections in immunocompromised patients, we have seen an emergence of
invasive mycoses caused by pathogenic molds. These infections contribute in
a significant way to the adverse outcomes observed in some of these patients
and represent a diagnostic and therapeutic challenge for clinicians caring
for them. Fortunately, several recent advances in the epidemiology,
prevention, early diagnosis, and therapy of the opportunistic mold
infections have been presented at this year's ICAAC meeting.
Epidemiology
In a study of invasive fungal infections in hematopoietic and solid organ
transplant recipients, invasive mold infections -- particularly
aspergillosis -- accounted for almost half of the cases of fungal
infections, followed by candidiasis (~40%) and other infections (~10% each:
cryptococcosis, endemic mycoses, other yeasts, and pneumocystosis).
Aspergillosis predominated in the hematopoietic stem cell transplant (HSCT)
population (~70% of all fungal infections). The overall 3-month mortality
rate of patients with mold infections was 60% and significantly higher among
recipients of HSCTs (68% vs 29% for solid organ transplant recipients).[1]
Two studies described a high rate of dissemination and death associated
with invasive aspergillosis among liver, lung, and heart transplant
recipients.[2,3] The
authors identified several risk factors for mortality, including
dissemination, mechanical ventilation, need for blood transfusion,[2]
posttransplant dialysis, reoperation, concomitant viral infection, and
exposure to another case of aspergillosis in the same unit.[3] Antifungal use was associated with improved survival.[2,3]
The risk factors for invasive aspergillosis were evaluated in a large
population of allogeneic stem cell transplant recipients. Risk factors for
early infection (< 40 days) were older age, myelodysplastic syndrome, and
nonmyeloablative conditioning regimen with fludarabine and campath-containing
regimens; whereas graft vs host disease, use of steroids, or campath
represented important risk factors for late infection (> 90 days). Both
early and late aspergillosis infections were associated with high mortality
(~70%).[4]
Diagnosis
Early diagnosis of mold infections has long been a challenge for
clinicians caring for highly immunocompromised patients. Several new
diagnostic modalities have been described in the past few years. However,
agreement on the interpretation of the results of these tests remained
elusive. At this year's ICAAC, several important presentations focused on
new diagnostic methods and their reproducibility among centers.
Systematic chest computed tomography (CT) scan has been known to allow
the early diagnosis of aspergillosis in high-risk neutropenic cancer
patients, resulting in a positive impact on survival. A large study of
systematic chest CT scans (baseline and regular follow-up) in 235 patients
with aspergillosis was presented. Pulmonary findings included the presence
of nodules (96%) that were associated with a halo sign (61 %) or the air
crescent sign (39%). Among patients with hematologic cancers, the halo sign
was more frequently observed among neutropenic patients (82%) than among
those with adequate neutrophil counts (~50%). The lowest rate of a halo sign
was seen in patients without an underlying hematologic condition (~25%). The
halo sign associated with nodules was an early and transient finding but
quite useful as a tool of the early diagnosis of invasive pulmonary
aspergillosis.[5]
Investigators described their results with a new diagnostic test, the
Glucatell assay, which detects circulating (1  3)-beta-D-Glucan.
The study was conducted at various centers and included 163 patients with
fungal infections and 170 healthy controls. The test was found to have high
sensitivity; specificity; positive and negative predictive value for
aspergillosis, candidiasis, and fusariosis; and was highly reproducible
among centers.[6,7]
Infections with non- or low-beta-D-Glucan-producing species, such as the
zygomycetes and Cryptococci, were unlikely to be detected.
Detection of circulating galactomannan (GM) antigen was found to be a
useful diagnostic test for aspergillosis[8]
in a study of patients with hematologic cancers but was plagued by poor
sensitivity among lung transplant recipients.[9]
False-positive results were also observed with the use of piperacillin/tazobactam
and amoxicillin/clavulanate.[10,11]
Decreased sensitivity was shown in children, and may also occur in patients
with circulating aspergillus antibodies and those receiving antifungal
agents active against Aspergillus species . The cut-off point for true
positive GM ranges from 0.5-1.5, though a consensus may be emerging for a
0.5-0.7 cut-off point for positivity. The detection of GM in the
bronchoalveolar lavage (BAL) of animals with pulmonary aspergillosis was
shown to be highly sensitive and specific for this infection and correlated
well with circulating GM levels and response to antifungal therapy.[12]
Nested polymerase chain reaction (PCR) was evaluated in 2 studies and
found to be a promising and reproducible diagnostic test for aspergillosis.[8,13]
The high-pressure liquid chromatography (HPLC) detection of gliotoxin in
lungs of mice with aspergillosis was found to correlate with tissue fungal
burden, and gliotoxin was also detected in the serum of patients with
aspergillosis.[14]
Therapy
Therapy of mold infections remains a challenge for clinicians caring for
high-risk immunosuppressed patients. In this meeting, several reports
suggested an improved outcome with novel therapies.
Primary Therapy for Established Infection
An open-label study of voriconazole in HIV-positive patients with
invasive Penicillium marneffei infection concluded that the drug was
effective and well tolerated for the treatment of systemic infections due to
. marneffei.[15] In
a small study, high-dose (10 mg/kg/day) liposomal amphotericin B (AmBisome,
LAmB) was associated with a high response rate as primary therapy for
aspergillosis in immunocompromised patients and was well tolerated.[16]
In a diabetic murine model of mucormycosis (Rhizoctonia oryzae),
caspofungin appeared to be as effective as amphotericin B (AmB) in
prolonging survival, but neither agent reduced fungal burden.[17] However, prophylaxis with either agent significantly
reduced R oryzae fungal burden in brain and, to a lesser extent, in
kidneys.
Combination Therapy for Established Infection
Combination therapy of lipid AmB (LAmB or amphotericin B lipid complex [ABLC])
and an echinocandin (caspofungin or micafungin) was evaluated in a
retrospective study of aspergillosis in immunocompromised patients.[18]
Thirty-five patients with invasive aspergillosis received combination
therapy (n = 22) or monotherapy (n = 13). Severe toxicity was not observed
in either treatment group and mortality was higher in the monotherapy group;
however, this difference was not significant. A combination of posaconazole
and caspofungin was tested in a murine model of aspergillosis and found to
result in greater survival than therapy with each agent alone.[19]
Caspofungin and LAmB improved the survival and fungal burden of mice with
disseminated Scedosporium infection, and the combination was more
effective than either agent alone. LAmB appeared to be the most effective of
the two.[20]
In a murine model of disseminated Scedosporium prolificans
infection, posaconazole decreased the liver but not the brain fungal burden,
while granulocyte-macrophage colony-stimulating factor decreased the fungal
burden in brain and liver. The combination of both agents did not improve
outcome.[21]
Salvage Therapy
Successful salvage therapy of mold infections in immunocompromised
patients was reported with voriconazole and posaconazole.
Voriconazole. One study of 87 patients with Aspergillus terreus
infections suggested that receipt of voriconazole within 1 week of diagnosis
of aspergillosis was associated with decreased mortality compared with
amphotericin B therapy.[22]
A 34% response rate to voriconazole was observed in a study of 86 patients
with central nervous system aspergillosis (13 of these patients received
voriconazole as primary therapy). The drug was well tolerated, with only 7
patients discontinuing therapy as a result of a drug-related adverse event.[23]
Nineteen patients with aspergillus osteomyelitis were treated with
voriconazole with a 52% response rate.[24]
Posaconazole. An open-label study of posaconazole (400 mg twice
daily) for patients with localized zygomycosis enrolled 24 patients who were
refractory to or intolerant of conventional antifungal agents. The overall
success rate was an impressive 70%, and the drug was well tolerated.[25]
Additional information on concomitant therapies (eg, surgery, correction of
diabetic acidosis) and the immune status of the host would help us better
appreciate the role of this potentially important agent.
Five of 15 patients with refractory mold infections responded to
posaconazole,[26] and a
high response rate of 40% was observed in patients with brain abscesses due
to filamentous fungi treated with this agent.[27]
Empiric therapy. A randomized study compared caspofungin (CAS) (70
mg; then 50 mg/day) in 556 patients to LAmB (3 mg/kg/day) in 539 patients
for empiric antifungal therapy of persistently febrile neutropenic patients
with hematologic malignancy.[28]
Successful outcome was defined as survival to 7 days posttreatment,
successful outcome of baseline invasive fungal infections (IFI), no
breakthrough IFI to 7 days posttreatment , no premature discontinuation due
to lack of efficacy or study drug toxicity, and fever resolution during
neutropenia. Caspofungin was equivalent to LAmB in terms of overall success
(33.9 vs 33.7%) but was better tolerated. A surprisingly high rate (35%) of
infusion-related toxicity with caspofungin was reported.
A systematic review that evaluated outcome in 2331 patients treated with
LAmB formulations for fever and neutropenia concluded that LAmB and
voriconazole constituted appropriate therapy for prolonged fever and
neutropenia.[29]
Prophylaxis
A randomized study compared intravenous itraconazole (200 mg every 12
hours for 2 days, then 200 mg IV/day; n = 86) to caspofungin (50 mg IV/day,
n = 106 ) for prophylaxis in patients with hematologic malignancies
undergoing induction chemotherapy.[30]
Eleven patients developed IFI; 5 on itraconazole (3 candidemia and 2
pulmonary aspergillosis) and 8 on caspofungin (3 pulmonary aspergillosis, 1
curvularia pneumonia, 1 candidemia, 1 trichosporon fungemia, and 2
cellulitis [1 fusarium ,1 trichosporon]). Reversible grade >/= 3
hyperbilirubinemia (5% per arm) was the most frequent adverse event observed
with both agents. Induction mortality and survival rates were similar.
In a pilot study of 12 allogeneic HSCT recipients, long-term (120-360
days) itraconazole prophylaxis was effective at preventing fungal
infections.[31] No
breakthrough IFIs occurred within 12 weeks of end of therapy, and no
significant toxicities attributable to itraconazole were noted.
A meta-analysis of antifungal prophylaxis in 1254 solid organ transplant
recipients[32] showed that
fluconazole reduced early proven IFIs, proven/possible IFIs, and fungal
colonization, but not mortality.
New Antifungal Agents, Drug Delivery, and Pharmacodynamics
The efficacy of allicin, the reactive molecule of garlic, showed in vitro
and in vivo activity against Aspergillus species.[33]
Good minimum inhibitory concentrations and minimal fungicidal concentrations
were observed against 32 strains of Aspergillus spp, and allicin
therapy significantly prolonged survival of infected mice without serious
toxicity.
GL48656, a novel heterocyclic antifungal compound, was shown to be safe
and to have fungicidal activity against molds, including Aspergillus
fumigatus in vitro and in a murine model of aspergillosis.[34,35]
The efficacy of nebulized vs IV LAmB and IV AmB was evaluated in a rat
model of pulmonary aspergillosis.[36]
Lung weight and chitin quantification were used as efficacy parameters in
animals treated > 5 days. Nebulized LAmB was more effective than IV LAmB or
AmB.
A 3-fold increase of posaconazole AUC was observed when normal volunteers
were given nutritional supplement (boost plus).[37]
A study of the various AmB formulations indicated that ABLC had the
highest accumulation in lung tissue and pulmonary alveolar macrophages,
whereas LAmB achieved the highest concentrations in epithelial lining fluid
of the lungs and in serum.[38]
A study evaluated the in vivo pharmacokinetics and pharmacodynamics of
AmB, LAmB, and ABLC in a murine model of disseminated candidiasis. The
highest drug concentration in the serum was achieved with LAmB, while ABLC
resulted in the highest drug levels in lung tissues.[39]
The in vivo potency of AmB was the highest in all infected organs.
In conclusion, the recent availability of reliable diagnostic tests and
antifungal agents with excellent activity and a good safety profile promises
to have an important impact on the morbidity and mortality of invasive mold
infections.
References
1.
Pappas PG, Morgan J, Hajjeh RA. Prospective surveillance for
invasive fungal infections (IFIs) in hematopoietic stem cell (HSCTs) and
solid organ transplant recipients (SOTs) in the United States.
Program and abstracts of the 43rd Interscience Conference on Antimicrobial
Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-1010.
2.
Len O, Gavalda J, San Juan R, et al. Invasive aspergillosis (IA) in
solid organ transplant (SOT) recipients. Risk factors (RF) of death. Program
and abstracts of the 43rd Interscience Conference on Antimicrobial Agents
and Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract M-999.
3.
Munoz P, Rodriguez C, Palomo J, et al. Risk factors for invasive
aspergillosis (IA) after heart transplantation (HT): protective role of oral
itraconazole. Program and abstracts of the 43rd Interscience Conference on
Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago,
Illinois. Abstract K-1376.
4.
Almyroudis N, Jaffe D, Sepkowitz KA, et al. Risk factors for late
invasive aspergillosis (IA) after allogeneic stem cell transplantation.
Program and abstracts of the 43rd Interscience Conference on Antimicrobial
Agents and Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract M-1006.
5.
Herbrecht R. Erly diagnosis: CT, antigen, or PCR? Program and
abstracts of the 43rd Interscience Conference on Antimicrobial Agents and
Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract 1328.
6.
Ostrosky-Zeichner L, Alexander B, Kett D, et al. Multicenter
Clinical Evaluation of the (1--3) B-D-Glucan (BG) assay (Glucatell™) as an
aid to diagnosis of invasive fungal infections (IFI) in humans. Program and
abstracts of the 43rd Interscience Conference on Antimicrobial Agents and
Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract M-1034a.
7.
Odabasi Z, Mattiuzzi G, Estey E, H K, Rex JH, Ostrosky-Zeichner L.
(1-3)-B -D-Glucan (BG) for the diagnosis of invasive fungal infections (IFI)
in leukemia patients on antifungal prophylaxis. Program and abstracts of the
43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-1028
8.
Morrissey
CO, Halliday C, Chen S, Slavin M, Wesselingh S, Sorrell T. Comparison of the
sensitivity and specificity of Aspergillus galactomannan (GM) sandwich ELISA
and a nested Aspergillus PCR assay for the diagnosis of invasive
aspergillosis (IA). Program and abstracts of the 43rd Interscience
Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003;
Chicago, Illinois. Abstract M-1019.
9.
Husain S, Kwak EJ, Mclaughlin L, et al. Prospective assessment of
Platelia®TM Aspergillus galactomannan (GM) EIA antigen for the diagnosis of
invasive aspergillosis (IA) in lung transplant recipients. Program and
abstracts of the 43rd Interscience Conference on Antimicrobial Agents and
Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-1020.
10.
Sulahian A, Touratier S, Leblanc T, Rousselot P, Derouin F, Ribaud
P. False positive Aspergillus antigenemia related to concomitant
administration of tazocillin. Program and abstracts of the 43rd Interscience
Conference on Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago,
Illinois. Abstract M-2062a.
11.
Viscoli C, Machetti M, Cappallano P, Bucci B, Bruzzi P, Bacigalupo
A. False-Positive Platelia Aspergillus (PA) Test in Patients (pts) Receiving
Piperacillin-Tazobactam (P/T). Program and abstracts of the 43rd
Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-2062b.
12.
Petraitiene R, Petraitis V, Kelaher AM, et al. Expression of
galactomannan antigen in bronchoalveolar lavage fluid of experimental
invasive pulmonary aspergillosis in persistently neutropenic rabbits.
Program and abstracts of the 43rd Interscience Conference on Antimicrobial
Agents and Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract M-370.
13.
Morrissey
CO, Halliday C, Chen S, Slavin M, Wesselingh S, Sorrell T. The intra- and
interlaboratory reproducibility of a nested Aspergillus PCR assay for the
diagnosis of invasive aspergillosis (IA) in immunocompromised haematology
patients. Program and abstracts of the 43rd Interscience Conference on
Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-1018.
14.
Lewis RE, Chi J, Wiederhold NP, Kontoyannis DP, Han X, Prince RA.
Detection of gliotoxin, an immunologically-active metabolite secreted by
Aspergillus fumigatus, in animals and humans with invasive aspergillosis
(IA). Program and abstracts of the 43rd Interscience Conference on
Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract M-1015.
15.
Schlamm HT, Supparatinyo K. Voriconazole as therapy for systemic
infections caused by Penicillium marneffei in patients with HIV
infection. Program and abstracts of the 43rd Interscience Conference on
Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago,
Illinois. Abstract M-963.
16.
Ruiz I, Olive T, Gavalda J, et al. High doses of Ambisome in the
treatment of invasive aspergillosis (IA). Program and abstracts of the 43rd
Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-966.
17.
Ibrahim
AS, Bowman JC, Avanssian V, Douglas CM, Edwards Jr JE. Efficacy of caspofungin
acetate (CAS) in a diabetic murine model of induced mucormycosis. Program
and abstracts of the 43rd Interscience Conference on Antimicrobial Agents
and Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract M-371.
18.
O'Connor CM, Hilts A, Barron M, Mcsweeney P, Zeng C, Baron A.
Clinical experience of monotherapy vs combination antifungal therapy for the
treatment of invasive aspergillus (IA) in patients (Pts) with a hematologic
malignancy (HM), solid organ transplant (SOT), or hematopoietic stem cell
transplant (HSCT). Program and abstracts of the 43rd Interscience Conference
on Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago,
Illinois. Abstract M-997.
19.
Sabatelli F. In vitro and in vivo interaction of posaconazole (POS)
and caspofungin (CSP) against Aspergillus. Program and abstracts of the 43rd
Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-990.
20.
Bocanegra R, Najvar LK, Hernandez S, Graybill JR. Novel antifungal
agents in murine scedosporiosis. Program and abstracts of the 43rd
Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-368.
21.
Simitsopoulou M, Gil-Lamaignere C, Avramidis N, et al. Activity of
posaconazole (POS) and granulocyte-macrophage colony-stimulating factor (GM-CSF)
in a murine model of invasive infection due to Scedosporium
prolificans. Program and abstracts of the 43rd Interscience Conference
on Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract M-364.
22.
Steinbach WJ, Benjamin Jr DK, Kontoyannis DP, et al. Invasive
aspergillosis (IA) caused by Aspergillus terreus: Multicenter
retrospective analysis of 87 cases. Program and abstracts of the 43rd
Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M 1753.
23.
Troke PF, Schwartz S, Ruhnke M, et al. Voriconazole (VRC) therapy
(Rx) in 86 patients (pts) with CNS aspergillosis (CNSA): a retrospective
analysis. Program and abstracts of the 43rd Interscience Conference on
Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago,
Illinois. Abstract M-1755.
24.
Lortholary O, Mouas-Dupuy H, Dupont B, Lustar I, Fain O.
Voriconazole (VCZ) for bone aspergillosis (BA): a worldwide experience of 19
cases. Program and abstracts of the 43rd Interscience Conference on
Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago,
Illinois. Abstract M-979.
25.
Greenberg N, Anstead G, Herbrecht R, et al. Posaconazole (POS)
experience in the treatment of zygomycosis. Program and abstracts of the
43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-1757.
26.
Ullmann AJ, Cornely OA, Burchardt A, et al. Safety and efficacy of
posaconazole (POS) in a pharmacokinetic study in patients with febrile
neutropenia (FN) or refractory invasive fungal infections (rIFI). Program
and abstracts of the 43rd Interscience Conference on Antimicrobial Agents
and Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract M-1257.
27.
Pitisuttithium P, Gaona-Flores V, Negroni R, et al. Efficacy of
posaconazole (POS) in treatment of central nervous system (CNS) fungal
infections: results of an open-label study. Program and abstracts of the
43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-978.
28.
Walsh TJ, Sable C, Depauw B, et al. A randomized, double-blind,
multicenter trial of caspofungin (CAS) vs liposomal amphotericin B (LAMB)
for empirical antifungal therapy (EAFRx) of persistently febrile neutropenic
(PFN) patients (Pt). Program and abstracts of the 43rd Interscience
Conference on Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago,
Illinois. Abstract M-1761.
29.
Frothingham R. Systematic review of outcome measures in 2331
patients enrolled in randomized controlled trials of lipid amphotericin B
formulations for fever and neutropenia. Program and abstracts of the 43rd
Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-975.
30.
Mattiuzzi G, Kantarjian H, Alvarado G, et al. Intravenous
itraconazole (ITRA) vs caspofungin (CASPO) prophylaxis (P) in patients (PTS)
with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS)
undergoing induction chemotherapy (IC). Program and abstracts of the 43rd
Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-984.
31.
Segal BH, Proefrock A, Balli D, et al. A pilot study of antifungal
prophylaxis with itraconazole (ITRA) in allogeneic hematopoietic transplant
(Allo-HSCT) recipients after neutrophil recovery. Program and abstracts of
the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-974.
32.
Playford EG, Webster AC, Craig JC, Sorrell T. Antifungal
prophylaxis in solid organ transplant recipients: a meta-analysis. Program
and abstracts of the 43rd Interscience Conference on Antimicrobial Agents
and Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract M-968.
33.
Osherov N, Shemesh E, Mirelman D, et al. Efficacy of allicin, the
reactive molecule of garlic, in inhibiting Aspergillus spp. in vitro, and in
a murine model of disseminated aspergillosis. Program and abstracts of the
43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-960.
34.
Velligan MD, Congpachith A, Hancock C, et al. GL48656: a novel
antifungal compound demonstrates fungicidal activity against Aspergillus
fumigatus. Program and abstracts of the 43rd Interscience Conference on
Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago,
Illinois. Abstract F-1231.
35.
Velligan MD, Singh G, Clemons KV, et al. GL48656: a novel
fungicidal compound efficacious in a murine model of systemic aspergillosis.
Program and abstracts of the 43rd Interscience Conference on Antimicrobial
Agents and Chemotherapy; September
14-17, 2003; Chicago, Illinois. Abstract F-1232.
36.
Gavalda J, Lopez P, Martin M, et al. Efficacy of nebulized
liposomal amphotericin B (N-LAb) in the treatment of experimental pulmonary
aspergillosis (EPA). Program and abstracts of the 43rd Interscience
Conference on Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago,
Illinois. Abstract M-356.
37.
Courtney R, Sansone A, Calzetta A, Martinho M, Laughlin M. The
effect of a nutritional supplement (Boost Plus) on the oral bioavailability
of posaconazole. Program and abstracts of the 43rd Interscience Conference
on Antimicrobial Agents and Chemotherapy; September
14-17, 2003; Chicago,
Illinois. Abstract A-1604.
38.
Groll AH, Lyan CA, Petraitis
V, et al. Compartmentalized intrapulmonary concentrations of four licensed
amphotericin B formulations in noninfected rabbits. Program and abstracts of
the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago,
Illinois. Abstract M-359.
39.
Andes NS, Marchillo K, Conklin R. In vivo pharmacokinetic (PK)
and pharmacodynamic (PD) comparison of amphotericin B (AmB), liposomal
amphotericin (L-AmB), and ABLC in various organs against C. albicans.
Program and abstracts of the 43rd Interscience Conference on Antimicrobial
Agents and Chemotherapy. September 14-17, 2003; Chicago, Illinois. Abstract
A-1579.
Copyright © 2003 Medscape.
[Home] [Up] [Mold-Terms] [EPA-Mold-Information] [How Mold Grows] [WHO-Mold-Report] [Mold-Info-Websites] [Ten-Mold-Facts] [Environmental-Mold-Home-Report] [Mold-Respiratory-Hazards] [Mold-Health-Threat] [Mold-Medical-Diagnosis] [Mold-Infection-Therapies] [Mold-Health-Symptoms] [Damp-Indoor-Spaces-Mold] |
