scholarly journals Comparative Efficacies of Conventional Amphotericin B, Liposomal Amphotericin B (AmBisome), Caspofungin, Micafungin, and Voriconazole Alone and in Combination against Experimental Murine Central Nervous System Aspergillosis

2005 ◽  
Vol 49 (12) ◽  
pp. 4867-4875 ◽  
Author(s):  
Karl V. Clemons ◽  
Marife Espiritu ◽  
Rachana Parmar ◽  
David A. Stevens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Antifungal Agents ◽  
Severe Disease ◽  
Fungal Burden ◽  
Enhanced Activity ◽  
Current Therapies ◽  
Immunosuppressed Mice

ABSTRACT Central nervous system (CNS) aspergillosis is a severe disease that responds poorly to current therapies. The current studies examined the efficacies of several antifungal agents alone or in combination with a murine model of CNS aspergillosis. Immunosuppressed mice were infected intracerebrally with Aspergillus fumigatus and treated with an amphotericin B preparation, an echinocandin, or voriconazole (VCZ) given alone or in combination. Monotherapy studies showed that micafungin (MICA), caspofungin (CAS), VCZ, conventional amphotericin B (AMB), Abelcet (ABLC) (a lipid-carried AMB formulation; Enzon Pharmaceuticals, Inc.), and AmBisome (AmBi) (liposomal AMB; Gilead Sciences, Inc.) were efficacious. However, doses of AmBi above 15 mg/kg of body weight showed reduced efficacy. Neither MICA nor CAS showed dose responsiveness at the doses tested (1, 5, or 10 mg/kg). Only the 40-mg/kg dose of VCZ was effective. AmBi and ABLC showed dose responsiveness, with 10-mg/kg doses causing a significant reduction in fungal burden; they had equivalent activities at the 10-mg/kg dose. Suboptimal dosages of AmBi in combination with MICA, CAS, or VCZ were effective in prolonging survival. However, significantly enhanced activity was demonstrated only with AmBi and VCZ in combination. AmBi in combination with MICA or CAS showed a trend toward enhanced activity, but the combination was not significantly superior to monotherapy. The use of AmBi with CAS or VCZ at optimal doses did not improve efficacy. Cure was not attained with any dosage combinations. These results indicate that AmBi in combination with VCZ may be superior for treatment of CNS aspergillosis; combinations of AmBi and MICA or CAS were not antagonistic and may have a slight benefit.

Rhinocerebral mucormycosis: Use of liposomal amphotericin B

1991 ◽  
Vol 105 (7) ◽  
pp. 575-577 ◽  
Author(s):  
Edward W. Fisher ◽  
Abbad Toma ◽  
Phillip H. Fisher ◽  
Anthony D. Cheesman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Supportive Therapy ◽  
Liposomal Amphotericin B ◽  
Rhinocerebral Mucormycosis ◽  
System A ◽  
The Central Nervous System ◽  
Liposomal Delivery

AbstractRhinocerebral mucormycosis is a rare but often fatal condition characterized by an aggressive necrotizing infection spreading from the nose to the paranasal sinuses, orbit and hence to the central nervous system. A case is reported in which a diabetic male with advanced mucormycosis was successfully treated by a combination of surgery, supportive therapy and liposomal amphotericin B. Liposomal delivery allows the drug to be both less toxic and more effective, and this is the first reported case of its use in rhinocerebral mucormycosis.

scholarly journals Anidulafungin Treatment of Candidal Central Nervous System Infection in a Murine Model

2009 ◽  
Vol 53 (8) ◽  
pp. 3576-3578 ◽  
Author(s):  
Cheol-In Kang ◽  
Mark S. Rouse ◽  
Jayawant N. Mandrekar ◽  
James M. Steckelberg ◽  
Robin Patel
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Candida Albicans ◽  
Brain Tissue ◽  
Amphotericin B ◽  
Murine Model ◽  
Potential Role ◽  
Central Nervous System Infection ◽  
Cns Infection ◽  
Fungal Burden

ABSTRACT We established a murine model of Candida albicans central nervous system (CNS) infection and evaluated the efficacy of anidulafungin. Ten milligrams/kg/day anidulafungin, amphotericin B, or voriconazole significantly reduced mortality and fungal burden in brain tissue, although amphotericin B and 10 mg/kg/day anidulafungin reduced fungal burden in brain tissue to a greater extent than did voriconazole. This suggests a potential role for anidulafungin in the treatment of candidal CNS infection.

scholarly journals Efficacy of Amphotericin B or Itraconazole in a Murine Model of Central Nervous System Aspergillus Infection

2003 ◽  
Vol 47 (2) ◽  
pp. 813-815 ◽  
Author(s):  
Tom M. Chiller ◽  
Raymond A. Sobel ◽  
Javier Capilla Luque ◽  
Karl V. Clemons ◽  
David A. Stevens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amphotericin B ◽  
Therapeutic Strategies ◽  
Once Daily ◽  
Aspergillus Infection ◽  
Results Of Treatment ◽  
Current Therapies ◽  
Therapeutic Alternatives ◽  
Intracerebral Infection

ABSTRACT Given the greater than 90% lethality of clinical central nervous system (CNS) aspergillosis despite current therapies, there is a need for an animal model to study therapeutic strategies. We previously established a model of CNS aspergillosis by intracerebral infection and report here the results of treatment with the two therapies with the greatest clinical experience, i.e., treatments with amphotericin B (AMB) and itraconazole (ITZ). Mice were given cyclophosphamide to produce pancytopenia. AMB was given intraperitoneally (i.p.; 3 mg/kg of body weight) or intravenously (i.v.; 0.8 mg/kg) once daily. ITZ in cyclodextrin was given by gavage once daily at a dose of 100 mg/kg or twice daily at 50 mg/kg. Treatments were started at day 1 postinfection and given for 10 days. At day 15, survivors were euthanatized. Ninety percent of the mice given no treatment died by day 6, and 100% died by day 10. Mice treated with AMB either i.p. or i.v. had 40% survival. Mice treated with ITZ either once or twice per day had a median survival time of 10 days, compared with 4 days for control animals, but a survival rate of only 10%. AMB and ITZ prolonged survival (P, <0.0001 to <0.05) compared with controls. Brains from surviving mice had CFU of Aspergillus fumigatus. This model can be used to compare newer antifungals and to study combination therapy or immunotherapy to find better therapeutic alternatives.

scholarly journals Cladophialophora bantianaBrain Abscess in an Immunocompetent Patient

2011 ◽  
Vol 22 (4) ◽  
pp. 149-150 ◽  
Author(s):  
Sanjay G. Revankar
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amphotericin B ◽  
Brain Abscess ◽  
Liposomal Amphotericin ◽  
Brain Lesion ◽  
Central Nervous System Infection ◽  
Surgical Excision ◽  
Immunocompetent Patient ◽  
Immunocompetent Patients

Cladophialophora bantianais a dematiaceous mold with a predilection for causing central nervous system infection, particularly in normal hosts. A case involving a 79-year-old immunocompetent woman who presented with left-sided weakness and a ring-enhancing brain lesion is reported. She underwent surgical excision, which revealed a brain abscess due toC bantiana. The patient was treated with liposomal amphotericin B for several weeks, then switched to voriconazole and flucytosine, but eventually succumbed to the infection. Therapy is not standardized for this rare mycosis, and mortality remains high, even in immunocompetent patients. Additional studies to understand the pathogenesis of this infection and to improve outcomes are needed.

scholarly journals Combination Echinocandin-Polyene Treatment of Murine Mucormycosis

2008 ◽  
Vol 52 (4) ◽  
pp. 1556-1558 ◽  
Author(s):  
Ashraf S. Ibrahim ◽  
Teclegiorgis Gebremariam ◽  
Yue Fu ◽  
John E. Edwards ◽  
Brad Spellberg
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Class Effect ◽  
Lipid Complex ◽  
Enhanced Activity ◽  
Amphotericin B Lipid Complex ◽  
Disseminated Mucormycosis

ABSTRACT We previously found that caspofungin synergized with amphotericin B lipid complex in treating murine mucormycosis. We now report a similarly enhanced activity of liposomal amphotericin combined with micafungin or anidulafungin in mice with disseminated mucormycosis. The efficacy of combination echinocandin-polyene therapy for mucormycosis is a class effect.

#14: Blastomycosis in 64 Wisconsin Children: Unanticipated Infection Risk and Severity in Urban Residents

2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S8-S8
Author(s):  
Jaimee M Hall ◽  
Peter L Havens ◽  
Errin A Mitchell ◽  
Gabriel N De Vela ◽  
Lauren L Titus ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Disease Severity ◽  
Environmental Exposure ◽  
Care Center ◽  
Severe Disease ◽  
Tertiary Care ◽  
Urban Children ◽  
Urban Environments ◽  
Exposure Source

Abstract Background Blastomycosis is an endemic mycosis of immunocompetent individuals, typically seen after exposure to wooded areas near rivers, lakes, and streams in rural locations, and often not considered a disease of urban environments. Disease can be isolated to lung, or disseminate to skin, bone, or central nervous system. Factors influencing disease acquisition and severity in children are unknown. Methods We analyzed acquisition risk factors and disease characteristics of blastomycosis in children treated at a tertiary care center from 1998–2018 to identify exposure source and measure disease severity, to identify cases without “typical exposure”, and to measure the effect of race on disease severity. Results Of 64 children, median age was 13.3 years, 72% were male, 38% resided in urban counties, and 50% had typical environmental exposure. Isolated pulmonary infection occurred in 33 (52%). The remaining children had evidence of dissemination including skin (N=13), bone (N=16; 7 clinically silent), and central nervous system (N=7; 3 clinically silent). Infection was moderate/severe in 19 (30%). Two children (3%) died. 79% of children with moderate/severe disease (p=0.008) and 71% of urban children (p=0.007) had no typical environmental exposure. Comparing children from urban counties to other residences, 63% versus 5% were black (p&lt;0.001) and 71% versus 35% developed extrapulmonary dissemination (p=0.006). Moderate/severe disease occurred in 7/17 (42%) black and 12/47 (26%) children of other race (p=0.23). Conclusions Blastomycosis, endemic in urban children in the absence of typical exposure history, has frequent, sometimes clinically silent, extrapulmonary dissemination, with a trend toward more severe disease in black children.

scholarly journals Age-Dependent Resistance to Lethal Alphavirus Encephalitis in Mice: Analysis of Gene Expression in the Central Nervous System and Identification of a Novel Interferon-Inducible Protective Gene, Mouse ISG12

2002 ◽  
Vol 76 (22) ◽  
pp. 11688-11703 ◽  
Author(s):  
Lucia Labrada ◽  
Xiao Huan Liang ◽  
Wei Zheng ◽  
Christine Johnston ◽  
Beth Levine
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Virus Infection ◽  
Sindbis Virus ◽  
Expressed Sequence Tag ◽  
Severe Disease ◽  
Altered Expression ◽  
Age Dependent ◽  
Old Mice

ABSTRACT Several different mammalian neurotropic viruses produce an age-dependent encephalitis characterized by more severe disease in younger hosts. To elucidate potential factors that contribute to age-dependent resistance to lethal viral encephalitis, we compared central nervous system (CNS) gene expression in neonatal and weanling mice that were either mock infected or infected intracerebrally with a recombinant strain, dsTE12Q, of the prototype alphavirus Sindbis virus. In 1-day-old mice, infection with dsTE12Q resulted in rapidly fatal disease associated with high CNS viral titers and extensive CNS apoptosis, whereas in 4-week-old mice, dsTE12Q infection resulted in asymptomatic infection with lower CNS virus titers and undetectable CNS apoptosis. GeneChip expression comparisons of mock-infected neonatal and weanling mouse brains revealed developmental regulation of the mRNA expression of numerous genes, including some apoptosis regulatory genes, such as the proapoptotic molecules caspase-3 and TRAF4, which are downregulated during development, and the neuroprotective chemokine, fractalkine, which is upregulated during postnatal development. In parallel with increased neurovirulence and increased viral replication, Sindbis virus infection in 1-day-old mice resulted in both a greater number of host inflammatory genes with altered expression and greater changes in levels of host inflammatory gene expression than infection in 4-week-old mice. Only one inflammatory response gene, an expressed sequence tag similar to human ISG12, increased by a greater magnitude in infected 4-week-old mouse brains than in infected 1-day-old mouse brains. Furthermore, we found that enforced neuronal ISG12 expression results in a significant delay in Sindbis virus-induced death in neonatal mice. Together, our data identify genes that are developmentally regulated in the CNS and genes that are differentially regulated in the brains of different aged mice in response to Sindbis virus infection.

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