scholarly journals 718. Posaconazole Versus Standard of Care for Treatment of Invasive Mold Infections

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S458-S459
Author(s):  
Ann-Marie Idusuyi ◽  
Christopher McCoy ◽  
Howard Gold
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Infection Type ◽  
Standard Of Care ◽  
Oral Formulation ◽  
Liposomal Amphotericin B ◽  
Severe Neutropenia ◽  
Data Repository ◽  
Therapeutic Drug ◽  
Invasive Mold Infections

Abstract Background Invasive mold infections (IMIs) including Aspergillus spp. are a significant cause of morbidity and mortality in immunocompromised patients. Voriconazole is recommended as first line treatment for primary IA. Liposomal amphotericin B and isavuconazole are also recommended alternative therapies. Posaconazole has activity against mold species including those not covered by voriconazole, is available as an IV and oral formulation with a distinct adverse effect profile making it a potential effective alternative for treatment. This study investigated the clinical outcomes of treatment of invasive mold infections (IMIs) with posaconazole compared to standard of care (voriconazole, isavuconazole, liposomal amphotericin B). Methods A retrospective, single center, cohort study was completed to evaluate patients with IMIs treated with posaconazole versus those treated with standard of care therapy. Medication orders for posaconazole or standard of care therapy between January 2012 and December 2020 were identified from a clinical data repository. Only patients with antifungal orders with a listed indication for “treatment of fungal infection” were included. Data collected for each group included baseline demographics, underlying conditions, site of infection, type of mold, therapeutic drug monitoring and classification of IMI. Results A total of 120 patients met inclusion criteria, with 35 patients in the posaconazole group and 85 patients in the SOC group. Baseline characteristics were similar except for increased severe neutropenia in the posaconazole group (p< 0.0001), more probable IMIs in the SOC group (p=0.009) and more possible IMIs in the posaconazole group (p=0.043). In the posaconazole group 37.1% (13/35) of patients were treatment experienced vs. 29.4% (25/85) of patients in the SOC group. More patients achieved a complete/partial response in the SOC group compared to the posaconazole group (p=0.0001) and more patients experienced treatment failure in the posaconazole group (p=0.01). A higher proportion of patients experienced adverse effects in the SOC group compared to the posaconazole group (p=0.0001). Conclusion Posaconazole was not as effective as SOC in treating invasive mold infections but patients experienced comparatively fewer adverse events. Disclosures All Authors: No reported disclosures

scholarly journals Real-Life Considerations on Antifungal Treatment Combinations for the Management of Invasive Mold Infections after Allogeneic Cell Transplantation

2021 ◽  
Vol 7 (10) ◽  
pp. 811
Author(s):  
Emmanouil Glampedakis ◽  
Romain Roth ◽  
Stavroula Masouridi-Levrat ◽  
Yves Chalandon ◽  
Anne-Claire Mamez ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Cell Transplantation ◽  
Antifungal Therapy ◽  
Combination Treatment ◽  
Liposomal Amphotericin ◽  
Antifungal Susceptibility ◽  
Real Life ◽  
Antifungal Treatment ◽  
Liposomal Amphotericin B ◽  
Invasive Mold Infections

Background: Antifungal combination treatment is frequently administered for invasive mold infections (IMIs) after allogeneic hematopoietic cell transplantation (HCT). Here, we describe the indications, timing, and outcomes of combination antifungal therapy in post-HCT IMI. Methods: A single-center, 10-year, retrospective cohort study including all adult HCT recipients with proven/probable IMI between 1 January 2010 and 1 January 2020 was conducted. Results: During the study period, 515 patients underwent HCT, of whom 47 (9.1%) presented 48 IMI episodes (46 patients with one IMI episode and 1 patient with two separate IMI episodes): 33 invasive aspergillosis (IA) and 15 non-IA IMIs. Almost half (51%) of the patients received at least one course of an antifungal combination (median: 2/patient): 23 (49%), 20 (42%), and 4/47 (9%) patients received pure monotherapy, mixed monotherapy/combination, and pure combination treatment, respectively. Combination treatment was started at a median of 8 (IQR: 2, 19) days post-IMI diagnosis. Antifungal management was complex, with 163 treatment courses prescribed overall, 48/163 (29.4%) concerning antifungals in combination. The clinical reasons motivating the selection of initial combination antifungal therapy included severe IMI (18, 38%), lack of antifungal susceptibility data (14, 30%), lack of pathogen identification (5, 11%), and combination treatment until reaching a therapeutic azole serum level (6, 13%). The most common combination treatments were azole/liposomal amphotericin-B (28%) and liposomal amphotericin-B/echinocandin (21%). Combination treatment was administered cumulatively for a median duration of 28 days (IQR: 7, 47): 14 (IQR: 6, 50) days for IA and 28 (IQR: 21, 34) days for non-IA IMI (p = 0.18). Overall, 12-week mortality was 30%. Mortality was significantly higher among patients receiving ≥ 50% of treatment as combination (logrank = 0.04), especially those with non-IA IMI (logrank = 0.03). Conclusions: Combination antifungal treatment is frequently administered in allogeneic HCT recipients with IMI to improve clinical efficacy, albeit in an inconsistent and variable manner, suggesting a lack of relevant data and guidance, and an urgent need for new studies to improve therapeutic options.

Methods for particle size reduction of liposomal amphotericin B

2018 ◽  
Vol 60 (1) ◽  
pp. 42-45
Author(s):  
Tuan Quang Nguyen ◽  
Van Lam Nguyen ◽  
Thai Son Nguyen ◽  
Thi Minh Hue Pham ◽  
◽  
...  
Keyword(s):  
Particle Size ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Size Reduction ◽  
Liposomal Amphotericin B ◽  
Particle Size Reduction

scholarly journals Efficacy of Intravenous Liposomal Amphotericin B (AmBisome) against Coccidioidal Meningitis in Rabbits

2002 ◽  
Vol 46 (8) ◽  
pp. 2420-2426 ◽  
Author(s):  
Karl V. Clemons ◽  
Raymond A. Sobel ◽  
Paul L. Williams ◽  
Demosthenes Pappagianis ◽  
David A. Stevens
Keyword(s):  
Spinal Cord ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
White Blood Cells ◽  
Clinical Signs ◽  
Liposomal Amphotericin B ◽  
Coccidioides Immitis ◽  
Lower Protein ◽  
Motor Abnormalities ◽  
The Brain

ABSTRACT The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB). Male New Zealand White rabbits were infected by intracisternal inoculation of arthroconidia of Coccidioides immitis. Starting 5 days postinfection, animals received one of the following: 5% dextrose water diluent; AMB given at 1 mg/kg of body weight; AmBi given at 7.5, 15, or 22.5 mg/kg intravenously three times per week for 3 weeks; or oral FLC given at 80 mg/kg for 19 days. One week after the cessation of therapy, all survivors were euthanatized, the numbers of CFU remaining in the spinal cord and brain were determined, and histological analyses were performed. All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (P < 0.0001). Treated groups had significantly lower numbers of white blood cells and significantly lower protein concentrations in the cerebrospinal fluid compared with those for the controls (P < 0.01 to 0.0005) and had fewer clinical signs of infection (e.g., weight loss, elevated temperature, and neurological abnormalities including motor abnormalities). The mean histological scores for AmBi-treated rabbits were lower than those for FLC-treated and control rabbits (P < 0.016 and 0.0005, respectively); the scores for AMB-treated animals were lower than those for the controls (P < 0.0005) but were similar to those for FLC-treated rabbits. All regimens reduced the numbers of CFU in the brain and spinal cord compared with those for the controls (P ≤0.0005). AmBi-treated animals had 3- to 11-fold lower numbers of CFU than FLC-treated rabbits and 6- to 35-fold lower numbers of CFU than AmB-treated rabbits. Three of eight animals given 15 mg of AmBi per kg had no detectable infection in either tissue, whereas other doses of AmBi or FLC cleared either the brain or the spinal cord of infection in fewer rabbits. In addition, clearance of the infection from both tissues was achieved in none of the rabbits, and neither tissue was cleared of infection in AMB-treated animals. Overall, these data indicate that intravenously administered AmBi is superior to oral FLC or intravenous AMB and that FLC is better than AMB against experimental coccidioidal meningitis. These data indicate that AmBi may offer an improvement in the treatment of coccidioidal meningitis. Additional studies are warranted.

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