scholarly journals Efficacy of Liposomal Amphotericin B and Posaconazole in Intratracheal Models of Murine Mucormycosis

2013 ◽  
Vol 57 (7) ◽  
pp. 3340-3347 ◽  
Author(s):  
Guanpingsheng Luo ◽  
Teclegiorgis Gebremariam ◽  
Hongkyu Lee ◽  
Samuel W. French ◽  
Nathan P. Wiederhold ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Intratracheal Instillation ◽  
Cortisone Acetate ◽  
Liposomal Amphotericin B ◽  
Immunocompromised Patients ◽  
Content Type ◽  
Pulmonary Mucormycosis ◽  
Life Threatening

ABSTRACTMucormycosis is a life-threatening fungal infection almost uniformly affecting diabetics in ketoacidosis or other forms of acidosis and/or immunocompromised patients. Inhalation ofMucoralesspores provides the most common natural route of entry into the host. In this study, we developed an intratracheal instillation model of pulmonary mucormycosis that hematogenously disseminates into other organs using diabetic ketoacidotic (DKA) or cyclophosphamide-cortisone acetate-treated mice. Various degrees of lethality were achieved for the DKA or cyclophosphamide-cortisone acetate-treated mice when infected with different clinical isolates ofMucorales. In both DKA and cyclophosphamide-cortisone acetate models, liposomal amphotericin B (LAmB) or posaconazole (POS) treatments were effective in improving survival, reducing lungs and brain fungal burdens, and histologically resolving the infection compared with placebo. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies, and evaluate drug efficacies against life-threateningMucoralesinfections.

scholarly journals Lichtheimia corymbifera Colonization Leading to Pulmonary Infection Can Be Prevented with Liposomal Amphotericin B in a New Murine Model

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Thomas Brunet ◽  
Kévin Brunet ◽  
Grégory Jouvion ◽  
Estelle Cateau ◽  
Sandrine Marchand ◽  
...  
Keyword(s):  
Mouse Model ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
High Efficiency ◽  
Antifungal Drugs ◽  
Liposomal Amphotericin B ◽  
Content Type ◽  
Pulmonary Mucormycosis ◽  
Lung Colonization ◽  
Lichtheimia Corymbifera

ABSTRACT The incidence of pulmonary mucormycosis is constantly increasing, especially in hematological patients staying in high-efficiency particulate air-filtered rooms. Pulmonary inhalation of spores may occur outside the hospital, leading to invasive disease once patients received chemotherapies. We developed a new pulmonary mucormycosis mouse model mimicking the expected pathophysiology in human to study antifungal drugs. Naive mice were inoculated intratracheally with Lichtheimia corymbifera spores. After 3 days, mice received corticosteroids and cyclophosphamide and secondarily developed the disease, while only 5% of the initial inoculum was present in the lungs at day 3. Lung colonization with L. corymbifera spores in immunocompetent mice can last at least 44 days. Antifungal drug was administered the day of immunosuppression. Injection of a single 15 mg/kg of body weight dose of liposomal amphotericin B significantly improved survival and pulmonary fungal burden compared with controls, whereas 80 mg/kg oral posaconazole did not. These results show that a unique dose of liposomal amphotericin B offers a real potential decolonization treatment to prevent infection in our mouse model of L. corymbifera lung colonization followed by lung infection.

scholarly journals Intrahepatic Administration of Liposomal Amphotericin B (Ambisome) for the Management of a Liver Abscess from Candida albicans in a Preterm Infant

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Cinzia Auriti ◽  
Maria Paola Ronchetti ◽  
Iliana Bersani ◽  
Fabrizio Gennari ◽  
Fiammetta Piersigilli
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Preterm Neonate ◽  
Neonatal Period ◽  
Newborn Infants ◽  
Liposomal Amphotericin B ◽  
Content Type ◽  
Life Threatening ◽  
Intralesional Administration

ABSTRACT Hepatic fungal abscesses are rare in the neonatal period and often constitute a severe complication of the catheterization of the umbilical vessels. Such life-threatening lesions are observed more frequently in preterm than in other newborn infants and the optimal treatment remains uncertain. We present the case of a preterm neonate, who developed an intrahepatic lesion due to parenteral extravasation, successively contaminated by Candida albicans. Despite the maximal pharmacological therapies, the treatment that led to the definitive resolution of the abscess was the placement of surgical drainage followed by the direct intralesional administration of liposomal amphotericin B (Ambisome), never described in neonates in the literature, which turned out to be a safe and effective approach.

scholarly journals 1554. Nebulized Liposomal Amphotericin B for Treatment of Murine Pulmonary Mucormycosis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S567-S568
Author(s):  
Adilene Sandoval ◽  
Jill Adler-Moore
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Rhizopus Oryzae ◽  
Liposomal Amphotericin B ◽  
High Dose ◽  
Spore Viability ◽  
Drug Levels ◽  
Pulmonary Mucormycosis ◽  
Life Threatening

Abstract Background Pulmonary mucormycosis, a life-threatening infection of immunocompromised individuals, can have a 95% mortality rate, even with treatment. Intravenous (IV) liposomal amphotericin B (AmBisomeâ, AmBi) is used to treat the infection, but rapid growth of the pathogen can limit the drug’s effectiveness. In the present study we investigated whether nebulized (nebz) AmBi could improve treatment outcome using a neutropenic murine model of pulmonary mucormycosis. Methods Rhizopus oryzae (ATCC MYA4621) was grown on Potato Dextrose Agar for 3–7 days, followed by spore harvesting, and determination of spore viability. Male ICR mice were immunosuppressed with 200 mg/kg of cyclophosphamide d-2, d0, d+2, d+4, and d0 challenged intranasally with 1 × 106 spores. In Study 1, mice (n = 16 mice/gp) were given AmBi at 7.5 or 10 mg/kg IV for 6 days, or nebz AmBi for 20 minutes (1.33 mg/mL AmBi in reservoir) for 4 days. In Study 2, 16 mice/gp were given AmBi at 15 mg/kg IV for 6 days or nebz AmBi for 7 days. PBS was the control. Lungs and kidneys were collected d+6 to determine drug concentration by a bioassay (n = 7–8 mice/gp) and morbidity (n = 8 mice/gp) monitored to d+21. Results In Study 1, survival was significantly better with nebz AmBi for 4 days (50%) or 10 mg/kg IV AmBi (33%) vs. 7.5 mg/kg IV AmBi (0%) (P < 0.003). In Study 2 with 13% survival in the PBS mice, 7 days of nebz AmBi produced 100% survival and 15 mg/kg IV AmBi gave 83% survival (P < 0.02 vs. PBS), underscoring the need for more intensive treatments. In Study 2, we also observed that average lung drug levels with nebz AmBi were significantly lower (3 μg/g lung) than with 15mg/kg AmBi IV (19 μg/g lung) (P = 0.003), even though both treatments were comparably effective. Kidney drug levels with 15 mg/kg AmBi IV were 13 μg/g and in comparison, nebz AmBi produced no detectable drug. Conclusion Daily nebulization of AmBi for one week or a high dose of IV AmBi at 15 mg/kg for 6 days protected the mice from severe pulmonary mucormycosis caused by R. oryzae, delivering effective drug levels to the lungs. The IV treatment yielded elevated levels of drug in the kidneys, while nebulization with AmBi produced no detectable drug in the kidneys. This indicated that nebz AmBi would be a less nephrotoxic, but still very effective route for drug delivery. Disclosures All authors: No reported disclosures.

scholarly journals Pulmonary Mucormycosis with Diabetes Mellitus: A Case Report

2018 ◽  
Vol 2 (2) ◽  
pp. 33-34
Author(s):  
Shikha Jain ◽  
Bharat Sharma
Keyword(s):  
Diabetes Mellitus ◽  
Case Report ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Immunocompromised Patients ◽  
Pulmonary Mucormycosis ◽  
Life Threatening

Mucormycosis is an uncommon but life threatening fungal infection that generally occurs mostly in immunocompromised patients. Patients do not respond to the antibiotics and so the condition may prove to be fatal if not timely detected. In this report, we summarize a case of pulmonary mucormycosis in a patient with diabetes mellitus who was cured using Amphotericin B.

scholarly journals In Vivo Efficacy of Liposomal Amphotericin B against Wild-Type and Azole-Resistant Aspergillus fumigatus Isolates in Two Different Immunosuppression Models of Invasive Aspergillosis

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Seyedmojtaba Seyedmousavi ◽  
Johan W. Mouton ◽  
Willem J. G. Melchers ◽  
Paul E. Verweij
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Treated Group ◽  
Liposomal Amphotericin B ◽  
Wild Type ◽  
Resistance Mutations ◽  
Content Type

ABSTRACT Using an immunocompetent murine model of invasive aspergillosis (IA), we previously reported that the efficacy of liposomal amphotericin B (L-AmB) (Ambisome) is not hampered by the presence of azole resistance mutations in Aspergillus fumigatus (S. Seyedmousavi, W. J. G. Melchers, J. W. Mouton, and P. E. Verweij, Antimicrob Agents Chemother 57:1866–1871, 2013, https://doi.org/10.1128/AAC.02226-12 ). We here investigated the role of immune suppression, i.e., neutropenia and steroid treatment, in L-AmB efficacy in mice infected with wild-type (WT) A. fumigatus and with azole-resistant A. fumigatus harboring a TR34/L98H mutation in the cyp-51A gene. Survival of treated animals at day 14 in both immunosuppressed models was significantly better than that of nontreated controls. A dose-response relationship was observed that was independent of the azole-resistant mechanism and the immunosuppression method used. In the neutropenic model, 100% survival was reached at an L-AmB dose of 16 mg/kg of body weight for the WT strain and the TR34/L98H isolate. In the steroid-treated group, 90.9% survival and 100% survival were achieved for the WT isolate and the TR34/L98H isolate with an L-AmB dose of 16 mg/kg, respectively. The 50% effective dose (ED50) was 1.40 mg/kg (95% confidence interval [CI], 0.66 to 3.00 mg/kg) for the WT isolate and 1.92 mg/kg (95% CI, 0.60 to 6.17 mg/kg) for the TR34/L98H isolate in the neutropenic model and was 2.40 mg/kg (95% CI, 1.93 to 2.97 mg/kg) for the WT isolate and 2.56 mg/kg (95% CI, 1.43 to 4.56 mg/kg) for the TR34/L98H isolate in the steroid-treated group. Overall, there were no significant differences between the two different immunosuppressed conditions in the efficacy of L-AmB against the wild-type and azole-resistant isolates (P > 0.9). However, the required L-AmB exposure was significantly higher than that seen in the immunocompetent model.

scholarly journals Pulmonary Mucormycosis: An Emerging Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Mohammed Muqeetadnan ◽  
Ambreen Rahman ◽  
Syed Amer ◽  
Salman Nusrat ◽  
Syed Hassan ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fungal Infection ◽  
Diabetic Patient ◽  
Patient Survival ◽  
Early Recognition ◽  
Immunocompromised Patients ◽  
Delay In Diagnosis ◽  
Pulmonary Mucormycosis ◽  
Aggressive Management ◽  
Life Threatening

Mucormycosis is a rare, but emerging, life-threatening, rapidly progressive, angioinvasive fungal infection that usually occurs in immunocompromised patients. We present a case of pulmonary mucormycosis in a diabetic patient who was on chronic steroid therapy for ulcerative colitis. Early recognition of this diagnosis, along with aggressive management, is critical to effective therapy and patient survival. The delay in diagnosis of this rapidly progressive infection can result in mortality.

scholarly journals Caspofungin at Catheter Lock Concentrations Eradicates Mature Biofilms of Candida lusitaniae and Candida guilliermondii

2014 ◽  
Vol 58 (8) ◽  
pp. 4953-4956 ◽  
Author(s):  
Maria Simitsopoulou ◽  
Daniela Kyrpitzi ◽  
Aristea Velegraki ◽  
Thomas J. Walsh ◽  
Emmanuel Roilides
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Candida Guilliermondii ◽  
Liposomal Amphotericin B ◽  
Antibiofilm Activity ◽  
Test Species ◽  
Content Type ◽  
Lock Therapy ◽  
Catheter Lock ◽  
Candida Lusitaniae

ABSTRACTThe antibiofilm activities of caspofungin, anidulafungin, micafungin, and liposomal amphotericin B were studied againstCandida lusitaniae,Candida guilliermondii, and aCandida albicanscontrol strain. While anidulafungin and micafungin (0.007 to 2,048 mg/liter) showed reduced activity against biofilms of both test species, caspofungin displayed concentration-dependent antibiofilm activity, reaching complete and persistent eradication at concentrations achievable during lock therapy (512 to 2,048 mg/liter,P< 0.05). Although liposomal amphotericin B strongly inhibited mature biofilms, it possessed lower antibiofilm activity than caspofungin (P< 0.05).

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