scholarly journals Isavuconazole and Liposomal Amphotericin B as Successful Combination Therapy of Refractory Invasive Candidiasis in a Liver Transplant Recipient: A Case Report and Literature Review

2021 ◽  
Author(s):  
Georgios Odysseos ◽  
Ulrich Mayr ◽  
Gabor Bozsaki ◽  
Christian Seidensticker ◽  
Ursula Ehmer ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Transplant Recipient ◽  
Liver Transplant ◽  
Amphotericin B ◽  
Invasive Candidiasis ◽  
Liposomal Amphotericin ◽  
Liver Transplant Recipient ◽  
Fungal Infections ◽  
Liposomal Amphotericin B ◽  
High Dose

AbstractInvasive fungal infections in liver transplant recipients are associated with elevated morbidity and mortality and pose a challenge to the treating physicians. Despite of lacking clinical data, the use of antifungal combination therapy is often considered to improve response rates in an immunocompromised patient population. We herein report a case of refractory invasive candidiasis in a liver transplant recipient treated successfully with a combination of isavuconazole und high-dose liposomal amphotericin B. The antimycotic combination treatment was able to clear a bloodstream infection with C. glabrata and led to regression of bilomas among tolerable side effects. The use of the above-mentioned antifungal combination therapy in a liver transplant recipient has not been reported previously. This case highlights the efficacy and safety of antifungal combination therapy in immunocompromised patients with refractory invasive candidiasis.

Cure of Rhizopus Sinusitis in a Liver Transplant Recipient with Liposomal Amphotericin B

1993 ◽  
Vol 16 (1) ◽  
pp. 183-183 ◽  
Author(s):  
W. Munckhof ◽  
R. Jones ◽  
F. A. Tosolini ◽  
A. Marzec ◽  
P. Angus ◽  
...  
Keyword(s):  
Transplant Recipient ◽  
Liver Transplant ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Liver Transplant Recipient ◽  
Liposomal Amphotericin B

scholarly journals A safety and feasibility study comparing an intermittent high dose with a daily standard dose of liposomal amphotericin B for persistent neutropenic fever

2009 ◽  
Vol 58 (11) ◽  
pp. 1474-1485 ◽  
Author(s):  
Michael Ellis ◽  
Roos Bernsen ◽  
Hussein Ali-Zadeh ◽  
Jörgen Kristensen ◽  
Ulla Hedström ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Feasibility Study ◽  
Liposomal Amphotericin ◽  
Drug Exposure ◽  
Fungal Infections ◽  
Lower Proportion ◽  
Liposomal Amphotericin B ◽  
High Dose ◽  
Group A ◽  
Group B

A high intermittent dose regimen (group A: 10 mg kg−1 on day 1, 5 mg kg−1 on days 3 and 6) was compared with standard dosing (group B: 3 mg kg−1 per day for 14 days) of liposomal amphotericin B (LAB) for empirical treatment of persistent febrile neutropenia. A total cumulative dose of 1275 mg (group A) and 2800 mg (group B) was administered. Infusion-related adverse drug events, mainly rigors/chills, occurred more frequently with group A (11/45, 24 % infusions) than with group B (12/201, 6 % infusions) (P=0.002), which extended the mean infusion time by 20 min (P=0.001). Creatinine levels were similar in the two regimens: the A : B ratio of the area under the curve for creatinine (AUCCREATININE) for days 2–7 was 1.09 (P=0.27) and for days 2–14 was 1.05 (P=0.51). Rises in creatinine were mild (clinical toxicity criteria 1) in all patients with elevations. Hypokalaemia tended to be less severe in group A with a lower proportion of hypokalaemic days [57/143 (39 %) vs 80/137 (58 %), P=0.21], a higher AUCPOTASSIUM (A : B ratio of 1.06, P=0.12), a lower proportion of patients with hypokalaemia at the end of study (10 vs 61 %, P=0.01) and fewer potassium-supplemented days [12/210 (6 %) vs 41/210 (19.5 %), P<0.1]. There were mildly elevated median levels of serum bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, which were similar for the two regimens and were usually associated with other co-existing co-morbid conditions. The AUC for these enzymes was also similar in the two groups. No patient had discontinuation of the study drug due to toxicity. Composite success was identical for each regimen (11/15 patients, 73 %). Three of the fifteen patients in group B and none in group A developed invasive fungal infections (IFIs). β-d-Glucan levels were similar in both groups for patients without an IFI [AUCGLUCAN of 362 and 683 (P=0.36) for groups A and B, respectively]. The rate of defervescence was similar for each regimen (P=0.75). This feasibility study suggests that a short intermittent high-dose course of 10/5/5 mg LAB kg−1 on days 1, 3 and 6 may be as safe and effective as a standard 14 day course of 3 mg kg−1 per day, with drug-acquisition cost savings and reduced drug exposure. A larger study is indicated for confirmation of this.

scholarly journals Safety and Efficacy of Intermittent High-Dose Liposomal Amphotericin B Antifungal Prophylaxis in Haemato-Oncology: An Eight-Year Single-Centre Experience and Review of the Literature

2020 ◽  
Vol 6 (4) ◽  
pp. 385
Author(s):  
Jonathan Youngs ◽  
Jen Mae Low ◽  
Laura Whitney ◽  
Clare Logan ◽  
Janice Chase ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Liposomal Amphotericin B ◽  
High Dose ◽  
Single Centre ◽  
Antifungal Stewardship ◽  
European Organization ◽  
Grade 3

Triazoles remain first-line agents for antifungal prophylaxis in high-risk haemato-oncology patients, but their use is increasingly contraindicated due to drug–drug interactions and additive toxicities with novel treatments. In this retrospective, single-centre, observational study, we present our eight-year experience of antifungal prophylaxis using intermittent high-dose liposomal Amphotericin B (L-AmB). All adults identified through our Antifungal Stewardship Programme as receiving L-AmB prophylaxis at 7.5 mg/kg once-weekly between February 2012 and January 2020 were included. Adverse reactions, including infusion reactions, electrolyte loss, and nephrotoxicity, were recorded. ‘Breakthrough’ invasive fungal infection (IFI) occurring within four weeks of L-AmB was classified using European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Moreover, 114 courses of intermittent high-dose L-AmB prophylaxis administered to 92 unique patients were analysed. Hypokalaemia was the most common grade 3–4 adverse event, with 26 (23%) courses. Grade 3 nephrotoxicity occurred in 8 (7%) and reversed in all six patients surviving to 90 days. There were two (1.8%) episodes of breakthrough IFI, one ‘probable’ and one ‘possible’. In this study, the largest evaluation of intermittent high-dose L-AmB prophylaxis conducted to date, toxicity was manageable and reversible and breakthrough IFI was rare. L-AmB prophylaxis represents a viable alternative for patients with a contraindication to triazoles.

scholarly journals Safety, Tolerance, and Pharmacokinetics of High-Dose Liposomal Amphotericin B (AmBisome) in Patients Infected withAspergillus Species and Other Filamentous Fungi: Maximum Tolerated Dose Study

2001 ◽  
Vol 45 (12) ◽  
pp. 3487-3496 ◽  
Author(s):  
Thomas J. Walsh ◽  
Jesse L. Goodman ◽  
Peter Pappas ◽  
Ihor Bekersky ◽  
Donald N. Buell ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Filamentous Fungi ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Liposomal Amphotericin B ◽  
High Dose ◽  
Time Curve ◽  
Days Of Therapy ◽  
Plasma Pharmacokinetics ◽  
Intent To Treat

ABSTRACT We conducted a phase I-II study of the safety, tolerance, and plasma pharmacokinetics of liposomal amphotericin B (L-AMB; AmBisome) in order to determine its maximally tolerated dosage (MTD) in patients with infections due to Aspergillus spp. and other filamentous fungi. Dosage cohorts consisted of 7.5, 10.0, 12.5, and 15.0 mg/kg of body weight/day; a total of 44 patients were enrolled, of which 21 had a proven or probable infection (13 aspergillosis, 5 zygomycosis, 3 fusariosis). The MTD of L-AMB was at least 15 mg/kg/day. Infusion-related reactions of fever occurred in 8 (19%) and chills and/or rigors occurred in 5 (12%) of 43 patients. Three patients developed a syndrome of substernal chest tightness, dyspnea, and flank pain, which was relieved by diphenhydramine. Serum creatinine increased two times above baseline in 32% of the patients, but this was not dose related. Hepatotoxicity developed in one patient. Steady-state plasma pharmacokinetics were achieved by day 7. The maximum concentration of drug in plasma (C max) of L-AMB in the dosage cohorts of 7.5, 10.0, 12.5, and 15.0 mg/kg/day changed to 76, 120, 116, and 105 μg/ml, respectively, and the mean area under the concentration-time curve at 24 h (AUC24) changed to 692, 1,062, 860, and 554 μg · h/ml, respectively, while mean CL changed to 23, 18, 16, and 25 ml/h/kg, respectively. These data indicate that L-AMB follows dose-related changes in disposition processing (e.g., clearance) at dosages of ≥7.5 mg/kg/day. Because several extremely ill patients had early death, success was determined for both the modified intent-to-treat and evaluable (7 days of therapy) populations. Response rates (defined as complete response and partial response) were similar for proven and probable infections. Response and stabilization, respectively, were achieved in 36 and 16% of the patients in the modified intent-to-treat population (n = 43) and in 52 and 13% of the patients in the 7-day evaluable population (n = 31). These findings indicate that L-AMB at dosages as high as 15 mg/kg/day follows nonlinear saturation-like kinetics, is well tolerated, and can provide effective therapy for aspergillosis and other filamentous fungal infections.

Safety and efficacy of dose escalated liposomal amphotericin B in adult leukemia patients with refractory invasive fungal infections: A single institution report.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6613-6613
Author(s):  
Sherry Mathew ◽  
Stephen Harnicar ◽  
Elizabeth Halton ◽  
Ellin Berman ◽  
Renier J. Brentjens ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Dose Escalation ◽  
Clinical Remission ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Chest Ct ◽  
Invasive Fungal Infections ◽  
Liposomal Amphotericin B ◽  
High Dose ◽  
Hepatic Toxicity

6613 Background: Leukemia patients are at risk for invasive fungal infections(IFI). Empiric therapy of suspected IFI is begun due to fever despite appropriate antibiotics during neutropenia or infiltrates on chest CT. Liposomal amphotericin B (L-AmB) is used for empiric anti-fungal therapy at 3-5 mg/kg. Data is lacking on the efficacy of L-AmB dose escalation in patients with CT progression and clinical decline. Methods: Patients who received 10 mg/kg of L-AmB from 2002-11. They were required to be ≥18 years old and escalated from 5 to 10 mg/kg L-Amb for at least 7 doses. Patient information was collected from pharmacy and medical records. Successful treatment was defined as resolution of fever at least 1 week after high dose L-AmB and/or improvement or stability on chest CT. Renal and hepatic toxicity was assessed. Clinical remission was defined as recovery of a normal neutrophil count. IRB approval was obtained for this study. Results: 58 patients were evaluated. At the time of presumed or probable IFI, 19 had completed induction therapy, 5 had received supportive therapy, and 34 had received 2 or more cycles of therapy. High dose L-AmB was begun for CT findings and fever, CT findings only, and fever only in 14, 26, and 17 patients, respectively. Patients received a median of 15 doses of high dose L-AmB, and all received concomitant therapy with an echinocandin except two: 1 received nothing and 1 received voriconazole. Treatment success was seen in 28 (48%) patients. Twenty-nine (50%) patients were alive at 12 weeks and 10 (17%) patients proceded to BMT. Only 11 (39%) of the responding patients achieved a clinical remission. All patients received IV hydration and electrolyte repletion. Six patients had a grade 2 increase in serum creatinine and 10 patients developed grade 2 or 3 hepatic toxicity. There were no grade 4 adverse events. Conclusions: Although it has been reported that L-AmB at 10mg/kg was inferior to 3 mg/kg in untreated patients, our study supports a safe dose escalation strategy to 10mg/kg in treating progressive presumed or probable IFI and should be considered a clinical alternative for these high risk patients.

Assessing the Efficacy and Safety of Liposomal Amphotericin B and Miltefosine in Combination for Treatment of Post Kala-Azar Dermal Leishmaniasis

2019 ◽  
Vol 221 (4) ◽  
pp. 608-617 ◽  
Author(s):  
V Ramesh ◽  
Keerti Kaumudee Dixit ◽  
Neha Sharma ◽  
Ruchi Singh ◽  
Poonam Salotra
Keyword(s):  
Combination Therapy ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Quantitative Polymerase Chain Reaction ◽  
Treatment Options ◽  
Parasite Load ◽  
Liposomal Amphotericin B ◽  
Rapid Decline ◽  
Kala Azar

Abstract Background No satisfactory canonical treatment is available for post-kala-azar dermal leishmaniasis (PKDL), clinical sequela of visceral leishmaniasis. Confined treatment options and substantial increase in relapse rate after miltefosine (MIL) treatment warrant the need to adapt resilient combination therapies. In this study, we assessed the safety and efficacy of combination therapy using liposomal amphotericin B (LAmB) and MIL for treating PKDL. Methods Thirty-two PKDL patients, confirmed by microscopy or quantitative polymerase chain reaction (qPCR), were included in the study. An equal number of cases (n = 16) were put on MIL monotherapy (100 mg/day for 90 days) or MIL and LAmB combination for 45 days (3 injections of LAmB, 5 mg/kg body weight, and 100 mg/day MIL). Parasite load in slit aspirate was monitored using qPCR. Results Patients treated with combination therapy demonstrated a rapid decline in parasite load and achieved 100% cure, with no reports of relapse. Those treated with MIL monotherapy attained clinical cure with a gradual decrease in parasite load; however, 25% relapsed within 18 months of follow-up. Conclusions Liposomal amphotericin B and MIL combination for treating PKDL is efficacious and safe, with high tolerability. Furthermore, this study established the utility of minimally invasive slit aspirate method for monitoring of parasite load and assessment of cure in PKDL.

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