A randomized, open-label study to evaluate the efficacy and safety of liposomal amphotericin B (AmBisome) versus miltefosine in patients with post-kala-azar dermal leishmaniasis

Background: Treatment of post-kala-azar dermal leishmaniasis cases is of paramount importance for kala-azar elimination; however, limited treatment regimens are available as of now. Aim: To compare the effectiveness of liposomal amphotericin B vs miltefosine in post-kala-azar dermal leishmaniasis patients. Methodology: This was a randomized, open-label, parallel-group study. A total of 100 patients of post kala azar dermal leishmaniasis, aged between 5 and 65 years were recruited, 50 patients in each group A (liposomal amphotericin B) and B (miltefosine). Patients were randomized to receive either liposomal amphotericin B (30 mg/kg), six doses each 5 mg/kg, biweekly for 3 weeks or miltefosine 2.5 mg/kg or 100 mg/day for 12 weeks. All the patients were followed at 3rd, 6th and 12th months after the end of the treatment. Results: In the liposomal amphotericin B group, two patients were lost to follow-up, whereas four patients were lost to follow-up in the miltefosine group. The initial cure rate by “intention to treat analysis” was 98% and 100% in liposomal amphotericin B and miltefosine group, respectively. The final cure rate by “per protocol analysis” was 74.5% and 86.9% in liposomal amphotericin B and miltefosine, respectively. Twelve patients (25.5%) in the liposomal amphotericin B group and six patients (13%) in the miltefosine group relapsed. None of the patients in either group developed any serious adverse events. Limitations: Quantitative polymerase chain reaction was not performed at all the follow-up visits and sample sizes. Conclusion: Efficacy of miltefosine was found to be better than liposomal amphotericin B, hence, the use of miltefosine as first-line therapy for post-kala-azar dermal leishmaniasis needs to be continued. However, liposomal amphotericin B could be considered as one of the treatment options for the elimination of kala-azar from the Indian subcontinent.

Download Full-text

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

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz486 ◽

2019 ◽

Vol 221 (4) ◽

pp. 608-617 ◽

Cited By ~ 2

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.

Download Full-text

Case Report: Post Kala-Azar Dermal Leishmaniasis with History of Visceral Leishmaniasis

International Journal of Research and Review ◽

10.52403/ijrr.20210510 ◽

2021 ◽

Vol 8 (5) ◽

pp. 69-72

Author(s):

Pavankumar Narapaka ◽

Kalpana Katikala

Keyword(s):

Visceral Leishmaniasis ◽

Amphotericin B ◽

Liposomal Amphotericin ◽

Liposomal Amphotericin B ◽

First Line ◽

Treatment Regimens ◽

First Line Therapy ◽

Kala Azar ◽

History Of

The complication of visceral leishmaniasis is post-kala-azar dermal leishmaniasis (PKDL). PKDL typically occurs as a result of treatment failure or parasite resistance to treatment regimens, as well as poor patient follow-up. In the treatment of visceral leishmaniasis and post-kala-azar dermal leishmaniasis, Liposomal Amphotericin B is considering as first-line therapy. We're going to show you a case where Liposomal Amphotericin B was used to treat it. Keywords: visceral leishmaniasis, post-kala-azar dermal leishmaniasis, PKDL, kala-azar

Download Full-text

Liposomal amphotericin B for complicated visceral leishmaniasis (kala-azar) in eastern Sudan: how effective is treatment for this neglected disease?

Tropical Medicine & International Health ◽

10.1111/tmi.12238 ◽

2014 ◽

Vol 19 (2) ◽

pp. 146-152 ◽

Cited By ~ 24

Author(s):

Niven A. Salih ◽

Johan van Griensven ◽

François Chappuis ◽

Annick Antierens ◽

Ann Mumina ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Amphotericin B ◽

Liposomal Amphotericin ◽

Liposomal Amphotericin B ◽

Neglected Disease ◽

Kala Azar ◽

Eastern Sudan

Download Full-text

Treatment experience with liposomal amphotericin B in pediatric patients with kala-azar

Abant Medical Journal ◽

10.5505/abantmedj.2015.15010 ◽

2015 ◽

Vol 4 (3) ◽

pp. 222-229

Author(s):

Can Acıpayam ◽

Gülnaz Çulha ◽

Ali Altunay ◽

Fazilet Akoğlu ◽

Alkan Yeral ◽

...

Keyword(s):

Amphotericin B ◽

Liposomal Amphotericin ◽

Pediatric Patients ◽

Liposomal Amphotericin B ◽

Treatment Experience ◽

Kala Azar

Download Full-text

Successful Treatment of Post Kala-azar Dermal Leishmaniasis and Disseminated Tuberculosis Co-infection With Liposomal Amphotericin B and Anti-tubercular Drugs in Bangladesh

Infectious Diseases in Clinical Practice ◽

10.1097/ipc.0000000000000502 ◽

2017 ◽

Vol 25 (5) ◽

pp. 279-281

Author(s):

Md. Mahbubur Rashid ◽

Proggananda Nath ◽

Mizanur Rahman ◽

Dinesh Mondal ◽

Abul Khair Mohammad Shamsuzzaman ◽

...

Keyword(s):

Amphotericin B ◽

Successful Treatment ◽

Liposomal Amphotericin ◽

Liposomal Amphotericin B ◽

Disseminated Tuberculosis ◽

Kala Azar

Download Full-text

Pharmacokinetics of Liposomal Amphotericin B for Injection in Chinese Healthy Subjects Based on a Bioequivalence Study

10.21203/rs.3.rs-416411/v1 ◽

2021 ◽

Author(s):

Xueyuan Zhang ◽

Huanhuan Qi ◽

Manman Wang ◽

Yuhuan Ji ◽

Chunlei Li ◽

...

Keyword(s):

Amphotericin B ◽

Liposomal Amphotericin ◽

Geometric Mean ◽

Plasma Concentrations ◽

Bioequivalence Study ◽

Liposomal Amphotericin B ◽

Pharmacokinetic Parameters ◽

Healthy Population ◽

Open Label ◽

Liposomal Form

Abstract Purpose: The aim of this study was to evaluate the pharmacokinetic characteristics and safety of Liposomal Amphotericin B for injection in healthy Chinese volunteers based on a pilot bioequivalence clinical trial between a generic formulation and Ambisome ® Methods: This randomized, two sequence, open label, single dose,two period crossover study was conducted in healthy volunteers at the dose of 2mg kg Blood samples were collected at pre defined time points up to 674 h after the start of the 2 h infusion. Plasma concentrations of total, unencapsulated and encapsulated amphotericin B were determined. Pharmacokinetic parameters were calculated using non compartmental model . The formulations were considered bioequivalent if the 90% confidence interval ls (CIs) of the geometric mean ratio of C max and AUC of both products for free and encapsulated amphotericin B were within80.00 1 25.00 for L n transformed data. Results and conclusion: All the 12subjects completed the two period study , no subjects withdrew the study. The plasma pharmacokinetic profile of liposomal amphotericin B based on free, encapsulated and total amphotericin B demonstrated the characteristics of a three compartment al model. The majority drug in the circulating system after IV infusion of liposomal amphotericin B is remained liposomal form . Pharmacokinetic behaviors in Chinese population w ere consistent with that in western healthy population based on total and unbound amphotericin B concentrations in plasma. The generic liposomal amphotericin B for injection is bioequivalent to Ambisome ® in terms of the Pharmacokinetic parameters for free, encapsulated and total amphotericin B. Trial registration number at National Medical Products Administration CTR20200885 . Date of registration: May 22 , 20 2 0.

Download Full-text

Liposomal amphotericin B (AmBisome): efficacy and safety of low-dose therapy in pulmonary fungal infections

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/49.suppl_1.49 ◽

2002 ◽

Vol 49 (suppl_1) ◽

pp. 49-50 ◽

Cited By ~ 9

Author(s):

Cosimo Lequaglie

Keyword(s):

Amphotericin B ◽

Liposomal Amphotericin ◽

Low Dose ◽

Fungal Infections ◽

Liposomal Amphotericin B ◽

Deep Mycosis ◽

Pulmonary Fungal Infections ◽

A Prospective Study ◽

Thoracic Malignancies

Abstract A prospective study of the treatment of fungal infections with low-dose AmBisome enrolled 36 of 52 patients with thoracic malignancies who developed pulmonary fungal infections in the National Cancer Centre, Milan, over a 3.5 year period. Thirty-three high-risk patients had received standard prophylaxis with iv fluconazole. In these patients, symptoms indicating deep mycosis were detected after 7–9 days of primary prophylactic therapy. Another three patients, not treated with fluconazole, showed similar symptoms. Bronchoalveolar lavage, blood culture and/or CT scan of chest diagnosed invasive aspergillosis in 29 patients and deep invasive Candida infection in seven. AmBisome was given at 1–2.2 mg/kg/day iv for 10 days to avoid or decrease toxicity normally induced by amphotericin B. The fungal infection was eradicated in all 36 patients. Negative cultures were obtained after 5 or 6 days of antifungal treatment. No adverse reactions attributed to AmBisome were detected. After a follow up of 5–48 months, 30 patients were still alive. Six patients had died, two due to adult respiratory distress syndrome and four due to progression of cancer. No mycotic relapses or reinfections were detected during follow up. In a subset of critically ill patients with thoracic malignancies, the administration of low-dose liposomal amphotericin B (AmBisome) resulted in complete eradication of pulmonary Aspergillus and Candida infections, and was remarkably well tolerated.

Download Full-text