Antileishmanial efficacy and tolerability of combined treatment with non-ionic surfactant vesicle formulations of sodium stibogluconate and paromomycin in dogs

Background Visceral leishmaniasis (VL) is one of the most neglected tropical infectious diseases. It is fatal if left untreated. The objective of this study was to assess the efficacy and safety of 17-day injections of combined regimen of sodium stibogluconate and paromomycin (SSG/PM) in HIV-negative VL patients. Methods A retrospective analysis of medical records of VL patients treated in the University of Gondar Hospital during period 2012–2019 was carried out. Results A total of 2836 patients were treated for VL from 2012 to 2019. Of these 1233 were treated with SSG-PM, and 1000 of them were included in the study. Initial cure was achieved in 922 (92.2%) patients. The frequency of treatment failure, treatment interruptions, default and deaths respectively were 30 (3%), 20 (2%), 13 (1.3%) and 15 (1.5%). Among 280 patients who completed 6-month follow up, the final cure was 93.9% (263/280), 4 (1.4%) relapsed and 13 (4.6%) developed post-kala-azar dermal leishmaniasis (PKDL). The most common adverse events (AEs) were raised liver transaminases (35.1%; 351 patients), injection site pain (29.1%, 291 patients) and raised serum alpha-amylase (29.1%, 291 patients). Factors associated with poor treatment outcomes were sepsis, pneumonia, and adverse events. Conclusion A combination of SSG at 20mg/kg with upper daily maximum dose of 850mg and PM was effective for achieving initial cure at end of treatment and safe for treatment of HIV negative VL patients in northwestern Ethiopia. Our data are consistent with previous reports and confirms effectiveness of SSG/PM treatment regimen in the Eastern African countries. Efficacy at 6-months (93.9%) was estimated on data derived from patients who completed follow up and needs to be interrogated by future studies.

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Visceral Leishmaniasis in the BALB/c Mouse: A Comparison of thein VivoActivity of Five Non-Ionic Surfactant Vesicle Preparations of Sodium Stibogluconate

Journal of Drug Targeting ◽

10.3109/10611869509015926 ◽

1995 ◽

Vol 3 (1) ◽

pp. 1-7 ◽

Cited By ~ 16

Author(s):

D. M. Williams ◽

K. C. Carter ◽

A. J. Baillie

Keyword(s):

Visceral Leishmaniasis ◽

Ionic Surfactant ◽

Sodium Stibogluconate

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The In Vivo Susceptibility of Leishmania donovani to Sodium Stibogluconate Is Drug Specific and Can Be Reversed by Inhibiting Glutathione Biosynthesis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.5.1529-1535.2003 ◽

2003 ◽

Vol 47 (5) ◽

pp. 1529-1535 ◽

Cited By ~ 36

Author(s):

K. C. Carter ◽

S. Sundar ◽

C. Spickett ◽

O. C. Pereira ◽

A. B. Mullen

Keyword(s):

Resistant Strain ◽

Leishmania Donovani ◽

Combined Treatment ◽

Sensitive Strain ◽

Cross Resistance ◽

Concomitant Treatment ◽

Sodium Stibogluconate ◽

Glutathione Biosynthesis ◽

Clinical Resistance

ABSTRACT Resistance to pentavalent antimonial (Sbv) agents such as sodium stibogluconate (SSG) is creating a major problem in the treatment of visceral leishmaniasis. In the present study the in vivo susceptibilities of Leishmania donovani strains, typed as SSG resistant (strain 200011) or SSG sensitive (strain 200016) on the basis of their responses to a single SSG dose of 300 mg of Sbv/kg of body weight, to other antileishmanial drugs were determined. In addition, the role of glutathione in SSG resistance was investigated by determining the influence on SSG treatment of concomitant treatment with a nonionic surfactant vesicle formulation of buthionine sulfoximine (BSO), a specific inhibitor of the enzyme γ-glutamylcysteine synthetase which is involved in glutathione biosynthesis, and SSG, on the efficacy of SSG treatment. L. donovani strains that were SSG resistant (strain 200011) and SSG sensitive (strain 200016) were equally susceptible to in vivo treatment with miltefosine, paromomycin and amphotericin B (Fungizone and AmBisome) formulations. Combined treatment with SSG and vesicular BSO significantly increased the in vivo efficacy of SSG against both the 200011 and the 200016 L. donovani strains. However, joint treatment that included high SSG doses was unexpectedly associated with toxicity. Measurement of glutathione levels in the spleens and livers of treated mice showed that the ability of the combined therapy to inhibit glutathione levels was also dependent on the SSG dose used and that the combined treatment exhibited organ-dependent effects. The SSG resistance exhibited by the L. donovani strains was not associated with cross-resistance to other classes of compounds and could be reversed by treatment with an inhibitor of glutathione biosynthesis, indicating that clinical resistance to antimonial drugs should not affect the antileishmanial efficacies of alternative drugs. In addition, it should be possible to identify a treatment regimen that could reverse antimony resistance.

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Efficacy of botulinum toxin A, serial casting, and combined treatment for spastic equinus: a retrospective analysis

Developmental Medicine & Child Neurology ◽

10.1017/s0012162205211295 ◽

2005 ◽

Vol 47 (09) ◽

pp. 635

Author(s):

Jean-Pierre Lin

Keyword(s):

Botulinum Toxin ◽

Retrospective Analysis ◽

Botulinum Toxin A ◽

Combined Treatment ◽

Toxin A ◽

Serial Casting

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Hybrid treatment of multilevel revascularization in patients with peripheral arterial disease – a multi-centre study in Korea

VASA ◽

10.1024/0301-1526/a000694 ◽

2018 ◽

Vol 47 (3) ◽

pp. 235-241 ◽

Cited By ~ 2

Author(s):

Soon Cheon Lee ◽

Jin Hyun Joh ◽

Jeong-Hwan Chang ◽

Hyung-Kee Kim ◽

Jang Yong Kim ◽

...

Keyword(s):

Endovascular Treatment ◽

Combined Treatment ◽

Ankle Brachial Index ◽

Primary Patency ◽

Limb Ischaemia ◽

University Hospitals ◽

Multi Centre Study ◽

Free Survival ◽

Technical Success Rate ◽

Hybrid Treatment

Abstract. Background: Endovascular treatment is an alternative first-line management for peripheral artery disease (PAD). Hybrid treatment (HT) is defined as a combined treatment for patients with PAD using endovascular and open surgery, simultaneously performed in an operating room. The results of HT are reportedly good for multilevel revascularization (MR) in patients with chronic limb ischaemia, and even in older high-risk patients. The goal of this study was to examine the clinical and haemodynamic outcomes of HT in patients who need MR. Patients and methods: Nine university hospitals in Korea participated in this multicentre study. A total of 134 patients with multilevel PAD underwent HT and MR. Patients were enrolled from July 2014 to June 2015 and were followed for 18 months. Results: The mean age of the patients was 68.8 ± 9.93 years and 88.1 % were men. Patients with Rutherford category 2 to 3 and 4 to 6 comprised 59.0 % and 42.0 % of the group, respectively. The technical success rate was 100 %. The primary patency rates at 12 and 18 months were 77.6 % and 63.9 %, respectively. The primary-assisted patency rates at 12 and 18 months were both 90.0 %. The pre-operative mean ankle brachial index (0.43 ± 0.23) increased to 0.87 ± 0.23 at six months post-operatively (t-test, p < 0.05). The amputation free survival rate was 97.1 %. Conclusions: Although outcomes of multilevel PAD are reportedly poor when endovascular treatment alone is used, we have shown that HT is a feasible alternative modality for patients with multilevel PAD, with satisfactory amputation-free survival and freedom from re-intervention rates.

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A Case of Catatonia in a 14-Year-Old Girl with Schizophrenia Treated with Electroconvulsive Therapy

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie ◽

10.1024/1422-4917/a000211 ◽

2013 ◽

Vol 41 (1) ◽

pp. 69-74 ◽

Cited By ~ 10

Author(s):

Frank Häßler ◽

Olaf Reis ◽

Steffen Weirich ◽

Jacqueline Höppner ◽

Birgit Pohl ◽

...

Keyword(s):

Case Report ◽

Treatment Response ◽

Electroconvulsive Therapy ◽

Rating Scale ◽

Combined Treatment ◽

Adolescent Patient

This article presents a case of a 14-year-old female twin with schizophrenia who developed severe catatonia following treatment with olanzapine. Under a combined treatment with amantadine, electroconvulsive therapy (ECT), and (currently) ziprasidone alone she improved markedly. Severity and course of catatonia including treatment response were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This case report emphasizes the benefit of ECT in the treatment of catatonic symptoms in an adolescent patient with schizophrenic illness.

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