Successful Treatment of Colombian Cutaneous Leishmaniasis with Four Injections of Pentamidine

Soto, Jaime; Buffet, Pierre; Grögl, Max; Berman, Jonathan

doi:10.4269/ajtmh.1994.50.107

Cited by 97 publications

(59 citation statements)

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“…Effectiveness and safety of this TTM has been previously demonstrated in patients not necessarily with contra-indications to the systemic use of MA. 12 Effectiveness of IL TTM was similar to that reported for higher IM doses of MA, [13][14][15] with less AE. [13][14][15] We recently reported a 44-patient series with older individuals who underwent low-dose intermittent IM MA, 16 with worse effectiveness and more AE.…”

supporting

confidence: 62%

Intralesional Meglumine Antimoniate for Treatment of Cutaneous Leishmaniasis Patients with Contraindication to Systemic Therapy from Rio de Janeiro (2000 to 2006)

Vasconcellos¹,

Pimentel²,

Schubach³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. We evaluated the effectiveness and safety of intralesional meglumine antimoniate (MA) in 24 not submitted to previous treatment patients with cutaneous leishmaniasis (CL) and with contraindication to systemic therapy. Each treatment consisted of one to four intralesional applications of MA at 15-day intervals. Patients' age ranged from 3 to 90 years; fourteen were females. Intralesional treatment in the absence of any relevant toxicity was successful in 20 (83.3%) patients. Three patients required additional treatment with amphotericin B and one required systemic MA. None of the patients developed mucosal lesions when followed up to 60 months. Intralesional MA is an effective and less toxic alternative treatment of patients with CL and contraindication to systemic therapy.American tegumentary leishmaniasis (ATL) affects the skin (cutaneous leishmaniasis, CL) and/or mucous membranes, and is caused by protozoa of the genus Leishmania, transmitted through the bite of sandflies. Research of IPEC; all patients signed a free informed consent form. All patients had a confirmed parasitological diagnosis of CL, had not been previously submitted to TTM, and had contraindication to systemic use of MA. A scale adapted from the Aids Table for Grading the Severity of Adverse Events 7 was used for the evaluation of AE and baseline clinical alterations, where G1 = mild, G2 = moderate, G3 = severe, and G4 = life-threatening. Contraindications to systemic antimonial therapy were 1) presence of baseline clinical alterations corresponding to G3; 2) presence of baseline laboratory alterations corresponding to G2; 3) presence of baseline electrocardiographic alterations corresponding to G3 or G4 (baseline adjusted QT interval [QT adj ] 0.46 ms was considered G3); 4) psychiatric disorders or high probability of low compliance with systemic TTM.AE were monitored by clinical examination, electrocardiogram (EKG), complete blood count and blood biochemistry, before, during, and soon after the end of TTM.The MA was supplied by the Brazilian Ministry of Health (Aventis Pharma, Sã o Paulo, Brazil). Each TTM consisted of 1-4 IL applications of MA, at 15-day intervals. The IL MA was injected subcutaneously until completely infiltrating the base of the lesion. Immediate cure was defined as epithelization up to 90 days after IL TTM. Lesion progression until complete healing was monitored through absence of crusts up to 1 month after epithelization, desquamation up to 3 months, infiltration up to 6 months, and erythema up to 9-12 months, as well as the absence of mucosal lesions. 8 Patients who presented lesion reactivation after TTM were retreated using the same or an alternative regimen; additional IL TTM or other medications were applied according to the presence or absence of EKG changes at the occasion of retreatment and/or therapeutic failure.The nonparametric Mann-Whitney test was used to compare the distribution of continuous variables (lesion area, volume of infiltrated medication per lesion area, etc.) between two groups (pres...

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supporting

confidence: 62%

Intralesional Meglumine Antimoniate for Treatment of Cutaneous Leishmaniasis Patients with Contraindication to Systemic Therapy from Rio de Janeiro (2000 to 2006)

Vasconcellos¹,

Pimentel²,

Schubach³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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“…The treatment with pentamidine is not fully effective and has also toxic side effects (Soto et al, 1994). Thus, the search for new antileishmanial drugs remains a priority since no currently available drug is both safe and active.…”

Section: L'action Antileishmanienne Du Tétraphénylborate D'ir-(cod)-pmentioning

confidence: 99%

In vivoantileishmanial action of Ir-(COD)-pentamidine tetraphenylborate onLeishmania donovaniandLeishmania majormouse models

et al. 2000

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Summary:lr-(COD)-pentamidine tetraphenylborate which has previously been studied on promastigote forms of Leishmania, was investigated for its antileishmanial properties compared with pentamidine used as reference compound. In vitro, the iridium complex had the same IC 50 value on intracellular forms of Leishmania as pentamidine (15 µM). In vivo, the compound could not be injected intravenously due to the DMSO excipient so that the treatments were performed intraperitoneally or subcutaneously. On the L. donovani LV9 /Balb/C mouse model, the iridium complex was not toxic after intraperitoneal treatment at 232 mg/kg/day x 5 or 147 µmoles/ kg/day x 5, whereas all the mice died within five days when treated at the same dose with pentamidine isethionate. However, only 23 % of parasite suppression was observed with the iridium complex. On a L. major MON 74/Balb/C mouse model, susceptible to intravenously administered pentamidine at 6.7 umoles/ kg/day x 5 (54 % of parasite suppression), the iridium complex exhibited 32 % of parasite suppression after a treatment at 76 umoles/ kg/day x 5 administered subcutaneously. This slight activity is of interest since pentamidine isethionate is not active under these conditions. Transmission electron microscopy of amastigotes from infected and treated mice show aggregation of ribosomal material, distension of the nuclear membrane and kDNA depolymerization. The mechanism of action therefore involves several targets: membranes, ribosomes and kDNA. According to our results, the Iridium complex is a suitable candidate to be encapsulated in drug carriers such as liposomes or nanoparticles.KEYWORDS : Iridium pentamidine complex, pentamidine, Leishmania, electron microscopy, mechani sm of action. MOTS CLÉS

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“…The largest lesion in this study was set at 500 mm 2 so that a maximum of 60 mg of pentamidine would be injected each day, for a total dose over three injections of approximately 3 mg/kg. Intramuscular pentamidine at 2 mg/kg/injection × four injections-total dose of 8 mg/kg-to 42 patients, resulted in myalgias in 16 patients and nausea in 3 patients, and no instances of sterile abscess, low blood pressure, or low glucose, 16 and we anticipated that a total IL dose of 3 mg/kg would not produce systemic adverse effects.…”

Section: 15mentioning

confidence: 99%

Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis

Soto¹,

Paz²,

Rivero³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. A novel therapy, intralesional (IL) pentamidine, was compared to intralesional therapy with antimony (ILSb), a World Health Organization-recommended therapy, for single Bolivian Leishmania braziliensis lesions. In Study 1, 90 patients were randomized equally between three injections of ILSb over 5 days, five injections of ILSb over 11 days, and three injections of IL pentamidine (120 μg/mm 2 lesion area [ILPenta-120-3]) over 5 days. Cure rates at 6 months were 57% for ILSb-3 injections, 73% for ILSb-5 injections, and 72% for ILPenta-120-3 injections. Adverse effects were local irritation and injection-site pain-ILSb (60 patients): mild (25), moderate (4); IL pentamidine (30 patients): mild (4), moderate (3). In Study 2, 60 patients were randomized equally between five injections of ILSb and three injections of a double dose of IL pentamidine (240 μg/mm 2 ). In Study 2, cure rates were 67% for ILSb-5 injections and 73% for ILPenta-240-3. For three IL injections of pentamidine, efficacy was optimized at a dose of 120 μg/mm 2 lesion area. The cure rate of that regimen was similar to that for ILSb-5 injections and nonstatistically larger than that of ILSb-3 injections. IL pentamidine is an attractive alternative to ILSb on the basis of efficacy for Bolivian L. braziliensis, the threat of Sb-resistant parasites, tolerance, and patient convenience of three visits over 5 days.

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Successful Treatment of Colombian Cutaneous Leishmaniasis with Four Injections of Pentamidine

Cited by 97 publications

References 0 publications

Intralesional Meglumine Antimoniate for Treatment of Cutaneous Leishmaniasis Patients with Contraindication to Systemic Therapy from Rio de Janeiro (2000 to 2006)

Intralesional Meglumine Antimoniate for Treatment of Cutaneous Leishmaniasis Patients with Contraindication to Systemic Therapy from Rio de Janeiro (2000 to 2006)

In vivoantileishmanial action of Ir-(COD)-pentamidine tetraphenylborate onLeishmania donovaniandLeishmania majormouse models

Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis

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