A retrospective cohort study of the effectiveness and adverse events of intralesional pentavalent antimonials in the treatment of cutaneous leishmaniasis

Rodrigues, Bruna Côrtes; Ferreira, Marina Freitas; Barroso, Daniel Holanda; Motta, Jorgeth Oliveira Carneiro da; Paula, Carmen Déa Ribeiro de; Porto, Cláudia Estrela; Martins, Sofia Sales; Gomes, Ciro Martins; Sampaio, Raimunda Nonata Ribeiro

doi:10.1016/j.ijpddr.2020.11.002

Cited by 10 publications

(18 citation statements)

References 28 publications

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“…There was a wide variation in the number of MA infiltration sessions, although the effectiveness of this therapeutic modality was similar to others studies [ 11 , 12 , 21 , 22 , 37 ].…”

Section: Discussionsupporting

confidence: 85%

“…Hypersensitivity reactions were more common than those observed in other studies [ 12 , 39 ], perhaps due to a larger number of IL infiltrations of the drug. Rodrigues and colleagues recently found an efficacy rate of 66.7% for IL treatment in a retrospective small cohort of 21 cases [ 22 ], this variation of effectiveness may be associated with the technique of application, personal variables of the patients and even the circulating strain. However, most patients from other Brazilian states included in this and other studies have been successfully treated with AR or IL [ 14 , 21 , 22 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Rodrigues and colleagues recently found an efficacy rate of 66.7% for IL treatment in a retrospective small cohort of 21 cases [ 22 ], this variation of effectiveness may be associated with the technique of application, personal variables of the patients and even the circulating strain. However, most patients from other Brazilian states included in this and other studies have been successfully treated with AR or IL [ 14 , 21 , 22 , 36 ]. In the nearby state of Minas Gerais, the effectiveness of the IL treatment of CL was 66.7% [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, most patients from other Brazilian states included in this and other studies have been successfully treated with AR or IL [ 14 , 21 , 22 , 36 ]. In the nearby state of Minas Gerais, the effectiveness of the IL treatment of CL was 66.7% [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

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An old drug and different ways to treat cutaneous leishmaniasis: Intralesional and intramuscular meglumine antimoniate in a reference center, Rio de Janeiro, Brazil

et al. 2021

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Background Treatment of cutaneous leishmaniasis (CL) remains challenging since the drugs currently used are quite toxic, thus contributing to lethality unrelated to the disease itself but to adverse events (AE). The main objective was to evaluate different treatment regimens with meglumine antimoniate (MA), in a reference center in Rio de Janeiro, Brazil. Methodology A historical cohort of 592 patients that underwent physical and laboratory examination were enrolled between 2000 and 2017. The outcome measures of effectiveness were epithelialization and complete healing of cutaneous lesions. AE were graded using a standardized scale. Three groups were evaluated: Standard regimen (SR): intramuscular (IM) MA 10–20 mg Sb5+/kg/day during 20 days (n = 46); Alternative regimen (AR): IM MA 5 mg Sb5+/kg/day during 30 days (n = 456); Intralesional route (IL): MA infiltration in the lesion(s) through subcutaneous injections (n = 90). Statistical analysis was performed through Fisher exact and Pearson Chi-square tests, Kruskal-Wallis, Kaplan-Meier and log-rank tests. Results SR, AR and IL showed efficacy of 95.3%, 84.3% and 75.9%, with abandonment rate of 6.5%, 2.4% and 3.4%, respectively. IL patients had more comorbidities (58.9%; p = 0.001), were mostly over 50 years of age (55.6%), and had an evolution time longer than 2 months (65.6%; p = 0.02). Time for epithelialization and complete healing were similar in IL and IM MA groups (p = 0.9 and p = 0.5; respectively). Total AE and moderate to severe AE that frequently led to treatment interruption were more common in SR group, while AR and IL showed less toxicity. Conclusions/Significance AR and IL showed less toxicity and may be good options especially in CL cases with comorbidities, although SR treatment was more effective. IL treatment was an effective and safe strategy, and it may be used as first therapy option as well as a rescue scheme in patients initially treated with other drugs.

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“…There was a wide variation in the number of MA infiltration sessions, although the effectiveness of this therapeutic modality was similar to others studies [ 11 , 12 , 21 , 22 , 37 ].…”

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

An old drug and different ways to treat cutaneous leishmaniasis: Intralesional and intramuscular meglumine antimoniate in a reference center, Rio de Janeiro, Brazil

et al. 2021

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“…Starting in the 1950s, pentavalent antimonial compounds were introduced as treatments against Leishmania species; however, these drugs are associated with several adverse events and are becoming increasingly ineffective due to the development of resistance [ 12 , 13 ]. Other drugs used to treat leishmaniasis include amphotericin B in a liposomal formulation, which significantly reduced the side effects and treatment duration associated with amphotericin B in the free form but is very expensive; and paromomycin and miltefosine, which are associated with high toxicity (particularly renal toxicity), increased resistance, and teratogenic and abortifacient effects [ 4 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I

et al. 2021

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The current treatments against Leishmania parasites present high toxicity and multiple side effects, which makes the control and elimination of leishmaniasis challenging. Natural products constitute an interesting and diverse chemical space for the identification of new antileishmanial drugs. To identify new drug options, an in-house database of 360 kauranes (tetracyclic diterpenes) was generated, and a combined ligand- and structure-based virtual screening (VS) approach was performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes were employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay. The half-maximal inhibitory concentration (IC50) values of selected bioactive compounds were examined using the random forest (RF) model (i.e., 2β-hydroxy-menth-6-en-5β-yl ent-kaurenoate (135) and 3α-cinnamoyloxy-ent-kaur-16-en-19-oic acid (302)) were below 10 μM. A compound similar to 302, 3α-p-coumaroyloxy-ent-kaur-16-en-19-oic acid (302a), was also synthesized and showed the highest activity against LmPTR1. Finally, molecular docking calculations and molecular dynamics simulations were performed for the VS-selected, most-active kauranes within the active sites of PTR1 hybrid models, generated from three Leishmania species that are known to cause cutaneous leishmaniasis in the new world (i.e., L. braziliensis, L. panamensis, and L. amazonensis) to explore the targeting potential of these kauranes to other species-dependent variants of this enzyme.

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Meglumine antimonate

2021

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Meglumine antimonate Elevation of hepatocellular enzymes and cardiotoxicity followed by off-label administration: 2 case reportsIn a retrospective cohort study of 240 patients between 1999 to 2017, at the University Hospital of Brasilia, Brazil, 2 patients [ages and sexes not stated] were described, who developed elevation of hepatocellular enzymes or cardiotoxicity during off-label treatment with meglumine antimonate for American cutaneous leishmaniasis [dosages and duration of treatment to reaction onsets not stated; not all outcome stated].The patients were diagnosed with American cutaneous leishmaniasis, and were enrolled in the study. Later, they started receiving off-label intralesional meglumine antimoniate (unapproved route of administration). Subsequently, they developed elevation of hepatocellular enzymes (n=1) and cardiotoxicity (n=1). The patient with cardiotoxicity recovered.Rodrigues BC, et al. A retrospective cohort study of the effectiveness and adverse events of intralesional pentavalent antimonials in the treatment of cutaneous leishmaniasis.

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A retrospective cohort study of the effectiveness and adverse events of intralesional pentavalent antimonials in the treatment of cutaneous leishmaniasis

Cited by 10 publications

References 28 publications

An old drug and different ways to treat cutaneous leishmaniasis: Intralesional and intramuscular meglumine antimoniate in a reference center, Rio de Janeiro, Brazil

An old drug and different ways to treat cutaneous leishmaniasis: Intralesional and intramuscular meglumine antimoniate in a reference center, Rio de Janeiro, Brazil

Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I

Meglumine antimonate

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