Ketoconazole in the Treatment of Cutaneous Leishmaniasis in Kuwait

Dvořák, Richard; Nanda, Arti

doi:10.1111/j.1365-4362.1995.tb00622.x

Cited by 37 publications

(22 citation statements)

References 13 publications

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“…Table IV demonstrates RCTs of azole drugs in the treatment of acute Old World CL. 5,[24][25][26][27][28][29][30][31][32][33] When the type of studied drugs, mode of administration, dosage, duration of treatment, and causative Leishmania species were considered, the heterogeneity of RCTs on azole agents in this review becomes evident. Among this group, 5 placebocontrolled trials assessed the efficacy of oral itraconazole with controversial results.…”

Section: Azole Agentsmentioning

confidence: 99%

Treatment of acute Old World cutaneous leishmaniasis: A systematic review of the randomized controlled trials

Khatami

Firooz

Gorouhi

et al. 2007

Journal of the American Academy of Dermatology

117

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Section: Azole Agentsmentioning

confidence: 99%

Treatment of acute Old World cutaneous leishmaniasis: A systematic review of the randomized controlled trials

Khatami

Firooz

Gorouhi

et al. 2007

Journal of the American Academy of Dermatology

117

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“…Most studies defined cure as complete re-epithelialization of all lesions. However, in one study, cure was defined by “ Leishmania donovani bodies negativity” [29], while another considered “reduction in the size of lesions by 80% up to complete clearance” [26], and a third considered “more than 90% re-epithelization and negative smear for Leishmania parasites” [33]. Systemic therapeutic regimens with azoles encompassed the use of itraconazole, ketoconazole or fluconazole.…”

Section: Resultsmentioning

confidence: 99%

“…After exclusion of studies assessing cure by criteria other than complete re-epithelization [26,29,33], the estimated initial response rate for all azoles was 50% (CI95%: 40–60%, I 2 = 85.7%) and the cure rates remained similar in the analysis of each azole group: 37% (CI95%: 14–67%, I 2 = 90%) for ketoconazole, 61% (CI95%: 50–70%, I 2 = 71.8%) for itraconazole and the same rate fluconazole (45%, CI95%: 29–62%, I 2 = 88.2%). The final efficacy rate considering all studies were similar among the fluconazole (61%, CI95%: 48–72%, I 2 = 81%), itraconazole (65%, CI95%: 56–72%, I 2 = 55%) and ketoconazole (64%, CI95%: 44–80%, I 2 = 85%) group arms (p = 0.89) (Fig 2).…”

Section: Resultsmentioning

confidence: 99%

Efficacy of azole therapy for tegumentary leishmaniasis: A systematic review and meta-analysis

2017

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BackgroundSeveral controlled and uncontrolled studies addressing azole antifungal drugs for cutaneous and mucosal leishmaniasis have been published with inconclusive results. We conducted a systematic literature review of studies evaluating the efficacy and toxicity associated with azole therapy for tegumentary leishmaniasis.MethodologyPRISMA guidelines for systematic reviews and the Cochrane manual were followed, and the review methodology was registered (PROSPERO; CRD42016048668). Sources included the EMBASE, Web of Science, MEDLINE, LILACS, and IBECS databases along with a manual search of references from evaluated studies. Additional resources such as Google Scholar and clinicaltrials.gov were also searched. We included all studies reporting cure rate after cutaneous or mucosal leishmaniasis treatment with systemic azole drugs, regardless of their design. R software was used to estimate global rates of success and adverse events with each drug. The main outcome of interest was clinical cure, defined as complete re-epithelialization of all lesions.ResultsA total of 37 studies involving 1259 patients that reported outcomes after fluconazole (9), ketoconazole (14) and itraconazole (15) treatments were included. Only 14 (38%) were randomized controlled trials (RCT). The pooled azole final efficacy rate was 64% (CI95%: 57–70%) for all studies and 60% (CI95%: 50–70%) (p = 0.41) if only RCTs studies were considered. Twenty-four studies were conducted in the Old World and 13 studies in the Americas. The final efficacy rate according to New and Old World were 62% (CI95%: 43–77%) and 66% (CI95%: 58–73%), respectively. The final efficacy rate of azoles according to species were 89% (CI95%: 50–98%) for L. mexicana; 88% for L. infantum (CI95%: 27–99%); 80% for L. donovani; 53% (CI95%: 29–76%) for L. major; 49% for L. braziliensis (CI95%: 21–78%); and 15% (CI95%: 1–84%) for L. tropica. The cure rates were similar among the fluconazole, ketoconazole and itraconazole group arms (p = 0.89), specifically 61% (CI95%: 48–72%), 64% (CI95%: 44–80%) 65% (CI95%: 56–72%), respectively. Adverse events during fluconazole, itraconazole and ketoconazole therapy were reported in 7% (CI95%: 3–14%), 12% (CI95% 8–19%) and 13% (CI95%: 6–29%) of treated patients, respectively, without difference among them (p = 0.35). This systematic review included studies with small samples and both non-comparative and non-randomized studies and the main limitation was the low quality of the available studies.ConclusionsAvailable evidence suggests that fluconazole, ketoconazole and itraconazole have similar and modest efficacy rates for tegumentary leishmaniasis treatment. There is insufficient evidence to support the exclusive use of azole therapy as a single agent for leishmaniasis treatment.

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“…Previous clinical trials studies showed the efficacy of ketoconazole alone in several Leishmania species around the world [17, 18, 19, 20], and the literature also pointed out that ketoconazole efficacy is comparable to those of antimonial based drugs [21, 22, 23]. However, to our knowledge, only one study focused on the combined therapy of ketoconazole and antimony.…”

Section: Discussionmentioning

confidence: 98%

In vitro additive interaction between ketoconazole and antimony against intramacrophage Leishmania (Leishmania) amazonensis amastigotes

et al. 2017

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Leishmaniasis is a group of diseases caused by protozoa of Leishmania genus. The currently available treatments for this disease are expensive, present high toxicity and are associated to difficulties of healing and parasite resistance. Therefore, the development of strategies for leishmaniasis treatment is indispensable and includes reposition of existing drugs, as well as drug combination therapy. The aim of this study was to assess the nature of ketoconazole and antimony association on the cytotoxic effect against Leishmania (Leishmania) amazonensis amastigotes. The calculated mean sum of fractional 50% inhibitory concentration (ΣFIC50) was 2.54 and 1.43 for free and intracellular amastigotes, respectively, values that suggest an additive interaction between ketoconazole and antimony concerning to Leishmania toxicity only in the intramacrophage parasite form. Despite the clinical efficacy of ketoconazole-antimony combination has been shown in the literature, our study is the first to describe the nature of ketoconazole-antimony interaction against L. (L.) amazonensis amastigotes. Moreover, our results point out the need for future in vivo studies to confirm the nature of ketoconazole-antimony interaction and also to determine possible effective dosage regimens related to ketoconazole administration in association with the optimal lower dose of antimony.

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Ketoconazole in the Treatment of Cutaneous Leishmaniasis in Kuwait

Cited by 37 publications

References 13 publications

Treatment of acute Old World cutaneous leishmaniasis: A systematic review of the randomized controlled trials

Treatment of acute Old World cutaneous leishmaniasis: A systematic review of the randomized controlled trials

Efficacy of azole therapy for tegumentary leishmaniasis: A systematic review and meta-analysis

In vitro additive interaction between ketoconazole and antimony against intramacrophage Leishmania (Leishmania) amazonensis amastigotes

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