Ketoconazole for Cutaneous Leishmaniasis in the Context of Drug Shortages: A Case Report from Madre de Dios, Peru

Abstract

Background

Cutaneous leishmaniasis (CL) is a neglected tropical disease endemic in the Peruvian Amazon. First-line treatment with pentavalent antimonials was unavailable in Madre de Dios, Peru in early 2024 due to a supply-chain crisis. Oral ketoconazole has shown in vitro activity and modest efficacy in small clinical series as a salvage therapy, though it is not established as standard treatment.

Case Presentation

A 41-year-old woman (body mass index 48 kg/m²) from a rural community in Madre de Dios presented with two ulcerative lesions (0.8 cm and 1.2 cm) on the dorsal aspect of the left little finger, of 4 weeks’ duration. CL was confirmed by Giemsa smear and PCR as Leishmania (Viannia) sp. (~98% homology with local reference strains). In the absence of antimonials, and after informed consent, she received oral ketoconazole 200 mg twice daily for 6 weeks. By week 4, total lesion area had contracted by ~65%, and follow-up polymerase chain reaction (PCR) turned negative. Near-complete re-epithelialization was achieved by week 6. No hepatotoxicity or serious adverse events occurred; only mild transient nausea was reported. At 12 months’ follow-up, there was no relapse.

Conclusions

In this single-patient experience, oral ketoconazole (200 mg every 12 hours for 6 weeks) appeared to be an effective and well-tolerated alternative for CL during an antimonial shortage. Given the possibility of spontaneous healing in CL and the lack of a control group, controlled clinical trials are warranted before broader adoption.

Introduction

Cutaneous leishmaniasis (CL) causes an estimated 1.5-2 million new cases globally each year [1]. The disease is endemic in tropical and subtropical regions, including the Amazon of Peru, where the burden remains high [2,3]. In early 2024, a disruption in the regional supply chain produced a shortage of pentavalent antimonials in Madre de Dios, leaving many patients without standard therapy [4,5]. This crisis underscored the need for safe, oral alternatives. Ketoconazole, a broad-spectrum imidazole antifungal, inhibits the parasite’s 14α-demethylase, disrupting ergosterol biosynthesis and membrane integrity, with downstream mitochondrial dysfunction and cell death demonstrated in vitro for North, Central, and South American species [6]. Small clinical series in the 1980s-1990s reported cure rates of approximately 60-76% with oral ketoconazole regimens [7,8]. However, ketoconazole is not part of current standard treatment for CL, and evidence remains limited [9]. We report a case of CL effectively managed with oral ketoconazole during a documented antimonial shortage, and we discuss feasibility, safety, and limitations of this approach in a resource-limited Amazonian setting.

Case Presentation

A 41-year-old female food-service worker from rural Madre de Dios, Peru, presented in March 2024 with a 4-week history of two enlarging ulcers on the left fifth finger. On examination, two adjacent ulcers (0.8 cm and 1.2 cm) were noted on the dorsal aspect, with raised indurated borders and a granulomatous base. Figure 1 provides a centimeter scale for reference. No lymphangitic streaking or lymphadenopathy was present. Giemsa-stained smear revealed intracellular Leishmania amastigotes; PCR confirmed Leishmania (Viannia) species with 98% similarity to local reference strains. Given the unavailability of antimonials, informed consent was obtained to initiate oral ketoconazole 200 mg every 12 hours with food for 6 weeks. Baseline liver function (AST/ALT) was within normal limits. No concomitant medications were used apart from acetaminophen as needed.

Figure 1.

Initial clinical presentation of cutaneous lesions on the left little finger (dorsal aspect). Two ulcers (≈0.8 cm and 1.2 cm) with raised borders and granulomatous bases.

By week 2, the indurated area had decreased by ~30% and lesion pain improved. Quantitative PCR on a lesion swab showed a drop in parasite DNA load from ~1.2×10^5 to 3.4×10^4 genomes/µg. At week 4, the total lesion area contracted by ~65% (larger ulcer ~0.63 cm²), inflammation subsided, and conventional PCR was negative. By week 6, both lesions had near-complete re-epithelialization (Figure 2). AST and ALT remained normal throughout (eg, AST 22 U/L, ALT 18 U/L at week 6). The only adverse effect was mild transient nausea, self-limited. Post-treatment follow-up occurred monthly for 3 months, then at 6 and 12 months: lesions fully healed by month 3, and no relapse or mucosal involvement occurred through month 12. Figure 3 summarizes the timeline of lesion size, PCR results, treatment, and liver tests.

Figure 2.

Six-week follow-up demonstrating near-complete re-epithelialization of both lesions.

Figure 3.

Timeline of lesion progression, ketoconazole treatment (weeks 0-6), PCR results, and liver function checkpoints through 12-month follow-up.

Patient Perspective

“When I saw the sore on my hand, I felt ashamed and feared losing my job because I work with food. Later, when I sought care, I worried I wouldn’t receive treatment due to the medicine shortage. I signed the consent form because I trusted the clinic staff and they explained everything clearly. After two weeks I already noticed improvement and was thrilled to watch it disappear bit by bit. Today, I only see a small scar and I’m grateful that this option was available when I needed it.”

Discussion

This case illustrates the real-world use of oral ketoconazole as a salvage therapy for CL during a regional shortage of first-line drugs. Peru remains a hotspot of CL, with a large share of cases in Amazonian departments including Madre de Dios [2,3]. Local ecological and occupational factors (eg, mining-related deforestation and migration) contribute to sustained transmission [10]. The antimonial stockout in early 2024 left patients at risk of prolonged disease and complications, highlighting the value of an oral, room-temperature, stable alternative [4,5].

Mechanistically, ketoconazole inhibits Leishmania 14α-demethylase and has been shown to induce mitochondrial dysfunction and parasite death in vitro, including in North, Central, and South American species [6]. Nevertheless, antiparasitic effects vary across species and strains; efficacy observed in one species may not generalize to others [3]. Clinically, small series reported modest cure rates with oral ketoconazole in North, Central, and South American CL [7,8], whereas high-dose fluconazole did not outperform placebo in a randomized trial [11]. Miltefosine remains the only widely used oral antileishmanial, but its cost and teratogenicity limit use in some settings [12]. Given these trade-offs, ketoconazole may have a role as a temporary option during supply disruptions when careful monitoring is feasible.

Safety is paramount. Oral ketoconazole can cause idiosyncratic hepatotoxicity; the US FDA restricts its use and recommends frequent liver function monitoring [13]. CDC guidance similarly recommends close monitoring during therapy [9]. In our resource-limited context, we obtained baseline and mid-treatment AST/ALT via sample transport to a regional lab and conducted clinical checks every 2 weeks. No hepatotoxicity occurred. Pragmatic stopping rules (eg, ALT > upper limit of normal confirmed on repeat testing, or ≥3× ULN with symptoms) should be pre-specified [13]. While some reviews suggest low rates of transient, asymptomatic LFT elevations with short courses [11], clinicians must remain vigilant.

Accurate diagnostics added value. We confirmed Leishmania (V.) by smear and PCR and used qPCR to document an objective decline in parasite load [15,16]. Where on-site lab capacity is limited, filter paper sampling and centralized PCR, or LAMP in district hospitals, can support species-level diagnosis and follow-up [10]. Because Leishmania (V.) infections carry a risk of mucosal dissemination, extended follow-up is appropriate even after apparent cure [3,17].

Limitations include the single-patient design and absence of a comparator. Uncomplicated CL can heal spontaneously over months to a year or more [17]; therefore, we cannot definitively attribute the cure to ketoconazole alone. The relatively rapid clinical and molecular response in this case is suggestive but not conclusive. Future randomized studies should assess ketoconazole versus standard therapy or other oral agents, stratified by species, and incorporate rigorous safety monitoring. Until such data exist, any use of ketoconazole for CL should remain individualized and cautiously monitored.

From a health-systems perspective, contingency planning for drug shortages could include maintaining limited emergency stocks of oral agents (eg, ketoconazole, where legally permissible), clear safety-monitoring protocols, and access pathways for confirmatory diagnostics [5,18].

Practical Hepatic Safety Monitoring for Oral Ketoconazole in Low-Resource Settings

• Baseline AST/ALT prior to therapy; avoid in known chronic liver disease or pregnancy [13].

• Preferred: weekly AST/ALT during treatment; minimum: baseline and mid-course with biweekly clinical checks [9,13].

• Stop ketoconazole if ALT rises above ULN and persists on repeat, or ≥3× ULN with symptoms of hepatitis; evaluate and report [13].

• Educate patient on warning symptoms: jaundice, pruritus, dark urine, RUQ pain, anorexia, fatigue [13].

Conclusions

Ketoconazole (200 mg every 12 hours for 6 weeks) achieved a clinical and parasitological cure in a case of CL during a documented antimonial shortage. This anecdotal experience suggests that repurposed azole therapy can serve as a stopgap option when standard treatments are inaccessible, provided that safety monitoring is feasible. However, controlled trials are needed before broader use can be recommended.

Glossary

CL

Cutaneous Leishmaniasis

PCR

Polymerase Chain Reaction

Ethics approval and consent

Written informed consent was obtained in the context of the antimonial shortage. The patient authorized publication of clinical data and images. Written informed consent was obtained from the patient prior to any diagnostic or therapeutic procedures, in accordance with the Declaration of Helsinki. The informed consent form, adapted to local ethical standards, is kept on file at Posta Médica Salvación and can be provided upon request.

Competing interests

The author declares no conflicts of interest.

Author Contributions

PJVP: Conceptualization; Supervision; Clinical data curation; Writing—Original Draft; Writing—Review & Editing; Informed consent coordination; Clinical image collection.

Funding Statement

This work received no external funding from public, commercial, or not-for-profit agencies.

Data Availability

No new datasets, sequence data, or plasmids were generated or deposited in public repositories. All clinical information, lesion photographs, and laboratory results are fully described in the manuscript and are available from the corresponding author upon reasonable request.