Abstract
Background
Miltefosine (Profounda, FL) is an oral alkylphospholipid drug which is approved by the Food and Drug Administration for the treatment of some species of New World cutaneous ...leishmaniasis. The maximal daily recommended dosage is 50 mg t.i.d for 28 days; yet there is some evidence that doses <2.5 mg/kg/day may be associated with lesser efficacy. We treated a healthy 30-year-old, 117 kg, 78 inches (low body fat) male with cutaneous Leishmania tropica infection with miltefosine after multiple unsuccessful treatment regimens. This presentation will provide the background considerations and the outcome of our approach of using higher daily dosages of miltefosine.
Methods
We used a miltefosine dose escalation of 50 mg t.i.d (1.28 mg/kg/day) for days 1–5 with fatty food, increasing to 50 mg. q.i.d. (1.71 mg/kg/day) for days 6–15. For days 16–28, the patient received 250 mg daily (2.13 mg/kg/day). Weekly blood testing was done for complete blood count, metabolic panel, and miltefosine pharmacokinetics. Plasma concentrations were assayed using a validated liquid chromatography coupled to tandem mass spectrometry methodology.
Results
The patient experienced a good clinical result with his two ulcerative lesions on the left leg healing with full epithelialization by day 28. He tolerated miltefosine well until he escalated to 250 mg daily when he noted 2 hours of fatigue and dizziness after the dose, nausea and after the fourth day he developed epididymitis. His serum creatinine was elevated (1.4 mg/dL). The epididymitis resolved after approximately a week, his other symptoms resolved soon after completing the day 28 dose. Serial miltefosine plasma levels accumulated during treatment to 30, 34, 44, and 53 μg/mL on days 7, 14, 21, and 27 after the start of treatment (dropping to 27 μg/mL 8 days post), with an apparent distribution half-life of 7 days.
Conclusion
Miltefosine yielded healing of recalcitrant L. tropica infection but was associated with adverse effects at the 250 mg daily dose that severely limited the activity of the patient for the final 8 days of therapy; however, they were not dose-limiting. Miltefosine accumulation appeared to be dose-proportional compared with reported concentrations with a median 1.8 mg/kg/day dose in Dutch cutaneous leishmaniasis patients (median weight 85 kg).
Disclosures
All authors: No reported disclosures.
Abstract
Background
Visceral leishmaniasis (VL) is a systemic vector-borne disease. In Iraq, VL is caused by Leishmania infantum, an intracellular parasite requiring a cell-mediated immune response. ...Most infections are asymptomatic, and evidence exists for latent disease that may activate, especially with immunosuppression. Since 2001, 22 cases of active VL have occurred among deployed service members and there is potential that many are latently infected.
Methods
A recent surveillance study tested 112 asymptomatic US service members previously deployed to Iraq for latent VL with interferon gamma release assays (IGRA), enzyme-linked immunosorbent assays (ELISA), rK39 immunochromatographic tests, and quantitative polymerase chain reactions (PCR). Persons with any positive result were offered a clinical consultation to assess for exposure risks, immune-suppressing conditions, and evidence of active VL, as well as to obtain baseline laboratory studies and abdominal imaging, as needed, and to provide counseling. This is a case series of the 18 subjects who underwent clinical evaluation.
Results
Among 18 latent VL subjects evaluated, 14 were IGRA+, 4 ELISA+, 0 rK39+, and 1 PCR+ (3 parasites/ml). All were male and median age was 38.5 years. Initial deployments were in 2003–2008 and median total duration in Iraq was 17 months. Musculoskeletal disease was the most common comorbidity. Four subjects previously had cutaneous leishmaniasis. One subject had psoriatic arthritis and prior TNF-α inhibitor exposure, but no other substantial risks for immunosuppression were identified. There was no evidence of active VL, although one subject had thrombocytopenia and two had elevated liver enzymes. There was no abnormal imaging. No subjects were treated and those that were PCR+ and ELISA+ are being followed clinically.
Conclusion
This series highlights the first 18 US service members diagnosed with latent VL. No patients have active disease, most have an appropriate immune response (IGRA), four have a TH2 humoral immune response (one of whom is immunosuppressed), and one has evidence of ineffective immune control with circulating parasites. We have developed an approach to the assessment and counseling of latent VL. Further studies are needed to assess the natural history and treatment of latent VL.
Disclosures
N. E. Aronson, UpToDate: Chapter Author for several leishmaniasis chapters, Licensing agreement or royalty. Elsevier: Associate editor for Hunter’s Tropical Medicine and Emerging Infectious Diseases, Licensing agreement or royalty
Indinavir is a protease inhibitor that was approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in March 1996. It is widely used as combination therapy for HIV ...infection. Indinavir is primarily hepatically cleared; <20% is excreted in the urine, including 11% in the form of the unchanged drug. The solubility of indinavir in water is pH dependent, with increased solubility at pH of <5.5. In the clinical trials leading to the new drug application, the major serious adverse effect was nephrolithiasis, which usually presented with flank pain with or without hematuria in approximately 4% (79 of 2,205) of patients. In general, nephrolithiasis was not associated with renal dysfunction and resolved with hydration and temporary interruption of therapy; only 9.2% of patients had to discontinue therapy. Subsequent reports describe renal toxicity including nephrolithiasis necessitating surgical intervention, acute renal failure, interstitial nephritis, symptomatic crystalluria, and indinavir crystalline nephropathy. The persistence of indinavir stones after drug discontinuation has not been noted. We describe two patients in whom nephrolithiasis persisted for >6 months after discontinuing therapy with indinavir.
Cutaneous leishmaniasis in Central and South America is caused most commonly by Leishmania braziliensis, Leishmania guyanensis, Leishmania panamensis, and Leishmania mexicana, and the recommended ...treatment is one of the pentavalent antimonial compounds (meglumine antimoniate or sodium stibogluconate). Recent reports of visceral leishmaniasis (kala-azar) have suggested that treatment with lipid formulations of amphotericin B may be as or more effective than antimony.
U.S. military researchers have made major contributions to the discovery, diagnosis, treatment, and prevention of a number of parasitic diseases. We review the paramount U.S. military contributions ...to the understanding of leishmaniasis, filariasis, schistosomiasis, trypanosomiasis, gastrointestinal parasites, intestinal capillariasis, and angiostrongyliasis.
A review of 84 patients with cutaneous leishmaniasis treated with sodium stibogluconate (Pentostam) at our institution revealed that three had developed herpes zoster during or shortly after ...receiving therapy. Because zoster has been associated with depressed cellular immunity, we prospectively followed serial lymphocyte subpopulations in eight patients with cutaneous leishmaniasis who received Pentostam. By day 7 of therapy, the white blood cell count had fallen by a median of 1.15/mm3, the total lymphocyte count by a median of 804/mm3, and the CD4+ lymphocyte count by a median of 306/mm3 (67% of baseline; confidence interval, 52%–78%). An in vitro cell-viability assay demonstrated that Pentostam is not toxic to human mononuclear cells. The administration of Pentostam for the treatment of cutaneous leishmaniasis results in lymphopenia that may be related to the subsequent occurrence of herpes zoster.
Amphotericin B is recommended for the treatment of systemic infection caused by Sporothrix schenckii. However, this agent is toxic, its use is frequently followed by relapse, and some isolates of S. ...schenckii are resistant. Recent studies suggest that newer azole compounds, such as itraconazole, are effective in cutaneous and lymphocutaneous sporotrichosis, but data on their efficacy in systemic infections are scarce. We used itraconazole in the sequential treatment of six patients with systemic sporotrichosis: three with bone and joint disease and three with disseminated infection manifested by subcutaneous nodules. In all six cases, symptoms and signs of infection improved, with resolution of subcutaneous nodules, normalization of imaging studies, cessation of wound drainage, and return of joint mobility and function. No toxicity was noted. One patient with disseminated infection had a relapse while receiving 100 mg of itraconazole daily. The average duration of follow-up was 18 months. Thus itraconazole appears promising for the treatment of systemic sporotrichosis. A dose of at least 200 mg/d appears to be needed to prevent relapse.
Campylobacter-like organisms, now renamed Helicobacter, have been isolated from the gastrointestinal tract and blood of patients infected with HIV. These organisms are typically slow growing and ...require special culture methods for isolation. We report a case of bacteremia due to Helicobacter cinaedi that recurred even though the patient had received 1 month of ciprofloxacin therapy.
Recognizing a potential interaction between isoniazid (INH), a weak monoamine oxidase inhibitor, and serotonin reuptake inhibitors (SSRIs), we assessed medication discontinuation rates in human ...immunodeficiency virus-infected individuals taking an SSRI, INH, or both.
We retrospectively reviewed treatment records to determine if patients on an SSRI, INH, or both completed drug therapy in accordance with a treatment plan (e.g., 12 months of INH therapy). Patients on both medications constituted the study group; patients taking either an SSRI or INH alone constituted comparison groups.
There were no significant differences between the groups based on age, gender, CD4%, or CD4 count. Seven of the 10 patients (70%) in the study group discontinued therapy, which was significantly greater than the 2 of 14 (14%) in the SSRI group (P = 0.01) and the 4 of 18 (22%) in the INH group (p = 0.02) who discontinued therapy.
Medication discontinuation rates for patients prescribed an SSRI coincident with INH were significantly higher than for individuals prescribed these medications separately. These differences cannot be accounted for on the basis of age, gender, or CD4%, but they may be attributable to increased side effects caused by interactions between these medications.
PDF
