Posaconazole as Salvage Therapy for Zygomycosis

Abstract

Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.Zygomycosis (also known as mucormycosis) is an infection caused by saprophytic fungi of the class Zygomycetes, which are primarily opportunists that invade immunocompromised hosts and produce angioinvasive disease (49). Transmission is mainly through inhalation of small airborne spores, by traumatic skin implantation, or by ingestion and translocation of the organism through the gut. Patients at highest risk for zygomycosis are those with (i) immunosuppression related to neutropenia, corticosteroid use, hematologic malignancies, and solid-organ transplants, (ii) diabetes mellitus, especially those with ketoacidosis, (iii) conditions of iron overload with associated desferoxamine use, and (iv) skin disruption by trauma or other serious conditions, such as burns or heatstroke. In recipients of a hematopoietic stem cell transplant (HSCT), infection often occurs during periods of graft-versus-host disease due to escalation of immunosuppressant regimens (1,4,12,21,25,27,36,41,44). Common sites of infection include pulmonary, rhinocerebral, or disseminated disease (36). The outcome of zygomycosis is closely related to the overall health of the patients and the control of their underlying diseases.Roden and associates analyzed 929 cases of zygomycosis reported since 1885 (38). Survival was reported in 65% of patients with no underlying condition, 56% with diabetes, and 34% with malignancy. Survival varied with infection site: localized skin, 90%; rhinocerebral, 38%; lung, 24...

Pulmonary Mucormycosis Presenting as Nonresolving Pneumonia in a Patient With Diabetes Mellitus

“…In a study of 24 subjects for whom posaconazole was used as salvage therapy, the duration varied from 8 to 1,004 d, with a median duration of 182 d. Posaconazole at 200 mg 4 times per day or 400 mg twice per day has shown favorable response rates of 60% and 79%, respectively. 8 In a retrospective series of invasive mucormycosis, posaconazole therapy was successful in 60% of subjects with diabetes mellitus, and its overall success rate was 65% in those with pulmonary mucormycosis. 9 Despite motivation and pursuance, our patient could not continue posaconazole beyond 4 weeks because of cost.…”

Management of rhinomaxillary mucormycosis with Posaconazole in immunocompetent patients

“…Two case series and more than 20 case reports of successful treatment with Posaconazole have been published and all conclude a significantly good and complete response. 17,18 It is also cost effective compared with Amphotericin B. A maximum dose of 3 g of lyophilized Amphotericin B in a month long treatment will cost the patient approximately 200,000-300,000 INR (3000 USD approx.)…”

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

“…Further, 6 of the 7 patients experienced complete resolution of infection [131]. Another report including data from 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections showed that 2 children ages 7 and 17 years of age had partial response to posaconazole and 1 child age 18 had a complete response [132]. To our knowledge, there are no reports on the use of posaconazole in neonates, and we would only consider its use as salvage therapy.…”