Posaconazole as rescue therapy in African histoplasmosis

Gonçalves, Daniel; Ferraz, Catarina; Vaz, Luísa Guedes

doi:10.1016/j.bjid.2012.06.027

Cited by 25 publications

(27 citation statements)

References 13 publications

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“…Despite its less favorable side effect profile, supportive therapy and close monitoring allowed our patient to safely receive her treatment as an outpatient. Immune reconstitution inflammatory syndrome is not commonly associated with histoplasmosis and was not observed in our case [12]. Lifelong suppression with antifungal agents should be considered in cases of relapse despite appropriate treatment or with prolonged immunosuppression [4].…”

Section: Discussionmentioning

confidence: 99%

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Successful Use of Multidisciplinary Palliative Care in the Outpatient Treatment of Disseminated Histoplasmosis in an HIV Positive Child

et al. 2021

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Histoplasmosis is an uncommon opportunistic infection in human immunodeficiency virus (HIV) positive children. The most common form is primary disseminated histoplasmosis, characterized by persistent fever and failure to thrive. A 10-year-old HIV positive girl presented to the Baylor College of Medicine Children’s Foundation—Tanzania Mbeya Center of Excellence (COE) with ulcerated skin lesions and a violaceous facial rash. She also had persistent fevers, severe acute malnutrition, and severe anemia. At diagnosis, the patient was failing first line antiretroviral therapy (ART) with a cluster of differentiation 4 immune cells (CD4) of 24 cells/µL and an HIV viral load (VL) of 196,658 cp/mL. The patient was changed to a second line ART regimen (abacavir, lamivudine, and ritonavir-boosted lopinavir) and received nutritional support, blood transfusions, multiple antibiotics, and meticulous wound care. She also received comprehensive symptom management, psychosocial support, and emergency housing through the COE’s palliative care program. Biopsy of a lesion showed intracytoplasmic organisms consistent with Histoplasmosis capsulatum var capsulatum. The patient was treated with conventional amphotericin B and oral itraconazole and she achieved wound healing as well as immune reconstitution and HIV viral suppression. Amphotericin infusions were given as an outpatient despite the resource constraints of the setting in southwestern Tanzania. Histoplasmosis should be considered in the differential diagnosis of the immunocompromised host with unusual skin manifestations and persistent fever.

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Section: Discussionmentioning

confidence: 99%

“…Fluconazole is less efficacious and has been associated with drug resistance [13]. Posaconazole and isovuconazole have been successfully used as salvage therapy [12,[14][15][16] but are rarely available in most LMIC settings.…”

Section: Discussionmentioning

confidence: 99%

Successful Use of Multidisciplinary Palliative Care in the Outpatient Treatment of Disseminated Histoplasmosis in an HIV Positive Child

et al. 2021

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“…In the present study, PCZ was used in six patients with infection by other moulds (two Fusarium spp, two Scedosporium spp, one Paecylomyces spp) and one with Histoplasma tendinitis. There are several communications that report a favourable response to PCZ in these types of infections . The patients with yeast infections in this series were included initially or sequentially by a better sensitivity profile to PCZ, including a patient with cryptococcal meningitis with a MIC to fluconazole of 8 μg/mL and a CMI to PCZ of 1 μg/mL.…”

Section: Discussionmentioning

confidence: 99%

Posaconazole salvage therapy: The Posifi study

Fortün

Gioia

Cardozo

et al. 2019

Mycoses

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Background: Posaconazole (PCZ) is used mainly for the prevention of invasive fungal infection (IFI). Methods:A multicentre retrospective, investigational study using a non-randomized, single-arm design carried out in six tertiary hospitals in Spain to evaluate the use of PCZ in different forms of administration in the (non-prophylactic) treatment of IFI. Results:Over an eight-year-period, 67 patients were included in this study. PCZ was administered as salvage therapy (intolerant or refractory to a previous antifungal agent) in 65/67 (97%); of these, it was used against Aspergillosis (68.6%), Zygomycosis (13.4%), other moulds (8.9%) and yeast (10.5%). The median duration of PCZ therapy was 75 days. The oral solution was associated with low serum levels (<0.7 mg/L) in 63% of available patients. Clinical response at 3 and 12 months of PCZ therapy were for aspergillosis: 47.8% and 41.3%; for zygomycosis: 55.5% and 55.5%; and for other mycoses: 69.2% and 69.2%, respectively. Suspension by toxicity was only observed in 6% and 7.5% of patients at 3 and 12 months, respectively, mainly with grade III/IV elevations of liver function test (LFTs). Conclusions:Posaconazole salvage therapy, especially oral tablets, can be an effective alternative option for patients with IFI who cannot tolerate or do not respond to other antifungal therapies. | 527FORTUN eT al.

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“…Occasional treatment successes have also been reported with posaconazole for endemic mycoses including blastomycosis 11,89 and histoplasmosis, 14,90,91 and there are relatively more, though still limited, data on the use of posaconazole for treatment of coccidioidomycosis, 12,13,92-94 but posaconazole has not been approved for these infections and is not considered first-line therapy.…”

Section: Endemic Mycosesmentioning

confidence: 99%

“…110,111 In a study of 17 AIDS patients with histoplasmosis who failed fluconazole therapy, posaconazole retained activity against all isolates, whereas 12 and 7 isolates, respectively, exhibited a fourfold or greater decrease in susceptibility to fluconazole and voriconazole. 34 Both voriconazole 102,105,[112][113][114] and posaconazole 14,91,115 have been effective as salvage therapy for histoplasmosis. In one study of six patients with histoplasmosis (disseminated in five) failing prior antifungal therapy, posaconazole was efficacious in all six patients (duration 6-34 weeks).…”

Section: Histoplasmosismentioning

confidence: 99%

Posaconazole: Use in the Prophylaxis and Treatment of Fungal Infections

Clark

Grim

Lynch

2015

Semin Respir Crit Care Med

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Posaconazole, a fluorinated triazole antifungal drug, is approved by the U.S. Food and Drug Administration (FDA) for (1) prophylaxis against Aspergillus and Candida infections in immunocompromised patients at high risk for these infections and (2) oropharyngeal candidiasis (OPC), including cases refractory to fluconazole and/or itraconazole. The European Medicines Agency (EMA) has approved posaconazole for (1) treatment of aspergillosis, fusariosis, chromoblastomycosis, and coccidioidomycosis in patients who are refractory to or intolerant of other azoles or amphotericin B; (2) first-line therapy for OPC for severe disease or in those unlikely to respond to topical therapy; and (3) prophylaxis of invasive fungal infections in high-risk hematologic patients and stem cell transplant recipients. In addition to approved indications, posaconazole has been used with success as salvage therapy for invasive mold infections and endemic mycoses in patients who are refractory to or intolerant of other antifungal agents, and as prophylaxis or salvage therapy in children, for whom indications are more limited owing to a paucity of data. Posaconazole has potent in vitro activity against a broad range of fungi and molds, including Aspergillus, Candida, Cryptococcus, filamentous fungi, and endemic mycoses including coccidioidomycosis, histoplasmosis, and blastomycosis. Importantly, posaconazole is much more active than other azoles against many Mucorales species and the combination of posaconazole with other antifungal agents may be synergistic. Hence, posaconazole is a potential candidate as a single or combination agent for difficult-to-treat fungal infections. Posaconazole has an excellent safety profile; to date, serious side effects are rare, even with prolonged use. However, newer posaconazole formulations achieve higher blood levels and it remains to be seen whether this may lead to an increase in the rate of adverse effects. Currently, posaconazole is used predominantly for prophylaxis and salvage therapy of fungal infections in adults. Indications for use as initial therapy of fungal infections and for broader use in children will depend on the accrual of additional clinical data.

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Posaconazole as rescue therapy in African histoplasmosis

Cited by 25 publications

References 13 publications

Successful Use of Multidisciplinary Palliative Care in the Outpatient Treatment of Disseminated Histoplasmosis in an HIV Positive Child

Successful Use of Multidisciplinary Palliative Care in the Outpatient Treatment of Disseminated Histoplasmosis in an HIV Positive Child

Posaconazole salvage therapy: The Posifi study

Posaconazole: Use in the Prophylaxis and Treatment of Fungal Infections

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