Efficacy and Safety Assessment of Antifungal Sequential Therapy from Micafungin to Liposomal Amphotericin B for Antibiotics-Refractory Febrile Neutropenia in Patients with Hematologic Malignancies

Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.

Antifungal therapy for treatment of cryptococcal meningitis

Objective To compare the curative effects of three different antifungal regimens in the treatment of cryptococcal meningitis Methods Twenty two patients were divided into 3 groups: Group Ⅰ was given intravenous amphotericin B alone or combination with flucytosine therapy Group Ⅱ received intravenous fluconazole alone or combination with flucytosine The treatment of Group Ⅲ was divided into two steps, where the patients received intrathecal amphotericin B plus intravenous amphotericin B with or without intravenous fluconazole until the mycological culture of cerebrospinal fluid (CSF) turned negative, followed by oral fluconazole or itraconazole as maintenance therapy until direct microscopic examination of CSF showed negative once a week for three consecutive weeks Results Of the twenty two patients, 17 (77 3%) were cured, 2 (9 1%) improved, 3 (13 6%) died, and one (4 5%) relapsed Of the 8 patients in Group Ⅰ, 5 were cured, 2 improved, one died and one relapsed; Of the 4 patients in Group Ⅱ, 2 were cured, and 2 died; All the 10 patients in Group Ⅲ were cured without any recurrence Conclusion The two step therapeutic regimen may be suited to the treatment of cryptococcal meningitis

A Bronchopulmonary Onset of Candidemia Revealing a Granulomatosis with Polyangiitis

Candidemia is defined as being a yeast infection confirmed by the presence of at least one positive Candida blood culture. It is a life threatening infection causing high mortality. The clinical signs are generally compatible with the causative agent (whether there is a deep venous catheter or not). On the other hand and according to the 2012 Revised Chapel Hill Classification, granulomatosis with polyangiitis GPA is classified as a vasculitis associated with antineutrophil cytoplasmic antibodies ANCA. It is a systemic disease characterized by the anatomopathological aspect of granuloma. We report the case of a patient who presented an atypical and a very rare revealing mode of GPA which was a bronchopulmonary candidiasis complicated by candidemia. Despite its controversy, the combination in the acute phase of antifungal treatment based on intravenous voriconazole and glucocorticoid therapy has made it possible to control candidemia and calm vasculitis.

A Case of Invasive Pulmonary Aspergillosis Resulted from the Treatment of Chronic Eczema

This was an advanced male(87-year-old)with refractory chronic eczema for over 40 years,based on his allergic constitution,accompanied with chronic kidney disease due to primary hypertension(CKD,phase 3).It was so difficult to tolerate the severe itching that the glucocorticoids(GC)had to be applied to it,but some new-onset respiratory symptoms,such as cough,dyspnea after exertion etc.,occurred to this patient.Some classical IPA images were found on his pulmonary CT scanning,which were further comfirmed by the positive findings of GM-test,and then a final diagno­sis of IPA was accordingly established.Unfortunately,a persistent fever emerged after starting an antifungal therapy to the patient,and his IL-2 level was detected to be superhigh.As a response to allergic fever,GC was carefully given intravenously again to treat it,and it turned out to be totally improved since then;suggesting that systemic thinking(integrated with the other clinical evidences)is essential to diagnose IPA,and GC can also be used to improve its symptoms with the existence of antifungal therapy.

Evidence for a ‘preinvasive’ variant of fungal sinusitis: Tissue invasion without angioinvasion

Clinical experience has suggested the existence of an intermediate form of fungal sinusitis between the categories of non-invasive fungal sinusitis (non-IFS) and invasive fungal sinusitis (IFS).This fungal sinusitis variant demonstrates unhealthy mucosa by endoscopy with fungal invasion,but lacks angioinvasion microscopically,representing what clinically behaves as a ‘pre-invasive’ subtype of fungal sinusitis.Unlike non-IFS disease,patients with preinvasive fungal sinusitis were still felt to require anti-fungal medications due to histologic presence of invasive fungus.While sharing some clinical features of IFS,these ‘intermediate’ patients were successfully spared extended and repeated surgical debridements given the microscopic findings,and have been successfully treated with shorter courses of antifungal therapy.These select patients have had favorable outcomes when managed in a judicious and semi-aggressive manner,in an undefined zone between the treatments for routine fungal ball and aggressive IFS.

Phospholipid/protein co-mediated assembly of Cu_(2)O nanoparticles for specific inhibition of growth and biofilm formation of pathogenic fungi

As the increasing number of the individuals suffering from AIDs,chemotherapy,and radiotherapy,pathogenic fungi,which may rapidly grow and invade the host tissues in these immune-compromised patients,is becoming great threat to human health.In this study,we constructed a novel fungal pathogen-responsive assembly of cuprous oxide(Cu_(2)O)nanoparticles(NPs)for specific targeting and inhibiting growth and biofilm formation of the representative fungal pathogen,Candida albicans(C.albicans).This assembly was formed by coating the initial Cu_(2)O NPs with both phosphatidylethanolamine(PE)and bovine serum albumin(BSA),followed by hydrophobic/electrostatic interaction-driven formation of the Cu_(2)O-PE-BSA microaggregates.The formed microaggregates could be induced for disassembly by the fungal pathogen C.albicans,leading to close binding of the NPs to the cell wall of the pathogen.Both confocal microscopy and viability assays showed that the assembly strongly inhibited growth and biofilm formation of the pathogen,but had extreme low toxicity to mammalian cells.In vivo mouse wound model further revealed that the assembly had high capacity of healing the fungus-infected wounds and reduced the fungal burden of the wound tissues.This study sheds a novel light on facile development of pathogen-responsive nano-assemblies for efficient and safe antifungal therapy.

PULMONARY MUCORMYCOSIS: A CASE REPORT AND SYSTEMIC REVIEW OF LITERATURE

Pulmonary mucormycosis is an increasingly emerging life-threatening infection caused by the order Mucorales (class Zygomycetes). A high index of suspicion in the appropriate clinical setting with prompt diagnosis and optimal treatment is recommended. We made a systemic analysis of 82 reported cases in literature in order to improve clinical knowledge of pulmonary mucormycosis. We described a patient with localized pulmonary mucormycosis diagnosed by histological examination in our hospital. Optimal therapy consists of antifungal medication, surgical resection and control of the patient's underlying illness.