Candida albicans is one of the most common pathogens causing invasive fungal infections,with a mortality rate of up to 20%-50%.Amphotericin B(AmB),a biopharmaceutics classification system(BCS)IV drug,significantly inh...Candida albicans is one of the most common pathogens causing invasive fungal infections,with a mortality rate of up to 20%-50%.Amphotericin B(AmB),a biopharmaceutics classification system(BCS)IV drug,significantly inhibits Candida albicans.AmB is primarily administered via oral and intravenous infusion,but severe infusion adverse effects,nephrotoxicity,and potential hepatotoxicity limit its clinical application.Deep eutectic solvents(DESs),with excellent solubilization ability and skin permeability,are attractive for transdermal delivery.Herein,we used DESs to deliver AmB for antifungal therapy transdermally.We first prepared and characterized DESs with different stoichiometric ratios of choline(Ch)and geranate(Ge).DESs increased the solubility of AmB by a thousand-fold.In vitro and in vivo,skin permeation studies indicated that DES_(1:2)(Ch and Ge in 1:2 ratio)had the most outstanding penetration and delivered fluorescence dye to the dermis layer.Then,DES_(1:2)-AmB was prepared and in vitro antifungal tests demonstrated that DES_(1:2)-AmB had superior antifungal effects compared to AmB and DES_(1:2).Furthermore,DES_(1:2)-AmB was skin-irritating and biocompatible.In conclusion,DES-AmB provides a new and effective therapeutic solution for fungal infections.展开更多
In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B（AmB）, microemulsion vehicles composed of isopropyl myristate（IPM）, Tween 80, isopropyl a...In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B（AmB）, microemulsion vehicles composed of isopropyl myristate（IPM）, Tween 80, isopropyl alcohol and water for transdermal delivery of AraB were designed. The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conductivities（σ）. The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus. To obtain a high solubization of AmB, three different methods were tested to incorporate AmB into microemulsion. The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature（PIT） of the emulsifier obtains the maximum drug content（2.96 mg/mL）. The pH value of the system could be adjusted to pH〉8.5 or pH〈5.2, in this range AraB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets, drug precipitate is no more than 5%, and the formulations were corresponding to the characterizations of microemulsion. At pH 5.14, AmB microemulsion with Km 1：1, O/SC 1：9（mass ratio of oil phase to surfactant/cosurfactant blend）, water content 64.6%, drug content （2.93±0.08） mg/mL, showed the maximum permeation rate （3.255 ±0.64） μg·cm^-2.h^-1 which is stable for a long time.展开更多
Amphotericin B (Am B), a polyene antibiotic, is one of the gold standards for the treatment of systemic fungal infections and leishmaniasis. Nowadays, only intravenous administration of Am B has been available;because...Amphotericin B (Am B), a polyene antibiotic, is one of the gold standards for the treatment of systemic fungal infections and leishmaniasis. Nowadays, only intravenous administration of Am B has been available;because Am B is poorly absorbed from the gastrointestinal (GI) tract due to its low aqueous solubility. Currently, 2 forms of Am B are available.展开更多
Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB agg...Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer,which heat treatment(curing)modifies.Although toxicity was found related to aggregation status-loose aggregates significantly more toxic than tight aggregates-the precise mechanism linking aggregation and toxicitywas notwell understood.This study directlymeasured drug release rate fromvarious AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state,drug release,and in vitro toxicity.UV–Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features:a∼25nm blue-shift of the main absorption peak(λ_(max))in aqueous buffer and a decrease in the OD_(346)/OD_(322) ratio upon thermal curing,reflecting tighter aggregation.In vitro release testing(IVRT)data showed,by applying and fitting first-order release kinetic models for one or two pools,that curing impacts two significant changes:a 3–5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated,more thermodynamically stable drug pool.The kinetic data thus corroborated the trend independently deduced from the UV–Vis spectral data.The in vitro toxicity assay indicated a decreased toxicity with curing,as shown by the significantly increased concentration,causing half-maximal potassium release(TC50).The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation.This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release(directly measured rate constants),providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.展开更多
Our study related to the renal toxicity of Wistar rats induced by solutions of amphotericin B prepared under extreme conditions of pH (5.4 and 10.8). The results obtained show that with pH 5.4 of stock solution, urea ...Our study related to the renal toxicity of Wistar rats induced by solutions of amphotericin B prepared under extreme conditions of pH (5.4 and 10.8). The results obtained show that with pH 5.4 of stock solution, urea and creatinin rate blood is not disturbed. These means that the renal function is not deteriorated by the amphotericin B. Furthers, treatment of animals infected by the yeast Candida albicans, with the solution of amphotericin B prepared at pH 5.4 and injected at 0.5 mg of AmB/Kg every 24 hours, seems to be effective.展开更多
BACKGROUND Rhizopus microsporus(R.microsporus)lung infection is an invasive fungal disease with high mortality that is increasingly common in immunocompromised patients.However,it is very rare in immunocompetent patie...BACKGROUND Rhizopus microsporus(R.microsporus)lung infection is an invasive fungal disease with high mortality that is increasingly common in immunocompromised patients.However,it is very rare in immunocompetent patients.Here,we present the case of a 19-year-old girl who developed R.microsporus lung infection without any known immunodeficiency.CASE SUMMARY The patient presented to our hospital because of hemoptysis and irritative cough without expectoration.She was first treated for community-acquired pneumonia until the detection of R.microsporus in bronchoalveolar lavage fluid by metagenomics next-generation sequencing(mNGS).After a combination therapy of intravenous inhalation and local airway perfusion of amphotericin B,she eventually recovered,with significant absorption of lung infections.CONCLUSION Early diagnosis and treatment are very important for pulmonary mucormycosis.Compared to fungal culture,mNGS is a relatively precise and convenient method to obtain pathogenic results.A combination therapy of intravenous inhalation and local airway perfusion of amphotericin B may be a promising strategy for the treatment of pulmonary mucormycosis in the future.展开更多
Increasing reports on application and safety of liposomal amphotericin B (Amphotec) in the treatment of deep fungal infections have been described recently. This is the first report that a case of liver abscess due to...Increasing reports on application and safety of liposomal amphotericin B (Amphotec) in the treatment of deep fungal infections have been described recently. This is the first report that a case of liver abscess due to Candida albicans was completely cured with intra-abscess and intravenous administration of liposomal amphotericin B without recurrence in three-year follow-up period.展开更多
Objective: To understand the condition of adverse drug reactions and the treatment procedures of amphotericin B for injection in patients with AIDS complicated with fungal infection. Methods: For the research object, ...Objective: To understand the condition of adverse drug reactions and the treatment procedures of amphotericin B for injection in patients with AIDS complicated with fungal infection. Methods: For the research object, a retrospective analysis of adverse reactions of amphotericin B injection in 121 patients of AIDS complicated with fungal infection was reported in our hospital from October 2017 to June 2021 to observe the adverse drug reactions of patients after treatment with amphotericin B for injection, 87 cases with general degree (regarded as the general group) and 34 cases with serious degree (regarded as the serious group), and analyze the general data, medication and course of disease of the two groups for symptomatic treatment. Results: Adverse reactions such as hypokalemia, abnormal liver function, renal impairment, leucopenia and drug fever were more common in the two groups, and there were also many adverse reactions such as bone marrow suppression, rash, anemia, thrombocytopenia, nausea, vomiting, fatigue, dizziness, pruritus, angina pectoris, vertigo, abdominal pain and diarrhea. The rates of leukopenia and drug fever in general group were significantly lower than those in severe group (P < 0.05);in the dose of amphotericin B used, the rate of using 25 mg and more than 25 mg in the general group was significantly lower than that in the severe group (P < 0.05). After symptomatic treat-ment, most patients have improved, and a few are unknown or have not improved. Con-clusion: Amphotericin B for injection has great side effects and will cause different degrees of adverse drug reactions. The dose of amphotericin B for clinical treatment should be ad-justed and disposed according to the adverse reactions to avoid serious consequences.展开更多
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...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.展开更多
Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for t...Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.展开更多
Background Amphotericin B （0.7 mg/kg） with flucytosine is the standard treatment for cryptococcal meningitis.However,the long treatment course can induce adverse reactions in patients; therefore,reducing the dose ma...Background Amphotericin B （0.7 mg/kg） with flucytosine is the standard treatment for cryptococcal meningitis.However,the long treatment course can induce adverse reactions in patients; therefore,reducing the dose may decrease such reactions.We performed a retrospective analysis of treatment effects and adverse reactions when amphotericin B （0.4 mg/kg or 0.7 mg/kg per day） and flucytosine were used together to treat HIV-negative patients with cryptococcal meningitis.Methods Retrospective analysis was conducted on inpatients at the First Affiliated Hospital,College of Medicine,Zhejiang University （January 2005 to December 2009）.Low- or high-dose amphotericin B （0.4 or 0.7 mg/kg per day,respectively） plus flucytosine was used.The negative conversion rate of Cryptococcus in the cerebrospinal fluid （CSF）,patient mortality,and the incidence of side effects for the two groups （low- vs.high-dose） were compared immediately after treatment and 2 and 10 weeks later.Data were analyzed by the Student＇s t test,chi-square tests using SPSS 12.0 statistical soitware.Results Two weeks post-treatment,Cryptococcus negative CSF rates were 78% （18/23） in the low-dose group and 87% （13/15） in the high-dose group （P=0.28）.Ten weeks post-treatment,both groups were negative.The mortality rate was 8% （2/25） in the low-dose group and 17% （3/18） in the high-dose group （P=-0.25）.There was a statistically significant difference in the incidence of adverse events between the groups,48% （12/25） and 78% （14/18） in the low- and high-dose groups,respectively （P=0.04）.Adverse events that required a change in treatment program in the low-dose group were 12% （3/25） compared to 39% （7/18） in the high-dose group （P=-0.04）.Conclusion Low-dose treatment regimens were better tolerated展开更多
Background Nowadays,there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B （L-AmB）.However,these studies have a modest sample size and convey inconclusive results.The ai...Background Nowadays,there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B （L-AmB）.However,these studies have a modest sample size and convey inconclusive results.The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections （IFIs）,compared with L-AmB.Methods Electronic databases （up to July 31,2013） PubMed and Embase databases,the Cochrane Library,and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB.Analyses of efficacy and adverse outcomes were performed by relative risks （RRs） and 95% confidence intervals （C/s）.Heterogeneity was assessed by x2-test and the/2-statistic.Results Three trials were included in this meta-analysis with 1249 modified intention-to-treat （MITT） patients.The results showed that caspofungin produced equal efficacy in favorable overall response （RR=1.02,95% Cl 0.88-1.18; P=0.81） and mortality rate （RR=1.53,95% Cl 0.38-6.27,P=0.55）,safer in clinical adverse events （RR=0.20,95% Cl 0.08-0.54; P=0.001）,laboratory adverse events （RR=0.69,95% Cl 0.57-0.84; P=0.0002）,and discontinuation rate （RR=0.26,95% Cl 0.08-0.83,P=0.02）,compared with L-AmB in the treatment of patients with IFls.Conclusion Based on the results of this meta-analysis,it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.展开更多
Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) ...Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current,clinically approved lipid-based formulations.The objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an in vitro model.Methods:Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at air-liquid interface until well-differentiated.Cultures were exposed to ND-AMB vs AMB and changes in K+ permeability and resistance were measured and recorded via Ussing chamber assay.Ciliary beat frequency (CBF) was analyzed in parallel as well as cytotoxic assay.Potency was assessed using real-time PCR measurement of the Aspergillus fumigatus 18S rRNA.Results:Ussing chamber studies revealed K+ currents that increased rapidly within 30 s of adding AMB (10 μg/mL) to the apical side,indicating apical membranes had become permeable to K+ ions.In contrast,negligible induction of K+ current was obtained following addition of NDAMB [AMB =(107.7 ± 15.9) μA/cm2 AMB vs ND-AMB =(2.3 ± 0.7) μA/cm2 ND-AMB;P =0.005].ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P ＜ 0.05).There was no difference in ciliary beat frequency between the two groups (P =0.96).The expression of A.fumigatus 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB (P ＜ 0.05).Conclusions:Data from the present study suggests ND-AMB protects human nasal epithelia membranes from AMB toxicity by protecting against apical cell K+ permeability while maintaining uncompromised antifungal property compared to AMB.ND-AMB could provide a novel topical therapy for sinonasal fungal diseases.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81872823,82073782,and 82241002)the Key R&D Plan of Ganjiang New District of Jiangxi(No.2023010).
文摘Candida albicans is one of the most common pathogens causing invasive fungal infections,with a mortality rate of up to 20%-50%.Amphotericin B(AmB),a biopharmaceutics classification system(BCS)IV drug,significantly inhibits Candida albicans.AmB is primarily administered via oral and intravenous infusion,but severe infusion adverse effects,nephrotoxicity,and potential hepatotoxicity limit its clinical application.Deep eutectic solvents(DESs),with excellent solubilization ability and skin permeability,are attractive for transdermal delivery.Herein,we used DESs to deliver AmB for antifungal therapy transdermally.We first prepared and characterized DESs with different stoichiometric ratios of choline(Ch)and geranate(Ge).DESs increased the solubility of AmB by a thousand-fold.In vitro and in vivo,skin permeation studies indicated that DES_(1:2)(Ch and Ge in 1:2 ratio)had the most outstanding penetration and delivered fluorescence dye to the dermis layer.Then,DES_(1:2)-AmB was prepared and in vitro antifungal tests demonstrated that DES_(1:2)-AmB had superior antifungal effects compared to AmB and DES_(1:2).Furthermore,DES_(1:2)-AmB was skin-irritating and biocompatible.In conclusion,DES-AmB provides a new and effective therapeutic solution for fungal infections.
基金Supported by the Grant from the Agriculture Technologies R & D Program of Shanxi Province, China(No. 2007032013).
文摘In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B（AmB）, microemulsion vehicles composed of isopropyl myristate（IPM）, Tween 80, isopropyl alcohol and water for transdermal delivery of AraB were designed. The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conductivities（σ）. The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus. To obtain a high solubization of AmB, three different methods were tested to incorporate AmB into microemulsion. The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature（PIT） of the emulsifier obtains the maximum drug content（2.96 mg/mL）. The pH value of the system could be adjusted to pH〉8.5 or pH〈5.2, in this range AraB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets, drug precipitate is no more than 5%, and the formulations were corresponding to the characterizations of microemulsion. At pH 5.14, AmB microemulsion with Km 1：1, O/SC 1：9（mass ratio of oil phase to surfactant/cosurfactant blend）, water content 64.6%, drug content （2.93±0.08） mg/mL, showed the maximum permeation rate （3.255 ±0.64） μg·cm^-2.h^-1 which is stable for a long time.
文摘Amphotericin B (Am B), a polyene antibiotic, is one of the gold standards for the treatment of systemic fungal infections and leishmaniasis. Nowadays, only intravenous administration of Am B has been available;because Am B is poorly absorbed from the gastrointestinal (GI) tract due to its low aqueous solubility. Currently, 2 forms of Am B are available.
基金financially supported by the Offi ce of Research and Standards, Office of Generic Drugs, CDER at the FDA (75F40120C00055)
文摘Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer,which heat treatment(curing)modifies.Although toxicity was found related to aggregation status-loose aggregates significantly more toxic than tight aggregates-the precise mechanism linking aggregation and toxicitywas notwell understood.This study directlymeasured drug release rate fromvarious AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state,drug release,and in vitro toxicity.UV–Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features:a∼25nm blue-shift of the main absorption peak(λ_(max))in aqueous buffer and a decrease in the OD_(346)/OD_(322) ratio upon thermal curing,reflecting tighter aggregation.In vitro release testing(IVRT)data showed,by applying and fitting first-order release kinetic models for one or two pools,that curing impacts two significant changes:a 3–5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated,more thermodynamically stable drug pool.The kinetic data thus corroborated the trend independently deduced from the UV–Vis spectral data.The in vitro toxicity assay indicated a decreased toxicity with curing,as shown by the significantly increased concentration,causing half-maximal potassium release(TC50).The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation.This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release(directly measured rate constants),providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.
文摘Our study related to the renal toxicity of Wistar rats induced by solutions of amphotericin B prepared under extreme conditions of pH (5.4 and 10.8). The results obtained show that with pH 5.4 of stock solution, urea and creatinin rate blood is not disturbed. These means that the renal function is not deteriorated by the amphotericin B. Furthers, treatment of animals infected by the yeast Candida albicans, with the solution of amphotericin B prepared at pH 5.4 and injected at 0.5 mg of AmB/Kg every 24 hours, seems to be effective.
文摘BACKGROUND Rhizopus microsporus(R.microsporus)lung infection is an invasive fungal disease with high mortality that is increasingly common in immunocompromised patients.However,it is very rare in immunocompetent patients.Here,we present the case of a 19-year-old girl who developed R.microsporus lung infection without any known immunodeficiency.CASE SUMMARY The patient presented to our hospital because of hemoptysis and irritative cough without expectoration.She was first treated for community-acquired pneumonia until the detection of R.microsporus in bronchoalveolar lavage fluid by metagenomics next-generation sequencing(mNGS).After a combination therapy of intravenous inhalation and local airway perfusion of amphotericin B,she eventually recovered,with significant absorption of lung infections.CONCLUSION Early diagnosis and treatment are very important for pulmonary mucormycosis.Compared to fungal culture,mNGS is a relatively precise and convenient method to obtain pathogenic results.A combination therapy of intravenous inhalation and local airway perfusion of amphotericin B may be a promising strategy for the treatment of pulmonary mucormycosis in the future.
文摘Increasing reports on application and safety of liposomal amphotericin B (Amphotec) in the treatment of deep fungal infections have been described recently. This is the first report that a case of liver abscess due to Candida albicans was completely cured with intra-abscess and intravenous administration of liposomal amphotericin B without recurrence in three-year follow-up period.
文摘Objective: To understand the condition of adverse drug reactions and the treatment procedures of amphotericin B for injection in patients with AIDS complicated with fungal infection. Methods: For the research object, a retrospective analysis of adverse reactions of amphotericin B injection in 121 patients of AIDS complicated with fungal infection was reported in our hospital from October 2017 to June 2021 to observe the adverse drug reactions of patients after treatment with amphotericin B for injection, 87 cases with general degree (regarded as the general group) and 34 cases with serious degree (regarded as the serious group), and analyze the general data, medication and course of disease of the two groups for symptomatic treatment. Results: Adverse reactions such as hypokalemia, abnormal liver function, renal impairment, leucopenia and drug fever were more common in the two groups, and there were also many adverse reactions such as bone marrow suppression, rash, anemia, thrombocytopenia, nausea, vomiting, fatigue, dizziness, pruritus, angina pectoris, vertigo, abdominal pain and diarrhea. The rates of leukopenia and drug fever in general group were significantly lower than those in severe group (P < 0.05);in the dose of amphotericin B used, the rate of using 25 mg and more than 25 mg in the general group was significantly lower than that in the severe group (P < 0.05). After symptomatic treat-ment, most patients have improved, and a few are unknown or have not improved. Con-clusion: Amphotericin B for injection has great side effects and will cause different degrees of adverse drug reactions. The dose of amphotericin B for clinical treatment should be ad-justed and disposed according to the adverse reactions to avoid serious consequences.
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.81872823,81871477 and 82073782)the Double First-Class(CPU2018PZQ13,China)of the China Pharmaceutical University+3 种基金the Shanghai Science and Technology Committee(No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(TCM-201905,China)the Guangdong Basic and Applied Basic Research Foundation,China(No.2020A1515010593)the Fundamental Research Funds for Central Universities(No.20ykpy111,China)
文摘Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.
文摘Background Amphotericin B （0.7 mg/kg） with flucytosine is the standard treatment for cryptococcal meningitis.However,the long treatment course can induce adverse reactions in patients; therefore,reducing the dose may decrease such reactions.We performed a retrospective analysis of treatment effects and adverse reactions when amphotericin B （0.4 mg/kg or 0.7 mg/kg per day） and flucytosine were used together to treat HIV-negative patients with cryptococcal meningitis.Methods Retrospective analysis was conducted on inpatients at the First Affiliated Hospital,College of Medicine,Zhejiang University （January 2005 to December 2009）.Low- or high-dose amphotericin B （0.4 or 0.7 mg/kg per day,respectively） plus flucytosine was used.The negative conversion rate of Cryptococcus in the cerebrospinal fluid （CSF）,patient mortality,and the incidence of side effects for the two groups （low- vs.high-dose） were compared immediately after treatment and 2 and 10 weeks later.Data were analyzed by the Student＇s t test,chi-square tests using SPSS 12.0 statistical soitware.Results Two weeks post-treatment,Cryptococcus negative CSF rates were 78% （18/23） in the low-dose group and 87% （13/15） in the high-dose group （P=0.28）.Ten weeks post-treatment,both groups were negative.The mortality rate was 8% （2/25） in the low-dose group and 17% （3/18） in the high-dose group （P=-0.25）.There was a statistically significant difference in the incidence of adverse events between the groups,48% （12/25） and 78% （14/18） in the low- and high-dose groups,respectively （P=0.04）.Adverse events that required a change in treatment program in the low-dose group were 12% （3/25） compared to 39% （7/18） in the high-dose group （P=-0.04）.Conclusion Low-dose treatment regimens were better tolerated
文摘Background Nowadays,there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B （L-AmB）.However,these studies have a modest sample size and convey inconclusive results.The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections （IFIs）,compared with L-AmB.Methods Electronic databases （up to July 31,2013） PubMed and Embase databases,the Cochrane Library,and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB.Analyses of efficacy and adverse outcomes were performed by relative risks （RRs） and 95% confidence intervals （C/s）.Heterogeneity was assessed by x2-test and the/2-statistic.Results Three trials were included in this meta-analysis with 1249 modified intention-to-treat （MITT） patients.The results showed that caspofungin produced equal efficacy in favorable overall response （RR=1.02,95% Cl 0.88-1.18; P=0.81） and mortality rate （RR=1.53,95% Cl 0.38-6.27,P=0.55）,safer in clinical adverse events （RR=0.20,95% Cl 0.08-0.54; P=0.001）,laboratory adverse events （RR=0.69,95% Cl 0.57-0.84; P=0.0002）,and discontinuation rate （RR=0.26,95% Cl 0.08-0.83,P=0.02）,compared with L-AmB in the treatment of patients with IFls.Conclusion Based on the results of this meta-analysis,it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.
文摘Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current,clinically approved lipid-based formulations.The objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an in vitro model.Methods:Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at air-liquid interface until well-differentiated.Cultures were exposed to ND-AMB vs AMB and changes in K+ permeability and resistance were measured and recorded via Ussing chamber assay.Ciliary beat frequency (CBF) was analyzed in parallel as well as cytotoxic assay.Potency was assessed using real-time PCR measurement of the Aspergillus fumigatus 18S rRNA.Results:Ussing chamber studies revealed K+ currents that increased rapidly within 30 s of adding AMB (10 μg/mL) to the apical side,indicating apical membranes had become permeable to K+ ions.In contrast,negligible induction of K+ current was obtained following addition of NDAMB [AMB =(107.7 ± 15.9) μA/cm2 AMB vs ND-AMB =(2.3 ± 0.7) μA/cm2 ND-AMB;P =0.005].ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P ＜ 0.05).There was no difference in ciliary beat frequency between the two groups (P =0.96).The expression of A.fumigatus 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB (P ＜ 0.05).Conclusions:Data from the present study suggests ND-AMB protects human nasal epithelia membranes from AMB toxicity by protecting against apical cell K+ permeability while maintaining uncompromised antifungal property compared to AMB.ND-AMB could provide a novel topical therapy for sinonasal fungal diseases.
