scholarly journals Dual Invasive Infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of Phaeoacremonium Phaeohyphomycosis

2015 ◽  
Vol 53 (7) ◽  
pp. 2084-2094 ◽  
Author(s):  
Marie-Alice Colombier ◽  
Alexandre Alanio ◽  
Blandine Denis ◽  
Giovanna Melica ◽  
Dea Garcia-Hermoso ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Amphotericin B ◽  
Antifungal Therapy ◽  
Surgical Excision ◽  
Human Infection ◽  
Antifungal Drugs ◽  
Kidney Transplant Patient ◽  
Invasive Infection ◽  
Optimal Care ◽  
Content Type

Despite increasing reports of human infection, data about the optimal care ofPhaeoacremoniuminfections are missing. We report a case of an infection due toPhaeoacremonium parasiticumandParaconiothyrium cyclothyrioides, initially localized to skin and soft tissue, in a kidney transplant patient. Despite surgical drainage and excision of the lesion and combination antifungal therapy with voriconazole and liposomal amphotericin B, a disseminated infection involving the lungs and brain developed and led to death. We performed a systematic literature review to assess the general features and outcome of human infections due toPhaeoacremoniumspecies. Thirty-six articles were selected, and 42 patients, including ours, were reviewed. Thirty-one patients (74%) were immunocompromised because of organ or bone marrow transplantation (n= 17), diabetes or glucose intolerance (n= 10), rheumatoid arthritis or Still's disease (n= 4), chronic hematological diseases (n= 3), or chronic granulomatous disease (n= 3). Ten patients (24%) reported initial cutaneous trauma. Skin and soft tissue infections represented 57% of infections (n= 24), and disseminated infections, all occurring in immunocompromised patients, represented 14% of infections (n= 6). The main antifungal drugs used were azoles (n= 41) and amphotericin B (n= 16). Surgical excision or drainage was performed in 64% of cases (n= 27). The cure rate was 67% (n= 28). There were 10% cases of treatment failure or partial response (n= 4), 19% relapses (n= 8), and 7% losses to follow-up (n= 3). The death rate was 19% (n= 8). Management ofPhaeoacremoniuminfections is complex because of slow laboratory identification and limited clinical data, and treatment relies on a combination of surgery and systemic antifungal therapy.

scholarly journals Expression Turnover Profiling To Monitor the Antifungal Activities of Amphotericin B, Voriconazole, and Micafungin against Aspergillus fumigatus

2012 ◽  
Vol 56 (5) ◽  
pp. 2770-2772 ◽  
Author(s):  
Yanan Zhao ◽  
Padmaja Paderu ◽  
Steven Park ◽  
Aleksandra Dukhan ◽  
Meredith Senter ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Candidate Genes ◽  
Amphotericin B ◽  
Antifungal Therapy ◽  
Treatment Efficacy ◽  
Antifungal Drugs ◽  
Live Cells ◽  
Content Type ◽  
Kinetics Of ◽  
Potential Biomarkers

ABSTRACTEight highly expressed candidate genes were selected for mRNA profiling to monitor the transcriptome kinetics ofAspergillus fumigatusstrains exposed to antifungal drugs as potential biomarkers of live cells to assess treatment efficacy. Mycelia were treated with fungicidal drugs amphotericin B and voriconazole, as well as the fungistatic drug micafungin. Transcription was monitored at 0, 4, 8, and 24 h posttreatment. The expression turnover profile provides a possible tool to assess antifungal therapy effects.

scholarly journals Dectin-2-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Suresh Ambati ◽  
Emma C. Ellis ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
Zachary A. Lewis ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Effective Dose ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Drugs ◽  
Extracellular Matrices ◽  
Content Type ◽  
Order Of Magnitude ◽  
Life Threatening

ABSTRACT Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus cause life-threatening candidiasis, cryptococcosis, and aspergillosis, resulting in several hundred thousand deaths annually. The patients at the greatest risk of developing these life-threatening invasive fungal infections have weakened immune systems. The vulnerable population is increasing due to rising numbers of immunocompromised individuals as a result of HIV infection or immunosuppressed individuals receiving anticancer therapies and/or stem cell or organ transplants. While patients are treated with antifungals such as amphotericin B, all antifungals have serious limitations due to lack of sufficient fungicidal effect and/or host toxicity. Even with treatment, 1-year survival rates are low. We explored methods of increasing drug effectiveness by designing fungicide-loaded liposomes specifically targeted to fungal cells. Most pathogenic fungi are encased in cell walls and exopolysaccharide matrices rich in mannans. Dectin-2 is a mammalian innate immune membrane receptor that binds as a dimer to mannans and signals fungal infection. We coated amphotericin-loaded liposomes with monomers of Dectin-2’s mannan-binding domain, sDectin-2. sDectin monomers were free to float in the lipid membrane and form dimers that bind mannan substrates. sDectin-2-coated liposomes bound orders of magnitude more efficiently to the extracellular matrices of several developmental stages of C. albicans, C. neoformans, and A. fumigatus than untargeted control liposomes. Dectin-2-coated amphotericin B-loaded liposomes reduced the growth and viability of all three species more than an order of magnitude more efficiently than untargeted control liposomes and dramatically decreased the effective dose. Future efforts focus on examining pan-antifungal targeted liposomal drugs in animal models of fungal diseases. IMPORTANCE Invasive fungal diseases caused by Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus have mortality rates ranging from 10 to 95%. Individual patient costs may exceed $100,000 in the United States. All antifungals in current use have serious limitations due to host toxicity and/or insufficient fungal cell killing that results in recurrent infections. Few new antifungal drugs have been introduced in the last 2 decades. Hence, there is a critical need for improved antifungal therapeutics. By targeting antifungal-loaded liposomes to α-mannans in the extracellular matrices secreted by these fungi, we dramatically reduced the effective dose of drug. Dectin-2-coated liposomes loaded with amphotericin B bound 50- to 150-fold more strongly to C. albicans, C. neoformans, and A. fumigatus than untargeted liposomes and killed these fungi more than an order of magnitude more efficiently. Targeting drug-loaded liposomes specifically to fungal cells has the potential to greatly enhance the efficacy of most antifungal drugs.

scholarly journals In VitroActivities of Nine Antifungal Drugs against 81 Phialophora and Cyphellophora Isolates

2012 ◽  
Vol 56 (11) ◽  
pp. 6044-6047 ◽  
Author(s):  
Peiying Feng ◽  
M. Javad Najafzadeh ◽  
Jiufeng Sun ◽  
Sarah Ahmed ◽  
Liyan Xi ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Drugs ◽  
Content Type

ABSTRACTCyphellophora guyanensis(n= 15), otherCyphellophoraspecies (n= 11),Phialophora europaea(n= 43), and otherPhialophoraspecies (n= 12) were testedin vitroagainst nine antifungal drugs. The MIC90s across all of the strains (n= 81) were, in increasing order, as follows: posaconazole, 0.063 μg/ml; itraconazole, 0.5 μg/ml; voriconazole, 1 μg/ml; micafungin, 1 μg/ml; terbinafine, 2 μg/ml; isavuconazole, 4 μg/ml; caspofungin, 4 μg/ml; fluconazole, 8 μg/ml; amphotericin B, 16 μg/ml.

scholarly journals Protection againstStaphylococcus aureusColonization and Infection by B- and T-Cell-Mediated Mechanisms

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Fan Zhang ◽  
Olivia Ledue ◽  
Maria Jun ◽  
Cibelly Goulart ◽  
Richard Malley ◽  
...  
Keyword(s):  
T Cell ◽  
Soft Tissue ◽  
Bacterial Infections ◽  
Vaccine Development ◽  
Pathological Condition ◽  
Treatment Options ◽  
Immune Defense ◽  
Invasive Infection ◽  
Content Type ◽  
Increased Risk

ABSTRACTStaphylococcus aureusis a major cause of morbidity and mortality worldwide.S. aureuscolonizes 20 to 80% of humans at any one time and causes a variety of illnesses. Strains that are resistant to common antibiotics further complicate management.S. aureusvaccine development has been unsuccessful so far, largely due to the incomplete understanding of the mechanisms of protection against this pathogen. Here, we studied the role of different aspects of adaptive immunity induced by anS. aureusvaccine in protection againstS. aureusbacteremia, dermonecrosis, skin abscess, and gastrointestinal (GI) colonization. We show that, depending on the challenge model, the contributions of vaccine-inducedS. aureus-specific antibody and Th1 and Th17 responses to protection are different: antibodies play a major role in reducing mortality duringS. aureusbacteremia, whereas Th1 or Th17 responses are essential for prevention ofS. aureusskin abscesses and the clearance of bacteria from the GI tract. Both antibody- and T-cell-mediated mechanisms contribute to prevention ofS. aureusdermonecrosis. Engagement of all three immune pathways results in the most robust protection under each pathological condition. Therefore, our results suggest that eliciting multipronged humoral and cellular responses toS. aureusantigens may be critical to achieve effective and comprehensive immune defense against this pathogen.IMPORTANCES. aureusis a leading cause of healthcare- and community-associated bacterial infections.S. aureuscauses various illnesses, including bacteremia, meningitis, endocarditis, pneumonia, osteomyelitis, sepsis, and skin and soft tissue infections.S. aureuscolonizes between 20 and 80% of humans; carriers are at increased risk for infection and transmission to others. The spread of multidrug-resistant strains limits antibiotic treatment options. Vaccine development againstS. aureushas been unsuccessful to date, likely due to an inadequate understanding about the mechanisms of immune defense against this pathogen. The significance of our work is in illustrating the necessity of generating multipronged B-cell, Th1-, and Th17-mediated responses toS. aureusantigens in conferring enhanced and broad protection againstS. aureusinvasive infection, skin and soft tissue infection, and mucosal colonization. Our work thus, provides important insights for future vaccine development against this pathogen.

scholarly journals Lactoferrin Is Broadly Active against Yeasts and Highly Synergistic with Amphotericin B

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Kenya E. Fernandes ◽  
Kerry Weeks ◽  
Dee A. Carter
Keyword(s):  
Amphotericin B ◽  
Galleria Mellonella ◽  
Comprehensive Evaluation ◽  
Yeast Species ◽  
Phenotypic Diversity ◽  
Antifungal Drugs ◽  
Fungal Cell ◽  
Content Type ◽  
Iron Saturation ◽  
Capsule Size

ABSTRACT Lactoferrin (LF) is a multifunctional milk protein with antimicrobial activity against a range of pathogens. While numerous studies report that LF is active against fungi, there are considerable differences in the level of antifungal activity and the capacity of LF to interact with other drugs. Here we undertook a comprehensive evaluation of the antifungal spectrum of activity of three defined sources of LF across 22 yeast and 24 mold species and assessed its interactions with six widely used antifungal drugs. LF was broadly and consistently active against all yeast species tested (MICs, 8 to 64 μg/ml), with the extent of activity being strongly affected by iron saturation. LF was synergistic with amphotericin B (AMB) against 19 out of 22 yeast species tested, and synergy was unaffected by iron saturation but was affected by the extent of LF digestion. LF-AMB combination therapy significantly prolonged the survival of Galleria mellonella wax moth larvae infected with Candida albicans or Cryptococcus neoformans and decreased the fungal burden 12- to 25-fold. Evidence that LF directly interacts with the fungal cell surface was seen via scanning electron microscopy, which showed pore formation, hyphal thinning, and major cell collapse in response to LF-AMB synergy. Important virulence mechanisms were disrupted by LF-AMB treatment, which significantly prevented biofilms in C. albicans and C. glabrata, inhibited hyphal development in C. albicans, and reduced cell and capsule size and phenotypic diversity in Cryptococcus. Our results demonstrate the potential of LF-AMB as an antifungal treatment that is broadly synergistic against important yeast pathogens, with the synergy being attributed to the presence of one or more LF peptides.

scholarly journals In VitroActivities of a Wide Panel of Antifungal Drugs against Various Scopulariopsis and Microascus Species

2015 ◽  
Vol 59 (9) ◽  
pp. 5827-5829 ◽  
Author(s):  
Magdalena Skóra ◽  
Małgorzata Bulanda ◽  
Tomasz Jagielski
Keyword(s):  
Amphotericin B ◽  
Effective Concentration ◽  
Antifungal Drugs ◽  
Antifungal Effect ◽  
Content Type ◽  
Minimal Effective Concentration

ABSTRACTThein vitroactivities of 11 antifungal drugs against 68ScopulariopsisandMicroascusstrains were investigated. Amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, voriconazole, and ciclopirox showed no or poor antifungal effect. The best activities were exhibited by terbinafine and caspofungin, where the MIC and MEC (minimal effective concentration) ranges were 0.0313 to >16 μg/ml and 0.125 to 16 μg/ml, respectively. The MIC and MEC modes were both 1 µg/ml for terbinafine and caspofungin; the MIC50and MEC50were 1 µg/ml for both drugs, whereas the MIC90and MEC90were 4 µg/ml and 16 µg/ml, respectively.

scholarly journals Potent Activities of Luliconazole, Lanoconazole, and Eight Comparators against Molecularly Characterized Fusarium Species

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Mahdi Abastabar ◽  
Abdullah M. S. Al-Hatmi ◽  
Mohammad Vafaei Moghaddam ◽  
G. Sybren de Hoog ◽  
Iman Haghani ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Topical Treatment ◽  
Fusarium Species ◽  
Geometric Mean ◽  
Antifungal Drugs ◽  
Content Type

ABSTRACT A collection of clinical ( n = 47) and environmental ( n = 79) Fusarium isolates were tested against 10 antifungal drugs, including 2 novel imidazoles. Luliconazole and lanoconazole demonstrated very low geometric mean MIC values of 0.005 and 0.013 μg/ml, respectively, compared with 0.51 μg/ml for micafungin, 0.85 μg/ml for efinaconazole, 1.12 μg/ml for natamycin, 1.18 μg/ml for anidulafungin, 1.31 μg/ml for voriconazole, 1.35 μg/ml for caspofungin, 1.9 μg/ml for amphotericin B, and 4.08 μg/ml for itraconazole. Results show that these drugs are potential candidates for (topical) treatment of skin and nail infections due to Fusarium species.

scholarly journals In VitroAntifungal Susceptibility of Cladophialophora carrionii, an Agent of Human Chromoblastomycosis

2013 ◽  
Vol 57 (4) ◽  
pp. 1974-1977 ◽  
Author(s):  
S. Deng ◽  
G. S. de Hoog ◽  
H. Badali ◽  
L. Yang ◽  
M. J. Najafzadeh ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Drugs ◽  
Content Type ◽  
Cladophialophora Carrionii

ABSTRACTA global collection ofCladophialophora carrioniistrains (n= 81) was tested against nine antifungal drugs. MIC90s of all strains were as follows in increasing order: itraconazole and posaconazole, 0.063 μg/ml; terbinafine, 0.125 μg/ml; isavuconazole and voriconazole, 0.25 μg/ml; caspofungin, 2 μg/ml; micafungin, 4 μg/ml; amphotericin B, 8 μg/ml; and fluconazole, 64 μg/ml.

scholarly journals In VitroInteraction between Alginate Lyase and Amphotericin B against Aspergillus fumigatus Biofilm Determined by Different Methods

2012 ◽  
Vol 57 (3) ◽  
pp. 1275-1282 ◽  
Author(s):  
Francesca Bugli ◽  
Brunella Posteraro ◽  
Massimiliano Papi ◽  
Riccardo Torelli ◽  
Alessandro Maiorana ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Extracellular Polymeric Substances ◽  
Alginate Lyase ◽  
Antifungal Drugs ◽  
Antibiofilm Activity ◽  
Content Type ◽  
Time Kill

ABSTRACTAspergillus fumigatusbiofilms represent a problematic clinical entity, especially because of their recalcitrance to antifungal drugs, which poses a number of therapeutic implications for invasive aspergillosis, the most difficult-to-treatAspergillus-related disease. While the antibiofilm activities of amphotericin B (AMB) deoxycholate and its lipid formulations (e.g., liposomal AMB [LAMB]) are well documented, the effectiveness of these drugs in combination with nonantifungal agents is poorly understood. In the present study,in vitrointeractions between polyene antifungals (AMB and LAMB) and alginate lyase (AlgL), an enzyme degrading the polysaccharides produced as extracellular polymeric substances (EPSs) within the biofilm matrix, againstA. fumigatusbiofilms were evaluated by using the checkerboard microdilution and the time-kill assays. Furthermore, atomic force microscopy (AFM) was used to image and quantify the effects of AlgL-antifungal combinations on biofilm-growing hyphal cells. On the basis of fractional inhibitory concentration index values, synergy was found between both AMB formulations and AlgL, and this finding was also confirmed by the time-kill test. Finally, AFM analysis showed that whenA. fumigatusbiofilms were treated with AlgL or polyene alone, as well as with their combination, both a reduction of hyphal thicknesses and an increase of adhesive forces were observed compared to the findings for untreated controls, probably owing to the different action by the enzyme or the antifungal compounds. Interestingly, marked physical changes were noticed inA. fumigatusbiofilms exposed to the AlgL-antifungal combinations compared with the physical characteristics detected after exposure to the antifungals alone, indicating that AlgL may enhance the antibiofilm activity of both AMB and LAMB, perhaps by disrupting the hypha-embedding EPSs and thus facilitating the drugs to reach biofilm cells. Taken together, our results suggest that a combination of AlgL and a polyene antifungal may prove to be a new therapeutic strategy for invasive aspergillosis, while reinforcing the EPS as a valuable antibiofilm drug target.

scholarly journals Candida Infective Endocarditis: an Observational Cohort Study with a Focus on Therapy

2015 ◽  
Vol 59 (4) ◽  
pp. 2365-2373 ◽  
Author(s):  
Christopher J. Arnold ◽  
Melissa Johnson ◽  
Arnold S. Bayer ◽  
Suzanne Bradley ◽  
Efthymia Giannitsioti ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cohort Study ◽  
Infective Endocarditis ◽  
Mortality Rate ◽  
Amphotericin B ◽  
Prospective Cohort Study ◽  
Antifungal Therapy ◽  
Subgroup Analysis ◽  
Prospective Cohort ◽  
Content Type

ABSTRACTCandidainfective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens forCandidainfective endocarditis. This prospective cohort study was based on 70 cases ofCandidainfective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion,Candidainfective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.

Sign in / Sign up

Export Citation Format

Share Document