scholarly journals Species-Specific and Drug-Specific Differences in Susceptibility of Candida Biofilms to Echinocandins: Characterization of Less Common Bloodstream Isolates

2013 ◽  
Vol 57 (6) ◽  
pp. 2562-2570 ◽  
Author(s):  
Maria Simitsopoulou ◽  
Pavla Peshkova ◽  
Efthymia Tasina ◽  
Aspasia Katragkou ◽  
Daniela Kyrpitzi ◽  
...  
Keyword(s):  
Candida Guilliermondii ◽  
Growth Effect ◽  
Planktonic Cells ◽  
Content Type ◽  
Fungal Damage ◽  
Paradoxical Growth ◽  
Candida Lusitaniae ◽  
Species Specific ◽  
High Mics

ABSTRACTCandidaspecies other thanCandida albicansare increasingly recognized as causes of biofilm-associated infections. This is a comprehensive study that compared thein vitroactivities of all three echinocandins against biofilms formed by different common and infrequently identifiedCandidaisolates. We determined the activities of anidulafungin (ANID), caspofungin (CAS), and micafungin (MFG) against planktonic cells and biofilms of bloodstream isolates ofC. albicans(15 strains),Candida parapsilosis(6 strains),Candida lusitaniae(16 strains),Candida guilliermondii(5 strains), andCandida krusei(12 strains) by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. Planktonic and biofilm MICs were defined as ≥50% fungal damage. Planktonic cells of allCandidaspecies were susceptible to the three echinocandins, with MICs of ≤1 mg/liter. By comparison, differences in the MIC profiles of biofilms in response to echinocandins existed among theCandidaspecies. Thus,C. lusitaniaeandC. guilliermondiibiofilms were highly recalcitrant to all echinocandins, with MICs of ≥32 mg/liter. In contrast, the MICs of all three echinocandins forC. albicansandC. kruseibiofilms were relatively low (MICs ≤ 1 mg/liter). While echinocandins exhibited generally high MICs againstC. parapsilosisbiofilms, MFG exhibited the lowest MICs against these isolates (4 mg/liter). A paradoxical growth effect was observed with CAS concentrations ranging from 8 to 64 mg/liter againstC. albicansandC. parapsilosisbiofilms but not againstC. krusei,C. lusitaniae, orC. guilliermondii. While non-albicans Candidaplanktonic cells were susceptible to all echinocandins, there were drug- and species-specific differences in susceptibility among biofilms of the variousCandidaspecies, withC. lusitaniaeandC. guilliermondiiexhibiting profiles of high MICs of the three echinocandins.

scholarly journals Molecular Identification and Antifungal Susceptibility of Yeast Isolates Causing Fungemia Collected in a Population-Based Study in Spain in 2010 and 2011

2013 ◽  
Vol 58 (3) ◽  
pp. 1529-1537 ◽  
Author(s):  
Jesús Guinea ◽  
Óscar Zaragoza ◽  
Pilar Escribano ◽  
Estrella Martín-Mazuelos ◽  
Javier Pemán ◽  
...  
Keyword(s):  
Hot Spot ◽  
Antifungal Susceptibility ◽  
Point Mutations ◽  
Population Based ◽  
Candida Guilliermondii ◽  
Population Based Study ◽  
Content Type ◽  
Candida Lusitaniae ◽  
Species Specific

ABSTRACTWe report the molecular identifications and antifungal susceptibilities of the isolates causing fungemia collected in the CANDIPOP population-based study conducted in 29 Spanish hospitals. A total of 781 isolates (from 767 patients, 14 of them having mixed fungemia) were collected. The species found most frequently wereCandida albicans(44.6%),Candida parapsilosis(24.5%),Candida glabrata(13.2%),Candida tropicalis(7.6%),Candida krusei(1.9%),Candida guilliermondii(1.7%), andCandida lusitaniae(1.3%). OtherCandidaand non-Candidaspecies accounted for approximately 5% of the isolates. The presence of cryptic species was low. Compared to findings of previous studies conducted in Spain, the frequency ofC. glabratahas increased. Antifungal susceptibility testing was performed by using EUCAST and CLSI M27-A3 reference procedures; the two methods were comparable. The rate of fluconazole-susceptible isolates was 80%, which appears to be a decrease compared to findings of previous studies, explained mainly by the higher frequency ofC. glabrata. Using the species-specific breakpoints and epidemiological cutoff values, the rate of voriconazole and posaconazolein vitroresistance was low (<2%). In the case ofC. tropicalis, using the EUCAST procedure, the rate of azole resistance was around 20%. There was a correlation between the previous use of azoles and the presence of fluconazole-resistant isolates. Resistance to echinocandins was very rare (2%), and resistance to amphotericin B also was very uncommon. The sequencing of the hot spot (HS) regions fromFKS1orFKS2genes in echinocandin-resistant isolates revealed previously described point mutations. The decrease in the susceptibility to fluconazole in Spanish isolates should be closely monitored in future studies.

scholarly journals A Revised Species Concept for OpportunisticMucorSpecies Reveals Species-Specific Antifungal Susceptibility Profiles

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Lysett Wagner ◽  
Sybren de Hoog ◽  
Ana Alastruey-Izquierdo ◽  
Kerstin Voigt ◽  
Oliver Kurzai ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Species Concept ◽  
Antifungal Susceptibility ◽  
Content Type ◽  
Mucor Indicus ◽  
Species Specific ◽  
Susceptibility Profiles ◽  
High Mics

ABSTRACTRecently, the species concept of opportunisticMucor circinelloidesand its relatives has been revised, resulting in the recognition of its classical formae as independent species and the description of new species. In this study, we used isolates of all clinically relevantMucorspecies and performed susceptibility testing using the EUCAST reference method to identify potential species-specific susceptibility patterns.In vitrosusceptibility profiles of 101 mucoralean strains belonging to the genusMucor(72), the closely related speciesCokeromyces recurvatus(3),Rhizopus(12),Lichtheimia(10), andRhizomucor(4) to six antifungals (amphotericin B, natamycin, terbinafine, isavuconazole, itraconazole, and posaconazole) were determined. The most active drug for all Mucorales was amphotericin B. Antifungal susceptibility profiles of pathogenicMucorspecies were specific for isavuconazole, itraconazole, and posaconazole. The species formerly united inM. circinelloidesshowed clear differences in their antifungal susceptibilities.Cokeromyces recurvatus,Mucor ardhlaengiktus,Mucor lusitanicus(M. circinelloidesf.lusitanicus), andMucor ramosissimusexhibited high MICs to all azoles tested.Mucor indicuspresented high MICs for isavuconazole and posaconazole, andMucor amphibiorumandMucor irregularisshowed high MICs for isavuconazole. MIC values ofMucorspp. for posaconazole, isavuconazole, and itraconazole were high compared to those forRhizopusand the Lichtheimiaceae (LichtheimiaandRhizomucor). Molecular identification combined within vitrosusceptibility testing is recommended forMucorspecies, especially if azoles are applied in treatment.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

scholarly journals Glycoside Hydrolases Degrade Polymicrobial Bacterial Biofilms in Wounds

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Derek Fleming ◽  
Laura Chahin ◽  
Kendra Rumbaugh
Keyword(s):  
Glycoside Hydrolase ◽  
Bacterial Population ◽  
Chronic Wounds ◽  
Glycoside Hydrolases ◽  
Bacterial Biofilms ◽  
Planktonic Cells ◽  
Content Type ◽  
Biomass Dissolution

ABSTRACT The persistent nature of chronic wounds leaves them highly susceptible to invasion by a variety of pathogens that have the ability to construct an extracellular polymeric substance (EPS). This EPS makes the bacterial population, or biofilm, up to 1,000-fold more antibiotic tolerant than planktonic cells and makes wound healing extremely difficult. Thus, compounds which have the ability to degrade biofilms, but not host tissue components, are highly sought after for clinical applications. In this study, we examined the efficacy of two glycoside hydrolases, α-amylase and cellulase, which break down complex polysaccharides, to effectively disrupt Staphylococcus aureus and Pseudomonas aeruginosa monoculture and coculture biofilms. We hypothesized that glycoside hydrolase therapy would significantly reduce EPS biomass and convert bacteria to their planktonic state, leaving them more susceptible to conventional antimicrobials. Treatment of S. aureus and P. aeruginosa biofilms, grown in vitro and in vivo, with solutions of α-amylase and cellulase resulted in significant reductions in biomass, dissolution of the biofilm, and an increase in the effectiveness of subsequent antibiotic treatments. These data suggest that glycoside hydrolase therapy represents a potential safe, effective, and new avenue of treatment for biofilm-related infections.

scholarly journals Antifungal Activity of SCY-078 and Standard Antifungal Agents against 178 Clinical Isolates of Resistant and Susceptible Candida Species

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Wiley A. Schell ◽  
A. M. Jones ◽  
Katyna Borroto-Esoda ◽  
Barbara D. Alexander
Keyword(s):  
Candida Glabrata ◽  
Antifungal Agents ◽  
Candida Parapsilosis ◽  
Candida Krusei ◽  
Wild Type ◽  
Content Type ◽  
Clinical Resistance ◽  
Excellent Activity ◽  
Candida Lusitaniae

ABSTRACT SCY-078 in vitro activity was determined for 178 isolates of resistant or susceptible Candida albicans, Candida dubliniensis, Candida glabrata, Candida krusei, Candida lusitaniae, and Candida parapsilosis, including 44 Candida isolates with known genotypic (FKS1 or FKS2 mutations), phenotypic, or clinical resistance to echinocandins. Results were compared to those for anidulafungin, caspofungin, micafungin, fluconazole, and voriconazole. SCY-078 was shown to have excellent activity against both wild-type isolates and echinocandin- and azole-resistant isolates of Candida species.

scholarly journals Echinocandins for the Treatment of Invasive Aspergillosis: from Laboratory to Bedside

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Marion Aruanno ◽  
Emmanouil Glampedakis ◽  
Frédéric Lamoth
Keyword(s):  
Invasive Aspergillosis ◽  
Fungal Infections ◽  
Heat Shock Protein 90 ◽  
Hyphal Growth ◽  
Content Type ◽  
Complex Interactions ◽  
Drug Classes ◽  
Paradoxical Growth ◽  
Glucan Synthesis

ABSTRACT Echinocandins (caspofungin, micafungin, anidulafungin), targeting β-1,3-glucan synthesis of the cell wall, represent one of the three currently available antifungal drug classes for the treatment of invasive fungal infections. Despite their limited antifungal activity against Aspergillus spp., echinocandins are considered an alternative option for the treatment of invasive aspergillosis (IA). This drug class exhibits several advantages, such as excellent tolerability and its potential for synergistic interactions with some other antifungals. The objective of this review is to discuss the in vitro and clinical efficacy of echinocandins against Aspergillus spp., considering the complex interactions between the drug, the mold, and the host. The antifungal effect of echinocandins is not limited to direct inhibition of hyphal growth but also induces an immunomodulatory effect on the host’s response. Moreover, Aspergillus spp. have developed important adaptive mechanisms of tolerance to survive and overcome the action of echinocandins, such as paradoxical growth at increased concentrations. This stress response can be abolished by several compounds that potentiate the activity of echinocandins, such as drugs targeting the heat shock protein 90 (Hsp90)-calcineurin axis, opening perspectives for adjuvant therapies. Finally, the present and future places of echinocandins as prophylaxis, monotherapy, or combination therapy of IA are discussed in view of the emergence of pan-azole resistance among Aspergillus fumigatus isolates, the occurrence of breakthrough IA, and the advent of new long-lasting echinocandins (rezafungin) or other β-1,3-glucan synthase inhibitors (ibrexafungerp).

scholarly journals Efficacy of Humanized High-Dose Meropenem, Cefepime, and Levofloxacin against Enterobacteriaceae Isolates Producing Verona Integron-Encoded Metallo-β-Lactamase (VIM) in a Murine Thigh Infection Model

2015 ◽  
Vol 59 (11) ◽  
pp. 7145-7147 ◽  
Author(s):  
Islam M. Ghazi ◽  
Jared L. Crandon ◽  
Emil P. Lesho ◽  
Patrick McGann ◽  
David P. Nicolau
Keyword(s):  
Murine Model ◽  
Infection Model ◽  
High Dose ◽  
Content Type ◽  
High Mics

ABSTRACTWe aimed to describe thein vivoactivity of humanized pharmacokinetic exposures of meropenem and comparators against Verona integron-encoded metallo-β-lactamase (MBL) (VIM)-producingEnterobacteriaceaein a murine model. Levofloxacin activity was predicted by its MIC, and cefepime activity displayed variability, whereas meropenem produced a >1 log CFU reduction against all isolates despite high MICs indicative of resistance. Our results suggest that despitein vitroresistance, high-dose meropenem may be a possible option against infections caused byEnterobacteriaceaeproducing MBL-type carbapenemases.

scholarly journals Caspofungin at Catheter Lock Concentrations Eradicates Mature Biofilms of Candida lusitaniae and Candida guilliermondii

2014 ◽  
Vol 58 (8) ◽  
pp. 4953-4956 ◽  
Author(s):  
Maria Simitsopoulou ◽  
Daniela Kyrpitzi ◽  
Aristea Velegraki ◽  
Thomas J. Walsh ◽  
Emmanuel Roilides
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Candida Guilliermondii ◽  
Liposomal Amphotericin B ◽  
Antibiofilm Activity ◽  
Test Species ◽  
Content Type ◽  
Lock Therapy ◽  
Catheter Lock ◽  
Candida Lusitaniae

ABSTRACTThe antibiofilm activities of caspofungin, anidulafungin, micafungin, and liposomal amphotericin B were studied againstCandida lusitaniae,Candida guilliermondii, and aCandida albicanscontrol strain. While anidulafungin and micafungin (0.007 to 2,048 mg/liter) showed reduced activity against biofilms of both test species, caspofungin displayed concentration-dependent antibiofilm activity, reaching complete and persistent eradication at concentrations achievable during lock therapy (512 to 2,048 mg/liter,P< 0.05). Although liposomal amphotericin B strongly inhibited mature biofilms, it possessed lower antibiofilm activity than caspofungin (P< 0.05).

scholarly journals ModifiedmarinerTransposons for Random Inducible-Expression Insertions and Transcriptional Reporter Fusion Insertions in Bacillus subtilis

2011 ◽  
Vol 78 (3) ◽  
pp. 778-785 ◽  
Author(s):  
Eric R. Pozsgai ◽  
Kris M. Blair ◽  
Daniel B. Kearns
Keyword(s):  
Bacillus Subtilis ◽  
Insertional Mutagenesis ◽  
Inducible Promoter ◽  
Insertion Sequences ◽  
Content Type ◽  
Transcriptional Reporter ◽  
Species Specific ◽  
Genetically Manipulated

ABSTRACTTransposons are mobile genetic elements bounded by insertion sequences that are recognized by a specific mobilizing transposase enzyme. The transposase may mobilize not only the insertion sequences but also intervening DNA.marineris a particularly efficient transposon for the random chromosomal integration of genes and insertional mutagenesis. Here, we modify an existingmarinertransposon, TnYLB, such that it can easily be genetically manipulated and introduced intoBacillus subtilis. We generate a series of three newmarinerderivatives that mobilize spectinomycin, chloramphenicol, and kanamycin antibiotic resistance cassettes. Furthermore, we generate a series of transposons with a strong, outward-oriented, optionally isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible promoter for the random overexpression of neighboring genes and a series of transposons with a promoterlesslacZgene for the random generation of transcriptional reporter fusions. We note that the modification of the base transposon is not restricted toB. subtilisand should be applicable to anymariner-compatible host organism, provided thatin vitromutagenesis or anin vivospecies-specific delivery vector is employed.

scholarly journals Antifungal Resistance to Fluconazole and Echinocandins Is Not Emerging in Yeast Isolates Causing Fungemia in a Spanish Tertiary Care Center

2014 ◽  
Vol 58 (8) ◽  
pp. 4565-4572 ◽  
Author(s):  
Laura Judith Marcos-Zambrano ◽  
Pilar Escribano ◽  
Carlos Sánchez ◽  
Patricia Muñoz ◽  
Emilio Bouza ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Molecular Level ◽  
Care Center ◽  
Antifungal Susceptibility ◽  
Tertiary Care ◽  
Candida Guilliermondii ◽  
Antifungal Resistance ◽  
Its2 Region ◽  
Content Type

ABSTRACTAccurate knowledge of fungemia epidemiology requires identification of strains to the molecular level. Various studies have shown that the rate of resistance to fluconazole ranges from 2.5% to 9% inCandidaspp. isolated from blood samples. However, trends in antifungal resistance have received little attention and have been studied only using CLSI M27-A3 methodology. We assessed the fungemia epidemiology in a large tertiary care institution in Madrid, Spain, by identifying isolates to the molecular level and performing antifungal susceptibility testing according to the updated breakpoints of European Committee for Antimicrobial Susceptibility Testing (EUCAST) definitive document (EDef) 7.2. We studied 613 isolates causing 598 episodes of fungemia in 544 patients admitted to our hospital (January 2007 to December 2013). Strains were identified after amplification and sequencing of the ITS1-5.8S-ITS2 region and further tested forin vitrosusceptibility to amphotericin B, fluconazole, posaconazole, voriconazole, micafungin, and anidulafungin. Resistance was defined using EUCAST species-specific breakpoints, and epidemiological cutoff values (ECOFFs) were applied as tentative breakpoints. Most episodes were caused byCandida albicans(46%),Candida parapsilosis(28.7%),Candida glabrata(9.8%), andCandida tropicalis(8%). Molecular identification enabled us to better detect cryptic species ofCandida guilliermondiiandC. parapsilosiscomplexes and episodes of polyfungal fungemia. The overall percentage of fluconazole-resistant isolates was 5%, although it was higher inC. glabrata(8.6%) and non-Candidayeast isolates (47.4%). The rate of resistance to echinocandins was 4.4% and was mainly due to the presence of intrinsically resistant non-Candidaspecies. Resistance mainly affected non-Candidayeasts. The rate of resistance to fluconazole and echinocandins did not change considerably during the study period.

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