scholarly journals Activities of Systemically Administered Echinocandins againstIn VivoMature Candida albicans Biofilms Developed in a Rat Subcutaneous Model

2013 ◽  
Vol 57 (5) ◽  
pp. 2365-2368 ◽  
Author(s):  
Soňa Kucharíková ◽  
Nidhi Sharma ◽  
Isabel Spriet ◽  
Johan Maertens ◽  
Patrick Van Dijck ◽  
...  
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Rat Model ◽  
Model System ◽  
Content Type ◽  
Cell Numbers ◽  
Candida Albicans Biofilms

ABSTRACTThis study addresses the effects of micafungin, caspofungin, and anidulafungin againstCandida albicansbiofilms developed in a subcutaneous catheter rat model system. Doses of 5, 10, and 30 mg/kg (of body weight)/day (the last only for micafungin) were given intravenously for 5, 7, and 10 days. All three echinocandins caused a significant reduction of theCandidacell numbers on the implanted catheters and are thus promising for the treatment of biofilm-related infections.

scholarly journals In Vivo Efficacy of Anidulafungin against Mature Candida albicans Biofilms in a Novel Rat Model of Catheter-Associated Candidiasis

2010 ◽  
Vol 54 (10) ◽  
pp. 4474-4475 ◽  
Author(s):  
Soňa Kucharíková ◽  
Hélène Tournu ◽  
Michelle Holtappels ◽  
Patrick Van Dijck ◽  
Katrien Lagrou
Keyword(s):  
Candida Albicans ◽  
Rat Model ◽  
Systemic Administration ◽  
In Vivo Efficacy ◽  
Cell Numbers ◽  
Candida Albicans Biofilms

ABSTRACT The present study demonstrates the efficacy of anidulafungin on mature Candida albicans biofilms in vivo. One hundred fifty-seven catheter fragments challenged with C. albicans were implanted subcutaneously in rats. After formation of biofilms, rats were treated with daily intraperitoneal injections of anidulafungin for 7 days. Catheters retrieved from treated animals showed reduced cell numbers compared to those retrieved from untreated and fluconazole-treated animals. Systemic administration of anidulafungin is promising for the treatment of mature C. albicans biofilms.

scholarly journals Candida glabrataHas No Enhancing Role in the Pathogenesis ofCandida-Associated Denture Stomatitis in a Rat Model

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Junko Yano ◽  
Alika Yu ◽  
Paul L. Fidel ◽  
Mairi C. Noverr
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Rat Model ◽  
Tissue Damage ◽  
Biofilm Formation ◽  
Candida Glabrata ◽  
Dimorphic Fungus ◽  
Content Type ◽  
Denture Stomatitis ◽  
Ldh Release

ABSTRACTDenture stomatitis (DS) is a condition characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers.Candida-associated DS is predominantly caused byCandida albicans, a dimorphic fungus that readily colonizes and forms biofilms on denture materials. Previous studies showed a requirement forCandidabiofilm formation on both palate and dentures in infection and identified fungal morphogenic transcription factors, Efg1 and Bcr1, as key players in DS pathogenesis. While bothC. albicansandCandida glabrataare frequently coisolated in mucosal candidiasis, a pathogenic role forC. glabratain DS remains unknown. Using an established rat model of DS, we sought to determine whetherC. glabrataalone or coinoculation withC. albicansestablishes colonization and causes palatal tissue damage and inflammation. Rats fitted with custom dentures were inoculated withC. albicansand/orC. glabrataand monitored over a 4-week period for fungal burden (denture/palate), changes in body weight, and tissue damage via lactate dehydrogenase (LDH) release as well as palatal staining by hematoxylin and eosin (H&E) and immunohistochemistry for myeloperoxidase (MPO) as measures of inflammation.C. glabratacolonized the denture/palate similarly toC. albicans. In contrast toC. albicans, colonization byC. glabrataresulted in minimal changes in body weight, palatal LDH release, and MPO expression. Coinoculation with both species had no obvious modulation ofC. albicans-mediated pathogenic effects. These data suggest thatC. glabratareadily establishes colonization on denture and palate but has no apparent role for inducing/enhancingC. albicanspathogenesis in DS.IMPORTANCEMany denture wearers suffer fromCandida-associated denture stomatitis (DS), a fungal infection of the hard palate in contact with dentures. Biofilm formation byCandida albicanson denture/palate surfaces is considered a central process in the infection onset. AlthoughCandida glabratais frequently coisolated withC. albicans, its role in DS pathogenesis is unknown. We show here, using a contemporary rat model that employed a patented intraoral denture system, thatC. glabrataestablished stable colonization on the denture/palate. However, in contrast toC. albicansinoculated rats, rats inoculated withC. glabrataexhibited minimal changes in weight gain or palatal tissue damage. Likewise, coinoculation with the twoCandidaspecies resulted in no exacerbation ofC. albicans-induced DS pathology. Together, our findings indicate thatC. glabratahas no inducing/enhancing role in DS pathogenesis.

scholarly journals The Novel Arylamidine T-2307 MaintainsIn VitroandIn VivoActivity against Echinocandin-Resistant Candida albicans

2014 ◽  
Vol 59 (2) ◽  
pp. 1341-1343 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Annette W. Fothergill ◽  
Rosie Bocanegra ◽  
Marcos Olivo ◽  
...  
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Invasive Candidiasis ◽  
Placebo Control ◽  
The Novel ◽  
Content Type ◽  
Fungal Burden ◽  
Potential Use

ABSTRACTWe evaluated thein vitroandin vivoactivities of the investigational arylamidine T-2307 against echinocandin-resistantCandida albicans. T-2307 demonstrated potentin vitroactivity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistantC. albicansinfections.

scholarly journals Influence of Inoculum Effect on the Efficacy of Daptomycin Monotherapy and in Combination with β-Lactams against Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Razieh Kebriaei ◽  
Seth A. Rice ◽  
Kavindra V. Singh ◽  
Kyle C. Stamper ◽  
An Q. Dinh ◽  
...  
Keyword(s):  
Body Weight ◽  
Bloodstream Infection ◽  
Clinical Isolate ◽  
Rat Model ◽  
Enterococcus Faecium ◽  
Dose Regimen ◽  
Clinical Isolates ◽  
Content Type ◽  
Inoculum Effect ◽  
Derivatives Of

ABSTRACT Enterococcus faecium isolates that harbor LiaFSR substitutions but are phenotypically susceptible to daptomycin (DAP) by current breakpoints are problematic, since predisposition to resistance may lead to therapeutic failure. Using a simulated endocardial vegetation (SEV) pharmacokinetic/pharmacodynamic (PK/PD) model, we investigated DAP regimens (6, 8, and 10 mg/kg of body weight/day) as monotherapy and in combination with ampicillin (AMP), ceftaroline (CPT), or ertapenem (ERT) against E. faecium HOU503, a DAP-susceptible strain that harbors common LiaS and LiaR substitutions found in clinical isolates (T120S and W73C, respectively). Of interest, the efficacy of DAP monotherapy, at any dose regimen, was dependent on the size of the inoculum. At an inoculum of ∼109 CFU/g, DAP doses of 6 to 8 mg/kg/day were not effective and led to significant regrowth with emergence of resistant derivatives. In contrast, at an inoculum of ∼107 CFU/g, marked reductions in bacterial counts were observed with DAP at 6 mg/kg/day, with no resistance. The inoculum effect was confirmed in a rat model using humanized DAP exposures. Combinations of DAP with AMP, CPT, or ERT demonstrated enhanced eradication and reduced potential for resistance, allowing de-escalation of the DAP dose. Persistence of the LiaRS substitutions was identified in DAP-resistant isolates recovered from the SEV model and in DAP-resistant derivatives of an initially DAP-susceptible clinical isolate of E. faecium (HOU668) harboring LiaSR substitutions that was recovered from a patient with a recurrent bloodstream infection. Our results provide novel data for the use of DAP monotherapy and combinations for recalcitrant E. faecium infections and pave the way for testing these approaches in humans.

scholarly journals Efficacy of Ceftaroline against Methicillin-Susceptible Staphylococcus aureus Exhibiting the Cefazolin High-Inoculum Effect in a Rat Model of Endocarditis

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Kavindra V. Singh ◽  
Truc T. Tran ◽  
Esteban C. Nannini ◽  
Vincent H. Tam ◽  
Cesar A. Arias ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Infective Endocarditis ◽  
Rat Model ◽  
Type A ◽  
Treated Group ◽  
Content Type ◽  
High Inoculum ◽  
Inoculum Effect

ABSTRACT Certain Staphylococcus aureus strains exhibit an inoculum effect (InE) with cefazolin (CFZ) that has been associated with therapeutic failures in high-inoculum infections. We assessed the in vitro activities of ceftaroline (CPT), CFZ, and nafcillin (NAF) against 17 type A β-lactamase (βla)-producing, methicillin-susceptible S. aureus (MSSA) strains, including the previously reported TX0117, which exhibits the CFZ InE, and its βla-cured derivative, TX0117c. Additionally, we determined the pharmacokinetics of CPT in rats after single intramuscular doses of 20 and 40 mg/kg of body weight and evaluated the activities of CPT (40 mg/kg every 8 h [q8h]), CFZ, and NAF against TX0117 and TX0117c in a rat model of infective endocarditis. No InE was observed for CPT or NAF, whereas a marked InE was detected for CFZ (MIC, 8 to ≥128 μg/ml). CPT and NAF treatment against TX0117 resulted in mean bacterial counts of 2.3 and 2.1 log10 CFU/g in vegetations, respectively, compared to a mean of 5.9 log10 CFU/g in the CFZ-treated group (CPT and NAF versus CFZ, P = 0.001; CPT versus NAF, P = 0.9830). Both CFZ and CPT were efficacious against the βla-cured derivative, TX0117c, compared to time zero (t 0) (P = <0.0001 and 0.0015, respectively). Our data reiterate the in vivo consequences of the CFZ InE and show that CPT is not affected by this phenomenon. CPT might be considered for high-inoculum infections caused by MSSA exhibiting the CFZ InE.

scholarly journals In VitroAnalyses of Ethanol Activity against Candida albicans Biofilms

2012 ◽  
Vol 56 (8) ◽  
pp. 4487-4489 ◽  
Author(s):  
Hallie S. Rane ◽  
Stella M. Bernardo ◽  
Carla J. Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Bloodstream Infections ◽  
Optimal Dose ◽  
Limited Data ◽  
Common Cause ◽  
Content Type ◽  
Treatment And Prevention ◽  
Lock Therapy ◽  
Candida Albicans Biofilms

ABSTRACTCandida albicansis a common cause of catheter-related bloodstream infections (CR-BSI). Ethanol (EtOH) lock therapy has been attempted despite limited data on optimal dose and duration. Concentrations of 35% EtOH or higher for a minimum of 4 h demonstrated a >99% reduction in matureC. albicansbiofilm metabolic activity and prevented regrowth. Concentrations of 10% EtOH or higher reducedC. albicansbiofilm formation by >99%. Further investigation of EtOH lock therapy for treatment and prevention ofC. albicansCR-BSI is warranted.

scholarly journals Echinocandin Treatment of Candida albicans Biofilms Enhances Neutrophil Extracellular Trap Formation

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Amanda R. Hoyer ◽  
Chad J. Johnson ◽  
Matthew R. Hoyer ◽  
John F. Kernien ◽  
Jeniel E. Nett
Keyword(s):  
Candida Albicans ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Extracellular Trap ◽  
Host Defenses ◽  
Nosocomial Pathogen ◽  
Antimicrobial Proteins ◽  
Content Type ◽  
Extracellular Traps ◽  
The Face ◽  
Candida Albicans Biofilms

ABSTRACT The nosocomial pathogen Candida albicans forms biofilms on medical devices that persist in the face of antifungals and host defenses. Echinocandins, the most effective antibiofilm drugs, have recently been shown to augment the activity of neutrophils against biofilms through an unknown mechanism. Here, we show that treatment of C. albicans biofilms with subinhibitory concentrations of echinocandins promotes the formation of neutrophil extracellular traps (NETs), structures of DNA, histones, and antimicrobial proteins with antifungal activity.

scholarly journals Artemisinins, New Miconazole Potentiators Resulting in Increased Activity against Candida albicans Biofilms

2014 ◽  
Vol 59 (1) ◽  
pp. 421-426 ◽  
Author(s):  
Kaat De Cremer ◽  
Ellen Lanckacker ◽  
Tanne L. Cools ◽  
Marijke Bax ◽  
Katrijn De Brucker ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Drug Repositioning ◽  
Antibiofilm Activity ◽  
Content Type ◽  
Structural Homologues ◽  
Increased Activity ◽  
Candida Albicans Biofilms ◽  
Concentration Indices

ABSTRACTMucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole againstCandida albicansbiofilms. We screened 1,600 compounds of a drug-repositioning library in combination with a subinhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate, and artesunate act synergistically with miconazole in affectingC. albicansbiofilms. Synergy was most pronounced for artesunate and structural homologues thereof. No synergistic effect could be observed between artesunate and fluconazole, caspofungin, or amphotericin B. Our data reveal enhancement of the antibiofilm activity of miconazole by artesunate, pointing to potential combination therapy consisting of miconazole and artesunate to treatC. albicansbiofilm-related infections.

scholarly journals The Investigational Agent E1210 Is Effective in Treatment of Experimental Invasive Candidiasis Caused by Resistant Candida albicans

2014 ◽  
Vol 59 (1) ◽  
pp. 690-692 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Annette W. Fothergill ◽  
Dora I. McCarthy ◽  
Rosie Bocanegra ◽  
...  
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Invasive Candidiasis ◽  
Content Type ◽  
Fungal Burden ◽  
Investigational Agent ◽  
Oral Doses ◽  
Potential Use

ABSTRACTThein vitroandin vivoactivity of the inositol acyltransferase inhibitor E1210 was evaluated against echinocandin-resistantCandida albicans. E1210 demonstrated potentin vitroactivity, and in mice with invasive candidiasis caused by echinocandin-resistantC. albicans, oral doses of 10 and 40 mg E1210/kg of body weight twice daily significantly improved survival and reduced fungal burden compared to those of controls and mice treated with caspofungin (10 mg/kg/day). These results demonstrate the potential use of E1210 against resistantC. albicansinfections.

scholarly journals Garcinia xanthochymus Benzophenones Promote Hyphal Apoptosis and Potentiate Activity of Fluconazole against Candida albicans Biofilms

2015 ◽  
Vol 59 (10) ◽  
pp. 6032-6038 ◽  
Author(s):  
Desmond N. Jackson ◽  
Lin Yang ◽  
ShiBiao Wu ◽  
Edward J. Kennelly ◽  
Peter N. Lipke
Keyword(s):  
Cell Death ◽  
Candida Albicans ◽  
Dna Fragmentation ◽  
Phosphatidyl Serine ◽  
Content Type ◽  
Garcinia Xanthochymus ◽  
Biofilm Development ◽  
Germ Tubes ◽  
Candida Albicans Biofilms

ABSTRACTXanthochymol and garcinol, isoprenylated benzophenones purified fromGarcinia xanthochymusfruits, showed multiple activities againstCandida albicansbiofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic, with MICs of 1 to 3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatidyl serine and DNA fragmentation, as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms, xanthochymol and garcinol caused the death of biofilm hyphae, with 50% effective concentrations (EC50s) of 30 to 50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50from >1,024 μg/ml to 13 μg/ml. Therefore, xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis.

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