scholarly journals Treatment of Candida glabrata using topical amphotericin B and flucytosine

2003 ◽  
Vol 79 (3) ◽  
pp. 265-a-266 ◽  
Author(s):  
S Shann
2007 ◽  
Vol 52 (2) ◽  
pp. 513-517 ◽  
Author(s):  
Elisabetta Spreghini ◽  
Carmelo Massimo Maida ◽  
Maria Eleonora Milici ◽  
Giorgio Scalise ◽  
Francesco Barchiesi

ABSTRACT We evaluated the effects of sequential therapy with caspofungin (CAS) or amphotericin B (AMB) followed by posaconazole (POS) against Candida glabrata. The susceptibilities to POS of yeast cells pre-exposed to CAS or AMB were identical to those of untreated cells as shown by standard Clinical and Laboratory Standards Institute broth dilution, cell viability, and disk diffusion methods. We then investigated the activity of sequential regimens in an experimental model of disseminated candidiasis. CAS given at 1 mg/kg/day for 2 days followed by POS at either 15 or 30 mg/kg/day significantly reduced the counts compared to the controls, but this treatment was not superior to the use of CAS alone. Also, sequential regimens with AMB given at 1 mg/kg/day for 2 days followed by POS (AMB/POS) were effective at reducing the fungal burden against the controls. In addition, AMB/POS with both doses of the triazole were significantly more effective than AMB alone. Overall, our data showed that there is no therapeutic advantage in using CAS followed by POS, whereas an induction therapy with AMB followed by a maintenance regimen with POS might be a suitable strategy in managing C. glabrata infections.


2010 ◽  
Vol 5 (3) ◽  
pp. 318-323 ◽  
Author(s):  
Soňa Kucharíková ◽  
Patrick Dijck ◽  
Magdaléna Lisalová ◽  
Helena Bujdáková

AbstractIn the last decade, infections caused by Candida glabrata have become more serious, particularly due to its decreased susceptibility to azole derivatives and its ability to form biofilm. Here we studied the resistance profile of 42 C. glabrata clinical isolates to different azoles, amphotericin B and echinocandins. This work was also focused on the ability to form biofilm which plays a role in the development of antifungal resistance. The minimal inhibitory concentration testing to antifungal agents was performed according to the CLSI (Clinical and Laboratory Standards Institute) M27-A3 protocol. Quantification of biofilm was done by XTT reduction assay. All C. glabrata clinical isolates were resistant to itraconazole and sixteen also showed resistance to fluconazole. All isolates remained susceptible to voriconazole. Amphotericin B was efficient in a concentration range of 0.125–1 mg/L. The most effective antifungal agents were micafungin and caspofungin with the MIC100 values of ≤0.0313–0.125 mg/L. Low concentrations of these agents reduced biofilm formation as well. Our results show that resistance of different C. glabrata strains is azole specific and therefore a single azole resistance cannot be assumed to indicate general azole resistance. Echinocandins proved to have very high efficacy against clinical C. glabrata strains including those with ability to form biofilm.


2005 ◽  
Vol 49 (11) ◽  
pp. 4757-4759 ◽  
Author(s):  
Marçal Mariné ◽  
Carolina Serena ◽  
Belkys Fernández-Torres ◽  
F. Javier Pastor ◽  
Josep Guarro

ABSTRACT We compared the efficacies of amphotericin B, fluconazole, flucytosine, and micafungin in a systemic murine infection by three isolates of Candida glabrata. Amphotericin B showed the best results, although none of the drugs dramatically reduced mortality or tissue burden in liver or spleen.


2002 ◽  
Vol 46 (5) ◽  
pp. 1240-1245 ◽  
Author(s):  
Justina Y. Ju ◽  
Cynthia Polhamus ◽  
Kieren A. Marr ◽  
Steven M. Holland ◽  
John E. Bennett

ABSTRACT Candida glabrata is the second leading cause of adult candidemia, resulting in high mortality. Amphotericin B is considered the treatment of choice, while the efficacy of fluconazole is controversial and caspofungin efficacy is unknown. To ascertain drug efficacy in vivo, the utility of a murine model of C. glabrata infection was investigated. C. glabrata was found to cause progressive, lethal infection when injected intravenously into C57BL/6 mice with reduced oxidative microbicidal capacity due to knockout of the p47phox gene. Spleen and kidney organ CFU counts were determined in groups of mice 2 days after the mice completed 6 days of daily intraperitoneal drug treatment, which began on the day of infection. Daily injections of fluconazole at 80 mg/kg did not reduce spleen or kidney CFU counts after infection with C. glabrata strains having in vitro fluconazole MICs of 2, 32, or 256 μg/ml compared to saline-treated controls. However, this fluconazole regimen reduced spleen CFU counts in mice infected with Candida albicans, an infection that is known to be responsive to fluconazole. Caspofungin at 5 mg/kg and amphotericin B at 5 mg/kg were both effective in reducing fungal burden in spleens and kidneys of C. glabrata-infected mice. Ten mice treated for 6 days with caspofungin at 1 mg/kg survived for 15 days, though all 10 saline-injected mice died or were so ill that they had to be sacrificed by 96 h postinfection. This murine model provided evidence of the efficacy of amphotericin B and caspofungin but not of fluconazole against C. glabrata infection.


2012 ◽  
Vol 56 (8) ◽  
pp. 4223-4232 ◽  
Author(s):  
Claire M. Hull ◽  
Josie E. Parker ◽  
Oliver Bader ◽  
Michael Weig ◽  
Uwe Gross ◽  
...  

ABSTRACTWe identified a clinical isolate ofCandida glabrata(CG156) exhibiting flocculent growth and cross-resistance to fluconazole (FLC), voriconazole (VRC), and amphotericin B (AMB), with MICs of >256, >256, and 32 μg ml−1, respectively. Sterol analysis using gas chromatography-mass spectrometry (GC-MS) revealed that CG156 was a sterol 14α-demethylase (Erg11p) mutant, wherein 14α-methylated intermediates (lanosterol was >80% of the total) were the only detectable sterols.ERG11sequencing indicated that CG156 harbored a single-amino-acid substitution (G315D) which nullified the function of native Erg11p. In heterologous expression studies using a doxycycline-regulatableSaccharomyces cerevisiae erg11strain, wild-typeC. glabrataErg11p fully complemented the function ofS. cerevisiaesterol 14α-demethylase, restoring growth and ergosterol synthesis in recombinant yeast; mutated CG156 Erg11p did not. CG156 was culturable using sterol-free, glucose-containing yeast minimal medium (glcYM). However, when grown on sterol-supplementedglcYM (with ergosta 7,22-dienol, ergosterol, cholestanol, cholesterol, Δ7-cholestenol, or desmosterol), CG156 cultures exhibited shorter lag phases, reached higher cell densities, and showed alterations in cellular sterol composition. Unlike comparator isolates (harboring wild-typeERG11) that became less sensitive to FLC and VRC when cultured on sterol-supplementedglcYM, facultative sterol uptake by CG156 did not affect its azole-resistant phenotype. Conversely, CG156 grown usingglcYM with ergosterol (or with ergosta 7,22-dienol) showed increased sensitivity to AMB; CG156 grown usingglcYM with cholesterol (or with cholestanol) became more resistant (MICs of 2 and >64 μg AMB ml−1, respectively). Our results provide insights into the consequences of sterol uptake and metabolism on growth and antifungal resistance inC. glabrata.


2013 ◽  
Vol 176 (1-2) ◽  
pp. 165-169 ◽  
Author(s):  
Laura Bedin Denardi ◽  
Débora Alves Nunes Mario ◽  
Érico Silva de Loreto ◽  
Cristina Wayne Nogueira ◽  
Janio Morais Santurio ◽  
...  

2012 ◽  
Vol 56 (3) ◽  
pp. 1403-1406 ◽  
Author(s):  
Claire S. Danby ◽  
Dina Boikov ◽  
Rina Rautemaa-Richardson ◽  
Jack D. Sobel

ABSTRACTThe treatment of vulvovaginal candidiasis (VVC) due toCandida glabratais challenging, with limited therapeutic options. Unexplained disappointing clinical efficacy has been reported with systemic and topical azole antifungal agents in spite ofin vitrosusceptibility. Given that the vaginal pH of patients with VVC is unchanged at 4 to 4.5, we studied the effect of pH on thein vitroactivity of 11 antifungal agents against 40C. glabrataisolates and compared activity against 15 fluconazole-sensitive and 10 reduced-fluconazole-susceptibilityC. albicansstrains.In vitrosusceptibility to flucytosine, fluconazole, voriconazole, posaconazole, itraconazole, ketoconazole, clotrimazole, miconazole, ciclopirox olamine, amphotericin B, and caspofungin was determined using the CLSI method for yeast susceptibility testing. Test media were buffered to pHs of 7, 6, 5, and 4. Under conditions of reduced pH,C. glabrataisolates remained susceptible to caspofungin and flucytosine; however, there was a dramatic increase in the MIC90for amphotericin B and every azole drug tested. Although susceptible to other azole drugs tested at pH 7,C. albicansstrains with reduced fluconazole susceptibility also demonstrated reduced susceptibility to amphotericin B and all azoles at pH 4. In contrast, fluconazole-sensitiveC. albicansisolates remained susceptible at low pH to azoles, in keeping with clinical observations. In selecting agents for treatment of recurrentC. glabratavaginitis, clinicians should recognize the limitations ofin vitrosusceptibility testing utilizing pH 7.0.


Sign in / Sign up

Export Citation Format

Share Document