scholarly journals Comparison of the Fungicidal Activities of Caspofungin and Amphotericin B against Candida glabrata

2005 ◽  
Vol 49 (12) ◽  
pp. 4989-4992 ◽  
Author(s):  
Francesco Barchiesi ◽  
Elisabetta Spreghini ◽  
Serena Tomassetti ◽  
Daniela Arzeni ◽  
Daniele Giannini ◽  
...  
Keyword(s):  
Body Weight ◽  
Mouse Model ◽  
Amphotericin B ◽  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Fungicidal Activity ◽  
Disseminated Infection ◽  
Fungicidal Effect ◽  
Time Kill

ABSTRACT We investigated the fungicidal activity of caspofungin (CAS) and amphotericin B (AMB) against 16 clinical isolates of Candida glabrata. The minimum fungicidal concentrations (MFCs) of CAS were similar to those of AMB, ranging from 2.0 to >8.0 μg/ml. Time-kill assays performed on selected isolates showed that AMB was fungicidal at concentrations four times the MIC while CAS was not. A neutropenic-mouse model of disseminated infection was utilized to determine the residual fungal kidney burden. While doses as low as 0.3 and 1 mg/kg of body weight/day of CAS and AMB, respectively, were effective at reducing the counts with respect to controls, organ sterilization was reached when both drugs were administered at 5 mg/kg/day. Our study reveals that, similar to AMB, CAS has the potential for a fungicidal effect in vivo against this difficult-to-treat fungal pathogen.

scholarly journals Assessment of Candida auris Response to Antifungal Drugs Using Time–Kill Assays and an Animal Model

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S73-S73 ◽  
Author(s):  
Ronen Ben-Ami ◽  
Liat Ashkenazi ◽  
Judith Berman ◽  
Nuphar Korolker ◽  
Anna Novikov
Keyword(s):  
Amphotericin B ◽  
Fungicidal Activity ◽  
Antifungal Drugs ◽  
Rank Test ◽  
Infection Model ◽  
Candida Auris ◽  
Fungistatic Activity ◽  
Kill Curve ◽  
Time Kill

Abstract Background Candida auris is an emerging nosocomial pathogen that is resistant to Fluconazole and variably susceptible to other systemic drug classes. Treatment with echinocandins has been recommended based on MICs in the susceptible range, but supporting in vivo data is lacking. Methods We tested the MIC of C. auris strains (n = 12) to fluconazole, voriconazole, posaconazole. anidulafungin, amphotericin B and flucytosine. Representative C. auris strains from Israel and South Africa, and a reference C. albicans strain were analysed using time–kill curve assays. Fungicidal activity was defined as reduction of ≥3 log from baseline CFU/ml. Response to caspofungin treatment was assessed in BALB/c mice immunosuppressed with cyclophosphamide and inoculated with 7 × 107C. auris cells by tail vein injection. Mice were treated from day +1 to day +7 with caspofungin (IP) at doses of 1 or 5 mg/kg and compared with sham-treated controls. Survival was assessed daily. Kaplan-Meier survival analyses were performed and treatment arms were compared using the log-rank test. Results Drug susceptibility results (MIC50 and MIC90) were: fluconazole, 64 and 128 mg/l; voriconazole, 0.5 and 24 mg/l; posaconazole, 0.5 and 27 mg/l; anidulafungin, 0.03 and 0.06 mg/l; amphotericin B, 2 and 8 mg/l; flucytosine, 0.3 and 1 mg/l. Time–kill curve analyses showed log reduction from baseline CFU concentration of −3.0 to −2.8 for fluconazole (MIC ×1), 5.6–6.1 for amphotericin B (MIC ×4) and −0.4 to −0.9 for caspofungin (MIC ×16), consistent with fungicidal activity of amphotericin B and weak fungistatic activity of caspofungin. In the mouse model, survival rate was similar with sham treatment (33%) and treatment with caspofungin 1 mg/kg/day (44%) and 5 mg/kg/day (22%), P = 0.7. Conclusion Despite generally low MIC, caspofungin has only mild fungistatic activity on C. auris and no effect on survival in a mouse infection model. Amphotericin B has fungicidal activity against C. auris. Disclosures All authors: No reported disclosures.

scholarly journals In Vivo Activity of Posaconazole against Mucor spp. in an Immunosuppressed-Mouse Model

2002 ◽  
Vol 46 (7) ◽  
pp. 2310-2312 ◽  
Author(s):  
Qiu N. Sun ◽  
Laura K. Najvar ◽  
Rosie Bocanegra ◽  
David Loebenberg ◽  
John R. Graybill
Keyword(s):  
Body Weight ◽  
Mouse Model ◽  
Amphotericin B ◽  
Immunosuppressed Mouse ◽  
Tissue Burden

ABSTRACT The in vivo activities of posaconazole, itraconazole, and amphotericin B in neutropenic mice with zygomycosis were compared. The in vitro MICs of posaconazole and itraconazole for the strains of Mucor spp. used in this study ranged from 0.125 to 8 μg/ml and 0.25 to 8 μg/ml, respectively. The in vitro MIC range for amphotericin B is 0.125 to 0.25 μg/ml. At twice-daily doses of ≥15 mg/kg of body weight, posaconazole prolonged the survival of the mice and reduced tissue burden.

scholarly journals Combination therapy with amphotericin B and fluconazole against invasive candidiasis in neutropenic-mouse and infective-endocarditis rabbit models.

1997 ◽  
Vol 41 (6) ◽  
pp. 1345-1348 ◽  
Author(s):  
H Sanati ◽  
C F Ramos ◽  
A S Bayer ◽  
M A Ghannoum
Keyword(s):  
Infective Endocarditis ◽  
Combination Therapy ◽  
Mouse Model ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Combined Therapy ◽  
Rabbit Model ◽  
Model Treatment ◽  
The Brain

Although there are an increasing number of new antifungal agents available, the morbidity and mortality due to invasive mycoses remain high. The high rates of polyene toxicities and the development of azole resistance have raised the issue of using antifungal agents of these classes in combination, despite theoretical concerns regarding antagonism between such agents. This study was designed to evaluate the in vivo efficacy of combined therapy with amphotericin B and fluconazole against Candida albicans. Two distinct animal models were used in this study: a neutropenic-mouse model of hematogenously disseminated candidiasis and the infective-endocarditis rabbit model. Treatment efficacy was assessed by determining reductions in mortality as well as decreases in tissue fungal densities. In the neutropenic-mouse model, amphotericin B, as well as combination therapy, significantly prolonged survival compared to untreated controls (P < 10(-5) and P = 0.001, respectively). The fungal densities in the kidneys of neutropenic mice were significantly reduced with either amphotericin B monotherapy or amphotericin B-fluconazole combined therapy compared to those of controls (P < 10(-6)). Fluconazole monotherapy also reduced fungal densities in the kidneys; however, this decrease was not statistically significant (P = 0.17). In contrast, treatment with either fluconazole alone or combined with amphotericin B (but not amphotericin B monotherapy) significantly decreased fungal densities in the brain (P = 0.025). In the rabbit endocarditis model, amphotericin B monotherapy or combined therapy significantly decreased fungal densities in cardiac vegetations (P < 0.01 versus the controls). Although no significant antagonism was seen when fluconazole was given in combination with amphotericin B, combination therapy did not augment the antifungal activity of amphotericin B.

scholarly journals Treatment of murine Candida krusei or Candida glabrata infection with L-743,872.

1997 ◽  
Vol 41 (9) ◽  
pp. 1937-1939 ◽  
Author(s):  
J R Graybill ◽  
R Bocanegra ◽  
M Luther ◽  
A Fothergill ◽  
M J Rinaldi
Keyword(s):  
Body Weight ◽  
Broad Spectrum ◽  
Candida Glabrata ◽  
Clinical Development ◽  
Candida Krusei ◽  
Murine Models ◽  
Fungal Cell ◽  
Significant Potential ◽  
Cell Counts

L-743,872 is a broad-spectrum pneumocandin antifungal drug developed by Merck Research Co., and in the present work it was evaluated in vivo in murine models of Candida krusei and Candida glabrata infection. Mice were infected intravenously with two isolates of C. krusei and treated with fluconazole or L-743,872. Fluconazole was beneficial only in immune-competent mice infected with isolate 94-2696. At > 0.5 mg/kg of body weight/day, L-743,872 was effective against both infecting isolates in immune-competent and immune-suppressed mice. Against C. glabrata, L-743,872 was effective, at doses > or = 0.5 mg/kg, in reducing fungal cell counts in the kidneys but not in the spleen. L-743,872 has significant potential for clinical development.

scholarly journals Activity of Tigecycline (GAR-936), a Novel Glycylcycline, against Enterococci in the Mouse Peritonitis Model

2003 ◽  
Vol 47 (2) ◽  
pp. 529-532 ◽  
Author(s):  
Esteban C. Nannini ◽  
Suresh R. Pai ◽  
Kavindra V. Singh ◽  
Barbara E. Murray
Keyword(s):  
Body Weight ◽  
Mouse Model ◽  
Protective Effect ◽  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Tetracycline Resistance ◽  
Resistance Determinant ◽  
Subcutaneous Dose ◽  
Peritonitis Model

ABSTRACT A novel glycylcycline agent, tigecycline (GAR-936), was evaluated in vivo in the mouse model of peritonitis against three Enterococcus faecalis and four Enterococcus faecium isolates with different susceptibilities to vancomycin and tetracyclines, all of which were inhibited by ≤0.125 μg of tigecycline/ml. Using a single subcutaneous dose, tigecycline displayed a protective effect (50% protective dose, ≤5.7 mg/kg of body weight) against all strains tested, including two with Tn925 (from the Tn916 family), which contains the Tet(M) tetracycline resistance determinant, as well as VanA and VanB strains. As expected, tetracycline and minocycline were ineffective against the isolates carrying Tn925.

scholarly journals Activities of Flucytosine, Fluconazole, Amphotericin B, and Micafungin in a Murine Model of Disseminated Infection by Candida glabrata

2005 ◽  
Vol 49 (11) ◽  
pp. 4757-4759 ◽  
Author(s):  
Marçal Mariné ◽  
Carolina Serena ◽  
Belkys Fernández-Torres ◽  
F. Javier Pastor ◽  
Josep Guarro
Keyword(s):  
Amphotericin B ◽  
Murine Model ◽  
Candida Glabrata ◽  
Disseminated Infection ◽  
Tissue Burden

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.

scholarly journals Efficacies of Fluconazole, Caspofungin, and Amphotericin B in Candida glabrata-Infected p47phox−/− Knockout Mice

2002 ◽  
Vol 46 (5) ◽  
pp. 1240-1245 ◽  
Author(s):  
Justina Y. Ju ◽  
Cynthia Polhamus ◽  
Kieren A. Marr ◽  
Steven M. Holland ◽  
John E. Bennett
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Murine Model ◽  
Knockout Mice ◽  
Candida Glabrata ◽  
Drug Efficacy ◽  
Fungal Burden ◽  
Lethal Infection

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.

scholarly journals Potency of omadacycline against Mycobacteroides abscessus clinical isolates in vitro and in a mouse model of pulmonary infection

2021 ◽  
Author(s):  
Danielle A. Nicklas ◽  
Emily C. Maggioncalda ◽  
Elizabeth Story-Roller ◽  
Benjamin Eichelman ◽  
Chavis Tabor ◽  
...  
Keyword(s):  
Mouse Model ◽  
Opportunistic Pathogen ◽  
Current Treatment ◽  
Clinical Isolates ◽  
Control Group ◽  
Chronic Infections ◽  
Human Dose ◽  
Time Kill

The incidence of nontuberculous mycobacterial diseases in the US is rising and has surpassed tuberculosis. Most notable among the nontuberculous mycobacteria is Mycobacteroides abscessus , an emerging environmental opportunistic pathogen capable of causing chronic infections. M. abscessus disease is difficult to treat and the current treatment recommendations include repurposed antibiotics, several of which are associated with undesirable side effects. In this study, we have evaluated the activity of omadacycline, a new tetracycline derivative, against M. abscessus using in vitro and in vivo approaches. Omadacycline exhibited an MIC 90 of 0.5 μg/ml against a panel of 32 contemporary M. abscessus clinical isolates several of which were resistant to antibiotics that are commonly used for treatment of M. abscessus disease. Omadacycline when combined with clarithromycin, azithromycin, cefdinir, rifabutin or linezolid also exhibited synergism against several M. abscessus strains and did not exhibit antagonism when combined with an additional nine antibiotics also commonly considered to treat M. abscessus disease. Concentration-dependent activity of omadacycline was observed in time-kill assessments. Efficacy of omadacycline was evaluated in a mouse model of lung infection against four M. abscessus strains. A dose equivalent to the 300 mg standard oral human dose was used. Compared to the untreated control group, within four weeks of treatment, 1 to 3 log 10 fewer M. abscessus colony forming units were observed in the lungs of mice treated with omadacycline. Treatment outcome was biphasic, with bactericidal activity observed after the first two weeks of treatment against all four M. abscessus strains.

scholarly journals In Vitro Activity of a New Polyene, SPA-S-843, against Yeasts

1998 ◽  
Vol 42 (11) ◽  
pp. 3012-3013 ◽  
Author(s):  
C. Rimaroli ◽  
T. Bruzzese
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Candida Tropicalis ◽  
Candida Glabrata ◽  
Fungicidal Activity ◽  
Candida Krusei ◽  
Water Soluble ◽  
Vitro Activity ◽  
In Vitro Activity

ABSTRACT The in vitro activity of a new water-soluble polyene, SPA-S-843, was evaluated against 116 strains of Candida,Cryptococcus, and Saccharomyces spp. and compared with that of amphotericin B. SPA-S-843 demonstrated better inhibitory activity against all of the yeasts examined and better fungicidal activity against Candida albicans, Candida glabrata, Candida krusei, and Candida tropicalis than did amphotericin B.

In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum.

1996 ◽  
Vol 40 (10) ◽  
pp. 2237-2242 ◽  
Author(s):  
K Hata ◽  
J Kimura ◽  
H Miki ◽  
T Toyosawa ◽  
T Nakamura ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Good Activity ◽  
Time Curve ◽  
Concentration Time ◽  
Wide Range ◽  
Systemic Infections

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. ER-30346, with MICs at which 90% of the strains tested are inhibited (MIC90s) ranging from 0.025 to 0.78 microgram/ml, was 4 to 32 times more active than itraconazole, fluconazole, and amphotericin B against Candida albicans, Candida parapsilosis, and Candida glabrata. Against Candida tropicalis, ER-30346, with an MIC90 of 12.5 micrograms/ml, was 2 to > 8 times more active than itraconazole and fluconazole, but was 16 times less active than amphotericin B. ER-30346 (MIC90, 0.78 microgram/ml) was four to eight times more active than fluconazole and amphotericin B and had activity comparable to that of itraconazole against Trichosporon beigelli. The MIC90s of ER-30346 were 0.10 microgram/ml for Cryptococcus neoformans and 0.39 microgram/ml for Aspergillus fumigatus. ER-30346 was 2 to 8 times more active than itraconazole and amphotericin B and 32 to > 256 times more active than fluconazole. ER-30346 also showed good activity against dermatophytes, with MICs ranging from 0.05 to 0.39 microgram/ml, and its activity was comparable to or 2 to 16 times higher than those of itraconazole and amphotericin B and > 32 times higher than that of fluconazole. In vivo activity was evaluated with systemic infections in mice. Against systemic candidiasis and cryptococcosis, ER-30346 was comparable in efficacy to fluconazole and was more effective than itraconazole. Of the drugs tested, ER-30346 was the most effective drug against systemic aspergillosis. We studied the levels of ER-30346 in mouse plasma. The maximum concentration of drug in plasma and the area under the concentration-time curve for ER-30346 showed good linearity over a range of doses from 2 to 40 mg/kg of body weight.

Sign in / Sign up

Export Citation Format

Share Document